INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo BISOHEXAL™ 5 mg film-coated tablets
BISOHEXAL™ 10 mg film-coated tablets

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

BISOHEXAL™ 5 mg film-coated tablets
BISOHEXAL™ 10 mg film-coated tablets

COMPOSITION
Each Bisohexal 5 mg film-coated tablet contains 5 mg
bisoprolol fumarate (2:1).
Bisoprolol is (+)-1-[[alpha-(2-isopropoxyethoxy)-p-tolyl]oxy]-3-(isopropylamino)-2-propanol fumarate (2:1).
Each Bisohexal 10 mg film-coated tablet contains 10 mg bisoprolol fumarate (2:1).
Bisoprolol is (+)-1-[[alpha-(2-isopropoxyethoxy)-p-tolyl]oxy]-3-(isopropylamino)-2-propanol fumarate (2:1).

PHARMACOLOGICAL CLASSIFICATION
A.5.2 Adrenolytics (sympathicolytics)

PHARMACOLOGICAL ACTION
Bisoprolol is a selective beta
1-adrenoceptor antagonist devoid of intrinsic sympathomimetic and membrane-stabilising activity.
Pharmacokinetics:
Bisoprolol is well absorbed following oral administration with a resultant bioavailability of about 90%. Bisoprolol undergoes minimal hepatic first-pass metabolism. About 50% of a dose is metabolised in the liver and the remainder is excreted unchanged via the kidneys. The plasma elimination half-life is approximately 10 to 12 hours and the duration of action is about 24 hours.

INDICATIONS
Bisohexal is indicated for the management of mild to moderate hypertension and angina pectoris.

CONTRA-INDICATIONS
Hypersensitivity to bisoprolol or to any of the ingredients
Uncontrolled asthma
Second and third-degree heart block and bradycardia (less than 50 beats per minute)
Pregnancy and lactation.
Uncontrolled cardiac failure
Metabolic acidosis
Sinus bradycardia (less than 50 beats per minute)
Phaeochromocytoma
Hyperthyroidism, as clinical manifestations may be masked
Particular caution should be exercised with patients suffering from the following: asthma, bronchitis, chronic respiratory diseases, peripheral vascular diseases and Raynaud's phenomenon.
The normal dose should be reduced in elderly patients, or in patients suffering from renal dysfunction. In the perioperative period it is generally unwise to reduce the dosage to which the patient is accustomed, as there may be danger of aggravation of angina pectoris or hypertension. A patient’s normal tachycardic response to hypovolaemia or blood loss may be obscured during or after surgery. Particular caution should be taken in this regard and in diabetes mellitus, as symptoms and signs of hypoglycaemia may be masked, and as responses to hypoglycaemia is diminished.

WARNINGS
Safety and efficacy in children have not been established.
If the decision is made to withdraw Bisohexal before anaesthesia, at least 48 hours should be allowed to elapse between the last dose and surgery. If the medicine is to be continued, care should be taken when using anaesthetics such as ether, cyclopropane and trichloroethylene. Atropine (1-2 mg I.V.) may be used to correct vagal dominance. The patient must be maintained on their usual dosage perioperatively to avoid aggravation of angina pectoris or hypertension.
Tachycardia responses may be obscured. Particular caution should be taken in this regard.
The dosage of Bisohexal should be adjusted in severe renal impairment.
(See DOSAGE AND DIRECTIONS FOR USE)
Care should be taken in prescribing Bisohexal together with Class 1 antidysrhythmic agents such as disopyramide, myocardial depressants and inhibitors of AV conduction such as calcium antagonists.
Caution should be exercised when transferring a patient from clonidine, as the withdrawal of clonidine may result in the release of large amounts of catecholamines that may give rise to a hypertensive crisis. If Bisohexal is administered in these circumstances, the unopposed alpha receptor stimulation may potentiate this effect. If Bisohexal and clonidine are given concurrently, the clonidine should not be discontinued until several days after the withdrawal of Bisohexal as severe rebound hypertension may occur.
Bisohexal should be used with caution in combination with verapamil in patients with impaired ventricular function. This combination should not be given to patients with conduction abnormalities. Neither drug should be administered intravenously within 48 hours of discontinuing the other. The intravenous administration of calcium antagonists and antiarrthythmic agents is not recommended during therapy with Bisohexal.
Bisohexal modifies the tachycardia associated with hypoglycaemia.
Patients with phaeochromocytoma usually require treatment with an alpha-adrenergic blocker
INTERACTIONS
Concomitant use of Bisohexal with hypoglycaemic agents, phenothiazines and various antiarrhythmic agents can have life-threatening consequences, e.g.
  • profound hypoglycaemia with oral hypoglycaemic agents and insulin;
  • myocardial depression with antiarrhythmic agents.
Beta-adrenoceptor stimulating agents (e.g. isoprenaline) may antagonise the effects of Bisohexal.
Alpha-adrenoceptor stimulants as well as adrenergic neurone blocking agents such as guanethidine and reserpine may lead to life-threatening vasoconstriction in combination with Bisohexal.
Bisohexal and digoxin may be used concomitantly for patients with congestive heart failure provided that the pulse rate and patient response is monitored.

PREGNANCY AND LACTATION
Administration of Bisohexal to pregnant mothers, shortly before birth or during labour may result in hypotonia, collapse or hypoglycaemia in the newborn. (See CONTRA-INDICATIONS)

DOSAGE AND DIRECTIONS FOR USE
Adults: 5 to 10 mg once a day in the morning with or without food. The dose must be individualised according to response and tolerance. The maximum recommended daily dose is 20 mg daily.
Severe renal impairment (creatinine clearance <20 mL/min) or severe hepatic impairment:
Do not exceed the daily dose of 10 mg.
Elderly:
The normal dose should be reduced in these patients.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Side-effects:
Haematological:
Blood disorders such as leukopenia and thrombocytopenia
Cardiovascular system:
Bradycardia and congestive cardiac failure, heart block, fluid retention, exacerbation of peripheral vascular disease or the development of Raynaud's phenomenon, peripheral gangrene may be precipitated. Congestive cardiac failure and marked bradycardia may occur.
Central nervous system:
Lassitude, dizziness, mild headache, sleeps disorders, restlessness, cold extremeties, hypotension, paradoxical hypertension, depression, paraesthesia, hallucinations, psychosis
Endocrine/Metabolic:
Metabolic disturbances, hypoglycaemia, increase in uric acid levels, hypercholesterolaemia
Gastrointestinal:
Nausea, vomiting, diarrhoea, constipation, mass gain, stomatitis
Liver:
Raised liver enzymes
Musculoskeletal:
Muscle cramps, myopathy, skeletal muscle weakness
Ocular:
Disturbances of vision
Skin:
Perspiration, skin rash, alopecia
Other:
Transient hearing loss, hypersensitivity reactions, sexual impotence
Respiratory system disorders:
Bronchoconstriction may occur in patients suffering from asthma, bronchitis and other chronic pulmonary diseases.
Adverse reactions are more common in patients with renal decompensation.
Special Precautions:
Abrupt discontinuation of therapy may cause exacerbation of angina pectoris in patients suffering from ischaemic heart disease. Discontinuation of therapy should be gradual, and patients should be advised to limit the extent of their physical activity during the period that the medicine is being discontinued.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
(See SIDE-EFFECTS AND SPECIAL PRECAUTIONS)
Overdosage may produce bradycardia and severe hypotension. Bronchospasm and heart failure may be produced in certain individuals.
Cases of overdose should be observed for at least 4 hours, as apnoea and cardiovascular collapse may appear suddenly.
Repeated activated charcoal may be necessary in overdose.
Atropine may be used to treat severe bradycardia. If the response is inadequate, glucagon may be give intravenously. Alternatively, dobutamine may be required to reverse beta-blockade. Cardiac pacing may be required for severe bradycardia. Bronchospasm should be treated with IV aminophylline or inhaled or IV beta-agonist eg. salbutamol.

IDENTIFICATION
Bisohexal 5 mg: yellow coloured, round, “Snap Tab” film-coated tablets, with a crossed break mark and a one-sided embossment “BIS 5”.
Diameter : 5.4 –5.8 mm
Height : 2.1 –2.7 mm
Bisohexal 10 mg: apricot coloured, round and biconvex film-coated tablets with a crossed break mark and a one-sided embossment “BIS 10”
Diameter : 6.9 –7.2 mm
Height : 2.7 –3.3 mm

PRESENTATION
Aluminium blister packs of 30’s.

STORAGE INSTRUCTIONS
Store below 25°C in airtight containers and protect from light.
KEEP OUT OF THE REACH OF CHILDREN.

REGISTRATION NUMBERS
Bisohexal 5 mg: 37/5.2/0516
Bisohexal 10 mg: 37/5.2/0517

NAME AND BUSINESS ADDRESS OF APPLICANT
HEXAL Pharma (SA) Pty LTD
46 Mahogany Road
Mahogany Ridge
Pinetown
3610

DATE OF PUBLICATION OF PACKAGE INSERT
02/2005

New addition to this site: February 2005
Source: Pharmaceutical Industry

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