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Drug overview for METHYLDOPA-HYDROCHLOROTHIAZIDE (methyldopa/hydrochlorothiazide):
Generic name: METHYLDOPA/HYDROCHLOROTHIAZIDE (METH-il-DOE-pa/HYE-droe-KLOR-oh-THYE-a-zide)
Drug class: Diuretics
Therapeutic class: Cardiovascular Therapy Agents
Hydrochlorothiazide is a thiazide diuretic and antihypertensive agent. Methyldopa is a centrally acting hypotensive agent.
No enhanced Uses information available for this drug.
Generic name: METHYLDOPA/HYDROCHLOROTHIAZIDE (METH-il-DOE-pa/HYE-droe-KLOR-oh-THYE-a-zide)
Drug class: Diuretics
Therapeutic class: Cardiovascular Therapy Agents
Hydrochlorothiazide is a thiazide diuretic and antihypertensive agent. Methyldopa is a centrally acting hypotensive agent.
No enhanced Uses information available for this drug.
DRUG IMAGES
METHYLDOPA-HCTZ 250-15 MG TAB
METHYLDOPA-HCTZ 250-25 MG TAB
The following indications for METHYLDOPA-HYDROCHLOROTHIAZIDE (methyldopa/hydrochlorothiazide) have been approved by the FDA:
Indications:
Hypertension
Professional Synonyms:
Elevated blood pressure
Essential hypertension
Hyperpiesia
Hyperpiesis
Hypertensive disorder
Systemic arterial hypertension
Indications:
Hypertension
Professional Synonyms:
Elevated blood pressure
Essential hypertension
Hyperpiesia
Hyperpiesis
Hypertensive disorder
Systemic arterial hypertension
The following dosing information is available for METHYLDOPA-HYDROCHLOROTHIAZIDE (methyldopa/hydrochlorothiazide):
Dosage of hydrochlorothiazide should be individualized according to the patient's requirements and response. The lowest dosage necessary to produce the desired clinical effect should be used. If hydrochlorothiazide is added to the regimen of a patient stabilized on a potent hypotensive agent, dosage of the hypotensive agent should initially be reduced to avoid the possibility of severe hypotension.
Dosage of methyldopa must be adjusted according to the patient's blood For the management of hypertension in adults, the manufacturers recommend pressure response and tolerance. Adverse effects such as drowsiness may be an initial hydrochlorothiazide dosage of 12.5-25 mg once daily and a usual minimized by starting dosage increases in the evening or by giving a larger maximum dosage of 50 mg daily (in 1 or 2 divided doses).
Dosages of 25-100 dose at bedtime than in the morning. Geriatric patients may respond to mg daily (in 1 or 2 divided doses) have been used in randomized controlled smaller doses of methyldopa. studies; experts recommend a dosage of 25-50 mg daily for optimal balance
between efficacy and safety in the management of hypertension in adults. Dosages exceeding 50 mg daily usually are associated with marked hypokalemia; some manufacturers state that such dosages are not recommended.
In children 6 months to 12 years of age, the usual dosage of hydrochlorothiazide for the management of hypertension or for diuresis is 1-2 mg/kg daily given as a single dose or in 2 divided doses. Infants younger than 6 months of age may require up to 3 mg/kg daily in 2 divided doses. The total daily dosage should not exceed 37.5
mg for children up to 2 years of age or 100 mg for children 2-12 years of age. Experts recommend initiation of the drug at the low end of the dosage range; the dosage may be increased every 2-4 weeks until blood pressure is controlled, the maximum dosage is reached, or adverse effects occur. For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Because an increased incidence of adverse effects to hydrochlorothiazide When parenteral drug therapy is indicated, the usual IV dosage of and excessive reduction in blood pressure may occur in geriatric patients methyldopate hydrochloride in adults is 250-500 mg every 6 hours as (older than 65 years of age), hydrochlorothiazide should be initiated at required; the maximum dosage is 1 g every 6 hours. the lowest dosage (12.5 mg daily); dosage may be adjusted in increments of
12.5 mg if needed. The usual IV dosage of methyldopate hydrochloride in pediatric patients is
20-40 mg/kg per 24 hours, administered in equally divided doses at 6-hour intervals. The maximum IV dosage in children is 65 mg/kg daily or 3 g daily, whichever is less. When blood pressure is controlled, oral therapy should be substituted using the same dosage as the parenteral dosage.
Patients with impaired renal function may respond to smaller doses of methyldopa.
Dosage of methyldopa must be adjusted according to the patient's blood For the management of hypertension in adults, the manufacturers recommend pressure response and tolerance. Adverse effects such as drowsiness may be an initial hydrochlorothiazide dosage of 12.5-25 mg once daily and a usual minimized by starting dosage increases in the evening or by giving a larger maximum dosage of 50 mg daily (in 1 or 2 divided doses).
Dosages of 25-100 dose at bedtime than in the morning. Geriatric patients may respond to mg daily (in 1 or 2 divided doses) have been used in randomized controlled smaller doses of methyldopa. studies; experts recommend a dosage of 25-50 mg daily for optimal balance
between efficacy and safety in the management of hypertension in adults. Dosages exceeding 50 mg daily usually are associated with marked hypokalemia; some manufacturers state that such dosages are not recommended.
In children 6 months to 12 years of age, the usual dosage of hydrochlorothiazide for the management of hypertension or for diuresis is 1-2 mg/kg daily given as a single dose or in 2 divided doses. Infants younger than 6 months of age may require up to 3 mg/kg daily in 2 divided doses. The total daily dosage should not exceed 37.5
mg for children up to 2 years of age or 100 mg for children 2-12 years of age. Experts recommend initiation of the drug at the low end of the dosage range; the dosage may be increased every 2-4 weeks until blood pressure is controlled, the maximum dosage is reached, or adverse effects occur. For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Because an increased incidence of adverse effects to hydrochlorothiazide When parenteral drug therapy is indicated, the usual IV dosage of and excessive reduction in blood pressure may occur in geriatric patients methyldopate hydrochloride in adults is 250-500 mg every 6 hours as (older than 65 years of age), hydrochlorothiazide should be initiated at required; the maximum dosage is 1 g every 6 hours. the lowest dosage (12.5 mg daily); dosage may be adjusted in increments of
12.5 mg if needed. The usual IV dosage of methyldopate hydrochloride in pediatric patients is
20-40 mg/kg per 24 hours, administered in equally divided doses at 6-hour intervals. The maximum IV dosage in children is 65 mg/kg daily or 3 g daily, whichever is less. When blood pressure is controlled, oral therapy should be substituted using the same dosage as the parenteral dosage.
Patients with impaired renal function may respond to smaller doses of methyldopa.
Hydrochlorothiazide is administered orally. Methyldopa is administered orally; methyldopate hydrochloride is administered by IV infusion. IM or subcutaneous administration of methyldopate hydrochloride is not recommended because of unpredictable absorption.
Methyldopate hydrochloride IV infusions are prepared by adding the required dose of the drug to 100 mL of 5% dextrose injection. Alternatively, the required dose may be administered in 5% dextrose injection in a concentration of 100 mg/10 mL. The IV infusion should be administered slowly over a period of 30-60 minutes.
ADD-Vantage(R) vials labeled as containing 50 mg/mL of methyldopate hydrochloride should be diluted and administered according to the manufacturer's directions. Vials containing solutions of methyldopate hydrochloride for injection and reconstituted solutions of the drug should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Methyldopate hydrochloride IV infusions are prepared by adding the required dose of the drug to 100 mL of 5% dextrose injection. Alternatively, the required dose may be administered in 5% dextrose injection in a concentration of 100 mg/10 mL. The IV infusion should be administered slowly over a period of 30-60 minutes.
ADD-Vantage(R) vials labeled as containing 50 mg/mL of methyldopate hydrochloride should be diluted and administered according to the manufacturer's directions. Vials containing solutions of methyldopate hydrochloride for injection and reconstituted solutions of the drug should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| METHYLDOPA-HCTZ 250-15 MG TAB | Maintenance | Adults take 1 tablet by oral route 2 times per day |
| METHYLDOPA-HCTZ 250-25 MG TAB | Maintenance | Adults take 1 tablet by oral route 2 times per day |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| METHYLDOPA-HCTZ 250-15 MG TAB | Maintenance | Adults take 1 tablet by oral route 2 times per day |
| METHYLDOPA-HCTZ 250-25 MG TAB | Maintenance | Adults take 1 tablet by oral route 2 times per day |
The following drug interaction information is available for METHYLDOPA-HYDROCHLOROTHIAZIDE (methyldopa/hydrochlorothiazide):
There are 2 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Dofetilide/Thiazide Diuretics SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Thiazide diuretics may decrease the excretion of dofetilide and may decrease potassium levels.(1) CLINICAL EFFECTS: Concurrent use of dofetilide with a thiazide diuretic may result in elevated levels and clinical effects of dofetilide, as well as prolongation of the QT interval.(1) PREDISPOSING FACTORS: Renal impairment may increase risk for excessive QTc prolongation as dofetilide is primarily renally eliminated. To prevent increased serum levels and risk for ventricular arrhythmias, dofetilide must be dose adjusted for creatinine clearance < or = to 60 mL/min.(1) The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, and advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: The manufacturer of dofetilide states that the concurrent use of dofetilide with hydrochlorothiazide, alone or in combination with triamterene, is contraindicated.(1) Other thiazides should also be considered contraindicated as well. If concurrent therapy is deemed medically necessary, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: In a study, hydrochlorothiazide (50 mg daily) alone or hydrochlorothiazide/triamterene (50 mg/100 mg daily) was administered with dofetilide (500 mcg twice daily) for 5 days following 2 days of diuretic use at half-dose. In patients receiving hydrochlorothiazide alone, the area-under-curve (AUC) and maximum concentration (Cmax) of dofetilide increased by 27% and by 21%, respectively. The pharmacodynamic effects of dofetilide increased by 197% (QTc increase over time) and by 95% (maximum QTc increase). In patients on combination hydrochlorothiazide/triamterene, dofetilide AUC and Cmax increased by 30% and by 16%, respectively. The pharmacodynamic effects of dofetilide increased by 190% (QTc increase over time) and by 84% (maximum QTc increase).(1) Dofetilide clearance was 16% lower in patients receiving thiazide diuretics.(1) |
DOFETILIDE, TIKOSYN |
| Methyldopa/MAOIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Monoamine oxidase inhibitors (MAOI's) may inhibit the antihypertensive effects of methyldopa.(1) CLINICAL EFFECTS: Concurrent use of MAOI's and methyldopa may result in hypertensive crisis(2) and/or hallucinations.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The Australian,(4) UK,(1) and US(5,6) manufacturers of methyldopa state that concurrent use of MAOI's is contraindicated. The US manufacturer of phenelzine states that concurrent use of methyldopa is contraindicated.(2) DISCUSSION: In a case report, a patient maintained on pargyline developed hallucinations following the increase of her methyldopa from 250 mg daily to 250 mg twice daily.(2) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(7,8) Metaxalone is a weak inhibitor of MAO.(9,10) |
AZILECT, EMSAM, FURAZOLIDONE, LINEZOLID, LINEZOLID-0.9% NACL, LINEZOLID-D5W, MARPLAN, MATULANE, METAXALONE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, RASAGILINE MESYLATE, SELEGILINE HCL, TRANYLCYPROMINE SULFATE, XADAGO, ZELAPAR, ZYVOX |
There are 7 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 |
|---|---|
| Lithium/Thiazide Diuretics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lithium is eliminated unchanged by the kidney; thiazide induced sodium elimination may lead to decreased renal clearance of lithium. CLINICAL EFFECTS: Lithium has a narrow therapeutic range; even modest, unintended increases in lithium concentration may result in lithium toxicity. Early symptoms of lithium toxicity may include: lethargy, muscle weakness or stiffness, new onset or coarsening of hand tremor, vomiting, diarrhea, confusion, ataxia, blurred vision, tinnitus and nystagmus. Severe toxicity may produce multiple organ dysfunction (e.g. seizures, coma, renal failure, cardiac arrhythmias, cardiovascular collapse) and may be fatal. PREDISPOSING FACTORS: Risk factors for lithium toxicity include: renal impairment or worsening of existing renal disease, dehydration, low sodium diet, and concomitant use of multiple medications which may impair renal elimination of lithium (e.g. ARBs, ACE Inhibitors, NSAIDs, diuretics). Patients who require higher therapeutic lithium levels to maintain symptom control are particularly susceptible to these factors. PATIENT MANAGEMENT: If concurrent therapy cannot be avoided, monitor closely to decrease the risk for lithium toxicity. Evaluate renal function and most recent lithium levels. If renal function is not stable, it would be prudent to withhold combination therapy until renal function is stable. If a thiazide diuretic is started, or if the dose is increased in a patient stabilized on lithium therapy, consider empirically lowering the lithium dose, and recheck lithium levels 5 to 7 days after diuretic initiation. Adjust lithium or thiazide dose as required and continue frequent (e.g. weekly) monitoring of lithium until levels have stabilized. If lithium is to be started in a patient stabilized on a thiazide diuretic, consider starting with a lower lithium dose and titrate slowly as half-life may be prolonged. Monitor lithium concentrations until stabilized on the combination. Counsel patient to assure they know signs and symptoms of lithium toxicity and understand the importance of follow-up laboratory testing. DISCUSSION: This interaction is well documented.(1-15) |
LITHIUM CARBONATE, LITHIUM CARBONATE ER, LITHIUM CITRATE, LITHIUM CITRATE TETRAHYDRATE, LITHOBID |
| Methyldopa/Beta-Blockers (Nonselective) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Unopposed alpha-adrenergic vasoconstriction produced by alpha-methylnorepinephrine in the presence of beta-blockade. CLINICAL EFFECTS: Severe hypertension. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor blood pressure during concomitant administration of methyldopa and a nonselective beta-blocker. If hypertension occurs, treatment with phentolamine should be considered. DISCUSSION: Although methyldopa and propranolol have been used together to treat hypertension, severe increases in blood pressure, including death in one patient, has been reported during administration of these drugs. In addition, methyldopa alone has been reported to cause paradoxical hypertension. Additional studies are needed to define the specific population at risk. |
BETIMOL, BRIMONIDINE TARTRATE-TIMOLOL, CARVEDILOL, CARVEDILOL ER, COMBIGAN, COREG, COREG CR, CORGARD, COSOPT, COSOPT PF, DORZOLAMIDE-TIMOLOL, HEMANGEOL, INDERAL LA, INDERAL XL, INNOPRAN XL, ISTALOL, LABETALOL HCL, LABETALOL HCL-WATER, NADOLOL, PINDOLOL, PROPRANOLOL HCL, PROPRANOLOL HCL ER, PROPRANOLOL-HYDROCHLOROTHIAZID, TIMOLOL, TIMOLOL MALEATE, TIMOLOL-BIMATOPROST, TIMOLOL-BRIMONI-DORZOL-BIMATOP, TIMOLOL-BRIMONIDIN-DORZOLAMIDE, TIMOLOL-DORZOLAMIDE-BIMATOPRST, TIMOPTIC OCUDOSE |
| Methenamine-Sodium Phosphate/Thiazides; Carbonic Anhydrase Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Thiazide diuretics and carbonic anhydrase inhibitors may elevate urinary ph preventing the conversion of methenamine to formaldehyde and mandelic acid.(1) CLINICAL EFFECTS: Concurrent administration may result in alkalinization of the urine causing methenamine to be less effective.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for urinary ph and any worsening symptoms of their infection, including dysuria, flank pain, or fever.(1) DISCUSSION: Administration of thiazide diuretics and carbonic anhydrase inhibitors may result in alkalinization of the urine resulting in therapeutic failure of methenamine. Formaldehyde is released by acid hydrolysis from methenamine resulting in bactericidal concentrations at urinary ph 5.0 to 5.5. Above urinary ph 6.0 there is insufficient quantities of formaldehyde and methenamine released to achieve a therapeutic response.(1) |
UROQID-ACID NO.2 |
| Sodium Phosphate Bowel Cleanser/Diuretics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Bowel cleansing with sodium phosphate causes dehydration, decreased intravascular volume and hyperphosphatemia, which increases phosphate levels in the renal tubules. Abnormally high levels of calcium and phosphate in the renal tubules may precipitate out, resulting in renal injury.(1) CLINICAL EFFECTS: Use of sodium phosphate for bowel cleansing in patients maintained on diuretics may increase the risk of acute phosphate nephropathy, which is an acute kidney injury associated with deposits of calcium phosphate crystal in the renal tubules that may result in permanent renal function impairment. Acute phosphate nephropathy presents as acute kidney injury with minimal proteinuria and a bland urine sediment.(2) Use of oral sodium phosphate products at laxative doses has not been associated with acute kidney injury.(3) PREDISPOSING FACTORS: Patients who may be at an increased risk of acute phosphate nephropathy include those who are over age 55; are hypovolemic or have decreased intravascular volume; have baseline kidney disease, bowel obstruction, or active colitis; and who are using medications that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotension receptor blockers (ARBs) and possibly nonsteroidal anti-inflammatory drugs (NSAIDs).(2) PATIENT MANAGEMENT: If possible, use an alternative agent for bowel cleansing.(1) Use sodium phosphate products with caution in patients taking medications that affect kidney function or perfusion, such as diuretics. Obtain baseline and post-procedure labs (electrolytes, calcium, phosphate, BUN, creatinine, and [in smaller, frail individuals] glomerular filtration rate). Instruct patients to drink sufficient quantities of clear fluids before, during, and after bowel cleansing and to avoid other laxatives that contain sodium phosphate. Consider hospitalization and intravenous hydration during bowel cleansing to support frail patients who may be unable to drink an appropriate volume of fluid or who may be without assistance at home.(2) Use of an electrolyte solution for rehydration may decrease the risk of acute phosphate nephropathy.(4,5) DISCUSSION: Since May 2006, the FDA has received 20 reports of acute phosphate nephropathy associated with the use of Osmo Prep. Concomitant medications included ACE inhibitors or ARBs (11), diuretics (6), and NSAIDs (4).(2) In a retrospective review of colonoscopy patients, simultaneous use of ACE inhibitors or ARBs significantly increased the risk of acute kidney injury from oral sodium phosphate. Diuretic use was also a risk factor.(6) In a case series study of 21 cases of acute phosphate nephropathy in patients who had used oral sodium phosphate, 14 patients received an ACE inhibitor or ARB, 4 used a diuretic, and 3 used an NSAID.(7) Cases have also been reported with rectal products.(8) |
MB CAPS, SODIUM PHOSPHATE DIBASIC, URIMAR-T, URNEVA |
| Aminolevulinic Acid/Selected Photosensitizers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Aminolevulinic acid, anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are all known photosensitizers.(1) CLINICAL EFFECTS: Concurrent use of aminolevulinic acid in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer states that aminolevulinic acid should be avoided in patients receiving photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides for 24 hours before and after administration of aminolevulinic acid.(1) DISCUSSION: Because of the risk of increased photosensitivity, the US manufacturer states that aminolevulinic acid should be avoided in patients receiving photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides for 24 hours before and after administration of aminolevulinic acid.(1) |
AMINOLEVULINIC ACID HCL, GLEOLAN |
| Porfimer/Selected Photosensitizers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Porfimer causes photosensitivity due to residual drug which is present in all parts of the skin. Anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are other known photosensitizers.(1) CLINICAL EFFECTS: Concurrent use of porfimer in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1) PREDISPOSING FACTORS: Patients with any hepatic impairment and patients with severe renal impairment have reduced drug elimination and may remain photosensitive for 90 days or longer.(1) PATIENT MANAGEMENT: The US manufacturer of porfimer states that concurrent use of porfimer with photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides should be avoided.(1) Since the photosensitive effect of porfimer may persist for at least 30 days (and for 90 days in some patients), it would be prudent to avoid other photosensitizing agents for at least 30 days after administration of porfimer. DISCUSSION: All patients who have received porfimer become photosensitive. It is unknown what the risk of photosensitivity reactions is when porfimer is used concurrently with other photosensitizing agents. When porfimer was used in clinical trials, photosensitivity reactions occurred in about 20% of cancer patients and in 69% of high-grade dysplasia in Barretts esophagus patients. Most of the reactions were mild to moderate erythema, but they also included swelling, pruritus, burning sensation, feeling hot, or blisters. The majority of reactions occurred within 90 days of porfimer administration.(1) |
PHOTOFRIN |
| Methoxsalen/Selected Photosensitizers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Methoxsalen causes photosensitivity due to residual drug which is present in all parts of the skin from photopheresis. Anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are other known photosensitizers.(1) CLINICAL EFFECTS: Concurrent use of methoxsalen in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of methoxsalen states that concurrent use of methoxsalen with anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides should be avoided.(1) DISCUSSION: All patients who have received methoxsalen become photosensitive. It is unknown what the risk of photosensitivity reactions is when methoxsalen is used concurrently with other photosensitizing agents.(1) |
METHOXSALEN, UVADEX |
There are 12 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 |
|---|---|
| Digitalis Glycosides/Kaluretics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Potassium-losing diuretics may result in potassium depletion which can predispose patients to digitalis toxicity. CLINICAL EFFECTS: May observe increased arrhythmias, resulting from an increase in the cardiac response to digitalis. Symptoms of digoxin toxicity can include anorexia, nausea, vomiting, headache, fatigue, malaise, drowsiness, generalized muscle weakness, disorientation, hallucinations, visual disturbances, and arrhythmias. PREDISPOSING FACTORS: Low body weight, advanced age, impaired renal function, hypokalemia, hypercalcemia, and/or hypomagnesemia may increase the risk of digoxin toxicity. PATIENT MANAGEMENT: Monitor serum potassium status and give potassium replacements as needed. DISCUSSION: This interaction is well documented. Most patients taking diuretics do not develop significant potassium depletion if they are on low doses of diuretics and have adequate potassium intake. |
DIGITEK, DIGOXIN, DIGOXIN MICRONIZED, LANOXIN, LANOXIN PEDIATRIC |
| Thiazide & Related Diuretics/Cholestyramine; Colestipol SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Cholestyramine and colestipol, anionic exchange resins, bind thiazides and furosemide, preventing their absorption. CLINICAL EFFECTS: Concurrent administration may result in decreased absorption of the diuretic, as well as decreased clinical effects. Decreased absorption of furosemide by 80-90% has been reported. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Available data suggest that colestipol may be preferable to cholestyramine. Separating administration times lessens the the extent of this interaction but still remains significant. Separate the administration of cholestyramine and the thiazide by at least four hours and that of colestipol by at least two hours. Separate the administration of furosemide and cholestyramine or colestipol by two to three hours. DISCUSSION: Administration of cholestyramine or colestipol decreased total urinary excretion of hydrochlorothiazide by 85% and 43% respectively. These studies indicate that no dosing schedule will eliminate this interaction. Even four hours of separation reduces the absorption of hydrochlorothiazide by 35%. Similar reductions occurred to serum hydrochlorothiazide concentrations. In a study in six subjects, the concurrent administration of cholestyramine and furosemide resulted in a decrease in furosemide area-under-curve (AUC) by 90% and a decrease in furosemide's diuretic effects. Concurrent administration of furosemide and colestipol resulted in a decrease in furosemide AUC by 80% and a decrease in furosemide's diuretic effects. |
CHOLESTYRAMINE, CHOLESTYRAMINE LIGHT, CHOLESTYRAMINE RESIN, COLESTID, COLESTIPOL HCL, PREVALITE, QUESTRAN, QUESTRAN LIGHT |
| Thiazides/Antidiabetics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Thiazides antagonize hypoglycemic effects of antidiabetics due to intrinsic hyperglycemic activity. CLINICAL EFFECTS: Impaired glucose tolerance and diminished hypoglycemic effects of antidiabetics may occur. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Caution when starting or stopping thiazides in diabetic patients. Adjust the antidiabetic dose as needed based on blood glucose levels. DISCUSSION: This interaction is likely to occur based upon well documented properties of the interacting drugs. However, there is individual variability in its occurrence. A cross-sectional study of 425 outpatients found 46 patients with 86 suspected drug interactions resulting in uncontrolled glycemia. Recorded drug interactions included hydrochlorothiazide-gliclazide (22.1%), hydrochlorothiazide-insulins (2.3%), and chlorothiazide-gliclazide (1.2%). Using the drug interaction probability scale (DIPS), these drug interactions were categorized as possible.(2) |
ACARBOSE, ADMELOG, ADMELOG SOLOSTAR, AFREZZA, APIDRA, APIDRA SOLOSTAR, BASAGLAR KWIKPEN U-100, BASAGLAR TEMPO PEN U-100, DUETACT, FIASP, FIASP FLEXTOUCH, FIASP PENFILL, FIASP PUMPCART, GLIMEPIRIDE, GLIPIZIDE, GLIPIZIDE ER, GLIPIZIDE XL, GLIPIZIDE-METFORMIN, GLUCOTROL XL, GLYBURIDE, GLYBURIDE MICRONIZED, GLYBURIDE-METFORMIN HCL, HUMALOG, HUMALOG JUNIOR KWIKPEN, HUMALOG KWIKPEN U-100, HUMALOG KWIKPEN U-200, HUMALOG MIX 50-50 KWIKPEN, HUMALOG MIX 75-25, HUMALOG MIX 75-25 KWIKPEN, HUMALOG TEMPO PEN U-100, HUMULIN R U-500, HUMULIN R U-500 KWIKPEN, INSULIN ASPART, INSULIN ASPART FLEXPEN, INSULIN ASPART PENFILL, INSULIN ASPART PROT MIX 70-30, INSULIN DEGLUDEC, INSULIN DEGLUDEC PEN (U-100), INSULIN DEGLUDEC PEN (U-200), INSULIN GLARGINE MAX SOLOSTAR, INSULIN GLARGINE SOLOSTAR, INSULIN GLARGINE-YFGN, INSULIN LISPRO, INSULIN LISPRO JUNIOR KWIKPEN, INSULIN LISPRO KWIKPEN U-100, INSULIN LISPRO PROTAMINE MIX, LANTUS, LANTUS SOLOSTAR, LYUMJEV, LYUMJEV KWIKPEN U-100, LYUMJEV KWIKPEN U-200, LYUMJEV TEMPO PEN U-100, MIGLITOL, MYXREDLIN, NATEGLINIDE, NOVOLOG, NOVOLOG FLEXPEN, NOVOLOG MIX 70-30, NOVOLOG MIX 70-30 FLEXPEN, NOVOLOG PENFILL, PIOGLITAZONE-GLIMEPIRIDE, PRECOSE, REZVOGLAR KWIKPEN, SEMGLEE (YFGN), SEMGLEE (YFGN) PEN, SOLIQUA 100-33, TOUJEO MAX SOLOSTAR, TOUJEO SOLOSTAR, TRESIBA, TRESIBA FLEXTOUCH U-100, TRESIBA FLEXTOUCH U-200, XULTOPHY 100-3.6 |
| Sympathomimetics (Direct, Mixed-Acting)/Methyldopa SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown. CLINICAL EFFECTS: The pressor response to sympathomimetics may be increased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Start with low doses of sympathomimetics and monitor blood pressure of patients during concurrent administration of sympathomimetics and methyldopa. DISCUSSION: The pressor response to sympathomimetics has been reported to be increased during methyldopa administration. In addition to increased duration of pressor response, severe hypertension has been reported. |
ADRENALIN, AKOVAZ, ARTICADENT DENTAL, ARTICAINE-EPINEPHRINE, ARTICAINE-EPINEPHRINE BIT, BIORPHEN, BROMFED DM, BROMPHENIRAMINE-PSEUDOEPHED-DM, BUFFERED LIDOCAINE-EPINEPHRINE, BUPIVACAINE HCL-EPINEPHRINE, BUPIVACAINE-DEXAMETH-EPINEPHRN, CITANEST FORTE DENTAL, CLARINEX-D 12 HOUR, DOBUTAMINE HCL, DOBUTAMINE HCL-D5W, DOPAMINE HCL, DOPAMINE HCL IN 5% DEXTROSE, DROXIDOPA, EMERPHED, EPHEDRINE HCL, EPHEDRINE SULFATE, EPHEDRINE SULFATE-0.9% NACL, EPHEDRINE SULFATE-NACL, EPINEPHRINE, EPINEPHRINE BITARTR-0.9% NACL, EPINEPHRINE BITARTRATE, EPINEPHRINE BITARTRATE-NACL, EPINEPHRINE CONVENIENCE KIT, EPINEPHRINE HCL-0.9% NACL, EPINEPHRINE HCL-D5W, EPINEPHRINE-0.9% NACL, EPINEPHRINE-D5W, EPINEPHRINE-NACL, IMMPHENTIV, ISOPROTERENOL HCL, ISOPROTERENOL HCL-0.9% NACL, ISUPREL, LEVOPHED, LIDOCAINE HCL-EPINEPHRINE, LIDOCAINE HCL-EPINEPHRINE-NACL, LIDOCAINE-EPINEPHRINE, LIGNOSPAN STANDARD, MARCAINE-EPINEPHRINE, MIDODRINE HCL, NOREPINEPHRINE BITAR-0.9% NACL, NOREPINEPHRINE BITARTRAT-WATER, NOREPINEPHRINE BITARTRATE, NOREPINEPHRINE BITARTRATE-D5W, NORTHERA, ORABLOC, PHENYLEPHRINE HCL, PHENYLEPHRINE HCL-0.9% NACL, PHENYLEPHRINE HCL-NACL, PHENYLEPHRINE HCL-WATER, PROMETHAZINE VC, PROMETHAZINE-PHENYLEPHRINE HCL, PSEUDOEPHEDRINE HCL, R.E.C.K.(ROPIV-EPI-CLON-KETOR), RACEPINEPHRINE HCL, RESPA A.R., REZIPRES, SENSORCAINE-EPINEPHRINE, SENSORCAINE-MPF EPINEPHRINE, SEPTOCAINE, VAZCULEP, VIVACAINE, XYLOCAINE DENTAL-EPINEPHRINE, XYLOCAINE WITH EPINEPHRINE, XYLOCAINE-MPF WITH EPINEPHRINE |
| Entacapone; Opicapone/COMT-Metabolized Agents SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Entacapone and opicapone are selective and reversible inhibitors of catechol-O-methyltransferase (COMT) and drugs that are metabolized by COMT can not be fully metabolized when given with entacapone or opicapone.(1) CLINICAL EFFECTS: COMT-metabolized agents can interact with entacapone or opicapone and may result in an increased heart rates, arrhythmias, or an excessive change in blood pressure.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturers of entacapone and opicapone recommend using caution when administering entacapone or opicapone and a COMT-metabolized agent regardless of the route of administration (including inhalation).(1-3) DISCUSSION: In an interaction study, ventricular tachycardia was observed after epinephrine and entacapone administration.(1) Another study on the effect of entacapone given with isoproterenol and epinephrine concluded that entacapone may potentiate the chronotropic and arrhythmogenic effects of isoproterenol and epinephrine.(4) |
CARBIDOPA-LEVODOPA-ENTACAPONE, ENTACAPONE, ONGENTYS |
| Zoledronic Acid/Diuretics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of zoledronic acid and a diuretic may have adverse effects on the renal system.(1,2) CLINICAL EFFECTS: Concurrent use of zoledronic acid and a diuretic may result in renal dysfunction. Deterioration in renal function, acute renal failure requiring dialysis, and death have been reported.(1) PREDISPOSING FACTORS: The interaction may be more likely in elderly patients, patients who are taking other drugs that impact renal function, patients with pre-existing renal compromise, and patients who are dehydrated.(1) PATIENT MANAGEMENT: Patients should be adequately hydrated with 500 ml (2 glasses of water) before and after zoledronic acid administration.(1) Creatinine clearance should be monitored before and after therapy and zoledronic acid should not be administered in patients with a creatinine clearance less than 35 ml/min.(1,3) DISCUSSION: Zoledronic acid has been associated with renal dysfunction, including deterioration in renal function, acute renal failure requiring dialysis, and death. Risk factors include advanced age, concomitant nephrotoxic agents, and dehydration.(1) The FDA has received 16 reports of fatal acute renal failure and 9 reports of renal injury requiring dialysis following the administration of Reclast (zoledronic acid).(3) |
RECLAST, ZOLEDRONIC ACID |
| Oral Methyldopa/Oral Iron SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Iron, in several forms, binds strongly to methyldopa, producing iron complexes thereby reducing methyldopa absorption. CLINICAL EFFECTS: Concomitant use of methyldopa with iron supplementation may decrease the clinical efficacy of methyldopa. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients requiring iron supplementation should be advised to take methyldopa two hours prior to any iron products. DISCUSSION: In a randomized crossover trial with 12 subjects, concurrent use of methyldopa (500 mg daily) and ferrous sulfate (325 mg daily) showed a 28.4% decrease in the proportion of "free" methyldopa (p<0.01), a 28% increase in the proportion excreted as methyldopa sulfate (p<0.01), and a 21.2% decrease in total absorbed methyldopa (p<0.01). Similar results were found when administering ferrous gluconate (600 mg daily). Antihypertensive effects of methyldopa while taking ferrous sulfate were also assessed in five patients chronically taking methyldopa. All participants showed an increase in systolic blood pressure (p=0.03) after two weeks of ferrous sulfate administration. Diastolic blood pressure increased in four patients (p>0.05). After 14 days, three patients had an increase in systolic pressure greater than 15 mm Hg and two patients had an increase of greater than 10 mm Hg in diastolic blood pressures. Both systolic and diastolic pressures decreased after ferrous sulfate was discontinued.(2) |
ACCRUFER, AUROVELA 24 FE, AUROVELA FE, AURYXIA, BALCOLTRA, BLISOVI 24 FE, BLISOVI FE, CHARLOTTE 24 FE, FEIRZA, FERRIC CITRATE, FINZALA, GEMMILY, HAILEY 24 FE, HAILEY FE, JOYEAUX, JUNEL FE, JUNEL FE 24, KAITLIB FE, LARIN 24 FE, LARIN FE, LAYOLIS FE, LEVONORG-ETH ESTRAD-FE BISGLYC, LO LOESTRIN FE, LOESTRIN FE, MERZEE, MIBELAS 24 FE, MICROGESTIN FE, MINZOYA, NORETHIN-ETH ESTRA-FERROUS FUM, NORETHINDRONE-E.ESTRADIOL-IRON, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TAYTULLA, TILIA FE, TRI-LEGEST FE, VELPHORO, WYMZYA FE, XARAH FE, XELRIA FE |
| Topiramate/Hydrochlorothiazide SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Hydrochlorothiazide may increase levels of topiramate. Also, both agents may decrease potassium levels.(1,2) CLINICAL EFFECTS: Concurrent use of hydrochlorothiazide may result in elevated levels of topiramate and hypokalemia.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor serum potassium and topiramate in patients receiving concurrent therapy. The dosage of topiramate may need to be adjusted, an alternative diuretic or potassium supplement may be needed. DISCUSSION: In a study in 23 healthy subjects, concurrent hydrochlorothiazide (25 mg daily) increased the maximum concentration (Cmax) and area-under-curve (AUC) of topiramate (96 mg BID) by 27% and 29%, respectively. During concurrent therapy, 61% of patients had a serum potassium level less than 3.5 mEq/L, compared with 27% with topiramate alone and 25% with hydrochlorothiazide alone. During concurrent therapy, the mean decrease in serum potassium levels was -0.60 mEq/L, compared with -0.25 mEq/L with topiramate alone and -0.12 mEq/L with hydrochlorothiazide alone.(1) |
EPRONTIA, QSYMIA, TOPAMAX, TOPIRAMATE, TOPIRAMATE ER, TOPIRAMATE ER SPRINKLE, TROKENDI XR |
| Desmopressin/Agents with Hyponatremia Risk SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Carbamazepine, chlorpromazine, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants increase the risk of hyponatremia.(1-3) CLINICAL EFFECTS: Concurrent use may increase the risk of hyponatremia with desmopressin.(1-3) PREDISPOSING FACTORS: Predisposing factors for hyponatremia include: polydipsia, renal impairment (eGFR < 50 ml/min/1.73m2), illnesses that can cause fluid/electrolyte imbalances, age >=65, medications that cause water retention and/or increase the risk of hyponatremia (glucocorticoids, loop diuretics). PATIENT MANAGEMENT: The concurrent use of agents with a risk of hyponatremia with desmopressin may increase the risk of hyponatremia. If concurrent use is deemed medically necessary, make sure serum sodium levels are normal before beginning therapy and consider using the desmopressin nasal 0.83 mcg dose. Consider measuring serum sodium levels more frequently than the recommended intervals of: within 7 days of concurrent therapy initiation, one month after concurrent therapy initiation and periodically during treatment. Counsel patients to report symptoms of hyponatremia, which may include: headache, nausea/vomiting, feeling restless, fatigue, drowsiness, dizziness, muscle cramps, changes in mental state (confusion, decreased awareness/alertness), seizures, coma, and trouble breathing. Counsel patients to limit the amount of fluids they drink in the evening and night-time and to stop taking desmopressin if they develop a stomach/intestinal virus with nausea/vomiting or any nose problems (blockage, stuffy/runny nose, drainage).(1) DISCUSSION: In clinical trials of desmopressin for the treatment of nocturia, 4 of 5 patients who developed severe hyponatremia (serum sodium <= 125 mmol/L) were taking systemic or inhaled glucocorticoids. Three of these patients were also taking NSAIDs and one was receiving a thiazide diuretic.(2) Drugs associated with hyponatremia may increase the risk, including loop diuretics, carbamazepine, chlorpromazine, glucocorticoids, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants.(1,3-4) |
DDAVP, DESMOPRESSIN ACETATE, NOCDURNA |
| Tizanidine/Guanfacine; Methyldopa SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tizanidine is an alpha-2 agonist. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1) CLINICAL EFFECTS: Concurrent use of antihypertensives and tizanidine may result in hypotension.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. The risk of hypotension may be decreased by careful titration of tizanidine dosages and monitoring for hypotension prior to dose advancement. Counsel patients about the risk of orthostatic hypotension.(1) DISCUSSION: Severe hypotension has been reported following the addition of tizanidine to existing lisinopril therapy.(2-4) |
TIZANIDINE HCL, ZANAFLEX |
| Apomorphine/Selected Antihypertensives and Vasodilators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Apomorphine causes dose-dependent decreases in blood pressure. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1) CLINICAL EFFECTS: Concurrent use of antihypertensives and apomorphine may result in orthostatic hypotension with or without dizziness, nausea, or syncope.(1) PREDISPOSING FACTORS: The risk of orthostatic hypotension may be increased during dose escalation of apomorphine and in patients with renal or hepatic impairment.(1) PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. Counsel patients about the risk of orthostatic hypotension.(1) DISCUSSION: Healthy volunteers who took sublingual nitroglycerin (0.4 mg) concomitantly with apomorphine experienced a mean largest decrease in supine systolic blood pressure (SBP) of 9.7 mm Hg and in supine diastolic blood pressure (DBP) of 9.3 mm Hg, and a mean largest decrease in standing SBP and DBP of 14.3 mm Hg and 13.5 mm Hg, respectively. The maximum decrease in SBP and DBP was 65 mm Hg and 43 mm Hg, respectively. When apomorphine was taken alone, the mean largest decrease in supine SBP and DBP was 6.1 mm Hg and 7.3 mm Hg, respectively, and in standing SBP and DBP was 6.7 mm Hg and 8.4 mm Hg, respectively.(1) |
APOKYN, APOMORPHINE HCL, ONAPGO |
| Allopurinol/Thiazide Diuretics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown. Allopurinol has been documented to cause Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), and Drug reaction with eosinophilia and systemic symptoms (DRESS).(1) CLINICAL EFFECTS: Concurrent administration of allopurinol with thiazides may result in an increased incidence of rash which may be severe. PREDISPOSING FACTORS: Patients who are HLA-B*58:01 positive or have impaired renal function may be at increased risk. PATIENT MANAGEMENT: The manufacturer of allopurinol recommends monitoring renal function and reducing the dose of allopurinol in patients with concomitant thiazide diuretic use and impaired renal function. Discontinue allopurinol at the first appearance of skin rash or other signs which may indicate a hypersensitivity reaction when used with thiazide diuretics. Instruct patients to seek medical attention for any peeling skin rash or blisters.(1) DISCUSSION: There are case reports of patients on concurrent thiazide diuretics and allopurinol developing SJS, TEN, or DRESS.(1,2) |
ALLOPURINOL, ALLOPURINOL SODIUM, ALOPRIM, DUZALLO, ZYLOPRIM |
The following contraindication information is available for METHYLDOPA-HYDROCHLOROTHIAZIDE (methyldopa/hydrochlorothiazide):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 4 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Anuria |
| Hepatic cirrhosis |
| Pheochromocytoma |
| Severe hepatic disease |
There are 14 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Autoimmune hemolytic anemia |
| Dehydration |
| Depression |
| Gout |
| Hepatic failure |
| Hyperuricemia |
| Hypochloremic alkalosis |
| Hypokalemia |
| Hypomagnesemia |
| Hyponatremia |
| Hypotension |
| Hypovolemia |
| Neonatal hyperbilirubinemia |
| Porphyria |
There are 16 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Anemia |
| Angina |
| Basal cell carcinoma of skin |
| Chronic heart failure |
| Diabetes mellitus |
| Disease of liver |
| Edema |
| Hypercalcemia |
| Hypercholesterolemia |
| Hyperparathyroidism |
| Kidney disease with reduction in glomerular filtration rate (GFr) |
| Parkinsonism |
| Severe cerebrovascular disease |
| Squamous cell carcinoma of skin |
| Sympathectomy |
| Systemic lupus erythematosus |
The following adverse reaction information is available for METHYLDOPA-HYDROCHLOROTHIAZIDE (methyldopa/hydrochlorothiazide):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 47 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Hypochloremic alkalosis Hypokalemia Hyponatremia Hypotension Peripheral edema |
Altered mental status Drug fever Hyperglycemia Hypomagnesemia Kidney disease with reduction in glomerular filtration rate (GFr) Nephrotoxicity |
| Rare/Very Rare |
|---|
|
Acute pancreatitis Acute respiratory distress syndrome Agranulocytosis Anaphylaxis Aplastic anemia Autoimmune hemolytic anemia Cholestasis Choroidal effusion Colitis Drug-induced hepatitis Erythema multiforme Exfoliative dermatitis Gout Granulocytopenic disorder Hemolytic anemia Hepatitis Hepatocellular damage Hypercalcemia Hyperparathyroidism Hypersensitivity angiitis Hyperuricemia Interstitial nephritis Interstitial pneumonitis Jaundice Leukopenia Myocarditis Myopia Obstructive hyperbilirubinemia Purpura Secondary angle-closure glaucoma Squamous cell carcinoma of skin Stevens-johnson syndrome Systemic lupus erythematosus Thrombocytopenic disorder Toxic epidermal necrolysis Vasculitis |
There are 36 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Drowsy Headache disorder Xerostomia |
Abdominal pain with cramps Abnormal sexual function Anorexia Diarrhea Dizziness Erectile dysfunction Fatigue Libido changes Nasal congestion Nausea Orthostatic hypotension Vomiting |
| Rare/Very Rare |
|---|
|
Basal cell carcinoma of skin Blurred vision Constipation Erectile dysfunction Fever Gastrointestinal irritation General weakness Headache disorder Hypercholesterolemia Hyperprolactinemia Hypertriglyceridemia Muscle spasm Nervousness Paresthesia Sialoadenitis Sinus bradycardia Skin rash Urticaria Vertigo Vomiting Xanthopsia |
The following precautions are available for METHYLDOPA-HYDROCHLOROTHIAZIDE (methyldopa/hydrochlorothiazide):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Reproduction studies in mice, rabbits, and rats using oral methyldopa in dosages of 1000, 200, and 100 mg/kg, respectively, have not revealed evidence of harm to the fetus. These dosages are 16.6, 3.3,
and 1.7 times, respectively, the maximum daily human dosage when compared on the basis of body weight and 1.4, 1.1,
and 0.2 times, respectively, the maximum daily human dosage when compared on the basis of body surface area. Methyldopa has been used for many years in the management of hypertension in pregnant women, and the drug is generally considered safe for mother and fetus when used in association with careful prenatal management.
Uteroplacental blood flow and fetal hemodynamics have been reported to be stable during therapy with the drug. Although no teratogenic effects have been reported, the possibility that methyldopa may cause fetal injury (e.g., secondary to reduced placental blood flow or fetotoxicity) cannot be excluded. In neonates born to women treated with methyldopa, systolic blood pressure may be decreased during the first 2-3 days after delivery; in some neonates, tremors have also been reported.
Studies to date, including a long-term follow-up study, of children born to women who received methyldopa during pregnancy have not revealed evidence of substantial adverse effects of the drug on the offspring; however, in the longest follow-up study, treatment with methyldopa was associated with a smaller head circumference (without an apparent effect on intelligence quotient) in male offspring of those women whose therapy was initiated between 16 and 20 weeks' gestation. At 4 years of age, the developmental delay commonly seen in children born to hypertensive mothers was less evident in those whose mothers received methyldopa during pregnancy than in those whose mothers were untreated. Children born to mothers receiving methyldopa scored consistently higher on indices of intellectual and motor development than children born to untreated hypertensive mothers; however, these differences were not apparent by 7.5
years of age. Methyldopa should be used during pregnancy only when clearly needed. In addition, excessive reduction in blood pressure should be avoided, and a conservative approach to treatment generally should be followed. (See Hypertension during Pregnancy under Uses: Hypertension.)
and 1.7 times, respectively, the maximum daily human dosage when compared on the basis of body weight and 1.4, 1.1,
and 0.2 times, respectively, the maximum daily human dosage when compared on the basis of body surface area. Methyldopa has been used for many years in the management of hypertension in pregnant women, and the drug is generally considered safe for mother and fetus when used in association with careful prenatal management.
Uteroplacental blood flow and fetal hemodynamics have been reported to be stable during therapy with the drug. Although no teratogenic effects have been reported, the possibility that methyldopa may cause fetal injury (e.g., secondary to reduced placental blood flow or fetotoxicity) cannot be excluded. In neonates born to women treated with methyldopa, systolic blood pressure may be decreased during the first 2-3 days after delivery; in some neonates, tremors have also been reported.
Studies to date, including a long-term follow-up study, of children born to women who received methyldopa during pregnancy have not revealed evidence of substantial adverse effects of the drug on the offspring; however, in the longest follow-up study, treatment with methyldopa was associated with a smaller head circumference (without an apparent effect on intelligence quotient) in male offspring of those women whose therapy was initiated between 16 and 20 weeks' gestation. At 4 years of age, the developmental delay commonly seen in children born to hypertensive mothers was less evident in those whose mothers received methyldopa during pregnancy than in those whose mothers were untreated. Children born to mothers receiving methyldopa scored consistently higher on indices of intellectual and motor development than children born to untreated hypertensive mothers; however, these differences were not apparent by 7.5
years of age. Methyldopa should be used during pregnancy only when clearly needed. In addition, excessive reduction in blood pressure should be avoided, and a conservative approach to treatment generally should be followed. (See Hypertension during Pregnancy under Uses: Hypertension.)
Since methyldopa is distributed into milk, the drug should be used with caution in nursing women; the possibility of adverse effects on a nursing infant cannot be excluded. The extent to which methyldopa distributes into milk has not been clearly established, but the amount of drug a nursing infant would ingest is believed to be too small to be clinically important; however, if a woman receiving methyldopa breastfeeds, the infant (particularly if preterm) should be monitored for potential systemic effects of the drug (e.g., decreased respiration, blood pressure, or alertness).
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for METHYLDOPA-HYDROCHLOROTHIAZIDE (methyldopa/hydrochlorothiazide):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for METHYLDOPA-HYDROCHLOROTHIAZIDE (methyldopa/hydrochlorothiazide)'s list of indications:
| Hypertension | |
| I10 | Essential (primary) hypertension |
| I11 | Hypertensive heart disease |
| I11.0 | Hypertensive heart disease with heart failure |
| I11.9 | Hypertensive heart disease without heart failure |
| I12 | Hypertensive chronic kidney disease |
| I12.0 | Hypertensive chronic kidney disease with stage 5 chronic kidney disease or end stage renal disease |
| I12.9 | Hypertensive chronic kidney disease with stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease |
| I13 | Hypertensive heart and chronic kidney disease |
| I13.0 | Hypertensive heart and chronic kidney disease with heart failure and stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease |
| I13.1 | Hypertensive heart and chronic kidney disease without heart failure |
| I13.10 | Hypertensive heart and chronic kidney disease without heart failure, with stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease |
| I13.11 | Hypertensive heart and chronic kidney disease without heart failure, with stage 5 chronic kidney disease, or end stage renal disease |
| I13.2 | Hypertensive heart and chronic kidney disease with heart failure and with stage 5 chronic kidney disease, or end stage renal disease |
| I15.1 | Hypertension secondary to other renal disorders |
Formulary Reference Tool