CDSCO Orders Label Changes for Carbimazole, Doxycycline After PvPI Flags New ADR Signals

New Delhi: In a move underscoring its sharpened focus on patient safety and rational drug use, India's drug regulator, the Central Drugs Standard Control Organisation (CDSCO), has asked State Drugs Controllers to direct manufacturers to update Prescribing Information Leaflets (PILs), incorporating agranulocytosis as an ADR for Carbimazole and CNS side effects (restlessness, anxiety, irritability, nervousness, and dizziness) for Doxycycline.

The directive comes following recommendations from the Pharmacovigilance Programme of India (PVPI), which identified the necessity for stronger risk communication based on accumulated adverse event reports and safety evaluations.

The National Coordination Centre for Pharmacovigilance Programme of India (NCC-PvPI), Indian Pharmacopoeia Commission (IPC), Ghaziabad, forwarded recommendations arising from the assessment of Adverse Drug Reaction (ADR) reports pertaining to Carbimazole and Doxycycline formulations, which were discussed at the 26th Signal Review Panel meeting held on 24th March, 2025.

In the meeting, PvPI evaluated the Patient Population Incidence of adverse Drug Reactions (PPI-ADRs) based on Individual Case Study Reports (ICSRs) and recommended that CDSCO take necessary measures to incorporate “agranulocytosis” as an adverse drug reaction in the Prescribing Information Leaflet (PIL) of Carbimazole-based medical products, and “CNS Side Effects (Restlessness, Anxiety, Irritability, Nervousness, and Dizziness)” as adverse drug reactions in the PIL of Doxycycline-based medical products marketed in the country.

Carbimazole is an antithyroid agent that decreases the uptake and concentration of inorganic iodine by the thyroid; it also reduces the formation of di-iodotyrosine and thyroxine. Once converted to its active form of methimazole, it prevents the thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4.

Doxycycline is a broad-spectrum antibiotic synthetically derived from oxytetracycline. It is a second-generation tetracycline. Doxycycline is used to treat a wide variety of gram-positive and gram-negative bacterial infections. It is also used to treat acne and malaria.

The recommendations of NCC-PvPI were subsequently reviewed by the Subject Expert Committees (SEC)—Endocrinology and Metabolism and Antimicrobial and Antiparasitic during their meetings held on 06.01.2026 at CDSCO HQ, New Delhi.

After detailed deliberations, the committees recommended that CDSCO request the State Drugs Controllers to direct manufacturers to incorporate agranulocytosis associated with Carbimazole and CNS side effects (Restlessness, Anxiety, Irritability, Nervousness, and Dizziness) with Doxycycline as ADRs in the corresponding Prescribing Information Leaflets (PILs) of the drugs.

Further, the committee recommended inclusion of the above CNS side effects in the caution section of the PIL.

Considering the above recommendation of the SEC, the CDSCO asked all State/UT Licensing Authorities

"You are requested to direct the manufacturers of Carbimazole formulations under your jurisdiction to mention “agranulocytosis” as an adverse drug reaction in the Prescribing Information Leaflet (PIL) / Promotional Literature of the drug.

You are requested to direct the manufacturers of Doxycycline formulations under your jurisdiction to mention “CNS Side Effects (Restlessness, Anxiety, Irritability, Nervousness, and Dizziness)” as adverse drug reactions in the caution section of the Package Insert / Promotional Literature of the drug."

Further, it noted that action taken in this regard may be intimated to this office.

To view the official notices, click the link below: