LINEZOLID
Please note linezolid is not licensed for the treatment of tuberculosis in the UK.
Linezolid is not usually recommended for the treatment of MDRTB. When it is used, it should be counted as half a drug in a treatment regimen.
DOSAGE
By mouth or intravenous infusion.
Adults: 600mg once a day (oral or intravenous). Consider reducing to 300mg once daily if serious adverse effects develop.
Children ≤11 years: 10mg/kg three times daily
Children >11 years: 10mg/kg twice daily (maximum 600mg in 24 hours)
PREPARATIONS
Oral: 600mg tablets.
100mg/5mL granules for oral suspension.
Parenteral: 600mg/300mL solution for infusion.
DRUG LEVEL MONITORING
Indications for monitoring:
· Known or suspected malabsorption.
· Poor treatment response.
Target Level: 12-24 mg/L (peak).
Timing of sample:
· 2 hours post-oral dose or 1 hour post IV infusion.
Frequency of Levels:
· No need for regular monitoring.
ADVERSE EFFECTS
COMMON:
Gastrointestinal: Diarrhoea (4%), nausea (3%), vomiting.
Neurological: Headache (2%).
Infections: Candidiasis, particularly oral and vaginal (1%).
Hepatic: Transient increases in LFTs.
SERIOUS:
Metabolic: Lactic acidosis.
Dermatological: Urticaria, rash; (rare): Bullous disorders such as Stevens-Johnson syndrome & toxic epidermal necrolysis.
Haematologic: Myelosupression.
Neurological: Peripheral neuropathy, seizure, serotonin syndrome.
Ophthalmic: Optic neuropathy – increased risk with prolonged treatment.
ADVERSE EFFECTS: MONITORING
FBC: Weekly for the first 4 months. 2 weekly between 4 and 6 months. Consider reducing to monthly if stable thereafter.
NOTE: Some papers suggest using a lower dose of 300mg may be better tolerated in terms of myelosuppression.
VISUAL ACUITY & COLOUR DISCRIMINATION: Ask patients whether there have been any changes to their vision, and consider performing visual acuity and colour discrimination testing (Snellen & Ishihara charts) every month. Refer to ophthalmology if necessary.
PERIPHERAL NEUROPATHY: Encourage patients to report any symptoms suggestive of peripheral neuropathy and arrange nerve conduction studies should these arise.
Routine tests as per generic MDR-TB treatment monitoring guidelines.
INTERACTONS
Clarithromycin: increases linezolid serum levels with risk of toxicity (consider drug level monitoring).
Patients should avoid consuming large amounts of tyramine-rich foods (such as mature cheese, yeast extracts, undistilled alcoholic beverages, and fermented soya bean products). In addition, linezolid should not be given with another MAOI or within 2 weeks of stopping another MAOI. Unless close observation and blood-pressure monitoring is possible, avoid in those receiving SSRIs, 5HT1 agonists (‘triptans’), tricyclic antidepressants, sympathomimetics, dopaminergics, buspirone, pethidine and possibly other opioid analgesics.
This information is not inclusive of all drug interactions. Please discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contraindications:
Hypersensitivity: To linezolid.
Mono-amine oxidase inhibitors: Avoid concomitant use of other drugs that inhibit monoamine oxidases A or B (e.g. phenelzine, isocarboxazid, selegiline, moclobemide) or within two weeks of taking any such medicinal product.
Avoid in patients with: Uncontrolled hypertension, phaechromocytoma, carcinoid tumour, thyrotoxicosis, bipolar depression, schizophrenia or acute confusional states.
Breast-feeding
Cautions:
Pregnancy
Avoid: Consumption of large amounts of tyramine rich foods.
Epilepsy/history of seizures: Increased risk of convulsions.
Renal impairment: No dose adjustment is required. However two primary metabolites may accumulate in severe renal impairment, but the clinical significance of this is unknown. Use with caution and monitor for adverse effects closely (see above).
Liver disease: No dose adjustment is required. However due to limited clinical data, use with caution and monitor for adverse effects closely (see above).
Peripheral and optic neuropathy: Patients should be advised to report symptoms of visual 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.
Sample Type: Serum.
Volume Required: 2ml (min 0.1mL).
Sample Container: Plain plastic (non SST).
Container Type: Any.
Availability: NS
Turnaround Time: Telephoned same day if received 9am-3pm Mon-Fri. Written confirmation report will be sent by 1st Class post.
The sample must be heat-treated before dispatch if HIV positive.
Please telephone at least one day in advance of the sample.
Linezolid is not usually recommended for the treatment of MDRTB. When it is used, it should be counted as half a drug in a treatment regimen.
DOSAGE
By mouth or intravenous infusion.
Adults: 600mg once a day (oral or intravenous). Consider reducing to 300mg once daily if serious adverse effects develop.
Children ≤11 years: 10mg/kg three times daily
Children >11 years: 10mg/kg twice daily (maximum 600mg in 24 hours)
PREPARATIONS
Oral: 600mg tablets.
100mg/5mL granules for oral suspension.
Parenteral: 600mg/300mL solution for infusion.
DRUG LEVEL MONITORING
Indications for monitoring:
· Known or suspected malabsorption.
· Poor treatment response.
Target Level: 12-24 mg/L (peak).
Timing of sample:
· 2 hours post-oral dose or 1 hour post IV infusion.
Frequency of Levels:
· No need for regular monitoring.
ADVERSE EFFECTS
COMMON:
Gastrointestinal: Diarrhoea (4%), nausea (3%), vomiting.
Neurological: Headache (2%).
Infections: Candidiasis, particularly oral and vaginal (1%).
Hepatic: Transient increases in LFTs.
SERIOUS:
Metabolic: Lactic acidosis.
Dermatological: Urticaria, rash; (rare): Bullous disorders such as Stevens-Johnson syndrome & toxic epidermal necrolysis.
Haematologic: Myelosupression.
Neurological: Peripheral neuropathy, seizure, serotonin syndrome.
Ophthalmic: Optic neuropathy – increased risk with prolonged treatment.
ADVERSE EFFECTS: MONITORING
FBC: Weekly for the first 4 months. 2 weekly between 4 and 6 months. Consider reducing to monthly if stable thereafter.
NOTE: Some papers suggest using a lower dose of 300mg may be better tolerated in terms of myelosuppression.
VISUAL ACUITY & COLOUR DISCRIMINATION: Ask patients whether there have been any changes to their vision, and consider performing visual acuity and colour discrimination testing (Snellen & Ishihara charts) every month. Refer to ophthalmology if necessary.
PERIPHERAL NEUROPATHY: Encourage patients to report any symptoms suggestive of peripheral neuropathy and arrange nerve conduction studies should these arise.
Routine tests as per generic MDR-TB treatment monitoring guidelines.
INTERACTONS
Clarithromycin: increases linezolid serum levels with risk of toxicity (consider drug level monitoring).
Patients should avoid consuming large amounts of tyramine-rich foods (such as mature cheese, yeast extracts, undistilled alcoholic beverages, and fermented soya bean products). In addition, linezolid should not be given with another MAOI or within 2 weeks of stopping another MAOI. Unless close observation and blood-pressure monitoring is possible, avoid in those receiving SSRIs, 5HT1 agonists (‘triptans’), tricyclic antidepressants, sympathomimetics, dopaminergics, buspirone, pethidine and possibly other opioid analgesics.
This information is not inclusive of all drug interactions. Please discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contraindications:
Hypersensitivity: To linezolid.
Mono-amine oxidase inhibitors: Avoid concomitant use of other drugs that inhibit monoamine oxidases A or B (e.g. phenelzine, isocarboxazid, selegiline, moclobemide) or within two weeks of taking any such medicinal product.
Avoid in patients with: Uncontrolled hypertension, phaechromocytoma, carcinoid tumour, thyrotoxicosis, bipolar depression, schizophrenia or acute confusional states.
Breast-feeding
Cautions:
Pregnancy
Avoid: Consumption of large amounts of tyramine rich foods.
Epilepsy/history of seizures: Increased risk of convulsions.
Renal impairment: No dose adjustment is required. However two primary metabolites may accumulate in severe renal impairment, but the clinical significance of this is unknown. Use with caution and monitor for adverse effects closely (see above).
Liver disease: No dose adjustment is required. However due to limited clinical data, use with caution and monitor for adverse effects closely (see above).
Peripheral and optic neuropathy: Patients should be advised to report symptoms of visual 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.
Sample Type: Serum.
Volume Required: 2ml (min 0.1mL).
Sample Container: Plain plastic (non SST).
Container Type: Any.
Availability: NS
Turnaround Time: Telephoned same day if received 9am-3pm Mon-Fri. Written confirmation report will be sent by 1st Class post.
The sample must be heat-treated before dispatch if HIV positive.
Please telephone at least one day in advance of the sample.
