Professional Information

Propranolol Hydrochloride

Pronunciation: (pro-PRAN-oh-lahl HIGH-droe-KLOR-ide)
Class: Beta-adrenergic blocking agent

Trade Names:
Inderal
- Injection 1 mg/mL

Trade Names:
Inderal LA
- Capsules, sustained-release 60 mg
- Capsules, sustained-release 80 mg
- Capsules, sustained-release 120 mg
- Capsules, sustained-release 160 mg

Trade Names:
InnoPran XL
- Capsules, extended-release 80 mg
- Capsules, extended-release 120 mg

Trade Names:
Propranolol Hydrochloride
- Tablets 10 mg
- Tablets 20 mg
- Tablets 40 mg
- Tablets 60 mg
- Tablets 80 mg

Trade Names:
Propranolol Intensol
- Solution, concentrated oral 80 mg/mL

Apo-Propranolol (Canada)

Pharmacology

Blocks beta receptors, primarily affecting the CV system (decreased heart rate, decreased cardiac contractility, decreased BP) and lungs (promotes bronchospasm).

Pharmacokinetics

Absorption

Well-absorbed from the GI tract. Extent of absorption is less than 90%. Bioavailability is 30% (immediate release) and 9% to 18% (long acting). Food enhances bioavailability. T _max is 1 to 1.5 h (immediate release) and 6 h (long acting).

Distribution

Protein binding is 90%. Readily enters the CNS. Crosses the placenta.

Metabolism

Significant first-pass hepatic metabolism.

Elimination

Urine is less than 1% excreted unchanged. Plasma t _½ is 3 to 5 h (immediate release) and 8 to 11 h (long acting).

Indications and Usage

Angina pectoris (except InnoPran XL ); cardiac arrhythmias (except sustained release); essential tremor (except sustained release); hypertension; hypertrophic subaortic stenosis (except InnoPran XL ); migraine prophylaxis (except InnoPran XL ); MI (except sustained release); pheochromocytoma (except sustained release).

Contraindications

Hypersensitivity to beta-blockers; greater than first-degree heart block; CHF unless secondary to tachyarrhythmia or untreated hypertension treatable with beta-blockers; overt cardiac failure; sinus bradycardia; cardiogenic shock; untreated bronchial asthma or bronchospasm, including severe COPD.

Dosage and Administration

Angina
Adults

PO 80 to 320 mg/day in 2 to 4 divided doses or 80 mg/day of sustained-release medication (max, 320 mg/day).

Arrhythmias
Adults

PO 10 to 30 mg 3 to 4 times daily before meals and at bedtime.

Arrhythmias (Life-Threatening)
Adults

IV 1 to 3 mg at rate of 1 mg/min; may repeat after 2 min; give subsequent doses every 4 h.

Essential Tremor
Adults

PO 40 mg twice daily initially; titrate to response. The maintenance dose is 120 to 320 mg/day in 2 to 3 divided doses (max, 320 mg/day).

Hypertension
Adults

PO The initial dose is 40 mg twice daily initially or 80 mg sustained-release medication/day; titrate to response. The usual maintenance dose is 120 to 240 mg/day in 2 to 3 divided doses or 120 to 160 mg/day sustained-release medication, except for InnoPran XL (do not exceed 120 mg/day). Do not exceed 640 mg/day.

Children

PO 0.5 mg/kg twice daily; titrate every 3 to 5 days to max dose of 16 mg/kg/day.

Hypertrophic Aortic Stenosis
Adults

PO 20 to 40 mg 3 to 4 times daily before meals and at bedtime or 80 to 160 mg sustained-release medication once daily.

Migraine
Adults

PO 80 mg in divided doses daily or once daily (sustained release); titrate to response (max dose, 240 mg/day); discontinue after 6 wk if no response.

MI
Adults

PO 180 to 240 mg/day in 3 to 4 divided doses up to 240 mg/day.

Pheochromocytoma
Adults

PO 60 mg/day for 3 days prior to surgery, given with alpha-blocker.

General Advice

Immediate-release and extended-release dose forms may not be interchangeable on a mg to mg basis. Be prepared to retitrate dose to maintain desired therapeutic effect.

Immediate-release tablets
Administer without regard to meals but administer with food if GI upset occurs.

Extended-release capsules
Administer prescribed dose once daily ( InnoPran XL should be administered at bedtime).
Administer without regard to meals but administer with food if GI upset occurs. Administer consistently either with or without food.
Have patient swallow capsules whole; do not crush, chew, break, or open capsule.

Oral solution
Measure and administer prescribed dose using dosing syringe, spoon, or cup.
Administer without regard to meals but administer with food if GI upset occurs.

Concentrated oral solution
Use supplied dropper to measure prescribed dose. Squeeze dropper contents into a liquid (eg, water, juice, soda, soda-like beverage) or semisolid food (eg, applesauce, pudding) and mix by gently stirring the mixture. Entire amount of mixture should be consumed immediately.
Do not prepare mixtures ahead of time and store for future use.

Injection
For IV administration only. Not for intradermal, subcutaneous, IM, or intraarterial administration.
Do not administer if solution is discolored or cloudy, or if particulate matter is noted.
Administer IV bolus dose at rate not exceeding 1 mg (1 mL) per minute. A second dose may be administered 2 min later if response to first dose is inadequate. Additional drug should not be given in less than 4 h.
Discard any unused solution. Do not save for future use.

Storage/Stability

Store extended-release capsules at controlled room temperature (59° to 86°F). Store immediate-release tablets, oral solution, concentrated oral solution, and injection at controlled room temperature (68° to 77°F). Protect from light, freezing, or excessive heat. Protect tablets and capsules from moisture.

Drug Interactions

ACE inhibitors (eg, captopril)

Increased risk of hypotension, especially in patients with acute MI; bronchial hyper-reactivity may be increased.

Aluminum hydroxide gel

Greatly reduces GI absorption of propranolol.

Amiodarone

Has additive antiarrhythmic and negative chronotropic properties with propranolol.

Anesthetic agents (eg, methoxyflurane, trichloroethylene)

Depression in myocardial contractility may occur.

Barbiturates

Decreased bioavailability of propranolol.

Cimetidine

Increased propranolol levels.

Clonidine

Attenuation or reversal of antihypertensive effect; potentially life-threatening increases in BP, especially on withdrawal.

Disopyramide

Has been associated with severe bradycardia, asystole, and heart failure, when given with propranolol.

Dobutamine, isoproterenol

May reverse effects of propranolol.

Epinephrine

Initial hypertensive episode followed by bradycardia.

Ergot derivatives

Peripheral ischemia, manifested by cold extremities and possible gangrene.

Ethanol

Slows rate of propranolol absorption.

Hydantoins, rifabutin, rifampin

Decreased effects of propranolol.

Hydralazine

Increased serum levels of both drugs.

Insulin

Prolonged hypoglycemia with masking of symptoms.

Lidocaine

Increased lidocaine levels, leading to toxicity.

Methimazole, propafenone, propylthiouracil, quinidine

Increased effects of propranolol.

NSAIDs

Some agents may impair antihypertensive effect.

Phenothiazines

Increased effects of either drug.

Prazosin

Increased orthostatic hypotension.

Reserpine

Hypotension, marked bradycardia, vertigo, syncopal attacks, and orthostatic hypotension may result from excessive reduction of resting sympathetic nervous activity caused by reserpine-induced catecholamine-depletion.

Theophylline

Reduces elimination of theophylline; pharmacologic antagonism.

Thyroxine

May result in decreased T ₃ concentration when coadministered with propranolol.

Verapamil

Increased effects of both drugs.

Laboratory Test Interactions

May interfere with glaucoma screening tests; may increase BUN, serum transaminases, alkaline phosphatase, or LDH.

Adverse Reactions

Cardiovascular

AV block; bradycardia; CHF; edema; hypotension; peripheral ischemia; torsades de pointes; worsening angina.

CNS

Bizarre dreams; decreased performance on neuropsychometric tests; depression; dizziness; emotional lability; fatigue; hallucinations; insomnia; lethargy; short-term memory loss; sleep disturbances; slightly clouded sensorium; tiredness; weakness.

Dermatologic

Erythema multiforme; exfoliative dermatitis; pruritus; rash; Stevens-Johnson syndrome; toxic epidermal necrolysis; urticaria.

EENT

Dry eyes; visual disturbances.

GI

Dyspepsia; nausea; vomiting; diarrhea; dry mouth; epigastric distress; abdominal cramping; constipation; mesenteric arterial thrombosis; ischemic colitis.

Genitourinary

Impotence; urinary retention; difficulty with urination.

Hematologic

Agranulocytosis; nonthrombocytopenic and thrombocytopenic purpura.

Hepatic

Elevated liver enzymes.

Metabolic

Hyperglycemia; hypoglycemia.

Respiratory

Wheezing; dyspnea; bronchospasm; difficulty breathing.

Miscellaneous

Decreased exercise tolerance; hypersensitivity, including anaphylactic/anaphylactoid reactions; increased sensitivity to cold (Raynaud phenomenon); oculomucocutaneous reactions; pharyngitis, agranulocytosis, erythematous rash, fever, laryngospasm, and respiratory distress; psoriasis-like eruptions; skin necrosis; systemic lupus erythematosus.

Precautions

Warnings

Abrupt withdrawal

In patients with angina pectoris or coronary artery disease (CAD), abrupt withdrawal may cause exacerbation of angina, occurrence of MI, and ventricular arrhythmias. Monitor patients closely. Because CAD is common and unrecognized, it may be prudent not to discontinue beta-blocker therapy abruptly in patients treated only for hypertension.

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established. IV use not recommended, but oral propranolol has been used.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Renal Function

Reduce dose.

Hepatic Function

Reduce dose.

Abrupt withdrawal

A beta-blocker withdrawal syndrome (eg, hypertension, tachycardia, anxiety, angina, MI) may occur 1 to 2 wk after sudden discontinuation of systemic beta-blockers. If possible, gradually withdraw therapy over 1 to 2 wk.

Anaphylaxis

Deaths have occurred; aggressive therapy may be required.

CHF

Avoid in patients with overt CHF; administer cautiously in patients whose CHF is controlled by digitalis and diuretics.

Diabetes mellitus

May mask symptoms of hypoglycemia (eg, tachycardia, BP changes). May potentiate insulin-induced hypoglycemia.

Nonallergic bronchospastic diseases

Give drug with caution in patients with bronchospastic diseases.

Peripheral vascular disease

May precipitate or aggravate symptoms of arterial insufficiency.

Thyrotoxicosis

May mask clinical signs (eg, tachycardia) of developing or continuing hyperthyroidism. Abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm.

Wolff-Parkinson-White syndrome

In several cases, tachycardia was replaced by severe bradycardia requiring a demand pacemaker.

Overdosage

Symptoms

Bradycardia, hypotension, CHF, AV block, intraventricular conduction defects, asystole, bronchospasm, coma.

Patient Information

Advise patient to read patient information leaflet before using the first time and to reread each time the medication is renewed.
Advise patient or caregiver that IV propranolol will be prepared and administered by health care professionals in a medical setting and that conversion to oral therapy will be made as soon as possible.
Advise patient using oral dose forms to take prescribed dose without regard to meals but to take with food if stomach upset occurs. Advise patient to take propranolol consistently either with or without food.
Caution patient not to change the dose or stop taking unless advised by health care provider.
Advise patient taking immediate-release tablets to take 2 to 4 times daily as prescribed.
Advise patient taking extended-release products to take once daily as prescribed. Caution patient to swallow extended-release products whole and not to crush, chew, break, or open the capsule.
Advise patient or caregiver using oral solution to measure and administer prescribed dose using dosing syringe, spoon, or cup.
Advise patient or caregiver using concentrated oral solution to use supplied dropper to measure prescribed dose then squeeze dropper contents into a liquid (eg, water, juice, soda, soda-like beverage) or semisolid food (eg, applesauce, pudding) and mix by gently stirring the mixture. Advise patient or caregiver that entire amount of mixture should be consumed immediately. Caution patient or caregiver not to prepare mixtures ahead of time and store for future use.
Advise patient that if a dose is missed to take it as soon as remembered. However, if the next regular dose is less than 4 h away (8 h for extended-release capsule) to skip the missed dose and take the next dose at the regularly scheduled time. Caution patient never to double the dose to catch up.
Inform patient or caregiver that drug controls, but not does cure, condition being treated and to continue taking as prescribed even when condition or symptoms are controlled.
Caution patients to never stop taking propranolol on their own because sudden discontinuation could cause worsening angina pectoris or a heart attack. Advise patient that if treatment is to be discontinued, it will usually be done gradually over a period of several weeks.
Instruct patient to continue taking other medications for the condition as prescribed by health care provider.
Instruct patient in BP and pulse measurement skills.
Advise patient to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also advise patient to take record of BP and pulse to each follow-up visit.
Caution patient with insulin-dependent diabetes that propranolol may reduce or minimize warning signs and symptoms (eg, pulse rate and BP changes) associated with a hypoglycemic reaction.
Instruct patient to lie or sit down if experiencing dizziness or lightheadedness when standing.
Instruct patient to notify health provider immediately if any of the following occur: weakness, lethargy, unexplained drowsiness, slow or irregular heartbeat, depressed feeling, new or worsening chest pain, swelling of feet or ankles, unexplained shortness of breath or difficulty breathing, skin rash or itching.
Emphasize to hypertensive patient importance of other modalities on BP control: Weight control, regular exercise, smoking cessation, moderate intake of alcohol and salt.