Clinical medicine profile
Bisoprolol
Therapeutic agent (verify pharmacological class)
- Route
- See product SmPC
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
Contraindications
- CONTRAINDICATIONS Bisoprolol fumarate tablets are contraindicated in patients with cardiogenic shock, overt cardiac failure, second or third degree AV block, and marked sinus bradycardia.
Precautions
- WARNINGS Click here to enter 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 tablets 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 tablets over approximately one week with the patient under careful observation.
- If withdrawal symptoms occur, bisoprolol fumarate tablets 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.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
DOSAGE AND ADMINISTRATION The dose of bisoprolol fumarate tablets 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 tablets.
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
Indications
- INDICATIONS AND USAGE Bisoprolol fumarate tablets are indicated in the management of hypertension.
- It may be used alone or in combination with other antihypertensive agents.
- Clinical selection for Bisoprolol should follow culture results where relevant, Kenya STG/EML recommendations, and the current product SmPC.
- Class context: Therapeutic agent (verify pharmacological class).
- Confirm site-specific dose, duration and monitoring before prescribing.
Adverse effects
- 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 5-20 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 (2.5-40 mg), as well as for a subgroup that was treated with doses within the recommended dosage range (5-20 mg).
- Of the adverse events listed in the table, bradycardia, diarrhea, asthenia, fatigue, and sinusitis appear to be dose related.
- Body System/Adverse Experience All Adverse Experiences (% a ) Bisoprolol Fumarate Placebo (n=132) % 5-20 mg (n=273) % 2.5-40 mg (n=404) % Skin increased sweating 1.5 0.7 1.0 Musculoskeletal arthralgia 2.3 2.2 2.7 Central Nervous System dizziness 3.8 2.9 3.5 headache 11.4 8.8 10.9 hypoaesthesia 0.8 1.1 1.5 Autonomic Nervous System dry mouth 1.5 0.7 1.3 Heart Rate/Rhythm bradycardia 0 0.4 0.5 Psychiatric vivid dreams 0 0 0 insomnia 2.3 1.5 2.5 depression 0.8 0 0.2 Gastrointestinal diarrhea 1.5 2.6 3.5 nausea 1.5 1.5 2.2 vomiting 0 1.1 1.5 Respiratory 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 Body 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 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.
Drug interactions
Open multi-drug checker ↗- Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
- Document allergy status and key interactions.
Mechanism & disposition
of its antihypertensive effects has not been completely established.
Read complete mechanism
of its antihypertensive effects has not been completely established. Factors which may be involved include: 1) Decreased cardiac output, 2) Inhibition of renin release by the kidneys, 3) Diminution of tonic sympathetic outflow from the vasomotor centers in the brain. In normal volunteers, bisoprolol fumarate tablets therapy resulted in a reduction of exercise- and isoproterenol-induced tachycardia. The maximal effect occurred within 1-4 hours post-dosing. Effects persisted for 24 hours at doses equal to or greater than 5 mg. Electrophysiology studies in man have demonstrated that bisoprolol fumarate tablets significantly decreases heart rate, increases sinus node recovery time, prolongs AV node refractory periods, and, with rapid atrial stimulation, prolongs AV nodal conduction. Beta 1 -selectivity of bisoprolol fumarate tablets has been demonstrated in both animal and human studies. No effects at therapeutic doses on beta 2 -adrenoceptor density have been observed. Pulmonary function studies have been conducted in healthy volunteers, asthmatics, and patients with chronic obstructive pulmonary disease (COPD). Doses of bisoprolol fumarate tablets ranged from 5 to 60 mg, atenolol from 50 to 200 mg, metoprolol from 100 to 200 mg, and propranolol from 40 to 80 mg. In some studies, slight, asymptomatic increases in airways resistance (AWR) and decreases in forced expiratory volume (FEV 1 ) were observed with doses of bisoprolol fumarate 20 mg and higher, similar to the small increases in AWR also noted with the other cardioselective beta-blockers. The changes induced by beta- blockade with all agents were reversed by bronchodilator therapy. Bisoprolol fumarate tablets had minimal effect on serum lipids during antihypertensive studies. In U.S. placebo-controlled trials, changes in total cholesterol averaged +
Product-specific
Product-specific
See product SmPC
is not affected by the presence of food. The first pass
The absolute bioavailability after a 10 mg oral dose of bisoprolol fumarate is about 80%.
half-life is 9-12 hours and is slightly longer in elderly patients, in part because of decreased renal function in that population. Steady state is attained within 5 days of once daily dosing. In both young and elderly populations, plasma accumulation is low; the accumulation fac...
is 9-12 hours and is slightly longer in elderly patients, in part because of decreased renal function in that population. Steady state is attained within 5 days of once daily dosing. In both young and elderly populations, plasma accumulation is low; the accumulation factor ranges...
Pregnancy, lactation & diet
Pregnancy In rats, bisoprolol fumarate was not teratogenic at doses up to 150 mg/kg/day which is 375 and 77 times the MRHD on the basis of body weight and body surface area, respectively. Bisoprolol fumarate was fetotoxic (increased late resorptions) at 50 mg/kg/day and maternotoxic (decreased food intake and body weight gain) at 150 mg/kg/day. The fetotoxicity in rats occurred at 125 times the MRHD on a body weight basis and 26 times the MRHD on the basis of body surface area. The maternotoxicity occurred at 375 times the MRHD on a body weight basis and 77 times the MRHD on the basis of body surface area. In rabbits, bisoprolol fumarate was not teratogenic at doses up to 12.5 mg/kg/day, which is 31 and 12 times the MRHD based on body weight and body surface area, respectively, but was embryolethal (increased early resorptions) at 12.5 mg/kg/day. There are no adequate and well-controlled studies in pregnant women. Bisoprolol fumarate tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers Small amounts of bisoprolol fumarate (< 2% of the dose) have been detected in the milk of lactating rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk caution should be exercised when bisoprolol fumarate is administered to nursing women.
Brands & loaded prices
| Brand | Manufacturer | Pack | Observed price |
|---|---|---|---|
| Betafix 2.5mg Tablet | Healthcare Pharmaceuticals Limited | Tablet 2.5mg | Unavailable |
| Betafix 5mg Tablet | Healthcare Pharmaceuticals Limited | Tablet 5mg | Unavailable |
| BISOPRESS-5 | Oman Pharmaceutical Products Co., LLC | Tablet | Unavailable |
| BIZOLOL | Not recorded | 5MG TABS 30*S | KES 411.19Daima Chemist price-list reference ↗ Source date not recorded · verify current price |
| CONCOR | DAIMA BIASHARA / Wholesale Import | 5MG TABS * 30`S | KES 1,180.35Daima Chemist price-list reference ↗ Source date not recorded · verify current price |
Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.