Inderal (propranolol hydrochloride) tablets for oral use

Inderal (propranolol hydrochloride) tablets

Active Ingredient

Administration Route

Alcohol Warning

Available Strength

Breastfeeding Warning

The relative infant dose (RID) of propranolol is 1% when calculated using the highest breast milk concentration located and compared to an infant therapeutic dose of 1 mg/kg/day.

In general, breastfeeding is considered acceptable when the RID is <10.

Using the highest milk concentration (0.075 mcg/mL), the estimated daily infant dose via breast milk is 11.25 mcg/kg/day. This milk concentration was obtained following maternal administration of propranolol 1.2 mg/kg/day. Using data collected from three women, the same study found the overall half-life of propranolol in breast milk to be 6.5 ± 3.4 hours. Peak milk concentrations are reported to occur between 2 to 3 hours after an oral dose

Bradycardia was reported in an infant exposed to propranolol via breast milk. In general, propranolol may be compatible with breastfeeding when used at usual doses. Mothers should closely monitor their breastfeeding infants for bradycardia, cyanosis, and hypoglycemia. Propranolol may be a preferred beta-blocker in breastfeeding females.

Clinical Pharmacology

Propranolol is a beta-adrenergic receptor antagonist used to treat hypertension. Propranolol has a long duration of action as it is given once or twice daily depending on the indication. When patients abruptly stop taking propranolol, they may experience exacerbations of angina and myocardial infarctions.

Pharmacokinetics

Onset of action: Beta-blockade: Oral: 1 to 2 hours; Peak effect: Hypertension: A few days to several weeks

Duration: Immediate release: 6 to 12 hours; Extended-release formulations: ~24 to 27 hours

Absorption: Oral: Rapid and complete

Distribution: Vd: 4 L/kg (adults); crosses the blood-brain barrier

Protein binding: Newborns: 68%; Adults: ~90% (S-isomer primarily to alpha-1 acid glycoprotein; R-isomer primarily to albumin)

Metabolism: Extensive first-pass effect, hepatically metabolized to active and inactive compounds; the 3 main metabolic pathways include: Aromatic hydroxylation (primarily 4-hydroxylation), N-dealkylation followed by further side-chain oxidation and direct glucuronidation; the 4 primary metabolites include: Propranolol glucuronide, naphthyloxylactic acid, and sulfate and glucuronic acid conjugates of 4-hydroxy propranolol; Note: Aromatic hydroxylation is catalyzed primarily by isoenzyme CYP2D6; side chain oxidation is mainly via CYP1A2, but also CYP2D6; 4-hydroxypropranolol possesses beta-adrenergic receptor blocking activity and is a weak inhibitor of CYP2D6.

Bioavailability: ~25% reaches systemic circulation due to high first-pass metabolism; oral bioavailability may be increased in Down syndrome children; protein-rich foods increase bioavailability by ~50%

Half-life elimination: Neonates: Possible increased half-life; Infants (35 to 150 days of age): Median 3.5 hours; Children: 3.9 to 6.4 hours; Adults: Immediate release formulation: 3 to 6 hours; Extended-release formulations: 8 to 10 hours

Time to peak: Immediate release: Adults: 1 to 4 hours; Infants: ≤2 hours (Hemangeol); Extended release capsule (Inderal XL, InnoPran XL): 12 to 14 hours; Long acting capsule (Inderal LA): 6 hours

Excretion: Metabolites are excreted primarily in urine (96% to 99%); <1% excreted in urine as unchanged drug

Cost

• 10 mg (per each): $0.35 – $0.41
• 20 mg (per each): $0.51 – $1.34
• 40 mg (per each): $0.72
• 60 mg (per each): $1.22 – $1.74
• 80 mg (per each): $0.90 – $0.97

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Form

Dose Schedule

Immediate-release formulations: 60 to 80 mg every 4 hours

Thyrotoxicosis (off-label use):

Immediate-release formulations: 10 to 40 mg every 6 to 8 hours; may also consider administering once-daily ER or sustained-release formulations.

Pheochromocytoma:

Immediate-release formulations: 30 to 60 mg/day in divided doses

Akathisia, antipsychotic-induced (off-label use):

Immediate-release formulations Initial: 10 mg twice daily or 10 mg 3 times daily; adjust dose based on response and tolerability up to 120 mg/day. Treatment guidelines recommend doses of 30 to 90 mg/day

Atrial fibrillation:

Immediate-release formulations: 10 to 30 mg/dose every 6 to 8 hours or a usual maintenance dose of 10 to 40 mg three or four times daily for rate control in patients with atrial fibrillation

Essential tremor:

Immediate-release formulations: Initial: 40 mg twice daily; maintenance doses: Usually 120 to 320 mg/day

Hypertension (alternative agents):

Immediate-release formulations: 40 mg twice daily; titrate weekly as needed based on patient response; usual dosage range: 40 to 80 mg twice daily; maximum dose: 640 mg/day

Migraine headache prophylaxis:

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

Obstructive hypertrophic cardiomyopathy:

Immediate-release formulations: 20 to 40 mg 3 to 4 times daily

Performance anxiety (off-label use):

Immediate-release formulations: 40 mg 60 to 90 minutes prior to anxiety-provoking event. Additional data may be necessary to further define the role of propranolol in this condition.

Post-MI mortality reduction: Oral: Immediate-release formulations: Initial: 40 mg 3 times daily; usual dosage range: 180 to 240 mg/day in 3 to 4 divided doses

Stable angina:  Immediate-release formulations: 80 to 320 mg/day in doses divided 2 to 4 times daily

Supraventricular tachycardias (eg, AV nodal re-entrant tachycardias):

Ongoing management (off-label use): Oral: Initial: 30 to 60 mg daily in divided doses (immediate-release) or once daily (ER); maximum maintenance dose: 160 mg daily in divided doses (immediate-release) or once daily (ER)

Drug Class

Drug Unit

Food Warning

Included In
Health Insurance Plan

Interacting Drugs

Propafenone has negative inotropic and beta-blocking properties that can be additive to those of propranolol.

Quinidine increases the concentration of propranolol and produces greater degrees of clinical beta-blockade and may cause postural hypotension.

Amiodarone is an antiarrhythmic agent with negative chronotropic properties that may be additive to those seen with β-blockers such as propranolol.

The clearance of lidocaine is reduced with administration of propranolol. Lidocaine toxicity has been reported following coadministration with propranolol.

Caution should be exercised when administering propranolol with drugs that slow A-V nodal conduction, e.g. digitalis, lidocaine and calcium channel blockers.

Digitalis Glycosides

Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Calcium Channel Blockers

Caution should be exercised when patients receiving a beta blocker are administered a calciumchannel-blocking drug with negative inotropic and/or chronotropic effects. Both agents may depress myocardial contractility or atrioventricular conduction.

There have been reports of significant bradycardia, heart failure, and cardiovascular collapse with concurrent use of verapamil and beta-blockers.

Co-administration of propranolol and diltiazem in patients with cardiac disease has been associated with bradycardia, hypotension, high-degree heart block, and heart failure.

ACE Inhibitors

When combined with beta-blockers, ACE inhibitors can cause hypotension, particularly in the setting of acute myocardial infarction.

The antihypertensive effects of clonidine may be antagonized by beta-blockers. Inderal should be administered cautiously to patients withdrawing from clonidine.

Alpha Blockers

Prazosin has been associated with prolongation of first dose hypotension in the presence of betablockers.

Postural hypotension has been reported in patients taking both beta-blockers and terazosin or doxazosin.

Reserpine

Patients receiving catecholamine-depleting drugs, such as reserpine, should be closely observed for excessive reduction of resting sympathetic nervous activity, which may result in hypotension, marked bradycardia, vertigo, syncopal attacks, or orthostatic hypotension.

Inotropic Agents

Patients on long-term therapy with propranolol may experience uncontrolled hypertension if administered epinephrine as a consequence of unopposed alpha-receptor stimulation.

Epinephrine is therefore not indicated in the treatment of propranolol overdose

Isoproterenol and Dobutamine

Propranolol is a competitive inhibitor of beta-receptor agonists, and its effects can be reversed by administration of such agents, e.g., dobutamine or isoproterenol. Also, propranolol may reduce sensitivity to dobutamine stress echocardiography in patients undergoing evaluation for myocardial ischemia.

Nonsteroidal Anti-Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDS) have been reported to blunt the antihypertensive effect of beta-adrenoreceptor blocking agents.

Administration of indomethacin with propranolol may reduce the efficacy of propranolol in reducing blood pressure and heart rate.

Antidepressants

The hypotensive effects of MAO inhibitors or tricyclic antidepressants may be exacerbated when administered with beta-blockers by interfering with the beta blocking activity of propranolol.

Anesthetic Agents

Methoxyflurane and trichloroethylene may depress myocardial contractility when administered with propranolol.

Warfarin

Propranolol when administered with warfarin increases the concentration of warfarin.

Prothrombin time, therefore, should be monitored.

Neuroleptic Drugs

Hypotension and cardiac arrest have been reported with the concomitant use of propranolol and haloperidol.

Thyroxine

Thyroxine may result in a lower than expected T3 concentration when used concomitantly with propranolol.

Is Available Generically

Is Proprietary

Label Details

Legal Status

Is not subject to the Controlled Substances Act.

Manufacturer

Maximum Intake

Mechanism of Action

Non Proprietary Name

Overdosage

General: If ingestion is or may have been recent, evacuate gastric contents, taking care to prevent pulmonary aspiration.

Supportive Therapy: Hypotension and bradycardia have been reported following propranolol overdose and should be treated appropriately. Glucagon can exert potent inotropic and chronotropic effects and may be particularly useful for the treatment of hypotension or depressed myocardial function after a propranolol overdose. Glucagon should be administered as 50 to 150 mcg/kg intravenously followed by continuous drip of 1 to 5 mg/hour for positive chronotropic effect. Isoproterenol, dopamine or phosphodiesterase inhibitors may also be useful. Epinephrine, however, may provoke uncontrolled hypertension. Bradycardia can be treated with atropine or isoproterenol. Serious bradycardia may require temporary cardiac pacing.

The electrocardiogram, pulse, blood pressure, neurobehavioral status and intake and output balance must be monitored. Isoproterenol and aminophylline may be used for bronchospasm.

Pregnancy Category

AU TGA pregnancy category: C

US FDA pregnancy category: C

Beta blockers may cause decreased placental perfusion, fetal and neonatal bradycardia, and hypoglycemia.

Pregnancy Warning

AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.

US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant.

Prescribing Info

Prescription Status

Proprietary Name

Related Drugs

RxCUI

8787

Warning

Psychiatric events have been reported in patients taking GnRH agonists. Events include emotional lability, such as crying, irritability, impatience, anger, and aggression. Monitor for development or worsening of psychiatric symptoms.

Convulsions have been observed in patients with or without a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and in patients on concomitant medications that have been associated with convulsions.