Drugs Details

Drugs Info of Inderal, Inderal LA, InnoPran XL
Drugs Details
  • Drugs Type  : Multum
  • Date : 30th Mar 2015 07:38 am
  • Brand Name : Inderal, Inderal LA, InnoPran XL
  • Generic Name : propranolol (Pronunciation: pro PRAN oh lol)
Descriptions

INNOPRAN XL contains propranolol hydrochloride, a nonselective, beta-adrenergic receptor-blocking agent for oral administration, as an extended-release product. INNOPRAN XL is available as 80-mg and 120-mg capsules which contain sustained-release beads. Each of the beads contains propranolol hydrochloride and is coated with dual membranes. These membranes are designed to retard release of propranolol hydrochloride for several hours after ingestion followed by the sustained release of propranolol.

The active ingredient in INNOPRAN XL is a synthetic beta-adrenergic receptor-blocking agent chemically described as 1-(Isopropylamino)-3-(1-naphthyloxy)-2-propanol hydrochloride. Its structural formula is:

 

INNOPRAN XL (propranolol hydrochloride) Structural Formula Illustration

Propranolol hydrochloride is a stable, white, crystalline solid, which is readily soluble in water and ethanol. Its molecular weight is 295.81. Each capsule for oral administration contains sugar spheres, ethylcellulose, povidone, hypromellose phthalate, diethyl phthalate, hypromellose, polyethylene glycol, gelatin, titanium dioxide, and black iron oxide. In addition, INNOPRAN XL 120-mg capsules contain yellow iron oxide.

What are the possible side effects of propranolol (Inderal, Inderal LA, InnoPran XL)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • fast, slow, or uneven heartbeats;
  • feeling light-headed, fainting;
  • feeling short of breath, even with mild exertion;
  • swelling of your ankles or feet;
  • nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or...

Read All Potential Side Effects and See Pictures of InnoPran XL »

What are the precautions when taking propranolol hydrochloride (InnoPran XL)?

Before taking propranolol, tell your doctor or pharmacist if you are allergic to it; or if you have had a serious reaction to other beta blockers (e.g., metoprolol); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: breathing problems (e.g., asthma, bronchitis, emphysema), heart failure, certain types of heart rhythm problems (sinus bradycardia, Wolff-Parkinson-White syndrome, second- or third-degree atrioventricular block), overactive thyroid (hyperthyroidism), kidney disease, liver disease, blood circulation problems (e.g., Raynaud's disease), a certain...

Read All Potential Precautions of InnoPran XL »


This monograph has been modified to include the generic and brand name in many instances.

Indications

INNOPRAN XL® is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including beta-blockers.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as montherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therap

Dosage Administration

INNOPRAN XL should be administered once daily at bedtime and should be taken consistently either on an empty stomach or with food. Initiate dosing at 80 mg and titrate to 120 mg daily as needed for blood pressure control. Doses above 120 mg have no additional effects on blood pressure [see Clinical Studies]. The time needed for full antihypertensive response is variable, but is usually achieved within 2 to 3 weeks.

How Supplied

Dosage Forms And Strengths

INNOPRAN XL Extended-Release Capsules are supplied as capsules containing either 80 mg, or 120 mg of propranolol hydrochloride imprinted with “InnoPran XL”. In addition, the 80 mg strength is a gray/white capsule imprinted with “80” and 2 segmented bands, while the 120 mg strength is a gray/off-white capsule imprinted with “120” and 3 segmented bands.

Storage And Handling

INNOPRAN XL (propranolol hydrochloride) Extended Release Capsules are supplied as capsules containing either 80 mg, or 120 mg propranolol hydrochloride imprinted with “InnoPran XL”.

 

Strength Color Bands NDC 24090-xxx-xx
Bottle/30 Bottle/100
80 mg Gray/white 2 450-85 450-88
120 mg Gray/off-white 3 451-85 451-88
Storage

Store at 25°C (77°F); excursions permitted to 15° and 30°C (59° and 86°F) [see USP Controlled Room Temperature] in a tightly closed container.

Manufactured for: Akrimax Pharmaceuticals, LLC Cranford, NJ 07016 By: Aptalis Pharmatech, Inc. Vandalia, OH 45377. Marketed and distributed by: Akrimax Pharmaceuticals, LLC Cranford, NJ 07016 Innopran XL®, a Diffucaps ® Drug Delivery Product Manufactured By Aptalis Pharmatech, Inc. Revised: Nov 2013


This monograph has been modified to include the generic and brand name in many instances.

Side Effects

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reactions occurring at a rate of ≥ 3%, excluding those reported more commonly in placebo, encountered in the INNOPRAN XL placebo-controlled hypertension trials and plausibly related to treatment are shown in Table 1.

Table 1: Treatment Emergent Adverse Reactions Reported In ≥ 3% of Subjects

Body System INNOPRAN XL
Placebo
(N=88)
80 mg
(N=89)
120 mg
(N=85)
Fatigue 3 (3%) 4 (5%) 6 (7%)
Dizziness (except vertigo) 2 (2%) 6 (7%) 3 (4%)
Constipation 0 3 (3%) 1 (1%)

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following reactions have been identified during post-marketing use of INNOPRAN XL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions were observed and have been reported with use of formulations of sustained-or immediate-release propranolol.

Allergic: Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions; pharyngitis and agranulocytosis; erythematous rash, fever combined with aching and sore throat, laryngospasm, and respiratory distress.

Autoimmune: Systemic lupus erythematosus (SLE).

Cardiovascular: exacerbation of peripheral arterial disease, arterial insufficiency, usually of the Raynaud type.

Central Nervous System: Light-headedness, mental depression, insomnia, lassitude, weakness, fatigue visual disturbances, hallucinations, vivid dreams, short-term memory loss, emotional lability, slightly clouded sensorium, paresthesia of hands

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

Genitourinary: Male impotence; Peyronie's disease.

Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura.

Musculoskeletal: Myopathy, myotonia

Skin and mucous membranes: Stevens-Johnson syndrome, toxic epidermal necrolysis, dry eyes, exfoliative dermatitis, erythema multiforme, urticaria, alopecia, SLE-like reactions, and psoriasisiform rashes.

Read the InnoPran XL (propranolol hydrochloride) Side Effects Center for a complete guide to possible side effects

Interactions

Pharmacokinetic Drug-Drug Interactions

Impact of Propranolol on Other Drugs

Warfarin: Warfarin concentrations are increased when administered with propranolol. Monitor prothrombin time accordingly [see CLINICAL PHARMACOLOGY].

Propafenone: Co-administration of propranolol increases the plasma concentrations of propafenone. Monitor patients for symptoms of excessive exposure to propafenone including bradycardia and postural hypotension [see CLINICAL PHARMACOLOGY].

Impact of Other Drugs on Propranolol

CYP2D6-, CYP1A2-and CYP2C19 Inhibitors: CYP2D6 inhibitors (e.g. bupropion, fluoxetine, paroxetine, quinidine), CYP1A2 inhibitors (e.g., ciprofloxacin, enoxamine, fluvoxamine) and CYP2C19 inhibitors (e.g., fluconazole, fluvoxamine, ticlopidine) increase exposure to propranolol when co-administered with INNOPRAN XL. Monitor patients for bradycardia and hypotension [see CLINICAL PHARMACOLOGY].

CYP1A2 and CYP2C19 Inducers: CYP1A2 inducers (e.g., phenytoin, montelukast, smoking) and CYP2C19 inducers (e.g. rifampin) decrease the plasma levels of propranolol resulting in a loss of efficacy [see CLINICAL PHARMACOLOGY].

Cholestyramine and Colestipol: Co-administered cholestyramine or colestipol significantly reduces the plasma concentrations of co-administered propranolol which may result in loss of efficacy [see CLINICAL PHARMACOLOGY].

Pharmacodynamic Drug-Drug Interactions

Adrenergic Agonists: Beta-blockers may antagonize the antihypertensive effects of clonidine, and rebound hypertension may result if clonidine is withdrawn abruptly. If clonidine and a beta-blocker are co-administered, withdraw the beta-blocker several days before the withdrawal of clonidine

Alpha Blockers: Co-administration of beta-blockers with alpha blocker (e.g., prazosin) has been associated with prolongation of first dose hypotension and syncope.

Dobutamine: Propranolol may reduce sensitivity to dobutamine stress echocardiography in patients undergoing evaluation for myocardial ischemia.

Antidepressants: The hypotensive effect of MAO inhibitors or tricyclic antidepressants may be exacerbated when administered with beta-blockers. Monitor patients for postural hypotension.

Nonsteroidal Anti-Inflammatory Drugs: Nonsteroidal anti-inflammatory drugs (NSAIDS) may attenuate the antihypertensive effect of beta-adrenoreceptor blocking agents. Monitor blood pressure.

Read the InnoPran XL Drug Interactions Center for a complete guide to possible interactions

Learn More »


This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Cardiac Ischemia After Abrupt Discontinuation

Following abrupt discontinuation of therapy with beta-blockers, exacerbations of angina pectoris and myocardial infarction have occurred.

When discontinuing chronically administered Innopran XL, particularly in patients with ischemic heart disease, gradually reduce the dose over a period of 1-2 weeks and monitor the patients. If angina markedly worsens or acute coronary insufficiency develops, promptly resume therapy, at least temporarily and take other measures appropriate for the management of unstable angina. Warn patients against interruption or discontinuation of therapy without physician's advice.

Because coronary artery disease is common and may be unrecognized, avoid abrupt discontinuation of Innopran XL therapy even in patients treated only for hypertension.

Cardiac Failure

Beta-blockers, like Innopran XL, can cause depression of myocardial contractility and may precipitate heart failure and cardiogenic shock. If signs or symptoms of heart failure develop, treat the patient according to recommended guidelines. It may be necessary to lower the dose of Innopran XL or to discontinue it.

Maintain During Major Surgery

Chronically administered beta-blocking therapy, including Innopran XL, should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

Masked Signs Of Hypoglycemia

Beta-blockers, like Innopran XL, may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected.

Thyrotoxicosis

Innopran XL may mask clinical signs of hyperthyroidism, such as tachycardia. Avoid abrupt withdrawal of beta-blockade, which may precipitate a thyroid storm.

Bradycardia

Bradycardia, including sinus pause, heart block, and cardiac arrest have occurred with the use of Innopran XL. Patients with first-degree atrioventricular block, sinus node dysfunction, or conduction disorders (including Wolff-Parkinson-White) may be at increased risk. The concomitant use of beta adrenergic blockers and non-dihydropyridine calcium channel blockers (e.g., verapamil and diltiazem), digoxin or clonidine increases the risk of significant bradycardia. Monitor heart rate and rhythm in patients receiving Innopran XL. If severe bradycardia develops, reduce or stop Innopran XL.

Reduced Effectiveness Of Epinephrine In Treating Anaphylaxis

Beta adrenergic blocker-treated patients treated with epinephrine for a severe anaphylactic reaction may be less responsive to the typical doses of epinephrine. In these patients, consider other medications (e.g., intravenous fluids, glucagon).

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

In dietary administration studies in which mice and rats were treated with propranolol HCl 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 MRHD of 640 mg propranolol HCl. In a study in which both male and female rats were exposed to propranolol HCl 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 2 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 propranolol HCl in bacteria (S. typhimurium strain TA 1538).

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well controlled studies in pregnant women. Intrauterine growth retardation, small placentas, and congenital anomalies have been reported for neonates whose mothers received propranolol HCl during pregnancy.

Animal Data

In a series of reproductive and developmental toxicology studies, propranolol 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 maximum recommended human oral daily dose (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). Propranolol HCl was also administered (in the feed) to rabbits (throughout pregnancy and lactation) at doses as high as 150 mg/kg/day (about 5 times the MRHD). No evidence of embryo or neonatal toxicity was noted.

Labor And Delivery

Neonates whose mothers received propranolol HCl at parturition have exhibited bradycardia, hypoglycemia, and/or respiratory depression. Adequate facilities for monitoring such infants at birth should be available.

Nursing Mothers

Propranolol is excreted in human milk.

Pediatric Use

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

Geriatric Use

Clinical studies of INNOPRAN XL did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger 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 decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Renal Impairment

The exposure to propranolol is increased in patients with renal impairment. Initiate INNOPRAN XL therapy in patients with impaired renal function at the lowest dose (80 mg) once daily and monitor patients for marked bradycardia and hypotension [see CLINICAL PHARMACOLOGY].

Hepatic Impairment

The exposure to propranolol is increased in patients with hepatic impairment. Initiate INNOPRAN XL therapy in patients with impaired hepatic function at the lowest dose (80 mg) once daily and monitor patients for marked bradycardia and hypotension [see CLINICAL PHARMACOLOGY].


This monograph has been modified to include the generic and brand name in many instances.

OverDose

Most overdoses of propranolol are mild and respond to supportive care.

Propranolol is not significantly dialyzable.

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 50-150 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.

Monitor the electrocardiogram, pulse, blood pressure, neurobehavioral status and intake and output balance. Isoproterenol and aminophylline may be used for bronchospasm.

ContrainDications

INNOPRAN XL is contraindicated in patients with:

  • Cardiogenic shock or decompensated heart failure
  • Sinus bradycardia, sick sinus syndrome, and greater than first-degree block unless a permanent pacemaker is in place
  • Bronchial asthma
  • Known hypersensitivity (e.g., anaphylactic reaction) to propranolol hydrochloride or any of the components of INNOPRAN XL.


This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Mechanism Of Action

The mechanism of the antihypertensive effect of propranolol has not been established. Among factors that contribute to the antihypertensive action are: (1) decreased cardiac output, (2) inhibition of renin release by the kidneys, and (3) diminution of tonic sympathetic nerve outflow from vasomotor centers in the brain. Although total peripheral resistance may increase initially, it readjusts to or below the pretreatment level with chronic use. Effects of propranolol on plasma volume appear to be minor and somewhat variable.

Pharmacodynamics

Propranolol 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. Of the 2 enantiomers of propranolol, the S-enantiomer blocks beta-adrenergic receptors. When access to beta-receptor sites is blocked by propranolol, chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation are decreased proportionately. At dosages greater than required for beta blockade, propranolol 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.

Pharmacokinetics

Absorption

Propranolol is highly lipophilic and is almost completely absorbed after oral administration. However, it undergoes high first-pass metabolism by the liver, and, on average, only about 25% of propranolol reaches the systemic circulation.

A single-dose, food-effect study in 36 healthy subjects showed that a high fat meal administered with INNOPRAN XL at 10 p.m., increased the lag time from 3 to 5 hours and the time to reach the maximum concentration from 11.5 to 15.4 hours, with no effect on the AUC.

Following multiple-dose administration of INNOPRAN XL at 10 p.m. under fasting conditions, the steady state lag time was between 4 and 5 hours and propranolol peak plasma concentrations were reached approximately 12 to 14 hours after dosing. Propranolol trough levels were achieved 24 to 27 hours after dosing, and persisted for 3 to 5 hours after the next dose.

The plasma levels of propranolol showed dose-proportional increases after single and multiple administration of 80-, 120-, and 160-mg of INNOPRAN XL.

At steady state, the bioavailability of a 160-mg dose of INNOPRAN XL and propranolol hydrochloride long-acting capsules did not differ significantly.

Distribution

Approximately 90% of circulating propranolol is bound to plasma proteins (albumin and alpha1 acid glycoprotein). The binding is enantiomer-selective. The S-isomer is preferentially bound to alpha1 glycoprotein and the R-isomer preferentially bound to albumin. The volume of distribution of propranolol is approximately 4 liters.

Metabolism and Elimination

Propranolol is extensively metabolized with most metabolites appearing in the urine. Propranolol is metabolized through 3 primary routes: Aromatic hydroxylation (mainly 4-hydroxylation), N-dealkylation followed by further side-chain oxidation, and direct glucuronidation. It has been estimated that the percentage contributions of these routes to total metabolism are 42%, 41%, and 17%, respectively, but with considerable variability between individuals. The 4 major metabolites are propranolol glucuronide, naphthyloxylactic acid, and glucuronic acid and sulfate conjugates of 4-hydroxy propranolol.

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

Propranolol is also a substrate for CYP2C19 and a substrate for the intestinal efflux transporter, p-glycoprotein (p-gp). Studies suggest however that p-gp is not dose-limiting for intestinal absorption of propranolol in the usual therapeutic dose range.

In healthy subjects, no difference was observed between CYP2D6 extensive metabolizers (EMs) and poor metabolizers (PMs) with respect to oral clearance or elimination half-life. Partial clearance to 4-hydroxy propranolol was significantly higher and to naphthyloxylactic acid was significantly lower in EMs than PMs.

In normal subjects receiving oral doses of racemic propranolol, S-enantiomer concentrations exceeded those of the R-enantiomer by 40 to 90% as a result of stereoselective hepatic metabolism.

The elimination half-life of propranolol was approximately 8 hours.

Specific Populations

Pediatric

The pharmacokinetics of INNOPRAN XL have not been investigated in patients younger than 18 years of age.

Geriatric

The pharmacokinetics of INNOPRAN XL have not been investigated in patients older than 65 years. In a study of 12 elderly (62 to 79 years old) and 12 young (25 to 33 years old) healthy subjects administered immediate-release propranolol, the clearance of the S-enantiomer of propranolol was decreased in the elderly. Additionally, the half-lives of both R-and Spropranolol were prolonged in the elderly compared with the young (11 hours versus 5 hours).

Gender

In a dose-proportionality study, the pharmacokinetics of INNOPRAN XL were evaluated in 22 male and 14 female healthy volunteers. Following single doses under fasting conditions, the mean AUC and Cmax were about 49% and 16% higher for females across the dosage range. The mean elimination half-life was longer in females than in males (11 hours versus 7.5 hours).

Race

A study conducted in 12 white and 13 African-American male subjects taking immediate-release propranolol showed, that at steady state, the clearance of R-and S-propranolol were about 76% and 53% higher in African-Americans than in whites, respectively.

Renal Impairment

The pharmacokinetics of propranolol after administration of INNOPRAN XL have not been evaluated in patients with renal impairment. In a study conducted in 5 patients with chronic renal failure, 6 patients on regular dialysis, and 5 healthy subjects, who received a single oral dose of 40 mg of propranolol, the peak plasma concentrations (Cmax) of propranolol in the chronic renal failure group were 3-to 5-fold (161±41 ng/mL) those observed in the dialysis patients (47±9 ng/mL) and in the healthy subjects (26±1 ng/mL). Propranolol 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 down regulation of hepatic cytochrome P450 activity.

Propranolol is not significantly dialyzable.

Hepatic Impairment

The pharmacokinetics of propranolol after administration of INNOPRAN XL have not been evaluated in patients with hepatic impairment. However, propranolol is extensively metabolized by the liver. In a study conducted in 7 patients with cirrhosis and 9 healthy subjects receiving 80-mg oral propranolol every 8 hours for 7 doses, the steady-state unbound propranolol concentration in patients with cirrhosis was 3-fold that of controls. In cirrhosis, the half-life increased to 11 hours compared to 4 hours.

Drug-Drug Interactions

Impact of Propranolol on Other Drugs

The effect of propranolol on exposure to other drugs is shown in Table 2.

Table 2 : Impact of propranolol on other drugs

Other drug Effect on their exposure
Amide anesthetics (lidocaine, bupivacaine, mepivicaine) Increased
Warfarin Increased
Propafenone Increased > 200%
Nifedipine Increased 80%
Verapamil None
Pravastatin, lovastatin Decreased 20%
Fluvastatin None
Zolmitriptan Increased 60%
Rizatriptan Increased 80%
Thioridazine Increased 370%
Diazepam Increased
Oxazepam, triazolam, lorazepam, alprazolam None
Theophylline Increased 70%
Impact of Other Drugs on Propranolol

The effect of propranolol on exposure to other drugs is shown in Table 3.

Table 3 : Impact of other drugs on exposure to propranolol

Other drug Effect on propranolol exposure
Inhibitors of CYP2D6, CYP1A2, or CYP2C19 Increased
Inducers of CYP1A2 or CYP2C19 Decreased
Quinidine Increased > 200%
Nisoldipine Increased 50%
Nicardipine Increased 80%
Chlorpromazine Increased 70%
Cimetidine Increased 50%
Cholestyramine, colestipol Decreased 50%
Alcohol Increased
Diazepam None
Verapamil None
Metochlopramide None
Ranitidine None
Lansoprazole None
Omeprazole None
Alcohol Increase acutely or decrease chronically
Propafenone Increased 200%
Quinidine Increased 200%
Cimetidine Increased 40%
Aluminum hydroxide Decreased 50%
Diazepam None
Nisoldipine, nicardipine, nifedipine Increased 50-80%
Verapamil None
Chlorpromazine Increased 70%

Clinical Studies

Hypertension

In a double-blind, parallel dose-response study in patients with mild-to-moderate hypertension (n=434), doses of INNOPRAN XL from 80 to 640 mg were taken once daily at approximately 10 p.m. INNOPRAN XL significantly lowered sitting systolic and diastolic blood pressure when measurements were taken approximately 16 hours later. The placebo-subtracted diastolic blood pressure effect for the 80-and 120-mg doses was -3.0 and -4.0 mm Hg, respectively. Higher doses of INNOPRAN XL (160, 640 mg) had no additional blood-pressure lowering effect when compared with 120 mg. The antihypertensive effects of INNOPRAN XL were seen in the elderly ( ≥ 65 years old) and men and women. There were too few non-white patients to assess the efficacy of INNOPRAN XL in these patients.


This monograph has been modified to include the generic and brand name in many instances.

Patient Information

Patient Advice

Advise patients:

  • Do not interrupt or discontinue using INNOPRAN XL without a physician's advice.
  • Patients with heart failure should consult their physician if they experience signs or symptoms of worsening heart failure such as weight gain or increasing shortness of breath.
  • Inform diabetic patients that certain signs of hypoglycemia may be masked. Patients should report any changes in blood sugar levels to their physician.

For further product information, please visit www.akrimax.com or call our medical communications department toll-free at 1-888-383-1733.


This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

PROPRANOLOL EXTENDED-RELEASE - ORAL

 

(pro-PRAN-oh-lol)

 

COMMON BRAND NAME(S): Innopran XL

 

WARNING: Do not stop using this drug without first consulting your doctor. Your condition may become worse when the drug is suddenly stopped, especially if you have chest pain (angina) or heart disease (e.g., coronary artery disease, ischemic heart disease, high blood pressure). If your doctor decides you should no longer use this drug, you must gradually decrease your dose according to your doctor's instructions.

When gradually stopping this medication, it is recommended that you temporarily limit physical activity to decrease strain on the heart. Seek immediate medical attention if you develop: worsening chest pain, tightness/pressure in the chest, chest pain spreading to the jaw/neck/arm, unusual sweating, trouble breathing, or fast/irregular heartbeat.

 

USES: This medication is a beta blocker used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks and kidney problems.

This drug works by blocking the action of certain natural chemicals in your body (such as epinephrine) that affect the heart and blood vessels. This results in a lowering of heart rate, blood pressure, and strain on the heart.

 

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

Propranolol has also been used for irregular heartbeats, shaking (tremors), and to control symptoms of anxiety or overactive thyroid (hyperthyroidism). It has been used after a heart attack to improve survival.

Propranolol may also be used to help prevent chest pain (angina) or migraine headaches. It should not be used to treat chest pain or migraines when they occur. Use other medications (e.g., nitroglycerin tablets placed under the tongue for chest pain, sumatriptan for migraines) to relieve sudden attacks as directed by your doctor. Consult your doctor or pharmacist for details.

 

HOW TO USE: See also Warning section.

Take this medication by mouth as directed by your doctor, usually once daily at bedtime. Swallow the capsules whole. Do not crush or chew the capsules. You may take this medication with or without food, but it is important to choose one way and take this medication the same way with every dose.

The dosage is based on your medical condition and response to treatment.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.

It may take 1 to 2 weeks before you get the full benefit of this drug.

If you also take certain drugs to lower your cholesterol (bile acid-binding resins such as cholestyramine or colestipol), take propranolol at least 1 hour before or at least 4 hours after these medications.

Tell your doctor if your condition worsens (e.g., your routine blood pressure readings increase).

Consumer Overview Side Effect

SIDE EFFECTS: See also Warning and Precautions sections.

Dizziness, lightheadedness, or tiredness may occur as your body adjusts to the medication. Nausea/vomiting, stomach pain, vision changes, trouble sleeping, and unusual dreams may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

This drug may reduce blood flow to your hands and feet, causing them to feel cold. Smoking may worsen this effect. Dress warmly and avoid tobacco use.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: shortness of breath, blue fingers/toes, swelling ankles/feet, mental/mood changes (e.g., depression), numbness/tingling of arms/legs, very slow heartbeat, fainting, decreased sexual ability, unexplained/sudden weight gain, increased thirst/urination.

Tell your doctor immediately if any of these rare but very serious side effects occur: easy bruising/bleeding, signs of infection (e.g., fever, persistent sore throat), aching/swollen joints.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the InnoPran XL (propranolol hydrochloride) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before taking propranolol, tell your doctor or pharmacist if you are allergic to it; or if you have had a serious reaction to other beta blockers (e.g., metoprolol); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: breathing problems (e.g., asthma, bronchitis, emphysema), heart failure, certain types of heart rhythm problems (sinus bradycardia, Wolff-Parkinson-White syndrome, second- or third-degree atrioventricular block), overactive thyroid (hyperthyroidism), kidney disease, liver disease, blood circulation problems (e.g., Raynaud's disease), a certain type of tumor (pheochromocytoma), mental/mood disorders (e.g., depression), certain muscle/nerve disease (myasthenia gravis), severe allergic reactions.

Before having surgery, tell your doctor or dentist that you are taking this medication.

If you have diabetes, this product may prevent the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). Other symptoms of a low blood sugar level, such as dizziness and sweating, are unaffected by this drug. This product also may make it harder to control your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor immediately if you have symptoms of high blood sugar such as increased thirst, hunger, and urination. Your anti-diabetic medication or diet may need to be adjusted.

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

During pregnancy, this medication should be used only when clearly needed. Infants exposed to this medication during pregnancy may have low birth weight, low blood sugar, or slow breathing/heartbeat. Discuss the risks and benefits with your doctor.

This drug passes into breast milk. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: See also How to Use section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: alpha blockers (e.g., prazosin), aluminum hydroxide, anticholinergics (e.g., atropine, scopolamine), calcium channel blockers (e.g., diltiazem, verapamil), chlorpromazine, diazepam, other drugs to treat high blood pressure (e.g., clonidine, hydralazine, methyldopa, reserpine), epinephrine, fingolimod, haloperidol, other heart medications (e.g., amiodarone, digoxin, disopyramide, propafenone, quinidine), mefloquine, rizatriptan, theophylline, thioridazine, thyroid hormones (e.g., levothyroxine), warfarin, drugs affecting liver enzymes that remove propranolol from your body (such as cimetidine, St. John's wort, certain SSRI antidepressants including fluoxetine/paroxetine/fluvoxamine, HIV protease inhibitors including ritonavir, rifamycins including rifabutin, certain anti-seizure medicines including carbamazepine).

Check the labels on all your medicines (such as cough-and-cold products, diet aids, or NSAIDs such as ibuprofen, naproxen) because they may contain ingredients that could increase your heart rate or blood pressure. Ask your pharmacist for more details.

This medication may interfere with certain laboratory tests (including glaucoma screening test, cardiovascular stress testing using arbutamine), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include unusually slow heartbeat, severe dizziness, slow or shallow breathing, weakness, or fainting.

 

NOTES: Do not share this medication with others. Lifestyle changes such as stress reduction programs, exercise and dietary changes may increase the effectiveness of this medicine. Talk to your doctor or pharmacist about lifestyle changes that might benefit you.

Have your blood pressure and pulse checked regularly while taking this medication. It may be best to learn how to monitor your own blood pressure and pulse. Discuss this with your doctor.

 

MISSED DOSE: If you miss a dose, take it as soon as you remember, but not if it is within 8 hours of the next dose. If it is within 8 hours of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

 

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

 

Information last revised December 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Inderal, Inderal LA, InnoPran XL

Generic Name: propranolol (Pronunciation: pro PRAN oh lol)

  • What is propranolol (InnoPran XL)?
  • What are the possible side effects of propranolol (InnoPran XL)?
  • What is the most important information I should know about propranolol (InnoPran XL)?
  • What should I discuss with my healthcare provider before taking propranolol (InnoPran XL)?
  • How should I take propranolol (InnoPran XL)?
  • What happens if I miss a dose (InnoPran XL)?
  • What happens if I overdose (InnoPran XL)?
  • What should I avoid while taking propranolol (InnoPran XL)?
  • What other drugs will affect propranolol (InnoPran XL)?
  • Where can I get more information?

What is propranolol (InnoPran XL)?

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 may also be used for purposes not listed in this medication guide.

Inderal 10 mg

hexagonal, orange, imprinted with INDERAL 10, I

What are the possible side effects of propranolol (InnoPran XL)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • fast, slow, or uneven heartbeats;
  • feeling light-headed, fainting;
  • feeling short of breath, even with mild exertion;
  • swelling of your ankles or feet;
  • nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
  • cold feeling in your hands and feet;
  • depression, confusion, hallucinations; or
  • severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Less serious side effects may include:

  • nausea, vomiting, diarrhea, constipation, stomach cramps;
  • decreased sex drive, impotence, or difficulty having an orgasm;
  • sleep problems (insomnia); or
  • tired feeling.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the InnoPran XL (propranolol hydrochloride) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about propranolol (InnoPran XL)?

You should not use this medication if you are allergic to propranolol, if you have asthma, a slow heart rate, or a serious heart condition such as "sick sinus syndrome" or "AV block" (unless you have a pacemaker).

If you need surgery, tell the surgeon ahead of time that you are using propranolol. You may need to stop using the medicine for a short time.

Do not skip doses or stop using propranolol without first talking to your doctor. You may need to use less and less before you stop the medication completely.

Avoid drinking alcohol. It may increase your blood levels of propranolol.

Propranolol is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

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Patient Detailed How Take

What should I discuss with my healthcare provider before taking propranolol (InnoPran XL)?

You should not use this medication if you are allergic to propranolol, if you have asthma, a slow heart rate, or a serious heart condition such as "sick sinus syndrome" or "AV block" (unless you have a pacemaker).

To make sure you can safely take propranolol, tell your doctor if you have any of these other conditions:

  • a muscle disorder;
  • bronchitis, emphysema, or other breathing disorders;
  • diabetes (propranolol can make it harder for you to tell when you have low blood sugar);
  • low blood pressure;
  • congestive heart failure;
  • depression;
  • liver or kidney disease;
  • a thyroid disorder;
  • pheochromocytoma; or
  • problems with circulation (such as Raynaud's syndrome).

FDA pregnancy category C. It is not known whether propranolol will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Propranolol can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take propranolol (InnoPran XL)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

You may take propranolol with or without food, but take it the same way each time.

Take the medicine at the same time each day.

Do not crush, chew, break, or open an extended-release capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time.

To be sure you get the correct dose, measure the liquid with a marked measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not skip doses or stop using propranolol without first talking to your doctor. You may need to use less and less before you stop the medication completely.

Your blood pressure will need to be checked often. Visit your doctor regularly.

If you need surgery, tell the surgeon ahead of time that you are using propranolol. You may need to stop using the medicine for a short time.

Propranolol is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using propranolol.

Store at room temperature away from moisture and heat.

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Patient Detailed Avoid Taking

What happens if I miss a dose (InnoPran XL)?

For regular (short-acting) propranolol: Take the missed dose as soon as you remember. Skip the missed dose if your next dose is less than 4 hours away.

For extended-release propranolol (Inderal LA, InnoPran XL and others): Take the missed dose as soon as you remember. Skip the missed dose if your next dose is less than 8 hours away.

Do not take extra medicine to make up the missed dose.

What happens if I overdose (InnoPran XL)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include slow or uneven heartbeats, dizziness, weakness, or fainting.

What should I avoid while taking propranolol (InnoPran XL)?

Avoid drinking alcohol. It may increase your blood levels of propranolol.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

What other drugs will affect propranolol (InnoPran XL)?

Tell your doctor about all other medications you use, especially:

  • cimetidine (Tagamet);
  • clonidine (Catapres);
  • digitalis (digoxin, Lanoxin);
  • dobutamine (Dobutrex);
  • haloperidol (Haldol);
  • isoproterenol (Isuprel);
  • a blood thinner such as warfarin (Coumadin, Jantoven);
  • an antidepressant such as amitriptyline (Elavil, Vanatrip, Limbitrol), clomipramine (Anafranil), desipramine (Norpramin), imipramine (Janimine, Tofranil), and others;
  • an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate);
  • aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others;
  • doxazosin (Cardura), prazosin (Minipress), terazosin (Hytrin);
  • heart or blood pressure medicine such as amlodipine (Norvasc, Caduet, Exforge, Lotrel, Tekamlo, Tribenzor, Twynsta, Amturnide), diltiazem (Cartia, Cardizem), nifedipine (Nifedical, Procardia), reserpine (Serpasil), verapamil (Calan, Covera, Isoptin, Verelan), and others;
  • amiodarone (Cordarone, Pacerone), propafenone (Rythmol), quinidine (Quin-G); or
  • an ACE inhibitor such as benazepril (Lotensin), captopril (Capoten), fosinopril (Monopril), enalapril (Vasotec), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), or trandolapril (Mavik).

This list is not complete and other drugs may interact with propranolol. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about propranolol.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 11.01. Revision date: 10/22/2012.

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