INDERIDE LA 80/50
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INDERIDE LA 80/50 (INDERIDE LA 80/50).
Combination of propranolol (non-selective beta-blocker) and hydrochlorothiazide (thiazide diuretic). Propranolol blocks beta-1 and beta-2 adrenergic receptors, reducing heart rate, myocardial contractility, and blood pressure. Hydrochlorothiazide inhibits sodium-chloride symporter in distal convoluted tubule, increasing excretion of sodium, chloride, and water, reducing plasma volume.
| Metabolism | Propranolol: extensive hepatic metabolism via CYP2D6 and CYP1A2 to active metabolite 4-hydroxypropranolol and other inactive metabolites; hydrochlorothiazide: not metabolized, excreted unchanged by kidneys. |
| Excretion | Renal elimination of propranolol and hydrochlorthiazide: propranolol is extensively metabolized in the liver, <1% excreted unchanged in urine; hydrochlorthiazide is excreted unchanged in urine (≥95% renal). |
| Half-life | Propranolol: 3-6 hours (poor metabolizers up to 10 hours). Hydrochlorthiazide: 6-15 hours (prolonged in renal impairment). |
| Protein binding | Propranolol: >90% bound primarily to albumin; hydrochlorthiazide: 40-68% bound to albumin. |
| Volume of Distribution | Propranolol: 3-5 L/kg (large Vd indicates extensive tissue distribution); hydrochlorthiazide: 0.8-1.2 L/kg (distributes into extracellular fluid). |
| Bioavailability | Propranolol: 25-30% (first-pass metabolism); hydrochlorthiazide: 65-75% (oral). |
| Onset of Action | Oral: Propranolol beta-blockade begins within 1-2 hours; hydrochlorthiazide diuresis begins within 2 hours. |
| Duration of Action | Propranolol: 12 hours (sustained-release). Hydrochlorthiazide: 6-12 hours (single dose), but antihypertensive effect persists for 24 hours. |
One capsule orally once daily, containing propranolol hydrochloride 80 mg (immediate release) and hydrochlorothiazide 50 mg. May be titrated based on response, with maximum propranolol dose 640 mg/day and maximum hydrochlorothiazide dose 50 mg/day.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | Contraindicated in anuria. For GFR 30-50 mL/min: reduce dose or extend interval; monitor electrolyte levels. For GFR <30 mL/min: avoid use or administer with extreme caution; thiazides are ineffective at GFR <30 mL/min. |
| Liver impairment | Child-Pugh Class A: no adjustment required. Child-Pugh Class B: reduce propranolol dose by 50% and monitor heart rate. Child-Pugh Class C: avoid use due to risk of hepatic encephalopathy and reduced clearance of propranolol. |
| Pediatric use | Not recommended for use in pediatric patients due to fixed combination and lack of safety/efficacy data. |
| Geriatric use | Initiate at lowest effective dose (e.g., one capsule of INDERIDE LA 40/25 daily). Monitor renal function, electrolytes, and orthostatic hypotension. Avoid in elderly with gout or hyperuricemia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INDERIDE LA 80/50 (INDERIDE LA 80/50).
| Breastfeeding | Propranolol is excreted into breast milk in low amounts (M/P ratio approximately 0.5). Infant dose estimated at <1% of maternal weight-adjusted dose. Not known to cause adverse effects in term infants; monitor for bradycardia, hypotension, hypoglycemia. Hydrochlorothiazide: Minimal excretion; may suppress lactation. Use caution, especially in preterm infants. |
| Teratogenic Risk | First trimester: Propranolol (beta-blocker) crosses placenta, associated with intrauterine growth restriction (IUGR) and small placental weight. Second/third trimester: Increased risk of fetal bradycardia, hypoglycemia, respiratory depression, and low Apgar scores. Avoid in pregnancy unless benefit outweighs risk; consider alternative agents. |
■ FDA Black Box Warning
Exacerbation of angina and myocardial infarction upon abrupt withdrawal of beta-blockers; taper dose over 1-2 weeks.
| Serious Effects |
Hypersensitivity to propranolol, hydrochlorothiazide, or sulfonamide-derived drugs; bronchial asthma; sinus bradycardia; heart block greater than first degree; cardiogenic shock; overt cardiac failure; anuria; concomitant use with verapamil (for propranolol).
| Precautions | May mask signs of thyrotoxicosis and hypoglycemia; exacerbation of peripheral vascular disease; bronchospasm in patients with asthma/COPD; cardiac failure; electrolyte imbalances (hypokalemia, hyponatremia) with thiazide; acute angle-closure glaucoma; systemic lupus erythematosus exacerbation; non-melanoma skin cancer risk with thiazides. |
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| Fetal Monitoring | Monitor maternal heart rate, blood pressure, and signs of hypoglycemia. Fetal monitoring includes growth ultrasound for IUGR, fetal heart rate monitoring for bradycardia (especially during labor), and neonatal assessment for bradycardia, hypoglycemia, and respiratory depression at delivery. |
| Fertility Effects | Propranolol may impair fertility in males by reducing sperm motility and count; in females, beta-blockers may reduce ovarian response. Hydrochlorothiazide has no known direct effects on fertility. Overall, limited data; potential reversible impairment. |