Rucaparib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of rucaparib.
Drugs List
Therapeutic Indications
Uses
Fallopian tube cancer
Platinum sensitive high grade epithelial ovarian cancer
Primary peritoneal cancer
Monotherapy maintenance treatment of adult patients with platinum sensitive relapsed high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.
Monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum based chemotherapy, and who are unable to tolerate further platinum based chemotherapy.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
There is no requirement for BRCA testing prior to using rucaparib for maintenance treatment. BRCA testing must be performed and confirmation of BRCA 1/BRCA 2 gene before treatment for relapsed or progressive high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer.
Adults
600mg twice daily, taken approximately 12 hours apart, continued until disease progression or unacceptable toxicity.
Patients should not start rucaparib until they have recovered from haematological toxicities caused by previous chemotherapy.
Maintenance treatment should start no later than 8 weeks after completion of the patient's final dose of the platinum containing regimen.
Additional Dosage Information
If the patient vomits
If a patient vomits after taking rucaparib, the patient should not retake the dose and should take at the next scheduled dose.
If a dose is missed
If a dose is missed, the patient should take rucaparib at the next scheduled dose.
Dose modifications
First dose reduction: 500mg twice daily.
Second dose reduction: 400mg twice daily.
Third dose reduction: 300mg twice daily.
Haematological toxicity
Moderate to severe (Grade 3 or 4) haematological reactions, including neutropenia, anaemia and thrombocytopenia: Manage through a combination of dose interruptions and/or dose reductions with blood counts monitored weekly until recovery. If levels have not recovered after 4 weeks, the patient should be referred to a haematologist for further investigation.
Liver enzyme elevations
Grade 1 to 3 elevations in aspartate aminotransferase and/or alanine aminotransferase: Can be managed without dose interruption or dose reduction. With Grade 3 elevations without other signs of liver dysfunction, monitor LFTs weekly until resolution to Grade less than or equal to 2. Continue rucaparib as long as bilirubin is less than ULN and alkaline phosphatase is less than 3 times ULN. Interrupt treatment if aspartate aminotransferase and/or alanine aminotransferase levels do not decline within 2 weeks, resume rucaparib when values are Grade less than or equal to 2 at the same or reduced dose.
Grade 4 elevations in aspartate aminotransferase and/or alanine aminotransferase: Manage through a combination of dose interruptions and/or dose reductions.With Grade 4 elevations, interrupt rucaparib until values are Grade less than or equal to 2. Resume rucaparib with a dose reduction and monitor LFTs weekly for 3 weeks.
Non-haematological toxicity
Moderate to severe non-haematological reactions, including vomiting and nausea: Manage through a combination of dose interruptions, dose reductions and appropriate symptomatic management.
Contraindications
Children under 18 years
Breastfeeding
Moderate hepatic impairment
Pregnancy
Severe renal impairment
Precautions and Warnings
Patients over 65 years
Advise ability to drive/operate machinery may be affected by side effects
Confirm BRCA1 or BRCA2 mutation status prior to treatment
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Non-significant increase in QT interval at therapeutic doses
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Perform blood counts before and at monthly intervals during treatment
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider G-CSF in severe neutropenia / agranulocytosis
Consider the use of anti-emetics before and during therapy
Risk of myelodysplasia/myeloid leukaemia requires haematological follow-up
Consider dose interruption & reduction in non-haematological toxicity
Consider treatment interruption & dose reduction in haematological toxicity
Discontinue if MDS or AML occurs requiring additional anticancer therapy
Interrupt or reduce dose if significant gastrointestinal disturbances occur
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 6 months after treatment
Breastfeeding: Do not breastfeed during & for 2 weeks after treatment
Advise patient to use SPF 50+ sunscreen and lip balm during treatment
Avoid direct exposure to sunlight
Pregnancy and Lactation
Pregnancy
Rucaparib is contraindicated during pregnancy.
Use of rucaparib during pregnancy is contraindicated by the manufacturer. At the time of writing there is limited data on the use of rucaparib in human pregnancy. Animals studies have shown reproductive toxicity, including embryofoetal toxicity. The drug's mechanism of action indicates potential foetal harm when administered to a pregnant woman.
Lactation
Rucaparib is contraindicated during breastfeeding.
The manufacturer states that breastfeeding is contraindicated during treatment with rucaparib and for 2 weeks after the final dose of rucaparib. At the time of writing it is unknown whether rucaparib or its metabolites is excreted in human breast milk. A risk to neonates and infants cannot be excluded.
Side Effects
Abdominal pain
Acute myeloid leukaemia
Alanine aminotransferase increased
Anaemia
Aspartate aminotransferase increased
Asthenia
Decreased appetite
Dehydration
Diarrhoea
Dizziness
Dysgeusia
Dyspepsia
Dyspnoea
Erythema
Fatigue
Febrile neutropenia
Hypercholesterolaemia
Impaired memory
Increase of liver transaminases
Lethargy
Leukopenia
Lymphopenia
Maculopapular rash
Myelodysplastic syndrome
Nausea
Neutropenia
Palmar-Plantar Erythrodysaesthesia syndrome
Photosensitivity
Pruritus
Pyrexia
Rash
Serum creatinine increased
Thrombocytopenia
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: November 2019
Reference Sources
Summary of Product Characteristics: Rubraca 200mg film-coated tablets. Clovis Oncology UK Ltd. Revised April 2019.
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.