Drug Interaction:
Strong CYP3A4 Inhibitors:
Reduce Jakafi starting dose to 10 mg twice daily for patients with a platelet count
greater than or equal to 100 X 109/L and concurrent use of strong CYP3A4 inhibitors
. Avoid in patients with platelet counts less than 100 X 109/L.
Indication:
JAKAFI (ruxolitinib) tablets, for oral use
Initial U.S. Approval: 2011
Drug Name- Jakafi
Active Ingredient - Ruxolitinib
To treat patients with bone marrow disease myelofibrosis
Indication-
Treat patients with bone marrow disease myelofibrosis
Approved by FDA on 16-11-2011 (Ref- FDA approved List- 2011)
Proprietary Name- JAKAFI-1 *
Established Name- Ruxolitib
Applicant- ICYTE CORPORATION
Indication- For the treatment of Patients with Polycythemia Vera(PV) who
had an inadequate response to or are more intolerent of hydroxyurea(HU)
Approval Date- 4/12/2014
Approved by U.S.FDA (Ref- FDA approved List- 2014)
New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Ruxolitinib tablet 5mg/15mg/20mg 28-01-2013
For the treatment of patients with Myelofibrosis including primary
Myelofibrosis , Post-Polycythemia Vera Myelosis or Post-essential
Thrombocythemia myelofibrosis
Adverse Reaction:
The most common hematologic adverse reactions (incidence > 20%) are
thrombocytopenia and anemia. The most common non-hematologic adverse
reactions (incidence >10%) are bruising, dizziness and headache.
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Thrombocytopenia, anemia and neutropenia can occur. Manage by dose reduction,
or interruption or transfusion.
Assess patients for signs and symptoms of infection and initiate appropriate
treatment promptly. Serious infections should have resolved before starting
therapy with Jakafi.
Dosages/ Overdosage Etc:
Indication-
Treat patients with bone marrow disease myelofibrosis
Jakafi is a kinase inhibitor indicated for treatment of patients with intermediate
or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia
vera myelofibrosis and post-essential thrombocythemia myelofibrosis.
DOSAGE AND ADMINISTRATION
The starting dose of Jakafi is 20 mg given orally twice daily for patients with a
platelet count greater than 200 X 109/L, and 15 mg twice daily for patients with a
platelet count between 100 X 109/L and 200 X 109/L.
Perform a complete blood count before initiating therapy with Jakafi.
Monitor complete blood counts every 2 to 4 weeks until doses are stabilized,
and then as clinically indicated. Modify dose for thrombocytopenia.
Increase dose based on response and as recommended to a maximum of 25 mg
twice daily. Discontinue after 6 months if no spleen reduction or symptom improvement
DOSAGE FORMS AND STRENGTHS
Tablets: 5 mg, 10 mg, 15 mg, 20 mg and 25 mg.
Patient Information:
What should I tell my healthcare provider before taking Jakafi?
Before taking Jakafi, tell your healthcare provider if you:
-have an infection.
-have or have had liver or kidney problems.
-are on dialysis. Jakafi should be taken after your dialysis.
-have any other medical conditions.
-are pregnant or plan to become pregnant. It is not known if Jakafi will
harm your unborn baby.
-are breast-feeding or plan to breast-feed. It is not known if Jakafi passes into your
breast milk. You and your healthcare provider should decide if you will take
Jakafi or breast-feed. You should not do both.
Tell your healthcare provider about all the medicines you take including prescription
and nonprescription medicines, vitamins and herbal supplements.
Taking Jakafi with certain other medicines may affect how Jakafi works.
Especially tell your healthcare provider if you take medicine for:
-Fungal infections
-Bacterial infections
-HIV-AIDS
Ask your healthcare provider or pharmacist if you are not sure if your medicine
is one listed above.
Know the medicines you take. Keep a list of them to show your healthcare provider
and pharmacist when you get a new medicine.
Pharmacology/ Pharmacokinetics:
1 Mechanism of Action
Ruxolitinib, a kinase inhibitor, inhibits Janus Associated Kinases (JAKs) JAK1
and JAK2 which mediate the signaling of a number of cytokines and growth
factors that are important for hematopoiesis and immune function.
JAK signaling involves recruitment of STATs (signal transducers and activators
of transcription) to cytokine receptors, activation and subsequent localization
of STATs to the nucleus leading to modulation of gene expression.
2.Pharmacokinetics
Absorption
In clinical studies, ruxolitinib is rapidly absorbed after oral Jakafi administration with
maximal plasma concentration (Cmax) achieved within 1 to 2 hours post-dose.
Based on a mass balance study in humans, oral absorption of ruxolitinib was
estimated to be at least 95%. Mean ruxolitinib Cmax and total exposure (AUC)
increased proportionally over a single dose range of 5 to 200 mg.
There were no clinically relevant changes in the pharmacokinetics of ruxolitinib
upon administration of Jakafi with a high-fat meal, with the mean Cmax moderately
decreased (24%) and the mean AUC nearly unchanged (4% increase
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy
Pregnancy Category C
There are no adequate and well-controlled studies of Jakafi in pregnant women.
In embryofetal toxicity studies, treatment with ruxolitinib resulted in an increase in
late resorptions and reduced fetal weights at maternally toxic doses.
Jakafi should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.
2. Nursing Mothers
Roflumilast and/or its metabolites are excreted into the milk of lactating rats.
Excretion of roflumilast and/or its metabolites into human milk is probable.
There are no human studies that have investigated effects of DALIRESP
on breast-fed infants. DALIRESP should not be used by women who are nursing.
3. Pediatric Use
COPD does not normally occur in children. The safety and effectiveness of
DALIRESP in pediatric patients have not been established.
4. Geriatric Use
Of the total number of myelofibrosis patients in clinical studies with Jakafi,
51.9% were 65 years of age and older. No overall differences in safety
or effectiveness of Jakafi were observed between these patients and
younger patients.
Manufacturer Details