Cardobis M®

Bisoprolol Fumarate USP and Amlodipine Besilate BP Film Coated Tablet
SKF

Cardobis M® is a combined preparation of Bisoprolol and Amlodipine. Bisoprolol is a potent, highly β1-selective adrenoreceptor-blocking agent devoid of intrinsic sympathomimetic activity (ISA) and without relevant membrane stabilizing activity. It only shows low affinity to the β2-receptor of the smooth muscles of bronchi and vessels as well as to the β2-receptors concerned with metabolic regulation. Therefore, Bisoprolol is generally not to be expected to influence the airway resistance and β2-mediated metabolic effects. Its β1-selectivity extends beyond the therapeutic dose range. Bisoprolol has no explicit negative inotropic effect. Amlodipine inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle (slow channel blocker or calcium ion antagonist). The mechanism of its antihypertensive action is due to a direct relaxant effect on vascular smooth muscle causing reduction in peripheral vascular resistance.

Cardobis M® is indicated for the treatment of hypertension as substitution therapy in patients adequately controlled with the individual products given concurrently at the same doses level as in the combination, but as separate tablets.

Recommended daily dose is one tablet. Treatment must not be abruptly discontinued, as it may lead to temporary deterioration of clinical condition. Treatment must not be abruptly discontinued especially in case of patients suffering from ischaemic heart disease. Gradual decrease of the dose is recommended.
Patients with hepatic impairment: In case of hepatic impairment elimination of Amlodipine may be elongated. In case of severe hepatic impairment the daily dose of Bisoprolol must not exceed 10 mg.
Patients with renal impairment: No dosage adjustment is required for patients with mild to moderate renal impairment. Amlodipine is not dialyzable. Amlodipine should be administered with particular caution to patients undergoing dialysis.
CONTRAINDICATIONS
In connection with Amlodipine:

  • Severe hypotension
  • Shock (including cardiogenic shock)
  • Obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis)
  • Hemodynamically unstable heart failure after acute myocardial infarction

    • In connection with Bisoprolol:
  • Acute heart failure or during episodes of heart failure requiring i.v. inotropic
    • therapy
  • Cardiogenic shock
  • Second or third degree AV block (without a pacemaker)
  • Sick sinus syndrome
  • Sinoatrial block
  • Bradycardia (heart rate less than 60 beats/min) prior to start of therapy
  • Hypotension (systolic blood pressure < 100mmHg)
  • Severe bronchial asthma or severe chronic obstructive pulmonary disease
  • Severe forms of peripheral arterial occlusive disease and severe forms of Raynaud's syndrome
  • Metabolic acidosis

    • Common: : • Headache • Dizziness • Vomitting • Oedemas (especially ankle oedema) • Increased fatigue • Nausea • Flush • Somnolence • Palpitation Uncommon: • Abdominal pain • Hypesthesia • Insomnia • Mood change • Depression

    Patients with heart failure should be treated with caution. In a long-term, placebo controlled study in patients with severe heart failure (NYHA class III and IV) the reported incidence of pulmonary oedema was higher in the Amlodipine treated group than in the placebo group, but this was not associated with worsening of the heart failure. Especially in case of patients suffering from ischaemic heart disease the cessation of therapy with Bisoprolol must not be done abruptly unless clearly indicated, as it may lead to temporary deterioration of heart disease. Bisoprolol should be administered with special caution in patients with hypertension or angina associated with heart failure..

    In connection with Amlodipine: Cardobis M® can be safely administered with thiazide diuretics, β-blockers, long-acting nitrates, sublingual glyceryl trinitrate preparations, non-steroidal anti-inflammatory drugs, antibiotics, oral hypoglycaemic drugs.
    Effects of other medicinal products on Amlodipine
    CYP3A4 inhibitors: Concomitant use of Amlodipine with strong or moderate inhibitors of CYP3A4 (e.g. protease inhibitors, azole antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) can be expected to increase the plasma concentrations of Amlodipine to a clinically relevant extent.
    CYP3A4 inducers: There is no data available regarding the effect of CYP3A4 inducers on Amlodipine. The concomitant use of CYP3A4 inducers (e.g. rifampicin, St. John´s wort (Hypericum perforatum) may give a lower plasma concentration of Amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.
    In connection with Bisoprolol:
    Combinations not recommended:
    Calcium antagonists of verapamil type and to a lesser extent of diltiazem type: Negative influence on contractility, atrio-ventricular conduction and blood pressure. Intravenous administration of verapamil in patients on β-blocker treatment may lead to profound hypotension and atrioventricular block. Centrally acting antihypertensive drugs such as clonidine, methyldopa, moxonodine, rilmenidine: Concomitant use of centrally acting antihypertensive drugs may lead to reduction of heart rate and cardiac output and vasodilation. Abrupt withdrawal of the drug may increase the risk of "rebound hypertension".

    Cardobis M® combination is not recommended during pregnancy unless clearly necessary. It is not known whether Bisoprolol or Amlodipine is excreted in human milk. Therefore, administration of this combination is not recommended during breast-feeding.

    Store below 25 °C temperature, away from light and wet place. Keep out of reach of children.

    Cardobis M® 2.5/5 FCT : Box containing 3 strips of 10 tablets each. Each tablet contains Bisoprolol Fumarate USP 2.5 mg and Amlodipine Besilate BP equivalent to Amlodipine 5 mg.