Pindolol

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Pindolol
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2], Sheng Shi, M.D. [3]

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Overview

Pindolol is a beta-adrenergic blocker that is FDA approved for the treatment of hypertension. Common adverse reactions include edema, arthralgia, myalgia, dizziness, nervouseness, insomnia, fatigue.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Hypertension

Dosing Information

  • The dosage of pindolol tablets should be individualized. The recommended initial dose of pindolol tablets 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 to 4 weeks, the dose may be adjusted in increments of 10 mg/day at these intervals up to a maximum of 60 mg/day.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Pindolol in adult patients.

Non–Guideline-Supported Use

Angina Pectoris

Dosing Information

  • 10 to 40 mg/day.[1]
Cardiac Disrythmia

Dosing Information

  • Monotherapy: 2.5 to 10 mg q6h.[2]
  • Combination therapy: pindolol 15 mg bid + digoxin 0.125 to 0.5 mg/day.[3]
Hyperthyroidism

Dosing Information

  • 5 to 30 mg daily.[4]
Syncope

Dosing information

  • 2.5 mg daily to 15 mg bid.[5]

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Pindolol FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

  • There is limited information regarding Off-Label Guideline-Supported Use of Pindolol in pediatric patients.

Non–Guideline-Supported Use

  • There is limited information regarding Off-Label Non–Guideline-Supported Use of Pindolol in pediatric patients.

Contraindications

Warnings

Cardiac Failure

In Patients Without History of Cardiac Failure

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, 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 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 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 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 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

Thyrotoxicosis

Adverse Reactions

Clinical Trials Experience

  • 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 as monotherapy, given various active control drugs as monotherapy, or given placebo. Data for pindolol and the positive controls were pooled from several trials because no striking differences were seen in the individual studies, with one exception. When considering all adverse reactions reported, the frequency of edema was noticeably higher in positive control trials (16% pindolol vs. 9% positive control) than in placebo controlled trials (6% 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 patients and other selected important reactions.
This image is provided by the National Library of Medicine.
  • The following selected (potentially important) adverse reactions were seen in 2% or fewer patients and their relationship to pindolol is uncertain:

Potential Adverse Effects

  • In addition, other adverse effects not aforementioned have been reported with other beta-blockers and should be considered potential adverse effects of pindolol:

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.

Postmarketing Experience

  • There is limited information regarding Postmarketing Experience of Pindolol in the drug label.

Drug Interactions

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): 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.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pindolol in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Pindolol during labor and delivery.

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.

Geriatic Use

There is no FDA guidance on the use of Pindolol in geriatric settings.

Gender

There is no FDA guidance on the use of Pindolol with respect to specific gender populations.

Race

There is no FDA guidance on the use of Pindolol with respect to specific racial populations.

Renal Impairment

Beta-blockers should be used with caution in patients with renal function. Poor renal function has only minor effects on pindolol clearance.

Hepatic Impairment

Beta-blockers should be used with caution in patients with hepatic impairment. Poor hepatic function may cause blood levels of pindolol to increase substantially.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Pindolol in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Pindolol in patients who are immunocompromised.

Administration and Monitoring

Administration

Oral

Monitoring

There is limited information regarding the monitorization of Pindolol in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Pindolol and IV administrations.

Overdosage

No specific information on emergency treatment of overdosage is available. Therefore, on the basis of the pharmacologic actions of 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 norepinephrine, with serial monitoring of blood pressure. (There is evidence that epinephrine may be the drug of choice.)
  • Bronchospasm: Administer a beta2 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 by a hypertensive patient. Blood pressure increased and heart rate was ≥ 80 beats/min. Recovery was uneventful. In another case, 250 mg of pindolol was taken with 150 mg diazepam and 50 mg nitrazepam, producing coma and hypotension. The patient recovered in 24 hours.

Pharmacology

PindololStructure.png
300px
1 : 1 mixture (racemate)Pindolol
Systematic (IUPAC) name
(RS)-1-(1H-indol-4-yloxy)-3-(isopropylamino)propan-2-ol
Identifiers
CAS number 13523-86-9
ATC code C07AA03
PubChem 4828
DrugBank DB00960
Chemical data
Formula C14H20N2O2 
Mol. mass 248.321 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 50% to 95%
Metabolism Hepatic
Half life 3–4 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

C(AU) B(US)

Legal status

Prescription only

Routes oral, iv

Mechanism of Action

  • The mechanism of the antihypertensive effects of beta-blockers has not been established, but several mechanisms have been postulated:
  • An effect on the central nervous system resulting in a reduced sympathetic outflow to the periphery
  • Competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic receptor sites, leading to decreased cardiac output
  • An inhibition of renin release.
  • These mechanisms appear less likely for pindolol than other beta-blockers in view of the modest effect on resting cardiac output and renin.

Structure

  • Pindolol, a synthetic beta-adrenergic receptor blocking agent with intrinsic sympathomimetic activity is 1-(Indol-4-yloxy)-3-(isopropylamino)-2-propanol.
This image is provided by the National Library of Medicine.
  • Pindolol, USP is a white to off-white, crystalline powder having a faint odor which is practically insoluble in water; slightly soluble in methanol; and very slightly soluble in chloroform.
  • Each tablet for oral administration contains pindolol and the following inactive ingredients: crospovidone, lactose, magnesium stearate, microcrystalline cellulose, and pregelatinized starch.

Pharmacodynamics

  • In standard pharmacologic tests in man and animals, pindolol attenuates increases in heart rate, systolic blood pressure, and cardiac output resulting from exercise and isoproterenol administration, thus confirming its beta-blocking properties. The ISA or partial agonist activity of pindolol is mediated directly at the adrenergic receptor sites and may be blocked by other beta-blockers. In catecholamine depleted animal experiments, ISA is manifested as an increase in the inotropic and chronotropic activity of the myocardium. In man, ISA is manifested by a smaller reduction in the resting heart rate (4 to 8 beats/min) than is seen with drugs lacking ISA. There is also a smaller reduction in resting cardiac output. The clinical significance of this observation has not been evaluated and there is no evidence, or reason to believe, that exercise cardiac output is less affected by pindolol.
  • In open, long-term studies up to 4 years, no evidence of diminution of the blood pressure lowering response was observed.
  • An average 3-pound increase in body weight has been noted in patients treated with pindolol alone, a larger increase than was observed with propranolol or placebo. The weight gain appeared unrelated to blood pressure response and was not associated with an increased risk of heart failure, although edema was more common than in control patients. Pindolol does not have a consistent effect on plasma renin activity.
  • Beta-blockade therapy is useful when it is necessary to suppress the effects of beta-adrenergic agonists in order to achieve therapeutic goals. However, in certain clinical situations, (e.g., cardiac failure, heart block, bronchospasm), the preservation of an adequate sympathetic tone may be necessary to maintain vital functions. Although a beta-antagonist with ISA such as pindolol does not eliminate sympathetic tone entirely, there is no controlled evidence that it is safer than other beta-blockers in such conditions as heart failure, heart block, or bronchospasm or is less likely to cause those conditions. In single-dose studies of the effects of beta-blockers on FEV1, pindolol was indistinguishable from other non-cardioselective agents in its reduction of FEV1, and its reduction in the effectiveness of an exogenous beta-agonist.

Pharmacokinetics

Absorption
  • Pindolol is rapidly and reproducibly absorbed (greater than 95%), achieving peak plasma concentrations within 1 hour of drug administration. Pindolol has no significant first-pass effect. The blood concentrations are proportional in a linear manner to the administered dose in the range of 5 mg to 20 mg. Upon repeated administration to the same subject, variation is minimal.
Distribution
  • After a single dose, intersubject variation for peak plasma concentrations was about 4-fold (e.g., 45 to 167 ng/mL for a 20 mg dose). Upon multiple dosing, intersubject variation decreased to 2- to 2.5-fold. Pindolol is only 40% bound to plasma proteins and is evenly distributed between plasma and red cells. The volume of distribution in healthy subjects is about 2 L/kg.
Metabolism and Elimination
  • Pindolol undergoes extensive metabolism in animals and man. In man, 35% to 40% is excreted unchanged in the urine and 60% to 65% is metabolized primarily to hydroxy-metabolites which are excreted as glucuronides and ethereal sulfates. The polar metabolites are excreted with a half-life of approximately 8 hours and thus multiple dosing therapy (q.8H) results in a less than 50% accumulation in plasma. About 6% to 9% of an administered intravenous dose is excreted by the bile into the feces.
  • The disposition of pindolol after oral administration is monophasic with a half-life in healthy subjects or hypertensive patients with normal renal function of approximately 3 to 4 hours. Following t.i.d. administration (q.8H), no significant accumulation of pindolol is observed.
  • In elderly hypertensive patients with normal renal function, the half-life of pindolol is more variable, averaging about 7 hours, but with values as high as 15 hours.
  • In hypertensive patients with renal diseases, the half-life is within the range expected for healthy subjects. However, a significant decrease (50%) in volume of distribution (VD) is observed in uremic patients and VD appears to be directly correlated to creatinine clearance. Therefore, renal drug clearance is significantly reduced in uremic patients, resulting in a significant decrease in urinary excretion of unchanged drug. Uremic patients with a creatinine clearance of less than 20 mL/min generally excreted less than 15% of the administered dose unchanged in the urine.
  • In patients with histologically diagnosed cirrhosis of the liver, the elimination of pindolol was more variable in rate and generally significantly slower than in healthy subjects. The total body clearance of pindolol in cirrhotic patients ranged from about 50 to 300 mL/min and was directly correlated to antipyrine clearance. The half-life ranges from 2.5 hours to greater than 30 hours. These findings strongly suggest that caution should be exercised in dosage adjustments of pindolol in such patients.
  • The bioavailability of pindolol is not significantly affected by coadministration of food, hydralazine, hydrochlorothiazide or aspirin. Pindolol has no effect on warfarin activity or the clinical effectiveness of digoxin, although small transient decreases in plasma digoxin concentrations were noted.

Nonclinical Toxicology

  • 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.

Clinical Studies

Hypertension

How Supplied

  • Pindolol Tablets, USP are available as 5 mg and 10 mg tablets.
  • The 5 mg tablets are round white tablets, debossed "MP 178" bisected on one side and blank on the other side. Bottles of 100 CRC NDC 57664-655-88
  • The 10 mg tablets are round white tablets, debossed "MP 183" bisected on one side and blank on the other side. Bottles of 100 CRC NDC 57664-656-88

Storage

  • Store at 20° to 25°C (68° to 77°F).

Images

Drug Images

Package and Label Display Panel

PindololPackage.png
This image of the FDA label is provided by the National Library of Medicine.

Patient Counseling Information

  • 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-blockers should be advised to consult the physician at the first sign or symptom of impending failure.

Precautions with Alcohol

  • Alcohol-Pindolol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

  • Visken

Look-Alike Drug Names

There is limited information regarding Pindolol Look-Alike Drug Names in the drug label.

Drug Shortage Status

Drug Shortage

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. Frishman W, Kostis J, Strom J, Hossler M, Elkayam U, Goldner S; et al. (1979). "Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 6. A comparison of pindolol and propranolol in treatment of patients with angina pectoris. The role of intrinsic sympathomimetic activity". Am Heart J. 98 (4): 526–35. PMID 39447.
  2. Frishman W, Davis R, Strom J, Elkayam U, Stampfer M, Ribner H; et al. (1979). "Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 5. Pindolol (LB-46) therapy for supraventricular arrhythmia: a viable alternative to propranolol in patients with bronchospasm". Am Heart J. 98 (3): 393–98. PMID 38659.
  3. James MA, Channer KS, Papouchado M, Rees JR (1989). "Improved control of atrial fibrillation with combined pindolol and digoxin therapy". Eur Heart J. 10 (1): 83–90. PMID 2702970.
  4. Schelling JL, Scazziga B, Dufour RJ, Milinkovic N, Weber AA (1973). "Effect of pindolol, a beta receptor antagonist, in hyperthyroidism". Clin Pharmacol Ther. 14 (2): 158–64. PMID 4695378.
  5. Iskos D, Dutton J, Scheinman MM, Lurie KG (1998). "Usefulness of pindolol in neurocardiogenic syncope". Am J Cardiol. 82 (9): 1121–4, A9. PMID 9817494.

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