Summary about Propranolol
Propranolol is a beta-blocker. Beta-blockers affect the heart and circulation (blood flow through arteries and veins).
Propranolol is used to treat tremors, angina (chest pain), hypertension (high blood pressure), heart rhythm disorders, and other heart or circulatory conditions. It is also used to treat or prevent heart attack, and to reduce the severity and frequency of migraine headaches.
Propranolol is also prescribed for the treatment of hyperthyroidism. Propranolol ameliorate the symptoms of hyperthyroidism that are caused by increased beta-adrenergic tone. These include palpitations, tachycardia, tremulousness, anxiety, and heat intolerance. Thus, a propranolol should be started (assuming there are no contraindications to its use) in most patients as soon as the diagnosis of hyperthyroidism is made, even before determining the cause of the hyperthyroidism. Therapy should be continued until resolution of hyperthyroidism.
Propranolol in high doses (above 160 mg/day) also slowly decreases serum triiodothyronine (T3) concentrations by as much as 30 percent, via inhibition of the 5′-monodeiodinase that converts thyroxine (T4) to T3. Propranolol is highly lipid soluble, allowing it to become sufficiently concentrated in tissues to inhibit monodeiodinase activity. This effect of propranolol is slow, occurring over 7 to 10 days, and contributes little to the therapeutic effects of the drug.
Despite this theoretical advantage of propranolol and related drugs, the small effect and slow onset severely limit their usefulness for reducing serum T3 concentrations. If deiodinase inhibition is considered important in a patient with severe hyperthyroidism (eg, thyroid storm or impending thyroid storm), it is best achieved by the addition of an iodinated radiocontrast agent to the medical regimen (these agents are currently not available in the United States), or the use of propylthiouracil (PTU).
In patients with Graves’ disease, propranolol is typically coadministered with a thionamide when a thionamide is chosen for initial treatment, and they are typically given to patients who are treated initially with radioiodine who do not require pretreatment with a thionamide.
Propranolol is relatively or, depending upon disease severity, absolutely contraindicated in patients with asthma or chronic obstructive pulmonary disease, severe peripheral vascular disease, Raynaud phenomenon, bradycardia, second- or third-degree heart block, and hypoglycemia-prone diabetics in whom the early warning symptoms of hypoglycemia may be masked.
Inderal (propranolol hydrochloride) tablets
|Alcohol may increase or decrease plasma levels of propranolol. Reports are variable and have shown both enhanced as well as inhibited hepatic metabolism of propranolol. Caution is advised with consumption of alcohol and heart rate and/or blood pressure changes should be monitored.|
|Propranolol hydrochloride is available as 10 mg, 20 mg, 40 mg and 80 mg tablets for oral administration.|
|Propranolol is present in breast milk. |
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.
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.
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
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.
|Tablets for oral administration|
|Thyroid storm (off-label use): |
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.
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
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
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)
|C07AA — Beta blocking agents, non-selective|
|Propranolol serum levels may be increased if taken with food. 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. Management: Tablets (immediate release) should be taken on an empty stomach. Capsules (extended release) may be taken with or without food, but be consistent with regard to food.|
|100% of Medicare Part D and Medicare Advantage plans cover this drug.|
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.
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.
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.
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.
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.
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.
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.
Methoxyflurane and trichloroethylene may depress myocardial contractility when administered with propranolol.
Propranolol when administered with warfarin increases the concentration of warfarin.
Prothrombin time, therefore, should be monitored.
Hypotension and cardiac arrest have been reported with the concomitant use of propranolol and haloperidol.
Thyroxine may result in a lower than expected T3 concentration when used concomitantly with propranolol.
Is Available Generically
Is not subject to the Controlled Substances Act.
|Akrimax Pharmaceuticals, LLC|
|4 mg/kg/day up to 640 mg/day|
Mechanism of Action
|Triptorelin is a synthetic agonist analog of gonadotropin releasing hormone (GnRH). Animal studies comparing triptorelin to native GnRH found that triptorelin had 13 fold higher releasing activity for luteinizing hormone, and 21-fold higher releasing activity for follicle-stimulating hormone.|
Non Proprietary Name
|Propranolol is not significantly dialyzable. In the event of overdosage or exaggerated response, the following measures should be employed: |
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.
|This drug is only recommended for use during pregnancy when there are no alternatives and the benefit outweighs the risk. |
AU TGA pregnancy category: C
US FDA pregnancy category: C
Beta blockers may cause decreased placental perfusion, fetal and neonatal bradycardia, and hypoglycemia.
|Propranolol has been used safely to treat a variety of conditions during pregnancy, including hypertension and pheochromocytoma in the mother, and tachyarrhythmias in both the mother and fetus. There are a number of abnormalities associated with the use of propranolol during pregnancy, but many of these may be attributable to underlying diseases. These abnormalities include some signs of beta-blockade, such as bradycardia, hypoglycemia, and respiratory depression. Other abnormalities that may be due to propranolol include intrauterine growth retardation, small placentas, polycythemia, thrombocytopenia, and hypocalcemia. |
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.
|Cloranolol, Penbutolol, Bupranolol, Bopindolol, Tertatolol. Careteolol, Nadolol, Mepindolol, Sotalol, Timolol, Pindolol, Oxprenolol, Alprenolol|
|Initial Rise of Gonadotropins and Sex Steroid Levels: An increase in clinical signs and symptoms of puberty may be observed during the first 2 4 weeks of therapy since gonadotropins and sex steroids rise above baseline because of the initial stimulatory effect of the drug. |
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.
Drugs.com [Internet]. Propranolol Information from Drugs.com; c1996-2019 [Updated: 9 December 2018, Cited: 28 November 2019]. Available from: https://www.drugs.com/propranolol.html
Drugbank.ca [Internet]. Propranolol Information from Drugbank.ca; c1996-2019 [Updated: 26 November 2019, Cited: 28 November 2019]. Available from: https://www.drugbank.ca/drugs/DB00571
Uptodate.com [Internet]. Propranolol Information from Uptodate.com; c1996-2019 [Updated: 21 November 2019, Cited: 28 November 2019]. Available from: https://www.uptodate.com/contents/propranolol-drug-information
Dailymed.nlm.nih.gov [Internet]. Propranolol hydrochloride tablet information from Dailymed.nlm.nih.gov; c1996-2019 [Updated: 1 August 2015, Cited: 28 November 2019]. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ab9e5678-db53-4354-998a-ed8bf1d33e90#modal-rx-norm
Al-Majed AA, Bakheit AHH, Abdel Aziz HA, Alajmi FM, AlRabiah H. Propranolol. Profiles Drug Subst Excip Relat Methodol. 2017;42:287-338. doi: 10.1016/bs.podrm.2017.02.006.
Srinivasan AV. Propranolol: A 50-Year Historical Perspective. Ann Indian Acad Neurol. 2019;22(1):21–26. doi:10.4103/aian.AIAN_201_18