Metolazone

 Action Increases urinary excretion of sodium and chloride by inhibiting reabsorption in ascending limb of loop of Henle and early distal tubules.

 Indications Treatment of edema and hypertension. Unlabeled use(s): Prevention of calcium nephrolithiasis; reduction of postmenopausal osteoporosis; reduction of urine volume in diabetes insipidus.

 Contraindications Anuria; renal decompensation; hepatic coma or precoma.

 Route/Dosage

ADULTS: PO 0.5–1 mg/day (Mykrox) or 2.5–20 mg/day (Zaroxolyn). Do not interchange Mykrox with Zaroxolyn. Mykrox s absorbed more rapidly and more completely than Zaroxolyn.

 Interactions

Cholestyramine, colestipol: May decrease effects of metolazone by decreasing absorption. Diazoxide: Concurrent use may produce severe hyperglycemia. Digitalis glycosides (eg, digoxin): Urinary loss of potassium and magnesium may predispose patient to digitalis-induced arrhythmia. Lithium: Metolazone may decrease renal elimination of lithium, resulting in toxicity. Loop diuretics (eg, furosemide): Concurrent use may produce profound diuresis and electrolyte abnormalities. Sulfonylureas (eg, tolbutamide): Metolazone may decrease hypoglycemic effect of Sulfonylureas by increasing blood glucose.

 Lab Test Interferences None well documented.

 Adverse Reactions

CV: Rapid-acting formulation: Orthostatic hypotension; palpitations; hest pain; cold extremities; edema. Slow-acting formulation: Venous thrombosis, palpitations; chest pain; excessive volume depletion; hemoconcentration. CNS: Rapid-acting formulation: Dizziness; headache; weakness; “weird” eeling; neuropathy; fatigue; lethargy; lassitude; depression. Slow-acting formulation: Dizziness; syncope; neuropathy; vertigo; headache; weakness; atigue; lethargy; lassitude; anxiety; depression; nervousness. DERM: Rapid-acting formulation: Necrotizing angiitis; vasculitis; utaneous vasculitis; dry skin. Slow-acting formulation: Photosensitivity; ecrotizing angiitis; vasculitis; cutaneous vasculitis. EENT: Bitter taste. GI: Rapid-acting formulation: Nausea. Slow-acting formulation: Nausea; anorexia; ancreatitis. GU: Slow-acting formulation: Impotence. HEMA: Slow-acting formulation: Leukopenia; agranulocytosis; aplastic anemia. HEPA: Slow-acting formulation: Jaundice; hepatitis. META: Hypokalemia; hyperuricemia; hyponatremia; hypochloremia; hypochloremic alkalosis. RESP: Rapid-acting formulation: Cough; epistaxis; sinus congestion; ore throat. OTHER: Rapid-acting formulation: Impotence; joint pain; back pain; itching eyes; tinnitus; muscle cramps and spasms. Slow-acting formulation: Swelling; hills; acute gouty attack; hyperglycemia; glucosuria; muscle cramps and spasms.

 Precautions

Pregnancy: Category B. Lactation: Undetermined. Children: Not recommended for children. Fluid and electrolytes: May be altered; periodic determinations of serum electrolytes, BUN, uric acid and glucose are indicated. Hepatic impairment: May precipitate hepatic coma; use drug with caution. Hypersensitivity: May occur; cross-sensitivity to sulfonamides or thiazides possible. Hyperuricemia: May increase serum uric acid and precipitate gout. Lipids: May cause increases in total serum cholesterol, triglycerides and LDL. Lupus erythematosus: May be activated or exacerbated. Post-sympathectomy patients: Antihypertensive effects may be increased. Renal impairment: May precipitate azotemia; use drug with caution. Tartrazine-sensitivity: Some products contain tartrazine, which may cause allergic-type reactions eg, bronchial asthma).

 Administration/Storage

• For treatment of edema, establish schedule for intermittent therapy every other day or 3–5 days/wk schedule to reduce potential for electrolyte imbalance.
• For treatment of hypertension, check orders for dosage adjustments of other agents to prevent hypotension.
• Do not interchange product with other brand or generic forms because some formulations are more rapidly bioavailable and not therapeutically equivalent at same doses of other thiazides.
• Administer medication in morning to prevent nocturia.
• Store at room temperature in tight, light-resistant container.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies.
• Assess for signs of fluid or electrolyte imbalance (dry mouth, thirst, confusion, muscle fatigue, hypotension, tachycardia).
• Maintain accurate I&O records.
• Monitor blood sugar closely for diabetic patients.
• Monitor serum uric acid levels periodically.
• Assess initial and periodic determinations of serum electrolytes and uric acid levels.
• For treatment of diabetic patients, monitor output. If output increases, dosage may need to be increased.

 Patient/Family Education

• Advise patient to take early in day to avoid sleep disruption.
• Tell patient to take with food if stomach upset occurs.
• Explain significance of potential potassium loss, and identify appropriate supplemental food sources (eg, bananas, orange juice, dates, citrus fruits, apricots). Teach patient signs and symptoms of hypokalemia (muscle weakness, cramping).
• Explain that dizziness or lightheadedness may occur if patient stands up too fast.
• Tell patient to avoid exposure to sunlight and to use sunscreen or wear protective clothing until tolerance to sunlight can be established.
• Explain that BP should be checked periodically by patient or family member.
• Review signs and symptoms of fluid imbalance.