Adverse reactions to drugs are not more common if FDCs are used. Nevertheless, whenever side-effects to one or more components in a FDC are suspected, there will be a need to switch to single-drug formulations. Reactions to FDCs which warrant withdrawal of drugs generally occur in only 3-6% of patients on TB treatment. These reactions may be more common in patients co-infected with HIV (e.g. when using thioacetazone); however FDCs are not contraindicated for these patients. Alimited stock of single drugs should therefore be available in referral centres, where patients with severe adverse reactions, although very rare, can be managed under the supervision of a TB specialist.
FDCs can be used in some special situations:
• Renal failure - in normal dosage range, rifampicin, isoniazid and pyrazinamide are considered to be safe. Patients with impaired renal function may require a reduced dosage of ethambutol as it is primarily excreted through the kidneys. Patients with severe renal failure should receive pyridoxine to prevent peripheral neuropathy.
• Liver disease - most anti-TB drugs can cause liver damage. Risk-benefit should be considered in patients experiencing severe side-effects (including symptoms of hepatitis and/or jaundice) or in patients who suffer from liver injuries. Jaundiced patients who develop TB should receive a treatment regimen adapted to their condition.
Further information on management of adverse drug reactions can be found in Interventions for tuberculosis control and elimination1.
1 Reider HL. Interventions for Tuberculosis Control and Elimination, Paris, International Union Against Tuberculosis and Lung Disease (IUATLD), 2002.