Ruxolitinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of ruxolitinib.
Drugs List
Therapeutic Indications
Uses
Myelofibrosis
Treatment of polycythemia vera
Treatment of disease related splenomegaly or symptoms in adult patients with primary myelofibrosis, post polycythemia vera or essential thrombocythaemia myelofibrosis.
Treatment of adult patients with polycythaemia vera who are resistant to or intolerant of hydroxyurea.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
Myelofibrosis
Platelet count greater than 200,000 per cubic mm: 20 mg twice daily.
Platelet count between 100,000 and 200,000 per cubic mm: 15 mg twice daily.
Platelet count between 50,000 and 100,000 per cubic mm: Maximum 5 mg twice daily, titrated cautiously.
Polycythaemia Vera
Platelet count greater than 100,000 per cubic mm: 10 mg twice daily.
Platelet count between 50,000 and 100,000 per cubic mm: Maximum 5 mg twice daily, titrated cautiously.
Patients with Renal Impairment
Creatinine clearance less than 30 ml per minute
Myelofibrosis: Reduce the initial dose based on platelet count by approximately 50% twice daily.
Polycythaemia Vera:5 mg twice daily.
End-stage renal disease (ESRD) when treatment includes haemodialysis
Administer ruxolitinib post-dialysis and only on the day of dialysis.
Myelofibrosis
Platelet count greater than 200,000 per cubic mm: 20 mg single dose or two doses of 10 mg, 12 hours apart.
Platelet count between 100,000 per cubic mm and 200,000 per cubic mm: 15 mg as a single dose.
Polycythaemia Vera
10 mg single dose or two doses of 5 mg, 12 hours apart.
Patients with Hepatic Impairment
The recommended initial dose based on platelet count should be reduced by approximately 50% twice daily.
Additional Dosage Information
Dose modifications
If efficacy is considered insufficient and platelet and neutrophil counts are adequate after the first four weeks of treatment the initial dose can be increased by a maximum of 5 mg twice daily and thereafter at two week intervals. Maximum dose is 25 mg twice daily.
Myelofibrosis
Platelet count decreases below 100,000 per cubic mm: Consider dose reduction.
Platelet counts less than 50,000 per cubic mm or absolute neutrophil counts less than 500 per cubic mm: Suspend treatment. After recovery of platelet and neutrophil counts above these levels, dosing may be re-started at 5 mg twice daily and gradually increased based on careful monitoring of complete blood cell count.
Polycythaemia vera
Platelet count decreases below 100,000 per cubic mm and/or haemoglobin below 12 g/dL: Consider dose reduction.
Haemoglobin below 10 g/dL: Reduce dose.
Platelet counts less than 50,000 per cubic mm or absolute neutrophil counts less than 500 per cubic mm and/or haemoglobin less than 8 g/dL: Suspend treatment. After recovery of blood counts above these levels, dosing may be re-started at 5 mg twice daily and gradually increased based on careful monitoring of complete blood cell count.
Contraindications
Absolute neutrophil count below 0.5 x 10 to the power of 9 / L
Children under 18 years
Platelet count below 50 x 10 to the power of 9 / L
Severe infection
Breastfeeding
Galactosaemia
Haemoglobin concentration below 8g / dL - if treating polycythemia vera
Pregnancy
Precautions and Warnings
Platelet count below 100 x 10 to the power of 9/ L
Glucose-galactose malabsorption syndrome
Haemoglobin concentration between 8-12g/dL - if treating polycythemia vera
Hepatic impairment
Hepatitis B
Lactose intolerance
Pre-malignant skin lesions
Renal impairment - creatinine clearance below 30 ml/minute
Tuberculosis
Monitor blood count in hepatic impairment every 1-2 weeks for 1st 6 weeks
Reduce dose in patients with creatinine clearance below 30ml/min
Reduce dose in patients with hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Before initiating screen all patients for hepatitis B infection
Determine susceptibility to tuberculosis prior to treatment
Monitor patients for non-melanoma skin cancer prior to and during treatment
Treatment to be initiated and supervised by a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Dose to be increased only after 4 weeks & at maximum of 2 weekly intervals
Staff: Not to be handled by pregnant staff
Monitor complete blood counts at start and every 2-4 weeks until stable
Monitor serum lipids
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report symptoms of infection immediately
Polycythemia: Consider dose reduction if haemoglobin falls below 12g/dL
False negative tuberculin test results in immunosupp./severely ill patients
Discontinue if 25% increase in spleen volume remains after 6 months
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Polycythemia: Suspend if haemoglobin falls below 8g/dL
Suspend or modify therapy if platelet count less than 50,000 per cubic mm
Suspend treatment if neutrophil count < 500 cells per cubic mm
Consider dose reduction if platelets below 100 x 10 to the power of 9/ L
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Female: Ensure adequate contraception during treatment
Advise patient to inform physician of any skin changes immediately
Advise patient to report symptoms of herpes zoster urgently
Patients should be assessed for the risk of developing serious bacterial, mycobacterial, fungal and viral infections. Therapy should be started after active serious infections have been resolved and patients receiving treatment should be observed for signs and symptoms of infections and treated promptly.
Tuberculosis has been reported in patients receiving ruxolitinib. Patients should therefore be evaluated for active and inactive ("latent") tuberculosis prior to treatment, as per local guidelines. This may include medical history, possible previous contact with tuberculosis, and/or appropriate screening such as lung x-ray, tuberculin test and/or interferon gamma release assay. Patients who are immunocompromised or severely ill may produce false negative tuberculin skin test results.
Patients with chronic hepatitis B infections should be monitored and treated according to clinical guidelines.
Treatment should be discontinued after 6 months; if there has been no reduction in spleen size, if there is sustained increase in spleen volume of approximately 25% (or increase in spleen length of 40%) compared with baseline size, or if there is no improvement in symptoms since initiation of therapy.
Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. If PML is diagnosed, treatment should be permanently discontinued.
Pregnancy and Lactation
Pregnancy
Ruxolitinib is contraindicated during pregnancy.
The manufacturer states that there are no data available on the use of ruxolitinib in pregnant women and safety in pregnancy has not been established. Animal studies have shown decreased foetal weight and post implantation loss.
Lactation
Ruxolitinib is contraindicated during breastfeeding.
The manufacturer states that studies in animals have shown excretion of ruxolitinib and its metabolites in milk. It is unknown whether ruxolitinib and its metabolites are excreted in human milk and risk to the breastfed child cannot be excluded.
Side Effects
Alanine aminotransferase increased
Anaemia
Aspartate aminotransferase increased
Bruising
Constipation
Dizziness
Epistaxis
Flatulence
Gastrointestinal bleeding
Haematuria
Headache
Herpes zoster
Hypercholesterolaemia
Hypertriglyceridaemia
Increased bleeding tendency
Increased blood pressure
Increased susceptibility to infection
Intracranial bleeding
Neutropenia
Non melanoma skin cancer
Pancytopenia
Pneumonia
Post operative wound haemorrhage
Progressive multifocal leukoencephalopathy (PML)
Reactivation of hepatitis B
Sepsis
Thrombocytopenia
Tuberculosis
Urinary tract infections
Weight gain
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: April 2020
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Jakavi 5mg, 10mg, 15mg and 20mg tablets. Novartis Limited. Revised December 2020.
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