Fixed dose drug combinations: Issues and challenges in India

Medicines are an integral part of healthcare. More than one drug is frequently used for treatment of either single ailment or multiple comorbid conditions. Sometimes, two or more drugs are combined in a fixed ratio into a single dosage form, which is termed as fixed dose combinations (FDCs). The FDCs are justified when they demonstrate clear benefits in terms of (a) potentiating the therapeutic efficacy, (b) reducing the incidence of adverse effect of drugs, (c) having pharmacokinetic advantage, (d) better compliance by reducing the pill burden, (e) reducing dose of individual drugs, (f) decreasing development of resistance, and (g) cheaper than individual drug because of reduced cost from packaging to distribution. It is important that the above claims are adequately supported by scientific evidence. The FDCs formulated without due diligence can pose problems namely (a) pharmacodynamic mismatch between the two components, one drug having additive/antagonistic effect leading to reduced efficacy or enhanced toxicity, (b) pharmacokinetic mismatch and having peak efficacy at different time, (c) chemical noncompatibility leading to decreased shelf life, (d) drug interactions because of the common metabolizing pathways, and (e) limitations of finer dosing titration of individual ingredients. Although FDCs are available in almost all therapeutic categories, many of them are bizarre combinations. The therapeutic categories having high number of FDCs are cough, cold, and fever preparations; analgesics and muscle relaxants; antimicrobials; drugs for hypertension, dyslipidemia, diabetes, and psychiatric disorders; and vitamins and minerals. The FDC formulation may have up to 5 or even more ingredients with or without rationality of their presence and in the quantity. Essential medicines are those that satisfy the priority health care needs of the population and intended to be available at all times, in adequate amount and at affordable price. The list is prepared with due consideration to disease prevalence, efficacy, safety, and comparative cost‑effectiveness of medicines. Out of the 414 medicines included in the 19 th list of WHO List of Essential Medicines, 27 are FDCs. We included 24 FDCs out of 376 entities in the National List of Essential Medicines of India (NLEM) 2015. These FDCs were included after due deliberations in national consultations with scientific justifications. Majority of the FDCs in both the lists belong to antimalarial, antitubercular, antiretroviral drugs, which emphasize the importance of FDC use in treatment adherence and prevention of drug resistance. Notwithstanding with the basic principle of formulating FDC, the Indian medicine market has become …