Sofenib

Uses

Hepatocellular Carcinoma: Sofenib is used for the treatment of patients with unresectablehepatocellular carcinoma (HCC).

Renal Cell Carcinoma: Sofenib is used for the treatment of patients with advanced renal cell carcinoma (RCC).

Sofenib is also used to associated treatment for these conditions: Advanced Renal Cell Carcinoma, Gastrointestinal Stromal Tumors, Hemangiosarcoma, Unresectable Hepatocellular Carcinoma, Locally recurrent refractory to radioactive iodine treatment Thyroid carcinoma, Metastatic refractory to radioactive iodine treatment Thyroid carcinoma

How Sofenib works

Sofenib interacts with multiple intracellular (CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-ß). Several of these kinases are thought to be involved in angiogenesis, thus sorafenib reduces blood flow to the tumor. Sofenib is unique in targeting the Raf/Mek/Erk pathway. By inhibiting these kinases, genetic transcription involving cell proliferation and angiogenesis is inhibited.

Dosage

Sofenib dosage

Advanced renal cell carcinoma: 400 mg bid. May continue until patient is no longer responding or unacceptable toxicity occurs.

Hepatic Impairment: No safety data is available for use in patients with Child-Pugh C hepatic impairment.

Should be taken on an empty stomach. May be taken with a low or moderate fat meal. If the patient intends to have a high fat meal, sorafenib should be taken on an empty stomach at least 1 hr before or 2 hr after meals. Swallow whole, do not chew/crush.

Side Effects

Rash and hand-foot skin reactions. Hypophosphataemia, hypertension, bleeding, tinnitus, depression and erectile dysfunction. Alopecia, pruritus, dry skin, erythema, acne, flushing, exfoliative dermatitis, hoarseness, GI disturbances, arthralgia, myalgia, asthenia, pain and peripheral neuropathy.

Toxicity

The highest dose of sorafenib studied clinically is 800 mg twice daily. The adverse reactions observed at this dose were primarily diarrhea and dermatologic events. No information is available on symptoms of acute overdose in animals because of the saturation of absorption in oral acute toxicity studies conducted in animals.

Precaution

Interrupt teatment if patient develops cardiac infarction, ischaemia and/or bleeding fatalities. Regular monitoring of BP, CBC and platelet is recommended. Monitor INR in patients who are on treatment with warfarin. Adequate contraception should be used during and for at least 2 wk after stopping treatment. May need to discontinue treatment if severe or persistent hypertension occurs.

Interaction

Inducers of isoenzyme CYP3A4 e.g. carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampicin may decrease sorafenib plasma concentration. Coadmin with sorafenib may increase the plasma concentration of doxorubicin and irinotecan.

Food Interaction

• Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum levels of sorafenib.
• Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce serum levels of sorafenib.
• Take on an empty stomach. Take sorafenib with at least one-hour separation before meals and two hours after meals.

[Moderate] ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of sorafenib.

According to the product labeling, sorafenib bioavailability was reduced by 29% when administered with a high-fat meal compared to administration in the fasted state.

When given with a moderate-fat meal, bioavailability was similar to that in the fasted state.

MANAGEMENT: To ensure maximal and consistent oral absorption, sorafenib should be taken at least one hour before or two hours after eating.

Sofenib Drug Interaction

Major: citalopram, sotalolModerate: ciprofloxacin, modafinilUnknown: aspirin, amphetamine / dextroamphetamine, zolpidem, amoxicillin, darbepoetin alfa, amoxicillin / clavulanate, rosuvastatin, omega-3 polyunsaturated fatty acids, ginkgo, heparin, potassium chloride, acetaminophen, vitamin a topical, bioflavonoids, metoprolol, valproic acid

Sofenib Disease Interaction

Moderate: lung toxicity

Elimination Route

The mean relative bioavailability is 38-49% for the tablet form, when compared to an oral solution. Sofenib reached peak plasma levels in 3 hours following oral administration. With a high-fat meal, bioavailability is reduced by 29% compared to administration in the fasted state.

Half Life

25-48 hours

Elimination Route

Following oral administration of a 100 mg dose of a solution formulation of sorafenib, 96% of the dose was recovered within 14 days, with 77% of the dose excreted in feces, and 19% of the dose excreted in urine as glucuronidated metabolites.

Pregnancy & Breastfeeding use

Pregnancy category D There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Sofenib is contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of Sofenib. Sofenib in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer

Acute Overdose

There is no specific treatment for Sofenib overdose. The highest dose of Sofenib studied clinically is 800 mg twice daily. The adverse reactions observed at this dose were primarily diarrhea and dermatologic. No information is available on symptoms of acute overdose in animals because of the saturation of absorption in oral acute toxicity studies conducted in animals. In cases of suspected overdose, Sofenib should be withheld and supportive care instituted.

Storage Condition

Store at 25° C.

Innovators Monograph

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