PROPRANOLOL HYDROCHLORIDE 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.
Propranolol is a nonselective beta-adrenergic receptor antagonist that blocks beta-1 and beta-2 receptors, decreasing 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.
| Metabolism | Propranolol is extensively metabolized in the liver via CYP2D6 and CYP1A2 to active metabolite 4-hydroxypropranolol. Hydrochlorothiazide is not metabolized and is excreted unchanged by the kidneys. |
| Excretion | Propranolol: <1% unchanged in urine; extensively metabolized in liver, metabolites (4-hydroxypropanolol and others) excreted renally (90%) and fecally (10%). Hydrochlorothiazide: >95% renally excreted unchanged; negligible biliary/fecal elimination. |
| Half-life | Propranolol: 3-6 hours (terminal) with significant interindividual variability; prolonged in hepatic impairment (up to 11 hours). Hydrochlorothiazide: 6-15 hours (terminal); prolonged in renal impairment (creatinine clearance <30 mL/min). |
| Protein binding | Propranolol: extensively bound (80-95%) primarily to albumin and alpha-1-acid glycoprotein, with saturable binding at high concentrations. Hydrochlorothiazide: weakly bound (40-70%) to albumin. |
| Volume of Distribution | Propranolol: Vd 3-5 L/kg; large Vd indicates extensive tissue distribution. Hydrochlorothiazide: Vd 0.2-0.8 L/kg; distributes mainly in extracellular fluid. |
| Bioavailability | Propranolol: Oral bioavailability is 30-40% (first-pass hepatic metabolism), low and variable; increases with chronic dosing due to saturation of first-pass effect. Hydrochlorothiazide: Oral bioavailability is 65-75% (fasting), reduced by food (10-20% decrease). |
| Onset of Action | Oral: propranolol antihypertensive effect may take 2-3 days to onset with maximal effect by 1-2 weeks; hydrochlorothiazide diuretic effect begins within 2 hours, peaks at 4-6 hours. |
| Duration of Action | Propranolol: antihypertensive effect lasts 24 hours with regular dosing due to active metabolites; HCl has a 6-12 hour duration of diuretic effect, but with once-daily dosing given combination product, continuous antihypertensive coverage maintained. |
Oral: 1 tablet (propranolol 40 mg / hydrochlorothiazide 25 mg) twice daily or as needed to control blood pressure; maximum propranolol 320 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: reduce dose or extend interval; GFR <30 mL/min: avoid hydrochlorothiazide component (ineffective); propranolol may be used with caution. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce propranolol dose by 50%; Child-Pugh C: avoid or use with extreme caution, consider alternative therapy. |
| Pediatric use | Not recommended for children under 18 years; safety and efficacy not established. |
| Geriatric use | Initiate at lowest dose (e.g., propranolol 40 mg / hydrochlorothiazide 25 mg once daily) and titrate slowly; monitor for hypotension, bradycardia, and electrolyte imbalance. |
| 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 | Propranolol is excreted in breast milk (M/P ratio approximately 0.5-2.0). HCTZ is excreted in low amounts. Monitor infant for bradycardia, hypotension, and electrolyte imbalance. Use caution, especially in premature or jaundiced neonates. |
| Teratogenic Risk |
■ FDA Black Box Warning
Exacerbation of ischemic heart disease following abrupt discontinuation: Exacerbation of angina and myocardial infarction have occurred after abrupt cessation of beta-blocker therapy. When discontinuing, taper dose over 1-2 weeks.
| Common Effects | angina |
| Serious Effects |
migraine prevention
| Precautions | May precipitate congestive heart failure; avoid abrupt withdrawal in coronary artery disease; may mask signs of hyperthyroidism; caution in diabetes (hypoglycemia masking); may cause bronchospasm in asthma/COPD; hypotension; bradycardia; may worsen peripheral vascular disease; hepatic impairment; renal impairment (hydrochlorothiazide); electrolyte imbalances; may cause fetal harm. |
Loading safety data…
| First trimester: Propranolol crosses placenta; risk of fetal bradycardia and hypoglycemia. HCTZ associated with neural tube defects? (not confirmed). Second/third trimester: Both drugs can cause fetal/neonatal adverse effects including bradycardia, hypotension, hypoglycemia (propranolol), and electrolyte disturbances, oligohydramnios (HCTZ). HCTZ may decrease placental perfusion. Avoid in pregnancy-induced hypertension. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, electrolytes, renal function. Fetal monitoring for growth, heart rate, and amniotic fluid volume (due to HCTZ). Neonatal monitoring for bradycardia, hypoglycemia, electrolyte disturbances. |
| Fertility Effects | Propranolol may impair male fertility via decreased libido and erectile dysfunction. HCTZ may cause electrolyte imbalances affecting ovulation. No definitive data on female fertility impairment. |