Bisoprolol Mylan

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet)

1.25 mg tablet only:
White, oval, biconvex film coated tablets; ‘BL’ & ‘1’ engraved on one face of the tablet; ‘M’ engraved on the other face of the tablet.

2.5 mg tablet only:
White to off-white, oval, biconvex film-coated tablets with side notches and debossed with "BL & 2" on either side of scoreline on one side and "M" on the other side.
White, oval, biconvex film coated tablets with side notches; ‘BL’ & ‘2’ engraved on either side of the scoreline on one face of the tablet; ‘M’ engraved on the other face of the tablet.

3.75 mg tablet only:
Cream, oval, biconvex film coated tablets with side notches; ‘BL’ & ‘3’ engraved on either side of the scoreline on one face of the tablet; ‘M’ engraved on the other face of the tablet.

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet)

2.5 mg tablet only:
GreyWhite, oval, biconvex film coated tablets with side notches; ‘BL’ & ‘2’ engraved on either side of the scoreline on one face of the tablet; ‘M’ engraved on the other face of the tablet.

6. PHARMACEUTICAL PARTICULARS

6.1     List of excipients

 

Strength	Tablet	Film-coat
1.25 mg tablet only:	Cellulose microcrystalline Lactose anhydrous Colloidal anhydrous silica Magnesium stearate Sodium lauril sulfate Croscarmellose sodium	Titanium dioxide (E171) Polydextrose FCC (E1200) Hypromellose (E464) Macrogol
2.5 mg tablet only:	Cellulose microcrystalline Lactose anhydrous Colloidal anhydrous silica Magnesium stearate Sodium lauril sulfate Iron oxide yellow (E172) Iron oxide red (E172) Croscarmellose sodium	Titanium dioxide (E171) Polydextrose FCC (E1200) Hypromellose (E464) Macrogol Iron oxide black (E172)

10. DATE OF REVISION OF THE TEXT

September January 20167

8. MARKETING AUTHORISATION NUMBER(S)

PA0577/153/001
PA0577/153/002
PA0577/153/003
PA0577/153/004
PA0577/153/005
PA0577/153/006

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 19th August 2011
Date of latest renewal: 10th October 2015

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet)

1.25 mg tablet only:
White, oval, biconvex film coated tablets; ‘BL’ & ‘1’ engraved on one face of the tablet; ‘M’ engraved on the other face of the tablet.

2.5 mg tablet only:
Grey, oval, biconvex film coated tablets with side notches; ‘BL’ & ‘2’ engraved on either side of the scoreline on one face of the tablet; ‘M’ engraved on the other face of the tablet.

3.75 mg tablet only:
Cream, oval, biconvex film coated tablets with side notches; ‘BL’ & ‘3’ engraved on either side of the scoreline on one face of the tablet; ‘M’ engraved on the other face of the tablet.

5 mg tablet only:
Pale yellow, oval, biconvex film coated tablets with side notches; ‘BL’ & ‘4’ engraved on either side of the scoreline on one face of the tablet; ‘M’ engraved on the other face of the tablet.

7.5 mg tablet only:
Yellow, oval, biconvex film coated tablets with side notches; ‘BL’ & ‘5’ engraved on either side of the scoreline on one face of the tablet; ‘M’ engraved on the other face of the tablet.

10 mg tablet only:
Pale orange to light orange, oval, biconvex film coated tablets with side notches; ‘BL’ & ‘6’ engraved on either side of the scoreline on one face of the tablet; ‘M’ engraved on the other face of the tablet.

2.5mg, 3.75 mg, 5 mg, 7.5 mg, 10 mg tablet only:
The tablet can be divided into equal doses.

4.2 Posology and method of administration

Special populations

Renal or liver Hepatic or renal impairment:
There is no information regarding pharmacokinetics of bisoprolol in patients with chronic heart failure and with impaired hepatic or renal function. Titration of the dose in these populations should therefore be made with particular caution.

4.3 Contraindications

Bisoprolol is contraindicated in chronic heart failure patients with:

• hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1
• acute heart failure or during episodes of heart failure decompensation requiring i.v. inotropic therapy
• cardiogenic shock
• second or third degree AV block
• sick sinus syndrome
• sinoatrial block
• symptomatic bradycardia
• symptomatic hypotension
• severe bronchial asthma or severe chronic obstructive pulmonary disease
• severe forms of peripheral arterial occlusive disease or severe forms of Raynaud's syndrome
• untreated phaeochromocytoma (see section 4.4)
• metabolic acidosis

4.4 Special warnings and precautions for use

Precautions

The initiation and cessation of treatment with bisoprolol necessitates regular monitoring. For the posology and method of administration please (see section 4.2).

There is no therapeutic experience of bisoprolol treatment in heart failure in patients with the following diseases and conditions:
- insulin dependent diabetes mellitus (type I)
- severely impaired renal function
- severely impaired liver hepatic function
- restrictive cardiomyopathy
- congenital heart disease
- haemodynamically significant organic valvular disease
- myocardial infarction within 3 months

Bisoprolol must be used with caution in:

• bronchospasm (bronchial asthma, obstructive airways diseases)
• diabetes mellitus with large fluctuations in blood glucose values; symptoms of hypoglycaemia (e.g. tachycardia, palpitations, sweating) can be masked
• strict fasting
• ongoing desensitisation therapy. As with other beta-blockers, bisoprolol may increase both the sensitivity towards allergens and the severity of anaphylactic reactions. Epinephrine treatment may not always yield the expected therapeutic effect.
• first degree AV block
• Prinzmetal's angina
• peripheral arterial occlusive disease.  Aggravation of symptoms may occur especially when starting therapy.
• general anaesthesia.

 
Combination of bisoprolol with calcium antagonists of the verapamil or diltiazem type, with Class I antiarrhythmic drugs and with centrally acting antihypertensive drugs is generally not recommended, for details please refer to section 4.5.

Although cardioselective (beta1) beta-blockers may have less effect on lung function than non-selective beta- blockers, as with all beta-blockers, these should be avoided in patients with obstructive airways diseases, unless there are compelling clinical reasons for their use. Where such reasons exist, bisoprolol may be used with caution. In patients with obstructive airways diseases, the treatment with bisoprolol should be started at the lowest possible dose and patients should be carefully monitored for new symptoms (e.g. dyspnoea, exercise intolerance, cough).

4.5 Interaction with other medicinal products and other forms of interaction

Combinations not recommended:

• Calcium antagonists of the verapamil type and to a lesser extent of the diltiazem type: Negative influence on contractility and atrio-ventricular conduction. Intravenous administration of verapamil in patients on beta-blocker treatment may lead to profound hypotension and atrioventricular block.
• Centrally acting antihypertensive drugs (e.g. clonidine, methyldopa, moxonodine moxonidine, rilmenidine): Concomitant use of centrally acting antihypertensive drugs may further decrease the central sympathetic tonus (and may thus lead to a reduction of heart rate and cardiac output, and to vasodilation). Abrupt withdrawal, particularly if prior to beta-blocker discontinuation, may increase risk of “rebound hypertension”.
• Class-I antiarrhythmic drugs (e.g. disopyramide, quinidine, lidocaine, phenytoin; flecainide, propafenone): Effect on atrio-ventricular conduction time may be potentiated and negative inotropic effect increased.

Combinations to be considered:

• Mefloquine: increased risk of bradycardia
• Monoamine oxidase inhibitors (except MAO-B inhibitors): Enhanced hypotensive effect of the beta-blockers but also risk for hypertensive crisis.
• Rifampicin: Slight reduction of the half-life of bisoprolol possible due to the induction of hepatic drug-metabolising enzymes. Normally no dosage adjustment is necessary.
• Ergotamine derivatives: Exacerbation of peripheral circulatory disturbances.

4.7 Effects on ability to drive and use machines

In a study of coronary heart disease patients, bisoprolol did not impair driving performance. However, depending on the individual patient’s response to treatment, an effect on the ability to drive a vehicle or to use machines cannot be excluded may be impaired. This should be considered particularly at the start of treatment and upon change of medication or in conjunction with alcohol.

4.8 Undesirable effects

Vascular disorders:
Common: feeling of coldness or numbness in the extremities, hypotension especially in patients with heart failure.
Uncommon: orthostatic hypotension.

Skin and subcutaneous tissue disorders:
Rare: hypersensitivity reactions such as itching, flush, rash.
Very rare: alopecia, beta-blockers may provoke or worsen psoriasis or induce psoriasis-like rash, alopecia.

4.9 Overdose

Symptoms

With overdose (e.g. daily dose of 15 mg instead of 7.5 mg) third degree AV-block, bradycardia, and dizziness have been reported. In general, Tthe most common signs expected with overdose of a beta-blocker are bradycardia, hypotension, bronchospasm, acute cardiac insufficiency and hypoglycaemia. There is limited experience with overdose of bisoprolol, only a few cases of overdose (maximum: 2000 mg) with bisoprolol have been reported in patients suffering from hypertension and/or coronary heart disease showing bradycardia and/or hypotension; : Bradycardia and/or hypotension were noted. Aall patients recovered. There is a wide inter-individual variation in sensitivity to one single high dose of bisoprolol and patients with heart failure are probably very sensitive. Therefore it is mandatory to initiate the treatment of these patients with a gradual uptitration according to the scheme given in section 4.2.

Management
In general, if overdose occurs, discontinuation of bisoprolol treatment and supportive and symptomatic treatment is recommended.

Based on the expected pharmacologic actions and recommendations for other beta-blockers, the following general measures may be considered when clinically warranted.

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 transvenous cardiac pacemaker insertiontemporary pacing.

5.2 Pharmacokinetic properties

ExcretionElimination
Bisoprolol is excreted from the body by two routes. 50% is metabolised by the liver to inactive metabolites which are then excreted by the kidneys. The remaining 50% is excreted by the kidneys in an unmetabolised form. Since the elimination takes place in the kidneys and the liver to the same extent a dosage adjustment is not required for patients with impaired liver function or renal insufficiency.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements

 8. MARKETING AUTHORISATION NUMBER(S)

PA0577/153/1
PA0577/153/2
PA0577/153/3
PA0577/153/4
PA0577/153/5
PA0577/153/6

 

Section 2: Qualitative & Quantitative Composition

0.174mg amended

None provided