Sorafenib tosylate is a white to yellowish or brownish solid with a molecular formula of c 21 h 16 clf 3 n 4 o 3 x c 7 h 8 o 3 s and a molecular weight of 637. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Intracranial bleeding during treatment with sorafenib for. Sorafenib tosylate is practically insoluble in aqueous media, slightly soluble in ethanol and soluble in peg 400 each red, round nexavar filmcoated tablet contains sorafenib tosylate 274 mg equivalent to 200 mg of. Sorafenib is taken without food, 1 hour before or 2 hours after a meal. Background no effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endo. The specialty pharmacy provider will fi ll your prescription and may be able to mail it to your home.
Sorafenib targets several enzymes on the surface of cancer cells, as well as targets within the cell. The gprotein ras is a key member of the mapk pathway, and it helps regulate the rafmekerk cascade. Call your doctor right away if you have chest pain or pressure, a fast or abnormal heartbeat, shortness of breath, a big weight gain, swelling in the arms or legs, or very bad dizziness or passing out. Sorafenib dose rampup in hepatocellular carcinoma hcc. The primary endpoint of the study is the total accumulated and median daily dose of sorafenib delivered at month 2 and 4.
A case report article pdf available in journal of medical case reports 41. See full prescribing information for complete boxed warning. The recommended dose of nexavar in adults is 400 mg sorafenib two tablets of 200 mg twice daily equivalent to a total daily dose of 800 mg. Nexavar tablets are round, biconvex, red filmcoated tablets, debossed with the bayer cross on one side and 200 on the other side. Braf and cell surface kinases kit, flt3, ret, vegfr1, vegfr3, and pdgfr. Dose increase or reduction is recommended based on individual safety and tolerability. Check with your physician if you have any of the following. Immune thrombocytopenia itp treatment nplate romiplostim. Official site for healthcare professionals nexavar sorafenib.
How sorafenib works, side effects, interactions and precautions. It is a chemotherapy drug that works by slowing or stopping the growth of cancer cells. Handfoot 30% skin reaction alopecia 27% pruritus 19% hypertension 17% 28% dyspnea 14% 28% based on package insert for sorafenib and sunitinib sorafenib and sunitinib are tyrosine ki nase inhibitors that target two different signaling pathways, signi. Initial treatment with sorafenib was started at the recommended dose 400 mg twice daily, and the dose was modified as recommended in the package insert. Grade 34 hypertension was observed in 56359 patients 16% receiving inlyta and 39355 patients 11% receiving sorafenib.
Other precautions for safely using sorafenib include warnings of. But in the hcc study, an excess of bleeding was not apparent. Sorafenib was shown to inhibit multiple intracellular ccraf, braf and mutant. A new disease for medical oncology thomas semrad md, mas, facp assistant professor of medicine division of hematologyoncology. If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful. Jan 25, 2020 sorafenib may increase the serum concentration of warfarin. Table adapted from sorafenib package insert for managing skin toxicities. Treatment strategies for managing skin toxicity and diarrhea can be found in lacouture et al. Nexavar is increased, the patient should be monitored carefully for toxicity see drug interactions 7.
Negative phase 3 study of 90y microspheres versus sorafenib in. It is our hypothesis that a dose escalation strategy for sorafenib will improve the tolerability and allow a greater percentage of patients to remain on drug. Severe and sometimes fatal hepatotoxicity has occurred in clinical trials. Highlights of prescribing information these highlights. Sorafenib for the treatment of advanced renal cell. Nexavar is used to treat liver cancer hepatocellular carcinoma thyroid cancer a type of. Sorafenib is used to treat kidney, liver, and thyroid cancer. Sorafenib received fda regular approval on december 20, 2005 for the treatment of advanced rcc based on the persuasive magnitude of improvement in pfs with acceptable safety. Metastatic colorectal cancer crc who have been previously treated with fluoropyrimidine, oxaliplatin and irinotecanbased chemotherapy, an anti vegf therapy, and, if ras wildtype, an antiegfr therapy. Sorafenib rechallenge in patients with metastatic renal cell. Grade 4 pancreatitis was reported in two sorafenib patients, although both patients subsequently resumed sorafenib, with one at full dose. Nexavar sorafenib is only available by prescription. See full prescribing information for complete boxed.
Figure 3 subungual hemorrhage splinter hemorrhage seen with sunitinib, can also be seen with sorafenib. Hypertensive crisis was reported in 2359 patients sorafenib. Continue treatment until disease progression or unacceptable toxicity. Chemical formula c21h16clf3n4o3 metabolism metabolized primarily in the liver 3. Blood glucose levels in diabetic patients should be checked regularly in order to assess if antidiabetic medicinal products dosage needs to be adjusted. However, in the adjuvant population, the cv effects of these agents remain unknown. Liver cancer is the fifth most common cancer in the world. Sorafenib codeveloped and comarketed by bayer and onyx pharmaceuticals as nexavar, is a kinase inhibitor drug approved for the treatment of primary kidney cancer advanced renal cell carcinoma, advanced primary liver cancer hepatocellular carcinoma, flt3itd positive aml and radioactive iodine resistant advanced thyroid carcinoma. Cancer diseases nexavar identifying genuine products of.
Sorafenib and sunitinib are potent inhibitors of multiple protein kinase targets involved in tumor cell proliferation and angiogenesis. Tell your healthcare provider about all the medicines you take, including prescription and overthecounter medicines, vitamins, and herbal supplements. The in vitro screening assay included the mutated oncogenic form of b. Gmcsf attracts dendritic cells, which present tumor ags to t cells programming them to destroy cancer cells throughout the body. Renal cell carcinoma treatment regimens cancer therapy. Dec 09, 2016 a two part study to determine the maximum tolerated dose andor recommended phase 2 dose of pdr001 in combination with sorafenib in patients with advanced hepatocellular carcinoma in first line. The following conditions are contraindicated with this drug. Nexavar active ingredient sorafenib, which is used all over the world as a cancer treatment. The study found that median survival and timetodiseaseprogression were nearly 3 months longer for patients treated with sorafenib nexavar than for patients who took placebo. Pdf sorafenib for the treatment of advanced hepatocellular. Do not breastfeed during treatment with nexavar and for 2 weeks after receiving the last dose of nexavar.
Increase frequency of inr monitoring during sorafenib therapy particularly when starting or stopping therapy, and increase monitoring for signs and symptoms of bleeding. Stivarga is a kinase inhibitor indicated for the treatment of patients with. Sorafenib rechallenge in patients with metastatic renal. Sorafenib in advanced hepatocellular carcinoma nejm. Mar 24, 2020 each red, round nexavar filmcoated tablet contains sorafenib tosylate 274 mg equivalent to 200 mg of sorafenib and the following inactive ingredients. Sorafenib is a multikinase inhibitor that decreases tumour cell proliferation in vitro. Nplate is a prescription medicine used to treat low blood platelet counts thrombocytopenia in adults with immune thrombocytopenia itp when certain medicines or surgery to remove your spleen have not worked well enough. Despite these precautions, dermatologic events were the most frequent cause of grade 34 drugrelated aes, the second cause of dose reduction. The nccn recommends cancer patient participation in clinical trials as the gold standard for treatment.
Effects of adjuvant sorafenib and sunitinib on cardiac. Each red, round nexavar filmcoated tablet contains sorafenib tosylate 274 mg equivalent to 200 mg of sorafenib and the following inactive ingredients. Download fulltext pdf download fulltext pdf late presentation of sorafenibassociated rash. Interrupt nexavar if qtc interval is greater than 500 milliseconds or for an increase from baseline of 60 milliseconds or greater. Other precautions for safely using sorafenib include warnings of potential drug interactions and allergic reactions.
Nexavar is used to treat liver cancer hepatocellular carcinoma thyroid cancer a type of kidney cancer called advanced renal cell carcinoma 4. Sorafenib in dtc monograph addendum updated version may be found at. Sorafenib for the treatment of advanced renal cell carcinoma. Over the course of treatment, patients who tolerate inlyta for at least two consecutive weeks with no adverse reactions grade 2 according to the common toxicity criteria for adverse events ctcae, are normotensive, and are not receiving antihypertension medication, may. The role of sorafenib in the treatment of advanced. The best response to initial sorafenib was partial response pr in two patients, stable disease sd in seven patients, and progressive disease pd in two patients, using the recist. Mar 11, 2020 heart problems like a type of abnormal heartbeat prolonged qt interval have happened with sorafenib. Nexavar sorafenib dosing, indications, interactions. Managing the side effects of sorafenib and sunitinib. Research continues to identify which cancers may be best treated with targeted.
Unfortunately, thirdparty companies are allowed to repackage and reimport original medicines see next. There will be a dose escalation part and a dose expansion part. We want our patients, as well as doctors, pharmacists, customs officials, etc. Nexavar sorafenib chemotherapy, side effects navigating care. Get emergency help right away if you get symptoms such as chest pain, shortness of breath, racing heartbeat, swelling in lower legs, feet and abdomen, feel lightheaded or faint. Sorafenib works by inhibiting several kinases in the mapk pathway figure 1a. Sunitinib and sorafenib are used widely in the treatment of renal cell carcinoma rcc. Study of safety and tolerability of pdr001 in combination. The nccn recommends cancer patient participation in clinical trials as the gold standard. Nexavar is contraindicated in patients with known severe hypersensitivity to sorafenib or. Tablets containing sorafenib tosylate 274 mg equivalent to 200 mg of sorafenib. Endpt durable response rate % pts w cr or pr maintained 6mo. You can get nexavar from your doctor, hospital, or specialty pharmacy provider spp.
Sorafenib was initially identified as an inhibitor of raf serinethreonine kinase isoforms, which are in the ras signaling pathway. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Not associated with pain or interference with function. Extreme high moderate low section 1 chemical product and company identification product name sorafenib tosylate statement of hazardous nature considered a hazardous substance according to osha 29 cfr 1910. Identifying genuine products of bayer healthcare product presentation, packaging design, and selected security features. Highlights of prescribing information these highlights do. Oct 25, 2019 renal cell carcinoma treatment regimens. Sorafenib and sunitinib kim 2009 the oncologist wiley.
A two part study to determine the maximum tolerated dose andor recommended phase 2 dose of pdr001 in combination with sorafenib in patients with advanced hepatocellular carcinoma in first line. Precautions and warnings with sorafenib prior to starting treatment with sorafenib, your healthcare provider needs to know if you have a history of problems with your liver, kidneys, or heart. How nexavar sorafenib chemotherapy works, side effects, interactions and precautions. Several of these targets are thought to be involved in angiogenesis making of blood vessels. Managing the side effects of sorafenib and sunitinib nursing management 5. Approval of nexavar for locally advancedmetastatic renal cell clear cell.
Typically, for this type of trial, a large sample size of about patients is required. How sorafenib works, side effects, interactions and. Sorafenib is classified as a, tyrosine kinase inhibitor, angiogenesis inhibitor, vegf inhibitor. Renal cell carcinoma treatment regimens cancer therapy advisor. Nexavar is indicated for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma dtc that is refractory to radioactive iodine treatment. Sorafenibinduced hepatitis is characterized by a hepatocellular pattern of liver damage with significant increases of transaminases which may result in hepatic failure and death. Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs. Nexavar, innsorafenib european medicines agency europa eu. These agents are associated with a significant incidence of cardiovascular cv dysfunction and left ventricular ejection fraction lvef declines, observed largely in the metastatic setting. Before taking nexavar, tell your healthcare provider about all of your medical conditions, including if you. Sorafenib induced hepatitis is characterized by a hepatocellular pattern of liver damage with significant increases of transaminases which may result in hepatic failure and death. Heart problems like a type of abnormal heartbeat prolonged qt interval have happened with sorafenib.