Levatol

Mechanism of Action

Beta adrenergic receptor blocker; intrinsic sympathomimetic activity (lowers BP with little decrease in HR)

Pharmacokinetics

Half-Life: 5 hr

Peak Plasma: 2-3 hr

Duration: >20 hr

Peak effect: 1.3-3 hr

Protein bound: 80-98%

Metabolism: Liver (oxidation and conjugation)

Excretion: Urine

This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

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:

• slow or uneven heartbeats;
• feeling short of breath, even with mild exertion;
• swelling, rapid weight gain; or
• feeling like you might pass out.

Less serious side effects may include:

• headache;
• feeling tired;
• dizziness;
• nausea, diarrhea, upset stomach;
• decreased interest in sex; or
• cold symptoms such as stuffy nose, sneezing, sore throat.

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.

levatol® is usually well tolerated in properly selected patients. Most adverse effects observed during clinical trials have been mild and reversible.

Table 1 lists the adverse reactions reported from 4 controlled studies conducted in the United States involving once-a-day administration of levatol® (at doses ranging from 10 to 120 mg) as monotherapy or in combination with hydrochlorothiazide. levatol® doses above 40 mg/day are not, however, recommended. The table includes only those events where the prevalence rate in the levatol® group was at least 1.5%, or where the reaction is of particular interest.

Over a dose range from 10 to 40 mg, once a day, fatigue, nausea, and sexual impotence occurred at a greater frequency as the dose was increased.

Table 1: ADVERSE REACTIONS DURING CONTROLLED US STUDIES

In a double-blind clinical trial comparing levatol® (40 mg and greater once a day) and propranolol (40 mg or more twice a day), heart rates of less than 60 beats/min. were recorded at least once in 25% of the patients in the group receiving levatol® and in 37% of the patients in the propranolol group. Corresponding figures for heart rates of less than 50 beats/min. were 1.2% and 6% respectively. No symptoms associated with bradycardia were reported.

Discontinuations of levatol® because of adverse reactions have ranged between 2.4% and 6.9% of patients in double-blind, parallel, controlled clinical trials, as compared to 1.8% to 4.1% in the corresponding control groups that were given placebo. The frequency and severity of adverse reactions have not increased during long-term administration of levatol®. The prevalence of adverse reactions reported from 4 controlled clinical trials (referred to in Table 1) as reasons for discontinuation of therapy by ≥ 0.5% of the levatol® group is listed in Table 2.

Table 2: DISCONTINUATIONS DURING CONTROLLED US STUDIES

Potential Adverse Effects: In addition, certain adverse effects not listed above have been reported with other β-blocking agents and should also be considered as potential adverse effects of levatol®.

Central Nervous System: Reversible mental depression progressing to catatonia (an acute syndrome characterized by disorientation for time and place), short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance (neuropsychometrics).

Cardiovascular: Intensification of AV block (see CONTRAINDICATIONS).

Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm, and respiratory distress.

Hematologic: Agranulocytosis, nonthrombocytopenic and thrombocytopenic purpura.

Gastrointestinal: Mesenteric arterial thrombosis and ischemic colitis.

Miscellaneous: Reversible alopecia and Peyronie's disease. The oculomucocutaneous syndrome associated with the β-blocker practolol has not been reported with levatol® during investigational use and extensive foreign clinical experience.

In the U.S.

• Levatol

Available Dosage Forms:

• Tablet

Therapeutic Class: Cardiovascular Agent

Pharmacologic Class: Penbutolol

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Chest pain
• difficult or labored breathing
• increased sweating
• pain in the limbs
• shortness of breath
• tightness in the chest
• wheezing

• Abdominal or stomach tenderness
• abdominal or stomach pain, usually after eating a meal
• black, tarry stools
• blood in the urine
• bloody nose
• bloody stools
• constipation
• cough or hoarseness
• diarrhea
• fever with or without chills or sore throat
• general feeling of tiredness or weakness
• heavier menstrual periods
• lower back or side pain
• nausea
• painful or difficult urination
• pinpoint red spots on the skin
• rectal bleeding
• skin rash
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting
• worsening of heart block

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Blurred vision
• chest pain or discomfort
• confusion
• difficulty with breathing
• dilated neck veins
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• extreme fatigue
• irregular breathing
• noisy breathing
• slow or irregular heartbeat
• sweating
• swelling of the face, fingers, feet, or lower legs
• weight gain

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Headache

• Acid or sour stomach
• belching
• body aches or pain
• chills
• difficulty with breathing
• ear congestion
• fever
• heartburn
• indigestion
• lack or loss of strength
• loss of voice
• nasal congestion
• nausea
• runny nose
• sleeplessness
• sneezing
• sore throat
• stomach discomfort, upset, or pain
• trouble sleeping
• unable to sleep

• Decreased interest in sexual intercourse
• inability to have or keep an erection
• loss in sexual ability, desire, drive, or performance

• Crying
• decreased awareness or responsiveness
• depersonalization
• dysphoria
• euphoria
• hair loss or thinning of the hair
• memory loss
• mental depression
• mimicry of speech or movements
• mutism
• negativism
• pain of the penis on erection
• paranoia
• peculiar postures or movements, mannerisms or grimacing
• quick to react or overreact emotionally
• rapidly changing moods
• reddened skin
• severe sleepiness
• skin rash

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• Keep taking Levatol as you have been told by your doctor or other health care provider, even if you feel well.
• To gain the most benefit, do not miss doses.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Levatol or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Levatol (penbutolol). This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Cardiac Failure: Sympathetic stimulation may be essential for supporting circulatory function in patients with heart failure, and its inhibition by ß-adrenergic receptor blockade may precipitate more severe failure. Although ß-blockers should be avoided in overt congestive heart failure, Levatol® can, if necessary, be used with caution in patients with a history of cardiac failure who are well compensated, on treatment with vasodilators, digitalis and/or diuretics. Both digitalis and penbutolol slow AV conduction. Beta-adrenergic receptor antagonists do not inhibit the inotropic action of digitalis on heart muscle. If cardiac failure persists, treatment with Levatol® should be discontinued.

Patients Without History of Cardiac Failure: Continued depression of the myocardium with ß-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first evidence of heart failure, patients receiving Levatol® should be given appropriate treatment, and the response should be closely observed. If cardiac failure continues despite adequate intervention with appropriate drugs, Levatol® should be withdrawn (gradually, if possible).

Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal: Hypersensitivity to catecholamines has been observed in patients who were withdrawn from therapy with ß-blocking agents; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy. When discontinuing Levatol®, particularly in patients with ischemic heart disease, the dosage should be reduced gradually over a period of 1 to 2 weeks and the patient should be monitored carefully. If angina becomes more pronounced or acute coronary insufficiency develops, administration of Levatol® should be reinstated promptly, at least on a temporary basis, and appropriate measures should be taken for the management of unstable angina. Patients should be warned against interruption or discontinuation of therapy without the physician’s advice. Because coronary artery disease is common and may not be recognized, it may not be prudent to discontinue Levatol® abruptly, even in patients who are being treated only for hypertension.

Nonallergic Bronchospasm (eg, chronic bronchitis,emphysema): Levatol® is contraindicated in bronchial asthma. In general, patients with bronchospastic diseases should not receive ß-blockers. Levatol® should be administered with caution because it may block bronchodilation produced by endogenous catecholamine stimulation of ß-2 receptors.

Major Surgery: Chronically administered beta-blocking therapy 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.

Diabetes Mellitus and Hypoglycemia: Beta-adrenergic receptor blockade may prevent the appearance of signs and symptoms of acute hypoglycemia, such as tachycardia and blood pressure changes. This is especially important in patients with labile diabetes. Beta-blockade also reduces the release of insulin in response to hyperglycemia; therefore, it may be necessary to adjust the dose of hypoglycemic drugs. Beta-adrenergic blockade may also impair the homeostatic response to hypoglycemia; in that event, the spontaneous recovery from hypoglycemia may be delayed during treatment with ß-adrenergic receptor antagonists.

Thyrotoxicosis: Beta-adrenergic blockade may mask certain clinical signs (eg, tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of ß-adrenergic receptor blockers that might precipitate a thyroid storm.

Substance Name

Penbutolol

CAS Registry Number

36507-48-9

Drug Class

Antihypertensive Agents

Adrenergic Beta-Antagonists

Antiarrhythmics