Pronunciation: proe-PRAN-oh-lol HYE-droe-KLOR-ide
Class: Beta-adrenergic blocking agent

Trade Names

Inderal
- Injection 1 mg/mL

Inderal LA
- Capsules, ER 60 mg
- Capsules, ER 80 mg
- Capsules, ER 120 mg
- Capsules, ER 160 mg

InnoPran XL
- Capsules, ER 80 mg
- Capsules, ER 120 mg

Propranolol Hydrochloride
- Tablets 10 mg
- Tablets 20 mg
- Tablets 40 mg
- Tablets 60 mg
- Tablets 80 mg

Propranolol
- Solution, oral 4 mg/mL
- Solution, oral 8 mg/mL

Apo-Propranolol (Canada)

Pharmacology

Nonselective, beta-adrenergic receptor blocking agent, primarily affecting the CV system (eg, decreased heart rate, decreased cardiac contractility, decreased BP) and lungs (promotes bronchospasm).

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Pharmacokinetics

Absorption

Well absorbed from the GI tract. Extent of absorption is less than 90%. Bioavailability is approximately 25% (immediate-release). Food enhances bioavailability for immediate-release and increases T _max from 11.5 to 15.4 h for InnoPran XL . T _max is 1 to 4 h (immediate-release) and 6 h (ER).

Distribution

Protein binding is 90%. Readily enters the CNS. Crosses the placenta; distributed into breast-milk.

Metabolism

Significant first-pass hepatic metabolism through 3 primary routes and produces 4 major metabolites.

Elimination

Urine is less than 1% excreted unchanged. Plasma half-life is 3 to 6 h (immediate-release) and about 10 h (ER). Most metabolites appear in the urine

Indications and Usage

Oral

Angina pectoris caused by coronary atherosclerosis (excluding InnoPran XL ); cardiac arrhythmias (excluding ER); essential tremor (excluding ER); hypertension; hypertrophic subaortic stenosis (excluding InnoPran XL ); migraine prophylaxis (excluding InnoPran XL ); MI (excluding ER); pheochromocytoma (excluding ER).

IV

Cardiac arrhythmias.

Contraindications

Hypersensitivity to propranolol; greater than first-degree heart block; sinus bradycardia; cardiogenic shock; bronchial asthma.

Dosage and Administration

Angina Pectoris Caused by Coronary Artherosclerosis
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).

Arrythmias
Adults

PO 10 to 30 mg (immediate-release) 3 to 4 times daily before meals and at bedtime.

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 The initial dosage is 40 mg of immediate-release twice daily; titrate to response. Max dosage is 320 mg/day in divided doses.

Hypertension
Adults

PO The initial dosage is 40 mg twice daily initially (or 80 mg/day of ER); titrate to response. The usual maintenance dosage is 120 to 240 mg/day in 2 to 3 divided doses or 120 to 160 mg/day of ER. For InnoPran XL , initial dosage is 80 mg once daily at bedtime (approximately 10 pm); titrate 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 Subaortic Stenosis
Adults

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

Migraine Prevention
Adults

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

MI
Adults

PO 40 mg (immediate-release) 3 times per day as initial dose; after 1 mo, titrate to 60 mg to 80 mg 3 times daily as tolerated. Maintenance dosage is 180 to 240 mg/day in divided doses.

Pheochromocytoma
Adults

PO 60 mg/day in divided doses for 3 days prior to surgery, given with alpha-blocker. 30 mg/day in divided doses, given with alpha-blocker for management of inoperable tumor.

General Advice

Immediate-release and ER doseforms 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.

• ER capsules
• Administer prescribed dose once daily ( InnoPran XL should be administered at bedtime at approximately 10 pm).
• 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.

• 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 min. 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 at 68° to 77°F. Protect from light, freezing, moisture, or excessive heat.

Drug Interactions

ACE inhibitors (eg, captopril)

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

Alcohol

Pharmacologic and therapeutic effects are difficult to predict. Reported increased plasma concentrations, and increased and decreased clearance of propranolol.

Aluminum salts (eg, aluminum carbonate, aluminum hydroxide)

Greatly reduces GI absorption of propranolol.

Antiarrhythmic agents (eg, amiodarone, propafenone, quinidine)

Inhibition of propranolol metabolism; may increase pharmacologic and toxic effects. Amiodarone has additive negative chronotropic properties to those of propranolol.

Barbiturates (eg, pentobarbital, phenobarbital, primidone), levothyroxine, phenytoin, rifampin

May result in decreased effects of propranolol.

Bile acid sequestrants (eg, cholestyramine, colestipol)

GI absorption of propranolol may be decreased.

Calcium channel blockers (eg, diltiazem, nicardipine, nifedipine, verapamil), flecainide, haloperidol, phenothiazines (eg, chlorpromazine, thioridazine), selective 5-HT ₁ receptor antagonists (eg, rizatriptan, zolmitriptan), sulfonylureas (eg, chlorpropamide, tolbutamide)

Increased serum levels and effects of both drugs.

Cigarette smoking

Increases clearance of propranolol by as much as 100%.

Cimetidine, ciprofloxacin, diphenhydramine, fluconazole, hydralazine, imipramine, isoniazid, methimazole, propafenone, propylthiouracil, ritonavir, SSRIs (eg, fluoxetine, fluvoxamine, paroxetine), teniposide, terbinafine, zileuton

Increased effects of propranolol.

Clonidine

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

Diazepam

Inhibition of diazepam metabolism.

Digoxin

Progressive bradycardia may occur.

Dobutamine, isoproterenol

May reverse effects of propranolol.

Epinephrine

Initial hypertensive episode followed by bradycardia.

Ergot derivatives (eg, dihydroergotamine, ergotamine)

Peripheral ischemia, manifested by cold extremities and possible gangrene.

HMG-CoA reductase inhibitors (eg, lovastatin, pravastatin)

Plasma concentrations may be increased.

Insulin

Prolonged hypoglycemia with masking of symptoms.

Lidocaine (IV)

Increased lidocaine levels, leading to toxicity.

MAOIs, tricyclic antidepressants

Coadministration may exacerbate the hypotensive effects of MAOIs.

NSAIDs (eg, ibuprofen, indomethacin, naproxen), salicylates (eg, aspirin)

Some agents may impair antihypertensive effect.

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.

Sympathomimetics (eg, albuterol, formoterol)

Pharmacologic effects may be antagonized by propranolol resulting in bronchospasm.

Theophylline

Reduced elimination of theophylline; propranolol concentrations may be increased.

Warfarin

The anticoagulant effect of warfarin may be increased.

Laboratory Test Interactions

May interfere with glaucoma screening tests.

Adverse Reactions

Cardiovascular

Arterial insufficiency usually of the Raynaud type, bradycardia, CHF, edema, hypotension, intensification of AV block.

CNS

Dizziness, fatigue (7%); decreased performance on neuropsychometric tests, disorientation, emotional lability, hallucinations, insomnia, lassitude, lethargy, light-headedness, mental depression progressing to catatonia, paraesthesia of the hands, short-term memory loss, slightly clouded sensorium, vivid dreams, weakness.

Dermatologic

Alopecia, erythema multiforme, exfoliative dermatitis, psoriasiform rashes, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria.

EENT

Dry eyes, visual disturbances.

GI

Abdominal cramping, constipation, diarrhea, epigastric distress, ischemic colitis, mesenteric arterial thrombosis, nausea, vomiting.

Genitourinary

Impotence.

Hematologic

Agranulocytosis, nonthrombocytopenic and thrombocytopenic purpura.

Hypersensitivity

Agranulocytosis, anaphylactic/anaphylactoid reactions, erythematous rash, fever combined with aching and sore throat, laryngospasm, pharyngitis, respiratory distress.

Lab Tests

Elevated levels of serum potassium, transaminases, and alkaline phosphatase.

Metabolic

Hyperglycemia, hypoglycemia.

Respiratory

Bronchospasm, difficulty breathing, dyspnea, wheezing.

Miscellaneous

Peyronie disease, SLE-like reactions, systemic lupus erythematosus.

Precautions

Warnings Angina pectoris 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. When discontinuance is planned, the dosage should be gradually reduced over at least a few weeks.

Pregnancy

Category C (first trimester); Category D (second and third trimesters).

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

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

Use with caution.

Hepatic Function

Reduce dose.

Discontinuation of therapy

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.

Hypertensive emergencies

Not indicated for treatment of hypertensive emergencies.

IOP

May cause reduction of IOP.

Major surgery

Withdrawal of treatment prior to surgery is controversial; it is thought that continued treatment may augment the risk of general anesthesia and surgical procedures.

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 treatment with a pacemaker.

Overdosage

Symptoms

Bradycardia, depressed myocardial function, hypotension.

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 a health care provider in a medical setting and that conversion to oral therapy will be made as soon as possible.
• Advise patient using oral doseforms 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.
• Advise patient that InnoPran XL should be taken once daily (approximately at 10 pm) and should be taken consistently with or without food.
• Advise patient taking immediate-release tablets to take 2 to 4 times daily as prescribed.
• Advise patient taking ER products to take once daily as prescribed. Caution patient to swallow ER 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.
• Inform patient or caregiver that drug controls, but does not 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 type 1 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 light-headedness 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.

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