fedratinib

Contraindicated in:

Thiamine deficiency (correct before starting therapy);
Severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Cardiovascular risk factors (↑ risk of cardiovascular death, MI, stroke);
Current or past history of smoking (↑ risk of malignancy, cardiovascular death, MI, or stroke);
Known malignancy;
Severe renal impairment (↓ dose);
Pedi: Safety and efficacy not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: ARTERIAL THROMBOSIS, CARDIOVASCULAR DEATH, DEEP VEIN THROMBOSIS, MI

F and E: hyponatremia

GI: constipation, diarrhea, ↑amylase, ↑lipase, ↑liver enzymes, nausea, vomiting, HEPATOTOXICITY

GU: ↑serum creatinine, dysuria

Hemat: anemia, neutropenia, thrombocytopenia

Metab: ↑weight

MS: muscle spasm, pain

Neuro: fatigue, dizziness, ENCEPHALOPATHY, headache, STROKE

Resp: PULMONARY EMBOLISM

Misc: SECONDARY MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including ketoconazole, may ↑ levels and risk of toxicity; avoid concurrent use. If concurrent use unavoidable, ↓ fedratinib dose.
Dual CYP3A4 and CYP2C19 inhibitors, including fluconazole, may ↑ levels and risk of toxicity.
Moderate or strong CYP3A4 inducers may ↓ levels and effectiveness; avoid concurrent use.
May ↑ levels of CYP3A4 substrates, CYP2C19 substrates, and CYP2D6 substrates.

Availability ⬆ ⬇

Capsules: 100 mg

Route/Dosage ⬆ ⬇

PO (Adults ): Platelet count >50 × 10⁹/L: 400 mg once daily. Concurrent use of strong CYP3A4 inhibitor: 200 mg once daily.

Renal Impairment

PO (Adults ): CCr 15–29 mL/min and platelet count >50 × 10⁹/L: 200 mg once daily.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits activated Janus-associated kinase 2 and FMS-like tyrosine kinase 3, which inhibits hematopoietic cell proliferation and causes apoptosis.

Therapeutic effects:

Reduction in spleen size and symptoms.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Protein Binding: ≥92%.

Metabolism/Excretion: Mostly metabolized in the liver via the CYP3A4 and CYP2C19 isoenzymes. Primarily excreted in feces (77%, 23% as unchanged drug), with 5% excreted in urine (3% as unchanged drug).

Half-Life: 114 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2–4 hr	24 hr

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication. Periodic lab tests will be needed.
Advise patient to notify health care professional immediately if signs and symptoms of encephalopathy (confusion, memory problems, drowsiness, problems with balance and movement, difficulty walking, double or blurred vision, abnormal eye movements) or GI toxicity (diarrhea, nausea, or vomiting that does not respond to treatment; rapid weight loss or weight loss that does not get better with treatment) occur.
Advise patient to report signs and symptoms of anemia (fatigue, dizziness, pale conjunctiva), thrombocytopenia (easy bruising, bleeding gums or nose, blood in urine), and neutropenia (fatigue, sore throat, swollen lymph nodes).
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy and for ≥1 mo after last dose.

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Indications ⬇

Contraind./Precautions ⬆ ⬇