Bisoprolol Fumarate
FDA Drug Information • Also known as: Bisoprolol, Bisoprolol Fumarate
- Brand Names
- Bisoprolol, Bisoprolol Fumarate
- Route
- ORAL
- Dosage Form
- TABLET, FILM COATED
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
DESCRIPTION BISOPROLOL FUMARATE USP is a synthetic, beta 1 -selective (cardioselective) adrenoceptor blocking agent. The chemical name for bisoprolol fumarate is (±)-1-[4-[[2- (1-Methylethoxy)ethoxy]methyl]phenoxy]-3-[(1-methylethyl)amino]-2-propanol (E)-2- butenedioate (2:1) (salt). It possesses an asymmetric carbon atom in its structure and is provided as a racemic mixture. The S(-) enantiomer is responsible for most of the beta- blocking activity. Its molecular formula is (C 18 H 31 NO 4 ) 2
What Is Bisoprolol Fumarate Used For?
INDICATIONS & USAGE Bisoprolol fumarate is indicated in the management of hypertension. It may be used alone or in combination with other antihypertensive agents.
Dosage and Administration
DOSAGE & ADMINISTRATION The dose of Bisoprolol fumarate must be individualized to the needs of the patient. The usual starting dose is 5 mg once daily. In some patients, 2.5 mg may be an appropriate starting dose (see Bronchospastic Disease in WARNINGS ). If the antihypertensive effect of 5 mg is inadequate, the dose may be increased to 10 mg and then, if necessary, to 20 mg once daily. Patients with Renal or Hepatic Impairment In patients with hepatic impairment (hepatitis or cirrhosis) or renal dysfunction (creatinine clearance less than 40 mL/min), the initial daily dose should be 2.5 mg and caution should be used in dose-titration. Since limited data suggest that bisoprolol fumarate is not dialyzable, drug replacement is not necessary in patients undergoing dialysis. Geriatric Patients It is not necessary to adjust the dose in the elderly, unless there is also significant renal or hepatic dysfunction (see above and Geriatric Use in PRECAUTIONS ). Pediatric Patients There is no pediatric experience with Bisoprolol fumarate.
Side Effects (Adverse Reactions)
ADVERSE REACTIONS Safety data are available in more than 30,000 patients or volunteers. Frequency estimates and rates of withdrawal of therapy for adverse events were derived from two U.S. placebo-controlled studies. In Study A, doses of 5, 10, and 20 mg bisoprolol fumarate were administered for 4 weeks. In Study B, doses of 2.5, 10, and 40 mg of bisoprolol fumarate were administered for 12 weeks. A total of 273 patients were treated with 5 to 20 mg of bisoprolol fumarate; 132 received placebo. Withdrawal of therapy for adverse events was 3.3% for patients receiving bisoprolol fumarate and 6.8% for patients on placebo. Withdrawals were less than 1% for either bradycardia or fatigue/lack of energy. The following table presents adverse experiences, whether or not considered drug related, reported in at least 1% of patients in these studies, for all patients studied in placebo-controlled clinical trials (2.5 to 40 mg), as we l as for a subgroup that was treated with doses within the recommended dosage range (5 to 20 mg). Of the adverse events listed in the table, bradycardia, diarrhea, asthenia, fatigue, and sinusitis appear to be dose related. B o d y Sys te m / Adv er s e Ex p erience All Adv e r s e E x p e r i e n c e s ( % a) B i s oprolol Fum a r a te P l a c ebo ( n = 132 ) % 5 to 20 mg 2 . 5 to 40 mg ( n = 273 ) % ( n = 404 ) % S kin increased sweating 1.5 0.7 1.0 M u s c u l o s k e l e t a l arthralgia 2.3 2.2 2.7 Central Nervous System dizziness 3.8 2.9 3.5 headache 11.4 8.8 10.9 hypoesthesia 0.8 1.1 1.5 Autonomic N er v ou s System dry mouth 1.5 0.7 1.3 H e a r t Rate / Rhythm bradycardia 0 0.4 0.5 Psy c h i at ric vivid dreams 0 0 0 insomnia 2.3 1.5 2.5 depression 0.8 0 0.2 Gas trointe s tin a l diarrhea 1.5 2.6 3.5 nausea 1.5 1.5 2.2 vomiting 0 1.1 1.5 R e s p i r a t o r y Bronchospasm 0 0 0 cough 4.5 2.6 2.5 dyspnea 0.8 1.1 1.5 pharyngitis 2.3 2.2 2.2 rhinitis 3.0 2.9 4.0 sinusitis 1.5 2.2 2.2 URI 3.8 4.8 5.0 B o d y as a Whole asthenia 0 0.4 1.5 chest pain 0.8 1.1 1.5 fatigue 1.5 6.6 8.2 edema (peripheral) 3.8 3.7 3.0 cough 4.5 2.6 2.5 dyspnea 0.8 1.1 1.5 pharyngitis 2.3 2.2 2.2 rhinitis 3.0 2.9 4.0 sinusitis 1.5 2.2 2.2 URI 3.8 4.8 5.0 a percentage of patients with event The following is a comprehensive list of adverse experiences reported with bisoprolol fumarate in worldwide studies, or in postmarketing experience (in italics): Central Nervous System Dizziness, unsteadiness , vertigo, syncope, headache, paresthesia, hypoesthesia, hyperesthesia, somnolence, sleep disturbances , anxiety/restlessness, decreased concentration/memory. Autonomic Nervous System Dry mouth Cardiovascular Bradycardia, palpitations and other rhythm disturbances, cold extremities, claudication, hypotension, orthostatic hypotension, chest pain, congestive heart failure, dyspnea on exertion Psychiatric Vivid dreams, insomnia, depression. Gastrointestinal Gastric/epigastric/abdominal pain, gastritis, dyspepsia, nausea, vomiting, diarrhea, constipation, peptic ulcer Musculoskeletal Muscle/joint pain, arthralgia , back/neck pain, muscle cramps, twitching/tremor. Skin Rash, acne, eczema, psoriasis , skin irritation, pruritus, flushing, sweating, alopecia, dermatitis, angioedema, exfoliative dermatitis , cutaneous vasculitis Special Senses Visual disturbances, ocular pain/pressure, abnormal lacrimation, tinnitus, decreased hearing, earache, taste abnormalities. Metabolic Gout Respiratory Asthma/bronchospasm, bronchitis, coughing, dyspnea, pharyngitis, rhinitis, sinusitis, URI. Genitourinary Decreased libido/impotence, Peyronie's disease , cystitis, renal colic, polyuria. Hematologic Purpura. General Fatigue, asthenia, chest pain, malaise, edema, weight gain, angioedema. In addition, a variety of adverse effects have been reported with other beta-adrenergic blocking agents and should be considered potential adverse effects of Bisoprolol fumarate: Central Nervous System Reversible mental depression progressing to catatonia, hallucinations, an...
Warnings and Precautions
WARNINGS Cardiac Failure Sympathetic stimulation is a vital component supporting circulatory function in the setting of congestive heart failure, and beta-blockade may result in further depression of myocardial contractility and precipitate more severe failure. In general, beta-blocking agents should be avoided in patients with overt congestive failure. However, in some patients with compensated cardiac failure it may be necessary to utilize them. In such a situation, they must be used cautiously. In Patients Without a History of Cardiac Failure Continued depression of the myocardium with beta-blockers can, in some patients, precipitate cardiac failure. At the first signs or symptoms of heart failure, discontinuation of Bisoprolol fumarate should be considered. In some cases, beta-blocker therapy can be continued while heart failure is treated with other drugs. Abrupt Cessation of Therapy Exacerbation of angina pectoris, and, in some instances, myocardial infarction or ventricular arrhythmia, have been observed in patients with coronary artery disease following abrupt cessation of therapy with beta-blockers. Such patients should, therefore, be cautioned against interruption or discontinuation of therapy without the physician's advice. Even in patients without overt coronary artery disease, it may be advisable to taper therapy with Bisoprolol fumarate over approximately one week with the patient under careful observation. If withdrawal symptoms occur, Bisoprolol fumarate therapy should be reinstituted, at least temporarily. Peripheral Vascular Disease Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. Caution should be exercised in such individuals. Bronchospastic Disease PATIENTS WITH BRONCHOSPASTIC DISEASE SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS. Because of its relative beta 1 -selectivity, however, Bisoprolol fumarate may be used with caution in patients with bronchospastic disease who do not respond to, or who cannot tolerate other antihypertensive treatment. Since beta1-selectivity is not absolute, the lowest possible dose of BISOPROLOL FUMARATE should be used, with therapy starting at 2.5 mg. A beta 2 agonist (bronchodilator) should be made available. 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 risk of general anesthesia and surgical procedures. Diabetes and Hypoglycemia Beta-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia. Nonselective beta-blockers may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels. Because of its beta1-selectivity, this is less likely with Bisoprolol fumarate. However, patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, should be...
Drug Interactions
DRUG INTERACTIONS Bisoprolol fumarate should not be combined with other beta-blocking agents. Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be closely monitored, because the added beta-adrenergic blocking action of Bisoprolol fumarate may produce excessive reduction of sympathetic activity. In patients receiving concurrent therapy with clonidine, if therapy is to be discontinued, it is suggested that Bisoprolol fumarate be discontinued for several days before the withdrawal of clonidine. Bisoprolol fumarate should be used with care when myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes), or antiarrhythmic agents, such as disopyramide, are used concurrently. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. Concurrent use of rifampin increases the metabolic clearance of Bisoprolol fumarate, resulting in a shortened elimination half-life of Bisoprolol fumarate. However, initial dose modification is generally not necessary. Pharmacokinetic studies document no clinically relevant interactions with other agents given concomitantly, including thiazide diuretics and cimetidine. There was no effect of Bisoprolol fumarate on prothrombin time in patients on stable doses of warfarin. 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.
Contraindications
CONTRAINDICATIONS Bisoprolol fumarate is contraindicated in patients with cardiogenic shock, overt cardiac failure, second or third degree AV block, and marked sinus bradycardia.
Overdosage
OVERDOSAGE The most common signs expected with overdosage of a beta-blocker are bradycardia, hypotension, congestive heart failure, bronchospasm, and hypoglycemia. To date, a few cases of overdose (maximum: 2000 mg) with bisoprolol fumarate have been reported. Bradycardia and/or hypotension were noted. Sympathomimetic agents were given in some cases, and all patients recovered. In general, if overdose occurs, Bisoprolol fumarate therapy should be stopped and supportive and symptomatic treatment should be provided. Limited data suggest that bisoprolol fumarate is not dialyzable. Based on the expected pharmacologic actions and recommendations for other beta-blockers, the following general measures should be considered when clinically warranted: Bradycardia Administer IV atropine. If the response is inadequate, isoproterenol or another agent with positive chronotropic properties may be given cautiously. Under some circumstances, transvenous pacemaker insertion may be necessary. Hypotension IV fluids and vasopressors should be administered. Intravenous glucagon may be useful. Heart Block (second or third degree) Patients should be carefully monitored and treated with isoproterenol infusion or transvenous cardiac pacemaker insertion, as appropriate. Congestive Heart Failure Initiate conventional therapy (i.e., digitalis, diuretics, inotropic agents, vasodilating agents). Bronchospasm Administer bronchodilator therapy such as isoproterenol and/or aminophylline. Hypoglycemia Administer IV glucose.
How Supplied
HOW SUPPLIED Bisoprolol fumarate is supplied as 5 mg and 10 mg tablets. The 5 mg tablet is pink colored, biconvex, round, film coated tablet debossed with N on one side and scored on the other side with 5 debossed on either side of the score. Bottles of 30: NDC 69339-236-03 Bottles of 100: NDC 69339-236-01 The 10 mg tablet is white colored, biconvex, round, film coated tablet debossed with N on one side and 10 on the other side. Bottles of 30: NDC 69339-237-03 Bottles of 100: NDC 69339-237-01 Store at 20° to 25°C (68° to 77°F). [see USP Control ed Room Temperature]. Protect from moisture. Dispense in tight, light-resistant containers. Please address medical inquiries to NATCO PHARMA LLC at 1-201-786-6500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Manufactured by: NATCO PHARMA LIMITED Kothur- 509 228, Telangana, India Manufactured for: NATCO Pharma USA LLC, Parsippany, NJ 07054, USA Revised: 9/2024
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.