Sorafenib
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From MedlinePlus, U.S. National Library of Medicine
Kinase Inhibitor
Dosing in kidney impairment
Renal Impairment No dose adjustment is necessary for patients with mild, moderate or severe renal impairment who are not on dialysis. The pharmacokinetics of sorafenib have not been studied in patients who are on dialysis [see Clinical Pharmacology] .
| Dose Reduction | Hepatocellular Carcinoma andRenal Cell Carcinoma | Differentiated Thyroid Carcinoma |
| First Dose Reduction | 400 mg orally once daily | 400 mg orally in the morning and 200 mg orally in the evening about 12 hours apart OR 200 mg orally in the morning and 400 mg orally in the evening about 12 hours apart |
| Second Dose Reduction | 200 mg orally once daily OR400 every other day | 200 mg orally twice daily |
| Third Dose Reduction | None | 200 mg orally once daily |
| Dermatologic Toxicity Grade | Occurrence | NEXAVAR Dosage Modification | |
| Hepatocellular and Renal Cell Carcinoma | Differentiated Thyroid Carcinoma | ||
| Grade 2: Painful erythema and swelling of the hands or feet and/or discomfort affecting the patient’s normal activities | 1st occurrence | Continue NEXAVAR and consider topical therapy for symptomatic relief.If no improvement within 7 days, see below. | Decrease NEXAVAR to 600 mg daily. If no improvement within 7 days, see below. |
| No improvement within 7 days at reduced dose OR 2nd and 3rd occurrence | Interrupt NEXAVAR until resolved or improved to Grade 0 to 1. | Interrupt NEXAVAR until completely resolved or improved to Grade1. | |
| When resuming treatment, decrease dose by 1 dose level. | When resuming treatment, decrease dose by 1 dose level for 2nd occurrence and 2 doses levels for 3rd occurrence. | ||
| 4th occurrence | Discontinue NEXAVAR treatment. | ||
| Grade 3: Moist desquamation, ulceration, blistering, or severe pain of the hands or feet, resulting in inability to work or perform activities of daily living | 1st occurrence | Interrupt NEXAVAR until resolved or improved to Grade 0 to 1 | Interrupt NEXAVAR until completely resolved or improved to Grade 1. |
| When resuming treatment, decrease dose by 1 dose level. | When resuming treatment, decrease dose by 1 dose level. | ||
| 2nd occurrence | Interrupt NEXAVAR until resolved or improved to Grade 0 to 1 | Interrupt NEXAVAR until completely resolved or improved to Grade 1. | |
| When resuming treatment, decrease dose by 1 dose level. | When resuming treatment, decrease dose by 2 dose levels. | ||
| 3rd occurrence | Discontinue NEXAVAR treatment. | ||
Dosing in liver impairment
Hepatic Impairment No dose adjustment is necessary for patients with mild or moderate hepatic impairment. The pharmacokinetics of sorafenib have not been studied in patients with severe (Child-Pugh C) hepatic impairment [see Clinical Pharmacology].
Drug interactions
Check sorafenib against a medication listLabel text (5 paragraphs)
7 DRUG INTERACTIONS • Strong CYP3A Inducers: Avoid strong CYP3A4 inducers. ( 7.1 )
7.1 Effect of Other Drugs on NEXAVAR Strong CYP3A4 Inducers The concomitant use of NEXAVAR with rifampin, a strong CYP3A4 inducer decreased the mean AUC of sorafenib, which may decrease the antitumor activity [see Clinical Pharmacology ( 12.3 )] . Avoid concomitant use of NEXAVAR with strong CYP3A4 inducers, when possible, because these drugs can decrease the systemic exposure to sorafenib. Neomycin The concomitant use of NEXAVAR with neomycin decreased the mean AUC of sorafenib, which may decrease the antitumor activity. Avoid concomitant use of NEXAVAR with neomycin.
The effects of other antibiotics on the pharmacokinetics of sorafenib have not been studied [see Clinical Pharmacology ( 12.3 )].
7.2 Concomitant Use of Warfarin The concomitant use of NEXAVAR and warfarin may increase the risk of bleeding or increased the INR. Monitor INR and for clinical bleeding episodes in patients taking warfarin while receiving NEXAVAR [see Warnings and Precautions ( 5.6 )].
7.3 Drugs That Prolong the QT Interval NEXAVAR is associated with QTc interval prolongation. Avoid coadministration of NEXAVAR with medicinal products with a known potential to prolong QT/QTc interval [see Warnings and Precautions ( 5.9 ), Clinical Pharmacology ( 12.2 )] .
Contraindications
4 CONTRAINDICATIONS • NEXAVAR is contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of NEXAVAR. • NEXAVAR in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer [see Warnings and Precautions ( 5.8 )] . • NEXAVAR is contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of NEXAVAR. ( 4 ) • NEXAVAR in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , NEXAVAR may cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform a drug-associated risk. In animal reproduction studies, oral administration of sorafenib to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal toxicities at maternal exposures that were significantly lower than human exposures at the recommended dose of 400 mg twice daily (see Data). Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In animal reproduction studies, sorafenib was teratogenic and induced embryo-fetal toxicity (including increased post-implantation loss, resorptions, skeletal retardations, and retarded fetal weight) when administered orally to pregnant rats and rabbits during the period of organogenesis.
The effects occurred at doses considerably below the recommended human dose of 400 mg twice daily (approximately 500 mg/m 2 /day on a body surface area basis). Adverse intrauterine development effects were seen at doses >0.2 .mg/kg/day (1.2 mg/m 2 /day) in rats and ≥0.3 mg/kg/day (≥3.6 mg/m 2 /day) in rabbits. These doses result in exposures (AUC) that are approximately 0.008 times the AUC in patients at the recommended dose.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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