Drug makers to include DPP4 inhibitors induced Arthralgia in package insert, says CDSCO panel
New Delhi: The Subject Expert Committee (SEC) functional under the Central Drugs Standard Control Organization (CDSCO) has recommended that CDSCO may request State Drugs Controllers to direct the manufacturers of the drug to include Dipeptidyl Peptidase-4 (DPP-4) Inhibitors induced Arthralgia in the package insert of the drug.
This came in line with the recommendation of the signal review panel, Pharmacovigilance Programme of India (PvPI), and the Indian Pharmacopoeia Commission (IPC), which was placed before the committee.
DPP-4 inhibitors are a class of prescription medicines that are used with diet and exercise to control high blood sugar in adults with type 2 diabetes.
DPP-4 inhibitors act by inhibiting the enzyme Dipeptidyl Peptidase -4, which is responsible for the inactivation of incretin hormones such as Glucagon like peptide or GLP1. Incretins are released throughout the day and upregulated in response to meals as part of glucose homeostasis. Reduced inhibition of incretins increases insulin synthesis and decreases glucagon release in a manner dependent on glucose concentrations.
Medicines in the DPP-4 inhibitor class include sitagliptin, saxagliptin, linagliptin, and alogliptin. A few popular brands of DPP-4 inhibitors include Bristol Myers Squibb's Onglyza 5mg Tab (Saxagliptin), Sun Pharma's Istavel 100mg Tablet (Sitagliptin), MSD Pharma's Januvia 100 Mg Tablet (Sitagliptin) and others.
Arthralgia means pain in a joint. Polyarthralgia means pain in several joints. The pharmacological inhibition of DPP-4 seems to induce adverse events related to cytokine-induced inflammation.
Several clinical cases regarding the association of DPP-4 inhibitors and the onset of arthritis/arthralgia have been reported in the literature. Various mechanisms could be responsible for DPP-4 inhibitor-induced arthritis/arthralgia, and the increase of cytokines, chemokines, matrix metalloproteinases (MMPs) and genetic factors plays an important role.
The USFDA published a safety announcement regarding the entire drug class, stating, "The U.S. Food and Drug Administration (FDA) is warning that the type 2 diabetes medicines sitagliptin, saxagliptin, linagliptin, and alogliptin may cause joint pain that can be severe and disabling. We have added a new warning and precaution about this risk to the labels of all medicines in this drug class, called "dipeptidyl peptidase-4 (DPP-4) inhibitors."
The recommendation of the signal review panel, PVPI, IPC, was placed before the committee at the recent SEC meeting for Endocrinology & Metabolism regarding the adverse reaction related to Dipeptidyl peptidase (DPP)-4 inhibitors, a class of oral drugs used to treat type 2 diabetes mellitus (T2DM).
In view of the above, after detailed deliberation, the committee recommended,
"CDSCO may request State Drugs Controllers to direct the manufacturers of the drug to include DPP4 inhibitors induced Arthralgia in the package insert of the drug."
