terizidone
Please note terizidone is not licensed for the treatment of tuberculosis in the UK.
It may be sourced from the specialist importer ‘Clinigen’.
DOSAGE
Terizidone is a structural analog that is a combination of two cycloserine molecules. It is thought to undergo hydrolysis of imine groups in terizidone to cycloserine and para-phthalate.
Please note: Cycloserine and terizidone are considered interchangeable (equivalent). The longer half-life of terizidone would make it more suitable for once daily dosing than cycloserine, although there is much less PK/PD data on terizidone.
Adults: Initially 250mg to 500mg per day (oral in one or two divided doses), increased to 1000mg per day (in two divided doses, or once a day if tolerated) depending on cycloserine serum concentrations.
The usual target dose in adults is 10-20mg/kg/day, given in two divided doses (or once a day if tolerated). Maximum 1g per day.
Avoid high-fat meals at the time of taking terizidone.
Children: 15-20 mg/kg once daily. Maximum 1g per day.
All patients must be prescribed pyridoxine whilst receiving terizidone. The usual dose ranges from 50 to 100mg daily, up to 50mg per 250mg of terizidone.
Renal failure:
Reduce dose if creatinine clearance < 30 ml/min, to 250mg once daily or intermittently 500mg on three days per week (for example Monday, Wednesday and Friday).
Dialysis patients should take terizidone after dialysis sessions. There are insufficient data to determine whether terizidone is clinically effective in people undergoing continuous forms of dialysis (e.g. continuous peritoneal dialysis).
PREPARATIONS
Oral: 250mg capusules.
DRUG LEVEL MONITORING
Indications for drug level monitoring:
Target Level of cycloserine: 20 – 35mg/L (peak)
10 – 20mg/L
Timing of sample:
Frequency of Levels:
ADVERSE EFFECTS
COMMON:
Neurological: Confusion, disorientation, dizziness, somnolence (increased risk if peak serum level >35mg/L).
SERIOUS:
Cardiovascular: Cardiac arrhythmias, and sudden development of congestive heart failure (rarely reported at doses greater than 1 to 1.5g daily).
Dermatological: Rash and photosensitivity, Stevens-Johnson syndrome (rare).
Haematological: Vitamin B12 and/ or folic acid deficiency, megaloblastic anaemia or sideroblastic anaemia (rare).
Psychiatric: Depression, seizure, psychotic disturbances (increased risk if peak serum level >35mg/L).
ADVERSE EFFECTS: MONITORING
Routine tests as per generic MDR-TB treatment monitoring guidelines.
INTERACTIONS
Alcohol: Increased risk of convulsions with terizidone.
Isoniazid: Increased risk of CNS toxicity when given with terizidone.
High fat meals: Delayed and reduced absorption of terizidone.
This information is not inclusive of all drug interactions. Please discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contraindications:
Hypersensitivity: To cycloserine or terizidone.
Neurological: Epilepsy, depression, severe anxiety, psychotic states. Alcohol Dependence.
Renal Disease: Severe renal impairment.
Cautions:
Pregnancy & Breast-feeding
Neurological: Stop or reduce dose if symptoms of central nervous system toxicity such as convulsions, psychosis, somnolence, depression, confusion, hyper-reflexia, headache, tremor, vertigo, paresis or dysarthria.
Dermatological: Stop or reduce dose if allergic dermatitis develops.
Renal Disease: Use with caution. Reduce dose in severe renal impairment.
LABORATORY INFORMATION
Please find up to date information at www.assayfinder.com regarding individual providers of drug level monitoring tests. Click on the provider to discover contact details. Turnaround time varies depending on the test and whether it is run locally or sent to an external lab. By contacting laboratories in advance, turnaround time can significantly be reduced.
It may be sourced from the specialist importer ‘Clinigen’.
DOSAGE
Terizidone is a structural analog that is a combination of two cycloserine molecules. It is thought to undergo hydrolysis of imine groups in terizidone to cycloserine and para-phthalate.
Please note: Cycloserine and terizidone are considered interchangeable (equivalent). The longer half-life of terizidone would make it more suitable for once daily dosing than cycloserine, although there is much less PK/PD data on terizidone.
Adults: Initially 250mg to 500mg per day (oral in one or two divided doses), increased to 1000mg per day (in two divided doses, or once a day if tolerated) depending on cycloserine serum concentrations.
The usual target dose in adults is 10-20mg/kg/day, given in two divided doses (or once a day if tolerated). Maximum 1g per day.
Avoid high-fat meals at the time of taking terizidone.
Children: 15-20 mg/kg once daily. Maximum 1g per day.
All patients must be prescribed pyridoxine whilst receiving terizidone. The usual dose ranges from 50 to 100mg daily, up to 50mg per 250mg of terizidone.
Renal failure:
Reduce dose if creatinine clearance < 30 ml/min, to 250mg once daily or intermittently 500mg on three days per week (for example Monday, Wednesday and Friday).
Dialysis patients should take terizidone after dialysis sessions. There are insufficient data to determine whether terizidone is clinically effective in people undergoing continuous forms of dialysis (e.g. continuous peritoneal dialysis).
PREPARATIONS
Oral: 250mg capusules.
DRUG LEVEL MONITORING
Indications for drug level monitoring:
- Ensure therapeutic dose.
- Ensure toxic levels are not reached.
- Renal impairment.
- If patients are switched to terizidone from cycloserine
Target Level of cycloserine: 20 – 35mg/L (peak)
10 – 20mg/L
Timing of sample:
- Peak: 2 hours post dose.
- Repeat at 6 hours if suspect delayed absorption.
- Trough levels – taken immediately prior to a dose.
Frequency of Levels:
- Serum levels after 7 days at target dose.
- Repeat fortnightly for one month and until stable. Serum levels may increase over a 2-week period despite a stable dose due to accumulation of cycloserine.
- Repeat at least 6 monthly.
- Repeat if suspect malabsorption, treatment failure, or neuropsychiatric side effects (should be monitored monthly).
- Patients with reduced renal function require more frequent monitoring, initially weekly until stable.
- High Peak Level: Reduce dose if level >35mg/L. If level is 35 to 50mg/L, consider reducing dose by 25% per day. If level >50mg/L, consider halving the dose. Recheck level after four days.
- Low Peak Level: Increase dose if level <15mg/L.
- Trough levels: Terizidone/Cycloserine absorption may be slow and consequently a 2-hour peak level may not capture the true Cmax. It is rare to see elevated peak levels in the absence of elevated trough levels, therefore a raised trough level may indicate potentially toxic ‘true’ peak levels. Consider serial peak serum level assays (e.g. at 2, 4 and 6 hours post dose), and dose reduction
ADVERSE EFFECTS
COMMON:
Neurological: Confusion, disorientation, dizziness, somnolence (increased risk if peak serum level >35mg/L).
SERIOUS:
Cardiovascular: Cardiac arrhythmias, and sudden development of congestive heart failure (rarely reported at doses greater than 1 to 1.5g daily).
Dermatological: Rash and photosensitivity, Stevens-Johnson syndrome (rare).
Haematological: Vitamin B12 and/ or folic acid deficiency, megaloblastic anaemia or sideroblastic anaemia (rare).
Psychiatric: Depression, seizure, psychotic disturbances (increased risk if peak serum level >35mg/L).
ADVERSE EFFECTS: MONITORING
Routine tests as per generic MDR-TB treatment monitoring guidelines.
INTERACTIONS
Alcohol: Increased risk of convulsions with terizidone.
Isoniazid: Increased risk of CNS toxicity when given with terizidone.
High fat meals: Delayed and reduced absorption of terizidone.
This information is not inclusive of all drug interactions. Please discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contraindications:
Hypersensitivity: To cycloserine or terizidone.
Neurological: Epilepsy, depression, severe anxiety, psychotic states. Alcohol Dependence.
Renal Disease: Severe renal impairment.
Cautions:
Pregnancy & Breast-feeding
Neurological: Stop or reduce dose if symptoms of central nervous system toxicity such as convulsions, psychosis, somnolence, depression, confusion, hyper-reflexia, headache, tremor, vertigo, paresis or dysarthria.
Dermatological: Stop or reduce dose if allergic dermatitis develops.
Renal Disease: Use with caution. Reduce dose in severe renal impairment.
LABORATORY INFORMATION
Please find up to date information at www.assayfinder.com regarding individual providers of drug level monitoring tests. Click on the provider to discover contact details. Turnaround time varies depending on the test and whether it is run locally or sent to an external lab. By contacting laboratories in advance, turnaround time can significantly be reduced.