DUTOPROL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DUTOPROL (DUTOPROL).
Combination of metoprolol tartrate (beta-1-selective adrenergic receptor blocker) and hydrochlorothiazide (thiazide diuretic inhibiting Na+/Cl- cotransporter in distal convoluted tubule).
| Metabolism | Metoprolol: primarily CYP2D6; Hydrochlorothiazide: not metabolized, excreted unchanged in urine. |
| Excretion | Renal: 40-50% as unchanged drug and metabolites (hydrochlorothiazide and bisoprolol); Fecal/Biliary: <15%. |
| Half-life | Bisoprolol: 10-12 hours, allowing once-daily dosing; Hydrochlorothiazide: 6-15 hours, prolonged in renal impairment. |
| Protein binding | Bisoprolol: 30% bound to albumin; Hydrochlorothiazide: 40-68% bound to plasma proteins (predominantly albumin). |
| Volume of Distribution | Bisoprolol: 3.5 L/kg, reflecting extensive tissue distribution; Hydrochlorothiazide: 0.83 L/kg, indicating distribution in extracellular fluid. |
| Bioavailability | Oral: Bisoprolol 90% (high, first-pass negligible); Hydrochlorothiazide 65-75%. |
| Onset of Action | Oral: Antihypertensive effect within 1-2 hours; maximal effect at 2-4 weeks. |
| Duration of Action | Bisoprolol: 24 hours (beta-blockade); Hydrochlorothiazide: 12-16 hours (diuresis); combined effect for 24-hour BP control. |
1 tablet (containing 12.5 mg hydrochlorothiazide and 50 mg losartan) orally once daily; may increase to 1 tablet (12.5 mg/100 mg) once daily if inadequate response.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | Contraindicated if GFR <30 mL/min/1.73 m². For GFR 30-60 mL/min/1.73 m²: no dose adjustment required, but monitor potassium and creatinine. For GFR <30 mL/min/1.73 m²: do not use. |
| Liver impairment | Child-Pugh Class A or B: no dose adjustment; use with caution. Child-Pugh Class C: not recommended. |
| Pediatric use | Not approved for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | Start at lowest possible dose; monitor renal function and electrolytes. No specific dose adjustment required if renal function normal, but elderly more susceptible to hypotension and electrolyte imbalance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DUTOPROL (DUTOPROL).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. Use with caution, monitor infant for bradycardia and hypotension. |
| Teratogenic Risk | Category D: First trimester exposure associated with fetal bradycardia, intrauterine growth restriction, and oligohydramnios; second and third trimester use may cause fetal hypotension, hypoglycemia, and decreased placental perfusion. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Sinus bradycardia, heart block greater than first degree, cardiogenic shock, overt cardiac failure.","Bronchial asthma or significant COPD.","Anuria or hypersensitivity to sulfonamide-derived drugs (thiazides)."]
| Precautions | ["Exacerbation of ischemic heart disease upon abrupt withdrawal of beta-blocker.","Bronchospasm in patients with bronchospastic disease.","May mask signs of hyperthyroidism or hypoglycemia.","Electrolyte disturbances (hypokalemia, hyponatremia) due to thiazide.","May increase serum uric acid and precipitate gout.","May cause photosensitivity reaction."] |
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| Maternal: blood pressure, heart rate, serum electrolytes, and renal function. Fetal: heart rate monitoring, ultrasound assessment of growth and amniotic fluid volume. |
| Fertility Effects | No known adverse effects on fertility in animal studies; human data insufficient. |