Drugs List

Therapeutic Indications

Uses

Pulmonary multidrug-resistant tuberculosis

For use as part of combination therapy for pulmonary multidrug-resistant tuberculosis (MDR-TB) when an effective treatment regimen cannot otherwise be composed due to resistance or tolerability.

Bedaquiline must only be used in an appropriate combination regimen for MDR-TB treatment as recommended by official guidelines, such as from WHO, to prevent development of resistance to bedaquiline.

The manufacturer suggests administering bedaquiline by directly observed therapy (DOT).

Contraindications

Children under 12 years
Children weighing less than 30kg
Breastfeeding
Galactosaemia
Long QT syndrome
QTc interval greater than or equal to 500 msec
Severe hepatic impairment
Torsade de pointes
Ventricular arrhythmias

Precautions and Warnings

Family history of long QT syndrome
Patients over 65 years
QTcF interval greater than 450msec at baseline
Bradyarrhythmia
Cardiac failure
Congenital long QT syndrome
Electrolyte imbalance
End stage renal disease
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Hypokalaemia
Hypothyroidism
Lactose intolerance
Moderate hepatic impairment
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute

Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Consult national/regional policy on the use of anti-infectives
Must be used in combination with other anti-tuberculous drugs
Treatment to be initiated and supervised by a specialist
Contains lactose
Advise patient to take with or after food
Monitor ECG before initiating and at least monthly thereafter
Monitor hepatic function before initiating and at monthly intervals
If syncope occurs obtain an ECG to detect QT prolongation
Monitor patients on prolonged therapy
Monitor serum electrolytes
Consider discontinuing treatment if ALT/AST > 5 times upper limit of normal
Discontinue treatment if arrhythmias occur
Discontinue treatment if QTc exceeds 500msec
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise patients on the importance of taking treatment regularly

In adolescents weighing between 30 and 40kg, average bedaquiline exposure is predicted to be higher compared to adult patients. This may be associated with an increased risk of QT prolongation or hepatotoxicity.

Pregnancy and Lactation

Pregnancy

Use bedaquiline with caution during pregnancy.

The manufacturer suggests bedaquiline should be avoided during pregnancy unless the benefit of therapy outweighs the risks.

At the time of writing, there are limited data on the use of bedaquiline in pregnant women. At clinically relevant exposures, animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

Lactation

Bedaquiline is contraindicated during breastfeeding.

The manufacturer suggests, because of the potential for adverse effects in breastfed infants, a decision must be made whether to discontinue breastfeeding or to discontinue bedaquiline therapy taking into account the benefit of therapy and the benefit of breastfeeding the infant.

It is not known whether bedaquiline or its metabolites are excreted in human milk. In rats, milk concentrations of bedaquiline were 6 to 12-fold higher than the maximum concentration observed in maternal plasma. Bodyweight decreases in pups were observed in high dose groups during the lactation period.

Side Effects

Arthralgia
Diarrhoea
Dizziness
Headache
Increase of liver transaminases
Myalgia
Nausea
Prolongation of QT interval
Vomiting

Presentation

Oral formulations of bedaquiline.

Drugs List

Therapeutic Indications

Uses

Pulmonary multidrug-resistant tuberculosis

For use as part of combination therapy for pulmonary multidrug-resistant tuberculosis (MDR-TB) when an effective treatment regimen cannot otherwise be composed due to resistance or tolerability.

Bedaquiline must only be used in an appropriate combination regimen for MDR-TB treatment as recommended by official guidelines, such as from WHO, to prevent development of resistance to bedaquiline.

The manufacturer suggests administering bedaquiline by directly observed therapy (DOT).

Dosage

Must be used in combination with at least three medicinal products to which the patient's isolate has shown to be susceptible in vitro. Treatment with other agents in the regimen should continue after completion of treatment with bedaquiline. If in vitro results are not available, treatment may be initiated with bedaquiline in combination with at least four medicinal products to which the patient's isolate is likely to be susceptible.

Duration of treatment is 24 weeks. In cases of extensive drug resistance, treatment beyond 24 weeks to obtain curative treatment may be considered on a case by case basis and under close safety surveillance.

Adults

Children

Additional Dosage Information

Contraindications

Children under 12 years
Children weighing less than 30kg
Breastfeeding
Galactosaemia
Long QT syndrome
QTc interval greater than or equal to 500 msec
Severe hepatic impairment
Torsade de pointes
Ventricular arrhythmias

Precautions and Warnings

Family history of long QT syndrome
Patients over 65 years
QTcF interval greater than 450msec at baseline
Bradyarrhythmia
Cardiac failure
Congenital long QT syndrome
Electrolyte imbalance
End stage renal disease
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Hypokalaemia
Hypothyroidism
Lactose intolerance
Moderate hepatic impairment
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute

Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Consult national/regional policy on the use of anti-infectives
Must be used in combination with other anti-tuberculous drugs
Treatment to be initiated and supervised by a specialist
Contains lactose
Advise patient to take with or after food
Monitor ECG before initiating and at least monthly thereafter
Monitor hepatic function before initiating and at monthly intervals
If syncope occurs obtain an ECG to detect QT prolongation
Monitor patients on prolonged therapy
Monitor serum electrolytes
Consider discontinuing treatment if ALT/AST > 5 times upper limit of normal
Discontinue treatment if arrhythmias occur
Discontinue treatment if QTc exceeds 500msec
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise patients on the importance of taking treatment regularly

In adolescents weighing between 30 and 40kg, average bedaquiline exposure is predicted to be higher compared to adult patients. This may be associated with an increased risk of QT prolongation or hepatotoxicity.

Pregnancy and Lactation

Pregnancy

Use bedaquiline with caution during pregnancy.

The manufacturer suggests bedaquiline should be avoided during pregnancy unless the benefit of therapy outweighs the risks.

At the time of writing, there are limited data on the use of bedaquiline in pregnant women. At clinically relevant exposures, animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

Lactation

Bedaquiline is contraindicated during breastfeeding.

The manufacturer suggests, because of the potential for adverse effects in breastfed infants, a decision must be made whether to discontinue breastfeeding or to discontinue bedaquiline therapy taking into account the benefit of therapy and the benefit of breastfeeding the infant.

It is not known whether bedaquiline or its metabolites are excreted in human milk. In rats, milk concentrations of bedaquiline were 6 to 12-fold higher than the maximum concentration observed in maternal plasma. Bodyweight decreases in pups were observed in high dose groups during the lactation period.

Side Effects

Arthralgia
Diarrhoea
Dizziness
Headache
Increase of liver transaminases
Myalgia
Nausea
Prolongation of QT interval
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: October 2020

Reference Sources

Summary of Product Characteristics: Sirturo 100 mg tablets. Janssen-Cilag Ltd. January 2020.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 07 October 2020