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 clearance, but poor hepatic function may cause blood levels of pindolol to increase substantially. Information for Patients Patients, especially those with evidence of coronary artery insufficiency, should be warned against interruption or discontinuation of pindolol therapy without the physician’s advice. Although cardiac failure rarely occurs in properly selected patients, patients being treated with beta-adrenergic blocking agents should be advised to consult the physician at the first sign or symptom of impending failure. Drug Interactions Catecholamine-depleting drugs (e.g., reserpine) may have an additive effect when given with beta-blocking agents. Patients receiving pindolol plus a catecholamine-depleting agent should, therefore, be closely observed for evidence of hypotension and/or marked bradycardia which may produce vertigo, syncope, or postural hypotension. Pindolol has been used with a variety of antihypertensive agents, including hydrochlorothiazide, hydralazine, and guanethidine without unexpected adverse interactions. Pindolol has been shown to increase serum thioridazine levels when both drugs are coadministered. Pindolol levels may also be increased with this combination. 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 reactions. Carcinogenesis, Mutagenesis, Impairment of Fertility In chronic oral toxicologic studies (1 to 2 years) in mice, rats, and dogs, 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 did not produce any neoplastic, preneoplastic, or nonneoplastic pathologic lesions. In fertility and general reproductive performance studies in rats, 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 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 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 Teratogenic Effects. 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, 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 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 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.