Avapritinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of avapritinib.
Drugs List
Therapeutic Indications
Uses
Unresectable or metastatic malignant gastrointestinal stromal tumour (GIST)
As monotherapy in adults for the treatment of unresectable or metastatic gastrointestinal stromal tumours (GIST) harbouring the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation.
Dosage
Adults
300mg once daily.
Additional Dosage Information
Recommended starting dose if concomitant use with moderate CYP3A inhibitor: 100mg once daily.
Dose reductions
Starting dose: 300mg once daily.
First dose reduction: 200mg once daily.
Second dose reduction: 100mg once daily.
Dose modifications for adverse reactions
Intracranial haemorrhage (all grades): Permanently discontinue.
Grade 1 cognitive effects: Continue at same dose or interrupt therapy until baseline or resolution. Resume at the same dose or at a reduced dose.
Grade 2 or 3 cognitive effects: Interrupt therapy until improvement to baseline, grade 1 or resolution. Resume at the same dose or at a reduced dose.
Grade 4 cognitive effects: Permanently discontinue.
Any other grade 3 or 4 adverse reaction: Interrupt therapy until grade 2 or lower, then resume at the same dose or at a reduced dose.
Missed dose
If a dose of avapritinib is missed, the patient to take the missed dose unless the next schedules dose is within 8 hours. If the dose has not been taken at least 8 hours prior to the next scheduled dose, then the dose should be omitted and treatment should be resumed with the next scheduled dose.
Contraindications
Children under 18 years
Breastfeeding
End stage renal disease
Long QT syndrome
Pregnancy
Severe hepatic impairment
Severe renal impairment
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
Predisposition to haemorrhage
Arterial aneurysm
Electrolyte imbalance
History of cerebrovascular accident
History of torsade de pointes
History of transient ischaemic attack
Recent intracranial haemorrhage
Severe thrombocytopenia
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Anti-emetics may be required during therapy
Maintain adequate hydration during therapy
Treatment to be initiated by specialist
Advise patient to take on an empty stomach 1 hr before or 2 hrs after food
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Monitor hepatic function before treatment and regularly during treatment
Perform ECG before and during treatment
Monitor coagulation values
Monitor for signs of fluid retention
Monitor for signs of neurological toxicity
Monitor for signs of rapid weight gain may indicate severe fluid retention
Monitor full blood count regularly
Monitor serum electrolytes
Patients with fluid retention should be treated with diuretics
Advise patient to report new or worsening cognitive symptoms
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Advise patient to seek advice at first indications of pregnancy
Interrupt if grade 2 cognitive effects occur
Permanently discontinue if grade 4 cognitive effects occur
Permanently discontinue if intracranial haemorrhage occurs
Suspend treatment if grade 3 or greater adverse reaction occurs
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Female: Contraception required during and for 1 month after treatment
Breastfeeding: Do not breastfeed during & for 2 weeks after treatment
Advise patient to avoid exposure to direct sunlight
Advise patient to use SPF 50+ sunscreen and lip balm during treatment
Intracranial haemorrhage
Patients who experience neurological signs and symptoms such as severe headache, vision problems, somnolence or focal weakness during treatment with avapritinib should report this to their healthcare professional immediately. Brain imaging by magnetic resonance imaging (MRI) or computed tomography (CT) may be performed.
Pregnancy and Lactation
Pregnancy
Avapritinib is contraindicated during pregnancy.
The manufacturer states that avapritinib is not recommended during pregnancy. There are no data available in the use of avapritinib in pregnant women, however animal studies have shown reproductive toxicity.
Lactation
Avapritinib is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding should be discontinued during avapritinib treatment and for 2 weeks after the final dose. It is unknown whether avapritinib or its metabolites are excreted in human milk, therefore a risk to the infant cannot be excluded.
Side Effects
Abdominal pain
Acute kidney injury
Alopecia
Anaemia
Anxiety
Aphasia
Arthralgia
Ascites
Asthenia
Back pain
Blurred vision
Changes in hair colour
Cognitive impairment
Conjunctival haemorrhage
Conjunctivitis
Constipation
Cough
Creatine phosphokinase increased
Decreased appetite
Dehydration
Depression
Diarrhoea
Dizziness
Dysphagia
Dyspnoea
Encephalopathy
Fatigue
Flatulence
Gastroesophageal reflux disease
Gastrointestinal bleeding
Haematuria
Headache
Hepatic haemorrhage
Hyperbilirubinaemia
Hyperpigmentation
Hypertension
Hypoalbuminaemia
Hypocalcaemia
Hypokalaemia
Hypokinesia
Hypomagnesaemia
Hyponatraemia
Hypophosphataemia
Impaired memory
Impairment of mental skills
Increase in lactate dehydrogenase
Increase in serum transaminases
Insomnia
Intracranial bleeding
Lacrimation
Loss of balance
Malaise
Muscle spasm
Myalgia
Nasal congestion
Nausea
Ocular haemorrhage
Oedema
Palmar-Plantar Erythrodysaesthesia syndrome
Pericardial effusion
Peripheral neuropathy
Photophobia
Photosensitivity
Pleural effusion
Prolongation of QT interval
Pruritus
Pyrexia
Rash
Reduced lymphocyte count
Reduced neutrophil count
Reversible confusional states
Salivary hypersecretion
Sensation of cold
Serum creatinine increased
Somnolence
Speech disturbances
Stomatitis
Taste disturbances
Thrombocytopenia
Tremor
Tumour haemorrhage
Vertigo
Vomiting
Weight gain
Weight loss
White blood cell count decreased
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: February 2021
Reference Sources
Summary of Product Characteristics: Ayvakyt 100mg, 200mg and 300mg film-coated tablets. Blueprint Medicines (Netherlands) B.V. Revised November 2020.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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