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metolazone (Zaroxolyn, Diulo, Mykrox)
Tradenames: Zaroxolyn, Diulo, Mykrox.
Indications:
1) treatment of hypertension & edema
2) may be more effective than thiazides for edema in patients with renal impairment
3) adjunctive therapy used with loop diuretic
- given 30 minutes before Lasix, may result in diuresis in refractory cases.
Dosage:
1) start 5 mg PO QD
2) max 20 mg/day
3) children: 0.2-0.4 mg/kg/day (QD or BID dosing)
Tabs: 2.5, 5, 10 mg
Pharmacokinetics:
1) incompletely & poorly absorbed after oral administration
2) 50-70% of drug is bound to erythrocytes
3) 33% of drug is bound to plasma proteins
4) onset of action is 30-60 minutes
5) 70-95% of the drug is excreted in the urine unchanged
6) elimination 1/2life is 14 hours
Adverse effects:
1) laboratory abnormalities
a) hyperuricemia
b) hypokalemia & K+ depletion
c) hypochloremic alkalosis
d) dilutional hyponatremia
e) hyperglycemia
f) increased low-density lipoprotein (LDL)
g) pre-renal azotemia
h) increased PTH with chronic use
1] hypercalcemia
2] hypophosphatemia
3] hypomagnesemia
2) pancreatitis
3) vasculitis (esp. exacerbation of SLE)
4) cross-sensitivity in patients with sulfa allergies
5) orthostatic hypotension
6) photosensitivity
7) uncommon (< 1%)
- drowsiness, paresthesias, rash, nausea/vomiting, anorexia, aplastic anemia, hemolytic anemia, leukopenia, agranulocytosis, thrombocytopenia, hepatitis, polyuria
Drug interactions:
1) drugs that lower serum K+
2) decreases Li+ clearance, resulting in increased Li+ plasma levels
3) increased requirements of hypoglycemic agents
a) insulin
b) sulfonylurea
4) probenecid
a) blocks thiazide-induced uric acid retention
b) enhances excretion of Ca+2, Mg+2, citrate
5) NSAIDs in combination increases risk of NSAID-induced renal toxicity
Mechanism of action:
1) thiazide-like diuretic
2) site of action: proximal & distal tubules
3) enhances secretion of Na+, Cl- & H2O by interfering with Na+ & Cl- transport across the renal tubular epithelium mediated by SLC12A3
4) effects excretion of other electrolytes including K+ & HCO3-
Interactions
drug interactions
drug adverse effects (more general classes)
monitor with thiazide diuretics
General
sulfonamide
thiazide diuretic
Properties
MISC-INFO: elimination route KIDNEY
LIVER
1/2life 14 HOURS
pregnancy-category B
safety in lactation ?
elimination by hemodialysis -
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996.
- Manual of Medical Therapeutics, 28th ed, Ewald &
McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 123
- Drug Information & Medication Formulary, Veterans Affairs,
Central California Health Care System, 1st ed., Ravnan et al
eds, 1998
- Kaiser Permanente Northern California Regional Drug
Formulary, 1998