Terizidone (Trd) Terizidone is part of a group of drugs used in the treatment of drug resistant TB called oral bacteriostatic second-line agents. It is used as part of treatment regimens, generally involving 5 medicines, to treat MDR and XDR TB. Terizidone is obtained by combining two molecules of cycloserine. Terizidone is used as part of South Africa’s standard treatment regimen for MDR TB. Dosage: Adults: Adults with liver damage - creatine clearance < 30 ml/min: Children: 15 – 20 mg/kg daily (max dose 1000 mg) N/A 10 – 20 mg/kg daily (max dose 1000 mg) Cycloserine is taken twice daily, generally one tablet (250 mg) in the daytime and 2 tablets (500 mg) at night. Cycloserine is taken during the intensive and continuation phases of treatment. All patients receiving terizidone should be given 50 mg of pyridoxine for every 250 mg of terizidone. How it works: Terizidone acts by preventing cell wall synthesis by inhibiting two necessary enzymes. Side effects: Terizidone is associated with neurologic and psychiatric disturbances. Symptoms can include severe depression, anxiety, panic attacks, psychosis, seeing and hearing things that do not exist, paranoia, dizziness, slurred speech and convulsions. Terizidone should be immediately halted if the patient is suicidal or psychotic. Terizidone should not be given to patients with epilepsy, severe depression or psychosis. Terizidone may also cause nausea, vomiting and skin allergies. Clinical evidence and approval: Terizidone is approved for the treatment of tuberculosis. Terizidone may be less toxic than cycloserine.1 It is better tolerated with less adverse effects. Studies on terizidone are scarce and there is little evidence demonstrating safety and efficacy. However, it should be used with caution in patients that are intolerant to cycloserine. One study found that terizidone was generally tolerable for dialysed patients receiving treatment for TB. Of 6 patients given terizidone, 5 showed good tolerability. One patient abandoned terizidone as it caused depressive symptoms.2 Pricing: SA Public sector (Aug 2009 – July 2011 tender)3 250 mg capsule R6.42 SA Public sector (August 2011 – July 2013 tender) Included in this tender. Prices not yet available. SA Private sector 250 mg R13.59 Global Drug Facility4 250 mg R11.17 US$1.65 * Price per lowest unit (single tablet) Advocacy issues: SA discontinued purchasing cycloserine as clinicians favoured terizidone, as they found the side effects associated with cycloserine more severe and less manageable that terizidone. Global supply of terizidone is extremely vulnerable. Further research is needed to establish the safety and efficacy of paediatric use. No paediatric formulations are available. [MSF] Further research is needed to understand potential interactions with antiretrovirals [MSF]. Manufacturers and suppliers: Today there is only one quality assured source of terizidone available. There are no manufacturers with dossiers submitted to WHO PQ, and no manufacturers likely to submit dossiers in 2011. The supply of quality-assured terizidone therefore remains extremely vulnerable to disruption. Additional manufacturers may exist in China, India, the former Soviet Union and other countries, but whether they comply with WHO quality standards is unknown.5 Source: MSF