Сорафениб
Сорафениб Uses, Dosage, Side Effects, Food Interaction and all others data.
Сорафениб is a kinase inhibitor that decreases tumor cell proliferation in vitro. Сорафениб 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-ß). Several of these kinases are thought to be involved in tumor cell signaling, angiogenesis, and apoptosis. Сорафениб inhibited tumor growth and angiogenesis of human hepatocellular carcinoma and renal cell carcinoma, and several other human tumor xenografts in immunocompromised mice.
No large changes in QTc interval were observed. After one 28-day treatment cycle, the largest mean QTc interval change of 8.5 ms (upper bound of two-sided 90% confidence interval, 13.3 ms) was observed at 6 hours post-dose on day 1 of cycle 2.
| Trade Name | Сорафениб |
| Availability | Prescription only |
| Generic | Sorafenib |
| Sorafenib Other Names | Sorafenib, Sorafénib, Sorafenibum |
| Related Drugs | Keytruda, Armour Thyroid, pembrolizumab, doxorubicin, Avastin, bevacizumab, Opdivo, nivolumab, NP Thyroid, Adriamycin |
| Type | |
| Formula | C21H16ClF3N4O3 |
| Weight | Average: 464.825 Monoisotopic: 464.08630272 |
| Protein binding | 99.5% bound to plasma proteins. |
| Groups | Approved, Investigational |
| Therapeutic Class | Targeted Cancer Therapy |
| Manufacturer | |
| Available Country | Russia |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Hepatocellular Carcinoma: Сорафениб is used for the treatment of patients with unresectablehepatocellular carcinoma (HCC).
Renal Cell Carcinoma: Сорафениб is used for the treatment of patients with advanced renal cell carcinoma (RCC).
Сорафениб 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 Сорафениб works
Сорафениб 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. Сорафениб is unique in targeting the Raf/Mek/Erk pathway. By inhibiting these kinases, genetic transcription involving cell proliferation and angiogenesis is inhibited.
Dosage
Сорафениб 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.
Сорафениб 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
Сорафениб Disease Interaction
Elimination Route
The mean relative bioavailability is 38-49% for the tablet form, when compared to an oral solution. Сорафениб 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
Сорафениб is contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of Сорафениб. Сорафениб in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer
Acute Overdose
There is no specific treatment for Сорафениб overdose. The highest dose of Сорафениб 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, Сорафениб should be withheld and supportive care instituted.
Storage Condition
Store at 25° C.
Innovators Monograph
You find simplified version here Сорафениб
FAQ
What is Сорафениб used for?
Сорафениб is used to treat advanced renal cell carcinoma a type of cancer that begins in the kidneys.
How safe is Сорафениб?
Сорафениб has a favorable safety profile, with a low incidence of serious or life-threatening AEs in patients with HCC.Сорафениб treatment results in long- term efficacy and low incidence of life-threatening toxicities. Although Сорафениб has demonstrated many benefits in patients, the adverse effects cannot be ignored.
How does Сорафениб work?
Сорафениб works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells.
What are the common side effects of Сорафениб?
The common side effects of Сорафениб are include:
- tiredness
- weakness
- skin redness
- hair loss
- itching
- dry or peeling skin
- loss of appetite
- constipation
- diarrhea
- dry mouth
- weight loss
- joint pain
- numbness, pain or tingling in hands or feet
- headache
Is Сорафениб safe during breastfeeding?
If you are a woman, do not use Сорафениб if you are pregnant. You may need to have a negative pregnancy test before starting this treatment. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 6 months after your last dose.
Is Сорафениб safe during pregnancy?
Use should be avoided.This drug can harm a nursing infant.
Can I drink alcohol with Сорафениб?
The drinking of alcohol does not appear to affect the safety or usefulness of Сорафениб. plan to have children, discuss this with your doctor before being treated with sorafenib. best to use birth control while being treated with Сорафениб.
How effective is Сорафениб?
Сорафениб was associated with a nonsignificant reduction in mortality at 3 months.
When is the best time to take Сорафениб?
Take this medication by mouth on an empty stomach at least 1 hour before or 2 hours after a meal as directed by your doctor, usually twice a day.
How long can I live with Сорафениб?
Median overall survival was 26.1 months with overall 6- and 12-month survival rates of 92.1 and 85%, respectively. Median time to radiological progression was 8 months.
Does Сорафениб cause hair loss?
These are less common side effects for patients receiving Nexavar, when compared with those receiving placebo: High blood pressure (particularly in first 6 weeks of treatment) Hair loss (thinning or patchy hair loss).
Is Сорафениб toxic?
Сорафениб treatment results in long- term efficacy and low incidence of life-threatening toxicities.
How is Сорафениб administered?
The recommended daily dose of Сорафениб is 400 mg taken twice daily without food (at least 1 hour before or 2 hours after a meal).Treatment should continue until the patient is no longer clinically benefiting from therapy or until unacceptable toxicity occurs.
Is Сорафениб a chemotherapy?
Сорафениб is a cancer (chemotherapeutic) medication used to treat a type of kidney cancer called advanced renal cell carcinoma. Nexavar is also used to treat liver cancer.
When should I stop taking Сорафениб?
Сорафениб was stopped in cases with severe side effects that recurred and impaired quality of life when reintroducing the dose of 400 mg/day, when toxicity was associated with tumor progression, or when the tumor progressed in the absence of symptomatic progression if a second-line trial was available.
Will Сорафениб affect my fertility?
Сорафениб adversely affects sperm count and sperm motility which are reversible after discontinuation of treatment.
Who should not take Сорафениб?
You should not use Сорафениб if you have squamous cell lung cancer and you are being treated with carboplatin and paclitaxel.
How should I take Сорафениб?
Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.
Take Сорафениб on an empty stomach, at least 1 hour before or 2 hours after eating.
What happens if I miss a dose of Сорафениб?
Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.
Can Сорафениб shrink tumors?
MRI scans showed rapid shrinkage of the tumor size during early Сорафениб treatment which indicated that rapid tumor shrinking on the imaging may be another indicator of the therapeutic effects of Сорафениб.
Can Сорафениб be crushed?
Do not crush, break, or chew it. Take the tablet on an empty stomach, at least 1 hour before or 2 hours after a meal.
