Migracool Capsules

Propranolol is a non-selective beta blocker mainly used in the treatment of hypertension. It was the first successful beta blocker developed. It is the only drug proven effective for the prophylaxis of migraines in children.

Pharmacokinetics : Propranolol competitively blocks β1- and β2-receptors resulting to decreased heart rate myocardial contractility, BP and myocardial oxygen demand. It only possesses membrane-stabilising properties.

Propranolol information from Drugs Update 

• P - Contraindicated in pregnancy
• L - Caution when used during lactation
• LI - Lab *

Absorption
Almost completely absorbed from the GI tract (oral); peak plasma concentrations after1 hour.

Distribution : Crosses the blood-brain barrier and placenta, enters breast milk. Protein-binding - 90%.

Metabolism : Hepatic; yields 4-hydroxypropranolol (biologically active).

Excretion : Via urine (as metabolites and small amounts of unchanged drug); 3-6 hours (elimination half-life). May be removed by dialysis.

Propranolol Adverse Reactions / Propranolol Side Effects : Cold extremities, insomnia, fatigue, dizziness, vivid dreams, lassitude, nausea, constipation or diarrhoea, vomiting, anorexia, stomach discomfort, impotence. Weakness, paraesthesia, wheezing, pharyngitis, bronchospasm. CNS disturbances at higher doses and mood alterations. Thrombocytopenic purpura, agranulocytosis, nonthrombocytopenic purpura, thrombocytopenia. Depression, confusion, cognitive dysfunction, emotional lability, fatigue, hallucinations.

Potentially Fatal : Heart failure, heart block and bronchospasm.

Precautions

• Propranolol should be used with caution in patients with impaired hepatic or renal function. Propranolol hydrochloride extended- release is not indicated for the treatment of hypertensive emergencies.
• Beta-adrenergic receptor blockade can cause reduction of intraocular pressure. Patients should be told that Propranolol hydrochloride extended-release may interfere with the glaucoma screening test. Withdrawal may lead to a return of increased intraocular pressure. While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

Overdosage : Severe and occasionally fatal CV depression.

Special Precautions : Compensated heart failure, peripheral vascular disease, diabetes. Switching from conventional to sustained-release preparations, elderly. Ischaemic heart disease, congestive cardiac failure, renal or hepatic dysfunction. Increased risk of bradycardia and hypotension in patients with underlying cardiac disorders. 1st degree heart block. May mask symptoms of hyperthyroidism and hypoglycaemia. May unmask myasthenia gravis. Abrupt withdrawal may lead to angina, MI, ventricular arrhythmias and death. Lactation.

Other Drug Interactions :
Decreased effect with aluminum and calcium salts, NSAIDs, ampicillin, rifampicin. Concurrent use with chlorpromazine results in raised blood levels of both drugs and additive hypotensive effect. Hypotensive effect reduced by indometacin. Additive effect with other antihypertensives and diuretics. May reduce the clearance of bupivacaine. Plasma levels may be increased by hydralazine and propafenone. Increased serum levels of thioridazine when used with propranolol.

Potentially Fatal : Marked hypertension and bradycardia with adrenaline. Rebound hypertension due to abrupt withdrawal of clonidine is potentiated. Severe bradycardia may occur with digitalis.

Dosage

• Oral
• Hypertension
• Adult - As conventional tablet or oral solution: Initially, 40-80 mg bid. Usual range: 160-320 mg daily. As extended release tablet: Initially, 80 mg once daily. Usual range: 120-160 mg once daily. Max - 640 mg daily.
• Child - Initially, 1 mg/kg daily in divided doses, may increase to 2-4 mg/kg daily in 2 divided doses.

Phaeochromocytoma

• Oral
• Adult - 60 mg daily given on the 3 days before the operation with α-blockade. Prolonged treatment of 30 mg daily may be given if tumour is inoperable.
• Child - 250-500 mcg/kg 3-4 times daily.

Myocardial infarction

• Oral
• Adult - 40 mg 4 times daily for 2-3 days followed by 80 mg bid. Alternatively, 180-240 mg daily in divided doses. Doses to be given within 5-21 days of MI.

Cardiac arrhythmias

• Oral
• Adult - 30-160 mg daily in divided doses.
• Child - 250-500 mcg/kg 3-4 times daily.

Prophylaxis of migraine

• Oral
• Adult - Initially, 40 mg bid-tid increased to 160 mg daily. Up to 240 mg daily may be necessary. Discontinue therapy if satisfactory response not obtained within 4-6 weeks after reaching max dose.
• Child - <12 years: 20 mg bid-tid.

Portal hypertension

• Oral
• Adult - Initially, 40 mg bid increased up to 160 mg bid.

Angina pectoris

• Oral
• Adult: As conventional tablet or oral solution: 40 mg bid-tid, may increase to 120-240 mg daily, up to 320 mg daily may be required in some patients. As extended release tablet: 80 mg once daily, increased as needed every 3-7 days, average
• dose 160 mg once daily, max: 320 mg daily.

Hypertrophic cardiomyopathy

• Oral
• Adult - 10-40 mg, given 3-4 times daily.

Hyperthyroidism

• Oral
• Adult - 10-40 mg, given 3-4 times daily.

Anxiety

• Oral
• Adult - 40 mg once daily, may increase to bid-tid

Essential tremor

• Oral
• Adult - 40 mg bid-tid. May increase at weekly intervals to 160 mg daily. Up to 320 mg daily may be necessary.

Intravenous

• Emergency treatment of cardiac arrhythmias
• Adult - 1 mg injected over a period of 1 minute, repeated every 2 minutes, if needed. Max: 10 mg in conscious patients and 5 mg in patients under anaesthesia.
• Child  - 25-50 mcg/kg via slow injection, may be repeated 3-4 times daily.

Intravenous

• Hyperthyroidism
• Adult - 1 mg, given over 1 minute, may repeat at 2-minute intervals until response is observed or a max of 10 mg is used in conscious patients or 5 mg in patients who are under anaesthesia.

Food(before/after) Capsule

• May be taken with or without food. (Take consistently either always with or always without meals.)
• Tablet
• Should be taken on an empty stomach. (Take before meals.)

List of Contraindications :

• Propranolol and Pregnancy
• Contraindicated in pregnancy

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
In 2nd & 3rd trimesters.

Category D : There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Propranolol and Lactation : Caution when used during lactation

• Propranolol and Children
• Safety and effectiveness of Propranolol in pediatric patients have not been established.
• Bronchospasm and congestive heart failure have been reported coincident with the administration of Propranolol therapy in pediatric patients.

Propranolol and Geriatic :In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of the decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Propranolol and Other Contraindications : Sinus bradycardia, cardiogenic shock, pulmonary oedema, severe hyperactive airway disease, compensated cardiac failure, Raynaud's disease, hypoglycaemia, severe haemorrhage, metabolic acidosis, severe peripheral arterial disease, 2nd or 3rd degree heart block. Pregnancy (2nd and 3rd trimesters).

Storage

• Intravenous
• Store at 20-25^oC
• Oral
• Store at 20-25^oC
• P - Contraindicated in pregnancy
• L - Contraindicated in lactation

Flunarizine is a drug classified as a calcium channel blocker. Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 blocking activity. It is effective in the prophylaxis of migraine, occlusive peripheral vascular disease, vertigo of central and peripheral origin, and as an adjuvant in the therapy of epilepsy. It may help to reduce the severity and duration of attacks of paralysis associated with the more serious form of alternating hemiplegia.

Pharmacokinetics : Flunarizine has H1-receptor blocking action and calcium-channel blocking effect. It has also been used as an adjunct epileptic therapy for patients refractory to standard treatment regimens.

Absorption : Absorbed well from the GI tract (oral).

Distribution :

• lipophilic. Protein-binding>90%.
• Metabolism
• Extensive.
• Excretion
• Via bile (as metabolites); 18 days (elimination half-life).

Flunarizine Adverse Reactions / Flunarizine Side Effects : Drowsiness. Rarely wt gain, headache, depression, gastric pain, dry mouth, insomnia, extrapyramidal reactions, galactorrhoea.

Special Precautions : Driving or operating machinery, epilepsy, elderly, CVS disease, glaucoma.

Other Drug Interactions : Plasma levels reduced by phenytoin, carbamazepine, valproic acid.

Dosage

• Oral
• Prophylaxis of migraine, Prophylaxis of vertigo and vestibular disorders, Prophylaxis of peripheral and cerebrovascular disorders
• Adult - 5-10 mg daily at bedtime.

Food(before/after) : May be taken with or without food

List of Contraindications

• Flunarizine and Pregnancy
• Contraindicated in pregnancy
• Flunarizine and Lactation
• Contraindicated in lactation
• Flunarizine and Other Contraindications
• Pregnancy, lactation, GI or urinary tract obstruction, acute porphyrias