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Metolazone

Dosage ;

Combinations ; - see below

Dosing: Adult

Edema: Oral: Initial: 2.5-10 mg once daily; may increase as necessary to 20 mg once daily (ACC/AHA 2009 Heart Failure Guidelines)

Hypertension: Oral: 2.5-5 mg/dose every 24 hours

Dosing: Geriatric

Oral: Initial: 2.5 mg/day or every other day

Dosing: Renal Impairment

Not dialyzable (0% to 5%) via hemo- or peritoneal dialysis; supplemental dose is not necessary

Dosage Forms: U.S.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, oral: 2.5 mg, 5 mg, 10 mg

Zaroxolyn®: 2.5 mg, 5 mg

Generic Equivalent Available: U.S.

Yes

Administration

May be taken with food or milk. Take early in day to avoid nocturia. Take the last dose of multiple doses no later than 6 PM unless instructed otherwise.

Use

Management of mild-to-moderate hypertension; treatment of edema in heart failure and nephrotic syndrome, impaired renal function

Adverse Reactions Significant

Frequency not defined.

Cardiovascular: Chest pain/discomfort, necrotizing angiitis, orthostatic hypotension, palpitation, syncope, venous thrombosis, vertigo, volume depletion

Central nervous system: Chills, depression, dizziness, drowsiness, fatigue, headache, lightheadedness, restlessness

Dermatologic: Petechiae, photosensitivity, pruritus, purpura, rash, skin necrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria

Endocrine & metabolic: Gout attacks, hypercalcemia, hyperglycemia, hyperuricemia, hypochloremia, hypochloremic alkalosis, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia

Gastrointestinal: Abdominal bloating, abdominal pain, anorexia, constipation, diarrhea, epigastric distress, nausea, pancreatitis, vomiting, xerostomia

Genitourinary: Impotence

Hematologic: Agranulocytosis, aplastic/hypoplastic anemia, hemoconcentration, leukopenia, thrombocytopenia

Hepatic: Cholestatic jaundice, hepatitis

Neuromuscular & skeletal: Joint pain, muscle cramps/spasm, neuropathy, paresthesia, weakness

Ocular: Blurred vision (transient)

Renal: BUN increased, glucosuria

Contraindications

Hypersensitivity to metolazone, any component of the formulation, other thiazides, and sulfonamide derivatives; anuria; hepatic coma; pregnancy (expert analysis)

Warnings/Precautions

Concerns related to adverse effects:

• Electrolyte disturbances: Hypokalemia, hypochloremic alkalosis, and hyponatremia can occur.

• Photosensitivity: Photosensitization may occur.

• Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with thiazide or 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 caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control.

• Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated.

• Hepatic impairment: Use with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.

• Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations.

• Hypokalemia: Use with caution in patients with hypokalemia; correct before initiating therapy.

• Renal impairment: Avoid in severe renal disease (ineffective).

• Systemic lupus erythematosus (SLE): Can cause SLE exacerbation or activation.

Concurrent drug therapy issues:

• Furosemide: Large or prolonged fluid and electrolyte losses may occur with concomitant furosemide administration