Therapeutic Equivalence of Generic Product Versus Reference Product of Ivabradine in patients with Chronic Heart Failure: A Comparative Study A thesis Submitted for the partial fulfillment of the Master’s Degree in Pharmaceutical Sciences (Clinical Pharmacy) By:

Abstract

Generic drugs are often sold at prices cheaper than their brand-name analogues, and therefore can enhance patient compliance to important medications and decrease health care expenditures. However, in contrast to innovator drugs, which have to demonstrate their clinical efficacy and safety, generics are considered therapeutically equivalent based on simple bioequivalence testing. So, whether generic drug products are truly therapeutically identical and interchangeable with their innovator counterparts is still a matter of debate and may compromise the response and/or safety of patients. Heart failure is a serious public health problem. It has remarkable limitations of function and quality of life of heart failure patients. Increasing in resting heart rate is directly proportion with increasing with morbidity and mortality rate of patients with heart failure with reduced ejection fraction. Moreover, there is considerable proof that the outcome of cardiovascular patients improved by reduction of elevated hear rate. Beta-blocking agents have been recommended for several along time in international guidelines as a standard treatment in CHF. Despite efforts to optimize β-blocker dose some patients cannot tolerate target dosages of β-blockers to achieve the ultimate reduction in heart rate. In addition, some patients have contraindications to the use of β-blockers. Ivabradine is an inhibitor of the cardiac pacemaker (If) current channel, which modifies pacemaker movement in the Sino-atrial node, giving pure heart rate lowering without affecting other cardiac function. Ivabradine was approved by the European Medicines Agency (EMA) in 2005 and by the United States Food and Drug Administration in 2015. It is incorporated in the European Society of Cardiology (ESC) guidelines for the management of heart failure since 2012 and is licensed as an additional drug or as an alternative to βblockers.

Two generic ivabradine have been introduced into the Egyptian market, Napibradine®

by Global Napi Pharmaceuticals (GNP) and Bradipect® by October Pharma.

Accordingly, although ivabradine generics are expected to have the same tolerability and

efficacy, head-to head comparison of generic and reference ivabradine in terms of efficacy

and tolerability was never performed.