Nexavar - Instructions For The Use Of Tablets, Price, Reviews, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Nexavar

Nexavar: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Drug interactions
14. 14. Analogs
15. 15. Terms and conditions of storage
16. 16. Terms of dispensing from pharmacies
17. 17. Reviews
18. 18. Price in pharmacies

Latin name: Nexavar

ATX code: L01XE05

Active ingredient: sorafenib (sorafenib)

Manufacturer: Bayer AG (Germany)

Description and photo updated: 2018-19-07

Prices in pharmacies: from 108,000 rubles.

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Nexavar is an anticancer drug.

Release form and composition

The dosage form of Nexavar is film-coated tablets: red, round biconvex, “200” is squeezed out on one side of the tablet, on the other - the company logo (in a cardboard box there are 4 blisters of 28 tablets and instructions for use of Nexavar).

Composition of 1 tablet:

• active substance: sorafenib - 200 mg (in the form of sorafenib tosylate - 274 mg);
• auxiliary components: sodium lauryl sulfate - 1.7 mg, microcrystalline cellulose - 16 mg, croscarmellose sodium - 36.4 mg, magnesium stearate - 2.55 mg, hypromellose 5 cP - 10.2 mg;
• shell: red iron oxide - 0.27 mg, hypromellose 15 cP - 6 mg, titanium dioxide - 1.73 mg, macrogol 3350 - 2 mg.

Pharmacological properties

Pharmacodynamics

Sorafenib - the active substance of Nexavar, is a multikinase inhibitor that helps to reduce the proliferation of tumor cells.

Sorafenib has been shown to inhibit numerous intracellular (c-CRAF, BRAF, and mutant BRAF) and cell-surface kinases (RET, KIT, FLT-3, PDGFR-β, VEGFR-1, -2 and -3). It is assumed that some of these kinases are involved in tumor cell signaling systems and in the processes of apoptosis and angiogenesis.

Sorafenib inhibits tumor growth in differentiated thyroid cancer, renal and hepatic cell carcinoma.

Pharmacokinetics

The average relative bioavailability of sorafenib after oral administration is 38–49%. C _max (maximum concentration of the substance) in plasma is reached in about 3 hours. When taken simultaneously with food with a moderate fat content, the bioavailability of the substance approximately corresponds to the value of the indicator when taken on an empty stomach. In the case of taking the drug with food with a high fat content, there is a decrease in the bioavailability of sorafenib (by about 29%).

When taking sorafenib by mouth in doses that exceed 400 mg 2 times a day, the average C _max and AUC (area under the concentration-time curve) increase disproportionately.

Taking repeated doses of sorafenib for 7 days leads to an increase in its accumulation (2.5-7 times) in comparison with the use of a single dose.

C _ss (equilibrium concentration) of sorafenib in blood plasma is reached within 7 days, the ratio of C _max to C _min (minimum concentration of the substance) is <2.

The highest exposure to sorafenib is found in patients with thyroid cancer, although there is high variability in exposure across all types of tumors. The clinical significance of this has not been established.

Sorafenib binds to blood plasma proteins at a level of 99.5%.

Metabolism of the substance occurs mainly in the liver by oxidation mediated by the isoenzyme CYP3A4, as well as glucuronidation mediated by UGT1A9.

Due to the activity of bacterial glucuronidase, sorafenib conjugates can be degraded in the gastrointestinal tract. This allows the unconjugated active substance to be reabsorbed. The combined use of neomycin affects this process (the average bioavailability of sorafenib decreases to 54%).

Once equilibrium is reached, sorafenib accounts for about 70–85%. Eight metabolites of sorafenib have been identified, of which 5 are in plasma. Pyridine N-oxide - the main circulating plasma metabolite, has an activity similar to sorafenib, it is approximately 9-16%.

After taking 100 mg of sorafenib for 14 days, 96% of the dose is excreted, including through the intestines - 77%, with urine (in the form of glucuronides) - 19%. In feces, 51% of the dose received is determined in the form of an unchanged substance.

T _1/2 (half-life) of sorafenib is about 25-48 hours.

The effect of impaired renal function on the pharmacokinetic parameters of sorafenib was not found. The pharmacokinetics of the substance in patients with severe hepatic insufficiency (on the Child-Pugh scale - class C) has not been studied.

Indications for use

• hepatocellular carcinoma;
• metastatic renal cell carcinoma;
• metastatic or locally advanced differentiated thyroid cancer that is resistant to radioactive iodine.

Contraindications

Absolute:

• pregnancy and lactation;
• age up to 18 years;
• individual intolerance to the components of the drug.

Relative (Nexavar is prescribed with caution):

• transferred myocardial infarction;
• unstable angina;
• skin diseases;
• a history of increased bleeding or bleeding;
• arterial hypertension;
• combined use with docetaxel and irinotecan.

Nexavar, instructions for use: method and dosage

The tablets should be swallowed whole with a glass of water. The drug is taken between meals or with food containing moderate or low fat.

The recommended daily dose is 400 mg 2 times a day.

Therapy is carried out until unacceptable toxic effects of sorafenib appear or until clinical efficacy persists.

If negative side effects appear, a short-term stopping of treatment or a reduction in the dose of Nexavar may be required.

Dose adjustment for metastatic renal and hepatocellular carcinoma

The daily dose, depending on the severity of the disorders, can be reduced to 400 mg once a day or once every two days.

At the first degree of skin toxicity, manifested in the form of numbness, dysesthesia, paresthesia, painless swelling, erythema or a feeling of discomfort in the soles of the feet or palms, which do not interfere with the patient's normal activity, the use of Nexavar is continued in combination with local symptomatic therapy, no matter what it is. by episode.

The second degree of cutaneous toxicity is characterized by erythema and swelling of the palms or soles of the feet, which occur with discomfort and / or pain that limits normal activity.

If this is the first episode, Nexavar is continued in conjunction with local symptomatic therapy. In the second and third episodes, as well as in the absence of improvement over seven days of symptomatic treatment of the first episode, Nexavar is canceled until the skin toxicity is stopped or its severity decreases to a state characteristic of the first degree of toxicity.

After the resumption of therapy, the dose is reduced to 400 mg once a day or once every two days.

If the fourth episode develops, Nexavar is canceled.

The third degree of skin toxicity is characterized by moist desquamation, ulceration, blistering, severe pain in the soles of the feet or palms, severe discomfort that prevents the patient from serving himself or performing professional duties.

In the case of the first or second episode, the cancellation of Nexavar is indicated until the skin toxicity is stopped or its severity decreases to the first degree.

After the resumption of therapy, the dose is reduced to 400 mg once a day or once every two days.

If the third episode develops, Nexavar is canceled.

Dose adjustment for differentiated thyroid cancer

If necessary, dose adjustment is reduced to 600 mg per day (take 2 tablets, then after 12 hours another 1 tablet).

According to indications, an additional dose reduction is possible: 1 or 2 times a day, 200 mg. The dose may be increased if the severity of adverse reactions (except for hematological) decreases.

The first degree of cutaneous toxicity is characterized by numbness, paresthesia, dysesthesia, painless swelling, discomfort or erythema in the palms or soles of the feet, while this does not interfere with the patient's normal activity. For any given episode, Nexavar treatment is continued in combination with local symptomatic therapy.

The second degree of cutaneous toxicity is characterized by erythema and swelling of the soles of the feet or palms, accompanied by a sensation of discomfort and / or pain that limits the patient's normal activity.

If symptoms are noted for the first time, Nexavar treatment is continued in combination with local symptomatic therapy.

If the episode recurs or there is no improvement after symptomatic treatment of the first episode for 7 days, the drug is stopped. The resumption of its intake is possible after the relief of skin toxicity or reduction of its severity to the first degree of toxicity.

When the use of Nexavar is resumed, its dose is reduced.

If a fourth episode is noted, the drug is discontinued.

Symptoms of the third degree of skin toxicity: ulceration, wet desquamation, blisters, severe pain in the soles of the feet or palms, severe discomfort in which the patient is unable to care for himself and carry out his professional duties.

At the first and second appearance of these signs, Nexavar is suspended until they stop or the severity of violations decreases to the first degree. The use of the drug is resumed at a reduced dose.

If a third episode develops, therapy should be discontinued.

Side effects

Possible adverse reactions, the development of which was noted during clinical trials and post-marketing observations (> 10% - very often;> 1% and 0.1% and 0.01% and <0.1% - rarely; with an unknown frequency - when fixing violations during post-marketing use or if it is impossible to establish the frequency of development):

• cardiovascular system: very often - bleeding (including hemorrhage in the brain, bleeding from the respiratory tract and gastrointestinal tract), increased blood pressure; often - hot flashes, chronic heart failure, heart attack and / or myocardial ischemia; infrequently - hypertensive crisis; rarely - lengthening of the QT interval;
• hematopoietic system: very often - lymphopenia; often - anemia, neutropenia, leukopenia, thrombocytopenia;
• respiratory system: often - dysphonia, rhinorrhea; infrequently - phenomena that are similar to interstitial lung disease (including interstitial pneumonia, pneumonia, acute respiratory distress syndrome, pneumonitis, radiation pneumonitis, pulmonitis);
• digestive system: very often - anorexia, vomiting, diarrhea, nausea, constipation; often - gastroesophageal reflux, xerostomia, stomatitis, glossodynia, dysphagia, dyspepsia; infrequently - cholangitis, cholecystitis, perforation of the gastrointestinal tract, gastritis, pancreatitis, increased concentration of bilirubin (including jaundice); rarely, medicinal hepatitis;
• skin / skin appendages: very often - pruritus, erythema, alopecia, skin rash, dry skin, palmar-plantar erythrodysesthesia; often - hyperkeratosis, folliculitis, exfoliative dermatitis, acne, keratoacanthoma / squamous cell carcinoma of the skin, peeling of the skin; infrequently - erythema multiforme, eczema; with an unknown frequency - toxic epidermal necrolysis, leukocytoclastic vasculitis, recurrent radiation dermatitis, Stevens-Johnson syndrome;
• immune system: infrequently - hypersensitivity reactions (including skin reactions and urticaria), anaphylactic reactions; with an unknown frequency - angioedema;
• nervous system: often - dysgeusia, peripheral sensory neuropathy; infrequently - syndrome of posterior reversible encephalopathy;
• urinary system: often - proteinuria, renal failure; rarely - nephrotic syndrome;
• endocrine system: often - hypothyroidism; infrequently - hyperthyroidism;
• reproductive function: often - erectile dysfunction; infrequently - gynecomastia;
• musculoskeletal system: very often - arthralgia; often - muscle spasms, myalgia; with an unknown frequency - jaw necrosis, rhabdomyolysis;
• organ of hearing: often - ringing in the ears;
• laboratory data: very often - an increase in the activity of amylase and lipase, hypophosphatemia; often - a transient increase in the activity of transaminases (alanine aminotransferase, aspartate aminotransferase), hypocalcemia, hyponatremia, hypokalemia; infrequently - hyponatremia, dehydration, transient increase in alkaline phosphatase activity, deviation of MHO and prothrombin values from the normal level;
• psyche: often - depression;
• others: very often - fever, weight loss, infections, fatigue, pain syndrome of various localization (including headache, pain in the abdomen, mouth, tumor area); often - flu-like syndrome, asthenia, inflammation of the mucous membranes.

When conducting clinical studies in patients with differentiated thyroid cancer, it was found that they have disorders in the form of palmar-plantar erythrodysesthesia, diarrhea, alopecia, weight loss, fever, hypocalcemia, keratoacanthoma / squamous cell carcinoma of the skin are observed much more often in comparison with patients with hepatocellular and renal cell carcinoma.

Overdose

The main symptoms: increased side effects, mainly skin reactions and diarrhea.

Therapy: symptomatic. The antidote is unknown.

special instructions

Nexavar should be used under the supervision of a physician who must have experience in anticancer therapy.

During the period of taking the drug, it is periodically necessary to monitor the indicators of peripheral blood (including the leukocyte formula and platelets).

Toxic reactions of the first and second severity are manifested mainly during the first 6 weeks of treatment. The most common cases are palmar-plantar erythrodysesthesia and rash. Symptomatic topical preparations can be used to treat toxic skin reactions.

During the use of Nexavar, cases of the development of arterial hypertension have been reported. Usually, this disorder is moderate or mild in nature, is observed at the beginning of treatment and can be stopped by standard antihypertensive drugs. In this regard, during the period of therapy, regular monitoring of blood pressure is indicated. In patients with persistent or severe arterial hypertension, as well as in the case of hypertensive crises, even against the background of adequate antihypertensive therapy, the advisability of further use of Nexavar should be assessed.

Taking the drug increases the risk of bleeding. Severe cases are rare. Any bleeding requiring medical attention is the basis for considering discontinuing Nexavar.

Since there is a high probability of bleeding, in differentiated thyroid cancer, prior to the appointment of Nexavar, local treatment of tumor infiltrates of the esophagus, bronchi and trachea is indicated.

When combined with warfarin, some patients rarely experienced bleeding episodes or increased MHO (international normalized ratio). With a combined appointment, regular determination of the following indicators is required: prothrombin time, MHO, clinical signs of bleeding.

If necessary, Nexavar should be temporarily canceled (a precaution). The question of the possibility of resuming therapy is decided individually, based on a clinical assessment of the adequacy of wound healing.

In case of myocardial infarction and / or ischemia, Nexavar is canceled temporarily or permanently.

It has been established that Nexavar therapy promotes prolongation of the QT / QT interval _c, while the likelihood of ventricular arrhythmias may increase. In this regard, caution is required with the current lengthening of the QT interval _c or if there is a risk of developing such a condition, namely:

• congenital long QT interval syndrome;
• high total dose anthracyclines;
• therapy with certain antiarrhythmic drugs or other drugs leading to prolongation of the QT interval;
• electrolyte disturbances, including hypokalemia, hypomagnesemia or hypocalcemia.

Such patients need periodic ECG monitoring and measurement of the concentration of electrolytes (potassium, magnesium, calcium).

In cases of perforation of the gastrointestinal tract, Nexavar is canceled.

With differentiated thyroid cancer, it is necessary to control the level of TSH (thyroid stimulating hormone).

Against the background of differentiated thyroid cancer, monitoring of the concentration of calcium in the blood is recommended. In clinical studies, patients with this diagnosis, especially those with a history of hypoparathyroidism, showed the development of more severe and frequent manifestations of hypocalcemia in comparison with patients with hepatic and renal cell carcinoma.

Caution is needed when Nexavar is combined with drugs that are metabolized and / or excreted mainly with the participation of UGT1A1 (for example, with irinotecan).

Application during pregnancy and lactation

Nexavar during pregnancy / lactation is not prescribed because the safety profile has not been studied.

Pregnancy should be avoided while using sorafenib. During therapy and for at least 14 days after its completion, you must use reliable methods of contraception.

Women of reproductive age should consider the potential risk of sorafenib to the fetus, including teratogenicity, embryotoxicity, and fetal survival problems.

Pediatric use

For patients under 18 years of age, the drug is not prescribed because the safety profile has not been studied.

With impaired renal function

There is no data on the use of sorafenib in severe renal failure (with creatinine clearance <30 ml / min) and in patients on hemodialysis.

For mild to moderate renal impairment, dose adjustment of sorafenib is not required.

For violations of liver function

The use of sorafenib for child-Pugh class C hepatitis and hepatic dysfunction has not been studied.

In case of impaired liver function of classes A and B according to the Child-Pugh classification, it is not necessary to adjust the dose of sorafenib.

Drug interactions

• CYP3A4 inducers (phenobarbital, phenytoin, rifampicin, carbamazepine, dexamethasone and preparations containing St. John's wort extract): the metabolism of sorafenib may increase, which leads to a decrease in its concentration. With long-term combined use with rifampicin, there is a significant decrease in the AUC of sorafenib;
• CYP3A4 substrates (warfarin): despite the lack of data indicating a change in the average MHO values and prothrombin time, all patients are advised to regularly determine the MHO;
• paclitaxel + carboplatin: there is an increase in exposure to sorafenib, paclitaxel and its active metabolite - 6-OH-paclitaxel (the clinical significance of this change is unknown); the pharmacokinetic parameters of carboplatin do not change;
• Capecitabine: there is an increase in the exposure of capecitabine and its metabolite (5-fluorouracil), the clinical significance of this change is unknown;
• doxorubicin, irinotecan: AUC of doxorubicin, irinotecan and its metabolite increases, the clinical significance of this change is unknown;
• docetaxel: its AUC and C _max increase; combined use requires caution;
• neomycin: the exposure of sorafenib is reduced, the clinical significance of this change is unknown; it is assumed that the effect of other antibacterial drugs will be determined by the ability to reduce glucuronidase activity.

Analogs

The analogue of Nexavar is Sorafenib-native.

Terms and conditions of storage

Store at temperatures up to 25 ° C. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Nexavar

Reviews of Nexavar indicate its high efficiency. Tumor growth is most often stopped. Adverse reactions are usually relieved by symptomatic treatment, but in some cases the drug must be abandoned.

The price of Nexavar in pharmacies

The approximate price for Nexavar (112 tablets) is 124,575-153,985 rubles.

Nexavar: prices in online pharmacies

Drug name Price Pharmacy

Nexavar 200 mg film-coated tablets 112 pcs. RUB 108,000 Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!