Pindolol

Contraindications

Overt heart failure, asthma/COPD, cardiogenic shock, hypersensitivity, sinus bradycardia, 2nd-3rd degree heart block, cardiogenic shock, sick sinus syndrome without permanent pacemaker

Cautions

Use caution in anesthesia/surgery (myocardial depression), bronchospastic disease, cerebrovascular insufficiency, CHF, cardiomegaly, DM, hyperthyroidism/thyrotoxicosis, myasthenia gravis, liver disease, renal impairment, peripheral vascular disease, use in pheochromocytoma, IDDM, history of psychiatric disease, pre-existing sick sinus syndrome or similar cardiac conditions

Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical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

Sudden discontinuation can exacerbate angina and lead to myocardial infarction

Less effective than thiazide diuretics in black and geriatric patients

Increased risk of stroke after surgery

Pindolol is part of the drug class:

• Beta blocking agents, non selective

Do not stop taking pindolol without talking to your doctor first. If pindolol is stopped suddenly, it may cause chest pain or heart attack in some people.

Pindolol can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

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

Call your doctor at once if you have any of these serious side effects:

• slow or uneven heartbeats;

• feeling light-headed, fainting;

• feeling short of breath, even with mild exertion;

• swelling of your ankles or feet;

• nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• depression; or

• cold feeling in your hands and feet.

Less serious side effects may include:

• decreased sex drive, impotence, or difficulty having an orgasm;

• sleep problems (insomnia);

• tired feeling; or

• anxiety, nervousness.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Hypertension:

Initial dose: 5 mg orally 2 times a day
Titration: The dose may be adjusted in increments of 10 mg per day every 3 to 4 weeks
Maximum dose: 60 mg per day

Comments:
-This drug may be taken with or without food.
-This drug may be given alone or in combination with other antihypertensive drugs.
-Antihypertensive response usually occurs within the first week of treatment.
-Maximal response may take 2 weeks or longer.

Use: For the management of hypertension as a single agent or concomitantly with other antihypertensive agents, particularly with a thiazide-type diuretic

Specific Drugs

Absorption

Bioavailability

Rapidly absorbed from the GI tract with peak plasma concentrations reached within 1–2 hours.1 2

Bioavailability 502 –95%.1 2

Onset

Effect on heart rate is seen within 3 hours.2

Hypotensive effect is usually seen within 1 week, but maximum therapeutic response may not be observed until 2 weeks or longer.1

Duration

Acute hemodynamic effects persist for 24 hours after administration.2

Food

Food may increase the rate,2 but not the extent of absorption.1

Special Populations

Bioavailability may be at the lower end of the range in uremic patients;2 extent of absorption may be decreased in patients with impaired renal function.19

Distribution

Extent

Distributed into milk.1

Plasma Protein Binding

Approximately 40–60%.1 2

Elimination

Metabolism

Extensively metabolized in the liver (approximately 60–65%) to metabolites.1 2

Elimination Route

Excreted in urine (35–50%) unchanged.1 2 18

Half-life

3–4 hours.1 2

Special Populations

In patients with creatinine clearances <20 mL/minute, <15% is excreted in urine unchanged.1 18 20

In patients with renal failure, plasma half-life is 3–11.5 hours.2 20

In geriatric patients, plasma half-life is 7–15 hours.1

In patients with hepatic cirrhosis, half-life is 2.5–30 hours.1

Storage

Oral

Tight, light-resistant containers at 15–30°C.1 31

• Inhibits response to adrenergic stimuli by competitively blocking β-adrenergic receptors within the myocardium (β1-receptors) and within bronchial and vascular smooth muscle (β2-receptors).2 4 5

• In addition, causes slight activation of the β-receptors, making the drug a partial β-agonist.2 4 5

• At higher than therapeutically obtained plasma concentrations, the drug has membrane-stabilizing activity or a quinidine-like effect.4

• Decreases stress- and exercise-stimulated heart rate.1 2 4 5 Has a lesser effect on resting heart rate (usually decreasing resting heart rate only by about 4–8 bpm or not at all),1 2 4 5 15 22 slowing of conduction in the AV node,4 and cardiac output,2 4 13 22 than do β-blockers that do not possess intrinsic sympathomimetic activity (ISA).1 2 4 5 15 22

• The precise mechanism of hypotensive effect has not been determined;1 the drug does not consistently affect cardiac output or renin release, and other mechanisms (e.g., decreased peripheral resistance) probably contribute to its hypotensive effect.1 15 16

• May increase airway resistance,1 2 4 depending on the patient’s pretreatment sympathetic tone; patients with high pretreatment tone show a decrease in forced expiratory volume in 1 second (FEV1), whereas those with low pretreatment tone may show little, if any, change in FEV1.17

In the U.S.

• Visken

In Canada

• Alti-Pindolol

Available Dosage Forms:

• Tablet

Therapeutic Class: Cardiovascular Agent

Pharmacologic Class: Beta-Adrenergic Blocker, Nonselective

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For pindolol, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to pindolol or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of pindolol in the pediatric population. Safety and efficacy have not been established .

Geriatric

No information is available on the relationship of age to the effects of pindolol in geriatric patients .

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking pindolol, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using pindolol with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Thioridazine

Using pindolol with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Bupropion
• Clonidine
• Crizotinib
• Diltiazem
• Dronedarone
• Epinephrine
• Fenoldopam
• Fingolimod
• Indacaterol
• Lacosamide
• Oxymetazoline
• Rivastigmine
• Verapamil

Using pindolol with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acarbose
• Aceclofenac
• Acemetacin
• Acetyldigoxin
• Albiglutide
• Alfuzosin
• Alogliptin
• Amiodarone
• Amtolmetin Guacil
• Arbutamine
• Aspirin
• Bromfenac
• Bufexamac
• Bunazosin
• Canagliflozin
• Celecoxib
• Chlorpropamide
• Choline Salicylate
• Clonixin
• Dapagliflozin
• Deslanoside
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Diflunisal
• Digitoxin
• Digoxin
• Dipyrone
• Doxazosin
• Droxicam
• Dulaglutide
• Empagliflozin
• Etodolac
• Etofenamate
• Etoricoxib
• Exenatide
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Flurbiprofen
• Glimepiride
• Glipizide
• Glyburide
• Ibuprofen
• Indomethacin
• Insulin Aspart, Recombinant
• Insulin Degludec
• Insulin Detemir
• Insulin Glargine, Recombinant
• Insulin Glulisine
• Insulin Human Inhaled
• Insulin Human Isophane (NPH)
• Insulin Human Regular
• Insulin Lispro, Recombinant
• Ketoprofen
• Ketorolac
• Linagliptin
• Liraglutide
• Lixisenatide
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Metformin
• Metildigoxin
• Mibefradil
• Miglitol
• Morniflumate
• Moxisylyte
• Nabumetone
• Naproxen
• Nateglinide
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Phenoxybenzamine
• Phentolamine
• Phenylbutazone
• Piketoprofen
• Pioglitazone
• Piroxicam
• Pramlintide
• Pranoprofen
• Prazosin
• Proglumetacin
• Propyphenazone
• Proquazone
• Repaglinide
• Rofecoxib
• Rosiglitazone
• Salicylic Acid
• Salsalate
• Saxagliptin
• Sitagliptin
• Sodium Salicylate
• St John's Wort
• Sulindac
• Tamsulosin
• Tenoxicam
• Terazosin
• Tiaprofenic Acid
• Tolazamide
• Tolbutamide
• Tolfenamic Acid
• Tolmetin
• Trimazosin
• Urapidil
• Valdecoxib
• Vildagliptin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of pindolol. Make sure you tell your doctor if you have any other medical problems, especially:

• Angina (severe chest pain)—May provoke chest pain if stopped too quickly .

• Asthma or
• Bradycardia (slow heartbeat) or
• Heart block or
• Heart failure—Should not use in patients with these conditions .

• Diabetes or
• Hyperthyroidism (overactive thyroid) or
• Hypoglycemia (low blood sugar)—May cover up some of the signs and symptoms of these diseases, such as a fast heartbeat .

• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal from the body .

• Lung disease (e.g., bronchitis, emphysema)—May cause difficulty with breathing in patients with this condition .

It is very important that your doctor check your progress at regular visits to make sure pindolol is working properly and to check for unwanted effects .

Pindolol may cause heart failure in some patients. Check with your doctor right away if you are having chest pain or discomfort; dilated neck veins; extreme fatigue; irregular breathing; an irregular heartbeat; shortness of breath; swelling of the face, fingers, feet, or lower legs; weight gain; or wheezing .

pindolol may cause changes in your blood sugar levels. Also, pindolol may cover up signs of low blood sugar, such as a rapid pulse rate. Check with your doctor if you have these problems or if you notice a change in the results of your blood or urine sugar tests .

Make sure any doctor or dentist who treats you knows that you are using pindolol. You may need to stop using pindolol several days before having surgery .

• It is used to treat high blood pressure.
• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Not able to sleep.
• Feeling tired or weak.
• Muscle or joint pain.
• Upset stomach.
• Feeling nervous and excitable.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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 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 A 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 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, particularly in patients with ischemic heart disease, the dosage should be gradually reduced over a period of 1 to 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 norepinephrine. 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.

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.

* Active Controls: Patients received either propranolol, α-methyldopa or a diuretic (hydrochlorothiazide or chlorthalidone).

The following selected (potentially important) adverse reactions were seen in 2% or fewer patients and their relationship to 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.

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 during investigational use and extensive foreign experience amounting to over 4 million patient-years.

In elderly hypertensive patients, the half-life is more variable, averaging 7 h.

Hypertension: Oral: Initial: 5 mg twice daily; increase as necessary by 10 mg daily every 3 to 4 weeks; usual range: 10 to 40 mg/day (JNC 7 [Chobanian 2003]); maximum: 60 mg/day

Antidepressant augmentation (off-label use): Oral: 2.5 to 5 mg 3 times daily (Ballesteros 2004; Geretsegger 2008; Portella 2011)

Atrial fibrillation (rate control) (off-label use): Initial: 5 mg twice daily; may increase at weekly intervals to 15 mg twice daily. May use in combination with digoxin (James 1989).