sorafenib

Contraindicated in:

Hypersensitivity;
Concurrent use with carboplatin and paclitaxel in patients with squamous cell lung cancer;
Congenital long QT syndrome;
OB: Pregnancy (may cause fetal harm);
Lactation: Lactation.

Use Cautiously in:

History of cardiovascular disease;
Drugs that affect the CYP3A4 or UGT1A9 systems; may result in significant interactions;
Heart failure, bradycardia, concurrent use of QT-interval prolonging drugs, or electrolyte abnormalities (↑ risk of QT interval prolongation);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: HF, MYOCARDIAL ISCHEMIA/INFARCTION, TORSADES DE POINTES, hypertension, QT interval prolongation

Derm: STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, acne, erythema, exfoliative dermatitis, flushing, hand-foot skin reaction, , pruritus, rash, dry skin, impaired wound healing

F and E: hypocalcemia, hypophosphatemia, hypokalemia

GI: HEPATOTOXICITY, anorexia, constipation, diarrhea, dyspepsia, dysphagia, ↑lipase/amylase, mucositis/stomatitis, nausea, vomiting

GU: erectile dysfunction, ↓fertility (males), nephrotic syndrome, proteinuria, renal failure

Hemat: anemia, bleeding, leukopenia, thrombocytopenia, lymphopenia

Metab: weight loss

MS: arthralgia, myalgia

Neuro: neuropathy, depression, fatigue, weakness

Resp: INTERSTITIAL LUNG DISEASE, hoarseness

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA), pain

Interactions ⬆ ⬇

Drug-drug:

May ↑ risk of bleeding with warfarin.
CYP3A4 inducers, including rifampin, phenytoin, phenobarbital, carbamazepine, and dexamethasone may ↓ levels and effectiveness.
Irinotecan, docetaxel, and doxorubicin may ↑ levels and risk of toxicity.
Neomycin may ↓ levels.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness.

Availability ⬆ ⬇

(Generic available)

Tablets: 200 mg

Route/Dosage ⬆ ⬇

PO (Adults ): 400 mg twice daily until disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits tumor growth by inhibiting multikinase enzyme, some of which are involved in angiogenesis.

Therapeutic effects:

Decreased growth and spread of advanced renal cell carcinoma, hepatocellular carcinoma and DTC.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: 38–49% absorbed following oral administration; absorption decreased by high fat meals.

Distribution: Unknown.

Protein Binding: 995% bound to plasma proteins.

Metabolism/Excretion: Mostly metabolized by the liver (CYP3A4 and UGT1A9 systems), some metabolites are pharmacologically active. Absorbed drug is eliminated in feces (51%); of absorbed drug, 77% is excreted in feces and 19% is renally eliminated.

Half-Life: 25–48 hr.

Time/Action Profile ⬆ ⬇

( blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	3 hr	12 hr

Patient/Family Teaching ⬆ ⬇

Instruct patient to take sorafenib as directed. If a dose is missed, skip dose and take next dose at regular time; do not double dose. Do not share medication with others; may be harmful. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Inform patient of risk of hand-foot skin reactions, hypertension and requirement for monitoring, risk of bleeding and cardiac ischemia. Advise patient to notify health care professional promptly if bleeding or chest pain occurs.
Advise patient to notify health care professional immediately if signs and symptoms of hepatotoxicity (yellow skin or white part of eyes, dark “tea-colored” urine, light-colored bowel movements, worsening nausea, worsening vomiting, abdominal pain), rash, blistering or peeling of skin or inside of mouth, shortness or breath, cough, dizziness, fainting, or fever occur.
Advise patient to notify health care professional of therapy prior to treatment, dental procedure, or surgery. Sorafenib therapy should be interrupted in patients undergoing major surgery.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's Wort.
Discuss with patient the possibility of hair loss. Explore coping strategies.
Rep: May cause teratogenic effects. Advise females of reproductive potential to use effective contraception during and for 6 months after stopping therapy. Advise males with female partners of reproductive potential to use effective contraception during and for 3 months after last dose. Advise female patients to avoid breastfeeding during and for 2 wks after last dose of therapy. May impair female and male fertility.

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Indications ⬇

Contraind./Precautions ⬆ ⬇