U.S. BRAND NAMES — Cytadren®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Aromatase Inhibitor
Enzyme Inhibitor
Hormonal Antagonist, Anti-Adrenal
Nonsteroidal Aromatase Inhibitor
DOSING: ADULTS
Cushing disease: Oral: 250 mg every 6 hours may be increased at 1- to 2-week intervals to a total of 2 g/day
Breast cancer, prostate cancer (unlabeled use): Oral: 250 mg 4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Dose reduction may be necessary.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet [scored]: 250 mg
DOSAGE FORMS: CONCISE
Tablet [scored]:
Cytadren®: 250 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer every 6 hours to reduce incidence of nausea and vomiting.
USE — Suppression of adrenal function in selected patients with Cushing's syndrome
USE - UNLABELED / INVESTIGATIONAL — Treatment of breast and prostate cancer (androgen synthesis inhibitor)
ADVERSE REACTIONS SIGNIFICANT — Most adverse effects will diminish in incidence and severity after the first 2-6 weeks
>10%:
Central nervous system: Headache, dizziness, drowsiness, lethargy, clumsiness
Dermatologic: Skin rash
Gastrointestinal: Nausea, anorexia
Hepatic: Cholestatic jaundice
Neuromuscular & skeletal: Myalgia
Renal: Nephrotoxicity
Respiratory: Pulmonary alveolar damage
1% to 10%:
Cardiovascular: Hypotension, tachycardia, orthostasis
Dermatologic: Hirsutism, pruritus
Endocrine & metabolic: Adrenocortical insufficiency
Gastrointestinal: Vomiting
<1% (Limited to important or life-threatening): Adrenal suppression, hepatotoxicity, hypercholesterolemia, hyperkalemia, hypothyroidism, goiter, masculinization of females, pulmonary hypersensitivity, urticaria; rare cases of neutropenia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis have been reported
CONTRAINDICATIONS — Hypersensitivity to aminoglutethimide, glutethimide, or any component of the formulation; pregnancy
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Hypothyroidism: With use, hypothyroidism may occur.
Other warnings/precautions: Blood pressure monitoring: In all patients, monitor blood pressure at appropriate intervals. Mineralocorticoid/glucocorticoid replacement: Mineralocorticoid replacement is necessary in up to 50% of patients. Glucocorticoid replacement is necessary in most patients.
DRUG INTERACTIONS — Induces CYP1A2 (strong), 2C19 (strong), 3A4 (strong)
CYP1A2 substrates: Aminoglutethimide may decrease the levels/effects of CYP1A2 substrates. Example substrates include aminophylline, estrogens, fluvoxamine, mirtazapine, ropinirole, and theophylline.
CYP2C19 substrates: Aminoglutethimide may decrease the levels/effects of CYP2C19 substrates. Example substrates include citalopram, diazepam, methsuximide, phenytoin, propranolol, proton pump inhibitors, sertraline, and voriconazole.
CYP3A4 substrates: Aminoglutethimide may decrease the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, clarithromycin, cyclosporine, erythromycin, estrogens, mirtazapine, nateglinide, nefazodone, nevirapine, protease inhibitors, tacrolimus, and venlafaxine.
Dexamethasone: Aminoglutethimide increases metabolism of dexamethasone; hydrocortisone is preferred if glucocorticoid treatment is needed.
Medroxyprogesterone: Aminoglutethimide increases medroxyprogesterone clearance.
Megestrol: Aminoglutethimide increases megestrol clearance.
Tamoxifen: Aminoglutethimide increases tamoxifen clearance.
Theophylline: Aminoglutethimide increases metabolism of theophylline.
Warfarin: Aminoglutethimide increases warfarin clearance.
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Suspected of causing virilization when given throughout pregnancy
LACTATION — Excretion in breast milk unknown/contraindicated
PRICING — (data from drugstore.com)
Tablets (Cytadren)
250 mg (30): $47.99
MONITORING PARAMETERS — Follow adrenal cortical response by careful monitoring of plasma cortisol until the desired level of suppression is achieved. Mineralocorticoid (fludrocortisone) replacement therapy may be necessary in up to 50% of patients. If glucocorticoid replacement therapy is necessary, 20-30 mg hydrocortisone orally in the morning will replace endogenous secretion.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include ataxia, somnolence, lethargy, dizziness, distress, fatigue, coma, hyperventilation, respiratory depression, hypovolemia, and shock. Treatment is supportive.
INTERNATIONAL BRAND NAMES — Aminoglutetimid (PL); Cytadren (AU, NZ); Mamomit (HR); Orimeten (AR, AT, BE, BF, BG, BJ, BR, CH, CI, CL, CN, CZ, DE, EG, ES, ET, FI, GH, GM, GN, HU, IT, KE, LR, MA, ML, MR, MU, MW, NE, NG, NL, NO, PL, PT, SC, SD, SE, SL, SN, TZ, UG, ZA, ZM, ZW); Orimetene (GR, HK, TW)
MECHANISM OF ACTION — Blocks the enzymatic conversion of cholesterol to delta-5-pregnenolone, thereby reducing the synthesis of adrenal glucocorticoids, mineralocorticoids, estrogens, aldosterone, and androgens
PHARMACODYNAMICS / KINETICS
Onset of action: Adrenal suppression: 3-5 days; following withdrawal of therapy, adrenal function returns within 72 hours
Absorption: 90%
Protein binding, plasma: 20% to 25%
Metabolism: Major metabolite is N-acetylaminoglutethimide; induces its own metabolism
Half-life elimination: 7-15 hours; shorter following multiple doses
Excretion: Urine (34% to 50% as unchanged drug, 25% as metabolites)
Sunday, May 11, 2008
Aminocaproic acid
U.S. BRAND NAMES — Amicar®
PHARMACOLOGIC CATEGORY
Hemostatic Agent
DOSING: ADULTS
Acute bleeding syndrome: Oral, I.V.: 4-5 g during the first hour, followed by 1 g/hour for 8 hours or until bleeding controlled (maximum daily dose: 30 g)
Control bleeding in thrombocytopenia (unlabeled use):
Initial: I.V.: 0.1 g/kg over 30-60 minutes
Maintenance: Oral: 1-3 g every 6 hours
Control oral bleeding in congenital and acquired coagulation disorder (unlabeled use): Oral: 50-60 mg/kg every 4 hours
Traumatic hyphema (unlabeled use): Oral: 100 mg/kg/dose every 4 hours (maximum daily dose: 30 g)
DOSING: PEDIATRIC
(For additional information see "Aminocaproic acid: Pediatric drug information")
Acute bleeding syndrome (unlabeled use): Oral, I.V.: 100-200 mg/kg during the first hour, followed by continuous infusion at 33.3 mg/kg/hour or 100 mg/kg (oral or I.V.) every 6 hours
Traumatic hyphema (unlabeled use): Oral: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — May accumulate in patients with decreased renal function.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: 250 mg/mL (20 mL)
Amicar®: 250 mg/mL (20 mL) [contains benzyl alcohol]
Solution, oral: 1.25 g/5 mL (240 mL, 480 mL)
Syrup:
Amicar®: 1.25 g/5 mL (480 mL) [raspberry flavor]
Tablet [scored]: 500 mg, 1000 mg
Amicar®: 500 mg, 1000 mg
DOSAGE FORMS: CONCISE
Injection, solution: 250 mg/mL (20 mL)
Amicar®: 250 mg/mL (20 mL)
Solution, oral: 1.25 g/5 mL (480 mL)
Syrup:
Amicar®: 1.25 g/5 mL
Tablet [scored]: 500 mg, 1000 mg
Amicar®: 500 mg, 1000 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — I.V.: May be administered over 30-60 minutes or by continuous infusion; rapid I.V. injection (IVP) should be avoided due to possible hypotension, bradycardia, and arrhythmia.
COMPATIBILITY — Stable in D5W, NS.
Compatibility when admixed: Compatible: Netilmicin.
USE — Treatment of excessive bleeding from fibrinolysis
USE - UNLABELED / INVESTIGATIONAL — Treatment of traumatic hyphema; control bleeding in thrombocytopenia; control oral bleeding in congenital and acquired coagulation disorders
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Arrhythmia, bradycardia, hypotension, peripheral ischemia, syncope, thrombosis
Central nervous system: Confusion, delirium, dizziness, fatigue, hallucinations, headache, intracranial hypertension, malaise, seizure, stroke
Dermatologic: Rash, pruritus
Gastrointestinal: Abdominal pain, anorexia, cramps, diarrhea, GI irritation, nausea
Genitourinary: Dry ejaculation
Hematologic: Agranulocytosis, bleeding time increased, leukopenia, thrombocytopenia
Neuromuscular & skeletal: CPK increased, myalgia, myositis, myopathy, rhabdomyolysis (rare), weakness
Ophthalmic: Watery eyes, vision decreased
Otic: Tinnitus
Renal: Failure (rare), myoglobinuria (rare)
Respiratory: Dyspnea, nasal congestion, pulmonary embolism
CONTRAINDICATIONS — Hypersensitivity to aminocaproic acid or any component of the formulation; disseminated intravascular coagulation (without heparin); evidence of an intravascular clotting process
WARNINGS / PRECAUTIONS — Avoid rapid I.V. administration; may induce hypotension, bradycardia, or arrhythmia. Aminocaproic acid may accumulate in patients with decreased renal function. Intrarenal obstruction may occur secondary to glomerular capillary thrombosis or clots in the renal pelvis and ureters. Do not use in hematuria of upper urinary tract origin unless possible benefits outweigh risks. Use with caution in patients with cardiac, renal, or hepatic disease. Do not administer without a definite diagnosis of laboratory findings indicative of hyperfibrinolysis. Inhibition of fibrinolysis may promote clotting or thrombosis; more likely due to the presence of DIC. Subsequently, use with great caution in patients with, or at risk for, veno-occlusive disease of the liver. Benzyl alcohol is used as a preservative in the injection, therefore, these products should not be used in the neonate. Do not administer with factor IX complex concentrates or anti-inhibitor coagulant complexes.
DRUG INTERACTIONS — Increased toxic effect with oral contraceptives, estrogens.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Reproductive studies have not been conducted.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)
Tablets (Amicar)
500 mg (30): $78.37
MONITORING PARAMETERS — Fibrinogen, fibrin split products, creatine phosphokinase (with long-term therapy)
REFERENCE RANGE — Therapeutic concentration: >130 mcg/mL (concentration necessary for inhibition of fibrinolysis)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include acute renal failure, delirium, diarrhea, hepatic necrosis, nausea, seizures, transient hypotension, and thromboembolism. Aminocaproic acid may be removed by hemodialysis.
INTERNATIONAL BRAND NAMES — Acidum e-aminocapronicum (PL); Amicar (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE, ZA); Caproamin (VE); Caprolisin (IT); Hamostat (IN); Ipsilon (AR, BR, JP, PY, UY); Resplamin (JP); Syrop acidi e-aminocapronici (PL)
MECHANISM OF ACTION — Competitively inhibits activation of plasminogen to plasmin, also, a lesser antiplasmin effect
PHARMACODYNAMICS / KINETICS
Onset of action: ~1-72 hours
Distribution: Widely through intravascular and extravascular compartments
Vd: Oral: 23 L, I.V.: 30 L
Metabolism: Minimally hepatic
Half-life elimination: 2 hours
Time to peak: Oral: Within 2 hours
Excretion: Urine (65% as unchanged drug, 11% as metabolite)
PATIENT INFORMATION — Report any signs of bleeding; change positions slowly to minimize dizziness
PHARMACOLOGIC CATEGORY
Hemostatic Agent
DOSING: ADULTS
Acute bleeding syndrome: Oral, I.V.: 4-5 g during the first hour, followed by 1 g/hour for 8 hours or until bleeding controlled (maximum daily dose: 30 g)
Control bleeding in thrombocytopenia (unlabeled use):
Initial: I.V.: 0.1 g/kg over 30-60 minutes
Maintenance: Oral: 1-3 g every 6 hours
Control oral bleeding in congenital and acquired coagulation disorder (unlabeled use): Oral: 50-60 mg/kg every 4 hours
Traumatic hyphema (unlabeled use): Oral: 100 mg/kg/dose every 4 hours (maximum daily dose: 30 g)
DOSING: PEDIATRIC
(For additional information see "Aminocaproic acid: Pediatric drug information")
Acute bleeding syndrome (unlabeled use): Oral, I.V.: 100-200 mg/kg during the first hour, followed by continuous infusion at 33.3 mg/kg/hour or 100 mg/kg (oral or I.V.) every 6 hours
Traumatic hyphema (unlabeled use): Oral: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — May accumulate in patients with decreased renal function.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: 250 mg/mL (20 mL)
Amicar®: 250 mg/mL (20 mL) [contains benzyl alcohol]
Solution, oral: 1.25 g/5 mL (240 mL, 480 mL)
Syrup:
Amicar®: 1.25 g/5 mL (480 mL) [raspberry flavor]
Tablet [scored]: 500 mg, 1000 mg
Amicar®: 500 mg, 1000 mg
DOSAGE FORMS: CONCISE
Injection, solution: 250 mg/mL (20 mL)
Amicar®: 250 mg/mL (20 mL)
Solution, oral: 1.25 g/5 mL (480 mL)
Syrup:
Amicar®: 1.25 g/5 mL
Tablet [scored]: 500 mg, 1000 mg
Amicar®: 500 mg, 1000 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — I.V.: May be administered over 30-60 minutes or by continuous infusion; rapid I.V. injection (IVP) should be avoided due to possible hypotension, bradycardia, and arrhythmia.
COMPATIBILITY — Stable in D5W, NS.
Compatibility when admixed: Compatible: Netilmicin.
USE — Treatment of excessive bleeding from fibrinolysis
USE - UNLABELED / INVESTIGATIONAL — Treatment of traumatic hyphema; control bleeding in thrombocytopenia; control oral bleeding in congenital and acquired coagulation disorders
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Arrhythmia, bradycardia, hypotension, peripheral ischemia, syncope, thrombosis
Central nervous system: Confusion, delirium, dizziness, fatigue, hallucinations, headache, intracranial hypertension, malaise, seizure, stroke
Dermatologic: Rash, pruritus
Gastrointestinal: Abdominal pain, anorexia, cramps, diarrhea, GI irritation, nausea
Genitourinary: Dry ejaculation
Hematologic: Agranulocytosis, bleeding time increased, leukopenia, thrombocytopenia
Neuromuscular & skeletal: CPK increased, myalgia, myositis, myopathy, rhabdomyolysis (rare), weakness
Ophthalmic: Watery eyes, vision decreased
Otic: Tinnitus
Renal: Failure (rare), myoglobinuria (rare)
Respiratory: Dyspnea, nasal congestion, pulmonary embolism
CONTRAINDICATIONS — Hypersensitivity to aminocaproic acid or any component of the formulation; disseminated intravascular coagulation (without heparin); evidence of an intravascular clotting process
WARNINGS / PRECAUTIONS — Avoid rapid I.V. administration; may induce hypotension, bradycardia, or arrhythmia. Aminocaproic acid may accumulate in patients with decreased renal function. Intrarenal obstruction may occur secondary to glomerular capillary thrombosis or clots in the renal pelvis and ureters. Do not use in hematuria of upper urinary tract origin unless possible benefits outweigh risks. Use with caution in patients with cardiac, renal, or hepatic disease. Do not administer without a definite diagnosis of laboratory findings indicative of hyperfibrinolysis. Inhibition of fibrinolysis may promote clotting or thrombosis; more likely due to the presence of DIC. Subsequently, use with great caution in patients with, or at risk for, veno-occlusive disease of the liver. Benzyl alcohol is used as a preservative in the injection, therefore, these products should not be used in the neonate. Do not administer with factor IX complex concentrates or anti-inhibitor coagulant complexes.
DRUG INTERACTIONS — Increased toxic effect with oral contraceptives, estrogens.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Reproductive studies have not been conducted.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)
Tablets (Amicar)
500 mg (30): $78.37
MONITORING PARAMETERS — Fibrinogen, fibrin split products, creatine phosphokinase (with long-term therapy)
REFERENCE RANGE — Therapeutic concentration: >130 mcg/mL (concentration necessary for inhibition of fibrinolysis)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include acute renal failure, delirium, diarrhea, hepatic necrosis, nausea, seizures, transient hypotension, and thromboembolism. Aminocaproic acid may be removed by hemodialysis.
INTERNATIONAL BRAND NAMES — Acidum e-aminocapronicum (PL); Amicar (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE, ZA); Caproamin (VE); Caprolisin (IT); Hamostat (IN); Ipsilon (AR, BR, JP, PY, UY); Resplamin (JP); Syrop acidi e-aminocapronici (PL)
MECHANISM OF ACTION — Competitively inhibits activation of plasminogen to plasmin, also, a lesser antiplasmin effect
PHARMACODYNAMICS / KINETICS
Onset of action: ~1-72 hours
Distribution: Widely through intravascular and extravascular compartments
Vd: Oral: 23 L, I.V.: 30 L
Metabolism: Minimally hepatic
Half-life elimination: 2 hours
Time to peak: Oral: Within 2 hours
Excretion: Urine (65% as unchanged drug, 11% as metabolite)
PATIENT INFORMATION — Report any signs of bleeding; change positions slowly to minimize dizziness
Aminocamptothecin
PHARMACOLOGIC CATEGORY Antineoplastic Agent, DNA Binding AgentEnzyme Inhibitor, Topoisomerase I Inhibitor
DOSING: ADULTS — I.V.: 45-59 mcg/m2/hour for 72 hours as a continuous infusion; repeat every 2 weeks or 35 mcg/m2/hour as a 72-hour continuous infusion
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection: 5 mg ampul
DOSAGE FORMS: CONCISE Injection: 5 mg ampul [not available in the U.S.; investigational]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer by continuous I.V. infusion.
USE - UNLABELED / INVESTIGATIONAL — Phase II trials: Relapsed lymphoma, refractory breast cancer, nonsmall cell lung cancer, untreated colorectal carcinoma
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Central nervous system: Fatigue
Dermatologic: Alopecia
Gastrointestinal: Nausea, vomiting, diarrhea, mucositis, anorexia
Hematologic: Neutropenia (may be dose limiting), thrombocytopenia (reversible, but may be dose limiting), anemia
CONTRAINDICATIONS — Hypersensitivity to aminocamptothecin or any component of the formulation
WARNINGS / PRECAUTIONS Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
RESTRICTIONS — Not available in U.S./Investigational
DRUG INTERACTIONS — Patients taking anticonvulsants that induce hepatic enzymes have less toxicity and can tolerate higher doses of aminocamptothecin.
MONITORING PARAMETERS — WBC with differential, platelet count
MECHANISM OF ACTION — Aminocamptothecin binds to topoisomerase I, stabilizing the cleavable DNA-topoisomerase I complex, resulting in arrest of the replication fork and inhibition of DNA synthesis.
PHARMACODYNAMICS / KINETICS — Ratio of lactone to total drug is 8.7% +/- 4.7% because of instability of aminocamptothecin lactone in plasma.
Distribution: Vd: 46-92 L
Metabolism: None identified
Half-life elimination: Terminal: 8-17 hours for total aminocamptothecin
Excretion: Urine (32% of total drug delivered)
DOSING: ADULTS — I.V.: 45-59 mcg/m2/hour for 72 hours as a continuous infusion; repeat every 2 weeks or 35 mcg/m2/hour as a 72-hour continuous infusion
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection: 5 mg ampul
DOSAGE FORMS: CONCISE Injection: 5 mg ampul [not available in the U.S.; investigational]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer by continuous I.V. infusion.
USE - UNLABELED / INVESTIGATIONAL — Phase II trials: Relapsed lymphoma, refractory breast cancer, nonsmall cell lung cancer, untreated colorectal carcinoma
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Central nervous system: Fatigue
Dermatologic: Alopecia
Gastrointestinal: Nausea, vomiting, diarrhea, mucositis, anorexia
Hematologic: Neutropenia (may be dose limiting), thrombocytopenia (reversible, but may be dose limiting), anemia
CONTRAINDICATIONS — Hypersensitivity to aminocamptothecin or any component of the formulation
WARNINGS / PRECAUTIONS Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
RESTRICTIONS — Not available in U.S./Investigational
DRUG INTERACTIONS — Patients taking anticonvulsants that induce hepatic enzymes have less toxicity and can tolerate higher doses of aminocamptothecin.
MONITORING PARAMETERS — WBC with differential, platelet count
MECHANISM OF ACTION — Aminocamptothecin binds to topoisomerase I, stabilizing the cleavable DNA-topoisomerase I complex, resulting in arrest of the replication fork and inhibition of DNA synthesis.
PHARMACODYNAMICS / KINETICS — Ratio of lactone to total drug is 8.7% +/- 4.7% because of instability of aminocamptothecin lactone in plasma.
Distribution: Vd: 46-92 L
Metabolism: None identified
Half-life elimination: Terminal: 8-17 hours for total aminocamptothecin
Excretion: Urine (32% of total drug delivered)
Amiloride and hydrochlorothiazide
PHARMACOLOGIC CATEGORY Diuretic, Combination
DOSING: ADULTS — Hypertension, edema: Oral: Initial: 1 tablet/day; may be increased to 2 tablets/day if needed; usually given in a single dose
DOSING: ELDERLY — Oral: Initial: 1/2 to 1 tablet/day
DOSING: RENAL IMPAIRMENT — See individual agents.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 5/50: Amiloride hydrochloride 5 mg and hydrochlorothiazide 50 mg
DOSAGE FORMS: CONCISE Tablet: 5/50: Amiloride 5 mg and hydrochlorothiazide 50 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Potassium-sparing diuretic; antihypertensive
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
WARNINGS / PRECAUTIONS Box warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Electrolyte disturbances: Hypochloremic alkalosis and hyponatremia can occur. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction. Photosensitivity: Photosensitization may occur with hydrochlorothiazide. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns: Diabetes: Use with extreme caution in patients with diabetes mellitus; may see a change in glucose control. Monitor closely; discontinue amiloride 3 days prior to glucose tolerance testing. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated with hydrochlorothiazide. Hepatic impairment: Use hydrochlorothiazide with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use hydrochlorothiazide with caution in patients with moderate or high cholesterol concentrations. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes). Renal impairment: Avoid use of hydrochlorothiazide in severe renal disease (ineffective). Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.
DRUG INTERACTIONS — See individual agents.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Refer to Hydrochlorothiazide.
LACTATION — Excretion in breast milk unknown/contraindicated
DIETARY CONSIDERATIONS — May be taken with food.
PRICING — (data from drugstore.com)Tablets (Amiloride-Hydrochlorothiazide) 5-50 mg (100): $27.99
CANADIAN BRAND NAMES — Apo-Amilzide®; Gen-Amilazide; Moduret; Novamilor; Nu-Amilzide
INTERNATIONAL BRAND NAMES — Adco-Retic (ZA); Add-Acten (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TZ, UG, YE, ZM, ZW); Ameride (ES); Amil-Co (GB); Amilco (DK); Amilco Mite (DK); Amilocomp beta (DE); Amiloretic (ZA); Amizide (AU, MY, NZ, TW, ZA); Amuretic (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Apo-Amilzide (CA, MY); Betaretic (ZA); Biduret (IN); Bildiuretic (TH); Gen-Amilazide (CA); Hyperetic (TH); Kaluril (IL); Lorinid (ID); Lorinid Mite (ID); Moduret (CA); Moduretic (AU, BE, BF, BJ, BR, CH, CI, CO, CZ, DE, DK, EC, ET, FI, GB, GH, GM, GN, GR, HK, IE, IT, KE, LR, MA, ML, MR, MU, MW, MX, MY, NE, NG, NL, PK, PT, PY, SC, SD, SE, SL, SN, TH, TW, TZ, UG, UY, VE, ZA, ZM, ZW); Moduretic Mite (NO); Moure-M (TH); Novamilor (CA); Nu-Amilzide (CA); Sefaretic (HK); Tiaden (TW); Uniretic (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Yostiretic (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
PHARMACODYNAMICS / KINETICS —
DOSING: ADULTS — Hypertension, edema: Oral: Initial: 1 tablet/day; may be increased to 2 tablets/day if needed; usually given in a single dose
DOSING: ELDERLY — Oral: Initial: 1/2 to 1 tablet/day
DOSING: RENAL IMPAIRMENT — See individual agents.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 5/50: Amiloride hydrochloride 5 mg and hydrochlorothiazide 50 mg
DOSAGE FORMS: CONCISE Tablet: 5/50: Amiloride 5 mg and hydrochlorothiazide 50 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Potassium-sparing diuretic; antihypertensive
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
WARNINGS / PRECAUTIONS Box warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Electrolyte disturbances: Hypochloremic alkalosis and hyponatremia can occur. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction. Photosensitivity: Photosensitization may occur with hydrochlorothiazide. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns: Diabetes: Use with extreme caution in patients with diabetes mellitus; may see a change in glucose control. Monitor closely; discontinue amiloride 3 days prior to glucose tolerance testing. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated with hydrochlorothiazide. Hepatic impairment: Use hydrochlorothiazide with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use hydrochlorothiazide with caution in patients with moderate or high cholesterol concentrations. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes). Renal impairment: Avoid use of hydrochlorothiazide in severe renal disease (ineffective). Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.
DRUG INTERACTIONS — See individual agents.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Refer to Hydrochlorothiazide.
LACTATION — Excretion in breast milk unknown/contraindicated
DIETARY CONSIDERATIONS — May be taken with food.
PRICING — (data from drugstore.com)Tablets (Amiloride-Hydrochlorothiazide) 5-50 mg (100): $27.99
CANADIAN BRAND NAMES — Apo-Amilzide®; Gen-Amilazide; Moduret; Novamilor; Nu-Amilzide
INTERNATIONAL BRAND NAMES — Adco-Retic (ZA); Add-Acten (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TZ, UG, YE, ZM, ZW); Ameride (ES); Amil-Co (GB); Amilco (DK); Amilco Mite (DK); Amilocomp beta (DE); Amiloretic (ZA); Amizide (AU, MY, NZ, TW, ZA); Amuretic (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Apo-Amilzide (CA, MY); Betaretic (ZA); Biduret (IN); Bildiuretic (TH); Gen-Amilazide (CA); Hyperetic (TH); Kaluril (IL); Lorinid (ID); Lorinid Mite (ID); Moduret (CA); Moduretic (AU, BE, BF, BJ, BR, CH, CI, CO, CZ, DE, DK, EC, ET, FI, GB, GH, GM, GN, GR, HK, IE, IT, KE, LR, MA, ML, MR, MU, MW, MX, MY, NE, NG, NL, PK, PT, PY, SC, SD, SE, SL, SN, TH, TW, TZ, UG, UY, VE, ZA, ZM, ZW); Moduretic Mite (NO); Moure-M (TH); Novamilor (CA); Nu-Amilzide (CA); Sefaretic (HK); Tiaden (TW); Uniretic (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Yostiretic (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
PHARMACODYNAMICS / KINETICS —
Amiloride
U.S. BRAND NAMES — Midamor® [DSC]
PHARMACOLOGIC CATEGORY Diuretic, Potassium Sparing
DOSING: ADULTS — Hypertension, edema (to limit potassium loss): Oral: Initial: 5-10 mg/day (up to 20 mg) Hypertension (JNC 7): 5-10 mg/day in 1-2 divided doses
DOSING: PEDIATRIC — Edema, hypertension: Oral: Although safety and efficacy in children have not been established by the FDA, a dosage range of 0.4-0.625 mg/kg/day (maximum: 20 mg/day) has been used in children weighing 6-20 kg.
(For additional information see "Amiloride: Pediatric drug information")
DOSING: ELDERLY — Oral: Initial: 5 mg once daily or every other day
DOSING: RENAL IMPAIRMENT — Oral:
Clcr 10-50 mL/minute: Administer 50% of normal dose.
Clcr <10 mL/minute: Avoid use.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 5 mg
DOSAGE FORMS: CONCISE Tablet: 5 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer with food or meals to avoid GI upset.
USE — Counteracts potassium loss induced by other diuretics in the treatment of hypertension or edematous conditions including CHF, hepatic cirrhosis, and hypoaldosteronism; usually used in conjunction with more potent diuretics such as thiazides or loop diuretics
USE - UNLABELED / INVESTIGATIONAL — Investigational: Cystic fibrosis; reduction of lithium-induced polyuria
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Central nervous system: Headache, fatigue, dizziness Endocrine & metabolic: Hyperkalemia (up to 10%; risk reduced in patients receiving kaliuretic diuretics), hyperchloremic metabolic acidosis, dehydration, hyponatremia, gynecomastia Gastrointestinal: Nausea, diarrhea, vomiting, abdominal pain, gas pain, appetite changes, constipation Genitourinary: Impotence Neuromuscular & skeletal: Muscle cramps, weakness Respiratory: Cough, dyspnea
<1% (Limited to important or life-threatening): Alopecia, arrhythmia, bladder spasms, chest pain, dyspnea, dysuria, GI bleeding, intraocular pressure increased, jaundice, orthostatic hypotension, palpitation, polyuria
CONTRAINDICATIONS — Hypersensitivity to amiloride or any component of the formulation; presence of elevated serum potassium levels (>5.5 mEq/L); if patient is receiving other potassium-conserving agents (eg, spironolactone, triamterene) or potassium supplementation (medicine, potassium-containing salt substitutes, potassium-rich diet); anuria; acute or chronic renal insufficiency; evidence of diabetic nephropathy. Patients with evidence of renal impairment or diabetes mellitus should not receive this medicine without close, frequent monitoring of serum electrolytes and renal function.
WARNINGS / PRECAUTIONS Box warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fluid/electrolyte loss: Excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction.
Disease-related concerns: Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Diabetes: Use with extreme caution in patients with diabetes mellitus; monitor closely. Discontinue amiloride 3 days prior to glucose tolerance testing. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes).
DRUG INTERACTIONS Amoxicillin's absorption may be reduced; avoid concurrent use or observe for clinical response.
ACE inhibitors or angiotensin receptor antagonists can cause hyperkalemia, especially in patients with renal impairment, potassium-rich diets, or on other drugs causing hyperkalemia; avoid concurrent use or monitor closely.
Cyclosporine or tacrolimus: Risk of hyperkalemia may be increased by concurrent therapy.
NSAIDs: May decrease the effect of diuretics.
Potassium supplements may further increase potassium retention and cause hyperkalemia; avoid concurrent use.
Quinidine and amiloride together may increase risk of malignant arrhythmias; avoid concurrent use.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Hyperkalemia may result if amiloride is taken with potassium-containing foods.
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Excretion in breast milk unknown/contraindicated
DIETARY CONSIDERATIONS — Take with food or meals to avoid GI upset. Do not use salt substitutes or low salt milk without checking with your healthcare provider; too much potassium can be as harmful as too little.
PRICING — (data from drugstore.com)Tablets (Amiloride HCl) 5 mg (30): $22.41
Tablets (Midamor) 5 mg (30): $18.99
MONITORING PARAMETERS — I & O, daily weights, blood pressure, serum electrolytes, renal function
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Clinical signs are consistent with dehydration and electrolyte disturbance. Large amounts may result in life-threatening hyperkalemia (>6.5 mEq/L). This can be treated with I.V. glucose (dextrose 25% in water), with rapid-acting insulin, with concurrent I.V. sodium bicarbonate and, if needed, Kayexalate® oral or rectal solutions in sorbitol. Persistent hyperkalemia may require dialysis.
CANADIAN BRAND NAMES — Apo-Amiloride®
INTERNATIONAL BRAND NAMES — Amiclaran (CZ); Amikal (SE); Amilo 5 (KR); Amilozid (HU); Apo-Amiloride (CA); Kaluril (AU, TW); Medamor (FI); Midamor (NZ)
MECHANISM OF ACTION — Interferes with potassium/sodium exchange (active transport) in the distal tubule, cortical collecting tubule, and collecting duct by inhibiting sodium, potassium-ATPase; decreases calcium excretion; increases magnesium loss
PHARMACODYNAMICS / KINETICS Onset of action: 2 hours
Duration: 24 hours
Absorption: ~15% to 25%
Distribution: Vd: 350-380 L
Protein binding: 23%
Metabolism: No active metabolites
Half-life elimination: Normal renal function: 6-9 hours; End-stage renal disease: 8-144 hours
Time to peak, serum: 6-10 hours
Excretion: Urine and feces (equal amounts as unchanged drug)
PATIENT INFORMATION — Report any muscle cramps, weakness, nausea, or dizziness. Use caution operating machinery or performing other tasks requiring alertness.
PHARMACOLOGIC CATEGORY Diuretic, Potassium Sparing
DOSING: ADULTS — Hypertension, edema (to limit potassium loss): Oral: Initial: 5-10 mg/day (up to 20 mg) Hypertension (JNC 7): 5-10 mg/day in 1-2 divided doses
DOSING: PEDIATRIC — Edema, hypertension: Oral: Although safety and efficacy in children have not been established by the FDA, a dosage range of 0.4-0.625 mg/kg/day (maximum: 20 mg/day) has been used in children weighing 6-20 kg.
(For additional information see "Amiloride: Pediatric drug information")
DOSING: ELDERLY — Oral: Initial: 5 mg once daily or every other day
DOSING: RENAL IMPAIRMENT — Oral:
Clcr 10-50 mL/minute: Administer 50% of normal dose.
Clcr <10 mL/minute: Avoid use.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 5 mg
DOSAGE FORMS: CONCISE Tablet: 5 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer with food or meals to avoid GI upset.
USE — Counteracts potassium loss induced by other diuretics in the treatment of hypertension or edematous conditions including CHF, hepatic cirrhosis, and hypoaldosteronism; usually used in conjunction with more potent diuretics such as thiazides or loop diuretics
USE - UNLABELED / INVESTIGATIONAL — Investigational: Cystic fibrosis; reduction of lithium-induced polyuria
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Central nervous system: Headache, fatigue, dizziness Endocrine & metabolic: Hyperkalemia (up to 10%; risk reduced in patients receiving kaliuretic diuretics), hyperchloremic metabolic acidosis, dehydration, hyponatremia, gynecomastia Gastrointestinal: Nausea, diarrhea, vomiting, abdominal pain, gas pain, appetite changes, constipation Genitourinary: Impotence Neuromuscular & skeletal: Muscle cramps, weakness Respiratory: Cough, dyspnea
<1% (Limited to important or life-threatening): Alopecia, arrhythmia, bladder spasms, chest pain, dyspnea, dysuria, GI bleeding, intraocular pressure increased, jaundice, orthostatic hypotension, palpitation, polyuria
CONTRAINDICATIONS — Hypersensitivity to amiloride or any component of the formulation; presence of elevated serum potassium levels (>5.5 mEq/L); if patient is receiving other potassium-conserving agents (eg, spironolactone, triamterene) or potassium supplementation (medicine, potassium-containing salt substitutes, potassium-rich diet); anuria; acute or chronic renal insufficiency; evidence of diabetic nephropathy. Patients with evidence of renal impairment or diabetes mellitus should not receive this medicine without close, frequent monitoring of serum electrolytes and renal function.
WARNINGS / PRECAUTIONS Box warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fluid/electrolyte loss: Excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction.
Disease-related concerns: Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Diabetes: Use with extreme caution in patients with diabetes mellitus; monitor closely. Discontinue amiloride 3 days prior to glucose tolerance testing. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes).
DRUG INTERACTIONS Amoxicillin's absorption may be reduced; avoid concurrent use or observe for clinical response.
ACE inhibitors or angiotensin receptor antagonists can cause hyperkalemia, especially in patients with renal impairment, potassium-rich diets, or on other drugs causing hyperkalemia; avoid concurrent use or monitor closely.
Cyclosporine or tacrolimus: Risk of hyperkalemia may be increased by concurrent therapy.
NSAIDs: May decrease the effect of diuretics.
Potassium supplements may further increase potassium retention and cause hyperkalemia; avoid concurrent use.
Quinidine and amiloride together may increase risk of malignant arrhythmias; avoid concurrent use.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Hyperkalemia may result if amiloride is taken with potassium-containing foods.
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Excretion in breast milk unknown/contraindicated
DIETARY CONSIDERATIONS — Take with food or meals to avoid GI upset. Do not use salt substitutes or low salt milk without checking with your healthcare provider; too much potassium can be as harmful as too little.
PRICING — (data from drugstore.com)Tablets (Amiloride HCl) 5 mg (30): $22.41
Tablets (Midamor) 5 mg (30): $18.99
MONITORING PARAMETERS — I & O, daily weights, blood pressure, serum electrolytes, renal function
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Clinical signs are consistent with dehydration and electrolyte disturbance. Large amounts may result in life-threatening hyperkalemia (>6.5 mEq/L). This can be treated with I.V. glucose (dextrose 25% in water), with rapid-acting insulin, with concurrent I.V. sodium bicarbonate and, if needed, Kayexalate® oral or rectal solutions in sorbitol. Persistent hyperkalemia may require dialysis.
CANADIAN BRAND NAMES — Apo-Amiloride®
INTERNATIONAL BRAND NAMES — Amiclaran (CZ); Amikal (SE); Amilo 5 (KR); Amilozid (HU); Apo-Amiloride (CA); Kaluril (AU, TW); Medamor (FI); Midamor (NZ)
MECHANISM OF ACTION — Interferes with potassium/sodium exchange (active transport) in the distal tubule, cortical collecting tubule, and collecting duct by inhibiting sodium, potassium-ATPase; decreases calcium excretion; increases magnesium loss
PHARMACODYNAMICS / KINETICS Onset of action: 2 hours
Duration: 24 hours
Absorption: ~15% to 25%
Distribution: Vd: 350-380 L
Protein binding: 23%
Metabolism: No active metabolites
Half-life elimination: Normal renal function: 6-9 hours; End-stage renal disease: 8-144 hours
Time to peak, serum: 6-10 hours
Excretion: Urine and feces (equal amounts as unchanged drug)
PATIENT INFORMATION — Report any muscle cramps, weakness, nausea, or dizziness. Use caution operating machinery or performing other tasks requiring alertness.
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