PRETOMANID
Please note pretomanid is not licensed for the treatment of tuberculosis in the UK.
NHS England commissioning is anticipated Mid-2024
It may be imported into the UK via Tanner CH or specialist importer.
DOSAGE
By mouth:
Adults and adolescents aged 14 years and older: 200mg once daily for 26 weeks as part of BPaLM / 39 weeks as part of BPaL regimen.
Paediatric dose: The safety and efficacy of pretomanid in children and adolescents have not yet been established
Pretomanid should be taken with food and should be swallowed with water.
PREPARATIONS
Oral: 200mg tablets
DRUG LEVEL MONITORING
ADVERSE EFFECTS
COMMON:
The most frequent adverse drug reactions when pretomanid is used in combination with bedaquiline and linezolid were nausea (36%), vomiting (28%) and transaminases increased (21%).
Gastrointestinal: Nausea, vomiting, dyspepsia, abdominal pain, diarrhoea, constipation, decreased appetite
Neurologic: peripheral neuropathy, headache, dysgeusia, dizziness
Hepatic: transient increases in transaminases, hyperbilirubinaemia
Dermatologic: rash, acne, pruritus, dry skin
SERIOUS:
Serious adverse drug reactions when pretomanid is used in combination with bedaquiline and linezolid were peripheral neuropathy (81%) and anaemia (37%), which occur with linezolid. Serious adverse drug reactions that are considered attributable to linezolid are marked with *.
Endocrine: lactic acidosis*
Haematologic: Myelosupression*
Neurologic : peripheral neuropathy*
Ophthalmic: optic neuropathy*
Cardiac: prolonged QTc interval
ADVERSE EFFECTS: MONITORING
LFT: At baseline, then weekly for one month, fortnightly for one month, then monthly. Treatment interruption is recommended if:
Potassium, Calcium and Magnesium: Check at baseline. Repeat if prolonged QTc occurs.
VISUAL ACUITY & COLOUR DISCRIMINATION: Encourage patients to report any changes to their vision and refer to ophthalmology if any reported. Routine monitoring 6 monthly.
ECG: At baseline, then monthly. Discontinue BPaLM regimen if the patient develops a clinically significant ventricular arrhythmia or a QTcF interval of greater than 500 ms (confirmed by repeat ECG).
INTERACTONS
Benzylpenicillin: Pretomanid inhibits OAT3 transporter, which nay result in increased concentrations of benzylpenicillin
Ciprofloxacin Pretomanid inhibits OAT3 transporter, which nay result in increased concentrations of ciprofloxacin
CYP3A4 inducers (e.g. efavirenz, etravirine, rifamycins including rifampicin, rifapentine and rifabutin, carbamazepine, phenytoin, St. John’s wort): Avoid co-administration due to expected acceleration of pretomanid metabolism, resulting in reduced effect
Efavirenez accelerated metabolism of pretomanid resulting in reduced effect. Avoid co-administration.
Indomethacin: Pretomanid inhibits OAT3 transporter, which nay result in increased concentrations of indomethacin
Methotrexate: Pretomanid inhibits OAT3 transporter, which nay result in increased concentrations of methotrexate
Paclitaxel: accelerated metabolism of paclitaxel
Rifampicin accelerated metabolism of pretomanid resulting in reduced effect. Avoid co-administration.
Warfarin: accelerated metabolism of warfarin. Monitor INR
BCRP substrates (e.g. rosuvastatin, prazosin, glyburide, sulfasalazine): Pretomanid inhibits BCRP and may increase their exposure. Monitor for drug-related adverse reactions
OATP1B3 substrates (e.g., valsartan, statins): Pretomanid inhibits OATP1B3 and may increase their exposure. Monitor for drug-related adverse reactions
P-gp substrates (e.g. digoxin, dabigatran etexilate, verapamil): Pretomanid inhibits P-gp and may increase their exposure. Monitor for drug-related adverse reactions
This information is not inclusive of all drug interactions. Please refer to the SPC or BNF for further information, or discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contra-indications
Hypersensitivity to pretomanid or other nitroimidazoles
Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
Children <14 years: The safety and effectiveness has not been established in children
Cautions:
Pregnanacy: Very limited data. Pretomanid should be used during pregnancy only if the benefit to the patient is considered to outweigh the potential risk to the foetus.
Breastfeeding: It is unknown whether pretomanid/metabolites are excreted in human milk.
Renal disease: The safety and efficacy of pretomanid in populations with hepatic impairment have not been established. Use in patients with renal impairment is not recommended.
Hepatic disease: The safety and efficacy of pretomanid in populations with hepatic impairment have not been established.
LABORATORY INFORMATION
n/a
NHS England commissioning is anticipated Mid-2024
It may be imported into the UK via Tanner CH or specialist importer.
DOSAGE
By mouth:
Adults and adolescents aged 14 years and older: 200mg once daily for 26 weeks as part of BPaLM / 39 weeks as part of BPaL regimen.
Paediatric dose: The safety and efficacy of pretomanid in children and adolescents have not yet been established
Pretomanid should be taken with food and should be swallowed with water.
PREPARATIONS
Oral: 200mg tablets
DRUG LEVEL MONITORING
- Not currently available
ADVERSE EFFECTS
COMMON:
The most frequent adverse drug reactions when pretomanid is used in combination with bedaquiline and linezolid were nausea (36%), vomiting (28%) and transaminases increased (21%).
Gastrointestinal: Nausea, vomiting, dyspepsia, abdominal pain, diarrhoea, constipation, decreased appetite
Neurologic: peripheral neuropathy, headache, dysgeusia, dizziness
Hepatic: transient increases in transaminases, hyperbilirubinaemia
Dermatologic: rash, acne, pruritus, dry skin
SERIOUS:
Serious adverse drug reactions when pretomanid is used in combination with bedaquiline and linezolid were peripheral neuropathy (81%) and anaemia (37%), which occur with linezolid. Serious adverse drug reactions that are considered attributable to linezolid are marked with *.
Endocrine: lactic acidosis*
Haematologic: Myelosupression*
Neurologic : peripheral neuropathy*
Ophthalmic: optic neuropathy*
Cardiac: prolonged QTc interval
ADVERSE EFFECTS: MONITORING
LFT: At baseline, then weekly for one month, fortnightly for one month, then monthly. Treatment interruption is recommended if:
- Aminotransferase elevations are accompanied by total bilirubin elevation greater than 2 times the upper limit of normal.
- Aminotransferase elevations are greater than 8 times the upper limit of normal.
- Aminotransferase elevations are greater than 5 times the upper limit of normal and persist beyond 2 weeks
Potassium, Calcium and Magnesium: Check at baseline. Repeat if prolonged QTc occurs.
VISUAL ACUITY & COLOUR DISCRIMINATION: Encourage patients to report any changes to their vision and refer to ophthalmology if any reported. Routine monitoring 6 monthly.
ECG: At baseline, then monthly. Discontinue BPaLM regimen if the patient develops a clinically significant ventricular arrhythmia or a QTcF interval of greater than 500 ms (confirmed by repeat ECG).
INTERACTONS
Benzylpenicillin: Pretomanid inhibits OAT3 transporter, which nay result in increased concentrations of benzylpenicillin
Ciprofloxacin Pretomanid inhibits OAT3 transporter, which nay result in increased concentrations of ciprofloxacin
CYP3A4 inducers (e.g. efavirenz, etravirine, rifamycins including rifampicin, rifapentine and rifabutin, carbamazepine, phenytoin, St. John’s wort): Avoid co-administration due to expected acceleration of pretomanid metabolism, resulting in reduced effect
Efavirenez accelerated metabolism of pretomanid resulting in reduced effect. Avoid co-administration.
Indomethacin: Pretomanid inhibits OAT3 transporter, which nay result in increased concentrations of indomethacin
Methotrexate: Pretomanid inhibits OAT3 transporter, which nay result in increased concentrations of methotrexate
Paclitaxel: accelerated metabolism of paclitaxel
Rifampicin accelerated metabolism of pretomanid resulting in reduced effect. Avoid co-administration.
Warfarin: accelerated metabolism of warfarin. Monitor INR
BCRP substrates (e.g. rosuvastatin, prazosin, glyburide, sulfasalazine): Pretomanid inhibits BCRP and may increase their exposure. Monitor for drug-related adverse reactions
OATP1B3 substrates (e.g., valsartan, statins): Pretomanid inhibits OATP1B3 and may increase their exposure. Monitor for drug-related adverse reactions
P-gp substrates (e.g. digoxin, dabigatran etexilate, verapamil): Pretomanid inhibits P-gp and may increase their exposure. Monitor for drug-related adverse reactions
This information is not inclusive of all drug interactions. Please refer to the SPC or BNF for further information, or discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contra-indications
Hypersensitivity to pretomanid or other nitroimidazoles
Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
Children <14 years: The safety and effectiveness has not been established in children
Cautions:
Pregnanacy: Very limited data. Pretomanid should be used during pregnancy only if the benefit to the patient is considered to outweigh the potential risk to the foetus.
Breastfeeding: It is unknown whether pretomanid/metabolites are excreted in human milk.
Renal disease: The safety and efficacy of pretomanid in populations with hepatic impairment have not been established. Use in patients with renal impairment is not recommended.
Hepatic disease: The safety and efficacy of pretomanid in populations with hepatic impairment have not been established.
LABORATORY INFORMATION
n/a