Comparative Pharmacology
Head-to-head clinical analysis: INDERIDE LA 80 50 versus INDERIDE 40 25.
Peer-Reviewed Evidence
Head-to-head clinical analysis: INDERIDE LA 80 50 versus INDERIDE 40 25.
INDERIDE LA 80/50 vs INDERIDE-40/25
Head-to-head clinical comparison of therapeutic indices and safety profiles.
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.
Inderide-40/25 is a combination of propranolol (non-cardioselective beta-blocker) and hydrochlorothiazide (thiazide diuretic). Propranolol reduces heart rate, myocardial contractility, and renin secretion via beta-adrenergic receptor blockade. Hydrochlorothiazide inhibits Na+/Cl- cotransporter in distal convoluted tubule, increasing excretion of Na+, Cl-, and water; also reduces peripheral vascular resistance.
HypertensionAngina pectoris (propranolol component)Migraine prophylaxis (propranolol component)Essential tremor (propranolol component)
HypertensionAdjunctive therapy in hypertension not adequately controlled with monotherapy
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.
One tablet (40 mg propranolol HCl/25 mg hydrochlorothiazide) orally twice daily; may increase to maximum of 160 mg propranolol/100 mg hydrochlorothiazide per day in divided doses.
None Documented
None Documented
Propranolol: 3-6 hours (poor metabolizers up to 10 hours). Hydrochlorthiazide: 6-15 hours (prolonged in renal impairment).
Propranolol: 3-6 hours (terminal); clinical context: dosing 2-3 times daily due to short half-life; may accumulate in hepatic impairment. Hydrochlorothiazide: 6-15 hours (terminal); clinical context: longer in renal impairment.
Propranolol: extensive hepatic metabolism via CYP2D6 and CYP1A2 to active metabolite 4-hydroxypropranolol and other inactive metabolites; hydrochlorothiazide: not metabolized, excreted unchanged by kidneys.
Propranolol: extensively metabolized by CYP2D6 and CYP1A2 to active metabolite 4-hydroxypropranolol; also undergoes glucuronidation. Hydrochlorothiazide: not metabolized, excreted unchanged by kidneys.
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).
Propranolol: extensively metabolized in liver via CYP2D6 and glucuronidation; <1% excreted unchanged in urine. Hydrochlorothiazide: ~70% excreted unchanged in urine via tubular secretion.
Propranolol: >90% bound primarily to albumin; hydrochlorthiazide: 40-68% bound to albumin.
Propranolol: 90% bound primarily to albumin; hydrochlorothiazide: 40-68% bound to plasma proteins.
Propranolol: 3-5 L/kg (large Vd indicates extensive tissue distribution); hydrochlorthiazide: 0.8-1.2 L/kg (distributes into extracellular fluid).
Propranolol: 3.0-4.7 L/kg (extensive tissue distribution; crosses blood-brain barrier). Hydrochlorothiazide: 0.8-1.2 L/kg (confined to extracellular fluid).
Propranolol: 25-30% (first-pass metabolism); hydrochlorthiazide: 65-75% (oral).
Propranolol: absolute oral bioavailability ~30% due to extensive first-pass metabolism; range 20-70% interindividual. Hydrochlorothiazide: oral bioavailability ~60-80% (50-80% in some sources).
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.
For GFR 30-50 mL/min: reduce dose by 50% or use alternative. For GFR <30 mL/min: contraindicated due to hydrochlorothiazide component.
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.
Child-Pugh A: no adjustment; Child-Pugh B: reduce propranolol dose by 50%; Child-Pugh C: avoid use.
Not recommended for use in pediatric patients due to fixed combination and lack of safety/efficacy data.
Not recommended for use in children; safety and efficacy not established.
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.
Initiate at lowest dose (one tablet once daily) and titrate slowly; monitor for hypotension, bradycardia, and electrolyte disturbances.
Exacerbation of angina and myocardial infarction upon abrupt withdrawal of beta-blockers; taper dose over 1-2 weeks.
Exacerbation of angina and myocardial infarction upon abrupt discontinuation: Beta-blocker withdrawal may precipitate angina and, in patients with coronary artery disease, myocardial infarction. Taper dose gradually over 1-2 weeks.
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.
Abrupt discontinuation, bronchospasm in asthmatics, masking of hypoglycemia in diabetics, bradycardia/heart block, worsening heart failure, hypotension, electrolyte disturbances (hypokalemia, hyponatremia), hyperuricemia, acute angle-closure glaucoma, exacerbation of peripheral vascular disease.
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).
Cardiogenic shock, sinus bradycardia, second- or third-degree AV block, severe asthma or COPD, hypersensitivity to sulfonamide-derived drugs (hydrochlorothiazide), anuria, concomitant treatment with MAOIs (except MAO-B inhibitors).
Data Pending Review
Data Pending Review
Avoid grapefruit juice which may alter propranolol metabolism. Avoid licorice (glycyrrhizin) as it can worsen hypokalemia from hydrochlorothiazide. Limit sodium intake to reduce edema and hypertension. Maintain adequate potassium intake (bananas, oranges) unless specified otherwise by physician.
Avoid excessive salt intake; potassium-rich foods (bananas, oranges) may be beneficial but monitor potassium levels if on other potassium-altering drugs. Grapefruit juice may increase propranolol levels; avoid concurrent use.
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.
First trimester: Avoid use due to possible association with congenital malformations (e.g., cardiovascular defects) based on limited studies. Second and third trimesters: Associated with fetal bradycardia, intrauterine growth restriction, oligohydramnios, and neonatal hypoglycemia. Risk of hypoperfusion and hypoxia in fetus if maternal hypotension occurs.
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.
Both propranolol and hydrochlorothiazide are excreted into breast milk. Propranolol milk-to-plasma ratio approximately 1.0. Hydrochlorothiazide M/P ratio 0.1–0.8. Use caution: potential for adverse effects in nursing infant (bradycardia, hypotension, electrolyte disturbances).
No specific dose adjustment is routinely recommended for propranolol in pregnancy, but increased clearance may require dose increment; monitor efficacy. Hydrochlorothiazide is generally avoided in pregnancy due to risk of volume depletion and uteroplacental hypoperfusion; if used, monitor for electrolyte imbalances. Individualize dosing based on maternal response and fetal tolerability.
Monitor maternal blood pressure and heart rate: dose may need reduction due to increased plasma volume and clearance changes. Hydrochlorothiazide: risk of volume depletion and electrolyte imbalances; use lowest effective dose. Propranolol: increased hepatic clearance may require dose adjustment; avoid abrupt discontinuation.
Category C
Category C
INDERIDE LA 80/50 is a fixed-dose combination of propranolol (80 mg long-acting) and hydrochlorothiazide (50 mg). Propranolol is a non-selective beta-blocker that can mask tachycardia in hypoglycemia and thyrotoxicosis; use caution in diabetes and hyperthyroidism. Hydrochlorothiazide may exacerbate gout, hypercalcemia, and hypokalemia. Avoid in patients with asthma, COPD, bradycardia, heart block, or anuria. Monitor electrolytes, renal function, and blood glucose.
Inderide 40/25 (propranolol 40mg/hydrochlorothiazide 25mg) is a fixed-dose combination for hypertension. Propranolol is a non-selective beta-blocker; avoid in asthma, COPD, and heart block. Hydrochlorothiazide may cause hypokalemia; monitor electrolytes. Use with caution in diabetes (masks hypoglycemia) and peripheral vascular disease. Taper beta-blockers slowly to avoid rebound hypertension.
Do not crush or chew the capsule; swallow whole.Take at the same time each day, usually in the morning to avoid nocturia from diuretic.Do not stop abruptly; withdrawal can cause chest pain or heart attack.Report slow heartbeat, dizziness, swelling, weight gain, or shortness of breath.May cause dizziness or drowsiness; avoid driving until effects known.Avoid alcohol and NSAIDs (e.g., ibuprofen) which can reduce effectiveness and increase side effects.Use sunscreen; may increase sun sensitivity (photosensitivity).Monitor for signs of low potassium (muscle cramps, weakness) or high uric acid (joint pain).
Take exactly as prescribed; do not skip doses or double up.May cause dizziness or fatigue; avoid driving until effects known.Avoid sudden discontinuation; can cause rapid heart rate or hypertension.Limit alcohol and NSAIDs; they may increase blood pressure or reduce effect.Report shortness of breath, unusual weight gain, or swelling of extremities.Monitor blood pressure regularly and keep appointments for lab tests (potassium, renal function).May increase sensitivity to cold; dress warmly.