DRUGS & SUPPLEMENTS

Inderal

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Inderal uses


DESCRIPTION

Inderal Hydrochloride, USP is a synthetic beta-adrenergic receptor blocking agent chemically described as (+)-1-(isopropylamino)-3-(1-naphthyloxy)-2-propanol hydrochloride. Its structural formula is:

Inderal Hydrochloride, USP is a stable, white, crystalline solid which is readily soluble in water and ethanol. Its molecular weight is 295.80.

Inderal Hydrochloride Injection, USP is available as a sterile injectable solution for intravenous administration. Each mL contains 1 mg of Inderal Hydrochloride, USP in Water for Injection, USP. The pH is adjusted with anhydrous Citric Acid, USP.

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CLINICAL PHARMACOLOGY

General

Inderal is a nonselective beta-adrenergic receptor blocking agent possessing no other autonomic nervous system activity. It specifically competes with beta-adrenergic receptor stimulating agents for available receptor sites. When access to beta-recceptor sites is blocked by Inderal, chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation are decreased proportionately. At doses greater than required for beta blockade, Inderal also exerts a quinidine-like or anesthetic-like membrane action, which affects the cardiac action potential. The significance of the membrane action in the treatment of arrhythmias is uncertain.

Mechanism of Action

The effects of Inderal are due to selective blockade of beta-adrenergic receptors, leaving alpha-adrenergic responses intact. There are two well-characterized subtypes of beta receptors (beta1 and beta2); Inderal interacts with both subtypes equally. Beta1-adrenergic receptors leads to a decrease in the activity of both normal and ectopic pacemaker cells and a decrease in A-V nodal conduction velocity. All of these actions can contribute to antiarrhythmic activity and control of ventricular rate during arrhythmias. Blockade of cardiac beta1-adrenergic receptors also decreases the myocardial force of contraction and may provoke cardiac decompensation in patients with minimal cardiac reserve.

Beta2-adrenergic receptors are found predominantly in smooth muscle-vascular, bronchial, gastrointestinal and genitourinary. Blockade of these receptors results in constriction. Clinically, Inderal may exacerbate respiratory symptoms in patients with obstructive pulmonary diseases such as asthma and emphysema.

Propranolol's beta blocking effects are attributable to its S(-) enantiomer.

Pharmacokinetics and Drug Metabolism

Distribution

Inderal has a distribution half-life (T1/2 alpha) of 5-10 minutes and a volume of distribution of about 4 to 5 L/kg. Approximately 90% of circulating Inderal is bound to plasma proteins. The binding is enantiomer-selective. The S-isomer is preferentially bound to alpha1 glycoprotein and the R-isomer is preferentially bound to albumin.

Metabolism and Elimination

The elimination half-life (T½ beta) is between 2 and 5.5 hours. Inderal is extensively metabolized with most metabolites appearing in the urine. The major metabolites include Inderal glucuronide, naphthyloxylactic acid, and glucuronic acid and sulfate conjugates of 4-hydroxy Inderal. Following single-dose intravenous administration, side-chain oxidative products account for approximately 40% of the metabolites, direct conjugation products account for approximately 45-50% of metabolites, and ring oxidative products account for approximately 10-15% of metabolites. Of these, only the primary ring oxidative product (4-hydroxypropranolol) possesses beta-adrenergic receptor blocking activity.

In vitro studies have indicated that the aromatic hydroxylation of Inderal is catalyzed mainly by polymorphic CYP2D6. Side‑chain oxidation is mediated mainly by CYP1A2 and to some extent by CYP2D6. 4-hydroxy Inderal is a weak inhibitor of CYP2D6.

Pharmacodynamics

As Inderal concentration increases, so does its beta-blocking effect, as evidenced by a reduction in exercise-induced tachycardia (n = 6 normal volunteers).

Special Populations

Pediatric

The pharmacokinetics of Inderal have not been investigated in patients under 18 years of age. Inderal injection is not recommended for treatment of cardiac arrhythmias in pediatric patients.

Geriatric

Elevated Inderal plasma concentrations, a longer mean elimination half-life (254 vs. 152 minutes), and decreased systemic clearance (8 vs. 13 mL/kg/min) have been observed in elderly subjects when compared to young subjects. However, the apparent volume of distribution seems to be similar in elderly and young subjects. These findings suggest that dose adjustment of Inderal injection may be required for elderly patients.

Gender

Intravenously administered Inderal was evaluated in 5 women and 6 men. When adjusted for weight, there were no gender-related differences in elimination half-life, volume of distribution, protein binding, or systemic clearance.

Obesity

In a study of intravenously administered Inderal, obese subjects had a higher AUC (161 versus 109 hr·mcg/L) and lower total clearance than did non-obese subjects. Inderal plasma protein binding was similar in both groups.

Renal Insufficiency

The pharmacokinetics of Inderal and its metabolites were evaluated in 15 subjects with varying degrees of renal function after Inderal administration via the intravenous and oral routes. When compared with normal subjects, an increase in fecal excretion of Inderal conjugates was observed in patients with increased renal impairment. Inderal was also evaluated in 5 patients with chronic renal failure, 6 patients on regular dialysis, and 5 healthy subjects, following a single oral dose of 40 mg of Inderal. The peak plasma concentrations (Cmax) of Inderal in the chronic renal failure group were 2- to 3-fold higher (161 ng/mL) than those observed in the dialysis patients (47 ng/‌mL) and in the healthy subjects (26 ng/mL). Inderal plasma clearance was also reduced in the patients with chronic renal failure.

Chronic renal failure has been associated with a decrease in drug metabolism via downregulation of hepatic cytochrome P-450 activity.

Hepatic Insufficiency

Inderal is extensively metabolized by the liver. In a study conducted in 6 normal subjects and 20 patients with chronic liver disease, including hepatic cirrhosis, 40 mg of R-propranolol was administered intravenously. Compared to normal subjects, patients with chronic liver disease had decreased clearance of Inderal, increased volume of distribution, decreased protein-binding, and considerable variation in half-life. Caution should be exercised when Inderal is used in this population. Consideration should be given to lowering the dose of intravenous Inderal in patients with hepatic insufficiency.

Thyroid Dysfunction

No pharmacokinetic changes were observed in hyperthyroid or hypothyroid patients when compared to their corresponding euthyroid state. Dosage adjustment does not seem necessary in either patient population based on pharmacokinetic findings.

Drug Interactions

Interactions with Substrates, Inhibitors or Inducers of Cytochrome P-450 Enzymes

Because propranolol’s metabolism involves multiple pathways in the cytochrome P-450 system (CYP2D6, 1A2, 2C19), administration of Inderal with drugs that are metabolized by, or affect the activity (induction or inhibition) of one or more of these pathways may lead to clinically relevant drug interactions.

Substrates or Inhibitors of CYP2D6

Blood levels of Inderal may be increased by administration of Inderal with substrates or inhibitors of CYP2D6, such as amiodarone, cimetidine, delavirdine, fluoxetine, paroxetine, quinidine, and ritonavir. No interactions were observed with either ranitidine or lansoprazole.

Substrates or Inhibitors of CYP1A2

Blood levels of Inderal may be increased by administration of Inderal with substrates or inhibitors of CYP1A2, such as imipramine, cimetidine, ciprofloxacin, fluvoxamine, isoniazid, ritonavir, theophylline, zileuton, zolmitriptan, and rizatriptan.

Substrates or Inhibitors of CYP2C19

Blood levels of Inderal may be increased by administration of Inderal with substrates or inhibitors of CYP2C19, such as fluconazole, cimetidine, fluoxetine, fluvoxamine, teniposide, and tolbutamide. No interaction was observed with omeprazole.

Inducers of Hepatic Drug Metabolism

Blood levels of Inderal may be decreased by administration of Inderal with inducers such as rifampin and ethanol. Cigarette smoking also induces hepatic metabolism and has been shown to increase up to 100% the clearance of Inderal, resulting in decreased plasma concentrations.

Cardiovascular Drugs

Antiarrhythmics

The AUC of propafenone is increased by more than 200% with co-administration of Inderal.

The metabolism of Inderal is reduced by co-administration of quinidine, leading to a 2- to 3-fold increased blood concentrations and greater beta-blockade.

The metabolism of lidocaine is inhibited by co-administration of Inderal, resulting in a 25% increase in lidocaine concentrations.

Calcium Channel Blockers

The mean Cmax and AUC of Inderal are increased respectively, by 50% and 30% by co-administration of nisoldipine and by 80% and 47%, by co-administration of nicardipine.

The mean values of Cmax and AUC of nifedipine are increased by 64% and 79%, respectively, by co-administration of Inderal.

Inderal does not affect the pharmacokinetics of verapamil and norverapamil. Verapamil does not affect the pharmacokinetics of Inderal.

Non-Cardiovascular Drugs

Migraine Drugs

Administration of zolmitriptan or rizatriptan with Inderal resulted in increased concentrations of zolmitriptan (AUC increased by 56% and Cmax by 37%) or rizatriptan (the AUC and Cmax were increased by 67% and 75%, respectively).

Theophylline

Co-administration of theophylline with Inderal decreases theophylline clearance by 33% to 52%.

Benzodiazepines

Inderal can inhibit the metabolism of diazepam, resulting in increased concentrations of diazepam and its metabolites. Diazepam does not alter the pharmacokinetics of Inderal.

The pharmacokinetics of oxazepam, triazolam, lorazepam, and alprazolam are not affected by co-administration of Inderal.

Neuroleptic Drugs

Co-administration of Inderal at doses greater than or equal to 160 mg/day resulted in increased thioridazine plasma concentrations ranging from 50% to 370% and increased thioridazine metabolites concentrations ranging from 33% to 210%.

Co-administration of chlorpromazine with Inderal resulted in increased plasma levels of both drugs (70% increase in Inderal concentrations).

Anti-Ulcer Drugs

Co-administration of Inderal with cimetidine, a non-specific CYP450 inhibitor, increased Inderal concentrations by about 40%. Co‑administration with aluminum hydroxide gel (1200 mg) resulted in a 50% decrease in Inderal concentrations.

Co-administration of metoclopramide with Inderal did not have a significant effect on propranolol’s pharmacokinetics.

Lipid Lowering Drugs

Co-administration of cholesteramine or colestipol with Inderal resulted in up to 50% decrease in Inderal concentrations.

Co-administration of Inderal with lovastatin or pravastatin decreased 20% to 25% the AUC of both, but did not alter their pharmacodynamics. Inderal did not have an effect on the pharmacokinetics of fluvastatin.

Warfarin

Concomitant administration of Inderal and warfarin has been shown to increase warfarin bioavailability and increase prothrombin time.

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CLINICAL STUDIES

In a series of 225 patients with supraventricular (n = 145), ventricular (n = 69), or both (n = 11) arrythmias resistant to digitalis, intravenous Inderal hydrochloride was administered in single doses, averaging 1 to 5 mg. Approximately one-quarter of the patients with supraventricular arrhythmias (generally those with sinus or atrial tachycardia) reverted to normal sinus rhythm. About one-half had symptoms ameliorated either by a decrease in ventricular rate or an attenuation of frequency or severity of paroxysmal attacks.

Approximately one-half of patients with ventricular arrhythmias (generally those with frequent PVCs) reverted to normal sinus rhythm or responded with a reduction in ventricular rate.

Similar findings were seen in a series of 25 Bantu patients with atrial fibrillation (n = 16), sinus tachycardia (n = 5), and multifocal ventricular extrasystoles (n = 9).

In another series, 7 of 8 patients with digitalis-related tachyarrhythmia had ventricular rate decreases after intravenous Inderal. Similarly limited clinical experience has shown that intravenous Inderal will slow the ventricular rate in patients with Wolff-Parkinson-White syndrome or with tachycardia associated with thyrotoxicosis.

Onset of activity is usually within five minutes.

INDICATIONS & USAGE

Cardiac Arrhythmias

Intravenous administration is usually reserved for life-threatening arrhythmias or those occurring under anesthesia.

1.  Supraventricular arrhythmias

Intravenous Inderal is indicated for the short-term treatment of supraventricular tachycardia, including Wolff‑Parkinson‑White syndrome and thyrotoxicosis, to decrease ventricular rate. Use in patients with atrial flutter or atrial fibrillation should be reserved for arrythmias unresponsive to standard therapy or when more prolonged control is required. Reversion to normal sinus rhythm has occasionally been observed, predominantly in patients with sinus or atrial tachycardia.

2.  Ventricular tachycardias

With the exception of those induced by catecholamines or digitalis, Inderal is not the drug of first choice. In critical situations when cardioversion techniques or other drugs are not indicated or are not effective, Inderal may be considered. If, after consideration of the risks involved, Inderal is used, it should be given intravenously in low dosage and very slowly, as the failing heart requires some sympathetic drive for maintenance of myocardial tone. Some patients may respond with complete reversion to normal sinus rhythm, but reduction in ventricular rate is more likely. Ventricular arrhythmias do not respond to Inderal as predictably as do the supraventricular arrhythmias.

Intravenous Inderal is indicated for the treatment of persistent premature ventricular extrasystoles that impair the well‑being of the patient and do not respond to conventional measures.

3.  Tachyarrhythmias of digitalis intoxication

Intravenous Inderal is indicated to control ventricular rate in life-threatening digitalis-induced arrhythmias. Severe bradycardia may occur.

4.  Resistant tachyarrhythmias due to excessive catecholamine action during anesthesia

Intravenous Inderal is indicated to abolish tachyarrhythmias due to excessive catecholamine action during anesthesia when other measures fail. These arrhythmias may arise because of release of endogenous catecholamines or administration of catecholamines. All general inhalation anesthetics produce some degree of myocardial depression. Therefore, when Inderal is used to treat arrhythmias during anesthesia, it should be used with extreme caution, usually with constant monitoring of the ECG and central venous pressure.

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CONTRAINDICATIONS

Inderal is contraindicated in 1) cardiogenic shock; 2) sinus bradycardia and greater than first-degree block; 3) bronchial asthma; and 4) in patients with known hypersensitivity to Inderal hydrochloride.

WARNINGS

Cardiac Failure

Sympathetic stimulation  may be a vital component supporting circulatory function in patients with congestive heart failure, and its inhibition by beta blockade may precipitate more severe failure. Although beta-blockers should be avoided in overt congestive heart failure, some have been shown to be highly beneficial when used with close follow-up in patients with a history of failure who are well compensazted and are receiving additional therapies, including diiuretics as needed. Beta-adrenergic blocking agents do not abolish the inotropic action of digitalis on heart muscle.

Nonallergic Bronchospasm (e.g., Chronic Bronchitis, Emphysema)

In general, patients with bronchospastic lung disease should not receive beta blockers. Inderal should be administered with caution in this setting since it may block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta-receptors.

Major Surgery

The necessity or desirability of withdrawal of beta-blocking therapy prior to major surgery is controversial. It should be noted, however, that the impaired ability of the heart to respond to reflex adrenergic stimuli in propranolol-treated patients might augment the risks of general anesthesia and surgical procedures.

Inderal is a competitive inhibitor of beta-receptor agonists, and its effects can be reversed by administration of such agents, e.g., dobutamine or isoproterenol. However, such patients may be subject to protracted severe hypotension.

Diabetes and Hypoglycemia

Beta-adrenergic blockade may prevent the appearance of certain premonitory signs and symptoms (pulse rate and pressure changes) of acute hypoglycemia, especially in labile insulin-dependent diabetics. In these patients, it may be more difficult to adjust the dosage of insulin.

Inderal therapy, particularly in infants and children, diabetic or not, has been associated with hypoglycemia especially during fasting, as in preparation for surgery. Hypoglycemia has been reported after prolonged physical exertion and in patients with renal insufficiency.

Thyrotoxicosis

Beta-adrenergic blockade may mask certain clinical signs of hyperthyroidism. Therefore, abrupt withdrawal of Inderal may be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm. Inderal may change thyroid-function tests, increasing T4 and reverse T3, and decreasing T3.

Wolff-Parkinson-White Syndrome

Beta-adrenergic blockade in patients with Wolff-Parkinson-White syndrome and tachycardia has been associated with severe bradycardia requiring treatment with a pacemaker. In one case this resulted after an initial 5 mg dose of intravenous Inderal.

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PRECAUTIONS

General

Inderal should be used with caution in patients with impaired hepatic or renal function.

Inderal is not indicated for the treatment of hypertensive emergencies.

Beta-adrenergic receptor blockade can cause reduction of intraocular pressure. Patients should be told that Inderal might interfere with the glaucoma screening test. Withdrawal may lead to a return of elevated intraocular pressure.

Risk of anaphylactic reaction. While taking beta blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

Angina Pectoris

There have been reports of exacerbation of angina and, in some cases, myocardial infarction, following abrupt discontinuance of Inderal therapy. Therefore, when discontinuance of Inderal is planned, the dosage should be gradually reduced over at least a few weeks, and the patient should be cautioned against interruption or cessation of therapy without a physician’s advice. If Inderal therapy is interrupted and exacerbation of angina occurs, it is usually advisable to reinstitute Inderal therapy and take other measures appropriate for the management of angina pectoris. Since coronary artery disease may be unrecognized, it may be prudent to follow the above advice in patients considered at risk of having occult atherosclerotic heart disease who are given Inderal for other indications.

Clinical Laboratory Tests

In patients with hypertension, use of Inderal has been associated with elevated levels of serum potassium, serum transaminases and alkaline phosphatase. In severe heart failure, the use of Inderal has been associated with increases in Blood Urea Nitrogen.

Drug Interactions

Caution should be exercised when Inderal is administered with drugs that have an effect on CYP2D6, 1A2, or 2C19 metabolic pathways. Co-administration of such drugs with Inderal may lead to clinically relevant drug interactions and changes in its efficacy and/or toxicity (see CLINICAL PHARMACOLOGY, DRUG INTERACTIONS.

Cardiovascular Drugs

Antirrhythmics

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

Quinidine increases the concentration of Inderal and produces a greater degree of clinical beta-blockade and may cause postural hypotension.

Disopyramide is a Type I antiarrhythmic drug with potent negative inotropic and chronotropic effects and has been associated with severe bradycardia, asystole and heart failure when administered with Inderal.

Amiodarone is an antiarrhythmic agent with negative chronotropic properties that may be additive to those seen with Inderal.

The clearance of lidocaine is reduced when administered with Inderal. Lidocaine toxicity has been reported following co-administration with Inderal.

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

Calcium Channel Blockers

Caution should be exercised when patients receiving a beta-blocker are administered a calcium-channel-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 Inderal 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.

ACE inhibitors have been reported to increase bronchial hyperreactivity when administered with Inderal.

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 beta-blockers.

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

Reserpine

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

Inotropic  Agents

Patients on long-term therapy with Inderal may experience uncontrolled hypertension if administered epinephrine as a consequence of unopposed alpha-receptor stimulation. Epinephrine is therefore not indicated in the treatment of Inderal 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, Inderal may reduce sensitivity to dobutamine stress echocardiography in patients undergoing evaluation for myocardial ischemia.

Non-Cardiovascular Drugs

Non-Steroidal Anti-Inflammatory Drugs

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

Administration of indomethacin with Inderal may reduce the efficacy of Inderal 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 Inderal.

Anesthetic Agents

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

Warfarin

Administration of Inderal with warfarin increases the concentration of warfarin. Therefore, the prothrombin time should be monitored.

Neuroleptic Drugs

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

Thyroxine

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

Carcinogenesis, Mutagenesis, Impairment of Fertility

In dietary administration studies in which mice and rats were treated with Inderal hydrochloride for up to 18 months at doses of up to 150 mg/kg/day, there was no evidence of drug-related tumorigenesis. On a body surface area basis, this dose in the mouse and rat is, respectively, about equal to and about twice the maximum recommended human oral daily dose (MRHD) of 640 mg Inderal hydrochloride. In a study in which both male and female rats were exposed to Inderal hydrochloride in their diets at concentrations of up to 0.05% (about 50 mg/kg body weight and less than the MRHD), from 60 days prior to mating and throughout pregnancy and lactation for two generations, there were no effects on fertility. Based on differing results from Ames Tests performed by different laboratories, there is equivocal evidence for a genotoxic effect of Inderal hydrochloride in bacteria (S. typhimurium strain TA 1538).

Pregnancy

Pregnancy Category C

In a series of reproductive and developmental toxicology studies, Inderal hydrochloride was given to rats by gavage or in the diet throughout pregnancy and lactation. At doses of 150 mg/kg/day, but not at doses of 80 mg/kg/day (equivalent to the MRHD on a body surface area basis), treatment was associated with embryotoxicity (reduced litter size and increased resorption rates) as well as neonatal toxicity (deaths). Inderal hydrochloride also was administered (in the feed) to rabbits (throughout pregnancy and lactation) at doses as high as 150 mg/kg/day (about 5 times the maximum recommended human oral daily dose). No evidence of embryo or neonatal toxicity was noted.

There are no adequate and well-controlled studies in pregnant women. Intrauterine growth retardation has been reported for neonates whose mothers received Inderal hydrochloride during pregnancy. Neonates whose mothers received Inderal hydrochloride at parturition have exhibited bradycardia, hypoglycemia, and respiratory depression. Adequate facilities for monitoring such infants at birth should be available. Inderal should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Inderal is excreted in human milk. Caution should be exercised when Inderal is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of Inderal in pediatric patients have not been established.

Geriatric Use

Clinical studies of intravenous Inderal did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly subjects have decreased clearance and a longer mean elimination half‑life. These findings suggest that dose adjustment of Inderal injection may be required for elderly patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of the decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Hepatic Insufficiency

Inderal is extensively metabolized by the liver. Compared to normal subjects, patients with chronic liver disease have decreased clearance of Inderal, increased volume of distribution, decreased protein-binding and considerable variation in half life. Consideration should be given to lowering the dose of intravenously administered Inderal in patients with hepatic insufficiency.

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ADVERSE REACTIONS

In a series of 225 patients, there were 6 deaths. Cardiovascular events (hypotension, congestive heart failure, bradycardia, and heart block) were the most common. The only other event reported by more than one patient was nausea.

Other adverse events for intravenous Inderal, reported during post-marketing surveillance include cardiac arrest, dyspnea, and cutaneous ulcers.

The following adverse events have been reported with use of formulations of sustained- or immediate-release oral Inderal and may be expected with intravenous Inderal.

Cardiovascular

Bradycardia; congestive heart failure; intensification of AV block; hypotension; paresthesia of hands; thrombocytopenic purpura; arterial insufficiency, usually of the Raynaud type.

Central Nervous System

Light-headedness; mental depression manifested by insomnia, lassitude, weakness, fatigue; reversible mental depression progressing to catatonia; visual disturbances; hallucinations; vivid dreams; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreaseed performance on neuropsychometrics. For immediate-release formulations, fatigue, lethargy, and vivid dreams appear dose-related.

Gastrointestinal

Nausea, vomiting, epigastric distress, abdominal cramping, diarrhea, constipation, mesenteric arterial thrombosis, ischemic colitis.

Allergic

Pharyngitis and agranulocytosis; erythematous rash, fever combined with aching and sore throat; laryngospasm, and respiratory distress.

Respiratory

Bronchospasm.

Hematologic

Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura.

Autoimmune

In extremely rare instances, systemic lupus erythematosus has been reported.

Miscellaneous

Alopecia, LE-like reactions, psoriform rashes, dry eyes, male impotence, and Peyronie's disease have been reported rarely. Oculomucocutaneous reactions involving the skin, serous membranes and conjunctivae reported for a beta-blocker (practolol) have not been associated with Inderal.

To report SUSPECTED ADVERSE REACTIONS, contact West-ward Pharmaceutical Corp. at 1-877-233-2001 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE

Inderal is not significantly dialyzable. In the event of overdose or exaggerated response, the following measures should be employed:

Hypotension and bradycardia have been reported following Inderal 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 Inderal overdose. Glucagon should be administered as 50-150 mcg/kg intravenously followed by continuous drip of 1-5 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 useful for bronchospasm.

DOSAGE & ADMINISTRATION

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

The usual dose is 1 to 3 mg administered under careful monitoring, such as electrocardiography and central venous pressure. The rate of administration should not exceed 1 mg (1 mL) per minute to diminish the possibility of lowering blood pressure and causing cardiac standstill. Sufficient time should be allowed for the drug to reach the site of action even when a slow circulation is present. If necessary, a second dose may be given after two minutes. Thereafter, additional drug should not be given in less than four hours. Additional Inderal hydrochloride should not be given when the desired alteration in rate or rhythm is achieved.

Transfer to oral therapy as soon as possible.

HOW SUPPLIED

Each mL contains 1 mg of Inderal Hydrochloride, USP in Water for Injection, USP. The pH is adjusted with anhydrous Citric Acid, USP. Supplied as: 1 mL vials in boxes of 10 (NDC 0143-9872-10).

Store at 20° to 25°C (68° to 77°F). Protect from freezing or excessive heat.

Manufactured by: HIKMA FARMACÊUTICA (PORTUGAL), S.A.

Estrada do Rio da Mó, 8, 8A e 8B – Fervença – 2705-906 Terrugem SNT, PORTUGAL

Distributed by: WEST-WARD PHARMACEUTICAL CORP.

Eatontown, NJ 07724 USA

Rev.: 05/2015

PIN166-WES/4

Inderal pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Inderal available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Inderal destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Inderal Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Inderal pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."PROPRANOLOL HYDROCHLORIDE TABLET [BRYANT RANCH PREPACK]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. "propranolol". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
  3. "propranolol". http://www.drugbank.ca/drugs/DB0057... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Inderal?

Depending on the reaction of the Inderal after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Inderal not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Inderal addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Inderal, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Inderal consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

One visitor reported frequency of use

How often in a day do you take the medicine?
Are you taking the Inderal drug as prescribed by the doctor?

Few medications can be taken Once in a day more than prescribed when the doctor's advice mentions the medicine can be taken according to frequency or severity of symptoms. Most times, be very careful and clear about the number of times you are taking the medication. The report of sDrugs.com website users about the frequency of taking the drug Inderal is mentioned below.
Visitors%
Once in a day1
100.0%

Two visitors reported doses

What is the dose of Inderal drug you are taking?
According to the survey conducted among sDrugs.com website users, the maximum number of people are using the following dose 51-100mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
Visitors%
51-100mg1
50.0%
6-10mg1
50.0%

One visitor reported age

Visitors%
> 601
100.0%

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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