Thalidomide in Transfusion-Dependent Beta-Thalassaemia in Pakistan: A Proposed Framework for Safe Prescribing, Risk-Stratified Monitoring, and Pharmacovigilance

Abstract

Background. Transfusion-dependent beta-thalassaemia (TDT) kills children in Pakistan. Mortality from iron overload complications, cardiac siderosis, and panhypopituitarism is common before adulthood in settings where access to regular transfusion and chelation is poor. In this context, thalidomide has been adopted at multiple centres as an off-label fetal haemoglobin (HbF) inducer to reduce transfusion dependence. It is being used, frequently, without patient registration, without any pregnancy risk assessment, and without pharmacovigilance reporting to the Drug Regulatory Authority of Pakistan (DRAP).

Clinical Context. Unlike Western populations or well-resourced Asian thalassaemia centres, the majority of female TDT patients in Pakistan never reach menarche. Iron-overload-driven hypogonadotrophic hypogonadism is documented in over 80% of Pakistani TDT patients. A framework that applies blanket pregnancy prevention rules to this population is both clinically inappropriate and practically undeliverable in remote settings. It also diverts attention from the patients who genuinely need those protections.

Objectives. To review the evidence for thalidomide in TDT, document its known risks in the Pakistani context, and propose a practical risk-stratified prescribing and monitoring framework adapted from the US S.T.E.P.S. programme.

Proposed Framework. Five components are proposed: (1) prescriber and centre registration; (2) risk-stratified reproductive assessment with targeted pregnancy prevention for those who actually need it; (3) structured haematological, neurological, and endocrine monitoring; (4) response assessment at six months; and (5) compulsory adverse event reporting through DRAP.

Conclusions. Thalidomide offers real benefit to a population with few alternatives. The teratogenic risk is real but applies to a minority of patients in Pakistan's TDT population. A framework that ignores the endocrine reality of Pakistani TDT patients protects no one and will not be followed. One that is honest about who needs protecting, and how, might be.