Propranolol

Oral
Hypertension
Adult: Monotherapy or in combination with other antihypertensive agents (e.g. thiazide diuretics): As conventional tab or oral solution: Initially, 40-80 mg bid, may be increased at weekly intervals according to response. Usual range: 160-320 mg daily. Max: 640 mg daily. As extended-release cap: Initially, 80 mg once daily, or 160 mg once daily. Dose may be increased if necessary until adequate response is achieved. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).

Oral
Angina pectoris
Adult: As conventional tab or oral solution: Initially, 40 mg 2-3 times daily, may be increased at weekly intervals according to response. Usual range: 120-240 mg daily. As extended-release cap: 80 mg once daily, may be increased to 160 mg once daily. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).

Oral
Prophylaxis of migraine
Adult: As conventional tab or oral solution: Initially, 40 mg 2-3 times daily, may be increased at weekly intervals according to response. Usual range: 80-160 mg daily. Max: 240 mg daily. As extended-release cap: Initially, 80 mg once daily, may be increased gradually to achieve optimum migraine prophylaxis. Usual range: 160-240 mg once daily.
Child: As conventional oral solution or tab: ≤12 years 10-20 mg 2-3 times daily; >12 years Same as adult dose.

Oral
Essential tremor
Adult: As conventional tab or oral solution: Initially, 40 mg 2-3 times daily, may be increased according to response. Usual range: 120-320 mg daily. As extended-release cap: 80 mg once daily. Dose may be increased to 160 mg daily and, if needed, further increased to 240 mg daily.

Oral
Cardiac arrhythmias
Adult: As conventional tab or oral solution: 10-40 mg 3-4 times daily.
Child: As conventional oral solution or tab: 0.25-0.5 mg/kg 3-4 times daily.

Oral
Post myocardial infarction
Adult: For long-term prophylaxis after recovery from acute MI: As conventional tab or oral solution: Initiate treatment within 5-21 days of MI. Initially, 40 mg 4 times daily for 2-3 days, followed by 80 mg bid. Alternatively, 180-240 mg daily in divided doses. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).

Oral
Phaeochromocytoma
Adult: As conventional tab or oral solution: As adjunctive treatment to α-receptor blocker: 60 mg daily for 3 days before the surgery. As adjunctive treatment to α-receptor blocker for inoperable cases: 30 mg daily.
Child: As conventional oral solution or tab: 0.25-0.5 mg/kg 3-4 times daily.

Oral
Hypertrophic cardiomyopathy
Adult: As conventional tab or oral solution: 10-40 mg 3-4 times daily.

Oral
Thyrotoxicosis
Adult: As adjunctive treatment: As conventional tab or oral solution: 10-40 mg 3-4 times daily. As extended-release cap: 80 mg once daily. Dose may be increased to 160 mg daily.
Child: As conventional oral solution or tab: 0.25-0.5 mg/kg 3-4 times daily. Adjust dose according to response.

Oral
Anxiety
Adult: As conventional tab or oral solution: For short-term relief of acute situational anxiety: 40 mg daily. For relief of generalised anxiety symptoms: 40 mg bid, may be increased if necessary to 40 mg tid. Dosage or treatment recommendations may vary among countries and individual products (refer to specific product guidelines).

Oral
Prophylaxis of variceal bleeding in portal hypertension
Adult: As conventional tab or oral solution: Initially, 40 mg bid, may be increased to 80 mg bid depending on heart rate response. Max: 160 mg bid.

Oral
Tetralogy of Fallot
Child: Infants and children As conventional oral solution: For treatment and prophylaxis of cyanotic attacks and for relief of right-ventricular outflow tract obstruction: Up to 1 mg/kg 3-4 times daily. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).

Oral
Proliferating infantile haemangioma
Child: ≥5 weeks Hemangeol (4.28 mg/mL oral solution) Patients weighing ≥2 kg: Start treatment between 5 weeks and 5 months of age. Initially, 0.6 mg/kg (0.15 mL/kg) bid for 7 days, then increase to 1.1 mg/kg (0.3 mL/kg) bid for additional 7 days and then increase to maintenance dose of 1.7 mg/kg (0.4 mL/kg) bid for 6 months. Doses are given at least 9 hours apart during or right after feeding or meals. Adjust dose periodically as the child's weight increases. Treatment may be restarted if haemangiomas recur. Treatment recommendations and product availability may vary between countries (refer to specific product guidelines).

Intravenous
Thyrotoxic crisis
Adult: 1 mg via IV inj over 1 minute, may be repeated every 2 minutes until response is achieved. Max: 10 mg in conscious patients or 5 mg in patients under anaesthesia. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).

Intravenous
Emergency treatment of cardiac arrhythmias
Adult: 1 mg via IV inj over 1 minute, may be repeated every 2 minutes until response is achieved. Max: 10 mg in conscious patients or 5 mg in patients under anaesthesia. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).

Tab: Should be taken on an empty stomach (i.e. At least one hour before food or two hours after food).
Cap: May be taken with or without food. Take consistently either always w/ or always w/o meals.

Current or history of bronchial asthma or bronchospasm; bradycardia, cardiogenic shock, hypotension, metabolic acidosis, after prolonged fasting, severe peripheral arterial circulatory disturbances, 2nd- or 3rd-degree heart block, sick sinus syndrome, Prinzmetal's angina, uncontrolled heart failure, phaeochromocytoma that has not been treated with α-receptor blocker. Additional contraindications for Hemangeol: Heart rate <80 bpm, blood pressure <50/30 mmHg; premature infants with corrected age <5 weeks and infants weighing <2 kg.

Patient with 1st-degree heart block, compensated heart failure, diabetes mellitus, myasthenia gravis, history of anaphylactic reaction to allergens, less severe peripheral circulatory disturbances, Wolff-Parkinson-White Syndrome. Patient undergoing surgery. Avoid abrupt withdrawal (particularly in patients with ischaemic heart disease); chronic therapy must not be routinely withdrawn before major surgery. May mask the signs and symptoms of hypoglycaemia and hyperthyroidism (particularly tachycardia). Renal and hepatic impairment. Neonates, children, and elderly. Pregnancy and lactation. Monitoring Parameters Monitor blood pressure, heart rate, ECG; serum glucose (in patients with diabetes mellitus). For infantile haemangioma: Monitor blood pressure and heart rate for 2 hours following initiation or increase in dose.

Significant: Bradycardia (including heart block, sinus pause, and cardiac arrest), cardiac failure, bronchospasm, hypoglycaemia; exacerbation of angina and acute MI following abrupt withdrawal. Blood and lymphatic system disorders: Rarely, thrombocytopenia. Eye disorders: Rarely, visual disturbances, dry eye. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation. General disorders and administration site conditions: Fatigue. Immune system disorders: Hypersensitivity reactions (including anaphylactic reactions). Investigations: Increased serum K, serum transaminases, alkaline phosphatase. Nervous system disorders: Rarely, dizziness. Psychiatric disorders: Sleep disturbances, nightmares. Rarely, hallucinations, psychoses, confusion, mood changes. Skin and subcutaneous tissue disorders: Rarely, alopecia, purpura, psoriasiform skin reaction, rash. Vascular disorders: Cold extremities, Raynaud's phenomenon.

Symptoms: Hypotension, bradycardia, pulmonary oedema, syncope, cardiogenic shock, QRS complex prolongation, ventricular tachycardia, 1st- to 3rd-degree heart block, ventricular fibrillation or asystole, drowsiness, confusion, seizures, hallucinations, dilated pupils, bronchospasm, hyperkalaemia, coma, and occasionally CNS-mediated respiratory depression. Management: Symptomatic and supportive treatment. Discontinue treatment in cases of overdose or extreme falls in heart rate or blood pressure. Clear the airway and monitor vital signs until stable. For recent ingestion, use gastric lavage, activated charcoal, and laxative to prevent absorption of any drug still present in the gastrointestinal tract. Administer plasma or plasma substitutes to treat hypotension and shock. Excessive bradycardia may be countered with 1-2 mg IV atropine and/or a cardiac pacemaker. This may be followed by an IV bolus dose of 10 mg glucagon if necessary, which may be repeated or followed by an IV infusion of glucagon (1-10 mg/hour) depending on the response. If the patient does not respond to glucagon or if glucagon is unavailable, a β-adrenoceptor stimulant (e.g. dobutamine 2.5-10 mcg/kg/min IV infusion) may be given. Bronchospasm may be treated by β₂-receptor agonist bronchodilators (e.g. salbutamol); oxygen or artificial ventilation may be required in severe cases.

May have additive negative inotropic effect with anti-arrhythmic agents (e.g. disopyramide, amiodarone, quinidine) and Ca channel blockers with negative inotropic effect (e.g. verapamil, diltiazem). May increase AV conduction time with digitalis glycoside. Increased plasma concentration with CYP2D6 and CYP1A2 inhibitors (e.g. cimetidine). May cause vasospastic reactions with ergotamine, dihydroergotamine or related compounds. May decrease hypotensive effect with NSAIDs (e.g. ibuprofen, indometacin). Increased risk of hypotension and attenuation of the reflex tachycardia with anaesthetic drugs. May enhance the hypoglycaemic effect of insulin. May exacerbate the rebound hypertension following the withdrawal of clonidine. May enhance the hypotensive effect of prazosin, reserpine, MAO inhibitors, and TCAs. Concurrent use with sympathomimetic agents (e.g. epinephrine) may counteract the effects of propranolol. Concomitant use of propranolol and chlorpromazine may result in increased plasma concentrations and enhanced effects of both drugs. May increase the plasma concentration of lidocaine, rizatriptan, and warfarin.

Alcohol may increase or decrease plasma levels of propranolol. Protein-rich foods may increase the bioavailability of propranolol.

May interfere with glaucoma screening, estimation of serum bilirubin by diazo method, and determination of catecholamines using fluorescence.

Propranolol, a nonselective β-adrenergic blocker, is a competitive antagonist at both β₁- and β₂-receptors resulting in decreased heart rate, myocardial contractility, blood pressure, and myocardial oxygen demand. It has negative inotropic effects and membrane-stabilising activities but does not possess intrinsic sympathomimetic activity.
Onset: β-blockade: 1-2 hours (oral); ≤5 minutes (IV).
Duration: 6-12 hours (immediate-release); approx 24-27 hours (extended-release).
Absorption: Rapidly and completely absorbed from the gastrointestinal tract. Bioavailability: Approx 25%; increased by approx 50% with protein-rich foods. Time to peak plasma concentration: Approx 1-4 hours (immediate-release); 12-14 hours (extended-release).
Distribution: Rapidly and widely distributed throughout the body with the highest concentrations in the brain, lungs, kidney, liver, and heart. Crosses the placenta and blood-brain barrier; enters breast milk. Volume of distribution: 4 L/kg. Plasma protein binding: Approx 80-95%.
Metabolism: Undergoes extensive first-pass effect. Metabolised in the liver into active and inactive metabolites, metabolic pathways include aromatic hydroxylation by CYP2D6, N-dealkylation followed by further side-chain oxidation mainly by CYP1A2, and to some extent by CYP2D6, and direct glucuronidation; primary metabolites include propranolol glucuronide, naphthyloxylactic acid, and glucuronic acid and sulfate conjugates of 4-hydroxypropranolol (active).
Excretion: Mainly via urine (96-99%, <1% as unchanged drug). Elimination half-life: Approx 3-6 hours (immediate-release); 8-10 hours (extended-release).

Intravenous: Store between 20-25°C. Protect from light or excessive heat. Storage recommendations may vary between products (refer to specific product guidelines). Oral: Oral solution: Store between 20-25°C. Protect from light or excessive heat. Do not refrigerate or freeze the oral solution. Storage recommendations may vary between products (refer to specific product guidelines).

Antimigraine Preparations / Beta-Blockers

C07AA05 - propranolol ; Belongs to the class of non-selective beta-blocking agents. Used in the treatment of cardiovascular diseases.