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DRUG IMAGES
CODEINE SULFATE 30 MG TABLET
The following indications for URETRON D-S (methenamine/methylene blue/sodium phos/pnyl sal/hyosc sul) have been approved by the FDA:
Indications:
None.
Professional Synonyms:
None.
Indications:
None.
Professional Synonyms:
None.
The following dosing information is available for URETRON D-S (methenamine/methylene blue/sodium phos/pnyl sal/hyosc sul):
Dosage of salicylate salts must be carefully adjusted according to Methenamine is commercially available as methenamine hippurate and individual requirements and response, using the lowest possible effective methenamine mandelate; dosage is expressed in terms of the salt.
dosage.
Unless otherwise directed by a clinician, choline salicylate, magnesium salicylate, sodium salicylate should not be used for self-medication of pain for longer than 10 days in adults; choline salicylate and sodium salicylate should not be used for self-medication of pain for longer than 5 days in children. Pain of such intensity and duration may indicate a pathologic condition requiring medical evaluation and supervised treatment. These preparations should not be used in adults or children for self-medication of marked fever (greater than 39.5degreesC), fever persisting longer than 3 days, or recurrent fever, unless otherwise directed by a clinician, since such fevers may indicate serious illness requiring prompt evaluation and treatment by a physician.
In addition, these preparations should not be used in adults or children for self-medication of sore throat for longer than 2 days, unless otherwise directed by a clinician.
To minimize the risk of overdosage, no more than 5 doses of any of these drugs should be administered to children for analgesia or antipyresis in any 24-hour period, unless otherwise directed by a clinician.
The usual adult oral dosage of hyoscyamine is 0.15-0.3 mg, given up to 4 times daily.
If the drug is used in older pediatric patients, dosage should be reduced in proportion to age and weight.
Dosage should be carefully titrated according to the condition, severity of symptoms, and the individual patient's response and tolerance to the drug. Geriatric patients may be more sensitive to the effects of the drug at usual adult dosages.
The usual dosage of hyoscyamine sulfate (as conventional, sublingual, or orally disintegrating tablets or as an oral solution or elixir) in adults and pediatric patients 12 years of age or older is 0.125-0.25 mg, given orally or sublingually every 4 hours or as needed, not to exceed a total dosage of 1.5
mg in a 24-hour period. One manufacturer (Symax(R) SL) recommends an oral or sublingual dosage of 0.125-0.25
mg 3 or 4 times daily. Alternatively, in adults and pediatric patients 12 years of age or older, 0.375-0.75
mg every 12 hours, not to exceed a total dosage of 1.5 mg in a 24-hour period, may be given orally as extended-release capsules or tablets. If dosage adjustment is required, extended-release capsules and tablets may be administered at a dosage of 0.375
mg every 8 hours. As with other antimuscarinics, higher than recommended dosage may be required for therapeutic effect. Dosage should be carefully titrated until therapeutic effect is achieved or adverse effects become intolerable, using the lowest possible effective dosage.
For pediatric patients 2-11 years of age, the usual dosage of hyoscyamine sulfate (as conventional, sublingual, or orally disintegrating tablets or as an oral solution) is 31.25-125 mcg (0.03125-0.125 mg) given orally or sublingually every 4 hours or as needed, not to exceed a total dosage of 750 mcg in a 24-hour period. One manufacturer (Symax(R) SL) recommends that pediatric patients 2-11 years of age receive an oral or sublingual dosage of 62.5-125
mcg (0.0625-0.125 mg) 3 or 4 times daily. Alternatively, some manufacturers state that pediatric patients 2-11 years of age may receive a dosage of 375 mcg (0.375 mg) every 12 hours (as extended-release capsules or tablets), not to exceed 750 mcg in a 24-hour period. Manufacturers of hyoscyamine sulfate elixir recommend that dosage in patients 2-11 years of age be determined based on body weight (see Table 1).
Table 1. Weight-based Dosing of Hyoscyamine Sulfate Elixir in Pediatric Patients 2-11 Years of Age
Body Weight Usual Dosage Maximum Dosage in a 24-hour Period 10 kg (22 lb) 1.25 mL (31.25 mcg) 7.5 mL (187.5 mcg) every 4 hours or as needed 20 kg (44 lb) 2.5
mL (62.5 mcg) every 15 mL (375 mcg) 4 hours or as needed 40 kg (88 lb) 3.75 mL (93.75 mcg) 22.5 mL (562.5 mcg) every 4 hours or as needed 50 kg (110 lb) 5 mL (125 mcg) every 4 30 mL (750 mcg) hours or as needed
For pediatric patients younger than 2 years of age, manufacturers of hyoscyamine sulfate oral solution (drops) recommend weight-based dosing (see Table 2).
Table 2. Weight-based Dosing of Hyoscyamine Sulfate Oral Solution (Drops) in Pediatric Patients Younger Than 2 Years of Age
Body Weight Usual Dosage Maximum Dosage in a 24-hour Period 3.4 kg (7.5 lb) 4 drops (15.63 mcg) 24 drops (93.75 mcg) every 4 hours or as needed 5 kg (11 lb) 5 drops (19.53 mcg) 30 drops (117.19 mcg) every 4 hours or as needed 7 kg (15 lb) 6 drops (23.44 mcg) 36 drops (140.63 mcg) every 4 hours or as needed 10 kg (22 lb) 8 drops (31.25 mcg) 48 drops (187.5 mcg) every 4 hours or as needed
Using the dropper provided by the manufacturer, which is calibrated to deliver approximately 32 drops/mL.
The usual IV, IM, or subcutaneous dosage of hyoscyamine sulfate for the treatment of GI disorders in adults is 0.25-0.5 mg every 4 hours, 2-4 times daily.
For the treatment of acute symptoms associated with GI disorders, a single parenteral dose of 0.25-0.5 mg may be sufficient.
Dosage should be adjusted according to the individual patient's response and tolerance.
For diagnostic procedures (e.g., endoscopy, hypotonic duodenography) in adults, 0.25-0.5 mg of hyoscyamine sulfate is administered by IV, IM, or subcutaneous injection 5-10 minutes prior to the diagnostic procedure.
As a preoperative medication in adults and pediatric patients older than 2 years of age, the usual dose of hyoscyamine sulfate is 5 mcg (0.005 mg) per kg given IV, IM, or subcutaneously 30-60 minutes prior to the anticipated time of induction of anesthesia or at the time other preanesthetic medications (e.g., opiates, sedatives) are administered. For intraoperative use to reverse drug-induced bradycardia, hyoscyamine sulfate is administered IV in 0. 125-mg increments, repeated as necessary.
To block adverse muscarinic effects of anticholinesterase agents (i.e., neostigmine, physostigmine, pyridostigmine) when these agents are used to reverse the neuromuscular blockade produced by curariform agents, the usual IV dose of hyoscyamine sulfate in adults and pediatric patients older than 2 years of age is 0.2 mg for each 1 mg of neostigmine methylsulfate or the equivalent dose of physostigmine salicylate or pyridostigmine bromide administered; hyoscyamine sulfate is administered concurrently with (but in a separate syringe) or a few minutes before the anticholinesterase agent. In the presence of bradycardia, hyoscyamine sulfate should be given IV before the anticholinesterase agent to increase the pulse rate to about 80 beats/minute.
For the treatment of muscarinic toxicity resulting from exposure to anticholinesterase compounds (e.g., organophosphate pesticides), the usual initial adult dose of hyoscyamine sulfate is 1-2 mg, preferably administered IV. Additional 1-mg doses may be administered IM or IV every 3-10 minutes until muscarinic signs and symptoms subside and repeated if they reappear. Up to 25 mg of the drug may be required during the first 24 hours of therapy.
Subsequently, 0.5-1 mg may be administered orally at intervals of several hours as maintenance therapy until signs and symptoms completely subside. A cholinesterase reactivator (e.g., pralidoxime) is administered concomitantly with antimuscarinic therapy.
dosage.
Unless otherwise directed by a clinician, choline salicylate, magnesium salicylate, sodium salicylate should not be used for self-medication of pain for longer than 10 days in adults; choline salicylate and sodium salicylate should not be used for self-medication of pain for longer than 5 days in children. Pain of such intensity and duration may indicate a pathologic condition requiring medical evaluation and supervised treatment. These preparations should not be used in adults or children for self-medication of marked fever (greater than 39.5degreesC), fever persisting longer than 3 days, or recurrent fever, unless otherwise directed by a clinician, since such fevers may indicate serious illness requiring prompt evaluation and treatment by a physician.
In addition, these preparations should not be used in adults or children for self-medication of sore throat for longer than 2 days, unless otherwise directed by a clinician.
To minimize the risk of overdosage, no more than 5 doses of any of these drugs should be administered to children for analgesia or antipyresis in any 24-hour period, unless otherwise directed by a clinician.
The usual adult oral dosage of hyoscyamine is 0.15-0.3 mg, given up to 4 times daily.
If the drug is used in older pediatric patients, dosage should be reduced in proportion to age and weight.
Dosage should be carefully titrated according to the condition, severity of symptoms, and the individual patient's response and tolerance to the drug. Geriatric patients may be more sensitive to the effects of the drug at usual adult dosages.
The usual dosage of hyoscyamine sulfate (as conventional, sublingual, or orally disintegrating tablets or as an oral solution or elixir) in adults and pediatric patients 12 years of age or older is 0.125-0.25 mg, given orally or sublingually every 4 hours or as needed, not to exceed a total dosage of 1.5
mg in a 24-hour period. One manufacturer (Symax(R) SL) recommends an oral or sublingual dosage of 0.125-0.25
mg 3 or 4 times daily. Alternatively, in adults and pediatric patients 12 years of age or older, 0.375-0.75
mg every 12 hours, not to exceed a total dosage of 1.5 mg in a 24-hour period, may be given orally as extended-release capsules or tablets. If dosage adjustment is required, extended-release capsules and tablets may be administered at a dosage of 0.375
mg every 8 hours. As with other antimuscarinics, higher than recommended dosage may be required for therapeutic effect. Dosage should be carefully titrated until therapeutic effect is achieved or adverse effects become intolerable, using the lowest possible effective dosage.
For pediatric patients 2-11 years of age, the usual dosage of hyoscyamine sulfate (as conventional, sublingual, or orally disintegrating tablets or as an oral solution) is 31.25-125 mcg (0.03125-0.125 mg) given orally or sublingually every 4 hours or as needed, not to exceed a total dosage of 750 mcg in a 24-hour period. One manufacturer (Symax(R) SL) recommends that pediatric patients 2-11 years of age receive an oral or sublingual dosage of 62.5-125
mcg (0.0625-0.125 mg) 3 or 4 times daily. Alternatively, some manufacturers state that pediatric patients 2-11 years of age may receive a dosage of 375 mcg (0.375 mg) every 12 hours (as extended-release capsules or tablets), not to exceed 750 mcg in a 24-hour period. Manufacturers of hyoscyamine sulfate elixir recommend that dosage in patients 2-11 years of age be determined based on body weight (see Table 1).
Table 1. Weight-based Dosing of Hyoscyamine Sulfate Elixir in Pediatric Patients 2-11 Years of Age
Body Weight Usual Dosage Maximum Dosage in a 24-hour Period 10 kg (22 lb) 1.25 mL (31.25 mcg) 7.5 mL (187.5 mcg) every 4 hours or as needed 20 kg (44 lb) 2.5
mL (62.5 mcg) every 15 mL (375 mcg) 4 hours or as needed 40 kg (88 lb) 3.75 mL (93.75 mcg) 22.5 mL (562.5 mcg) every 4 hours or as needed 50 kg (110 lb) 5 mL (125 mcg) every 4 30 mL (750 mcg) hours or as needed
For pediatric patients younger than 2 years of age, manufacturers of hyoscyamine sulfate oral solution (drops) recommend weight-based dosing (see Table 2).
Table 2. Weight-based Dosing of Hyoscyamine Sulfate Oral Solution (Drops) in Pediatric Patients Younger Than 2 Years of Age
Body Weight Usual Dosage Maximum Dosage in a 24-hour Period 3.4 kg (7.5 lb) 4 drops (15.63 mcg) 24 drops (93.75 mcg) every 4 hours or as needed 5 kg (11 lb) 5 drops (19.53 mcg) 30 drops (117.19 mcg) every 4 hours or as needed 7 kg (15 lb) 6 drops (23.44 mcg) 36 drops (140.63 mcg) every 4 hours or as needed 10 kg (22 lb) 8 drops (31.25 mcg) 48 drops (187.5 mcg) every 4 hours or as needed
Using the dropper provided by the manufacturer, which is calibrated to deliver approximately 32 drops/mL.
The usual IV, IM, or subcutaneous dosage of hyoscyamine sulfate for the treatment of GI disorders in adults is 0.25-0.5 mg every 4 hours, 2-4 times daily.
For the treatment of acute symptoms associated with GI disorders, a single parenteral dose of 0.25-0.5 mg may be sufficient.
Dosage should be adjusted according to the individual patient's response and tolerance.
For diagnostic procedures (e.g., endoscopy, hypotonic duodenography) in adults, 0.25-0.5 mg of hyoscyamine sulfate is administered by IV, IM, or subcutaneous injection 5-10 minutes prior to the diagnostic procedure.
As a preoperative medication in adults and pediatric patients older than 2 years of age, the usual dose of hyoscyamine sulfate is 5 mcg (0.005 mg) per kg given IV, IM, or subcutaneously 30-60 minutes prior to the anticipated time of induction of anesthesia or at the time other preanesthetic medications (e.g., opiates, sedatives) are administered. For intraoperative use to reverse drug-induced bradycardia, hyoscyamine sulfate is administered IV in 0. 125-mg increments, repeated as necessary.
To block adverse muscarinic effects of anticholinesterase agents (i.e., neostigmine, physostigmine, pyridostigmine) when these agents are used to reverse the neuromuscular blockade produced by curariform agents, the usual IV dose of hyoscyamine sulfate in adults and pediatric patients older than 2 years of age is 0.2 mg for each 1 mg of neostigmine methylsulfate or the equivalent dose of physostigmine salicylate or pyridostigmine bromide administered; hyoscyamine sulfate is administered concurrently with (but in a separate syringe) or a few minutes before the anticholinesterase agent. In the presence of bradycardia, hyoscyamine sulfate should be given IV before the anticholinesterase agent to increase the pulse rate to about 80 beats/minute.
For the treatment of muscarinic toxicity resulting from exposure to anticholinesterase compounds (e.g., organophosphate pesticides), the usual initial adult dose of hyoscyamine sulfate is 1-2 mg, preferably administered IV. Additional 1-mg doses may be administered IM or IV every 3-10 minutes until muscarinic signs and symptoms subside and repeated if they reappear. Up to 25 mg of the drug may be required during the first 24 hours of therapy.
Subsequently, 0.5-1 mg may be administered orally at intervals of several hours as maintenance therapy until signs and symptoms completely subside. A cholinesterase reactivator (e.g., pralidoxime) is administered concomitantly with antimuscarinic therapy.
Choline salicylate, magnesium salicylate, sodium salicylate, and combination preparations containing choline salicylate and magnesium salicylate are administered orally. The drugs should usually be given with food or a large quantity (240 mL) of water or milk to minimize gastric irritation. Although rarely necessary, sodium salicylate may also be administered by slow IV infusion.
Trolamine salicylate is applied topically. Hyoscyamine is administered orally. Hyoscyamine sulfate is usually administered orally or sublingually.
Hyoscyamine sulfate also may be administered by IV, IM, or subcutaneous injection when oral or sublingual administration is not feasible or when rapid therapeutic effect is necessary. Hyoscyamine sulfate is commercially available as conventional (immediate-release) tablets, extended-release capsules and tablets, oral solutions (drops), elixirs, sublingual tablets, orally disintegrating tablets, and injection. Immediate-release preparations of hyoscyamine sulfate (conventional, sublingual, or orally disintegrating tablets; oral solutions (drops); elixirs) generally are administered orally or sublingually 3-6 times daily.
Extended-release preparations of hyoscyamine sulfate should not be crushed or chewed. Symax(R) SR and Symax(R) DuoTab(R) tablets should be swallowed whole, while Levbid(R) tablets and certain generic preparations are scored and may be broken in order to titrate dosage. Extended-release preparations generally are administered every 12 hours, but preparations that are not scored may be administered every 8 hours if dosage adjustment is required.
Patients should be advised that extended-release preparations may not completely disintegrate and fragments may be excreted in stools in some patients. Sublingual tablets of hyoscyamine sulfate (i.e., Levsin(R)/SL, Symax(R) SL, generic preparations) may be administered sublingually or orally. Certain sublingual tablets (e.g., Levsin(R)/SL, certain generic preparations) also may be chewed.
The manufacturers of Levsin(R)/SL and certain generic preparations state that oral administration of the sublingual tablets results in similar pharmacologic effects as sublingual administration, although the onset may not be as rapid. Orally disintegrating tablets of hyoscyamine sulfate (i.e., NuLev(R), Symax(R) FasTab(R), generic preparations) are administered by placing a tablet on the tongue to dissolve and be swallowed with the saliva; orally disintegrating tablets may be administered with or without water. Individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that each 0.125-mg
NuLev(R), Symax(R) FasTab(R), or generic hyoscyamine sulfate (marketed by Ethex) orally disintegrating tablet contains aspartame (NutraSweet(R)), which is metabolized in the GI tract to provide about 1.7, 4.5, or 0.5
mg, respectively, of phenylalanine following oral administration. Because antacids may decrease absorption of oral hyoscyamine sulfate when these drugs are administered simultaneously, most manufacturers recommend administration of hyoscyamine sulfate before meals and administration of antacids postprandially. One manufacturer recommends routine administration of hyoscyamine sulfate (Symax(R) formulations) 30-60 minutes before meals.
Hyoscyamine sulfate injection may be administered by IV, IM, or subcutaneous injection without prior dilution. Parenteral hyoscyamine sulfate solutions should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Methylene blue is administered by slow IV injection over a period of several minutes (e.g., 5-30 minutes); high local concentrations of the drug should be avoided.
(See Cautions: Adverse Effects.) Methylene blue also has been given by IV infusion+. The manufacturer of the commercially available 5-mg/mL solution for IV use (Provayblue(R)) states that the drug may be diluted, if desired, in 50 mL of 5% dextrose injection to avoid local pain, particularly in pediatric patients. While methylene blue has been diluted in 0.9%
sodium chloride injection, some manufacturers recommend against this because chloride reduces the solubility of methylene blue. Methylene blue IV solutions should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The diluted solution of the drug should be used immediately after preparation.
Methylene blue has been administered orally+, but oral preparations are no longer commercially available in the US. It has been suggested that an oral solution can be prepared extemporaneously by diluting 5-10 mL of the commercially available 10-mg/mL solution for IV use in 100-200 mL of water. When used as a diagnostic (visualizing) dye+, methylene blue has been administered by local instillation or injection+.
In addition, methylene blue has been administered topically+ for photodynamic therapy+ (PDT). (See Cautions: Adverse Effects.) Methylene blue should not be administered by subcutaneous, intrathecal, or intraspinal injection. (See Cautions: Precautions and Contraindications.) Vital signs, electrocardiogram (ECG), and methemoglobin concentrations should be monitored during treatment with methylene blue and through resolution of methemoglobinemia.
Trolamine salicylate is applied topically. Hyoscyamine is administered orally. Hyoscyamine sulfate is usually administered orally or sublingually.
Hyoscyamine sulfate also may be administered by IV, IM, or subcutaneous injection when oral or sublingual administration is not feasible or when rapid therapeutic effect is necessary. Hyoscyamine sulfate is commercially available as conventional (immediate-release) tablets, extended-release capsules and tablets, oral solutions (drops), elixirs, sublingual tablets, orally disintegrating tablets, and injection. Immediate-release preparations of hyoscyamine sulfate (conventional, sublingual, or orally disintegrating tablets; oral solutions (drops); elixirs) generally are administered orally or sublingually 3-6 times daily.
Extended-release preparations of hyoscyamine sulfate should not be crushed or chewed. Symax(R) SR and Symax(R) DuoTab(R) tablets should be swallowed whole, while Levbid(R) tablets and certain generic preparations are scored and may be broken in order to titrate dosage. Extended-release preparations generally are administered every 12 hours, but preparations that are not scored may be administered every 8 hours if dosage adjustment is required.
Patients should be advised that extended-release preparations may not completely disintegrate and fragments may be excreted in stools in some patients. Sublingual tablets of hyoscyamine sulfate (i.e., Levsin(R)/SL, Symax(R) SL, generic preparations) may be administered sublingually or orally. Certain sublingual tablets (e.g., Levsin(R)/SL, certain generic preparations) also may be chewed.
The manufacturers of Levsin(R)/SL and certain generic preparations state that oral administration of the sublingual tablets results in similar pharmacologic effects as sublingual administration, although the onset may not be as rapid. Orally disintegrating tablets of hyoscyamine sulfate (i.e., NuLev(R), Symax(R) FasTab(R), generic preparations) are administered by placing a tablet on the tongue to dissolve and be swallowed with the saliva; orally disintegrating tablets may be administered with or without water. Individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that each 0.125-mg
NuLev(R), Symax(R) FasTab(R), or generic hyoscyamine sulfate (marketed by Ethex) orally disintegrating tablet contains aspartame (NutraSweet(R)), which is metabolized in the GI tract to provide about 1.7, 4.5, or 0.5
mg, respectively, of phenylalanine following oral administration. Because antacids may decrease absorption of oral hyoscyamine sulfate when these drugs are administered simultaneously, most manufacturers recommend administration of hyoscyamine sulfate before meals and administration of antacids postprandially. One manufacturer recommends routine administration of hyoscyamine sulfate (Symax(R) formulations) 30-60 minutes before meals.
Hyoscyamine sulfate injection may be administered by IV, IM, or subcutaneous injection without prior dilution. Parenteral hyoscyamine sulfate solutions should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Methylene blue is administered by slow IV injection over a period of several minutes (e.g., 5-30 minutes); high local concentrations of the drug should be avoided.
(See Cautions: Adverse Effects.) Methylene blue also has been given by IV infusion+. The manufacturer of the commercially available 5-mg/mL solution for IV use (Provayblue(R)) states that the drug may be diluted, if desired, in 50 mL of 5% dextrose injection to avoid local pain, particularly in pediatric patients. While methylene blue has been diluted in 0.9%
sodium chloride injection, some manufacturers recommend against this because chloride reduces the solubility of methylene blue. Methylene blue IV solutions should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The diluted solution of the drug should be used immediately after preparation.
Methylene blue has been administered orally+, but oral preparations are no longer commercially available in the US. It has been suggested that an oral solution can be prepared extemporaneously by diluting 5-10 mL of the commercially available 10-mg/mL solution for IV use in 100-200 mL of water. When used as a diagnostic (visualizing) dye+, methylene blue has been administered by local instillation or injection+.
In addition, methylene blue has been administered topically+ for photodynamic therapy+ (PDT). (See Cautions: Adverse Effects.) Methylene blue should not be administered by subcutaneous, intrathecal, or intraspinal injection. (See Cautions: Precautions and Contraindications.) Vital signs, electrocardiogram (ECG), and methemoglobin concentrations should be monitored during treatment with methylene blue and through resolution of methemoglobinemia.
No dosing information available.
No generic dosing information available.
The following drug interaction information is available for URETRON D-S (methenamine/methylene blue/sodium phos/pnyl sal/hyosc sul):
There are 6 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 |
|---|---|
| Methenamine/Sulfonamides 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: Methenamine is hydrolyzed to formaldehyde in acidic urine. Sulfonamides may form an insoluble precipitate with formaldehyde in the urine.(1,2) CLINICAL EFFECTS: The concurrent administration of methenamine and sulfamethizole or sulfathiazole is likely to form a precipitate in the urine.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Methenamine should not be administered to patients receiving sulfonamides.(1-3) DISCUSSION: Methenamine is hydrolyzed to formaldehyde in acidic urine. An in vitro study showed that addition of methenamine and mandelic acid to saturated solutions of sulfamethizole at pH 5.0 and 6.0 produced a precipitate in one hour.(4) |
ACETAZOLAMIDE, ACETAZOLAMIDE ER, ACETAZOLAMIDE SODIUM, AZULFIDINE, BACTRIM, BACTRIM DS, DICHLORPHENAMIDE, KEVEYIS, METHAZOLAMIDE, ORMALVI, SULFACETAMIDE, SULFACETAMIDE SOD MONOHYDRATE, SULFACETAMIDE SODIUM, SULFADIAZINE, SULFADIAZINE SODIUM, SULFAMERAZINE, SULFAMETHOXAZOLE, SULFAMETHOXAZOLE-TRIMETHOPRIM, SULFANILAMIDE, SULFAPYRIDINE, SULFASALAZINE, SULFASALAZINE DR, SULFATHIAZOLE, SULFATRIM, SULFISOXAZOLE |
| Ketorolac (Non-Injection)/NSAID; Aspirin (Greater Than 300 mg); Salicylates 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: Possible additive or synergistic side effects.(1,2) CLINICAL EFFECTS: Concurrent use of multiple doses of ketorolac with other non-steroidal anti-inflammatory agents (NSAIDs), salicylates or aspirin may result in an increase in NSAID-related side effects such as bleeding or renal impairment.(1-3) PREDISPOSING FACTORS: Patients with pre-existing renal impairment may be at an increased risk of adverse effects from this interaction. The risk for bleeding episodes may be greater in patients with multiple disease-associated factors (e.g. thrombocytopenia, advanced liver disease). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g., anticoagulants, antiplatelets, corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Risk of GI bleed may be increased in patients who are of older age, in poor health status, or who use alcohol or smoke. Risk may also be increased with longer duration of NSAID use and prior history of peptic ulcer disease and/or GI bleeding. PATIENT MANAGEMENT: Manufacturers of ketorolac state that concurrent use of ketorolac with either other NSAIDs or aspirin is contraindicated.(1,2) If concurrent therapy is deemed medically necessary, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Conduct periodic monitoring of renal function, especially in patients with renal impairment. Instruct patients to report any signs and symptoms of bleeding, such as unusual bruising; red or black, tarry stools; acute abdominal or joint pain and/or swelling. DISCUSSION: Based upon similar pharmacodynamic effects and potentially cumulative risks of serious NSAID-related adverse events, manufacturers of ketorolac state the concurrent administration of ketorolac with other NSAIDs or aspirin is contraindicated.(1,2) |
KETOROLAC TROMETHAMINE, SPRIX |
| Pramlintide/Anticholinergics; Antispasmodics 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: Pramlintide slows gastric emptying. Anticholinergics and antispasmodics may result in additive or synergistic effects on gastric emptying. CLINICAL EFFECTS: Concurrent use of pramlintide and anticholinergics or antispasmodics may result in additive or synergistic effects on gastric emptying. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of pramlintide states that pramlintide therapy should not be considered in patients requiring the use of drugs that alter gastrointestinal motility.(1) Patients receiving anticholinergics and antispasmodics should be evaluated for signs of systemic effects which may include constipation. DISCUSSION: Patients using drugs that alter gastrointestinal motility have not been studied in clinical trials for pramlintide.(1) Constipation has been reported as a side effect of anticholinergics and antispasmodics. |
SYMLINPEN 120, SYMLINPEN 60 |
| Ketorolac (Injectable)/NSAIDs; Aspirin (Greater Than 300 mg); Salicylates 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: Possible additive or synergistic side effects.(1) CLINICAL EFFECTS: Concurrent use of multiple doses of ketorolac with other non-steroidal anti-inflammatory agents (NSAIDs), salicylates or aspirin may result in an increase in NSAID-related side effects such as bleeding or renal impairment.(1-3) PREDISPOSING FACTORS: Patients with pre-existing renal impairment may be at an increased risk of adverse effects from this interaction. The risk for bleeding episodes may be greater in patients with multiple disease-associated factors (e.g. thrombocytopenia, advanced liver disease). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g., anticoagulants, antiplatelets, corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Risk of GI bleed may be increased in patients who are of older age, in poor health status, or who use alcohol or smoke. Risk may also be increased with longer duration of NSAID use and prior history of peptic ulcer disease and/or GI bleeding. PATIENT MANAGEMENT: The manufacturer of ketorolac states that concurrent use of ketorolac with either other NSAIDs, salicylates or aspirin is contraindicated.(1) If concurrent therapy is deemed medically necessary, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: Manufacturers of ketorolac state that concurrent use of ketorolac with either other NSAIDs, salicylates or aspirin is contraindicated.(1,2) If concurrent therapy is deemed medically necessary, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Conduct periodic monitoring of renal function, especially in patients with renal impairment. |
BUPIVACAINE-KETOROLAC-KETAMINE, KETOROLAC TROMETHAMINE, R.E.C.K.(ROPIV-EPI-CLON-KETOR), ROPIVACAINE-CLONIDINE-KETOROLC, ROPIVACAINE-KETOROLAC-KETAMINE, TORONOVA II SUIK, TORONOVA SUIK |
| Burosumab/Oral Phosphates; Active Vitamin D Analogs 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: Both burosumab and phosphates or vitamin D may increase serum phosphate levels. This combination may lead to greater increases in serum phosphate than anticipated. CLINICAL EFFECTS: The combination of burosumab with oral phosphates or active vitamin D analogs may result in hyperphosphatemia and may increase the risk of nephrocalcinosis.(1) PREDISPOSING FACTORS: Patients with renal impairment have alterations in mineral metabolism that may increase the risk of hyperphosphatemia.(1) PATIENT MANAGEMENT: The concomitant use of burosumab with oral phosphates or active vitamin D analogs is contraindicated. Discontinue oral phosphate and/or active vitamin D analogs one week before starting burosumab.(1) DISCUSSION: Burosumab restores dysfunctional renal phosphate reabsorption and renal production of 1,25-dihydroxyvitamin D to treat X-linked hypophosphatemia. Additional oral phosphates and/or active vitamin D analogs may raise serum phosphate higher than anticipated. |
CRYSVITA |
| Dichlorphenamide/Aspirin (Greater Than 325 mg); Salicylates 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: Dichlorphenamide may reduce blood pH, causing a shift of salicylates from plasma into tissues (eg, central nervous system).(1) Alternatively, toxicity may be due to salicylate-induced displacement of dichlorphenamide from its protein binding sites and inhibition of renal tubular secretion. CLINICAL EFFECTS: An increase in the pharmacologic effects of salicylates with possible toxicity may occur. Anorexia, tachypnea, lethargy, and coma have been reported.(1) PREDISPOSING FACTORS: High doses of salicylates, low body weight. PATIENT MANAGEMENT: The concurrent use of high-dose aspirin or other salicylates with dichlorphenamide is contraindicated. If it is necessary to administer a low-dose salicylate concurrently, use the lowest dose possible or replace it with a non-salicylate anti-inflammatory agent. Monitor salicylate levels and serum bicarbonate concentrations, and monitor the patient for symptoms of toxicity. Adjust the dose as needed.(1) DISCUSSION: An 8-year-old boy with unimpaired renal and hepatic function was found to have developed metabolic acidosis after treatment for glaucoma and joint pain with a combination of aloxiprin 3.6 gram daily and dichlorphenamide 25 mg three times daily. His symptoms resolved after discontinuation of both aloxiprin and dichlorphenamide and did not recur on subsequent therapy with naproxen and dichlorphenamide.(2) A 75-year old woman taking dichlorphenamide 100 mg to 150 mg daily for therapy of glaucoma and high doses of aspirin (975 mg 4 to 5 times daily) for arthritis developed severe acid-base imbalance and salicylate intoxication. The patient did not exhibit ill effects when taking high aspirin doses without dichlorphenamide.(3) |
DICHLORPHENAMIDE, KEVEYIS, ORMALVI |
There are 17 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 |
|---|---|
| Selected Anticoagulants (Vitamin K antagonists)/Aspirin (Greater Than 100 mg); Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Multiple processes are involved: 1) Salicylate doses greater than 3 gm daily decrease plasma prothrombin levels. 2) Salicylates may also displace anticoagulants from plasma protein binding sites. 3) Aspirin is an irreversible platelet inhibitor. Salicylates impair platelet function, resulting in prolonged bleeding time. 4) Salicylates may cause gastrointestinal(GI) bleeding due to irritation. CLINICAL EFFECTS: The concurrent use of anticoagulants and salicylates leads to blockade of two distinct coagulation pathways and may increase the risk for bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Avoid concomitant administration of these drugs. When aspirin is required for cardioprotection, a low dose (less than 100 mg daily) is recommended to decrease the risk for aspirin-induced GI bleeding. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: This interaction has been reported between aspirin and warfarin and between aspirin and dicumarol. Diflunisal, sodium salicylate, and topical methyl salicylate have been shown to interact with anticoagulants as well. Based on the proposed mechanisms, other salicylates would be expected to interact with anticoagulants as well. A self-controlled case study of 1,622 oral anticoagulant-precipitant drug pairs were reviewed and found 14% of drug pairs were associated with a statistically significant elevated risk of thromboembolism. Concurrent use of warfarin and diflunisal resulted in a ratio of rate ratios (RR) (95% CI) of 3.85 (1.34-11.03); warfarin and aspirin ratio of RR 2.13 (1.72-2.64); warfarin and dipyridamole ratio of RR 2.07 (1.65-2.6); and warfarin and clopidogrel ratio of RR 1.69 (1.56-1.84). A large systematic review was performed on 72 warfarin drug-drug interactions studies that reported on bleeding, thromboembolic events, or death. Most studies were retrospective cohorts. A meta-analysis of 38 of those studies found a higher rate of clinically significant bleeding in patients on warfarin and antiplatelets (OR=1.74; 95% CI 1.56-1.94). Increased bleeding risk was also seen in subgroup analyses with aspirin (OR=1.50; 95% CI 1.29-1.74), clopidogrel (OR=3.55; 95% CI 2.78-4.54), and aspirin plus clopidogrel or ticlopidine (OR=2.07, 95% CI 1.33-3.21).(17) |
ANISINDIONE, DICUMAROL, JANTOVEN, PHENINDIONE, WARFARIN SODIUM |
| Methotrexate (low strength injection, oral)/Select Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Salicylates may inhibit the renal tubular excretion of methotrexate. CLINICAL EFFECTS: The concurrent use of methotrexate and salicylates may result in an increase in the therapeutic and toxic effects of methotrexate, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression, including neutropenia. PREDISPOSING FACTORS: Risk factors for methotrexate toxicity include: - High-dose oncology regimens - Anti-inflammatory doses of aspirin/salicylates - impaired renal function, ascites, or pleural effusions PATIENT MANAGEMENT: US manufacturer prescribing information for methotrexate states nonsteroidal anti-inflammatory drugs, including salicylates should not be administered prior to or concomitantly with high doses of methotrexate. If concurrent therapy is warranted, methotrexate plasma levels should be monitored and patients should be observed for methotrexate toxicity. The dosage of methotrexate may need to be adjusted. Use caution when administering salicylates and low dose methotrexate. Salicylate doses > or = 2 grams per day have been associated with hepatic impairment or impaired renal elimination of methotrexate. It would be prudent to avoid high-dose aspirin, especially in patients with renal impairment or near the time of methotrexate dosage (in patients receiving weekly therapy). DISCUSSION: Several studies and case reports have reported increased and prolonged methotrexate levels in patients receiving concurrent aspirin. One study noted an effect with average weekly doses of methotrexate of 16.6 mg, but not weekly doses of 7.5 mg. Decreased renal function has also been reported with the combination. Single ingredient aspirin or buffered aspirin products with strengths < or = to 325 mg or formulations which are associated with once daily use for cardiovascular protection are not linked to this interaction. Other lower-strength aspirin formulations (e.g. headache, cough & cold, opioid combinations) which could be consumed multiple times a day remain linked to this interaction. |
JYLAMVO, METHOTREXATE, OTREXUP, RASUVO, TREXALL, XATMEP |
| Influenza Virus Vaccine Live/Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Use of salicylates during influenza infection has been associated with Reye's Syndrome.(1,2) CLINICAL EFFECTS: Use of the live influenza virus vaccine in children and adolescents (patients age 2-17 years) receiving salicylate therapy may increase the risk of Reye's Syndrome.(1,2) Symptoms of Reye's syndrome include drowsiness, confusion, seizures, coma. In severe cases, Reye's syndrome can result in death. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The use of live influenza virus vaccine in children and adolescents (patients age 2-17 years) receiving salicylate therapy is contraindicated.(1,2) Use of salicylates should be avoided for 4 weeks after administration of live influenza vaccine.(1) DISCUSSION: Because the use of salicylates during influenza infection has been associated with Reye's Syndrome, the use of live influenza virus vaccine in children and adolescents (patients age 2-17 years) receiving salicylate therapy is contraindicated.(1,2) |
FLUMIST TRIVALENT 2024-2025 |
| Solid Oral Potassium Tablets/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16) CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with anticholinergics may result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16) PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21) PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. Some lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17) |
KLOR-CON 10, KLOR-CON 8, KLOR-CON M10, KLOR-CON M15, KLOR-CON M20, POTASSIUM CHLORIDE, POTASSIUM CITRATE ER, UROCIT-K |
| Varicella Virus Vaccine Live/Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Use of salicylates during natural varicella infection has been associated with Reye's Syndrome.(1-4) CLINICAL EFFECTS: Use of the live varicella virus vaccine in patients receiving salicylate therapy or use of salicylates within 6 weeks after vaccination with the live varicella virus vaccine may increase the risk of Reye's Syndrome.(1-4) Symptoms of Reye's syndrome include drowsiness, confusion, seizures, coma. In severe cases, Reye's syndrome can result in death. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The Canadian, UK, and US manufacturers of live varicella virus vaccine indicated for the prevention of chicken pox state that vaccine recipients should avoid the use of salicylates for 6 weeks after vaccination.(1-4) There is no such restriction in the labeling for live varicella virus vaccine indicated for the prevention of shingles, which is only indicated for patients age 60 and older.(5) DISCUSSION: Because the use of salicylates during natural varicella infection has been associated with Reye's Syndrome, the use of salicylates for 6 weeks following vaccination with live varicella virus vaccine should be avoided.(1-4) |
PROQUAD, VARIVAX VACCINE |
| Solid Oral Potassium Capsules/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16)) CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with anticholinergics may result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16) PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21) PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. The lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17) |
POTASSIUM CHLORIDE |
| Methotrexate (Oncology-Injection)/Selected Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Salicylates may inhibit the renal tubular excretion of methotrexate. CLINICAL EFFECTS: The concurrent use of methotrexate and salicylates may result in an increase in the therapeutic and toxic effects of methotrexate, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression, including neutropenia. PREDISPOSING FACTORS: Risk factors for methotrexate toxicity include: - High-dose oncology regimens - Anti-inflammatory doses of aspirin/salicylates - Impaired renal function, ascites, or pleural effusions PATIENT MANAGEMENT: US manufacturer prescribing information for methotrexate states nonsteroidal anti-inflammatory drugs should not be administered prior to or concomitantly with high doses of methotrexate. If concurrent therapy is warranted, methotrexate plasma levels should be monitored and patients should be observed for methotrexate toxicity. The dosage of methotrexate may need to be adjusted. Use caution when administering higher doses of salicylates with lower doses of methotrexate. Salicylate doses > or = 2 grams per day have been associated with hepatic impairment or impaired renal elimination of methotrexate. It would be prudent to avoid high-dose aspirin, especially in patients with renal impairment or near the time of methotrexate dosage (in patients receiving weekly therapy). DISCUSSION: Several studies and case reports have reported increased and prolonged methotrexate levels in patients receiving concurrent aspirin. One study noted an effect with average weekly doses of methotrexate of 16.6 mg, but not weekly doses of 7.5 mg. Decreased renal function has also been reported with the combination. Single ingredient aspirin or buffered aspirin products with strengths < or = to 325 mg or formulations which are associated with once daily use for cardiovascular protection are not linked to this interaction. Other lower-strength aspirin formulations (e.g. headache, cough & cold, opioid combinations) which could be consumed multiple times a day remain linked to this interaction. |
METHOTREXATE, METHOTREXATE SODIUM |
| 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 |
| Iobenguane I 123/Agents that Affect Catecholamines SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Many compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells.(1) CLINICAL EFFECTS: Compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with imaging completed with iobenguane.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discuss the use of agents that affect catecholamines. Discontinue drugs that reduce catecholamine uptake or deplete catecholamine stores prior to imaging with iobenguane. Before imaging with iobenguane, discontinue agents that affect catecholamines for at least 5 biological half-lives, as clinically tolerated.(1) DISCUSSION: Many agents may reduce catecholamine uptake or deplete catecholamine stores.(1) Examples include: - CNS stimulants or amphetamines (e.g. cocaine, methylphenidate, dextroamphetamine) - norepinephrine and dopamine reuptake inhibitors (e.g. phentermine) - norepinephrine and serotonin reuptake inhibitors (e.g. tramadol) - monoamine oxidase inhibitors (e.g. phenelzine, linezolid) - central monoamine depleting drugs (e.g. reserpine) - non-select beta adrenergic blocking drugs (e.g. labetalol) - alpha agonists or alpha/beta agonists (e.g. pseudoephedrine, phenylephrine, ephedrine, phenylpropanolamine, naphazoline) - tricyclic antidepressants or norepinephrine reuptake inhibitors (e.g. amitriptyline, bupropion, duloxetine, mirtazapine, venlafaxine) - botanicals that may inhibit reuptake of norepinephrine, serotonin or dopamine (e.g. ephedra, ma huang, St. John's Wort, yohimbine) |
ADREVIEW |
| Erdafitinib/Serum Phosphate Level-Altering Drugs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Medications that alter serum phosphate may interfere with interpretation of phosphate levels that are needed to determine initial erdafitinib dose.(1) CLINICAL EFFECTS: Serum phosphate levels that are elevated by concomitant medications may result in an inappropriately low dose and decreased effectiveness of erdafitinib. Serum phosphate levels that are decreased by concomitant medications may result in an inappropriately high dose and increased toxicity from erdafitinib. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of erdafitinib states that agents that alter serum phosphate levels should be avoided before the initial dose increase period for erdafitinib based on serum phosphate levels (days 14 to 21).(1) DISCUSSION: Concomitant administration of serum phosphate level-altering agents during the initial dose increase period of erdafitinib based on serum phosphate levels (days 14 to 21) may interfere with serum phospate levels and lead to incorrect dosing of erdafitinib.(1) Agents that may alter serum phosphate levels linked to this monograph include: aluminum carbonate, aluminum hydroxide, calcium acetate, calcium carbonate, calcium citrate, cod liver oil, ferric citrate, lanthanum, magnesium carbonate, magnesium hydroxide, potassium phosphate, sevelamer, sodium phosphate, sucroferric oxyhydroxide, tenapanor, and vitamin D.(1) |
BALVERSA |
| Secretin/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Anticholinergic drugs may result in an incorrect secretin stimulation test result.(1) CLINICAL EFFECTS: Concurrent use of anticholinergic drugs may impact the accuracy of the secretin stimulation test.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of human secretin states concurrent use of anticholinergic drugs at the time of stimulation testing may cause the patient to be hyporesponsive to the testing and suggest false positive results for pancreatic disease. The manufacturer recommends discontinuing anticholinergic drugs at least 5 half-lives prior to stimulation testing. Consider additional testing and clinical assessment for diagnosis.(1) DISCUSSION: Concurrent use of anticholinergic drugs may impact the accuracy of the secretin stimulation test.(1) |
CHIRHOSTIM |
| 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 |
| Clozapine/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clozapine has potent anticholinergic properties and inhibits serotonin receptors, including 5-HT3.(1-4) Both of these properties may cause inhibition of gastrointestinal (GI) smooth muscle contraction, resulting in decreased peristalsis.(3,4) These effects may be compounded by concurrent use of anticholinergic agents.(1-6) CLINICAL EFFECTS: Concurrent use of clozapine with other anticholinergic agents may increase the risk of constipation (common) and serious bowel complications (uncommon), including complete bowel obstruction, fecal impaction, paralytic ileus and intestinal ischemia or infarction.(1-6) PREDISPOSING FACTORS: The risk for serious bowel complications is higher with increasing age, higher frequency of constipation, and in patients on higher doses of clozapine or multiple anticholinergic agents.(1,5) PATIENT MANAGEMENT: Avoid the use of other anticholinergic agents with clozapine.(1-6) If concurrent use is necessary, evaluate the patient's bowel function regularly. Monitor for symptoms of constipation and GI hypomotility, including having bowel movements less than three times weekly or less than usual, difficulty having a bowel movement or passing gas, nausea, vomiting, and abdominal pain or distention.(2) Consider a prophylactic laxative in those with a history of constipation or bowel obstruction.(2) Review patient medication list for other anticholinergic agents. When possible, decrease the dosage or number of prescribed anticholinergic agents, particularly in the elderly. Counsel the patient about the importance of maintaining adequate hydration. Encourage regular exercise and eating a high-fiber diet.(2) DISCUSSION: In a prospective cohort study of 26,720 schizophrenic patients in the Danish Central Psychiatric Research Registry, the odds ratio (OR) for ileus was 1.99 with clozapine and 1.48 with anticholinergics. The OR for fatal ileus was 6.73 with clozapine and 5.88 with anticholinergics. Use of anticholinergics with 1st generation antipsychotics (FGA) increased the risk of ileus compare to FGA alone, but this analysis was not done with clozapine.(5) A retrospective cohort study of 24,970 schizophrenic patients from the Taiwanese National Health Insurance Research Database found that the hazard ratio (HR) for clozapine-induced constipation increased from 1.64 when clozapine is used alone, to 2.15 when used concomitantly with anticholinergics. However, there was no significant difference in the HR for ileus when clozapine is used with and without anticholinergics (1.95 and 2.02, respectively).(6) In the French Pharmacovigilance Database, 7 of 38 cases of antipsychotic-associated ischemic colitis or intestinal necrosis involved clozapine, and 5 of these cases involved use of concomitant anticholinergic agents. Three patients died, one of whom was on concomitant anticholinergics.(3) In a case series, 4 of 9 cases of fatal clozapine-associated GI dysfunction involved concurrent anticholinergic agents.(4) |
CLOZAPINE, CLOZAPINE ODT, CLOZARIL, VERSACLOZ |
| Eluxadoline/Anticholinergics; Opioids SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Eluxadoline is a mixed mu-opioid and kappa-opioid agonist and delta-opioid antagonist and may alter or slow down gastrointestinal transit.(1) CLINICAL EFFECTS: Constipation related adverse events that sometimes required hospitalization have been reported, including the development of intestinal obstruction, intestinal perforation, and fecal impaction.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid use with other drugs that may cause constipation. If concurrent use is necessary, evaluate the patient's bowel function regularly. Monitor for symptoms of constipation and GI hypomotility, including having bowel movements less than three times weekly or less than usual, difficulty having a bowel movement or passing gas, nausea, vomiting, and abdominal pain or distention.(1) Instruct patients to stop eluxadoline and immediately contact their healthcare provider if they experience severe constipation. Loperamide may be used occasionally for acute management of severe diarrhea, but must be discontinued if constipation develops.(1) DISCUSSION: In phase 3 clinical trials, constipation was the most commonly reported adverse reaction (8%). Approximately 50% of constipation events occurred within the first 2 weeks of treatment while the majority occurred within the first 3 months of therapy. Rates of severe constipation were less than 1% in patients receiving eluxadoline doses of 75 mg and 100 mg.(1) |
VIBERZI |
| 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 |
| Fecal Microbiota Spores/Antibiotics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1) CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1) DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores. |
VOWST |
| Glucagon (Diagnostic)/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Glucagon and anticholinergic agents may have additive effects on inhibition of gastrointestinal motility.(1) CLINICAL EFFECTS: Concurrent use of glucagon with anticholinergic agents may increase the risk of gastrointestinal hypomotility, including constipation and bowel complications.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of glucagon as a diagnotic aid is not recommended with the use of anticholinergic agents.(1) If concurrent use is necessary, evaluate the patient's bowel function. Monitor for symptoms of constipation and gastrointestinal hypomotility. DISCUSSION: Both glucagon and anticholinergic agents may have additive effects on inhibition of gastrointestinal motility and increase the risk of gastrointestinal adverse effects.(1) |
GLUCAGON HCL |
There are 16 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 |
|---|---|
| Heparin/Selected Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Additive prolongation of bleeding time. CLINICAL EFFECTS: Increased risk of bleeding which may extend for several days beyond discontinuation of salicylates. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Avoid concomitant administration of these drugs. If this combination is used, monitor patients for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. A non-acetylated salicylate may be used to avoid antiplatelet activity. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. Single ingredient aspirin or buffered aspirin products with strengths < or = 325 mg and combination aspirin products which are used to treat cardiovascular disease (e.g. aspirin+statins, aspirin+dipyridamole) are not included in this interaction. DISCUSSION: This interaction is likely to occur. |
ARIXTRA, ELMIRON, ENOXAPARIN SODIUM, ENOXILUV, FONDAPARINUX SODIUM, FRAGMIN, HEPARIN SODIUM, HEPARIN SODIUM IN 0.45% NACL, HEPARIN SODIUM-0.45% NACL, HEPARIN SODIUM-0.9% NACL, HEPARIN SODIUM-D5W, LOVENOX, PENTOSAN POLYSULFATE SODIUM |
| Uricosurics/Aspirin (Greater Than 100 mg); Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Not clearly established. Protein binding displacement is a possibility. CLINICAL EFFECTS: May observe hyperuricemia and gout resulting from reduced uricosuric response. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid chronic, moderate to high doses of salicylates. DISCUSSION: This interaction is well documented. Occasional small doses of salicylates do not appear to inhibit the action of uricosurics. |
DUZALLO, PROBENECID, PROBENECID-COLCHICINE |
| Antidiabetics, Oral/Aspirin (Greater Than 100 mg); Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Complex. Salicylates appear to have intrinsic glucose lowering properties via several proposed mechanisms. Also, salicylates may cause protein binding displacement of antidiabetics. Decreased renal clearance may also occur. CLINICAL EFFECTS: Potentiation of hypoglycemic effects may be observed. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Hypoglycemic signs and blood glucose levels should be monitored. Adjust the antidiabetic dose as needed. Particular caution should be taken when salicylates are started or stopped in patients previously stabilized on antidiabetics. DISCUSSION: Additional documentation is necessary to confirm this potential interaction. |
DUETACT, GLIMEPIRIDE, GLIPIZIDE, GLIPIZIDE ER, GLIPIZIDE XL, GLIPIZIDE-METFORMIN, GLUCOTROL XL, GLYBURIDE, GLYBURIDE MICRONIZED, GLYBURIDE-METFORMIN HCL, NATEGLINIDE, PIOGLITAZONE-GLIMEPIRIDE |
| Angiotensin II Receptor Blocker (ARB)/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Angiotensin II receptor blockers (ARBs) can cause vasodilation of the efferent renal arteriole which may result in decreased glomerular filtration rate. NSAIDs inhibit prostaglandin synthesis which can lead to afferent arteriolar vasoconstriction and may negate any decrease in blood pressure. CLINICAL EFFECTS: Concurrent use of ARBs with NSAIDs may result in decreased antihypertensive effects. In patients with existing renal impairment, the use of these agents together may also result in further deterioration of renal clearance caused by renal hypoperfusion. Concurrent use of ARBs with NSAIDs and diuretics may result in increased risk of acute kidney injury (AKI). PREDISPOSING FACTORS: Low water intake/dehydration, drug sensitivity, greater than 75 years of age, and use of diuretics can lead to hypovolemia and increased risk of AKI. PATIENT MANAGEMENT: Patients maintained on ARBs should be monitored for a loss of blood pressure control and a change in renal function if an NSAID is added to their regimen. Patients receiving concurrent therapy may require higher doses of ARBs. If blood pressure control cannot be achieved or if the patient's renal function deteriorates, the NSAID may need to be discontinued. Patients should be monitored for hypotension if NSAIDs are withdrawn from concurrent ARB therapy. Concurrent use of ARBs with NSAIDs and diuretics should be used with caution and monitored for signs of AKI. DISCUSSION: In a computational study, the risk of AKI using triple therapy with a diuretic, renin-angiotensin system (RAS) inhibitor, and NSAID was assessed. The study found the following factors may increase an individual's susceptibility to AKI: low water intake, drug sensitivity, greater than 75 years of age, and renal impairment.(22,23) In an observational study, current use of a triple therapy combination was associated with an increased rate of acute kidney injury (rate ratio (RR) 1.31, 95% confidence interval (CI) 1.12-1.53). The highest risk of AKI associated with triple therapy were observed in the first 30 days of use (RR 1.82, CI 1.35-2.46).(24) In a population based cohort study, the concurrent use of NSAIDs with renin-angiotensin system (RAS) inhibitors in 5,710 hypertensive patients stabilized on antihypertensive therapy required hypertension treatment intensification. Adjusted hazard ratios (HR) for hypertension treatment intensification were 1.34 [95% CI 1.05-1.71] for NSAIDs in general, 1.79 (95% CI 1.15-2.78) for diclofenac and 2.02 (95% CI 1.09-3.77) for piroxicam. There were significant interactions between NSAIDs and angiotensin converting enzyme inhibitors (ACE inhibitors; HR 4.09, 95% CI 2.02-8.27) or angiotensin receptor blockers (ARBs; HR 3.62, 95% CI 1.80-7.31), but not with other antihypertensive drugs. |
AMLODIPINE-OLMESARTAN, AMLODIPINE-VALSARTAN, AMLODIPINE-VALSARTAN-HCTZ, ARBLI, ATACAND, ATACAND HCT, AVALIDE, AVAPRO, AZOR, BENICAR, BENICAR HCT, CANDESARTAN CILEXETIL, CANDESARTAN-HYDROCHLOROTHIAZID, COZAAR, DIOVAN, DIOVAN HCT, EDARBI, EDARBYCLOR, ENTRESTO, ENTRESTO SPRINKLE, EPROSARTAN MESYLATE, EXFORGE, EXFORGE HCT, HYZAAR, IRBESARTAN, IRBESARTAN-HYDROCHLOROTHIAZIDE, LOSARTAN POTASSIUM, LOSARTAN-HYDROCHLOROTHIAZIDE, MICARDIS, MICARDIS HCT, OLMESARTAN MEDOXOMIL, OLMESARTAN-AMLODIPINE-HCTZ, OLMESARTAN-HYDROCHLOROTHIAZIDE, TELMISARTAN, TELMISARTAN-AMLODIPINE, TELMISARTAN-HYDROCHLOROTHIAZID, TRIBENZOR, VALSARTAN, VALSARTAN-HYDROCHLOROTHIAZIDE |
| Acetazolamide; Methazolamide/Aspirin (Greater Than 100 mg); Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Acetazolamide and methazolamide may reduce blood pH, causing a shift of salicylates from plasma into tissues (eg, central nervous system). Alternatively, toxicity may be due to salicylate-induced displacement of the carbonic anhydrase inhibitor from its protein binding sites and inhibition of renal tubular secretion. CLINICAL EFFECTS: An increase in the pharmacologic effects of salicylates with possible toxicity may occur. PREDISPOSING FACTORS: High doses of salicylates, low body weight. PATIENT MANAGEMENT: Avoid the combination if possible. If it is necessary to administer these drugs concurrently, monitor salicylate levels and monitor the patient for symptoms of toxicity. Adjust the dose as needed. DISCUSSION: Two young patients with unimpaired renal and hepatic function were found to have developed metabolic acidosis after treatment for glaucoma and joint pain with a combination of salicylates and carbonic anhydrase inhibitors in normal doses.(1) A 67-year old woman and a 75-year old woman taking carbonic anhydrase inhibitors for therapy of glaucoma and high doses of aspirin for arthritis developed severe acid-base imbalance and salicylate intoxication.(2) Neither patient exhibited ill effects when taking high aspirin doses without a carbonic anhydrase inhibitor. Carbonic anhydrase inhibitor-induced acidemia increases the risk of developing salicylate intoxication in patients receiving high aspirin doses. Two elderly patients, who were chronically receiving aspirin developed lethargy, incontinence, and confusion after dosing with acetazolamide.(3) These effects could have been due to either drug (see mechanism). |
ACETAZOLAMIDE, ACETAZOLAMIDE ER, ACETAZOLAMIDE SODIUM, METHAZOLAMIDE |
| Triamterene; Amiloride/Selected NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown; however, nonsteroidal anti-inflammatory (NSAID) inhibition of prostaglandins may allow triamterene or amiloride- induced nephrotoxicity or hyperkalemia to occur in some patients. CLINICAL EFFECTS: Possible renal failure or hyperkalemia. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When possible, avoid concurrent therapy with triamterene or amiloride with NSAIDs. If these agents are used concurrently, monitor renal function and serum electrolytes. If decreased renal function or hyperkalemia develops, discontinue both agents. DISCUSSION: Although acute renal failure and hyperkalemia have only been reported in studies and case reports involving indomethacin, diclofenac, flurbiprofen, and ibuprofen with either triamterene or amiloride, the proposed mechanism suggests that all nonsteroidal anti-inflammatory agents may be capable of this interaction. Patients receiving diuretics are at an increased risk of NSAID-induced renal failure. |
AMILORIDE HCL, AMILORIDE-HYDROCHLOROTHIAZIDE, DYRENIUM, TRIAMTERENE, TRIAMTERENE-HYDROCHLOROTHIAZID |
| Select Antipsychotics;Select Phenothiazines/Anticholinergics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Multiple mechanisms may be involved: 1. additive peripheral and CNS blockade of muscarinic receptors. 2. anticholinergic-induced inhibition of gastrointestinal absorption of phenothiazines. 3. antagonism of the dopamine blocking effects of selected antipsychotics and phenothiazines. CLINICAL EFFECTS: The dopamine blocking effects of selected antipsychotic agents or phenothiazines may be decreased while anticholinergic adverse effects may be increased. PREDISPOSING FACTORS: The risk for severe anticholinergic toxicities, e.g. delirium, hyperthermia, paralytic ileus is increased in the elderly and in patients on multiple anticholinergic agents. PATIENT MANAGEMENT: Anticholinergic agents may be required to treat or prevent antipsychotic induced extrapyramidal symptoms. When other indications lead to co-prescribing of the combination, assess patient response to the combination. Review patient medication list for other anticholinergic agents. When needed, decrease the dosage or number of prescribed anticholinergic agents, particularly in the elderly. DISCUSSION: Although numerous studies have been published regarding a possible interaction between phenothiazines and anticholinergics, the earlier reports were not double-blind or placebo controlled and patients may have received other drugs concomitantly. These earlier investigations reported increased side effects as well as increased, decreased and no effect on the therapeutic outcome. Double-blind studies have also reported conflicting results. Anticholinergic therapy varied from having no effect on phenothiazine concentration or patient outcome, to increasing phenothiazine levels. The discrepancies reported may be due to interpatient variability including age of the patient, type and duration of illness and treatment setting. |
ADASUVE, CHLORPROMAZINE HCL, LOXAPINE, PERPHENAZINE, PERPHENAZINE-AMITRIPTYLINE, PHENERGAN, PROMETHAZINE HCL, PROMETHAZINE HCL-0.9% NACL, PROMETHAZINE VC, PROMETHAZINE-CODEINE, PROMETHAZINE-DM, PROMETHAZINE-PHENYLEPHRINE HCL, PROMETHEGAN, THIORIDAZINE HCL, THIORIDAZINE HYDROCHLORIDE, TRIFLUOPERAZINE HCL |
| Valproic Acid/Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Multiple mechanisms appear to be involved. Salicylates may displace valproic acid from plasma protein binding sites. Salicylates may also affect the metabolism of valproate by increasing conjugation and decreasing oxidation of valproic acid. CLINICAL EFFECTS: Concurrent use of salicylates may increase the unbound fraction of serum valproic acid concentration, resulting in toxicity. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving concurrent salicylate therapy should be observed for signs of valproic acid toxicity (e.g., ataxia, drowsiness, nystagmus, tremor). The dosage of valproic acid may need to be adjusted. DISCUSSION: In two studies involving 6 epileptic children taking valproic acid, concurrent aspirin led to an increase in serum valproic acid free fraction and an increased half-life. Renal clearance of free valproic acid was found to decrease.(1,2) In another study involving 5 children, concurrent valproic acid and aspirin resulted in a decrease in free valproic acid clearance although total valproic acid levels did not change significantly.(3) However, one study reported that the concurrent use of valproic acid and aspirin leads to an increased excretion of valproic acid and a decreased total salicylate excretion.(4) In 3 case reports, aspirin given to children taking valproic acid resulted in valproic acid toxicity (tremor, nystagmus, truncal ataxia). There was an increase in free valproic acid levels in two cases, however, a reduction in the free fraction and the total valproic acid levels occurred in the third patient.(5) In another case report, a patient was maintained on divalproex sodium (2500 mg/day) and aspirin (325 mg/day) with a trough valproate level of 24.7 ng/ml and a total valproate level of 64.0 ng/ml. Five days after aspirin was discontinued for a procedure, trough valproate levels fell to 3.9 ng/ml and a total valproate level fell to 36.0 ng/ml with no change in divalproex dosing.(6) In a study in 7 healthy males, concurrent diflunisal (250 mg twice daily) increased the unbound fraction of valproic acid (200 mg twice daily) by 20%. The area-under-curve (AUC) of 3-oxo-valproic acid increased by 35%. There were no effects on diflunisal levels.(7) |
DEPAKOTE, DEPAKOTE ER, DEPAKOTE SPRINKLE, DIVALPROEX SODIUM, DIVALPROEX SODIUM ER, SODIUM VALPROATE, VALPROATE SODIUM, VALPROIC ACID |
| Drospirenone/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Drospirenone has antimineralocorticoid activity and may cause hyperkalemia. NSAIDs may also increase potassium levels.(1) CLINICAL EFFECTS: Concurrent use of drospirenone and NSAIDs may result in hyperkalemia.(1) PREDISPOSING FACTORS: Renal insufficiency, hepatic dysfunction, adrenal insufficiency, and use of potassium supplements, ACE inhibitors, angiotensin II receptor antagonists, heparin, and potassium-sparing diuretics may increase potassium levels.(1) PATIENT MANAGEMENT: Patients receiving drospirenone with a NSAID should have their serum potassium level checked during the first treatment cycle.(1) DISCUSSION: Drospirenone has antimineralocorticoid activity comparable to 25 mg of spironolactone and may result in hyperkalemia. Concurrent use of NSAIDs may also increase potassium levels.(1) Occasional or chronic use of NSAIDs was not restricted in clinical trials of drospirenone.(1) |
ANGELIQ, BEYAZ, DROSPIRENONE-ETH ESTRA-LEVOMEF, DROSPIRENONE-ETHINYL ESTRADIOL, JASMIEL, LO-ZUMANDIMINE, LORYNA, NEXTSTELLIS, NIKKI, OCELLA, SAFYRAL, SLYND, SYEDA, VESTURA, YASMIN 28, YAZ, ZARAH, ZUMANDIMINE |
| Oral Itraconazole; Ketoconazole/Hyoscyamine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Hyoscyamine delays gastric emptying and may increase gastric pH, thereby decreasing the absorption of orally administered itraconazole and ketoconazole.(1) CLINICAL EFFECTS: Simultaneous administration of hyoscyamine may result in decreased levels and effectiveness of oral itraconazole and ketoconazole.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Oral itraconazole and ketoconazole should be administered at least 2 hours after hyoscyamine.(1) DISCUSSION: Hyoscyamine delays gastric emptying and may increase gastric pH, decreasing the amount of azole antifungal absorption.(1) |
ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KETOCONAZOLE, SPORANOX, TOLSURA |
| Aldosterone Receptor Antagonists/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown; however, nonsteroidal anti-inflammatory (NSAID) inhibition of prostaglandins may allow eplerenone, finerenone, or spironolactone-induced nephrotoxicity or hyperkalemia to occur in some patients.(1-3) In some patients, NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects of eplerenone, finerenone, or spironolactone.(1-3) CLINICAL EFFECTS: Concurrent use of eplerenone, finerenone, or spironolactone with NSAIDs may result in renal failure or hyperkalemia. The effects of the diuretic, natriuretic, or antihypertensive effects of eplerenone, finerenone, or spironolactone may be decreased.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When possible, avoid concurrent therapy with eplerenone, finerenone, or spironolactone with NSAIDs. If these agents are used concurrently, monitor renal function and serum electrolytes. If decreased renal function or hyperkalemia develops, discontinue both agents. The manufacturer of eplerenone recommends checking serum potassium and serum creatinine within 3-7 days of concurrent therapy with NSAIDs.(1) The manufacturer of spironolactone states concurrent use with NSAIDs may lead to severe hyperkalemia and extreme caution should be used during concurrent therapy.(2) DISCUSSION: Although acute renal failure and hyperkalemia have only been reported in studies and case reports involving indomethacin, diclofenac, flurbiprofen, and ibuprofen with either triamterene or amiloride, the proposed mechanism suggests that all nonsteroidal anti-inflammatory agents may be capable of this interaction with all potassium-sparing diuretics. Patients receiving diuretics are at an increased risk of NSAID-induced renal failure. |
ALDACTONE, CAROSPIR, EPLERENONE, INSPRA, KERENDIA, SPIRONOLACTONE, SPIRONOLACTONE-HCTZ |
| Aliskiren/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown. It is believed to be related to inhibition of prostaglandin synthesis by the NSAIDs. Use of an NSAID in combination with aliskiren, whose hypotensive effects may be related to the increase in hypotensive prostaglandins, may negate any decrease in blood pressure. CLINICAL EFFECTS: Concurrent use of aliskiren with NSAIDs may result in decreased antihypertensive effects. In patients with existing renal impairment, the use of these agents together may also result in further deterioration of renal clearance caused by renal hypoperfusion. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients maintained on aliskiren should be monitored for a loss of blood pressure control and a change in renal function if an NSAID is added to their regimen. Patients receiving concurrent therapy may require higher doses of aliskiren. If blood pressure control cannot be achieved or if the patient's renal function deteriorates, the NSAID may need to be discontinued. Patients should be monitored for hypotension if NSAIDs are withdrawn from concurrent aliskiren therapy. DISCUSSION: Indomethacin has been shown to inhibit the antihypertensive effect of captopril, cilazapril, enalapril, losartan, perindopril, and valsartan. Ibuprofen has been shown to decrease the antihypertensive effects of captopril. Two separate case reports describe individuals suspected of ACEI-associated angioedema precipitated by NSAIDs. Both cases reported symptom resolution after cessation of the NSAID. Studies have shown that sulindac does not affect the antihypertensive effects of captopril and enalapril. |
ALISKIREN, TEKTURNA |
| ACE Inhibitors/Selected NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: ACE inhibitors can cause vasodilation of the efferent renal arteriole which may result in decreased glomerular filtration rate. NSAIDs inhibit prostaglandin synthesis which can lead to afferent arteriolar vasoconstriction and may negate any decrease in blood pressure. CLINICAL EFFECTS: Concurrent use of ACE inhibitors with NSAIDs may result in decreased antihypertensive effects. In patients with existing renal impairment, the use of these agents together may also result in further deterioration of renal clearance caused by renal hypoperfusion. Concurrent use of ACE inhibitors with NSAIDs and diuretics may result in increased risk of acute kidney injury (AKI). PREDISPOSING FACTORS: Low water intake/dehydration, drug sensitivity, greater than 75 years of age, and renal impairment may increase an individuals susceptibility to AKI. PATIENT MANAGEMENT: Patients maintained on ACE inhibitors should be monitored for a loss of blood pressure control and a change in renal function if an NSAID is added to their regimen. Patients receiving concurrent therapy may require higher doses of ACE inhibitors. If blood pressure control cannot be achieved or if the patient's renal function deteriorates, the NSAID may need to be discontinued. Patients should be monitored for hypotension if NSAIDs are withdrawn from concurrent ACE inhibitor therapy. Concurrent use of ACE inhibitors with NSAIDs and diuretics should be used with caution and monitored closely for signs of AKI. DISCUSSION: In a computational study, the risk of AKI using triple therapy with a diuretic, renin-angiotensin system (RAS) inhibitor, and NSAID was assessed. The study found the following factors may increase an individual's susceptibility to AKI: low water intake, drug sensitivity, greater than 75 years of age, and renal impairment.(30,31) In an observational study, current use of a triple therapy combination was associated with an increased rate of acute kidney injury (rate ratio (RR) 1.31, 95% confidence interval (CI) 1.12-1.53). The highest risk of AKI associated with triple therapy were observed in the first 30 days of use (RR 1.82, CI 1.35-2.46).(32) Indomethacin has been shown to inhibit the antihypertensive effect of captopril, cilazapril, enalapril, losartan, perindopril, and valsartan. Ibuprofen has been shown to decrease the antihypertensive effects of captopril. Two separate case reports describe individuals suspected of ACEI-associated angioedema precipitated by NSAIDs. Both cases reported symptom resolution after cessation of the NSAID. Studies have shown that sulindac does not affect the antihypertensive effects of captopril and enalapril. One or more of the drug pairs linked to this monograph have been included in a list of interactions that could be considered for classification as "non-interruptive" in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology. |
ACCUPRIL, ACCURETIC, ALTACE, AMLODIPINE BESYLATE-BENAZEPRIL, BENAZEPRIL HCL, BENAZEPRIL-HYDROCHLOROTHIAZIDE, CAPTOPRIL, CAPTOPRIL-HYDROCHLOROTHIAZIDE, ENALAPRIL MALEATE, ENALAPRIL-HYDROCHLOROTHIAZIDE, ENALAPRILAT, EPANED, FOSINOPRIL SODIUM, FOSINOPRIL-HYDROCHLOROTHIAZIDE, LISINOPRIL, LISINOPRIL-HYDROCHLOROTHIAZIDE, LOTENSIN, LOTENSIN HCT, LOTREL, MOEXIPRIL HCL, PERINDOPRIL ERBUMINE, PRESTALIA, QBRELIS, QUINAPRIL HCL, QUINAPRIL-HYDROCHLOROTHIAZIDE, RAMIPRIL, TRANDOLAPRIL, TRANDOLAPRIL-VERAPAMIL ER, VASERETIC, VASOTEC, ZESTORETIC, ZESTRIL |
| Zonisamide/Anticholinergics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Zonisamide can cause decreased sweating and elevated body temperature. Agents with anticholinergic activity can predispose patients to heat-related disorders.(1-2) CLINICAL EFFECTS: Concurrent use of zonisamide with agents with anticholinergic activity may increase the incidence of oligohidrosis and hyperthermia, especially in pediatric or adolescent patients.(1-2) Overheating and dehydration can lead to brain damage and death. PREDISPOSING FACTORS: Pediatric and adolescent patients and patients with dehydration may be more likely to experience heat-related disorders.(1) PATIENT MANAGEMENT: The UK and US manufacturers of zonisamide state that caution should be used in adults when zonisamide is prescribed with other medicinal products that predispose to heat-related disorders, such as agents with anticholinergic activity.(1-2) Pediatric and adolescent patients must not take anticholinergic agents (e.g. clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine, and oxybutynin) concurrently with zonisamide.(1) Monitor for signs and symptoms of heat stroke: skin feels very hot with little or no sweating, confusion, muscle cramps, rapid heartbeat, or rapid breathing. Monitor for signs and symptoms of dehydration: dry mouth, urinating less than usual, dark-colored urine, dry skin, feeling tired, dizziness, or irritability. If signs or symptoms of dehydration, oligohidrosis, or elevated body temperature occur, discontinuation of zonisamide should be considered. DISCUSSION: Case reports of decreased sweating and elevated temperature have been reported, especially in pediatric patients. Some cases resulted in heat stroke that required hospital treatment and resulted in death.(1) |
ZONEGRAN, ZONISADE, ZONISAMIDE |
| Topiramate/Anticholinergics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Topiramate can cause decreased sweating and elevated body temperature. Agents with anticholinergic activity can predispose patients to heat-related disorders.(1-2) CLINICAL EFFECTS: Concurrent use of topiramate with agents with anticholinergic activity may increase the incidence of oligohidrosis and hyperthermia, especially in pediatric or adolescent patients.(1-2) Overheating and dehydration can lead to brain damage and death. PREDISPOSING FACTORS: Pediatric and adolescent patients and patients with dehydration may be more likely to experience heat-related disorders.(1) PATIENT MANAGEMENT: The manufacturer of topiramate states that caution should be used when topiramate is prescribed with other medicinal products that predispose to heat-related disorders, such as agents with anticholinergic activity (e.g. clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine, and oxybutynin) concurrently with zonisamide.(1) Monitor for signs and symptoms of heat stroke: skin feels very hot with little or no sweating, confusion, muscle cramps, rapid heartbeat, or rapid breathing. Monitor for signs and symptoms of dehydration: dry mouth, urinating less than usual, dark-colored urine, dry skin, feeling tired, dizziness, or irritability. If signs or symptoms of dehydration, oligohidrosis, or elevated body temperature occur, discontinuation of zonisamide should be considered. DISCUSSION: Case reports of decreased sweating and elevated temperature have been reported, especially in pediatric patients. Some cases resulted in heat stroke that required hospital treatment.(1) A 64-year old woman developed non-exertional hyperthemia while taking multiple psychiatric medications with topiramate.(2) |
EPRONTIA, QSYMIA, TOPAMAX, TOPIRAMATE, TOPIRAMATE ER, TOPIRAMATE ER SPRINKLE, TROKENDI XR |
| Sparsentan/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Sparsentan is an endothelin and angiotensin II receptor antagonist.(1) Angiotensin II receptor blockers can cause vasodilation of the efferent renal arteriole which may result in decreased glomerular filtration rate. NSAIDs inhibit prostaglandin synthesis which can lead to afferent arteriolar vasoconstriction. CLINICAL EFFECTS: Concurrent use of sparsentan with NSAIDs (including selective COX-2 inhibitors) may result in renal hypoperfusion and deterioration of renal clearance, including possible acute kidney injury (AKI). These effects are usually reversible.(1) PREDISPOSING FACTORS: Patients older than 75 years old, with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion (including from diuretic use and dehydration) may be at greater risk for AKI.(1-3) PATIENT MANAGEMENT: Monitor for signs of worsening renal function if an NSAID (including selective COX-2 inhibitors) is used concurrently with sparsentan. If renal function deteriorates, the NSAID may need to be discontinued.(1) DISCUSSION: In a computational study, the risk of AKI using triple therapy with a diuretic, renin-angiotensin system (RAS) inhibitor, and NSAID was assessed. The study found the following factors may increase an individual's susceptibility to AKI: low water intake, drug sensitivity, greater than 75 years of age, and renal impairment.(2,3) In an observational study, current use of a triple therapy combination was associated with an increased rate of acute kidney injury (rate ratio (RR) 1.31, 95% confidence interval (CI) 1.12-1.53). The highest risk of AKI associated with triple therapy were observed in the first 30 days of use (RR 1.82, CI 1.35-2.46).(4) |
FILSPARI |
The following contraindication information is available for URETRON D-S (methenamine/methylene blue/sodium phos/pnyl sal/hyosc sul):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 21 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Achalasia of esophagus |
| Atony of colon |
| Benign prostatic hyperplasia |
| Bladder outflow obstruction |
| Glaucoma |
| Glucose-6-phosphate dehydrogenase (g6Pd) deficiency |
| Hemoglobin H disease |
| Hemolytic anemia from pyruvate kinase and g6PD deficiencies |
| Hypernatremia |
| Hyperphosphatemia |
| Hypocalcemia |
| Hypovolemic shock |
| Kidney disease with reduction in glomerular filtration rate (GFr) |
| Lactation |
| Myasthenia gravis |
| Paralytic ileus |
| Pyloroduodenal obstruction |
| Severe dehydration |
| Severe hepatic disease |
| Severe ulcerative colitis |
| Toxic megacolon |
There are 7 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Chronic heart failure |
| Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min |
| 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 |
| Edema |
| Pregnancy |
There are 17 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Autonomic neuropathy |
| Cardiac arrhythmia |
| Child-pugh class A hepatic impairment |
| Child-pugh class B hepatic impairment |
| Child-pugh class C hepatic impairment |
| Chronic heart failure |
| Coronary artery disease |
| Disease of liver |
| Gastroesophageal reflux disease |
| Hepatic cirrhosis |
| Hiatal hernia |
| High fever >101 degrees fahrenheit |
| Hypertension |
| Hyperthyroidism |
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
| Kidney disease with reduction in glomerular filtration rate (GFr) |
| Severe hepatic disease |
The following adverse reaction information is available for URETRON D-S (methenamine/methylene blue/sodium phos/pnyl sal/hyosc sul):
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 17 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. |
Skin rash |
| Rare/Very Rare |
|---|
|
Acute cognitive impairment Allergic dermatitis Cardiac arrhythmia Dyspnea Hematuria Hypernatremia Hyperphosphatemia Hypocalcemia Nephrocalcinosis Ocular hypertension Oliguria Orthostatic hypotension Renal failure Seizure disorder Skin rash Urticaria |
There are 37 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Blurred vision Decreased sweating Urine discoloration |
Abdominal pain with cramps Breast milk flow decreased Constipation Diarrhea Dyspepsia Increased urinary frequency Mydriasis Nausea Nausea and vomiting Vomiting Xerostomia |
| Rare/Very Rare |
|---|
|
Accidental fall Acute abdominal pain Anticholinergic toxicity Arthralgia Bone pain Cramps Dizziness Drowsy Dysuria Fatigue Fever Flatulence General weakness Headache disorder Memory impairment Nausea Oral paresthesia Paresthesia Peripheral edema Polydipsia Pruritus of skin Vomiting Weight gain |
The following precautions are available for URETRON D-S (methenamine/methylene blue/sodium phos/pnyl sal/hyosc sul):
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 rats and rabbits using methenamine hippurate have not revealed evidence of harm to the fetus. A slight increase in the stillborn rate and slight impairment of weight gain and survival of live-born offspring was reported in a study in pregnant dogs using oral methenamine in dosages equivalent to the human dosage. There are no adequate and well-controlled studies to date using methenamine hippurate or methenamine mandelate in pregnant women, and the drugs should be used during pregnancy only when clearly needed.
Although safe use of methenamine or its salts during pregnancy has not been definitely established, the drugs have been used in pregnant women without adverse effects to the fetus. One manufacturer of methenamine hippurate states that safety during the last trimester is suggested, but not definitely proven. The effects of methenamine during labor and delivery are unknown and there are no recognized uses for the drug during labor or delivery.
Some manufacturers have stated that methylene blue is contraindicated in women who are or may become pregnant. There is epidemiologic evidence that methylene blue is a teratogen and can cause fetal harm if administered during pregnancy, especially during the second and third trimesters. Use of methylene blue in amniocentesis has been associated with intestinal atresia (e.g., ileum and jejunum), ileal occlusion, and other adverse effects in neonates.
Intra-amniotic injection of methylene blue to detect ruptured membranes should be avoided. Use of methylene blue during pregnancy has resulted in hemolytic anemia, hyperbilirubinemia, methemoglobinemia, respiratory distress, skin staining, and phototoxicity in neonates. If methylene blue is administered to a pregnant woman at term, the neonate should be observed for such adverse effects and appropriate supportive care instituted if needed. If methylene blue is used during pregnancy or if the patient becomes pregnant, the patient should be apprised of the potential fetal hazard.
Although safe use of methenamine or its salts during pregnancy has not been definitely established, the drugs have been used in pregnant women without adverse effects to the fetus. One manufacturer of methenamine hippurate states that safety during the last trimester is suggested, but not definitely proven. The effects of methenamine during labor and delivery are unknown and there are no recognized uses for the drug during labor or delivery.
Some manufacturers have stated that methylene blue is contraindicated in women who are or may become pregnant. There is epidemiologic evidence that methylene blue is a teratogen and can cause fetal harm if administered during pregnancy, especially during the second and third trimesters. Use of methylene blue in amniocentesis has been associated with intestinal atresia (e.g., ileum and jejunum), ileal occlusion, and other adverse effects in neonates.
Intra-amniotic injection of methylene blue to detect ruptured membranes should be avoided. Use of methylene blue during pregnancy has resulted in hemolytic anemia, hyperbilirubinemia, methemoglobinemia, respiratory distress, skin staining, and phototoxicity in neonates. If methylene blue is administered to a pregnant woman at term, the neonate should be observed for such adverse effects and appropriate supportive care instituted if needed. If methylene blue is used during pregnancy or if the patient becomes pregnant, the patient should be apprised of the potential fetal hazard.
Because methenamine is distributed into milk and because of the potential for serious adverse effects in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman. It is not known whether methylene blue is distributed into human milk. Because of the potential for serious adverse reactions in nursing infants to methylene blue, including genotoxicity, some manufacturers state that breast-feeding should be discontinued during and for up to 8 days following treatment with methylene blue.
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for URETRON D-S (methenamine/methylene blue/sodium phos/pnyl sal/hyosc sul):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for URETRON D-S (methenamine/methylene blue/sodium phos/pnyl sal/hyosc sul)'s list of indications:
No ICD codes found for this drug.
No ICD codes found for this drug.
Formulary Reference Tool