Drugs List

Therapeutic Indications

Uses

Seizures associated with Dravet syndrome

Treatment of seizures associated with Dravet syndrome as add-on therapy to other anti-epileptic medicines.

Contraindications

Children under 2 years
Within 2 weeks of discontinuing MAOIs
Breastfeeding
Moderate hepatic impairment
Pregnancy
Pulmonary hypertension
Valvular heart disease

Precautions and Warnings

Glucose-galactose malabsorption syndrome
History of anorexia nervosa
History of bulimia nervosa

Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Contains glucose
Contains hydroxybenzoate
Perform echocardiography before commencing therapy
May increase seizure frequency
Monitor patient for weight loss
Perform echocardiography at 6 monthly intervals during treatment
Avoid abrupt withdrawal
To discontinue, reduce dose gradually
Discontinue if patient develops decreased visual acuity +/or ocular pain
Advise patient not to take St John's wort concurrently
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient/carers to report signs of suicide ideation or behaviour

Prior to initiating treatment, patients must undergo an echocardiogram (echo) to establish a baseline and exclude any pre-existing valvular heart disease or pulmonary hypertension. An echo should be conducted every 6 months for the first 2 years and annually thereafter. If an echo shows pathological valvular changes, an earlier follow-up echo should be considered to evaluate whether the abnormality is persistent. If pathological abnormalities on the echo are observed, it is recommended to evaluate the benefit versus risk of continuing fenfluramine treatment with the prescriber, caregiver, and cardiologist. If treatment is discontinued due to aortic or mitral valvular heart disease, appropriate monitoring and follow-up should be provided in accordance to local guidelines.

If echo suggests pulmonary arterial hypertension, a repeat echo should be performed as soon as possible and within 3 months to confirm. If echo finding is confirmed suggestive of an increased probability of pulmonary arterial hypertension defined as 'intermediate probability' by the 2015 European Society of Cardiology (ESC) and the European Respiratory Society (ERS) Guidelines, a benefit-risk evaluation of continuation of fenfluramine by the prescriber, carer and cardiologist should be performed. If echo finding, after confirmation, suggests a high probability of pulmonary arterial hypertension, as defined by the 2015 ESC and ERS Guidelines, it is recommended that fenfluramine treatment is discontinued.

Pregnancy and Lactation

Pregnancy

Fenfluramine is contraindicated during pregnancy.

The manufacturer does not recommend using fenfluramine during pregnancy.

There is limited data from the use of fenfluramine during pregnancy. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity in the absence of paternal or maternal toxicity.

Lactation

Fenfluramine is contraindicated during breastfeeding.

The manufacturer advises that the patient either discontinues or abstains from fenfluramine or discontinues breastfeeding taking consideration the benefit of breastfeeding for the neonate and the benefit of the therapy to the women.

It is unknown whether fenfluramine and/or its metabolites are excreted in human breast milk. Animal studies have shown that fenfluramine/metabolites can be excreted in milk. A risk to the infant cannot be excluded.

Side Effects

Behavioural disturbances
Bronchitis
Constipation
Decreased appetite
Decreased blood glucose
Diarrhoea
Drowsiness
Ear infection
Echocardiogram abnormal (trace regurgitation)
Falls
Fatigue
Glaucoma (closed angle)
Increased susceptibility to infection
Irritability
Lethargy
Mydriasis
Pyrexia
Somnolence
Status epilepticus
Suicidal ideation
Tremor
Upper respiratory tract infection
Vomiting
Weight loss

Presentation

Oral formulations of fenfluramine.

Drugs List

Therapeutic Indications

Uses

Seizures associated with Dravet syndrome

Treatment of seizures associated with Dravet syndrome as add-on therapy to other anti-epileptic medicines.

Dosage

Fenfluramine is prescribed and dispensed according to the controlled access programme.

Adults

Children

Contraindications

Children under 2 years
Within 2 weeks of discontinuing MAOIs
Breastfeeding
Moderate hepatic impairment
Pregnancy
Pulmonary hypertension
Valvular heart disease

Precautions and Warnings

Glucose-galactose malabsorption syndrome
History of anorexia nervosa
History of bulimia nervosa

Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Contains glucose
Contains hydroxybenzoate
Perform echocardiography before commencing therapy
May increase seizure frequency
Monitor patient for weight loss
Perform echocardiography at 6 monthly intervals during treatment
Avoid abrupt withdrawal
To discontinue, reduce dose gradually
Discontinue if patient develops decreased visual acuity +/or ocular pain
Advise patient not to take St John's wort concurrently
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient/carers to report signs of suicide ideation or behaviour

Prior to initiating treatment, patients must undergo an echocardiogram (echo) to establish a baseline and exclude any pre-existing valvular heart disease or pulmonary hypertension. An echo should be conducted every 6 months for the first 2 years and annually thereafter. If an echo shows pathological valvular changes, an earlier follow-up echo should be considered to evaluate whether the abnormality is persistent. If pathological abnormalities on the echo are observed, it is recommended to evaluate the benefit versus risk of continuing fenfluramine treatment with the prescriber, caregiver, and cardiologist. If treatment is discontinued due to aortic or mitral valvular heart disease, appropriate monitoring and follow-up should be provided in accordance to local guidelines.

If echo suggests pulmonary arterial hypertension, a repeat echo should be performed as soon as possible and within 3 months to confirm. If echo finding is confirmed suggestive of an increased probability of pulmonary arterial hypertension defined as 'intermediate probability' by the 2015 European Society of Cardiology (ESC) and the European Respiratory Society (ERS) Guidelines, a benefit-risk evaluation of continuation of fenfluramine by the prescriber, carer and cardiologist should be performed. If echo finding, after confirmation, suggests a high probability of pulmonary arterial hypertension, as defined by the 2015 ESC and ERS Guidelines, it is recommended that fenfluramine treatment is discontinued.

Pregnancy and Lactation

Pregnancy

Fenfluramine is contraindicated during pregnancy.

The manufacturer does not recommend using fenfluramine during pregnancy.

There is limited data from the use of fenfluramine during pregnancy. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity in the absence of paternal or maternal toxicity.

Lactation

Fenfluramine is contraindicated during breastfeeding.

The manufacturer advises that the patient either discontinues or abstains from fenfluramine or discontinues breastfeeding taking consideration the benefit of breastfeeding for the neonate and the benefit of the therapy to the women.

It is unknown whether fenfluramine and/or its metabolites are excreted in human breast milk. Animal studies have shown that fenfluramine/metabolites can be excreted in milk. A risk to the infant cannot be excluded.

Side Effects

Behavioural disturbances
Bronchitis
Constipation
Decreased appetite
Decreased blood glucose
Diarrhoea
Drowsiness
Ear infection
Echocardiogram abnormal (trace regurgitation)
Falls
Fatigue
Glaucoma (closed angle)
Increased susceptibility to infection
Irritability
Lethargy
Mydriasis
Pyrexia
Somnolence
Status epilepticus
Suicidal ideation
Tremor
Upper respiratory tract infection
Vomiting
Weight loss

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: July 2021

Reference Sources

Summary of Product Characteristics: Fintepla 2.2mg/ml oral solution. Zogenix International Ltd. Revised May 2021.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 05 November 2021