METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE
Clinical safety rating: caution
Other drugs that lower heart rate or blood pressure can have additive effects Abrupt withdrawal may exacerbate angina pectoris or cause myocardial infarction.
Metoprolol is a cardioselective beta-1 adrenergic receptor antagonist that reduces heart rate, myocardial contractility, and blood pressure. Hydrochlorothiazide is a thiazide diuretic that inhibits the sodium-chloride symporter in the distal convoluted tubule, increasing excretion of sodium and water, thereby reducing plasma volume and blood pressure.
| Metabolism | Metoprolol is primarily metabolized by CYP2D6 to alpha-hydroxymetoprolol; Hydrochlorothiazide is not extensively metabolized and is excreted unchanged in urine. |
| Excretion | Metoprolol: <5% renal (unchanged), >95% hepatic metabolism, metabolites excreted renally. Hydrochlorothiazide: >95% renal (unchanged). |
| Half-life | Metoprolol: 3–7 h (terminal), clinical context: may require twice-daily dosing; prolonged in hepatic impairment. Hydrochlorothiazide: 6–15 h (terminal), clinical context: supports once-daily dosing; prolonged in renal impairment. |
| Protein binding | Metoprolol: <12% (mainly albumin). Hydrochlorothiazide: 40–68% (albumin). |
| Volume of Distribution | Metoprolol: 4.2 L/kg (extensive tissue distribution). Hydrochlorothiazide: 0.8 L/kg (confined to extracellular fluid). |
| Bioavailability | Metoprolol oral: ~50% (first-pass effect); food increases absorption. Hydrochlorothiazide oral: ~70%. |
| Onset of Action | Metoprolol oral: 1 h (beta-blockade). Hydrochlorothiazide oral: 2 h (diuresis). |
| Duration of Action | Metoprolol: 12–24 h (cardioprotective effects); note: antihypertensive effect may persist >24 h. Hydrochlorothiazide: 6–12 h (diuresis), up to 24 h (antihypertensive). |
Oral: 50-100 mg metoprolol tartrate/12.5-25 mg hydrochlorothiazide once or twice daily; maximum 200 mg metoprolol/50 mg hydrochlorothiazide per day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: No adjustment required; GFR <30 mL/min: Avoid hydrochlorothiazide component; use alternative. |
| Liver impairment | Child-Pugh A: No adjustment; Child-Pugh B: Reduce metoprolol dose by 50%; Child-Pugh C: Contraindicated. |
| Pediatric use | Not FDA-approved for pediatric use; limited data: metoprolol 1-2 mg/kg/day divided q12h, hydrochlorothiazide 1-2 mg/kg/day divided q12h; adjust based on response. |
| Geriatric use | Start at lowest available dose (e.g., 50 mg metoprolol/12.5 mg hydrochlorothiazide) once daily; titrate slowly; monitor hypotension, electrolyte imbalance, and renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other drugs that lower heart rate or blood pressure can have additive effects Abrupt withdrawal may exacerbate angina pectoris or cause myocardial infarction.
| FDA category | Animal |
| Breastfeeding | Metoprolol: Enters breast milk in small amounts (M/P ratio approximately 1.0); infant dose <2% maternal weight-adjusted dose. Considered compatible with caution; monitor infant for bradycardia, hypotension, and hypoglycemia. Hydrochlorothiazide: Excreted in breast milk in low concentrations; M/P ratio not well defined; may suppress lactation and cause infant electrolyte disturbances. Avoid high doses or use alternative if possible. |
■ FDA Black Box Warning
No FDA boxed warning exists for this combination product.
| Common Effects | angina |
| Serious Effects |
["Sinus bradycardia","Second- or third-degree heart block","Cardiogenic shock","Decompensated heart failure","Sick sinus syndrome (without pacemaker)","Severe peripheral arterial disease","Pheochromocytoma (untreated)","Hypersensitivity to metoprolol, hydrochlorothiazide, or sulfonamide-derived drugs (hydrochlorothiazide)","Anuria","Severe renal impairment (eGFR <30 mL/min/1.73 m²)"]
| Precautions | ["Exacerbation of ischemic heart disease upon abrupt discontinuation","Bronchospasm in patients with asthma/COPD","Bradycardia and heart block","Hypotension and electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia) due to thiazide","May mask signs of hypoglycemia or hyperthyroidism","May precipitate heart failure in patients with poor cardiac reserve","Renal impairment; monitoring required","May cause hyperuricemia and gout","May increase sensitivity to allergens","Potential for systemic lupus erythematosus exacerbation"] |
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| Teratogenic Risk |
| First trimester: Limited human data; metoprolol crosses placenta; potential for fetal bradycardia and hypoglycemia with beta-blocker use. Hydrochlorothiazide (HCTZ) associated with increased risk of congenital anomalies (e.g., neural tube defects) in retrospective studies. Second/third trimester: Metoprolol may cause fetal growth restriction, neonatal bradycardia, and hypoglycemia. HCTZ can cause fetal/neonatal electrolyte disturbances, thrombocytopenia, and is not recommended for gestational hypertension due to decreased placental perfusion. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate; fetal heart rate and growth via ultrasound; neonatal assessment for bradycardia, hypoglycemia, and electrolyte imbalances; periodic maternal serum electrolytes (Na, K, Ca) and renal function; monitor for signs of placental insufficiency. |
| Fertility Effects | Limited data; beta-blockers may impair sexual function (e.g., erectile dysfunction) in males; no direct evidence of altered fertility in females. Hydrochlorothiazide may cause mild zinc deficiency potentially affecting spermatogenesis; overall impact on fertility is likely minimal. |