Avatrombopag oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulation of avatrombopag.
Drugs List
Therapeutic Indications
Uses
Severe thrombocytopenia with chronic liver disease
Thrombocytopenia - immunogenic
Treatment of severe thrombocytopenia in adults with chronic liver disease who are scheduled to undergo an invasive procedure.
Treatment of primary chronic immune thrombocytopenia (ITP) in adults who are refractory to other treatments.
Dosage
The recommended daily dose of avatrombopag is based on the patient's platelet count.
Adults
Severe Thrombocytopenia with Chronic Liver Disease
Avatrombopag should not be taken for more than 5 days. Dosing should begin 10 to 13 days prior to the scheduled invasive procedure. The patient should undergo the procedure 5 to 8 days after the last dose of avatrombopag.
Platelet count of less than 40 x 10 to the power 9 per litre
60mg once daily for 5 days
Platelet count of greater than or equal to 40 x 10 to the power 9 per litre but less than 50 x 10 to the power 9 per litre
40mg once daily for 5 days
Primary Chronic Immune Thrombocytopenia (ITP)
Use the lowest dose to achieve and maintain a platelet count greater than or equal to 50 x 10 to the power 9 per litre.
Initial dose
20mg once daily with food
Avatrombopag dose levels for titration in patients with ITP
Dose Level 6: 40mg once daily
Dose Level 5: 40mg three times a week and 20mg on the four remaining days for each week
Dose Level 4: 20mg once daily
Dose Level 3: 20mg three times a week (three non-consecutive days a week e.g. Monday, Wednesday and Friday)
Dose Level 2: 20mg twice a week or 40mg once weekly (two non-consecutive days a week e.g. Monday and Friday)
Dose Level 1: 20mg once weekly (the same day each week)
Platelet count of less than 50 x 10 to the power 9 per litre after at least 2 weeks of avatrombopag treatment
Increase One Dose Level, wait 2 weeks to assess the effects of this regimen and any subsequent dose adjustments.
Platelet count of greater than 150 x 10 to the power 9 per litre and less than or equal to 250 x 10 to the power 9 per litre
Decrease One Dose Level,wait 2 weeks to assess the effects of this regimen and any subsequent dose adjustments.
Platelet count of greater than 250 x 10 to the power 9 per litre
Stop avatrombopag treatment. Increase platelet monitoring to twice weekly. When platelet count is less than 100x 10 to the power 9 per litre, decrease One Dose Level and reinitiate therapy.
Platelet count of less than 50 x 10 to the power 9 per litre after 4 weeks of avatrombopag 40mg once daily
Discontinue avatrombopag treatment.
Platelet count of greater than 250 x 10 to the power 9 per litre after 2 weeks of avatrombopag 20mg weekly
Discontinue avatrombopag treatment.
Additional Dosage Information
Missed doses
If a dose is missed, take as soon as it is remembered. Two doses should not be taken at one time to make up for the missed dose. The next dose should be taken at the usual time the following day.
Avatrombopag recommended starting doses for patients with ITP based on concomitant medications
Moderate or strong dual inhibitors of CYP2C9 and CYP3A4/5, or of CYP2C9 alone
20mg three times a week
Moderate or strong dual inducers of CYP2C9 and CYP3A4/5, or of CYP2C9 alone
40mg once daily
Contraindications
Children under 18 years
Breastfeeding
Galactosaemia
Pregnancy
Precautions and Warnings
Females of childbearing potential
Major surgery
Multiple risk factors for thromboembolic disease
CYP2C9 poor metaboliser genotype
Glucose-galactose malabsorption syndrome
Lactose intolerance
Severe hepatic impairment
Perform platelet count prior to treatment and on the day of procedure
Treatment to be initiated and supervised by a specialist
Contains lactose
Blood counts should be performed before and periodically during treatment
Monitor platelet count weekly
Perform peripheral blood smear prior to and during treatment
Monitor for bleeding during treatment
Monitor for signs and symptoms of hepatic encephalopathy
Monitor liver function in patients with hepatic impairment
Monitor platelet counts for 4 weeks following discontinuation
Interrupt treatment if platelet count above 250x10 to the power of 9/L
Discontinue if new or worsening morphological cell abnormalities develop
There is an increased risk for thromboembolic events in patients with chronic liver disease or ITP. Patients with chronic liver disease who had platelet counts greater than 200 x 10 to the power 9 per litre, when receiving a thrombopoietin receptor agonist, have reported an increased frequency of portal vein thrombosis.
Potential increased thrombotic risk when administering avatrombopag to patients with known risk factors for thromboembolism, including genetic prothrombotic conditions should be considered. Avatrombopag should not be administered to patients with chronic liver disease in an attempt to normalize platelet counts.
Consider the potential for reduced platelet counts if co-administering avatrombopag with interferon preparations.
The diagnosis of ITP should have been confirmed by the exclusion of other clinical entities presenting with thrombocytopenia, in particular the diagnosis of myelodysplastic syndrome (MDS) must be excluded. Consider performing a bone marrow aspirate and biopsy over the course of treatment, particularly in patients over 60 years of age, those with systemic symptoms or abnormal signs such as increased peripheral blast cells.
Pregnancy and Lactation
Pregnancy
Avatrombopag is contraindicated during pregnancy.
Use of avatrombopag during pregnancy and in women of childbearing potential not using contraception is contraindicated by the manufacturer. At the time of writing there is limited published literature regarding the use of avatrombopag during pregnancy. Potential risks are unknown.
Lactation
Avatrombopag is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues avatrombopag or discontinues breastfeeding. Animal data reports that avatrombopag is present in the breast milk, however presence in human breast milk and the effects on exposed infants are unknown.
Side Effects
Abdominal distension
Abdominal pain
Acne
Alanine aminotransferase increased
Alopecia
Anaemia
Arthralgia
Arthropathy
Aspartate aminotransferase increased
Asthenia
Back pain
Blood glucose disturbances
Bone pain
Cerebrovascular accident
Changes in mood
Chest discomfort
Cognitive impairment
Constipation
Decreased appetite
Deep vein thrombosis (DVT)
Dehydration
Diarrhoea
Discomfort in limb
Dizziness
Dry skin
Dysgeusia
Dyspnoea
Ear pain
Ecchymosis
Epistaxis
Eructation
Eye irritation
Eyelid pruritus
Eyelid swelling
Fatigue
Flatulence
Furuncle
Gastroesophageal reflux
Glossodynia
Haematuria
Haemoptysis
Haemorrhoids
Headache
Hunger
Hyperacusis
Hyperhidrosis
Hyperlipidaemia
Hypersensitivity reactions
Hypertension
Hypertriglyceridaemia
Hypoaesthesia
Impaired vision
Increase in lactate dehydrogenase
Increase in plasma triglyceride concentration
Increased appetite
Increased blood pressure
Increased lacrimation
Increased platelet count
Iron deficiency
Leukocytosis
Menorrhagia
Migraine
Muscle spasm
Muscle weakness
Musculoskeletal pain
Myalgia
Myelofibrosis
Myocardial infarction
Nasal congestion
Nausea
Nipple discomfort
Ocular discomfort
Oral paraesthesia
Painful extremities
Paraesthesia
Petechiae
Photophobia
Portal vein thrombosis
Pruritus
Pulmonary embolism
Pyrexia
Rash
Reduced platelet count
Retinal artery occlusion
Sensation of foreign body in eye
Sensory disturbances
Skin irritation
Skin pigmentation changes
Skin/soft tissue haemorrhage
Splenomegaly
Swelling
Thrombocytopenia
Thrombophlebitis
Tongue disorder
Tongue swelling
Transient ischaemic attack
Upper abdominal pain
Upper respiratory tract infection
Vasoconstriction
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: March 2021
Reference Sources
Summary of Product Characteristics: Doptelet 20mg film coated tablets. Swedish Orphan Biovitrum Ltd. Revised October 2021.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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