Pindolol Mylan

Pindolol Mylan ® (pindolol) is indicated in the management of hypertension. It may be used alone or concomitantly with other antihypertensive agents, particularly with a thiazide-type diuretic.

The dosage of Pindolol Mylan ® (pindolol) should be individualized. The recommended initial dose of Pindolol Mylan® (pindolol) is 5 mg b.i.d. alone or in combination with other antihypertensive agents. An antihypertensive response usually occurs within the first week of treatment. Maximal response, however, may take as long as or occasionally longer than 2 weeks. If a satisfactory reduction in blood pressure does not occur within 3-4 weeks, the dose may be adjusted in increments of 10 mg/day at these intervals up to a maximum of 60 mg/day.

Pindolol Mylan ® (pindolol) is contraindicated in: 1) bronchial asthma; 2) overt cardiac failure; 3) cardiogenic shock; 4) second and third degree heart block; 5) severe bradycardia. (See WARNINGS)

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, if necessary, Pindolol Mylan ® (pindolol) can be used with caution in patients with a history of failure who are well-compensated, usually with digitalis and diuretics. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase risk of bradycardia. Beta-adrenergic blocking agents do not abolish the inotropic action of digitalis on heart muscle.

In Patients Without History of Cardiac Failure

In patients with latent cardiac insufficiency, continued depression of the myocardium with beta-blocking agents over a period of time can in some cases lead to cardiac failure. At the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or be given a diuretic, and the response observed closely. If cardiac failure continues, despite adequate digitalization and diuretic, Pindolol Mylan ® (pindolol) therapy should be withdrawn (gradually if possible).

Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal

Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy. When discontinuing chronically administered Pindolol Mylan® (pindolol), particularly in patients with ischemic heart disease, the dosage should be gradually reduced over a period of 1-2 weeks and the patient should be carefully monitored. If angina markedly worsens or acute coronary insufficiency develops, Pindolol Mylan® (pindolol) administration should be reinstituted promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue Pindolol Mylan® (pindolol) therapy abruptly even in patients treated only for hypertension.

Nonallergic Bronchospasm (e.g., chronic bronchitis, emphysema) - Patients with Bronchospastic Diseases Should in General Not Receive Beta - Blockers

Pindolol Mylan ® (pindolol) should be administered with caution since it may block bronchodilation produced by endogenous or exogenous catecholamine stimulation of beta2 receptors.

Major Surgery

Because beta blockade impairs the ability of the heart to respond to reflex stimuli and may increase the risks of general anesthesia and surgical procedures, resulting in protracted hypotension or low cardiac output, it has generally been suggested that such therapy should be gradually withdrawn several days prior to surgery. Recognition of the increased sensitivity to catecholamines of patients recently withdrawn from beta-blocker therapy, however, has made this recommendation controversial. If possible, beta-blockers should be withdrawn well before surgery takes place. In the event of emergency surgery, the anesthesiologist should be informed that the patient is on beta-blocker therapy.

The effects of Pindolol Mylan ® (pindolol) can be reversed by administration of beta-receptor agonists such as isoproterenol, dopamine, dobutamine, or levarterenol. Difficulty in restarting and maintaining the heart beat has also been reported with beta-adrenergic receptor blocking agents.

Diabetes and Hypoglycemia

Beta-adrenergic blockade may prevent the appearance of premonitory signs and symptoms (e.g., tachycardia and blood pressure changes) of acute hypoglycemia. This is especially important with labile diabetics. Beta-blockade also reduces the release of insulin in response to hyperglycemia; therefore, it may be necessary to adjust the dose of antidiabetic drugs.

Thyrotoxicosis

Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-blockade which might precipitate a thyroid crisis.

PRECAUTIONS

Impaired Renal or Hepatic Function

Beta-blocking agents should be used with caution in patients with impaired hepatic or renal function. Poor renal function has only minor effects on Pindolol Mylan ® (pindolol) clearance, but poor hepatic function may cause blood levels of Pindolol Mylan® (pindolol) to increase substantially.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In chronic oral toxicologic studies (1-2 years) in mice, rats, and dogs, Pindolol Mylan ® (pindolol) did not produce any significant toxic effects. In 2-year oral carcinogenicity studies in rats and mice in doses as high as 59 mg/kg/day and 124 mg/kg/day (50 and 100 times the maximum recommended human dose), respectively, Pindolol Mylan® (pindolol) did not produce any neoplastic, preneoplastic, or nonneoplastic pathologic lesions. In fertility and general reproductive performance studies in rats, Pindolol Mylan® (pindolol) caused no adverse effects at a dose of 10 mg/kg.

In the male fertility and general reproductive performance test in rats, definite toxicity characterized by mortality and decreased weight gain was observed in the group given 100 mg/kg/day. At 30 mg/kg/day, decreased mating was associated with testicular atrophy and/or decreased spermatogenesis. This response is not clearly drug related, however, as there was no dose response relationship within this experiment and no similar effect on testes of rats administered Pindolol Mylan ® (pindolol) as a dietary admixture for 104 weeks. There appeared to be an increase in prenatal mortality in males given 100 mg/kg but development of offspring was not impaired.

In females administered Pindolol Mylan ® (pindolol) prior to mating through day 21 of lactation, mating behavior was decreased at 100 mg/kg and 30 mg/kg. At these dosages there also was increased mortality of offspring. Prenatal mortality was increased at 10 mg/kg but there was not a clear dose response relationship in this experiment. There was an increased resorption rate at 100 mg/kg observed in females necropsied on the 15th day of gestation.

Pregnancy

Category B

Studies in rats and rabbits exceeding 100 times the maximum recommended human doses, revealed no embryotoxicity or teratogenicity. Since there are no adequate and well-controlled studies in pregnant women, and since animal reproduction studies are not always predictive of human response, Pindolol Mylan ® (pindolol), as with any drug, should be employed during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Since Pindolol Mylan ® (pindolol) is secreted in human milk, nursing should not be undertaken by mothers receiving the drug.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Clinical Laboratory

Minor persistent elevations in serum transaminases (SGOT, SGPT) have been noted in 7% of patients during Pindolol Mylan ® (pindolol) administration, but progressive elevations were not observed. These elevations were not associated with any other abnormalities that would suggest hepatic impairment, such as decreased serum albumin and total proteins. During more than a decade of worldwide marketing, there have been no reports in the medical literature of overt hepatic injury. Alkaline phosphatase, lactic acid dehydrogenase (LDH), and uric acid are also elevated on rare occasions. The significance of these findings is unknown.

Most adverse reactions have been mild. The incidences listed in the following table are derived from 12-week comparative double-blind, parallel design trials in hypertensive patients given Pindolol Mylan ® (pindolol) as monotherapy, given various active control drugs as monotherapy, or given placebo. Data for Pindolol Mylan® (pindolol) and the positive controls were pooled from several trials because no striking differences were seen in the individual studies, with 1 exception. When considering all adverse reactions reported, the frequency of edema was noticeably higher in positive control trials [16% Pindolol Mylan® (pindolol) vs. 9% positive control] than in placebo controlled trials [6%Pindolol Mylan® (pindolol) vs. 3% placebo]. The table includes adverse reactions either volunteered or elicited, and at least possibly drug related, which were reported in greater than 2% of Pindolol Mylan® (pindolol) patients and other selected important reactions.

Adverse Reactions Which Were Volunteered or Elicited (and at least possibly drug related)

The following selected (potentially important) adverse reactions were seen in 2% or fewer patients and their relationship to Pindolol Mylan ® (pindolol) is uncertain. CENTRAL NERVOUS SYSTEM: anxiety, lethargy; AUTONOMIC NERVOUS SYSTEM: visual disturbances, hyperhidrosis; CARDIOVASCULAR: bradycardia, claudication, cold extremities, heart block, hypotension, syncope, tachycardia, weight gain; GASTROINTESTINAL: diarrhea, vomiting; RESPIRATORY: wheezing; UROGENITAL: impotence, pollakiuria; MISCELLANEOUS: eye discomfort or burning eyes.

Potential Adverse Effects

In addition, other adverse effects not aforementioned have been reported with other beta-adrenergic blocking agents and should be considered potential adverse effects of Pindolol Mylan ® (pindolol).

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

Cardiovascular : Intensification of AV block. (See CONTRAINDICATIONS)

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

Hematologic : Agranulocytosis; thrombocytopenic and nonthrombocytopenic purpura.

Gastrointestinal: Mesenteric arterial thrombosis; ischemic colitis.

Miscellaneous : Reversible alopecia; Peyronie's disease.

The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with Pindolol Mylan ® (pindolol) during investigational use and extensive foreign experience amounting to over 4 million patient-years.

No specific information on emergency treatment of overdosage is available. Therefore, on the basis of the pharmacologic actions of Pindolol Mylan ® (pindolol), the following general measures should be employed as appropriate in addition to gastric lavage:

Excessive Bradycardia : administer atropine; if there is no response to vagal blockade, administer isoproterenol cautiously.

Cardiac Failure : digitalize the patient and/or administer diuretic. It has been reported that glucagon may be useful in this situation.

Hypotension : administer vasopressors, e.g., epinephrine or levarterenol, with serial monitoring of blood pressure. (There is evidence that epinephrine may be the drug of choice.)

Bronchospasm : administer a beta 2 stimulating agent such as isoproterenol and/or a theophylline derivative.

A case of an acute overdosage has been reported with an intake of 500 mg of Pindolol Mylan ® (pindolol) by a hypertensive patient. Blood pressure increased and heart rate was ³80 beats/min. Recovery was uneventful. In another case, 250 mg of Pindolol Mylan® (pindolol) was taken with 150 mg diazepam and 50 mg nitrazepam, producing coma and hypotension. The patient recovered in 24 hours.