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Drug overview for DAPAGLIFLOZIN-METFORMIN ER (dapagliflozin propanediol/metformin hcl):
Generic name: DAPAGLIFLOZIN PROPANEDIOL/METFORMIN HCL (DAP-a-gli-FLOE-zin/met-FOR-min)
Drug class: Biguanides
Therapeutic class: Endocrine
Dapagliflozin propanediol, a sodium-glucose cotransporter 2 (SGLT2) Metformin hydrochloride is a biguanide antidiabetic agent. inhibitor, is an antidiabetic agent.
No enhanced Uses information available for this drug.
Generic name: DAPAGLIFLOZIN PROPANEDIOL/METFORMIN HCL (DAP-a-gli-FLOE-zin/met-FOR-min)
Drug class: Biguanides
Therapeutic class: Endocrine
Dapagliflozin propanediol, a sodium-glucose cotransporter 2 (SGLT2) Metformin hydrochloride is a biguanide antidiabetic agent. inhibitor, is an antidiabetic agent.
No enhanced Uses information available for this drug.
DRUG IMAGES
XIGDUO XR 5 MG-1,000 MG TABLET
XIGDUO XR 10 MG-1,000 MG TAB
The following indications for DAPAGLIFLOZIN-METFORMIN ER (dapagliflozin propanediol/metformin hcl) have been approved by the FDA:
Indications:
Type 2 diabetes mellitus
Professional Synonyms:
Adult onset diabetes mellitus
Adult onset diabetes
Adult onset DM
Diabetes mellitus type 2
Diabetes mellitus type II
Ketosis-resistant diabetes mellitus
Ketosis-resistant DM
Maturity onset diabetes mellitus
Maturity onset diabetes
Non-insulin dependent diabetes mellitus
Non-insulin-dependent diabetes mellitus
Type II diabetes mellitus
Indications:
Type 2 diabetes mellitus
Professional Synonyms:
Adult onset diabetes mellitus
Adult onset diabetes
Adult onset DM
Diabetes mellitus type 2
Diabetes mellitus type II
Ketosis-resistant diabetes mellitus
Ketosis-resistant DM
Maturity onset diabetes mellitus
Maturity onset diabetes
Non-insulin dependent diabetes mellitus
Non-insulin-dependent diabetes mellitus
Type II diabetes mellitus
The following dosing information is available for DAPAGLIFLOZIN-METFORMIN ER (dapagliflozin propanediol/metformin hcl):
For the management of type 2 diabetes mellitus in adults, the usual initial dosage of metformin hydrochloride as immediate-release tablets or immediate-release oral solution is 500 mg twice daily or 850 mg once daily with meals. Alternatively, an initial metformin hydrochloride dosage of 500 mg once daily has been suggested by some experts. Some manufacturers state that in general, clinically important responses are not observed at metformin hydrochloride dosages of less than 1.5
g daily.
When metformin hydrochloride is administered as an extended-release tablet preparation in adults, some manufacturers recommend an initial dosage of 500 mg once daily with the evening meal. The manufacturer of a certain extended-release tablet preparation (Fortamet(R)) recommends an initial dosage of 1 g once daily with the evening meal, although the manufacturer states that 500 mg once daily may be used when clinically appropriate. The recommended initial dosage of another extended-release preparation of metformin hydrochloride (Glumetza(R)) is 1 g once daily with the evening meal.
Subsequent dosage of metformin hydrochloride should be adjusted according to the patient's therapeutic response, using the lowest possible effective dosage. (See Dosage: Dosage Titration, under Dosage and Administration.)
Although satisfactory control of blood glucose concentrations may be achieved within a few days after dosage adjustment, the full effects of the drug may not be observed for up to 2 weeks.
Initial dosages of metformin hydrochloride in geriatric patients should be conservative (initiated at the low end of the dosage range) and should be titrated carefully; limited data suggest reducing dosage by approximately 33% in geriatric patients.
For the management of type 2 diabetes mellitus in children or adolescents 10-16 years of age, the usual initial dosage of metformin hydrochloride as immediate-release tablets or the immediate-release oral solution is 500 mg twice daily given in the morning and evening with meals. Safety and efficacy of Fortamet(R) and certain other extended-release tablet preparations of metformin hydrochloride have not been established in patients younger than 17 years of age; refer to labeling of specific preparations for details. Safety and efficacy of Glumetza(R), another extended-release tablet preparation, have not been established in patients younger than 18 years of age.
In adults receiving an initial metformin hydrochloride dosage of 500 mg twice daily as immediate-release tablets or the immediate-release oral solution, daily dosage may be increased by 500 mg at weekly intervals until the desired fasting blood glucose concentration is achieved or a dosage of 2.55 g daily is reached. In adults receiving an initial dosage of 500 mg of metformin hydrochloride once or twice daily (with breakfast and/or dinner), some experts recommend increasing the dosage to 850 mg or 1 g twice daily after 5-7 days if additional glycemic control is needed and the drug is well tolerated (e.g., no adverse GI effects).
If adverse GI effects appear during dosage titration of metformin hydrochloride, some experts suggest that dosage be decreased to the previous lower dosage, and further dosage increments attempted at a later time. In adults receiving an initial metformin hydrochloride dosage of 850 mg daily as immediate-release tablets or the immediate-release oral solution, daily dosage may be increased by 850 mg every other week (i.e., every 2 weeks) until the desired fasting blood glucose concentration is achieved or a total dosage of 2.55 g daily is reached.
For patients requiring additional glycemic control with metformin hydrochloride, a maximum daily dosage of 2.55 g as immediate-release tablets or the immediate-release oral solution may be used.
In adults (17-18 years of age or older) receiving Glumetza(R) or certain other extended-release metformin hydrochloride preparations, daily dosage may be increased by 500 mg at weekly intervals until the desired glycemic response is achieved or a maximum dosage of 2 g daily is reached. If glycemic control is not achieved with extended-release metformin hydrochloride tablets (e.g., Glumetza(R)) at a dosage of 2 g once daily, a dosage of 1 g twice daily should be considered. If a dosage exceeding 2 g daily is needed in patients receiving certain other extended-release metformin hydrochloride preparations, the manufacturers suggest that therapy be switched to immediate-release metformin hydrochloride tablets and dosage titrated up to a maximum dosage of 2.55
g daily in divided doses. Conversely, therapy with extended-release tablets may be substituted for immediate-release tablets at the same total daily dosage of immediate-release tablets, up to a dosage of 2 g once daily.
With another extended-release metformin hydrochloride preparation (Fortamet(R)), daily dosage may be increased by 500 mg at weekly intervals up to a maximum of 2.5 g once daily with the evening meal. In patients transferring from immediate-release tablets to an extended-release preparation, glycemic control should be closely monitored and dosage adjustments made accordingly.
Dosage in adults generally should not exceed 2.55 g daily when given as metformin hydrochloride immediate-release tablets or immediate-release oral solution, 2.5 g daily when given as certain extended-release tablets (e.g., Fortamet(R)), or 2 g daily when given as certain other extended-release tablet preparations.
Metformin hydrochloride dosages of up to 3 g daily have been associated with modestly greater effectiveness than 1.7 g daily. However, adverse GI effects may limit the maximum dosage that can be tolerated.
(Consult the manufacturer's labeling for product-specific details.) Dosages exceeding 2 g of metformin hydrochloride daily as immediate-release tablets or the immediate-release oral solution may be better tolerated if given in 3 divided doses daily with meals.
Metformin should be used with caution in geriatric patients since aging is associated with reduced renal function, and accumulation of the drug resulting in lactic acidosis may occur in patients with renal impairment. In addition, renal function should be monitored periodically in geriatric patients to determine the appropriate dosage of metformin hydrochloride. Any dosage adjustment in geriatric patients should be based on a careful assessment of renal function.
In children or adolescents 10-16 years of age receiving metformin hydrochloride 500 mg twice daily as immediate-release tablets or the immediate-release oral solution, daily dosage may be increased by 500 mg at weekly intervals until the desired glycemic response is achieved or a maximum dosage of 2 g daily given in 2 divided doses is reached.
Dosage of dapagliflozin propanediol is expressed in terms of dapagliflozin.
Because of the risk of lactic acidosis, which occurs rarely but may be fatal, metformin should not be used in patients with severe renal disease or dysfunction (eGFR less than 30 mL/minute per 1.73 m2) and should be avoided in those with clinical or laboratory evidence of hepatic disease. In patients with moderate renal disease, the benefits and risks of continuing metformin therapy should be assessed. (See Cautions: Lactic Acidosis.)
An FDA review of clinical studies evaluating the safety of metformin in patients with reduced kidney function suggests that metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function.
The manufacturers and FDA state that renal function (eGFR) should be assessed prior to initiation of metformin and at least annually; more frequent monitoring has been recommended in patients with an increased risk of developing renal impairment (e.g., geriatric patients). The manufacturers and FDA state that initiation of metformin therapy is not recommended in patients with an eGFR between 30-45 mL/minute per 1.73 m2 and that the benefits and risks of continuing the drug should be assessed in those already receiving metformin whose eGFR falls below 45 mL/minute per 1.73
m2. The manufacturers and FDA state that metformin is contraindicated in patients with an eGFR of less than 30 mL/minute per 1.73 m2 and that the drug should be discontinued in patients whose eGFR falls below 30 mL/minute per 1.73 m2 who are already receiving metformin.
g daily.
When metformin hydrochloride is administered as an extended-release tablet preparation in adults, some manufacturers recommend an initial dosage of 500 mg once daily with the evening meal. The manufacturer of a certain extended-release tablet preparation (Fortamet(R)) recommends an initial dosage of 1 g once daily with the evening meal, although the manufacturer states that 500 mg once daily may be used when clinically appropriate. The recommended initial dosage of another extended-release preparation of metformin hydrochloride (Glumetza(R)) is 1 g once daily with the evening meal.
Subsequent dosage of metformin hydrochloride should be adjusted according to the patient's therapeutic response, using the lowest possible effective dosage. (See Dosage: Dosage Titration, under Dosage and Administration.)
Although satisfactory control of blood glucose concentrations may be achieved within a few days after dosage adjustment, the full effects of the drug may not be observed for up to 2 weeks.
Initial dosages of metformin hydrochloride in geriatric patients should be conservative (initiated at the low end of the dosage range) and should be titrated carefully; limited data suggest reducing dosage by approximately 33% in geriatric patients.
For the management of type 2 diabetes mellitus in children or adolescents 10-16 years of age, the usual initial dosage of metformin hydrochloride as immediate-release tablets or the immediate-release oral solution is 500 mg twice daily given in the morning and evening with meals. Safety and efficacy of Fortamet(R) and certain other extended-release tablet preparations of metformin hydrochloride have not been established in patients younger than 17 years of age; refer to labeling of specific preparations for details. Safety and efficacy of Glumetza(R), another extended-release tablet preparation, have not been established in patients younger than 18 years of age.
In adults receiving an initial metformin hydrochloride dosage of 500 mg twice daily as immediate-release tablets or the immediate-release oral solution, daily dosage may be increased by 500 mg at weekly intervals until the desired fasting blood glucose concentration is achieved or a dosage of 2.55 g daily is reached. In adults receiving an initial dosage of 500 mg of metformin hydrochloride once or twice daily (with breakfast and/or dinner), some experts recommend increasing the dosage to 850 mg or 1 g twice daily after 5-7 days if additional glycemic control is needed and the drug is well tolerated (e.g., no adverse GI effects).
If adverse GI effects appear during dosage titration of metformin hydrochloride, some experts suggest that dosage be decreased to the previous lower dosage, and further dosage increments attempted at a later time. In adults receiving an initial metformin hydrochloride dosage of 850 mg daily as immediate-release tablets or the immediate-release oral solution, daily dosage may be increased by 850 mg every other week (i.e., every 2 weeks) until the desired fasting blood glucose concentration is achieved or a total dosage of 2.55 g daily is reached.
For patients requiring additional glycemic control with metformin hydrochloride, a maximum daily dosage of 2.55 g as immediate-release tablets or the immediate-release oral solution may be used.
In adults (17-18 years of age or older) receiving Glumetza(R) or certain other extended-release metformin hydrochloride preparations, daily dosage may be increased by 500 mg at weekly intervals until the desired glycemic response is achieved or a maximum dosage of 2 g daily is reached. If glycemic control is not achieved with extended-release metformin hydrochloride tablets (e.g., Glumetza(R)) at a dosage of 2 g once daily, a dosage of 1 g twice daily should be considered. If a dosage exceeding 2 g daily is needed in patients receiving certain other extended-release metformin hydrochloride preparations, the manufacturers suggest that therapy be switched to immediate-release metformin hydrochloride tablets and dosage titrated up to a maximum dosage of 2.55
g daily in divided doses. Conversely, therapy with extended-release tablets may be substituted for immediate-release tablets at the same total daily dosage of immediate-release tablets, up to a dosage of 2 g once daily.
With another extended-release metformin hydrochloride preparation (Fortamet(R)), daily dosage may be increased by 500 mg at weekly intervals up to a maximum of 2.5 g once daily with the evening meal. In patients transferring from immediate-release tablets to an extended-release preparation, glycemic control should be closely monitored and dosage adjustments made accordingly.
Dosage in adults generally should not exceed 2.55 g daily when given as metformin hydrochloride immediate-release tablets or immediate-release oral solution, 2.5 g daily when given as certain extended-release tablets (e.g., Fortamet(R)), or 2 g daily when given as certain other extended-release tablet preparations.
Metformin hydrochloride dosages of up to 3 g daily have been associated with modestly greater effectiveness than 1.7 g daily. However, adverse GI effects may limit the maximum dosage that can be tolerated.
(Consult the manufacturer's labeling for product-specific details.) Dosages exceeding 2 g of metformin hydrochloride daily as immediate-release tablets or the immediate-release oral solution may be better tolerated if given in 3 divided doses daily with meals.
Metformin should be used with caution in geriatric patients since aging is associated with reduced renal function, and accumulation of the drug resulting in lactic acidosis may occur in patients with renal impairment. In addition, renal function should be monitored periodically in geriatric patients to determine the appropriate dosage of metformin hydrochloride. Any dosage adjustment in geriatric patients should be based on a careful assessment of renal function.
In children or adolescents 10-16 years of age receiving metformin hydrochloride 500 mg twice daily as immediate-release tablets or the immediate-release oral solution, daily dosage may be increased by 500 mg at weekly intervals until the desired glycemic response is achieved or a maximum dosage of 2 g daily given in 2 divided doses is reached.
Dosage of dapagliflozin propanediol is expressed in terms of dapagliflozin.
Because of the risk of lactic acidosis, which occurs rarely but may be fatal, metformin should not be used in patients with severe renal disease or dysfunction (eGFR less than 30 mL/minute per 1.73 m2) and should be avoided in those with clinical or laboratory evidence of hepatic disease. In patients with moderate renal disease, the benefits and risks of continuing metformin therapy should be assessed. (See Cautions: Lactic Acidosis.)
An FDA review of clinical studies evaluating the safety of metformin in patients with reduced kidney function suggests that metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function.
The manufacturers and FDA state that renal function (eGFR) should be assessed prior to initiation of metformin and at least annually; more frequent monitoring has been recommended in patients with an increased risk of developing renal impairment (e.g., geriatric patients). The manufacturers and FDA state that initiation of metformin therapy is not recommended in patients with an eGFR between 30-45 mL/minute per 1.73 m2 and that the benefits and risks of continuing the drug should be assessed in those already receiving metformin whose eGFR falls below 45 mL/minute per 1.73
m2. The manufacturers and FDA state that metformin is contraindicated in patients with an eGFR of less than 30 mL/minute per 1.73 m2 and that the drug should be discontinued in patients whose eGFR falls below 30 mL/minute per 1.73 m2 who are already receiving metformin.
Metformin hydrochloride is administered orally. In patients receiving metformin hydrochloride immediate-release tablets at a dosage of 2 g or less daily, the drug usually can be given as 2 divided doses daily; however, in patients who require more than 2 g daily, the drug may be better tolerated if administered in 3 divided doses daily. Immediate-release metformin hydrochloride in fixed combination with canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, pioglitazone, alogliptin, linagliptin, or sitagliptin is administered in divided doses daily with meals to reduce the GI effects of the metformin hydrochloride component.
Although food decreases the extent and slightly delays absorption of metformin immediate-release tablets, the manufacturer recommends that the drug be taken with meals to decrease adverse GI effects. Metformin hydrochloride extended-release tablets usually are taken with the evening meal. The manufacturer of Fortamet(R) (metformin hydrochloride extended-release tablets) states that each dose of the drug should be taken with a full glass of water.
The matrix core of some extended-release tablet preparations (e.g., Glumetza(R)) usually is broken up in the GI tract, but patients should be advised that occasionally the biologically inert components of the tablet may remain intact and be passed in the stool as a soft, hydrated mass. Occasionally, Glumetza(R) may be eliminated in the feces as a soft, hydrated mass or an insoluble shell. The membrane coating surrounding the core of another extended-release tablet (Fortamet(R)) remains intact through the GI tract and is excreted in feces as a soft mass that may resemble the original tablet.
(See Chemistry and Stability: Stability.) Extended-release metformin hydrochloride in fixed combination with canagliflozin, dapagliflozin, or empagliflozin is administered once daily with the morning meal. The fixed combination of extended-release metformin hydrochloride and linagliptin should be administered once daily with a meal. The fixed combination of extended-release metformin hydrochloride and sitagliptin should be administered once daily with a meal, preferably with the evening meal.
Extended-release metformin hydrochloride in fixed combination with saxagliptin should be administered once daily with the evening meal. Extended-release metformin hydrochloride tablets and fixed-combination preparations containing the extended-release form of the drug must be swallowed whole and not chewed, cut, or crushed; inactive ingredients occasionally may be eliminated in feces as a soft mass that may resemble the original tablet. Dapagliflozin is administered orally once daily.
Dapagliflozin is commercially available as single-entity tablets that may be administered with or without food. Dapagliflozin is also available in fixed combination with saxagliptin (Qtern(R)) or extended-release metformin hydrochloride (Xigduo(R) XR); the fixed-combination dapagliflozin/saxagliptin tablets should be administered orally once daily in the morning, with or without food, and the fixed combination dapagliflozin/metformin tablets should be administered once daily in the morning with food to reduce the adverse GI effects of the metformin component. See the full prescribing information for additional administration instructions for the combination products.
If a dose of dapagliflozin is missed, the missed dose should be taken as soon as it is remembered followed by resumption of the regular schedule. If the missed dose is not remembered until it is almost time for the next dose, the missed dose should be skipped and the regular schedule resumed; the dose should not be doubled to replace a missed dose. Store dapagliflozin tablets at 20 to 25oC (excursions permitted between 15 and 30oC).
Although food decreases the extent and slightly delays absorption of metformin immediate-release tablets, the manufacturer recommends that the drug be taken with meals to decrease adverse GI effects. Metformin hydrochloride extended-release tablets usually are taken with the evening meal. The manufacturer of Fortamet(R) (metformin hydrochloride extended-release tablets) states that each dose of the drug should be taken with a full glass of water.
The matrix core of some extended-release tablet preparations (e.g., Glumetza(R)) usually is broken up in the GI tract, but patients should be advised that occasionally the biologically inert components of the tablet may remain intact and be passed in the stool as a soft, hydrated mass. Occasionally, Glumetza(R) may be eliminated in the feces as a soft, hydrated mass or an insoluble shell. The membrane coating surrounding the core of another extended-release tablet (Fortamet(R)) remains intact through the GI tract and is excreted in feces as a soft mass that may resemble the original tablet.
(See Chemistry and Stability: Stability.) Extended-release metformin hydrochloride in fixed combination with canagliflozin, dapagliflozin, or empagliflozin is administered once daily with the morning meal. The fixed combination of extended-release metformin hydrochloride and linagliptin should be administered once daily with a meal. The fixed combination of extended-release metformin hydrochloride and sitagliptin should be administered once daily with a meal, preferably with the evening meal.
Extended-release metformin hydrochloride in fixed combination with saxagliptin should be administered once daily with the evening meal. Extended-release metformin hydrochloride tablets and fixed-combination preparations containing the extended-release form of the drug must be swallowed whole and not chewed, cut, or crushed; inactive ingredients occasionally may be eliminated in feces as a soft mass that may resemble the original tablet. Dapagliflozin is administered orally once daily.
Dapagliflozin is commercially available as single-entity tablets that may be administered with or without food. Dapagliflozin is also available in fixed combination with saxagliptin (Qtern(R)) or extended-release metformin hydrochloride (Xigduo(R) XR); the fixed-combination dapagliflozin/saxagliptin tablets should be administered orally once daily in the morning, with or without food, and the fixed combination dapagliflozin/metformin tablets should be administered once daily in the morning with food to reduce the adverse GI effects of the metformin component. See the full prescribing information for additional administration instructions for the combination products.
If a dose of dapagliflozin is missed, the missed dose should be taken as soon as it is remembered followed by resumption of the regular schedule. If the missed dose is not remembered until it is almost time for the next dose, the missed dose should be skipped and the regular schedule resumed; the dose should not be doubled to replace a missed dose. Store dapagliflozin tablets at 20 to 25oC (excursions permitted between 15 and 30oC).
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| DAPAGLIFLOZIN-METFOR ER 5-1000 | Maintenance | Adults take 1 tablet by oral route once daily in the morning with food |
| DAPAGLIFLOZIN-METFO ER 10-1000 | Maintenance | Adults take 1 tablet by oral route once daily in the morning with food |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| DAPAGLIFLOZIN-METFOR ER 5-1000 | Maintenance | Adults take 1 tablet by oral route once daily in the morning with food |
| DAPAGLIFLOZIN-METFO ER 10-1000 | Maintenance | Adults take 1 tablet by oral route once daily in the morning with food |
The following drug interaction information is available for DAPAGLIFLOZIN-METFORMIN ER (dapagliflozin propanediol/metformin hcl):
There are 0 contraindications.
There are 3 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Metformin/Iodinated Contrast Materials SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Use of iodinated contrast materials may result in acute changes in renal function, resulting in a decrease in metformin clearance.(1-3) CLINICAL EFFECTS: Use of iodinated contrast materials may increase levels of metformin, which may result in lactic acidosis.(1-3) PREDISPOSING FACTORS: Pre-existing renal dysfunction may contribute to decreased clearance of metformin. Other factors which may increase the risk for lactic acidosis include age greater than 65 years, dehydration, metabolic acidosis, sepsis, a history of hepatic impairment, alcoholism, or heart failure.(1-4) PATIENT MANAGEMENT: Evaluate renal function prior to contrast procedure. According to manufacturer recommendations, discontinue metformin at the time of, or prior to, the contrast imaging procedure in patients with a history of liver disease, alcoholism, heart failure, or if contrast is to be administered intra-arterially. When contrast is to be administered by other routes, discontinue metformin at the time of, or prior to, the procedure for patients with an estimated glomerular filtration rate (eGFR) of 30 to 60 mL/min/1.73 m2. Re-evaluate eGFR 48 hours after the imaging procedure and restart metformin if renal function is stable. Discontinuation of metformin is not required if eGFR is > 60 mL/min/1.73 m2.(4) According to American College of Radiology guidelines, discontinue metformin at the time of, or prior to, the contrast imaging procedure in patients with acute kidney injury or chronic kidney disease (Stage IV or V or eGFR < 30 mL/min/1.73 m2), or who are undergoing arterial catheter studies that might result in emboli (atheromatous or other) to the renal arteries. Re-evaluate eGFR 48 hours after the imaging procedure and restart metformin if renal function is normal. Discontinuation of metformin is not required in patients with no evidence of acute kidney injury and with eGFR >= 30 mL/min/m2.(5) DISCUSSION: An FDA review of the medical literature showed that metformin may be safely used in patients with mild or moderate renal impairment, resulting in modifications of prescribing recommendations and method for evaluation of renal function.(4) A clinical review of 33 patients on metformin who had received contrast media showed elevations in serum creatinine of the four patients with baseline elevations. The 29 patients with normal baseline renal function showed no elevations after administration of contrast media. The authors recommend that a baseline serum creatinine is obtained for all patients and that metformin should only be discontinued in patients with baseline elevations.(6) A retrospective study of ninety-seven patients currently taking metformin underwent a radiologic procedure with contrast media. Of these patients, 4 developed contrast material associated nephropathy and eight patients had an increased risk of lactic acidosis, with a baseline serum creatinine <1.5mg/dl.(7) A prospective clinical trial with 50 diabetic patients on metformin with baseline serum creatinine <1.47mg/dl showed no statistical difference in renal function before and 48 hours after administration of contrast media. The authors recommend a baseline serum creatinine for all patients and suggest that temporary discontinuation of metformin may not be necessary when baseline renal function is <1.47mg/dl.(8) A systematic review of the literature reveals that 17 of 18 case reports of metformin-induced lactic acidosis involved patients with renal dysfunction prior to administration of contrast media. The authors recommend a baseline serum creatinine in all patients and if renal dysfunction is present, metformin should be discontinued for 48 hours before and after administration of contrast media. The authors recommend follow-up creatinine measurement in patients with prior renal impairment or known comorbidities affecting lactate levels.(9) |
CONRAY, CONRAY-30, CONRAY-43, CYSTO-CONRAY II, CYSTOGRAFIN, CYSTOGRAFIN-DILUTE, IODIXANOL, IODOQUINOL, IOHEXOL, IOMERON 350, IOPAMIDOL, IOPANOIC ACID, ISOVUE-200, ISOVUE-250, ISOVUE-300, ISOVUE-370, ISOVUE-M 200, ISOVUE-M 300, LIPIODOL, OMNIPAQUE, OPTIRAY 240, OPTIRAY 300, OPTIRAY 320, OPTIRAY 350, SINOGRAFIN, ULTRAVIST, VISIPAQUE |
| Antidiabetic Agents/Gatifloxacin SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. CLINICAL EFFECTS: Concurrent use of gatifloxacin may result in hypoglycemia and/or hyperglycemia.(1-4) Hypoglycemia is more common during the first three days of concurrent therapy. Hyperglycemia is more common after the first three days of concurrent therapy.(2) PREDISPOSING FACTORS: Elderly patients, especially those with decreased renal function may be predisposed to this interaction.(2) PATIENT MANAGEMENT: Patients receiving concurrent gatifloxacin should be closely monitored for hypoglycemia during the first three days of concurrent therapy and for hyperglycemia after the first three days of concurrent therapy. Patients should be instructed to discontinue gatifloxacin if hypoglycemia or hyperglycemia occur.(2) DISCUSSION: Hypoglycemia has been reported with gatifloxacin and glyburide(1,5,6) or glimepiride.(7) In a study in patients with type 2 diabetes mellitus, concurrent gatifloxacin (400 mg daily for 10 days) had no effect on the pharmacokinetics of glyburide (steady state daily regimen); however, pharmacodynamic interactions have been reported.(2) Health Canada has received 19 reports of hypoglycemia in patients taking gatifloxacin. Seventeen of these involved concurrent hypoglycemic agents. Health Canada has received 2 reports of hyperglycemia in patients taking gatifloxacin and hypoglycemic agents. Health Canada has received 2 reports of patients experiencing hypoglycemia and hyperglycemia during concurrent gatifloxacin and hypoglycemic agents.(3) In a study, 13 reports of dysglycemia were reported in patients taking gatifloxacin. Ten of these patients had diabetes mellitus and were on concurrent hypoglycemic agents. Of these ten patients, nine patients experienced hypoglycemia, while one patient experienced hyperglycemia.(8) |
GATIFLOXACIN SESQUIHYDRATE |
| Metformin/Tafenoquine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Metformin renal clearance is mediated by OCT2 and MATE1 transporters.(1) Tafenoquine inhibits elimination by these pathways.(2) CLINICAL EFFECTS: Use of tafenoquine may increase levels of metformin, which may result in lactic acidosis. PREDISPOSING FACTORS: Risk factors for metformin associated lactic acidosis include renal impairment, sepsis, dehydration, excessive alcohol intake, acute or chronic metabolic acidosis, hepatic insufficiency, acute heart failure, metformin plasma levels > 5 micrograms/mL, and conditions which may lead to tissue hypoxia. Geriatric patients may also be at higher risk due to slower metformin clearance and increased half-life in this population. PATIENT MANAGEMENT: The US labeling for metformin recommends the dose of metformin be adjusted as needed.(1) The manufacturer of tafenoquine states the concurrent administration of tafenoquine with OCT2 and MATE1 substrates, such as metformin, should be avoided. If coadministration cannot be avoided, monitor for drug-related toxicities.(2) Evaluate patient's renal function and consider discontinuation in patients with renal impairment. Monitor for signs and symptoms of metformin toxicity (lactic acidosis) such as malaise, myalgias, respiratory distress, increasing somnolence, and respiratory distress. Laboratory results which may signal lactic acidosis include: elevated blood lactate levels (greater than 5 mmol/L), low pH, an increased anion gap, and increased lactate to pyruvate ratio. DISCUSSION: Metformin renal clearance is mediated by OCT2 and MATE1 transporters.(1) Tafenoquine is believed to inhibit the OCT2 and MATE1 pathways.(2) |
ARAKODA, KRINTAFEL |
There are 13 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Metformin/MATE Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Inhibitors of the Multidrug and Toxin Extrusion (MATE) protein transporters in the kidneys may interfere with the renal tubular secretion of metformin.(1) CLINICAL EFFECTS: Concurrent use may result in increased plasma levels of metformin and toxicity such as lactic acidosis. Untreated lactic acidosis may be fatal. Symptoms of lactic acidosis include malaise, myalgias, respiratory distress, low pH, increased anion gap and elevated blood lactate. PREDISPOSING FACTORS: Risk factors for metformin associated lactic acidosis include renal impairment,sepsis, dehydration, excessive alcohol intake, acute or chronic metabolic acidosis, hepatic insufficiency, acute heart failure, metformin plasma levels > 5 micrograms/mL, and conditions which may lead to tissue hypoxia. Geriatric patients may also be at higher risk due to slower metformin clearance and increased half-life in this population. The risk for metabolic acidosis is higher with increased doses of either agent. PATIENT MANAGEMENT: Use an alternative agent if possible. If both drugs are given, monitor patient's renal function and for signs and symptoms of metformin toxicity (lactic acidosis) such as malaise, myalgias, respiratory distress, increasing somnolence, and respiratory distress. Laboratory results which may signal lactic acidosis include: low pH, an increased anion gap, and increased lactate to pyruvate ratio. Dosage of either agent may need to be adjusted.(1) DISCUSSION: In a study of normal healthy volunteers, concurrent metformin and oral cimetidine increased metformin maximum concentration (Cmax) in plasma and whole blood by 60% and increased metformin area-under-curve (AUC) levels in plasma and whole blood by 40%.(1) In a study in 7 subjects, concurrent metformin (250 mg daily) with cimetidine (400 mg twice daily) increased metformin AUC by 50%. Metformin renal clearance over 24 hours was reduced by 27%.(2) MATE inhibitors include: cimetidine, pyrimethamine, and risdiplam.(3) |
CIMETIDINE, DARAPRIM, EVRYSDI, PYRIMETHAMINE |
| Metformin/Cephalexin SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Cephalexin may inhibit the renal tubular secretion of metformin.(1,2) CLINICAL EFFECTS: Concurrent use of cephalexin may result in increased levels and clinical effects of metformin,(1,2) as well as an increased risk of lactic acidosis. PREDISPOSING FACTORS: Risk factors for metformin associated lactic acidosis include renal impairment, sepsis, dehydration, excessive alcohol intake, acute or chronic metabolic acidosis, hepatic insufficiency, acute heart failure, metformin plasma levels > 5 micrograms/mL, and conditions which may lead to tissue hypoxia. Geriatric patients may also be at higher risk due to slower metformin clearance and increased half-life in this population. PATIENT MANAGEMENT: Patients maintained on metformin should be closely monitored when cephalexin is initiated and discontinued. The dosage of metformin may need to be adjusted.(1) DISCUSSION: In a randomized, cross-over study in 12 healthy subjects, concurrent metformin (500 mg) and cephalexin (500 mg) increased the maximum concentration (Cmax) and area-under-curve (AUC) of metformin by 34% and 24%, respectively. Metformin renal clearance decreased by 14%.(1,2) |
CEPHALEXIN |
| Metformin/Ranolazine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ranolazine may decrease renal elimination of metformin by inhibiting OCT-2.(1) CLINICAL EFFECTS: Concurrent ranolazine may result in elevated levels of and toxicity from metformin.(1) PREDISPOSING FACTORS: Risk factors for metformin associated lactic acidosis include renal impairment, sepsis, dehydration, excessive alcohol intake, acute or chronic metabolic acidosis, hepatic insufficiency, acute heart failure, metformin plasma levels > 5 micrograms/mL, and conditions which may lead to tissue hypoxia. Geriatric patients may also be at higher risk due to slower metformin clearance and increased half-life in this population. PATIENT MANAGEMENT: Monitor patients receiving concurrent therapy with metformin and ranolazine. In patients receiving 1000 mg ranolazine twice daily, limit the dose of metformin to 1700 mg daily.(1) DISCUSSION: In healthy subjects, ranolazine (1000 mg twice daily) increased exposure of metformin by 80%. Ranolazine (500 mg BID) increased metformin exposure by 40%.(1) |
ASPRUZYO SPRINKLE, RANOLAZINE ER |
| SGLT2 Inhibitors/Loop Diuretics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: SGLT2 inhibitors cause intravascular volume contraction through osmotic diuresis, which can result in hypotension in patients who are volume depleted from loop diuretic use.(1-7) CLINICAL EFFECTS: Concurrent use of SGLT2 inhibitors with loop diuretics may result in dehydration, hypotension, and acute renal failure.(1-8) PREDISPOSING FACTORS: This interaction may be more severe in patients who have a eGFR of less than 60 ml/min/1.73m2, are also taking ACE inhibitors or ARBs and/or NSAIDs, are on a low sodium diet, have low systolic blood pressure prior to initiating SGLT2 inhibitors, and/or are 65 years of age or older.(1-7) PATIENT MANAGEMENT: Before initiating SGLT2 inhibitors in patients maintained on loop diuretics, assess volume status and correct if needed and also assess renal function. Patients receiving concurrent therapy should be monitored for hypotension and acute renal failure.(1-8) DISCUSSION: In clinical trials of canagliflozin, volume depletion-related adverse effects were associated with the use of loop diuretics, moderate renal impairment (eGFR 30 ml/min/1.73m2 to less than 60 ml/min/1.73m2), and age 75 years and older. In a pool of eight Phase 3 clinical trials, 2.3% of all patients taking 100 mg of canagliflozin experienced at least one volume depletion-related event, compared to 3.2% of patients taking 100 mg of canagliflozin with a loop diuretic. 3.4% of all patients taking 300 mg of canagliflozin experienced at least one volume depletion-related event, compared to 8.8% of patients taking 300 mg of canagliflozin with a loop diuretic.(1,2) Cases of acute renal failure, most requiring hospitalization, have been reported in patients receiving canagliflozin and dapagliflozin. Twenty-six of 101 cases involved concurrent use of diuretics.(7) In a post-hoc analysis of the EMPEROR-Preserve trial, the combination of empagliflozin and diuretics was associated with a higher incidence of volume depletion events (HR 1.34; 95% CI, 1.13-1.59). The most commonly reported events were hypotension, syncope, and dehydration. Coadministration of diuretics and empagliflozin did not result in a difference in the incidence of acute renal failure, hyperkalemia, or adverse events leading to trial discontinuation (including fatal events) compared to empagliflozin alone. There was also no change in the benefit of empagliflozin for the primary end point of first hospitalization for heart failure or cardiovascular death.(8) |
BUMETANIDE, EDECRIN, ETHACRYNATE SODIUM, ETHACRYNIC ACID, FUROSCIX, FUROSEMIDE, FUROSEMIDE-0.9% NACL, LASIX, SOAANZ, TORSEMIDE |
| Metformin/Carbonic Anhydrase Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Carbonic anhydrase inhibitors increase bicarbonate excretion which may cause metabolic acidosis.(1) High systemic concentrations of metformin may result in lactic acidosis.(2,3) Topiramate, a mild carbonic anhydrase inhibitor, may also increase systemic exposure to metformin.(1) CLINICAL EFFECTS: Carbonic anhydrase inhibitors may increase the risk for metformin associated lactic acidosis.(1-3) Untreated lactic acidosis may be fatal. Symptoms of lactic acidosis include malaise, myalgias, respiratory distress, low blood pH, increased anion gap and elevated blood lactate.(2) Carbonic anhydrase inhibitors linked to this monograph are acetazolamide, dichlorphenamide, methazolamide, sulthiame, topiramate, and zonisamide. PREDISPOSING FACTORS: Risk factors for metformin associated lactic acidosis include renal impairment,sepsis, dehydration, excessive alcohol intake, acute or chronic metabolic acidosis, hepatic insufficiency, acute heart failure, metformin plasma levels > 5 micrograms/mL, and conditions which may lead to tissue hypoxia. Geriatric patients may also be at higher risk due to slower metformin clearance and increased half-life in this population. The risk for metabolic acidosis is higher with increased doses of either agent. PATIENT MANAGEMENT: For patients receiving concurrent therapy, monitor renal function and assure that patient does not have risk factors for metformin associated lactic acidosis. Discontinue metformin when risk factors are present. If both drugs are given, monitor renal function and for signs and symptoms of metformin toxicity (lactic acidosis) such as malaise, myalgias, respiratory distress, increasing somnolence, and respiratory distress. Laboratory results which may signal lactic acidosis include: low pH, an increased anion gap, and increased lactate to pyruvate ratio. Manufacturer recommendations: the manufacturer of metformin recommends caution with concomitant use of carbonic anhydrase inhibitors due to an increased risk for metformin associated lactic acidosis.(2) The manufacturer of topiramate notes that topiramate can frequently cause metabolic acidosis and that metformin should not be used in patients with metabolic acidosis.(1) DISCUSSION: A literature search for lactic acidosis due solely to the combination of metformin and carbonic anhydrase inhibitors or topiramate did not reveal any case reports of symptomatic metabolic acidosis due to this combination. Never-the-less, since carbonic anhydrase inhibitors act by inhibiting the reabsorption of bicarbonate in the renal tubule, some lowering of systemic bicarbonate and pH is common and supports the plausibility of this interaction. In addition, a pharmacokinetic interaction has been described with topiramate. A study in healthy volunteers evaluated the effect of topiramate 100 mg every 12 hours on the kinetics of metformin 500 mg every 12 hours. Mean metformin exposure (area-under-curve or AUC) was increased 25%.(1) |
ACETAZOLAMIDE, ACETAZOLAMIDE ER, ACETAZOLAMIDE SODIUM, DICHLORPHENAMIDE, EPRONTIA, KEVEYIS, METHAZOLAMIDE, ORMALVI, QSYMIA, TOPAMAX, TOPIRAMATE, TOPIRAMATE ER, TOPIRAMATE ER SPRINKLE, TROKENDI XR, ZONEGRAN, ZONISADE, ZONISAMIDE |
| Metformin/Dolutegravir SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Dolutegravir may inhibit the renal organic cation transporter, OCT2, responsible for the elimination of metformin.(1) CLINICAL EFFECTS: Concurrent use may result in increased plasma levels of metformin and toxicity such as lactic acidosis. Untreated lactic acidosis may be fatal. Symptoms of lactic acidosis include malaise, myalgias, respiratory distress, low pH, increased anion gap and elevated blood lactate. PREDISPOSING FACTORS: Risk factors for metformin associated lactic acidosis include renal impairment,sepsis, dehydration, excessive alcohol intake, acute or chronic metabolic acidosis, hepatic insufficiency, acute heart failure, metformin plasma levels > 5 micrograms/mL, and conditions which may lead to tissue hypoxia. Geriatric patients may also be at higher risk due to slower metformin clearance and increased half-life in this population. PATIENT MANAGEMENT: With concomitant use, assess the benefit and risk of metformin in patients on dolutegravir. When starting or stopping dolutegravir, the metformin dose may require an adjustment. Monitor blood glucose when initiating concomitant use and after stopping dolutegravir.(1) Monitor patient's renal function and for signs and symptoms of metformin toxicity (lactic acidosis) such as malaise, myalgias, respiratory distress, increasing somnolence, and respiratory distress. Laboratory results which may signal lactic acidosis include: low pH, an increased anion gap, and increased lactate to pyruvate ratio.(1) DISCUSSION: Dolutegravir has been shown to inhibit OCT2 in vitro and in vivo and is expected to inhibit the excretion of metformin.(1) In a study in 15 subjects, concomitant metformin (500 mg twice daily) with dolutegravir (50 mg daily) increased the concentration maximum (Cmax) and area-under-curve (AUC) of metformin by 66% and 79%, respectively. In a study in 15 subjects, concomitant metformin (500 mg twice daily) with dolutegravir (50 mg twice daily) increased the Cmax and AUC of metformin by 111% and 145%, respectively.(1) |
DOVATO, JULUCA, TIVICAY, TIVICAY PD, TRIUMEQ, TRIUMEQ PD |
| Metformin/Trimethoprim SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Metformin renal clearance is mediated by OCT2 and MATE1 transport. Trimethoprim inhibits elimination by these pathways. CLINICAL EFFECTS: Use of trimethoprim may increase levels of metformin, which may result in lactic acidosis. PREDISPOSING FACTORS: Risk factors for metformin associated lactic acidosis include renal impairment,sepsis, dehydration, excessive alcohol intake, acute or chronic metabolic acidosis, hepatic insufficiency, acute heart failure, metformin plasma levels > 5 micrograms/mL, and conditions which may lead to tissue hypoxia. Geriatric patients may also be at higher risk due to slower metformin clearance and increased half-life in this population. PATIENT MANAGEMENT: The US labeling for metformin recommends the dose of metformin and/or trimethoprim be adjusted as needed. Consider the benefits and risks of concomitant use.(1) Evaluate patient's renal function and consider discontinuation of one or both agents in patients with renal impairment. Monitor for signs and symptoms of metformin toxicity (lactic acidosis) such as malaise, myalgias, respiratory distress, increasing somnolence, and respiratory distress. Laboratory results which may signal lactic acidosis include: elevated blood lactate levels (greater than 5 mmol/L), low pH, an increased anion gap, and increased lactate to pyruvate ratio. DISCUSSION: Trimethoprim was found to cause significant inhibition of net transcellular chloroquine transport in canine kidney-OCT2-MATE1 cells. Chloroquine is eliminated by renal tubular secretion involving multidrug and toxin extrusion protein 1 (MATE1). Trimethoprim caused concentration-dependent inhibition of net metformin intake in HEK293-MATE1 cells (human embryonic kidney). (2) A randomized, open-label, two-phase crossover study found that trimethoprim inhibited OCT2, MATE1, and MATE2-K-dependent transport of metformin. Trimethoprim increased metformin area under the curve (AUC) by 29.4% and decreased metformin renal clearance by 26.4%. (3) 24 healthy volunteers received metformin 500 mg three times daily for ten days and trimethoprim 200 mg twice daily from days 5-10. Trimethoprim significantly reduced the apparent systemic metformin clearance (CL/F) from 74 to 54 l/h and renal metformin clearance from 31 to 21 l/h. Metformin half-life was prolonged from 2.7 to 3.6h. The metformin plasma concentration (Cmax) increased 38% and the AUC by 37%. Trimethoprim was also associated with a decrease in creatinine clearance and an increase in plasma lactate. (4) |
BACTRIM, BACTRIM DS, PRIMSOL, SULFAMETHOXAZOLE-TRIMETHOPRIM, SULFATRIM, TRIMETHOPRIM, TRIMETHOPRIM MICRONIZED |
| Metformin/Vandetanib SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Renal tubular secretion of metformin is mediated by organic cation transporter 2 (OCT2) and the multidrug and toxin extrusion protein (MATE) transporter. Vandetanib inhibits elimination by the OCT2 and MATE pathways.(1) CLINICAL EFFECTS: Use of vandetanib may increase levels of metformin. Concurrent use may result in increased plasma levels of metformin and toxicity such as lactic acidosis. Untreated lactic acidosis may be fatal. Symptoms of lactic acidosis include malaise, myalgias, respiratory distress, low pH, increased anion gap and elevated blood lactate.(1) PREDISPOSING FACTORS: Risk factors for metformin associated lactic acidosis include renal impairment, sepsis, dehydration, excessive alcohol intake, acute or chronic metabolic acidosis, hepatic insufficiency, acute heart failure, metformin plasma levels > 5 micrograms/mL, and conditions which may lead to tissue hypoxia. Geriatric patients may also be at higher risk due to slower metformin clearance and increased half-life in this population. The risk for metabolic acidosis is higher with increased doses of either agent. PATIENT MANAGEMENT: Use an alternative agent if possible. The US labeling for vandetanib recommends caution with concomitant use of metformin and close monitoring for metformin toxicity.(1) Evaluate patient's renal function and consider discontinuation of one or both agents in patients with renal impairment. Monitor for signs and symptoms of metformin toxicity (lactic acidosis) such as malaise, myalgias, respiratory distress, increasing somnolence, and respiratory distress. Laboratory results which may signal lactic acidosis include: elevated blood lactate levels (greater than 5 mmol/L), low pH, an increased anion gap, and increased lactate to pyruvate ratio. DISCUSSION: A study in 13 healthy subjects receiving a single 1,000 mg dose of metformin 3 hours after a single 800 mg dose of vandetanib resulted in increases in metformin area-under-curve (AUC) of 74% and maximum concentration (Cmax) of 50% with coadministration compared to metformin alone.(1) In a study of normal healthy volunteers, concurrent metformin and oral cimetidine (MATE inhibitor) increased metformin maximum concentration (Cmax) in plasma and whole blood by 60% and increased metformin area-under-curve (AUC) levels in plasma and whole blood by 40%.(1) In a study in 7 subjects, concurrent metformin (250 mg daily) with cimetidine (400 mg twice daily) increased metformin AUC by 50%. Metformin renal clearance over 24 hours was reduced by 27%.(2) |
CAPRELSA |
| Patiromer/Metformin SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Patiromer may bind to metformin.(1) CLINICAL EFFECTS: Concurrent use may result in decreased gastrointestinal absorption and loss of efficacy of metformin.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of patiromer recommends that you administer patiromer at least 3 hours before or 3 hours after metformin.(1) DISCUSSION: A study in healthy volunteers showed that patiromer decreased the systemic exposure of coadministered metformin. No interaction was seen when these drugs were taken 3 hours apart.(1) |
VELTASSA |
| Metformin/Bictegravir SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Metformin renal clearance is mediated by OCT2 and MATE1 transport. Bictegravir inhibits elimination by these pathways.(1,2) CLINICAL EFFECTS: Use of bictegravir may increase levels of metformin, which may result in lactic acidosis. PREDISPOSING FACTORS: Risk factors for metformin associated lactic acidosis include renal impairment,sepsis, dehydration, excessive alcohol intake, acute or chronic metabolic acidosis, hepatic insufficiency, acute heart failure, metformin plasma levels > 5 micrograms/mL, and conditions which may lead to tissue hypoxia. Geriatric patients may also be at higher risk due to slower metformin clearance and increased half-life in this population. PATIENT MANAGEMENT: The US labeling for metformin recommends the dose of metformin be adjusted as needed.(1) Evaluate patient's renal function and consider discontinuation of one or both agents in patients with renal impairment. Monitor for signs and symptoms of metformin toxicity (lactic acidosis) such as malaise, myalgias, increasing somnolence, and respiratory distress. Laboratory results which may signal lactic acidosis include: elevated blood lactate levels (greater than 5 mmol/L), low pH, an increased anion gap, and increased lactate to pyruvate ratio. DISCUSSION: Bictegravir is an inhibitor of OCT2 and MATE1.(2) Trimethoprim, an inhibitor of OCT2 and MATE1, was found to cause significant inhibition of net transcellular chloroquine transport in canine kidney-OCT2-MATE1 cells. Chloroquine is eliminated by renal tubular secretion involving multidrug and toxin extrusion protein 1 (MATE1). Trimethoprim caused concentration-dependent inhibition of net metformin intake in HEK293-MATE1 cells (human embryonic kidney).(3) A randomized, open-label, two-phase crossover study found that trimethoprim inhibited OCT2, MATE1, and MATE2-K-dependent transport of metformin. Trimethoprim increased metformin area-under-curve (AUC) by 29.4% and decreased metformin renal clearance by 26.4%.(4) In a study in 24 healthy volunteers received metformin 500 mg three times daily for ten days and trimethoprim 200 mg twice daily from days 5-10. Trimethoprim significantly reduced the apparent systemic metformin clearance (CL/F) from 74 to 54 l/h and renal metformin clearance from 31 to 21 l/h. Metformin half-life was prolonged from 2.7 to 3.6h. The metformin plasma concentration (Cmax) increased 38% and the AUC by 37%. Trimethoprim was also associated with a decrease in creatinine clearance and an increase in plasma lactate. (5) |
BIKTARVY |
| Selected Antidiabetic Agents/Chloroquine; Hydroxychloroquine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown. Chloroquine and hydroxychloroquine may increase insulin sensitivity by inhibiting insulin metabolism and inflammation and increasing cellular uptake of glucose and glycogen synthesis.(1,2) These effects may result in additive hypoglycemia with anti-diabetic agents. CLINICAL EFFECTS: Concurrent use of chloroquine or hydroxychloroquine and antidiabetic agents may result in severe hypoglycemia.(3) Hypoglycemia can lead to coma. PREDISPOSING FACTORS: Elderly patients, especially those with decreased renal function may be predisposed to this interaction. PATIENT MANAGEMENT: Patients maintained on antidiabetic agents who require concurrent therapy with chloroquine or hydroxychloroquine should be closely monitored for hypoglycemia. A decrease in the dose of insulin or other anti-diabetic medications may be required. Patients should be advised of the risk and symptoms of hypoglycemia and to contact their doctor if hypoglycemia occurs.(3) Signs of hypoglycemia may include confusion, dizziness, feeling shaky, unusual hunger, headaches, irritability, pounding heart or very fast pulse, pale skin, sweating, trembling, weakness, or unusual anxiety. DISCUSSION: Hydroxychloroquine has been shown to cause severe hypoglycemia including loss of consciousness that could be life threatening.(3) Concomitant hypoglycemic agents may increase the risk and/or severity of this effect. A 77 year old man who was stable on twice daily insulin suffered two episodes of hypoglycemic coma 2 weeks after starting prednisone 5 mg daily and hydroxychloroquine 400 mg daily for rheumatoid arthritis. His insulin dosage required a decrease of 37%.(4) Many studies have investigated the glucose-lowering effect of hydroxychloroquine. In a clinical trial of type II diabetics on maximal doses of sulfonylureas, addition of hydroxychloroquine lowered hemoglobin A1C (HbA1C) up to 1% more than placebo.(5) Another clinical trial of type II diabetics on metformin and glimepiride or gliclazide found that hydroxychloroquine 400 mg daily reduced fasting blood glucose (FBG), post-prandial glucose (PPG), and HbA1C to a similar degree as pioglitazone 15 mg daily at 24 weeks.(6) In a prospective observational study, 250 uncontrolled type II diabetics on metformin, glimepiride, pioglitazone, sitagliptin, and a SGLT-2 inhibitor received hydroxychloroquine 400 mg daily for 48 weeks. HbA1C decreased from 8.83% to 6.44%, FBG decreased by 40.78%, and PPG decreased by 58.95%. The doses of metformin were reduced by 50%, glimepiride and sitagliptin by 75%, and SGLT-2 inhibitors were discontinued in most patients.(7) |
CHLOROQUINE PHOSPHATE, HYDROXYCHLOROQUINE SULFATE, PLAQUENIL, SOVUNA |
| Lithium/Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors may increase the renal excretion of lithium by impairing the proximal tubular reabsorption of lithium.(1,2) CLINICAL EFFECTS: Concurrent use of SGLT2 inhibitors may result in decreased levels and clinical effectiveness of lithium.(1-6) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Lithium levels should be monitored more frequently when starting or changing the dose of SGLT2 inhibitors. The dose of lithium may need to be adjusted.(3-6) DISCUSSION: A 29 year old patient stabilized on lithium with good therapeutic response was started on empagliflozin on day 10 of lithium therapy. Three days later, lithium level was subtherapeutic. Empagliflozin was stopped. After 1 week, lithium levels returned to therapeutic range. Two days later, the patient had another trial of empagliflozin and again developed subtherapeutic lithium levels.(1) A post hoc analysis of 2 dapagliflozin trials (IMPROVE and DapKid) examined the effects of dapagliflozin on volume status in diabetic patients with albuminuric kidney disease. Lithium excretion, which served as a marker of proximal tubular sodium excretion, was found to increase by 19.6% (p < 0.01).(2) |
LITHIUM CARBONATE, LITHIUM CARBONATE ER, LITHIUM CITRATE, LITHIUM CITRATE TETRAHYDRATE, LITHOBID |
| Metformin/OCT2 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Agents that inhibit the organic cation transporter 2 (OCT2) may inhibit the excretion of metformin by OCT2 in the kidneys.(1) CLINICAL EFFECTS: Concurrent use of OCT2 renal transport inhibitors may result in increased levels of and toxicity from metformin.(1) PREDISPOSING FACTORS: Risk factors for metformin associated lactic acidosis include renal impairment, sepsis, dehydration, excessive alcohol intake, acute or chronic metabolic acidosis, hepatic insufficiency, acute heart failure, metformin plasma levels higher than 5 micrograms/mL, and conditions which may lead to tissue hypoxia. Geriatric patients may also be at higher risk due to slower metformin clearance and increased half-life in this population. PATIENT MANAGEMENT: Consider the potential benefits against the risks of concurrent use of metformin with OCT2 renal transport inhibitors. If concurrent use is appropriate, monitor for toxicities of metformin and consider dosage reduction of metformin.(1) DISCUSSION: In a study, givinostat increased the levels of creatinine (OCT2 substrate) by 4.76 umol/L from baseline.(1) OCT2 inhibitors linked to this monograph include: arimoclomol, givinostat, trilaciclib, and vimseltinib.(2) |
DUVYZAT, MIPLYFFA, ROMVIMZA |
The following contraindication information is available for DAPAGLIFLOZIN-METFORMIN ER (dapagliflozin propanediol/metformin hcl):
Drug contraindication overview.
*History of serious hypersensitivity reaction to dapagliflozin or any ingredient in the formulation. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported in patients receiving the drug.
*History of serious hypersensitivity reaction to dapagliflozin or any ingredient in the formulation. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported in patients receiving the drug.
There are 8 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Alcohol intoxication |
| Alcohol use disorder |
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Dehydration |
| Metabolic acidosis |
| Sepsis |
| Shock |
There are 15 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Acute decompensated heart failure |
| Acute myocardial infarction |
| Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min |
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Disease of liver |
| Hypoglycemic disorder |
| Hypovolemia |
| Invasive surgical procedure |
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
| Necrotizing fasciitis of perineum or genital area |
| Pregnancy |
| Severe diarrhea |
| Severe hypoxemia |
| Severe vomiting |
There are 5 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Debilitation |
| Fever |
| Hypothyroidism |
| Infection |
| Vitamin b12 deficiency |
The following adverse reaction information is available for DAPAGLIFLOZIN-METFORMIN ER (dapagliflozin propanediol/metformin hcl):
Adverse reaction overview.
The most common adverse effects of dapagliflozin monotherapy (>=5% of patients) reported in clinical studies include female genital mycotic infections, nasopharyngitis, and urinary tract infections. The most common adverse effects of dapagliflozin in combination with extended-release metformin hydrochloride (>5% of patients) reported in clinical trials include female genital mycotic infections, nasopharyngitis, urinary tract infection, diarrhea, and headache. The most common adverse effects of dapagliflozin in combination with saxagliptin (>=5% of patients) reported in clinical trials include upper respiratory tract infection, urinary tract infection, and dyslipidemia.
The most common adverse effects of dapagliflozin monotherapy (>=5% of patients) reported in clinical studies include female genital mycotic infections, nasopharyngitis, and urinary tract infections. The most common adverse effects of dapagliflozin in combination with extended-release metformin hydrochloride (>5% of patients) reported in clinical trials include female genital mycotic infections, nasopharyngitis, urinary tract infection, diarrhea, and headache. The most common adverse effects of dapagliflozin in combination with saxagliptin (>=5% of patients) reported in clinical trials include upper respiratory tract infection, urinary tract infection, and dyslipidemia.
There are 27 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Urinary tract infection |
Dehydration Dyspnea Hypotension |
| Rare/Very Rare |
|---|
|
Abnormal hepatic function tests Acquired phimosis Acute kidney injury Acute respiratory distress syndrome Angioedema Autoimmune hemolytic anemia Autoimmune hepatitis Bacterial sepsis Cholestatic hepatitis Diabetic ketoacidosis Fracture Hepatocellular damage Hypersensitivity drug reaction Hypoglycemic disorder Ketoacidosis Lactic acidosis Malignant tumor of urinary bladder Megaloblastic anemia Metabolic acidosis Necrotizing fasciitis of perineum or genital area Pancreatitis Pyelonephritis Urosepsis |
There are 44 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Abdominal distension Diarrhea Dysgeusia Flatulence Headache disorder Nausea Pharyngitis Upper respiratory infection Vitamin b12 deficiency Vomiting Vulvovaginal candidiasis Weight loss |
Acute abdominal pain Back pain Candidal balanitis Chills Constipation Dizziness Dyspepsia Dysuria Flu-like symptoms Flushing General weakness Genital organ pruritus Genitourinary tract infections Hypercholesterolemia Hyperhidrosis Hyperphosphatemia Hypoglycemic disorder Hypovolemia Increased hemoglobin Increased urinary frequency Influenza Myalgia Nail disorders Nausea Orthostatic hypotension Palpitations Rhinitis |
| Rare/Very Rare |
|---|
|
Anticholinergic toxicity Drowsy Pruritus of skin Skin rash Urticaria |
The following precautions are available for DAPAGLIFLOZIN-METFORMIN ER (dapagliflozin propanediol/metformin hcl):
The safety and effectiveness of dapagliflozin as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus have been established in pediatric patients 10 years of age and older. Use of dapagliflozin for this indication is supported by a 26-week, placebo-controlled trial with a 26-week extension in 157 pediatric patients 10 to 17 years of age with type 2 diabetes mellitus, pediatric pharmacokinetic data, and trials in adults with type 2 diabetes mellitus. The safety profile observed in the placebo-controlled trial in pediatric patients with type 2 diabetes mellitus was similar to that observed in adults.
Safety and efficacy of dapagliflozin have not been established in pediatric patients younger than 10 years of age for glycemic control in type 2 diabetes mellitus. Safety and efficacy of dapagliflozin have not been established in pediatric patients for other indications.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Safety and efficacy of dapagliflozin have not been established in pediatric patients younger than 10 years of age for glycemic control in type 2 diabetes mellitus. Safety and efficacy of dapagliflozin have not been established in pediatric patients for other indications.
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Reproduction studies in rats and rabbits given metformin hydrochloride There is insufficient evidence with dapagliflozin in pregnant women to dosages of 600 mg/kg daily (about twice the maximum recommended human daily evaluate a drug-associated risk of major birth defects or miscarriage. Based on the results of reproductive and developmental toxicity studies in dosage based on body surface area or about 3 and 6 times the maximum animals, dapagliflozin use during pregnancy may affect renal development recommended human daily dosage of extended-release tablets (2 g) based on and maturation. Adverse renal pelvic and tubule dilatations that were not body surface area comparisons with rats and rabbits, respectively) have not fully reversible were observed in rats when dapagliflozin was administered revealed evidence of harm (e.g., teratogenicity) to the fetus. Determination of fetal concentrations of metformin suggest that a partial during a period of renal development corresponding to the late second and placental barrier to the drug exists.
Since abnormal maternal blood glucose third trimesters of human pregnancy at all doses tested, the lowest of concentrations during pregnancy may be associated with a higher incidence which provided an exposure 15 times the 10-mg clinical dosage. of congenital abnormalities, most experts recommend that insulin be used during pregnancy to maintain optimum control of blood glucose Poorly controlled diabetes mellitus and untreated heart failure also are associated with risks to the mother and fetus, including DKA, preeclampsia, concentration. spontaneous abortions, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia-related morbidity.
The The estimated background risk of major birth defects is 6-10% in women with manufacturer states that dapagliflozin therapy is not recommended in pre-gestational diabetes mellitus who have an HbA1c exceeding 7 and has been reported to be as high as 20-25% in women with a HbA1c exceeding 10. pregnant women during the second and third trimesters of pregnancy. The estimated background risk of miscarriage for the indicated population is unknown.
In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Available studies on the use of metformin in pregnant women have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes. Limited data from uncontrolled or retrospective studies are conflicting with regard to the effects of long-term maternal therapy with metformin hydrochloride (1.5-3 g daily) on neonatal morbidity (e.g., congenital malformations) and mortality.
Poorly controlled diabetes mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Metformin should be used during pregnancy only when clearly needed.
Since abnormal maternal blood glucose third trimesters of human pregnancy at all doses tested, the lowest of concentrations during pregnancy may be associated with a higher incidence which provided an exposure 15 times the 10-mg clinical dosage. of congenital abnormalities, most experts recommend that insulin be used during pregnancy to maintain optimum control of blood glucose Poorly controlled diabetes mellitus and untreated heart failure also are associated with risks to the mother and fetus, including DKA, preeclampsia, concentration. spontaneous abortions, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia-related morbidity.
The The estimated background risk of major birth defects is 6-10% in women with manufacturer states that dapagliflozin therapy is not recommended in pre-gestational diabetes mellitus who have an HbA1c exceeding 7 and has been reported to be as high as 20-25% in women with a HbA1c exceeding 10. pregnant women during the second and third trimesters of pregnancy. The estimated background risk of miscarriage for the indicated population is unknown.
In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Available studies on the use of metformin in pregnant women have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes. Limited data from uncontrolled or retrospective studies are conflicting with regard to the effects of long-term maternal therapy with metformin hydrochloride (1.5-3 g daily) on neonatal morbidity (e.g., congenital malformations) and mortality.
Poorly controlled diabetes mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Metformin should be used during pregnancy only when clearly needed.
Metformin is distributed into milk in lactating rats. Limited data indicate There are no data on the presence of dapagliflozin in human milk, the effects on the breast-fed child, or the effects on milk production. that small amounts of metformin also are distributed into breast milk in Dapagliflozin is distributed into milk in rats.
Since human kidney humans. In a study in 7 nursing women who received metformin hydrochloride (median dosage 1500 mg daily), the mean milk-to-plasma ratio for metformin maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human was 0.35 and the overall average concentration in milk over the dosing interval was 0.27
mg/L. Metformin was present in low or undetectable kidney. Use of dapagliflozin in women who are breast-feeding is not amounts in the plasma of 4 breast-fed infants, and no adverse effects were recommended.
noted in 6 infants that were evaluated. In another study, mean peak and trough metformin concentrations in 4 nursing women receiving metformin hydrochloride 500 mg twice daily were 1.06 and 0.42
mcg/mL, respectively, in serum and 0.42 and 0.39 mcg/mL, respectively, in breast milk.
The mean milk-to-serum ratio was 0.63 and the mean estimated infant dose as a percentage of the mother's weight-adjusted dose was 0.65%.
Blood glucose concentrations obtained in 3 infants 4 hours after breastfeeding were within normal limits (47-77 mg/dL). The developmental and health benefits of breastfeeding should be considered along with mother's clinical need for the drug and potential adverse effects on the breastfed child (e.g., hypoglycemia). Breastfed infants should be monitored for signs of hypoglycemia (e.g., jitters, cyanosis, apnea, hypothermia, excessive sleepiness, poor feeding, seizures).
Since human kidney humans. In a study in 7 nursing women who received metformin hydrochloride (median dosage 1500 mg daily), the mean milk-to-plasma ratio for metformin maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human was 0.35 and the overall average concentration in milk over the dosing interval was 0.27
mg/L. Metformin was present in low or undetectable kidney. Use of dapagliflozin in women who are breast-feeding is not amounts in the plasma of 4 breast-fed infants, and no adverse effects were recommended.
noted in 6 infants that were evaluated. In another study, mean peak and trough metformin concentrations in 4 nursing women receiving metformin hydrochloride 500 mg twice daily were 1.06 and 0.42
mcg/mL, respectively, in serum and 0.42 and 0.39 mcg/mL, respectively, in breast milk.
The mean milk-to-serum ratio was 0.63 and the mean estimated infant dose as a percentage of the mother's weight-adjusted dose was 0.65%.
Blood glucose concentrations obtained in 3 infants 4 hours after breastfeeding were within normal limits (47-77 mg/dL). The developmental and health benefits of breastfeeding should be considered along with mother's clinical need for the drug and potential adverse effects on the breastfed child (e.g., hypoglycemia). Breastfed infants should be monitored for signs of hypoglycemia (e.g., jitters, cyanosis, apnea, hypothermia, excessive sleepiness, poor feeding, seizures).
Among patients with type 2 diabetes mellitus in 21 clinical trials, 1424 (24%) were 65 years of age or older and 207 (3.5%) were 75 years of age or older. Efficacy of dapagliflozin was similar for patients younger than 65 years of age and those 65 years of age or older after controlling for renal function (eGFR). Geriatric patients receiving dapagliflozin for glycemic control were more likely to experience hypotension compared with patients treated with placebo.
In the DAPA-CKD, DAPA-HF, and DELIVER trials, safety and efficacy were similar for patients aged 65 years and younger and those older than 65 years of age. In the DAPA-CKD study, 42% of patients were older than 65 years of age. In the DAPA-HF study, 57% of patients were older than 65 years. In the DELIVER study, 76% of patients were older than 65 years.
In the DAPA-CKD, DAPA-HF, and DELIVER trials, safety and efficacy were similar for patients aged 65 years and younger and those older than 65 years of age. In the DAPA-CKD study, 42% of patients were older than 65 years of age. In the DAPA-HF study, 57% of patients were older than 65 years. In the DELIVER study, 76% of patients were older than 65 years.
The following prioritized warning is available for DAPAGLIFLOZIN-METFORMIN ER (dapagliflozin propanediol/metformin hcl):
WARNING: Rarely, too much metformin can build up in the body and cause a serious (sometimes fatal) condition called lactic acidosis. Lactic acidosis is more likely if you are an older adult, if you have kidney or liver disease, dehydration, heart failure, heavy alcohol use, if you have surgery, if you have X-ray or scanning procedures that use iodinated contrast, or if you are using certain drugs. For some conditions, your doctor may tell you to stop taking this medication for a short time.
Ask your doctor or pharmacist for more details. Stop taking this medication and get medical help right away if you have any symptoms of lactic acidosis, such as unusual tiredness, dizziness, severe drowsiness, chills, blue/cold skin, muscle pain, fast/difficult breathing, slow/irregular heartbeat, or stomach pain with nausea/vomiting/diarrhea.
WARNING: Rarely, too much metformin can build up in the body and cause a serious (sometimes fatal) condition called lactic acidosis. Lactic acidosis is more likely if you are an older adult, if you have kidney or liver disease, dehydration, heart failure, heavy alcohol use, if you have surgery, if you have X-ray or scanning procedures that use iodinated contrast, or if you are using certain drugs. For some conditions, your doctor may tell you to stop taking this medication for a short time.
Ask your doctor or pharmacist for more details. Stop taking this medication and get medical help right away if you have any symptoms of lactic acidosis, such as unusual tiredness, dizziness, severe drowsiness, chills, blue/cold skin, muscle pain, fast/difficult breathing, slow/irregular heartbeat, or stomach pain with nausea/vomiting/diarrhea.
The following icd codes are available for DAPAGLIFLOZIN-METFORMIN ER (dapagliflozin propanediol/metformin hcl)'s list of indications:
| Type 2 diabetes mellitus | |
| E08 | Diabetes mellitus due to underlying condition |
| E08.0 | Diabetes mellitus due to underlying condition with hyperosmolarity |
| E08.00 | Diabetes mellitus due to underlying condition with hyperosmolarity without nonketotic hyperglycemic-hyperosmolar coma (NKHHc) |
| E08.01 | Diabetes mellitus due to underlying condition with hyperosmolarity with coma |
| E08.1 | Diabetes mellitus due to underlying condition with ketoacidosis |
| E08.10 | Diabetes mellitus due to underlying condition with ketoacidosis without coma |
| E08.11 | Diabetes mellitus due to underlying condition with ketoacidosis with coma |
| E08.2 | Diabetes mellitus due to underlying condition with kidney complications |
| E08.21 | Diabetes mellitus due to underlying condition with diabetic nephropathy |
| E08.22 | Diabetes mellitus due to underlying condition with diabetic chronic kidney disease |
| E08.29 | Diabetes mellitus due to underlying condition with other diabetic kidney complication |
| E08.3 | Diabetes mellitus due to underlying condition with ophthalmic complications |
| E08.31 | Diabetes mellitus due to underlying condition with unspecified diabetic retinopathy |
| E08.311 | Diabetes mellitus due to underlying condition with unspecified diabetic retinopathy with macular edema |
| E08.319 | Diabetes mellitus due to underlying condition with unspecified diabetic retinopathy without macular edema |
| E08.32 | Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy |
| E08.321 | Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy with macular edema |
| E08.3211 | Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy with macular edema, right eye |
| E08.3212 | Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy with macular edema, left eye |
| E08.3213 | Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy with macular edema, bilateral |
| E08.3219 | Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy with macular edema, unspecified eye |
| E08.329 | Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy without macular edema |
| E08.3291 | Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy without macular edema, right eye |
| E08.3292 | Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy without macular edema, left eye |
| E08.3293 | Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy without macular edema, bilateral |
| E08.3299 | Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy without macular edema, unspecified eye |
| E08.33 | Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy |
| E08.331 | Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy with macular edema |
| E08.3311 | Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy with macular edema, right eye |
| E08.3312 | Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy with macular edema, left eye |
| E08.3313 | Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy with macular edema, bilateral |
| E08.3319 | Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy with macular edema, unspecified eye |
| E08.339 | Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy without macular edema |
| E08.3391 | Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy without macular edema, right eye |
| E08.3392 | Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy without macular edema, left eye |
| E08.3393 | Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy without macular edema, bilateral |
| E08.3399 | Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy without macular edema, unspecified eye |
| E08.34 | Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy |
| E08.341 | Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy with macular edema |
| E08.3411 | Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy with macular edema, right eye |
| E08.3412 | Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy with macular edema, left eye |
| E08.3413 | Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy with macular edema, bilateral |
| E08.3419 | Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy with macular edema, unspecified eye |
| E08.349 | Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy without macular edema |
| E08.3491 | Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy without macular edema, right eye |
| E08.3492 | Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy without macular edema, left eye |
| E08.3493 | Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy without macular edema, bilateral |
| E08.3499 | Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy without macular edema, unspecified eye |
| E08.35 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy |
| E08.351 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with macular edema |
| E08.3511 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with macular edema, right eye |
| E08.3512 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with macular edema, left eye |
| E08.3513 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with macular edema, bilateral |
| E08.3519 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with macular edema, unspecified eye |
| E08.352 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment involving the macula |
| E08.3521 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment involving the macula, right eye |
| E08.3522 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment involving the macula, left eye |
| E08.3523 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment involving the macula, bilateral |
| E08.3529 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment involving the macula, unspecified eye |
| E08.353 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment not involving the macula |
| E08.3531 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, right eye |
| E08.3532 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, left eye |
| E08.3533 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, bilateral |
| E08.3539 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, unspecified eye |
| E08.354 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment |
| E08.3541 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, right eye |
| E08.3542 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, left eye |
| E08.3543 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, bilateral |
| E08.3549 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, unspecified eye |
| E08.355 | Diabetes mellitus due to underlying condition with stable proliferative diabetic retinopathy |
| E08.3551 | Diabetes mellitus due to underlying condition with stable proliferative diabetic retinopathy, right eye |
| E08.3552 | Diabetes mellitus due to underlying condition with stable proliferative diabetic retinopathy, left eye |
| E08.3553 | Diabetes mellitus due to underlying condition with stable proliferative diabetic retinopathy, bilateral |
| E08.3559 | Diabetes mellitus due to underlying condition with stable proliferative diabetic retinopathy, unspecified eye |
| E08.359 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy without macular edema |
| E08.3591 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy without macular edema, right eye |
| E08.3592 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy without macular edema, left eye |
| E08.3593 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy without macular edema, bilateral |
| E08.3599 | Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy without macular edema, unspecified eye |
| E08.36 | Diabetes mellitus due to underlying condition with diabetic cataract |
| E08.37 | Diabetes mellitus due to underlying condition with diabetic macular edema, resolved following treatment |
| E08.37x1 | Diabetes mellitus due to underlying condition with diabetic macular edema, resolved following treatment, right eye |
| E08.37x2 | Diabetes mellitus due to underlying condition with diabetic macular edema, resolved following treatment, left eye |
| E08.37x3 | Diabetes mellitus due to underlying condition with diabetic macular edema, resolved following treatment, bilateral |
| E08.37x9 | Diabetes mellitus due to underlying condition with diabetic macular edema, resolved following treatment, unspecified eye |
| E08.39 | Diabetes mellitus due to underlying condition with other diabetic ophthalmic complication |
| E08.4 | Diabetes mellitus due to underlying condition with neurological complications |
| E08.40 | Diabetes mellitus due to underlying condition with diabetic neuropathy, unspecified |
| E08.41 | Diabetes mellitus due to underlying condition with diabetic mononeuropathy |
| E08.42 | Diabetes mellitus due to underlying condition with diabetic polyneuropathy |
| E08.43 | Diabetes mellitus due to underlying condition with diabetic autonomic (poly)neuropathy |
| E08.44 | Diabetes mellitus due to underlying condition with diabetic amyotrophy |
| E08.49 | Diabetes mellitus due to underlying condition with other diabetic neurological complication |
| E08.5 | Diabetes mellitus due to underlying condition with circulatory complications |
| E08.51 | Diabetes mellitus due to underlying condition with diabetic peripheral angiopathy without gangrene |
| E08.52 | Diabetes mellitus due to underlying condition with diabetic peripheral angiopathy with gangrene |
| E08.59 | Diabetes mellitus due to underlying condition with other circulatory complications |
| E08.6 | Diabetes mellitus due to underlying condition with other specified complications |
| E08.61 | Diabetes mellitus due to underlying condition with diabetic arthropathy |
| E08.610 | Diabetes mellitus due to underlying condition with diabetic neuropathic arthropathy |
| E08.618 | Diabetes mellitus due to underlying condition with other diabetic arthropathy |
| E08.62 | Diabetes mellitus due to underlying condition with skin complications |
| E08.620 | Diabetes mellitus due to underlying condition with diabetic dermatitis |
| E08.621 | Diabetes mellitus due to underlying condition with foot ulcer |
| E08.622 | Diabetes mellitus due to underlying condition with other skin ulcer |
| E08.628 | Diabetes mellitus due to underlying condition with other skin complications |
| E08.63 | Diabetes mellitus due to underlying condition with oral complications |
| E08.630 | Diabetes mellitus due to underlying condition with periodontal disease |
| E08.638 | Diabetes mellitus due to underlying condition with other oral complications |
| E08.64 | Diabetes mellitus due to underlying condition with hypoglycemia |
| E08.641 | Diabetes mellitus due to underlying condition with hypoglycemia with coma |
| E08.649 | Diabetes mellitus due to underlying condition with hypoglycemia without coma |
| E08.65 | Diabetes mellitus due to underlying condition with hyperglycemia |
| E08.69 | Diabetes mellitus due to underlying condition with other specified complication |
| E08.8 | Diabetes mellitus due to underlying condition with unspecified complications |
| E08.9 | Diabetes mellitus due to underlying condition without complications |
| E09 | Drug or chemical induced diabetes mellitus |
| E09.0 | Drug or chemical induced diabetes mellitus with hyperosmolarity |
| E09.00 | Drug or chemical induced diabetes mellitus with hyperosmolarity without nonketotic hyperglycemic-hyperosmolar coma (NKHHc) |
| E09.01 | Drug or chemical induced diabetes mellitus with hyperosmolarity with coma |
| E09.1 | Drug or chemical induced diabetes mellitus with ketoacidosis |
| E09.10 | Drug or chemical induced diabetes mellitus with ketoacidosis without coma |
| E09.11 | Drug or chemical induced diabetes mellitus with ketoacidosis with coma |
| E09.2 | Drug or chemical induced diabetes mellitus with kidney complications |
| E09.21 | Drug or chemical induced diabetes mellitus with diabetic nephropathy |
| E09.22 | Drug or chemical induced diabetes mellitus with diabetic chronic kidney disease |
| E09.29 | Drug or chemical induced diabetes mellitus with other diabetic kidney complication |
| E09.3 | Drug or chemical induced diabetes mellitus with ophthalmic complications |
| E09.31 | Drug or chemical induced diabetes mellitus with unspecified diabetic retinopathy |
| E09.311 | Drug or chemical induced diabetes mellitus with unspecified diabetic retinopathy with macular edema |
| E09.319 | Drug or chemical induced diabetes mellitus with unspecified diabetic retinopathy without macular edema |
| E09.32 | Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy |
| E09.321 | Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema |
| E09.3211 | Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, right eye |
| E09.3212 | Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, left eye |
| E09.3213 | Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, bilateral |
| E09.3219 | Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, unspecified eye |
| E09.329 | Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema |
| E09.3291 | Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, right eye |
| E09.3292 | Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, left eye |
| E09.3293 | Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, bilateral |
| E09.3299 | Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, unspecified eye |
| E09.33 | Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy |
| E09.331 | Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema |
| E09.3311 | Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, right eye |
| E09.3312 | Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, left eye |
| E09.3313 | Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, bilateral |
| E09.3319 | Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, unspecified eye |
| E09.339 | Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema |
| E09.3391 | Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, right eye |
| E09.3392 | Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, left eye |
| E09.3393 | Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, bilateral |
| E09.3399 | Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, unspecified eye |
| E09.34 | Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy |
| E09.341 | Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema |
| E09.3411 | Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, right eye |
| E09.3412 | Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, left eye |
| E09.3413 | Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, bilateral |
| E09.3419 | Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, unspecified eye |
| E09.349 | Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema |
| E09.3491 | Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, right eye |
| E09.3492 | Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, left eye |
| E09.3493 | Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, bilateral |
| E09.3499 | Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, unspecified eye |
| E09.35 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy |
| E09.351 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with macular edema |
| E09.3511 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with macular edema, right eye |
| E09.3512 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with macular edema, left eye |
| E09.3513 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with macular edema, bilateral |
| E09.3519 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with macular edema, unspecified eye |
| E09.352 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula |
| E09.3521 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, right eye |
| E09.3522 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, left eye |
| E09.3523 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, bilateral |
| E09.3529 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, unspecified eye |
| E09.353 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula |
| E09.3531 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, right eye |
| E09.3532 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, left eye |
| E09.3533 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, bilateral |
| E09.3539 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, unspecified eye |
| E09.354 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment |
| E09.3541 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, right eye |
| E09.3542 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, left eye |
| E09.3543 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, bilateral |
| E09.3549 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, unspecified eye |
| E09.355 | Drug or chemical induced diabetes mellitus with stable proliferative diabetic retinopathy |
| E09.3551 | Drug or chemical induced diabetes mellitus with stable proliferative diabetic retinopathy, right eye |
| E09.3552 | Drug or chemical induced diabetes mellitus with stable proliferative diabetic retinopathy, left eye |
| E09.3553 | Drug or chemical induced diabetes mellitus with stable proliferative diabetic retinopathy, bilateral |
| E09.3559 | Drug or chemical induced diabetes mellitus with stable proliferative diabetic retinopathy, unspecified eye |
| E09.359 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy without macular edema |
| E09.3591 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy without macular edema, right eye |
| E09.3592 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy without macular edema, left eye |
| E09.3593 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy without macular edema, bilateral |
| E09.3599 | Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy without macular edema, unspecified eye |
| E09.36 | Drug or chemical induced diabetes mellitus with diabetic cataract |
| E09.37 | Drug or chemical induced diabetes mellitus with diabetic macular edema, resolved following treatment |
| E09.37x1 | Drug or chemical induced diabetes mellitus with diabetic macular edema, resolved following treatment, right eye |
| E09.37x2 | Drug or chemical induced diabetes mellitus with diabetic macular edema, resolved following treatment, left eye |
| E09.37x3 | Drug or chemical induced diabetes mellitus with diabetic macular edema, resolved following treatment, bilateral |
| E09.37x9 | Drug or chemical induced diabetes mellitus with diabetic macular edema, resolved following treatment, unspecified eye |
| E09.39 | Drug or chemical induced diabetes mellitus with other diabetic ophthalmic complication |
| E09.4 | Drug or chemical induced diabetes mellitus with neurological complications |
| E09.40 | Drug or chemical induced diabetes mellitus with neurological complications with diabetic neuropathy, unspecified |
| E09.41 | Drug or chemical induced diabetes mellitus with neurological complications with diabetic mononeuropathy |
| E09.42 | Drug or chemical induced diabetes mellitus with neurological complications with diabetic polyneuropathy |
| E09.43 | Drug or chemical induced diabetes mellitus with neurological complications with diabetic autonomic (poly)neuropathy |
| E09.44 | Drug or chemical induced diabetes mellitus with neurological complications with diabetic amyotrophy |
| E09.49 | Drug or chemical induced diabetes mellitus with neurological complications with other diabetic neurological complication |
| E09.5 | Drug or chemical induced diabetes mellitus with circulatory complications |
| E09.51 | Drug or chemical induced diabetes mellitus with diabetic peripheral angiopathy without gangrene |
| E09.52 | Drug or chemical induced diabetes mellitus with diabetic peripheral angiopathy with gangrene |
| E09.59 | Drug or chemical induced diabetes mellitus with other circulatory complications |
| E09.6 | Drug or chemical induced diabetes mellitus with other specified complications |
| E09.61 | Drug or chemical induced diabetes mellitus with diabetic arthropathy |
| E09.610 | Drug or chemical induced diabetes mellitus with diabetic neuropathic arthropathy |
| E09.618 | Drug or chemical induced diabetes mellitus with other diabetic arthropathy |
| E09.62 | Drug or chemical induced diabetes mellitus with skin complications |
| E09.620 | Drug or chemical induced diabetes mellitus with diabetic dermatitis |
| E09.621 | Drug or chemical induced diabetes mellitus with foot ulcer |
| E09.622 | Drug or chemical induced diabetes mellitus with other skin ulcer |
| E09.628 | Drug or chemical induced diabetes mellitus with other skin complications |
| E09.63 | Drug or chemical induced diabetes mellitus with oral complications |
| E09.630 | Drug or chemical induced diabetes mellitus with periodontal disease |
| E09.638 | Drug or chemical induced diabetes mellitus with other oral complications |
| E09.64 | Drug or chemical induced diabetes mellitus with hypoglycemia |
| E09.641 | Drug or chemical induced diabetes mellitus with hypoglycemia with coma |
| E09.649 | Drug or chemical induced diabetes mellitus with hypoglycemia without coma |
| E09.65 | Drug or chemical induced diabetes mellitus with hyperglycemia |
| E09.69 | Drug or chemical induced diabetes mellitus with other specified complication |
| E09.8 | Drug or chemical induced diabetes mellitus with unspecified complications |
| E09.9 | Drug or chemical induced diabetes mellitus without complications |
| E11 | Type 2 diabetes mellitus |
| E11.0 | Type 2 diabetes mellitus with hyperosmolarity |
| E11.00 | Type 2 diabetes mellitus with hyperosmolarity without nonketotic hyperglycemic-hyperosmolar coma (NKHHc) |
| E11.01 | Type 2 diabetes mellitus with hyperosmolarity with coma |
| E11.1 | Type 2 diabetes mellitus with ketoacidosis |
| E11.10 | Type 2 diabetes mellitus with ketoacidosis without coma |
| E11.11 | Type 2 diabetes mellitus with ketoacidosis with coma |
| E11.2 | Type 2 diabetes mellitus with kidney complications |
| E11.21 | Type 2 diabetes mellitus with diabetic nephropathy |
| E11.22 | Type 2 diabetes mellitus with diabetic chronic kidney disease |
| E11.29 | Type 2 diabetes mellitus with other diabetic kidney complication |
| E11.3 | Type 2 diabetes mellitus with ophthalmic complications |
| E11.31 | Type 2 diabetes mellitus with unspecified diabetic retinopathy |
| E11.311 | Type 2 diabetes mellitus with unspecified diabetic retinopathy with macular edema |
| E11.319 | Type 2 diabetes mellitus with unspecified diabetic retinopathy without macular edema |
| E11.32 | Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy |
| E11.321 | Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema |
| E11.3211 | Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, right eye |
| E11.3212 | Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, left eye |
| E11.3213 | Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, bilateral |
| E11.3219 | Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, unspecified eye |
| E11.329 | Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema |
| E11.3291 | Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, right eye |
| E11.3292 | Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, left eye |
| E11.3293 | Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, bilateral |
| E11.3299 | Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, unspecified eye |
| E11.33 | Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy |
| E11.331 | Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema |
| E11.3311 | Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, right eye |
| E11.3312 | Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, left eye |
| E11.3313 | Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, bilateral |
| E11.3319 | Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, unspecified eye |
| E11.339 | Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema |
| E11.3391 | Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, right eye |
| E11.3392 | Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, left eye |
| E11.3393 | Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, bilateral |
| E11.3399 | Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, unspecified eye |
| E11.34 | Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy |
| E11.341 | Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema |
| E11.3411 | Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, right eye |
| E11.3412 | Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, left eye |
| E11.3413 | Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, bilateral |
| E11.3419 | Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, unspecified eye |
| E11.349 | Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema |
| E11.3491 | Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, right eye |
| E11.3492 | Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, left eye |
| E11.3493 | Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, bilateral |
| E11.3499 | Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, unspecified eye |
| E11.35 | Type 2 diabetes mellitus with proliferative diabetic retinopathy |
| E11.351 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with macular edema |
| E11.3511 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with macular edema, right eye |
| E11.3512 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with macular edema, left eye |
| E11.3513 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with macular edema, bilateral |
| E11.3519 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with macular edema, unspecified eye |
| E11.352 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula |
| E11.3521 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, right eye |
| E11.3522 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, left eye |
| E11.3523 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, bilateral |
| E11.3529 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, unspecified eye |
| E11.353 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula |
| E11.3531 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, right eye |
| E11.3532 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, left eye |
| E11.3533 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, bilateral |
| E11.3539 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, unspecified eye |
| E11.354 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment |
| E11.3541 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, right eye |
| E11.3542 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, left eye |
| E11.3543 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, bilateral |
| E11.3549 | Type 2 diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, unspecified eye |
| E11.355 | Type 2 diabetes mellitus with stable proliferative diabetic retinopathy |
| E11.3551 | Type 2 diabetes mellitus with stable proliferative diabetic retinopathy, right eye |
| E11.3552 | Type 2 diabetes mellitus with stable proliferative diabetic retinopathy, left eye |
| E11.3553 | Type 2 diabetes mellitus with stable proliferative diabetic retinopathy, bilateral |
| E11.3559 | Type 2 diabetes mellitus with stable proliferative diabetic retinopathy, unspecified eye |
| E11.359 | Type 2 diabetes mellitus with proliferative diabetic retinopathy without macular edema |
| E11.3591 | Type 2 diabetes mellitus with proliferative diabetic retinopathy without macular edema, right eye |
| E11.3592 | Type 2 diabetes mellitus with proliferative diabetic retinopathy without macular edema, left eye |
| E11.3593 | Type 2 diabetes mellitus with proliferative diabetic retinopathy without macular edema, bilateral |
| E11.3599 | Type 2 diabetes mellitus with proliferative diabetic retinopathy without macular edema, unspecified eye |
| E11.36 | Type 2 diabetes mellitus with diabetic cataract |
| E11.37 | Type 2 diabetes mellitus with diabetic macular edema, resolved following treatment |
| E11.37x1 | Type 2 diabetes mellitus with diabetic macular edema, resolved following treatment, right eye |
| E11.37x2 | Type 2 diabetes mellitus with diabetic macular edema, resolved following treatment, left eye |
| E11.37x3 | Type 2 diabetes mellitus with diabetic macular edema, resolved following treatment, bilateral |
| E11.37x9 | Type 2 diabetes mellitus with diabetic macular edema, resolved following treatment, unspecified eye |
| E11.39 | Type 2 diabetes mellitus with other diabetic ophthalmic complication |
| E11.4 | Type 2 diabetes mellitus with neurological complications |
| E11.40 | Type 2 diabetes mellitus with diabetic neuropathy, unspecified |
| E11.41 | Type 2 diabetes mellitus with diabetic mononeuropathy |
| E11.42 | Type 2 diabetes mellitus with diabetic polyneuropathy |
| E11.43 | Type 2 diabetes mellitus with diabetic autonomic (poly)neuropathy |
| E11.44 | Type 2 diabetes mellitus with diabetic amyotrophy |
| E11.49 | Type 2 diabetes mellitus with other diabetic neurological complication |
| E11.5 | Type 2 diabetes mellitus with circulatory complications |
| E11.51 | Type 2 diabetes mellitus with diabetic peripheral angiopathy without gangrene |
| E11.52 | Type 2 diabetes mellitus with diabetic peripheral angiopathy with gangrene |
| E11.59 | Type 2 diabetes mellitus with other circulatory complications |
| E11.6 | Type 2 diabetes mellitus with other specified complications |
| E11.61 | Type 2 diabetes mellitus with diabetic arthropathy |
| E11.610 | Type 2 diabetes mellitus with diabetic neuropathic arthropathy |
| E11.618 | Type 2 diabetes mellitus with other diabetic arthropathy |
| E11.62 | Type 2 diabetes mellitus with skin complications |
| E11.620 | Type 2 diabetes mellitus with diabetic dermatitis |
| E11.621 | Type 2 diabetes mellitus with foot ulcer |
| E11.622 | Type 2 diabetes mellitus with other skin ulcer |
| E11.628 | Type 2 diabetes mellitus with other skin complications |
| E11.63 | Type 2 diabetes mellitus with oral complications |
| E11.630 | Type 2 diabetes mellitus with periodontal disease |
| E11.638 | Type 2 diabetes mellitus with other oral complications |
| E11.64 | Type 2 diabetes mellitus with hypoglycemia |
| E11.641 | Type 2 diabetes mellitus with hypoglycemia with coma |
| E11.649 | Type 2 diabetes mellitus with hypoglycemia without coma |
| E11.65 | Type 2 diabetes mellitus with hyperglycemia |
| E11.69 | Type 2 diabetes mellitus with other specified complication |
| E11.8 | Type 2 diabetes mellitus with unspecified complications |
| E11.9 | Type 2 diabetes mellitus without complications |
| E13 | Other specified diabetes mellitus |
| E13.0 | Other specified diabetes mellitus with hyperosmolarity |
| E13.00 | Other specified diabetes mellitus with hyperosmolarity without nonketotic hyperglycemic-hyperosmolar coma (NKHHc) |
| E13.01 | Other specified diabetes mellitus with hyperosmolarity with coma |
| E13.1 | Other specified diabetes mellitus with ketoacidosis |
| E13.10 | Other specified diabetes mellitus with ketoacidosis without coma |
| E13.11 | Other specified diabetes mellitus with ketoacidosis with coma |
| E13.2 | Other specified diabetes mellitus with kidney complications |
| E13.21 | Other specified diabetes mellitus with diabetic nephropathy |
| E13.22 | Other specified diabetes mellitus with diabetic chronic kidney disease |
| E13.29 | Other specified diabetes mellitus with other diabetic kidney complication |
| E13.3 | Other specified diabetes mellitus with ophthalmic complications |
| E13.31 | Other specified diabetes mellitus with unspecified diabetic retinopathy |
| E13.311 | Other specified diabetes mellitus with unspecified diabetic retinopathy with macular edema |
| E13.319 | Other specified diabetes mellitus with unspecified diabetic retinopathy without macular edema |
| E13.32 | Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy |
| E13.321 | Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema |
| E13.3211 | Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, right eye |
| E13.3212 | Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, left eye |
| E13.3213 | Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, bilateral |
| E13.3219 | Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, unspecified eye |
| E13.329 | Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema |
| E13.3291 | Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, right eye |
| E13.3292 | Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, left eye |
| E13.3293 | Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, bilateral |
| E13.3299 | Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, unspecified eye |
| E13.33 | Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy |
| E13.331 | Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema |
| E13.3311 | Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, right eye |
| E13.3312 | Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, left eye |
| E13.3313 | Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, bilateral |
| E13.3319 | Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, unspecified eye |
| E13.339 | Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema |
| E13.3391 | Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, right eye |
| E13.3392 | Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, left eye |
| E13.3393 | Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, bilateral |
| E13.3399 | Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, unspecified eye |
| E13.34 | Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy |
| E13.341 | Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema |
| E13.3411 | Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, right eye |
| E13.3412 | Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, left eye |
| E13.3413 | Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, bilateral |
| E13.3419 | Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, unspecified eye |
| E13.349 | Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema |
| E13.3491 | Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, right eye |
| E13.3492 | Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, left eye |
| E13.3493 | Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, bilateral |
| E13.3499 | Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, unspecified eye |
| E13.35 | Other specified diabetes mellitus with proliferative diabetic retinopathy |
| E13.351 | Other specified diabetes mellitus with proliferative diabetic retinopathy with macular edema |
| E13.3511 | Other specified diabetes mellitus with proliferative diabetic retinopathy with macular edema, right eye |
| E13.3512 | Other specified diabetes mellitus with proliferative diabetic retinopathy with macular edema, left eye |
| E13.3513 | Other specified diabetes mellitus with proliferative diabetic retinopathy with macular edema, bilateral |
| E13.3519 | Other specified diabetes mellitus with proliferative diabetic retinopathy with macular edema, unspecified eye |
| E13.352 | Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula |
| E13.3521 | Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, right eye |
| E13.3522 | Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, left eye |
| E13.3523 | Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, bilateral |
| E13.3529 | Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, unspecified eye |
| E13.353 | Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula |
| E13.3531 | Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, right eye |
| E13.3532 | Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, left eye |
| E13.3533 | Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, bilateral |
| E13.3539 | Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, unspecified eye |
| E13.354 | Other specified diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment |
| E13.3541 | Other specified diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, right eye |
| E13.3542 | Other specified diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, left eye |
| E13.3543 | Other specified diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, bilateral |
| E13.3549 | Other specified diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, unspecified eye |
| E13.355 | Other specified diabetes mellitus with stable proliferative diabetic retinopathy |
| E13.3551 | Other specified diabetes mellitus with stable proliferative diabetic retinopathy, right eye |
| E13.3552 | Other specified diabetes mellitus with stable proliferative diabetic retinopathy, left eye |
| E13.3553 | Other specified diabetes mellitus with stable proliferative diabetic retinopathy, bilateral |
| E13.3559 | Other specified diabetes mellitus with stable proliferative diabetic retinopathy, unspecified eye |
| E13.359 | Other specified diabetes mellitus with proliferative diabetic retinopathy without macular edema |
| E13.3591 | Other specified diabetes mellitus with proliferative diabetic retinopathy without macular edema, right eye |
| E13.3592 | Other specified diabetes mellitus with proliferative diabetic retinopathy without macular edema, left eye |
| E13.3593 | Other specified diabetes mellitus with proliferative diabetic retinopathy without macular edema, bilateral |
| E13.3599 | Other specified diabetes mellitus with proliferative diabetic retinopathy without macular edema, unspecified eye |
| E13.36 | Other specified diabetes mellitus with diabetic cataract |
| E13.37 | Other specified diabetes mellitus with diabetic macular edema, resolved following treatment |
| E13.37x1 | Other specified diabetes mellitus with diabetic macular edema, resolved following treatment, right eye |
| E13.37x2 | Other specified diabetes mellitus with diabetic macular edema, resolved following treatment, left eye |
| E13.37x3 | Other specified diabetes mellitus with diabetic macular edema, resolved following treatment, bilateral |
| E13.37x9 | Other specified diabetes mellitus with diabetic macular edema, resolved following treatment, unspecified eye |
| E13.39 | Other specified diabetes mellitus with other diabetic ophthalmic complication |
| E13.4 | Other specified diabetes mellitus with neurological complications |
| E13.40 | Other specified diabetes mellitus with diabetic neuropathy, unspecified |
| E13.41 | Other specified diabetes mellitus with diabetic mononeuropathy |
| E13.42 | Other specified diabetes mellitus with diabetic polyneuropathy |
| E13.43 | Other specified diabetes mellitus with diabetic autonomic (poly)neuropathy |
| E13.44 | Other specified diabetes mellitus with diabetic amyotrophy |
| E13.49 | Other specified diabetes mellitus with other diabetic neurological complication |
| E13.5 | Other specified diabetes mellitus with circulatory complications |
| E13.51 | Other specified diabetes mellitus with diabetic peripheral angiopathy without gangrene |
| E13.52 | Other specified diabetes mellitus with diabetic peripheral angiopathy with gangrene |
| E13.59 | Other specified diabetes mellitus with other circulatory complications |
| E13.6 | Other specified diabetes mellitus with other specified complications |
| E13.61 | Other specified diabetes mellitus with diabetic arthropathy |
| E13.610 | Other specified diabetes mellitus with diabetic neuropathic arthropathy |
| E13.618 | Other specified diabetes mellitus with other diabetic arthropathy |
| E13.62 | Other specified diabetes mellitus with skin complications |
| E13.620 | Other specified diabetes mellitus with diabetic dermatitis |
| E13.621 | Other specified diabetes mellitus with foot ulcer |
| E13.622 | Other specified diabetes mellitus with other skin ulcer |
| E13.628 | Other specified diabetes mellitus with other skin complications |
| E13.63 | Other specified diabetes mellitus with oral complications |
| E13.630 | Other specified diabetes mellitus with periodontal disease |
| E13.638 | Other specified diabetes mellitus with other oral complications |
| E13.64 | Other specified diabetes mellitus with hypoglycemia |
| E13.641 | Other specified diabetes mellitus with hypoglycemia with coma |
| E13.649 | Other specified diabetes mellitus with hypoglycemia without coma |
| E13.65 | Other specified diabetes mellitus with hyperglycemia |
| E13.69 | Other specified diabetes mellitus with other specified complication |
| E13.8 | Other specified diabetes mellitus with unspecified complications |
| E13.9 | Other specified diabetes mellitus without complications |
Formulary Reference Tool