Exemed Pharmaceutical Gets CDSCO Panel Nod To Manufacture, Market Amlodipine, Bisoprolol FDC

New Delhi: Considering the request for bioequivalence (BE) and Phase III clinical trial (CT) waiver, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has granted approval to Exemed Pharmaceutical for manufacturing and marketing of the fixed dose combination (FDC) of Amlodipine besylate IPeq. to Amlodipine plus Bisoprolol Fumarate IP (2.5mg + 2.5mg, 2.5mg + 5mg).

However, this approval is subject to the condition to conduct the Phase IV clinical trial.

This came after Exemed Pharmaceutical presented their proposal along with justification for BE and phase III CT waiver before the committee.

The committee noted that the proposed FDC, i.e., S (-) Amlodipine besylate IP eq. to Amlodipine 2.5 mg plus Bisoprolol Fumarate USP 5 mg, is considered rational by the Prof. Kokate committee on 16.07.2015.

Furthermore, the expert panel noted that the FDC of S (-) Amlodipine Besilate Eq. to S (-) Amlodipine 2.5 mg/ 5 mg + HCTZ 12.5 mg / 12.5 mg tablet and Bisoprolol Fumarate 2.5 mg/ 5 mg + Hydrochlorthiazide 6.25 mg/ 6.25 mg tablet are already approved for the treatment of mild to moderate hypertension on 14.04.2004 and 13.05.1999, respectively.

Bisoprolol/amlodipine combination therapy improves blood pressure control in patients with essential hypertension following monotherapy failure. Bisoprolol is a beta-1 adrenergic blocking agent used to prevent myocardial infarction and heart failure and to treat mild to moderate hypertension.

Though the mechanism of action of bisoprolol has not been fully elucidated in hypertension, it is thought that therapeutic effects are achieved through the antagonism of β-1adrenoceptors to result in lower cardiac output. Bisoprolol is a competitive, cardioselective β1-adrenergic antagonist. When β1-receptors (located mainly in the heart) are activated by adrenergic neurotransmitters such as epinephrine, both the blood pressure and heart rate increase, leading to greater cardiovascular work and increasing the demand for oxygen. Bisoprolol reduces cardiac workload by decreasing contractility and the need for oxygen through competitive inhibition of β1-adrenergic receptors

Amlodipine is a calcium channel blocker used to treat hypertension and angina. Amlodipine is considered a peripheral arterial vasodilator that exerts its action directly on vascular smooth muscle to lead to a reduction in peripheral vascular resistance, causing a decrease in blood pressure. Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the influx of calcium ions into both vascular smooth muscle and cardiac muscle. Amlodipine blocks calcium ion influx across cell membranes with selectivity. A stronger effect of amlodipine is exerted on vascular smooth muscle cells than on cardiac muscle cells. Direct actions of amlodipine on vascular smooth muscle result in reduced blood pressure

At the recent SEC meeting for Cardiovascular held on 11th December 2024, the expert panel reviewed the proposal for a fixed dose combination (FDC) of Amlodipine besylate IPeq. to Amlodipine plus Bisoprolol Fumarate IP (2.5 mg + 2.5 mg, 2.5 mg + 5 mg) along with justification for BE and phase III CT waiver.

After detailed deliberation, the committee considered the request for BE and Phase III CT waiver and recommended the grant of permission for manufacturing and marketing of the FDC with the condition to conduct the Phase IV clinical trial.

Accordingly, the expert panel suggested that the firm should submit a Phase IV clinical trial protocol to CDSCO within 3 months of approval of the FDC for review by the committee.

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