Drugs List

Therapeutic Indications

Uses

Unlicensed product

For use as part of a combination regimen for pulmonary multi-drug resistant tuberculosis when an effective regimen cannot otherwise be given due to resistance or tolerability.

Delamanid must only be used in an appropriate combination regimen for multidrug-resistant tuberculosis treatment as recommended by WHO to prevent development of resistance to delamanid.

It is recommended that delamanid is administered by directly observed therapy (DOT).

Unlicensed Uses

Pulmonary multidrug-resistant tuberculosis

Contraindications

Children weighing less than 10kg
Serum albumin less than 2.8g/dL
Breastfeeding
Long QT syndrome
Moderate hepatic impairment
Pregnancy
QTc interval greater than or equal to 500 msec
Severe renal impairment
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Females of childbearing potential
Patients over 65 years
Serum albumin 2.8g/dL - 3.4g/dL
Bradycardia
Congestive cardiac failure with reduced left ventricular ejection fraction
Electrolyte imbalance
History of cardiac arrhythmias
History of left ventricular hypertrophy
History of torsade de pointes
Hypertrophic cardiomyopathy
QTc interval greater than 450 milliseconds in males
QTc interval greater than 470 milliseconds in female adults
Severe hypertension

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
Advise patient to take with or after food
Professional and patient should be aware that this is an unlicensed product
Perform ECG before and during treatment
Monitor serum albumin
Monitor serum electrolytes
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Advise patient to seek advice at first indications of pregnancy
Discontinue treatment if QTc exceeds 500msec
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment

The manufacturer suggests that ECGs should be obtained prior to initiating treatment and monthly during the course of treatment. If the QTc interval exceeds 450 milliseconds in males or 470 milliseconds in females during delamanid treatment, more frequent ECG monitoring is required.

Treatment initiated in patients with albumin ranging from 2.8 to 3.4 g/dL, or patients who experience a fall in serum albumin into this range during delamanid treatment should receive very frequent monitoring of ECGs throughout the full treatment period.

Patients also taking CYP3A4 inhibitors, quinolones or other medicinal products know to prolong the QTc interval during delamanid treatment should also receive very frequent monitoring of ECGs throughout the full treatment period.

Pregnancy and Lactation

Pregnancy

Delamanid is contraindicated during pregnancy.

The manufacturer does not recommend using delamanid during pregnancy or in women of childbearing potential unless they are using a reliable form of contraception.

At the time of writing, there are limited data from the use of delamanid in pregnant women. Studies in animals have shown reproductive toxicity.

Lactation

Delamanid is contraindicated during breastfeeding.

The manufacturer suggests women should not breastfeed during treatment with delamanid because a potential risk to the breastfed infant cannot be ruled out.

At the time of writing, it is unknown if delamanid or its metabolites are excreted in human breast milk. Available data in animals have shown excretion of delamanid and/or its metabolites in milk.

Side Effects

Abdominal pain
Acne
Aggression
Agitation
Allergic conjunctivitis
Alopecia
Anaemia
Anxiety
Arthralgia
Asthenia
Blood pressure changes
Chest pain
Constipation
Cough
Decreased appetite
Dehydration
Delusions
Depression
Dermatitis
Diarrhoea
Dizziness
Dry eyes
Dryness and irritation of throat
Dyspepsia
Dysphagia
Dysphoria
Dyspnoea
Dysuria
Ear pain
ECG changes
Eosinophilia
Eosinophilic pustular folliculitis
Erythematous rash
Extremity pain
First degree AV block
Flank pain
Gamma glutamyl transferase (GGT) increased
Gastritis
Haematoma
Haematuria
Haemoptysis
Headache
Hepatic impairment
Herpes zoster
Hot flushes
Hypercholesterolaemia
Hypercortisolism
Hyperhidrosis
Hypertriglyceridaemia
Hyperuricaemia
Hypoaesthesia
Hypocalcaemia
Hypokalaemia
Increase in serum transaminases
Increased libido
Increased partial thromboplastin time
Insomnia
Lethargy
Leukopenia
Loss of balance
Malaise
Musculoskeletal pain
Myalgia
Nausea
Neurosis
Nocturia
Oral paraesthesia
Oropharyngeal candidiasis
Oropharyngeal pain
Osteochondrosis
Pain
Palpitations
Panic attack
Paraesthesia
Peripheral neuropathy
Peripheral oedema
Photophobia
Pityriasis versicolor
Prolongation of QT interval
Pruritus
Psychotic disorder
Pyrexia
Radiculitis
Rash
Reduction in serum cortisol levels
Restlessness
Reticulocytosis
Rhinorrhoea
Sleep disorders
Somnolence
Thrombocytopenia
Tinnitus
Tremor
Urinary retention
Urticaria
Vomiting

Presentation

Oral formulations of delamanid.

Drugs List

Therapeutic Indications

Uses

Unlicensed product

For use as part of a combination regimen for pulmonary multi-drug resistant tuberculosis when an effective regimen cannot otherwise be given due to resistance or tolerability.

Delamanid must only be used in an appropriate combination regimen for multidrug-resistant tuberculosis treatment as recommended by WHO to prevent development of resistance to delamanid.

It is recommended that delamanid is administered by directly observed therapy (DOT).

Unlicensed Uses

Pulmonary multidrug-resistant tuberculosis

Dosage

Adults

Children

Contraindications

Children weighing less than 10kg
Serum albumin less than 2.8g/dL
Breastfeeding
Long QT syndrome
Moderate hepatic impairment
Pregnancy
QTc interval greater than or equal to 500 msec
Severe renal impairment
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Females of childbearing potential
Patients over 65 years
Serum albumin 2.8g/dL - 3.4g/dL
Bradycardia
Congestive cardiac failure with reduced left ventricular ejection fraction
Electrolyte imbalance
History of cardiac arrhythmias
History of left ventricular hypertrophy
History of torsade de pointes
Hypertrophic cardiomyopathy
QTc interval greater than 450 milliseconds in males
QTc interval greater than 470 milliseconds in female adults
Severe hypertension

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
Advise patient to take with or after food
Professional and patient should be aware that this is an unlicensed product
Perform ECG before and during treatment
Monitor serum albumin
Monitor serum electrolytes
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Advise patient to seek advice at first indications of pregnancy
Discontinue treatment if QTc exceeds 500msec
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment

The manufacturer suggests that ECGs should be obtained prior to initiating treatment and monthly during the course of treatment. If the QTc interval exceeds 450 milliseconds in males or 470 milliseconds in females during delamanid treatment, more frequent ECG monitoring is required.

Treatment initiated in patients with albumin ranging from 2.8 to 3.4 g/dL, or patients who experience a fall in serum albumin into this range during delamanid treatment should receive very frequent monitoring of ECGs throughout the full treatment period.

Patients also taking CYP3A4 inhibitors, quinolones or other medicinal products know to prolong the QTc interval during delamanid treatment should also receive very frequent monitoring of ECGs throughout the full treatment period.

Pregnancy and Lactation

Pregnancy

Delamanid is contraindicated during pregnancy.

The manufacturer does not recommend using delamanid during pregnancy or in women of childbearing potential unless they are using a reliable form of contraception.

At the time of writing, there are limited data from the use of delamanid in pregnant women. Studies in animals have shown reproductive toxicity.

Lactation

Delamanid is contraindicated during breastfeeding.

The manufacturer suggests women should not breastfeed during treatment with delamanid because a potential risk to the breastfed infant cannot be ruled out.

At the time of writing, it is unknown if delamanid or its metabolites are excreted in human breast milk. Available data in animals have shown excretion of delamanid and/or its metabolites in milk.

Side Effects

Abdominal pain
Acne
Aggression
Agitation
Allergic conjunctivitis
Alopecia
Anaemia
Anxiety
Arthralgia
Asthenia
Blood pressure changes
Chest pain
Constipation
Cough
Decreased appetite
Dehydration
Delusions
Depression
Dermatitis
Diarrhoea
Dizziness
Dry eyes
Dryness and irritation of throat
Dyspepsia
Dysphagia
Dysphoria
Dyspnoea
Dysuria
Ear pain
ECG changes
Eosinophilia
Eosinophilic pustular folliculitis
Erythematous rash
Extremity pain
First degree AV block
Flank pain
Gamma glutamyl transferase (GGT) increased
Gastritis
Haematoma
Haematuria
Haemoptysis
Headache
Hepatic impairment
Herpes zoster
Hot flushes
Hypercholesterolaemia
Hypercortisolism
Hyperhidrosis
Hypertriglyceridaemia
Hyperuricaemia
Hypoaesthesia
Hypocalcaemia
Hypokalaemia
Increase in serum transaminases
Increased libido
Increased partial thromboplastin time
Insomnia
Lethargy
Leukopenia
Loss of balance
Malaise
Musculoskeletal pain
Myalgia
Nausea
Neurosis
Nocturia
Oral paraesthesia
Oropharyngeal candidiasis
Oropharyngeal pain
Osteochondrosis
Pain
Palpitations
Panic attack
Paraesthesia
Peripheral neuropathy
Peripheral oedema
Photophobia
Pityriasis versicolor
Prolongation of QT interval
Pruritus
Psychotic disorder
Pyrexia
Radiculitis
Rash
Reduction in serum cortisol levels
Restlessness
Reticulocytosis
Rhinorrhoea
Sleep disorders
Somnolence
Thrombocytopenia
Tinnitus
Tremor
Urinary retention
Urticaria
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: September 2020

Reference Sources

Summary of Product Characteristics: Deltyba 50 mg film-coated tablets. Otsuka GmbH. Revised April 2020.