Yes

Antiarrhythmic Agent, Class II; Beta Blocker, Nonselective

Management of hypertension, angina pectoris, pheochromocytoma, essential tremor, tetralogy of Fallot cyanotic spells, and arrhythmias (such as atrial fibrillation and flutter, A-V nodal re-entrant tachycardias, and catecholamine-induced arrhythmias); prevention of myocardial infarction, migraine headache; symptomatic treatment of hypertrophic subaortic stenosis

C (per manufacturer); D (in 2nd and 3rd trimesters, per expert analysis)

Clinical effects on the fetus: Crosses the placenta. IUGR, hypoglycemia, bradycardia, respiratory depression, hyperbilirubinemia, polycythemia, polydactyly reported. IUGR probably related to maternal hypertension. Preterm labor has been reported. Available evidence suggests safe use during pregnancy and breast-feeding. Monitor breast-fed infant for symptoms of beta-blockade.

Breast-feeding/lactation: Crosses into breast milk. American Academy of Pediatrics considers compatible with breast-feeding.

Hypersensitivity to propranolol or any component; sinus bradycardia; sinus node dysfunction; heart block greater than first degree (except in patients with a functioning artificial pacemaker); cardiogenic shock; uncompensated cardiac failure unless the heart failure is due to a tachyarrhythmia; bronchospastic disease; pregnancy (2nd and 3rd trimesters)

Administer cautiously in compensated heart failure and monitor for a worsening of the condition (efficacy of propranolol in CHF has not been demonstrated). Avoid abrupt discontinuation in patients with a history of CAD; slowly wean while monitoring for signs and symptoms of ischemia. Use caution in patient with PVD. Use caution with concurrent use of beta-blockers and either verapamil or diltiazem; bradycardia or heart block can occur. Avoid concurrent I.V. use of both agents. Use cautiously in diabetics because it can mask prominent hypoglycemic symptoms. Can mask signs of thyrotoxicosis. Can cause fetal harm when administered in pregnancy. Use cautiously in hepatic dysfunction (dosage adjustment required). Use care with anesthetic agents which decrease myocardial function.

Cardiovascular: Bradycardia, congestive heart failure, reduced peripheral circulation, thrombocytopenia, purpura, chest pain, hypotension, impaired myocardial contractility, worsening of A-V conduction disturbance, cardiogenic shock

Central nervous system: Mental depression, lightheadedness, amnesia, emotional lability, confusion, hallucinations, dizziness, insomnia, fatigue, vivid dreams, lethargy, cold extremities, vertigo, syncope, cognitive dysfunction, psychosis, hallucinations, hypersomnolence

Dermatologic: Rash, alopecia, exfoliative dermatitis, psoriasiform eruptions, eczematous eruptions, hyperkeratosis, nail changes, pruritus, urticaria, ulcerative lichenoid, contact dermatitis

Endocrine & metabolic: Hypoglycemia, hyperglycemia, lipid abnormal, hyperkalemia

Gastrointestinal: Diarrhea, nausea, vomiting, stomach discomfort, constipation, anorexia

Genitourinary: Impotence, proteinuria (rare), oliguria (rare), interstitial nephritis (rare)

Hematologic: Agranulocytosis, thrombocytopenia

Neuromuscular & skeletal: Weakness, carpal tunnel syndrome (rare), paresthesias, myotonus, polyarthritis arthropathy

Respiratory: Wheezing, pharyngitis, bronchospasm, pulmonary edema

Ocular: Hyperemia of the conjunctiva, decreased tear production, decreased visual acuity, mydriasis

Symptoms of intoxication include cardiac disturbances, CNS toxicity, bronchospasm, hypoglycemia and hyperkalemia. The most common cardiac symptoms include hypotension and bradycardia; atrioventricular block, intraventricular conduction disturbances, cardiogenic shock, and asystole may occur with severe overdose, especially with membrane-depressant drugs (eg, propranolol); CNS effects include convulsions, coma, and respiratory arrest is commonly seen with propranolol and other membrane-depressant and lipid-soluble drugs.

Treatment includes symptomatic treatment of seizures, hypotension, hyperkalemia and hypoglycemia; bradycardia and hypotension resistant to atropine, isoproterenol or pacing may respond to glucagon; wide QRS defects caused by the membrane-depressant poisoning may respond to hypertonic sodium bicarbonate; repeat-dose charcoal, hemoperfusion, or hemodialysis may be helpful in removal of only those beta-blockers with a small V_d, long half-life or low intrinsic clearance (acebutolol, atenolol, nadolol, sotalol)

CYP1A2, 2C18, 2C19, and 2D6 enzyme substrate

Alpha-blockers (prazosin, terazosin): Concurrent use of beta-blockers may increase risk of orthostasis.

Antipyrine's clearance is reduced by 30% to 40%.

Cimetidine increases the plasma concentration of propranolol and its pharmacodynamic effects may be increased.

Clonidine: Hypertensive crisis after or during withdrawal of either agent.

Drugs which slow AV conduction (digoxin): Effects may be additive with beta-blockers.

Epinephrine (including local anesthetics with epinephrine): Propranolol may cause hypertension.

Flecainide: Pharmacological activity of both agents may be increased when used concurrently.

Fluoxetine may inhibit the metabolism of propranolol, resulting in cardiac toxicity.

Glucagon: Propranolol may blunt hyperglycemic action.

Haloperidol: Hypotensive effects may be potentiated.

Hydralazine: The bioavailability propranolol (rapid release) and hydralazine may be enhanced with concurrent dosing.

Insulin: Propranolol inhibits recovery and may cause hypertension and bradycardia following insulin-induced hypoglycemia. Also masks the tachycardia that usually accompanies insulin-induced hypoglycemia.

NSAIDs (ibuprofen, indomethacin, naproxen, piroxicam) may reduce the antihypertensive effects of beta-blockers.

Salicylates may reduce the antihypertensive effects of beta-blockers.

Sulfonylureas: Beta-blockers may alter response to hypoglycemic agents.

Verapamil or diltiazem may have synergistic or additive pharmacological effects when taken concurrently with beta-blockers; avoid concurrent I.V. use of both.

Compatible in saline, incompatible with HCO₃^-; protect injection from light; solutions have maximum stability at pH of 3 and decompose rapidly in alkaline pH; propranolol is stable for 24 hours at room temperature in D₅W or NS

Nonselective beta-adrenergic blocker (class II antiarrhythmic); competitively blocks response to beta₁- and beta₂-adrenergic stimulation which results in decreases in heart rate, myocardial contractility, blood pressure, and myocardial oxygen demand

Onset of beta-blockade: Oral: Within 1-2 hours

Duration: ~6 hours

Distribution: V_d: 3.9 L/kg in adults; crosses the placenta; small amounts appear in breast milk

Protein binding: Newborns: 68%; Adults: 93%

Metabolism: Extensive first-pass effect; metabolized in the liver to active and inactive compounds

Bioavailability: 30% to 40%; oral bioavailability may be increased in Down syndrome children

Half-life: Neonates and Infants: Possible increased half-life; Children: 3.9-6.4 hours; Adults: 4-6 hours

Elimination: Primarily in urine (96% to 99%)

Tachyarrhythmias:

Oral:

Children: Initial: 0.5-1 mg/kg/day in divided doses every 6-8 hours; titrate dosage upward every 3-7 days; usual dose: 2-4 mg/kg/day; higher doses may be needed; do not exceed 16 mg/kg/day or 60 mg/day

Adults: 10-30 mg/dose every 6-8 hours

Elderly: Initial: 10 mg twice daily; increase dosage every 3-7 days; usual dosage range: 10-320 mg given in 2 divided doses

I.V.:

Children: 0.01-0.1 mg/kg slow IVP over 10 minutes; maximum dose: 1 mg

Adults: 1 mg/dose slow IVP; repeat every 5 minutes up to a total of 5 mg

Hypertension: Oral:

Children: Initial: 0.5-1 mg/kg/day in divided doses every 6-12 hours; increase gradually every 3-7 days; maximum: 2 mg/kg/24 hours

Adults: Initial: 40 mg twice daily; increase dosage every 3-7 days; usual dose: less than or equal to 320 mg divided in 2-3 doses/day; maximum daily dose: 640 mg

Migraine headache prophylaxis: Oral:

Children: 0.6-1.5 mg/kg/day or

less than or equal to 35 kg: 10-20 mg 3 times/day

>35 kg: 20-40 mg 3 times/day

Adults: Initial: 80 mg/day divided every 6-8 hours; increase by 20-40 mg/dose every 3-4 weeks to a maximum of 160-240 mg/day given in divided doses every 6-8 hours; if satisfactory response not achieved within 6 weeks of starting therapy, drug should be withdrawn gradually over several weeks

Tetralogy spells: Children:

Oral: 1-2 mg/kg/day every 6 hours as needed, may increase by 1 mg/kg/day to a maximum of 5 mg/kg/day, or if refractory may increase slowly to a maximum of 10-15 mg/kg/day

I.V.: 0.15-0.25 mg/kg/dose slow IVP; may repeat in 15 minutes

Thyrotoxicosis:

Adolescents and Adults: Oral: 10-40 mg/dose every 6 hours

Adults: I.V.: 1-3 mg/dose slow IVP as a single dose

Adults: Oral:

Angina: 80-320 mg/day in doses divided 2-4 times/day

Pheochromocytoma: 30-60 mg/day in divided doses

Myocardial infarction prophylaxis: 180-240 mg/day in 3-4 divided doses

Hypertrophic subaortic stenosis: 20-40 mg 3-4 times/day

Essential tremor: 40 mg twice daily initially; maintenance doses: usually 120-320 mg/day

Dosing adjustment in renal impairment:

Cl_cr 31-40 mL/minute: Administer every 24-36 hours or administer 50% of normal dose.

Cl_cr 10-30 mL/minute: Administer every 24-48 hours or administer 50% of normal dose.

Cl_cr <10 mL/minute: Administer every 40-60 hours or administer 25% of normal dose.

Hemodialysis: Not dialyzable (0% to 5%); supplemental dose is not necessary.

Peritoneal dialysis: Supplemental dose is not necessary.

Dosing adjustment/comments in hepatic disease: Marked slowing of heart rate may occur in cirrhosis with conventional doses. Low initial dose and regular heart rate monitoring.

Avoid natural licorice (causes sodium and water retention and increases potassium loss); protein-rich foods may increase bioavailability; a change in diet from high carbohydrate/low protein to low carbohydrate/high protein may result in increased oral clearance

Blood pressure, EKG, heart rate, CNS and cardiac effects

Therapeutic: 50-100 ng/mL (SI: 190-390 nmol/L) at end of dose interval

thyroxine (S)

Hypertension: Beta-blocker therapy in the treatment of hypertension has been associated with improved cardiovascular outcomes. This class of drug is beneficial for elderly patients with hypertension. A recent UKPDS study showed that beta-blocker therapy (atenolol) was as effective as an ACE inhibitor in reducing cardiovascular events and that the benefits of therapy were related more to the degree of antihypertensive efficacy rather than the class of drug used.

Myocardial infarction: Beta-blockers, in general without intrinsic sympathomimetic activity (ISA), have been shown to decrease morbidity and mortality when initiated in the acute treatment of myocardial infarction and continued long-term. In this setting, therapy should be avoided in patients with hypotension, cardiogenic shock, or heart block.

Surgery: Atenolol has also been shown to improve cardiovascular outcomes when used in the perioperative period in patients with underlying cardiovascular disease who are undergoing noncardiac surgery. Bisoprolol in high-risk patients undergoing vascular surgery reduced the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction.

Atrial fibrillation: Beta-blocker therapy provides effective rate control in patients with atrial fibrillation.

Angina: Beta-blockers are effective in the treatment of angina as monotherapy or when combined with nitrates and/or calcium channel blockers. In patients with severe intractable angina requiring negative cardiac chronotropic medications, pacemaker placement has been carried out to maintain heart rate in the setting of large doses of beta-blockers and/or calcium channel blockers. Beta-blockers are ineffective in the treatment of pure vasospastic (Prinzmetal) angina.

Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.

Heart failure: There is emerging evidence that beta-blocker therapy, without intrinsic sympathomimetic activity (ISA), should be initiated in select patients with stable congestive heart failure (NYHA Class II-III). To date, carvedilol, sustained release metoprolol, and bisoprolol have demonstrated a beneficial effect on morbidity and mortality. It is important that beta-blocker therapy be instituted initially at very low doses with gradual and very careful titration.

Fatigue and malaise are common and often mistaken for depression; may also cause dizziness, confusion, insomnia, or hallucinations

Low-dose propranolol is considered by many to be the drug of choice for akathisia; concurrent use with psychotropic drugs may produce additive hypotensive effects; monitor blood pressure

Use with caution; epinephrine has interacted with nonselective beta-blockers to result in initial hypertensive episode followed by bradycardia

Noncardioselective beta-blockers (ie, propranolol, nadolol) enhance the pressor response to epinephrine, resulting in hypertension and bradycardia. Many nonsteroidal anti-inflammatory drugs such as ibuprofen and indomethacin can reduce the hypotensive effect of beta-blockers after 3 or more weeks of therapy with the NSAID. Short-term NSAID use (ie, 3 days) requires no special precautions in patients taking beta-blockers.

Take exactly as directed; do not increase, decrease, or discontinue without consulting prescriber. Take at the same time each day. Tablets may be crushed and taken with liquids. Do not alter dietary intake of protein or carbohydrates without consulting prescriber. You may experience orthostatic hypotension, dizziness, drowsiness, or blurred vision (use caution when driving, climbing stairs, or changing position - rising from sitting or lying to standing - or engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, or stomach discomfort (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); decreased sexual ability (reversible). If diabetic, monitor serum glucose closely. Report unusual swelling of extremities, difficulty breathing, unresolved cough, or unusual weight gain, cold extremities, persistent diarrhea, confusion, hallucinations, headache, nervousness, lack of improvement, or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Patient's therapeutic response may be evaluated by looking at blood pressure, apical and radial pulses, fluid I & O, daily weight, respirations, and circulation in extremities before and during therapy

Capsule, as hydrochloride, sustained action: 60 mg, 80 mg, 120 mg, 160 mg

Injection, as hydrochloride: 1 mg/mL (1 mL)

Solution, oral, as hydrochloride (strawberry-mint flavor): 4 mg/mL (5 mL, 500 mL); 8 mg/mL (5 mL, 500 mL)

Solution, oral, concentrate, as hydrochloride: 80 mg/mL (30 mL)

Tablet, as hydrochloride: 10 mg, 20 mg, 40 mg, 60 mg, 80 mg

Choi KL, Wat MS, Ip TP, et al, "Phaeochromocytoma Associated With Myasthenia Gravis Precipitated by Propranolol Treatment," Aust N Z J Med, 1995, 25(3):257.

Foster CA and Aston SJ, "Propranolol-Epinephrine Interaction: A Potential Disaster," Plast Reconstr Surg, 1983, 72(1):74-8.

Garson A Jr, Gillette PC, and McNamara DG, "Propranolol: The Preferred Palliation for Tetralogy of Fallot," Am J Cardiol, 1981, 47(5):1098-104.

Grandy W, "Severe Epinephrine-Propranolol Interaction," Ann Emerg Med, 1989, 18(1):98-9.

Jones JW, Clark MA, and Mullen BL, "Suicide by Ingestion of Propranolol," J Forensic Sci, 1982, 27(1):213-6.

Lai CW, Ziegler DK, Lansky LL, et al, "Hemiplegic Migraine in Childhood: Diagnostic and Therapeutic Aspects," J Pediatr, 1982, 101(5):696-9.

Love JN and Handler JA, "Toxic Psychosis: An Unusual Presentation of Propranolol Intoxication," Am J Emerg Med, 1995, 13(5):536-7.

Pickoff AS, Zies L, Ferrer PL, et al, "High-Dose Propranolol Therapy in the Management of Supraventricular Tachycardia," J Pediatr, 1979, 94(1):144-6.

Rasoulpour M and Marinelli KA, "Systemic Hypertension," Clin Perinatol, 1992, 19(1):121-37.

Sato S, Tsuji MH, Okubo N, et al, "Combined Use of Glucagon and Milrinone May Not Be Preferable for Severe Propranolol Poisoning in the Canine Model," J Toxicol Clin Toxicol, 1995, 33(4):337-42.

Shayne P and Hart A, "Thyrotoxic Periodic Paralysis Terminated With Intravenous Propranolol," Ann Emerg Med, 1994, 24(4):736-40.

Sinaiko AR, "Pharmacologic Management of Childhood Hypertension," Pediatr Clin North Am, 1993, 40(1):195-212.

Sowinski KM, Burlew BS, and Johnson JA, "Racial Differences in Sensitivity to the Negative Chronotropic Effects of Propranolol in Healthy Men," Clin Pharmacol Ther, 1995, 57(6):678-83.

Stoschitzky K, Kahr S, Donnerer J, et al, "Stereoselective Increase of Plasma Concentrations of the Enantiomers of Propranolol and Atenolol During Exercise," Clin Pharmacol Ther, 1995, 57(5):543-51.

Wong DG, Spence JD, Lamki L, et al, "Effect of Nonsteroidal Anti-inflammatory Drugs on Control of Hypertension of Beta-Blockers and Diuretics," Lancet, 1986, 1(8488):997-1001.

Wynn RL, "Dental Nonsteroidal Anti-inflammatory Drugs and Prostaglandin-Based Drug Interactions, Part Two," Gen Dent, 1992, 40(2):104, 106, 108.

Wynn RL, "Epinephrine Interactions With Beta-Blockers," Gen Dent, 1994, 42(1):16, 18.