Indever

Approved Indications:

• Hypertension (High Blood Pressure):
  Used alone or with other antihypertensive agents to reduce blood pressure and lower the risk of cardiovascular events (e.g., stroke, MI).
• Angina Pectoris:
  For long-term management of stable angina and to reduce frequency and severity of chest pain.
• Cardiac Arrhythmias:
  Treatment of supraventricular and ventricular arrhythmias, including atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia.
• Myocardial Infarction (Post-MI):
  For secondary prevention of mortality post-MI by reducing infarct size and risk of recurrent ischemic events.
• Migraine Prophylaxis:
  Effective for reducing the frequency and intensity of migraine attacks.
• Essential Tremor:
  Management of familial or benign essential tremor.
• Pheochromocytoma (Adjunct):
  Used with alpha-blockers in managing tachycardia and hypertension associated with catecholamine-secreting tumors.
• Hypertrophic Subaortic Stenosis (HOCM):
  Symptom relief in obstructive cardiomyopathy.

Clinically Accepted Off-Label Uses:

• Anxiety (Performance Anxiety):
  Acute management of physical symptoms of anxiety (e.g., tremors, palpitations).
• Thyrotoxicosis and Thyroid Storm:
  Controls tachycardia and tremors; reduces peripheral conversion of T4 to T3.
• Portal Hypertension/Esophageal Varices Prophylaxis:
  Reduces portal pressure and risk of variceal bleeding in cirrhotic patients.
• Infantile Hemangioma (Oral Solution):
  For proliferating infantile hemangioma requiring systemic therapy.

Route: Oral (tablets, extended-release capsules, solution), IV (in emergencies)

Adults:

• Hypertension:
• Initial: 40 mg PO twice daily
• Maintenance: 120–240 mg/day in divided doses (immediate-release)
• ER formulation: 80 mg once daily, titrated up to 120–240 mg/day
• Angina Pectoris:
• 80–320 mg/day PO in divided doses
• Arrhythmias:
• Oral: 10–30 mg PO 3–4 times/day
• IV (acute): 1–3 mg slow IV push (rate: 1 mg/min), may repeat after 2 minutes up to 10 mg total
• Post-MI:
• Oral: 180–240 mg/day in divided doses
• Migraine Prophylaxis:
• 80–160 mg/day PO in divided doses
• Essential Tremor:
• Initial: 40 mg PO twice daily
• Maintenance: 120–320 mg/day
• Pheochromocytoma (Adjunct):
• 60 mg/day in divided doses (with alpha-blocker)

Pediatrics:

• Arrhythmias:
• 0.5–1 mg/kg/day PO in divided doses (max 4 mg/kg/day)
• Migraine Prophylaxis:
• Typically 1–3 mg/kg/day in divided doses
• Infantile Hemangioma (Oral Solution):
• Start: 0.5 mg/kg twice daily
• Titrate to 1–3 mg/kg/day in two divided doses

Elderly:

• Begin at lower end of dosing range; monitor heart rate and BP closely due to increased sensitivity

Renal/Hepatic Impairment:

• Use with caution; dosage adjustment may be necessary due to altered drug clearance
• Start with lower doses and monitor response closely

Propranolol is a non-selective beta-adrenergic receptor antagonist that blocks both β1 and β2 receptors. By inhibiting β1 receptors in the heart, it reduces heart rate, myocardial contractility, and cardiac output, thereby lowering blood pressure and myocardial oxygen demand. β2 receptor blockade in vascular and bronchial smooth muscle may contribute to peripheral vasoconstriction and bronchoconstriction. It also reduces renin release from the kidneys, further aiding in blood pressure control. In the CNS, propranolol inhibits central sympathetic outflow, contributing to anxiolytic effects. Its membrane-stabilizing activity at high doses may also help in arrhythmia suppression.

• Absorption: Rapid and nearly complete after oral administration
• Bioavailability: ~25–35% (extensive first-pass hepatic metabolism)
• Distribution:
• Widely distributed; crosses blood-brain barrier and placenta
• Plasma protein binding: ~90–95%
• Metabolism: Hepatic metabolism via CYP1A2, CYP2D6, and CYP2C19
• Metabolites: 4-hydroxypropranolol (active) and others
• Elimination:
• Primarily renal (as metabolites)
• ~1% excreted unchanged in urine
• Half-life:
• Immediate-release: ~3–6 hours
• Extended-release: ~8–10 hours
• Onset of Action: Within 1 hour (oral), immediate (IV)
• Peak Effect: 1–2 hours (IR); 6 hours (ER)
• Duration: 6–12 hours (IR), up to 24 hours (ER)

• Pregnancy:
  Former FDA Category C.
  Use only if potential benefit justifies the potential risk to fetus. May cause fetal growth restriction, neonatal hypoglycemia, or bradycardia if used near delivery.
• Lactation:
  Propranolol is excreted in breast milk in low amounts.
  Generally considered compatible with breastfeeding. Monitor infants for bradycardia, hypotension, and hypoglycemia.

Caution advised during pregnancy and breastfeeding; use only when clinically necessary.

• Primary Class: Beta-Adrenergic Blocker
• Subclass: Non-selective Beta-Blocker (First-generation)

• Hypersensitivity to propranolol or formulation components
• Bronchial asthma or history of bronchospasm
• Severe bradycardia or heart block > first degree (unless pacemaker present)
• Cardiogenic shock
• Decompensated heart failure
• Sick sinus syndrome (without pacemaker)
• Severe peripheral arterial disorders

• Bronchospasm Risk: Contraindicated in asthma and reactive airway diseases
• Bradycardia & Heart Block: Can exacerbate pre-existing conduction abnormalities
• Hypoglycemia Risk: Masks signs of hypoglycemia (e.g., tachycardia); use cautiously in diabetics
• Abrupt Withdrawal: May cause rebound hypertension, angina, or MI; taper slowly over 1–2 weeks
• CNS Effects: Depression, hallucinations, and fatigue possible due to BBB penetration
• Peripheral Vascular Disease: May worsen symptoms due to β2 blockade
• Thyrotoxicosis: May mask symptoms; abrupt withdrawal may precipitate thyroid storm

Common:

• Cardiovascular: Bradycardia, hypotension, cold extremities
• CNS: Fatigue, dizziness, depression, sleep disturbances
• GI: Nausea, diarrhea, abdominal cramps

Serious/Rare:

• Heart failure exacerbation
• Bronchospasm (especially in asthmatics)
• AV block, severe bradycardia
• Depression, confusion, hallucinations
• Hypoglycemia (especially in children)
• Skin rash, pruritus, Stevens-Johnson Syndrome (rare)

Onset: Within hours to days of starting therapy; dose-dependent
Severity: Most are mild and reversible; serious effects are rare but require prompt attention

• Calcium Channel Blockers (e.g., verapamil, diltiazem):
• Additive bradycardia and hypotension; avoid or monitor closely
• Antiarrhythmics (e.g., amiodarone, digoxin):
• Increased risk of AV block and bradycardia
• CYP Inhibitors (e.g., cimetidine, fluoxetine):
• May increase propranolol plasma levels
• CYP Inducers (e.g., rifampin, phenytoin):
• May reduce propranolol efficacy
• NSAIDs:
• May reduce antihypertensive effect
• Insulin and Oral Hypoglycemics:
• Enhanced hypoglycemic effect; masking of symptoms like tachycardia
• Alcohol:
• Additive hypotensive and sedative effect

• Updated Guidance for Pediatric Hemangioma (Oral Solution):
  Approved by regulatory bodies for infantile hemangioma requiring systemic therapy. Use under specialist supervision.
• Enhanced Black Box Warning:
  Reaffirmation that abrupt discontinuation increases risk of angina, MI, and ventricular arrhythmias—especially in patients with ischemic heart disease.
• Guidelines for Portal Hypertension:
  Endorsed as a first-line non-selective beta-blocker for primary prevention of variceal bleeding in cirrhosis (per AASLD and EASL).

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15–30°C
• Humidity: Protect from moisture
• Light Protection: Store in a tightly closed container away from light
• Handling: Do not freeze oral solutions
• IV Form: Use immediately after dilution; discard unused portion