DELAMANID
Please note delamanid is not licensed for the treatment of tuberculosis in the UK. It may be sourced from the specialist importers ‘Clinigen’ and ‘Ascot’.
There are limited data available on delamanid. Clinicians are advised to monitor patients closely to ensure the safe and effective use of this drug. Delamanid has additional materials to minimise the risk during use which should be read in full before initiating therapy. Access via http://beta.medicines.org.uk/emc/medicine/28927
DOSAGE
Adults (aged 18 to 64 years): 100mg twice a day for 24 weeks.
Children:
* When available, delamanid 25mg dispersible tablets should be prioritised for young children over the 50mg tablet. Delamanid 50mg tablets dissolved in water have been shown to be bioequivalent to tablets swallowed whole.
Elderly (>65 years of age): No data are available in the elderly.
Delamanid should be taken with food.
PREPARATIONS
Oral: 50mg tablets.
DRUG LEVEL MONITORING
ADVERSE EFFECTS
There are currently limited data on adverse drug reactions cause by delamanid. Current data are based on one double-blind clinical trial in which 321 patients received delamanid in combination with an Optimised Background Regimen (OBR) to treat MDRTB. Refer to product SmPC for further information.
Report all suspected adverse drug reactions to the Medicines and Healthcare products Regulatory Agency (MHRA) through the Yellow Card Scheme.
COMMON:
Dermatological: Dermatitis & urticaria.
Gastrointestinal: Nausea, vomiting, diarrhoea.
Neurological: Dizziness, insomnia, paraesthesia, tremor
Respiratory: Haemoptysis
SERIOUS:
Cardiovascular: QTc prolongation (more common in hypoalbuminaemia (particularly below 2.8 g/dl), known congenital prolongation of the QTc-interval, or any condition or concomitant drug that may prolong the QTc-interval).
Haematological: Anaemia, eosinophilia, thrombocytopaenia, leucopaenia.
Hepatic: Increases in LFTs.
Metabolic: Hypertriglyceridaemia, hypercholesterolaemia
Psychiatric: Psychotic disorder, agitation, anxiety, depression, restlessness.
ADVERSE EFFECTS: MONITORING
ECG: Baseline and monthly throughout treatment.
•Discontinue delamanid and all other QT prolonging drugs if the patient develops:
Albumin: Baseline and monthly throughout treatment.
Routine tests as per generic MDR-TB treatment monitoring guidelines. (hyperlink)
INTERACTIONS
Many of the drugs listed below increase the risk of prolonged QT interval when used in combination with Delaminid. We therefore recommend increasing the frequency of ECG monitoring. There is no evidence for how much more frequently ECGs should be performed but we would recommend at least fortnightly for the first month and if the QTc interval remains within normal range to reduce this to monthly thereafter.
Anti-arrhythmics: (e.g. amiodarone, dysopyramide, procainamide, quinidine and sotalol). Risk of prolonged QT interval.
Antiretrovirals: Limited data. lopinavir/ritonavir increases exposure to the metabolite DM-6705, which has been associated with QTc prolongation. No effect on exposure to tenofovir, lopinavir/ritonavir and efavirenz.
Antidepressants, Tricylic: Risk of prolonged QT interval.
Antipsychotics (e.g. thioridazine, haloperidol, chlorpromazine, trifluoperazine, percycline, prochlorperazine, fluphenazine, sertindole, and pimozide). Risk of prolonged QT interval.
Antiemetics: domperidone. Risk of prolonged QT interval.
Azole antifungals (e.g. fluconazole, itraconazole, posaconazole, voriconazole): Risk of prolonged QT interval.
Ethambutol: steady state plasma concentrations of ethambutol increased by approximately 25%. The clinical relevance is unknown.
Fluoroquinolones (e.g. moxifloxacin): Risk of prolonged QT interval. Moxifloxacin is not recommended for use in patients treated with delamanid. Increase frequency of ECG monitoring when delamanid is used in combination with a fluoroquinolone.
Macrolides: Risk of prolonged QT interval.
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
Contraindications:
CYP3A inducers (e.g. carbamazepine).
Pregnancy & breast feeding.
Hypersensitivity: to delamanid.
Hypoalbuminaemia: Serum albumin < 2.8 g/dL.
Cautions:
Alcohol or substance misuse: Lack of data.
Complex extrapulmonary TB (e.g., meningitis, osteoarthritis).
Children aged <18 years: The safety and effectiveness has not been established in children.
Elderly patients ≥ 65 years: Lack of data in patients aged 65 and over to determine whether they respond differently from younger patients.
Cardiovascular: Due to the risk of QT prolongation with delamanid, ECGs should be monitored closely in patients:
•With serum calcium, magnesium, or potassium levels below the lower limits of normal
Diabetes: Lack of data.
HIV/TB co-infection: Limited or no information on the use of delamanid.
Liver disease: Lack of data in moderate to severe liver disease. No dose adjustment required in mild hepatic impairment.
Renal disease: Lack of data for use in patients with severe renal impairment or end stage renal disease requiring hemodialysis or peritoneal dialysis.
LABORATORY INFORMATION
Please find up to date information at www.assayfinder.com regarding individual providers of drug level monitoring tests. Click on the provider for contact details. Turnaround time is usually a few days to a week but this can be reduced by calling ahead and informing the laboratory in advance.
There are limited data available on delamanid. Clinicians are advised to monitor patients closely to ensure the safe and effective use of this drug. Delamanid has additional materials to minimise the risk during use which should be read in full before initiating therapy. Access via http://beta.medicines.org.uk/emc/medicine/28927
DOSAGE
Adults (aged 18 to 64 years): 100mg twice a day for 24 weeks.
Children:
* When available, delamanid 25mg dispersible tablets should be prioritised for young children over the 50mg tablet. Delamanid 50mg tablets dissolved in water have been shown to be bioequivalent to tablets swallowed whole.
Elderly (>65 years of age): No data are available in the elderly.
Delamanid should be taken with food.
PREPARATIONS
Oral: 50mg tablets.
DRUG LEVEL MONITORING
- Drug levels need not be routinely measured.
ADVERSE EFFECTS
There are currently limited data on adverse drug reactions cause by delamanid. Current data are based on one double-blind clinical trial in which 321 patients received delamanid in combination with an Optimised Background Regimen (OBR) to treat MDRTB. Refer to product SmPC for further information.
Report all suspected adverse drug reactions to the Medicines and Healthcare products Regulatory Agency (MHRA) through the Yellow Card Scheme.
COMMON:
Dermatological: Dermatitis & urticaria.
Gastrointestinal: Nausea, vomiting, diarrhoea.
Neurological: Dizziness, insomnia, paraesthesia, tremor
Respiratory: Haemoptysis
SERIOUS:
Cardiovascular: QTc prolongation (more common in hypoalbuminaemia (particularly below 2.8 g/dl), known congenital prolongation of the QTc-interval, or any condition or concomitant drug that may prolong the QTc-interval).
Haematological: Anaemia, eosinophilia, thrombocytopaenia, leucopaenia.
Hepatic: Increases in LFTs.
Metabolic: Hypertriglyceridaemia, hypercholesterolaemia
Psychiatric: Psychotic disorder, agitation, anxiety, depression, restlessness.
ADVERSE EFFECTS: MONITORING
ECG: Baseline and monthly throughout treatment.
•Discontinue delamanid and all other QT prolonging drugs if the patient develops:
- Clinically significant ventricular arrhythmia
- A QTc interval of > 500 ms (confirmed by repeat ECG)
- If QTc interval >450ms in males, or >470 in females:
- Monitor ECGs more frequently to confirm that the QTc interval has returned to baseline. We suggest increasing monitoring to 2 weekly.
- If syncope occurs, obtain an ECG to detect QT prolongation.
Albumin: Baseline and monthly throughout treatment.
- If serum albumin < 28g/L (2.8 g/dL): do not initiate treatment or continue treatment with delamanid.
- If serum albumin 28 to 34 g/L (2.8 to 3.4 g/dL): increase the frequency of ECG monitoring.
Routine tests as per generic MDR-TB treatment monitoring guidelines. (hyperlink)
INTERACTIONS
Many of the drugs listed below increase the risk of prolonged QT interval when used in combination with Delaminid. We therefore recommend increasing the frequency of ECG monitoring. There is no evidence for how much more frequently ECGs should be performed but we would recommend at least fortnightly for the first month and if the QTc interval remains within normal range to reduce this to monthly thereafter.
Anti-arrhythmics: (e.g. amiodarone, dysopyramide, procainamide, quinidine and sotalol). Risk of prolonged QT interval.
Antiretrovirals: Limited data. lopinavir/ritonavir increases exposure to the metabolite DM-6705, which has been associated with QTc prolongation. No effect on exposure to tenofovir, lopinavir/ritonavir and efavirenz.
Antidepressants, Tricylic: Risk of prolonged QT interval.
Antipsychotics (e.g. thioridazine, haloperidol, chlorpromazine, trifluoperazine, percycline, prochlorperazine, fluphenazine, sertindole, and pimozide). Risk of prolonged QT interval.
Antiemetics: domperidone. Risk of prolonged QT interval.
Azole antifungals (e.g. fluconazole, itraconazole, posaconazole, voriconazole): Risk of prolonged QT interval.
Ethambutol: steady state plasma concentrations of ethambutol increased by approximately 25%. The clinical relevance is unknown.
Fluoroquinolones (e.g. moxifloxacin): Risk of prolonged QT interval. Moxifloxacin is not recommended for use in patients treated with delamanid. Increase frequency of ECG monitoring when delamanid is used in combination with a fluoroquinolone.
Macrolides: Risk of prolonged QT interval.
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
Contraindications:
CYP3A inducers (e.g. carbamazepine).
Pregnancy & breast feeding.
Hypersensitivity: to delamanid.
Hypoalbuminaemia: Serum albumin < 2.8 g/dL.
Cautions:
Alcohol or substance misuse: Lack of data.
Complex extrapulmonary TB (e.g., meningitis, osteoarthritis).
Children aged <18 years: The safety and effectiveness has not been established in children.
Elderly patients ≥ 65 years: Lack of data in patients aged 65 and over to determine whether they respond differently from younger patients.
Cardiovascular: Due to the risk of QT prolongation with delamanid, ECGs should be monitored closely in patients:
- Taking other QT prolonging drugs (e.g fluoroquinolones, macrolides, clofazimine)
•With serum calcium, magnesium, or potassium levels below the lower limits of normal
Diabetes: Lack of data.
HIV/TB co-infection: Limited or no information on the use of delamanid.
Liver disease: Lack of data in moderate to severe liver disease. No dose adjustment required in mild hepatic impairment.
Renal disease: Lack of data for use in patients with severe renal impairment or end stage renal disease requiring hemodialysis or peritoneal dialysis.
LABORATORY INFORMATION
Please find up to date information at www.assayfinder.com regarding individual providers of drug level monitoring tests. Click on the provider for contact details. Turnaround time is usually a few days to a week but this can be reduced by calling ahead and informing the laboratory in advance.