Ambrisentan oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of ambrisentan.
Drugs List
Therapeutic Indications
Uses
Pulmonary arterial hypertension: functional grades II and III
Treatment of Pulmonary Arterial Hypertension (PAH) classified as WHO functional class II or III in adult patients, including use in combination therapy. Efficacy has been shown in idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with connective tissue disease.
Treatment of PAH classified as WHO functional class II or III in children aged 8 to 18 years, including use in combination therapy. Efficacy has been shown in idiopathic pulmonary arterial hypertension, familial, corrected congenital and pulmonary arterial hypertension associated with connective tissue disease.
Dosage
Adults
Initially 5mg once daily, this may be increased to 10mg daily depending on the individual's response and tolerability.
Children
Children aged 8 to 18 years
Body weight 50kg and over: Initial dose 5mg once daily. Maintenance doses can be titrated up to 10mg once daily.
Body weight 35kg to 50kg: Initial dose 5mg once daily. Maintenance doses can be titrated up to 7.5mg once daily.
Body weight 20kg to 35kg: Initial dose 2.5mg once daily. Maintenance doses can be titrated up to 5mg once daily.
Patients with Renal Impairment
Severe renal impairment - creatinine clearance less than 30ml/minute
Use with caution especially with a 10mg dose.
Additional Dosage Information
Co-administration with ciclosporin
All patients should be carefully monitored when ambrisentan is co-administered with ciclosporin.
Adults
Maximum dose of ambrisentan is 5mg once daily.
Children aged 8 to 18 years
Body weight 50kg and over: Maximum dose of ambrisentan is 5mg once daily.
Body weight of 20kg to 50kg: Maximum dose of ambrisentan is 2.5mg once daily.
Co-administration with tadalafil
Adults
Ambrisentan should be titrated up to 10mg once daily.
Contraindications
Children under 8 years
Breastfeeding
Galactosaemia
Hepatic cirrhosis
Pregnancy
Pulmonary fibrosis
Serum transaminases above 3 times upper limit of normal
Severe anaemia
Severe hepatic impairment
Precautions and Warnings
Children aged 8 to 18 years
Females of childbearing potential
Abnormal liver function test
Anaemia
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hypervolaemia
Lactose intolerance
Renal impairment - creatinine clearance below 30 ml/minute
Advise ability to drive/operate machinery may be affected by side effects
Not all available brands are licensed for all age groups
Treatment to be initiated and supervised by a specialist
Contains lactose
Contains soya or soya derivative
Exclude pregnancy prior to initiation of treatment
Monitor serum transaminases before therapy and at monthly intervals
Ensure negative monthly pregnancy tests throughout treatment
Monitor haemoglobin/haematocrit at 1 month, 3 months and then periodically
Consider veno-occlusive disease if pulmonary oedema occurs
Discontinue if hepatic enzymes (AST or ALT) become persistently raised
Discontinue if jaundice or other evidence of hepatic impairment occurs
Review dose/discontinue if decreases in haematocrit or haemoglobin
Female: Ensure adequate contraception during treatment
Remind patient of importance of carrying Alert Card with them at all times
Ambrisentan has not been studied in sufficient numbers of patients to establish the benefit/risk balance in pulmonary arterial hypertension WHO functional class I.
The efficacy of ambrisentan as monotherapy for pulmonary arterial hypertension WHO class IV has not been established, an alternative drug should be considered if the clinical condition deteriorates.
Reductions in the haematocrit and haemoglobin concentrations have been reported with ambrisentan. Most of these were detected during the first 4 weeks of treatment, and the haemoglobin concentrations generally stabilised after this time. Consider a dose reduction or discontinuation if a clinically significant decrease in haematocrit or haemoglobin is observed.
Peripheral oedema has been reported with ambrisentan, most cases were mild to moderate in severity. However peripheral oedema occurred with greater frequency and severity in patients over 65 years and with the 10mg dose.
Fluid retention has been reported to occur within weeks of initiating treatment and in some cases has required intervention with a diuretic or hospitalisation for fluid management or decompensated heart failure.
Fluid retention may occur without weight gain and therefore further evaluation should be undertaken to ascertain the cause (such as cardiac failure), and the need for treatment or discontinuation of ambrisentan. If patients have pre-existing fluid overload, this should be managed as clinically appropriate prior to starting ambrisentan.
The tablets contain the azo colouring agent Allura red AC Aluminium Lake (E129) which can cause allergic reactions.
Pregnancy and Lactation
Pregnancy
Ambrisentan is contraindicated during pregnancy.
Use of ambrisentan during pregnancy is contraindicated by the manufacturer. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.
Lactation
Ambrisentan is contraindicated during breastfeeding.
Use of ambrisentan when breastfeeding is contraindicated by the manufacturer. The presence of ambrisentan in human breast milk is unknown and the effects on exposed infants are unknown.
Side Effects
Abdominal pain
Acute hepatic injury
Anaemia
Angioedema
Asthenia
Autoimmune hepatitis
Blurred vision
Cardiac failure
Chest pain
Constipation
Decrease in haemoglobin and haematocrit
Diarrhoea
Dizziness
Dyspnoea
Epistaxis
Fatigue
Fluid retention
Flushing
Headache
Hypersensitivity reactions
Hypotension
Increase in serum ALT/AST
Migraine
Naso-sinus congestion
Nasopharyngitis
Nausea
Palpitations
Peripheral oedema
Pruritus
Rash
Rhinitis
Sinus headache
Sinusitis
Sudden deafness
Syncope
Tinnitus
Visual impairment (irreversible)
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: January 2020
Reference Sources
Summary of Product Characteristics: Volibris 2.5mg film coated tablets. GlaxoSmithKline UK. Revised August 2022.
Summary of Product Characteristics: Volibris 5mg film coated tablets. GlaxoSmithKline UK. Revised August 2022.
Summary of Product Characteristics: Volibris 10mg film coated tablets. GlaxoSmithKline UK. Revised August 2022.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 28 January 2020
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.