Ripretinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of ripretinib.
Drugs List
Therapeutic Indications
Uses
Advanced gastrointestinal stromal tumour (GIST)
Advanced gastrointestinal stromal tumour (GIST) in adult patients who have received prior treatment with three or more kinase inhibitors, including imatinib.
Dosage
Adults
150mg once a day.
Additional Dosage Information
Dose modifications
Recommended starting dose: 150mg once daily.
Reduced dose: 100mg once daily.
Dose modifications for adverse reactions
Grade 2 palmar-plantar erythrodysaethesia (PPES): Withhold ripretinib treatment until resolves to less than or equal to grade 1 or baseline. If the patient recovers within 7 days, then resume ripretinib at the same dose; otherwise resume at a reduced dose. Consider re-escalating the dose if PPES is maintained at less than or equal to grade 1 or baseline for at least 28 days. If PPES recurs, withhold ripretinib treatment until less than or equal to grade 1 or baseline and then resume at a reduced dose regardless of time to improvement.
Grade 3 palmar-plantar erythrodysaethesia (PPES): Withhold ripretinib treatment for at least 7 days or until resolves to less than or equal to grade 1 or baseline (maximum 28 days). Resume ripretinib treatment at a reduced dose. Consider re-escalating the dose if PPES is maintained at less than or equal to grade 1 or baseline for at least 28 days.
Grade 3 hypertension: If symptomatic, withhold ripretinib treatment until symptoms have resolved and blood pressure is controlled. If blood pressure is controlled to less than or equal to grade 1 or baseline, resume ripretinib treatment at the same dose; otherwise, resume at a reduced dose. If grade 3 hypertension recurs, withhold until symptoms have resolved and blood pressure is resolved. Resume ripretinib treatment at a reduced dose.
Grade 4 hypertension: Permanently discontinue ripretinib treatment.
Grade 3 or 4 left ventricular systolic dysfunction: Permanently discontinue ripretinib treatment.
Grade 2 arthralgia or myalgia: Withhold ripretinib treatment until resolves to less than or equal to grade 1 or baseline. If the patient recovers within 7 days, then resume ripretinib at the same dose; otherwise resume at a reduced dose. Consider re-escalating the dose if arthralgia or myalgia is maintained at less than or equal to grade 1 or baseline for at least 28 days. If arthralgia or myalgia recurs, withhold ripretinib treatment until less than or equal to grade 1 or baseline and then resume at a reduced dose regardless of time to improvement.
Grade 3 arthralgia or myalgia: Withhold ripretinib treatment for at least 7 days or until resolves to less than or equal to grade 1 or baseline (maximum 28 days). Resume ripretinib treatment at a reduced dose. Consider re-escalating the dose if arthralgia or myalgia is maintained at less than or equal to grade 1 or baseline for at least 28 days.
Grade 3 or 4 other adverse reactions: Withhold ripretinib treatment until resolves to less than or equal to grade 1 or baseline (maximum 28 days), and then resume ripretinib treatment at a reduced dose; otherwise permanently discontinue ripretinib treatment. Consider re-escalating the dose if no recurrence of the adverse reaction occurs for at least 28 days. If grade 3 or 4 adverse reaction recurs, permanently discontinue ripretinib treatment.
Missed dose
If a patient misses a dose of ripretinib within 8 hours of the usual dosage time, then the patient should be instructed to take the missed dose as soon as possible, then the next dose should be taken at the regularly scheduled time. If a dose is missed by more than 8 hours, the patient should be instructed not to take the missed dose, and should resume the usual dosing at the next scheduled dose.
Contraindications
Children under 18 years
Breastfeeding
Galactosaemia
Left ventricular ejection fraction value of 50% or less
Pregnancy
Uncontrolled hypertension
Precautions and Warnings
Glucose-galactose malabsorption syndrome
Lactose intolerance
Moderate hepatic impairment
Severe renal impairment
Consider withholding for 3 to 5 days pre and post surgery
Advise ability to drive/operate machinery may be affected by side effects
Ensure hypertension is controlled prior to treatment
Treatment to be prescribed under the supervision of a specialist
Contains lactose
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
Measurement of LV ejection fraction recommended before and during treatment
Ensure negative monthly pregnancy tests throughout treatment
Monitor skin changes
Refer suspicious skin lesions to a specialist
Treatment may adversely affect wound healing
Advise patient to seek advice at first indications of pregnancy
Discontinue if left ventricular systolic dysfunction develops
Interrupt therapy/reduce dose if palmar-plantar erythrodysaesthesia occurs
Permanently discontinue if grade 4 hypertension occurs
Suspend treatment if grade 3 or greater adverse reaction occurs
Suspend treatment in severe hypertension that cannot be controlled
Withhold treatment if grade 2 or 3 arthralgia or myalgia occurs
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
May cause impaired fertility
Female: Contraception required during and for 1 week after treatment
Male & female: Two methods of contraception required (including barrier)
Male: Contraception required during and for 1 week after treatment
Breastfeeding: Do not breastfeed during & for 1 week after treatment
Advise patient on appropriate sun protection methods
Advise patient to avoid exposure to sunlight and UV rays during treatment
Pregnancy and Lactation
Pregnancy
Ripretinib is contraindicated during pregnancy.
The manufacturer recommends that ripretinib should not be used during pregnancy unless the clinical condition of the woman requires treatment with ripretinib. There are no data of the use of ripretinib in pregnant women, although animal studies have shown reproductive toxicities. Based on the mechanism of action, ripretinib is suspected to cause foetal harm.
Lactation
Ripretinib is contraindicated during pregnancy.
The manufacturer recommends that breastfeeding should be discontinued during treatment with ripretinib and for at least 1 week after the final dose. It is unknown whether ripretinib or its metabolites are excreted in human milk, therefore a risk to the breastfed child cannot be excluded.
Side Effects
Abdominal pain
Alanine aminotransferase increased
Alopecia
Arthralgia
Back pain
Cardiac failure
Constipation
Cough
Depression
Dermatitis acneiform
Diarrhoea
Dry skin
Dyspnoea
Elevated serum lipase
Extremity pain
Fatigue
Fibrous histiocytoma
General pruritus
Headache
Hyperkeratosis
Hypertension
Hypophosphataemia
Hypothyroidism
Maculopapular rash
Melanocytic naevus
Muscle spasm
Muscle weakness
Musculoskeletal chest pain
Myalgia
Nausea
Palmar-Plantar Erythrodysaesthesia syndrome
Peripheral oedema
Peripheral sensory neuropathy
Pruritus
Seborrhoeic keratosis
Serum bilirubin increased
Skin papilloma
Squamous cell carcinoma
Stomatitis
Tachycardia
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: December 2022
Reference Sources
Summary of Product Characteristics: Qinlock 50 mg tablets. Deciphera Pharmaceuticals (Netherlands) B.V. Revised June 2022.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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