It Is an HIV-1 protease InhIbItor IndIcated for the treatment of HIV1 InfectIon In combInatIon wIth rItonavIr and other antIretrovIral agents In adults (over the age of 16 years).
Sorafenib is a kinase inhibitor that decreases tumor cell proliferation. Sorafenib was shown to inhibit multiple intracellular (CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT-3, RET, VEGFR-1, VEGFR-2, VEGFR-3, and PDGFR-β). Several of these kinases are thought to be involved in tumor cell signaling, angiogenesis, and apoptosis. Sorafenib inhibited tumor growth and angiogenesis of human hepatocellular carcinoma and renal cell carcinoma, and several other human tumor xenografts in immunocompromised mice.
It must be administered in combination with ritonavir. (2) ? Adults (over the age of 16 years ): It 1000 mg twice daily (5 x 200 mg capsules or 2 x 500 mg tablets) in combination with ritonavir 100 mg twice daily. ? Treatment-na?ve patients initiating treatment with It/ritonavir: First 7 days of treatment: It 500 mg twice daily with ritonavir 100 mg twice daily. After 7 days: It 1000 mg twice daily with ritonavir 100 mg twice daily. ? See Full Prescribing Information for dosing recommendations for patients switching immediately from treatment with another protease inhibitor taken with ritonavir or from a non-nucleoside reverse transcriptase inhibitor based regimen, without a wash-out period. ? It and ritonavir should be taken within 2 hours after a meal.
Carboplatin and Paclitaxel: Sorafenib in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer, due to increased mortality observed with the addition of Sorafenib compared to those treated with carboplatin and paclitaxel alone. No definitive cause was identified for this finding.
UGT1A1 and UGT1A9 Substrates: Systemic exposure to substrates of UGT1A1 and UGT1A9 may increase when co-administered with Sorafenib
Docetaxel: Concomitant use of Docetaxel (75 or 100 mg/m2 administered every 21 days) with Sorafenib (200 or 400 mg twice daily), administered with a 3-day break in dosing around administration of Docetaxel, resulted in a 36-80% increase in Docetaxel AUC and a 16-32% increase in Docetaxel Cmax. Caution is recommended when Sorafenib is co-administered with Docetaxel
Doxorubicin: Concomitant treatment with Sorafenib resulted in a 21% increase in the AUC of Doxorubicin. Caution is recommended when administering Doxorubicin with Sorafenib.
Fluorouracil: Both increases (21%-47%) and decreases (10%) in the AUC of Fluorouracil were observed with concomitant treatment with Sorafenib. Caution is recommended when Sorafenib is co-administered with Fluorouracil/Leucovorin.
CYP2B6 and CYP2C8 Substrates: Systemic exposure to substrates of CYP2B6 and CYP2C8 is expected to increase when co-administered with Sorafenib.
CYP3A4 Inducers: Continuous concomitant administration of Sorafenib and Rifampicin resulted in an average 37% reduction of Sorafenib AUC. Other inducers of CYP3A4 activity (for example, Hypericum perforatum also known as St. John’s wort, Phenytoin, Carbamazepine, Phenobarbital, and Dexamethasone) may also increase metabolism of Sorafenib and thus decrease Sorafenib concentrations.
CYP3A4 Inhibitors and CYP Isoform Substrates: Sorafenib metabolism is unlikely to be altered by CYP3A4 inhibitors and is unlikely to alter the metabolism of substrates of these enzymes.
P-glycoprotein Substrates: Sorafenib is an inhibitor of P-glycoprotein in vitro, therefore may increase the concentrations of concomitant drugs that are P-glycoprotein substrates.
CYP Enzyme Induction: CYP1A2 and CYP3A4 activities were not altered after treatment of cultured human hepatocytes with Sorafenib, indicating that Sorafenib is unlikely to be an inducer of CYP1A2 or CYP3A4.
Combination with other Antineoplastic Agents: Sorafenib had no effect on the pharmacokinetics of gemcitabine or oxaliplatin.
Neomycin: Coadministration of Sorafenib with oral Neomycin should be carefully considered because average plasma exposure (AUC) of Sorafenib was decreased by 54%.
Patients with congenital or documented acquired QT prolongation, patients with refractory hypokalemia or hypomagnesemia, or those on concomitant therapy with other drugs that prolong the QT interval. ? It is contraindicated in patients with complete atrioventricular (AV) block without implanted pacemakers, or patients who are at high risk of complete AV block. ? It is contraindicated in patients with clinically significant hypersensitivity (e.g., anaphylactic reaction, Stevens-Johnson syndrome) to saquinavir, saquinavir mesylate, or any of its ingredients. ? It when administered with ritonavir is contraindicated in patients with severe hepatic impairment. ? Coadministration of It/ritonavir with CYP3A substrates for which increased plasma levels may result in serious or life-threatening reactions. ? Coadministration of It/ritonavir with rifampin due to the risk of severe hepatotoxicity.
nausea, vomiting, diarrhea, fatigue, pneumonia, lipodystrophy and abdominal pain
Pregnancy: Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers: Do not breastfeed if HIV-1-infected mothers are receiving It therapy.
There is no specific treatment for Sorafenib overdose. The highest dose of Sorafenib studied clinically is 800 mg twice daily. The adverse reactions observed at this dose were primarily diarrhea and dermatologic.
Store at room temperature below 30°C. Do not remove desiccant. Dispense in original bottle.
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