Sopalol 2.5/Sopalol 5

Sopalol 2.5/Sopalol 5

bisoprolol

Manufacturer:

Intas Pharmaceuticals

Distributor:

Berlin Pharm
Full Prescribing Info
Contents
Bisoprolol fumarate.
Description
Each tablet contains bisoprolol fumarate 2.5 mg and 5.0 mg, respectively.
Action
Pharmacology: Pharmacodynamics: Mechanism of Action: Bisoprolol is a β1-selective adrenergic blocking agent. Bisoprolol is related structurally to acebutolol, atenolol and metoprolol in that the drugs contain substituents in the para position of the benzene ring; the presence of large substituents in the para position is believed to account in part for the selective β1-adrenergic blocking effect of these drugs. The commercially available drug is a racemic mixture of the 2 optical isomers; however, only the l-isomer of bisoprolol has substantial β-adrenergic blocking activity. The drug does not exhibit the intrinsic sympathomimetic activity seen with pindolol or the membrane-stabilizing activity possessed by propranolol or pindolol. At low dosages, bisoprolol selectivity inhibits response to adrenergic stimuli by competitively blocking cardiac β1-adrenergic receptors, while having little effect on the β2-adrenergic receptors of bronchial and vascular smooth muscle. At high doses (e.g. 20 mg or higher), the selectivity of bisoprolol on β1-adrenergic receptors usually diminishes, and the drug will competitively inhibit β1 and β2-adrenergic receptors. The drug is commercially available as the fumarate.
Pharmacokinetics: Pharmacokinetics parameters: Onset of action: 1-2 hours.
Absorption: Rapid and almost complete.
Distribution: Widely; highest concentrations in heart, liver, lungs and saliva; crosses blood-brain barrier.
Protein binding: ~30%.
Metabolism: Extensively hepatic; significant first-pass effect (~20%); 50% is metabolized by liver to inactive metabolites which are then excreted by kidneys (Sopalol 5 only).
Bioavailability: ~80% (Sopalol 2.5 only).
Half-life elimination: normal renal function 9-12 hours, and renal dysfunction (ClCr <40 mL/minute) 27-36 hours, hepatic cirrhosis 8-22 hours (Sopalol 2.5 only).
Time to peak: 2-4 hours.
Excretion: Urine (50% as uncharged drug, remainder as inactive metabolites), feces (<2%).
Indications/Uses
Treatment of hypertension, alone or in combination with other agents.
Sopalol 5: Treatment of coronary heart disease (stable angina pectoris).
To prevent or delay the overt of heart failure in patient with asymptomatic systolic left ventricular dysfunction, and a history of myocardial infarction (MI).
Dosage/Direction for Use
Sopalol 2.5: Adult: Hypertension: Initial: 5 mg once daily. In some patients 2.5 mg may be appropriate.
Dosage titration: 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.
Renal function impairment: In patients with renal dysfunction (creatinine clearance less than 40 mL/min), use and initial daily dose of 2.5 mg and use caution in dose titration. Because limited data suggest that bisoprolol is not dialyzable, drug replacement is not necessary in patients undergoing hemodialysis.
Hepatic function impairment: In patients with hepatic impairment (hepatitis or cirrhosis), use an initial daily dose of 2.5 mg and use caution in dose titration.
Sopalol 5: Adult: Sopalol should be taken in morning and can be taken with food. Food does not affect drug absorption.
Hypertension and Angina Pectoris: Initial: 5 mg once daily or 2.5 mg once daily in the elderly.
Maximum dose: 20 mg once daily.
Dosage titration: If the effect of 5 mg is inadequate, the dose may be increased to 10 mg once daily and then, if necessary, to 20 mg once daily.
Dose adjustment in renal function impairment: In patients with renal dysfunction (creatinine clearance less than 40 mL/min), use an initial daily dose of 2.5 mg and use with caution on dose titration. In patients with severe renal impairment (creatinine clearance less than 20 mL/min), the dose should not exceed 10 mg once daily which may eventually be divided into halves.
Dose adjustment in hepatic function impairment: In patients with hepatic impairment (hepatitis or cirrhosis), use an initial daily dose of 2.5 mg and use with caution on dose titration.
Discontinuation of treatment: Treatment should not be stopped abruptly. The dosage should be diminished slowly by a weekly halving of the dose.
Elderly: Use a low initial dose of 2.5 mg and use the lowest dose that responses to the treatment.
Congestive heart Failure: Before initiating use of bisoprolol, the patient should be examined and ensured that the disease is stable (without acute heart failure). Use of this drug in patients with heart failure should be seriously cautious because it may cause transient worsening of heart failure, hypotension, or bradycardia during the titration period and thereafter.
Titration phase: The treatment with bisoprolol should be started with the lowest dose and gradually up titration according to the following steps: 1.25 mg once daily (in the morning) for 1 week, if well tolerated increase to; 2.5 mg once daily for a further week, if well tolerated increase to; 3.75 mg once daily for a further week, if well tolerated increase to; 5 mg once daily for the 4 following week, if well tolerated increase to; 7.5 mg once daily for the 4 following week, if well tolerated increase to; 10 mg once daily for the maintenance therapy, the maximum recommended dose. Dosage titration can increase until to the maximum dose tolerated.
Dose adjustment in renal and hepatic functions impairment: There is no information, regarding pharmacokinetics of bisoprolol in patients with chronic heart failure. Up titration of the dose should, therefore, be made with caution.
Children: There is no paediatric experience with bisoprolol, therefore its use cannot be recommended for children.
Sopalol 2.5/Sopalol 5: Mode of Administration: Bisoprolol fumarate is administered orally. GI absorption of the drug does not appear to be affected by food.
Overdosage
Overdose: Sopalol 2.5: The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate) not necessarily inclusive: bradycardia, dizziness, severe or fainting, hypotension, irregular heartbeat, difficulty breathing, bluish-colored fingernails or palms of hands or seizures.
Sopalol 5: The most common signs expected with overdose of a beta-blocker are bradycardia, severe dizziness/fainting, hypotension, hypoglycaemia, irregular heartbeat, difficulty breathing (bronchospasm), bluish-colored fingernails/palms of hands, or seizures. Heart failure patient will be high risk by toxicity of bisoprolol.
Treatment: Sopalol 2.5: Decreased absorption: Gastric lavage and administration of activated charcoal.
Sopalol 5: Decreased absorption: Gastric lavage and administration of activated charcoal then supportive and symptomatic treatment is recommended.
Bradycardia: Administer intravenous atropine. If the response is inadequate, isoprenaline or another agent with positive chronotropic properties may be given cautiously. Under some circumstances, transvenous pacemaker insertion may be necessary.
Hypotension: Intravenous fluids and vasopressors should be administered. Intravenous glucagon may be useful.
AV block (second or third degree): Patients should be carefully monitored and treated with isoprenaline infusion or temporary pacing.
Acute worsening of heart failure: Administer i.v. diuretics, inotropic agents, vasodilating agents.
Bronchospasm: Administer bronchodilator therapy such as isoprenaline, beta2-sympathomimetic drugs and/or aminophylline.
Hypoglycaemia: Administer i.v. glucose.
Contraindications
Do not use the drug in the following cases: Cardiogenic shock.
Sopalol 2.5: Overt cardiac failure, marked sinus bradycardia or heart block greater than first-degree (except in patients with a functioning artificial pacemaker).
Sopalol 5: Acute heart failure or during episodes of heart failure decompensation requiring IV. Inotropic therapy (overt HF); cardiogenic shock; second or third degree AV block (without a pacemaker); severe sick sinus syndrome; sinoatrial block; symptomatic bradycardia; symptomatic hypotension; severe bronchial asthma or severe chronic obstructive pulmonary disease; late stages of peripheral arterial occlusive disease or Raynaud's syndrome; untreated phaeochromocytoma; metabolic acidosis; hypersensitivity to bisoprolol or to any of the excipients.
Special Precautions
Sopalol 2.5: Consider pre-existing conditions such as sick sinus syndrome before initiating.
Use with caution in the following patients: Heart failure; use gradual and careful titration; monitor for symptoms of congestive heart failure.
Myasthenia gravis, psychiatric disease (may cause CNS depression), bronchospastic disease, undergoing anesthesia and in those with impaired hepatic function.
Bradycardia may be observed more frequently in elderly patients (>65 years of age), dosage reductions may be necessary.
Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD) but gradually tapered to avoid acute tachycardia, hypertension and/or ischemia.
Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.
Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud's disease, use with caution and monitor for progression of arterial obstruction.
Concurrent use of digoxin, verapamil, or diltiazem, bradycardia or heart block may occur.
Receiving inhaled anesthetic agents known to depress myocardial contractility.
Bisoprolol, with beta1-selectivity may be used cautiously in bronchospastic disease with close monitoring.
Diabetes because it can mask prominent hypoglycemic symptoms.
May mask signs of hyperthyroidism (e.g. tachycardia) use caution if hyperthyroidism is suspected, abrupt withdrawal may precipitate thyroid storm.
Dosage adjustment is required in patients with significant hepatic or renal dysfunction.
Adequate alpha-blockade is required prior to use of any beta-blocker for patients with untreated pheochromocytoma. May induce or exacerbate psoriasis.
Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (e.g. epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
Sopalol 5: Before initiating use of bisoprolol in patients, physicians must ensure that the patient is not pre-existing conditions such as sick sinus syndrome.
Using bisoprolol in patients with heart failure must start with gradually increasing dosages as recommended (titration phase) and constantly monitor congestive heart failure symptom, particularly, the heart failure patients with restrictive cardiomyopathy, congenital heart disease, haemodynamically significant organic valvular disease, or insulin dependent diabetes mellitus (Type 1), severely impaired hepatic/renal function because of no therapeutic experience of bisoprolol treatment in those patients.
Bradycardia may be observed more frequently in elderly patients (>65 years of age), dosage reductions may be necessary and should not be withdrawn abruptly. In patients with CAD (angina pectoris), use gradual and careful titration to avoid acute tachycardia, hypertension and/or ischemia. In case of no withdrawal of bisoprolol before anesthesia, anesthetist should gradually reduce bisoprolol dose and stop the drug at least 48 hours before anesthesia.
Cautiously using bisoprolol in patients with bronchial asthma or chronic obstructive lung diseases (COLD) or emphysema, because asthma symptoms may occur. Therefore, the dose of beta2-agonists (bronchodilators) may need to be increasingly adjusted be increased.
Diabetes mellitus patients taking bisoprolol and poor blood sugar control may in danger of hypoglycaemia without sign which can be masked by disoprolol.
Bisoprolol may mask signs of hyperthyroidism e.g. tachycardia, abrupt withdrawal of bisoprolol may precipitate thyroid storm.
For patients with untreated pheochromocytoma, adequate alpha-blockade is required prior to use of any beta-blocker.
Bisoprolol may induce or exacerbate psoriasis.
This drug causes artery constriction, it should not be used in patients with narrow peripheral arterial disease or occlusive, or Raynaud's disease.
Dosage adjustment is required in patients with significant hepatic or renal dysfunction.
Patient are thought necessary to withdraw bisoprolol before anesthesia, this should be done gradually and completed about 48 hours.
Concurrent use of digoxin, verapamil, or diltiazem may cause bradycardia or heart block may occur.
In patients taking beta-blocker and with allergy reaction anaphylaxis as epinepharine may be used for treatment but can increase more severity.
Use In Pregnancy & Lactation
Pregnancy: Pregnancy risk factor C.
Sopalol 2.5: Adverse events were observed in animal reproduction studies; therefore, the manufacturer classifies bisoprolol as pregnancy category C. In a cohort study, an increased risk of cardiovascular defects was observed following maternal use of beta-blocker during pregnancy. Intrauterine growth restriction (IUGR), small placentas, as well as, fetal/neonatal bradycardia, hypoglycemia, and/or respiratory depression have been observed following in utero exposure to beta-blockers as a class. Adequate facilities for monitoring infants at birth should be available. Untreated chronic maternal hypertension and pre-eclampsia are also associated with adverse events in the fetus, infant, and mother. Limited information is available related to the use of bisoprolol for the treatment of hypertension in pregnancy; other agents may be more appropriate for use.
Sopalol 5: Bisoprolol is not recommended in pregnancy, except physician considers, it is necessary, because adverse events were observed in animal reproduction studies. Therefore, the manufacturer classifies bisoprolol as pregnancy category C. In a cohort study, an increased risk of cardiovascular defects was observed following maternal use of beta-blocker during pregnancy.
Bisoprolol affects intrauterine growth restriction (IUGR) because of reducing placental perfusion, which has been associated with small placentas, and may be intrauterine death or preterm labor. Hypoglyceamia, bradycardia, and/or respiratory depression may occur in fetus and newborn infant therefore adequate facilities for monitoring infants at birth should be available. Symptoms of hypoglycaemia and bradycardia are generally to be expected within the first 3 days. Untreated chronic maternal hypertension and pre-eclampsia are also associated with adverse events in the fetus, infant, and mother. Not recommended use of bisoprolol for the theatment of hypertension in pregnancy. If treatment with bisoprolol is considered necessary, selective beta-adrenergic blocker are preferable.
Lactation: Sopalol 2.5: Excretion unknown/use caution.
Sopalol 5: There are no data on the excretion of bisoprolol excreted in human milk. Therefore, administration of bisoprolol is not recommended during. Breast-feeding.
Adverse Reactions
>10%: Sopalol 5: Bradycardia in patients with chronic heart failure.
1% to 10%: Sopalol 2.5/Sopalol 5: Cardiovascular: Chest pain (1% to 2%), worsening of pre-existing heart failure in patients with chronic heart failure (Sopalol 5 only).
Central nervous system: Fatigue (dose related 6% to 8%), insomnia (2% to 3%), hypoesthesia (1% to 2%).
Gastrointestinal: Diarrhea (dose related 3% to 4%), nausea (2%), vomiting (1% to 2%).
Neuromuscular & skeletal: Arthralgia (2% to 3%), weakness (dose related ≤ 2%).
Respiratory: Upper respiratory infection (5%), rhinitis (3% to 4%), sinusitis (dose related 2%), dyspnea (1% to 2%).
<1% (limited to important or life-threatening): Sopalol 2.5: Abdominal pain, acne, alopecia, angioedema, anxiety, arrhythmia, asthma, back/neck pain, bradycardia (dose related), bronchitis, bronchospasm, BUN /creatinine increased, claudication, cold extremities, confusion (especially in the elderly), congestive heart failure, constipation, coughing, cutaneous vasculitis, cystitis, depression, dermatitis, dizziness, dyspepsia, dyspnea on exertion, eczema, edema, exfoliative dermatitis, flushing, gastritis, gout, hallucinations, headache, hearing decreased, hyperesthesia, hyperglycemia, hyperkalemia, hyperphosphatemia, hypertriglyceridemia, hypotension, impotence, lacrimation (abnormal), leukopenia, libido decreased, malaise, memory loss, muscle cramps, muscle/joint pain, nervousness, ocular pain/pressure, orthostatic hypotension, palpitations, paresthesia, peptic ulcer, Peyronie's disease, pharyngitis, polyuria, positive ANA titers, pruritus, psoriasis, psoriasiform eruption, purpura, rash, renal colic, restlessness, rhythm disturbances, sleep disturbances, somnolence, syncope, taste abnormality, thrombocytopenia, tinnitus, transaminases increased, tremor, twitching, uric acid increased, vasculitis, vertigo, visual disturbances, weight gain, xerostomia.
Sopalol 5: AV-conduction disturbances, bradycardia in patients with hypertension or angina pectoris, worsening of pre-existing heart failure in patients with hypertension or angina pectoris, reduced tear in patient with contact lenses, and conjunctivitis.
Drug Interactions
Metabolism/Transport effects: Substrate of CYP2D6 (minor), CYP3A4 (major). Assignment of major/minor substrate status based on clinically relevant drug interaction potential (Sopalol 2.5 only).
Avoid concomitant use of bisoprolol with any of the following drugs: Conivaptan, floctafenine, methacholine.
Increased effect/toxicity: Bisoprolol may increase the levels/effects of alpha-/beta-agonists (direct-acting), alpha 1-blockers, alpha 2-agonists, amifostine, antihypertensives, antipsychotic agents (phenothiazines), bupivacaine, cardiac glycosides, cholinergic agonists, ergot derivatives, fingolimod, hypotensive agents, insulin, lidocaine (systemic), lidocaine (topical), mepivacaine, methacholine, midodrine, rituximab, sulfonylureas.
Sopalol 5: Oral anti-diabetic medicines, mefloquine.
The levels/effects of bisoprolol may be increased by acetylcholinesterase inhibitors, alpha 2-agonists, aminoquinolines (antimalarial), amiodarone, anilidopiperidine, opioids, antipsychotic agents (phenothiazines), calcium channel blockers (dihydropyridine), calcium channel blockers (nondihydropyridine), conivaptan, CYP3A4 inhibitors (moderate), CYP3A4 inhibitors (strong), dasatinib, diazoxide, dipyridamole, disopyramide, dronedarone, floctafenine, herbs (hypotensive properties), ivacaftor, MAO inhibitors, mifepristone, pentoxyfylline, phosphodiesterase 5 inhibitors, propafenone, prostacyclin analogues, quinidine, reserpine.
Sopalol 5: Flecainide, phenytoin, topical beta-blockers (eye drops for glaucoma treatment), anaesthetic agents, antihypertensive agents and other medicines with blood pressure lowering potential (tricyclic anti-depressants, barbiturates, phenothiazines).
Decreased effect: Bisoprolol may decrease the levels/effects of beta 2-agonists (e.g. salbutamol, terbutaline, salmeterol, procaterol, etc.), theophylline derivatives.
The levels/effects of bisoprolol may be decreased by barbiturates, CYP3A4 inducers (strong), deferasirox, herbs (enzyme CYP3A4 inducers e.g. St. Johns Wort), herbs (hypertensive properties), methylphenidate, nonsteroidal anti-inflammatory agents, peginterferon alfa-2b, rifamycin derivatives, tocilizumab, yohimbine.
Ethanol/Nutrition/Herb interaction: Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid garlic (may have increased antihypertensive effect).
Storage
Store below 30°C.
MIMS Class
ATC Classification
C07AB07 - bisoprolol ; Belongs to the class of selective beta-blocking agents. Used in the treatment of cardiovascular diseases.
Presentation/Packing
Tab 2.5 mg (white to off white, round, biconvex, debossed "b1" on one side and breakline on other side) x 10 x 10's. 5 mg (white to off white, round, biconvex, debossed "b2" on one side and break-line on other side) x 10 x 10's.
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