DUTOPROL
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 528.53 |
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 | Avoid due to risk of fetal bradycardia and hypotension; first-trimester exposure associated with potential organogenesis effects. |
| 2nd trimester | Use only if benefit outweighs risk; monitor fetal heart rate and amniotic fluid index. |
| 3rd trimester | Contraindicated in third trimester due to risk of neonatal bradycardia, hypotension, and hypoglycemia. |
Clinical note
Comprehensive clinical and safety monograph for DUTOPROL (DUTOPROL).
| Placental transfer | Dutasteride crosses the placenta; demonstrated in animal studies and inferred from human case reports. |
| Breastfeeding | Dutasteride is excreted into human breast milk; potential for serious adverse effects in nursing infants, including feminization of male infants. Breastfeeding is not recommended during therapy and for 6 months after last dose. |
| Lactation Rating | L5 (Contraindicated) |
| 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 | 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
PregnancyWomen of childbearing potential (unless using effective contraception)Hypersensitivity to dutasteride or any componentSevere hepatic impairment (Child-Pugh Class C)
| 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. |
| Food/Dietary | DUTOPROL should be taken 30 minutes after the same meal each day to reduce variability in absorption. Grapefruit juice inhibits CYP3A4 and can increase dutasteride levels; avoid concomitant consumption. High-fat meals may alter absorption, but consistent timing with a meal minimizes fluctuations. No other specific food interactions are known, but maintain a balanced diet and avoid excessive alcohol, which can worsen dizziness or hypotension. |
| Clinical Pearls | DUTOPROL is a fixed-dose combination of dutasteride (0.5 mg) and tamsulosin (0.4 mg) used for benign prostatic hyperplasia (BPH). Due to dutasteride's long half-life (~5 weeks), clinical effect on prostate volume may take 3–6 months. Tamsulosin, an alpha-1 blocker, can cause orthostatic hypotension, especially when initiated; titrate cautiously in elderly or those on antihypertensives. Avoid concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole) as they increase dutasteride exposure. Measure PSA before starting and periodically thereafter; dutasteride halves PSA levels after 6 months, so adjust interpretation. Do not use in women or children. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily, 30 minutes after the same meal each day to maintain consistent absorption. · Do not crush, chew, or open the capsules; swallow them whole to avoid irritation. · This drug can cause dizziness, lightheadedness, or fainting, especially when first starting or if you take blood pressure medications. Get up slowly from sitting or lying down. · Avoid grapefruit juice and grapefruit products as they may affect how the drug works. · Inform your doctor if you experience any of the following: severe dizziness, difficulty urinating, chest pain, or signs of an allergic reaction (rash, itching, swelling). · Do not donate blood while taking this medication and for at least 6 months after stopping, as the drug can be present in blood and cause harm to a pregnant woman or her baby. · If you are having cataract surgery, tell your surgeon you are taking this drug, as it may increase the risk of intraoperative floppy iris syndrome (IFIS). · This medication may cause a decrease in sexual desire, difficulty with erections, or reduced semen volume. These side effects are generally reversible after stopping treatment. · Women who are pregnant or could become pregnant should avoid handling crushed or broken capsules due to risk of harm to the unborn baby. · Regular follow-ups with your healthcare provider for PSA testing and symptom monitoring are important to assess treatment response and adjust dose if needed. |
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