Tafinlar

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

Tafinlar: instructions for use and reviews

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

Latin name: Tafinlar

ATX code: L01XE23

Active ingredient: dabrafenib (Dabrafenib)

Producer: Glaxo Operations UK Limited (Great Britain); Glaxo Wellcome S. A. (Glaxo Wellcome SA) (Spain); OOO Skopinsky Pharmaceutical Plant (OOO SKOPINFARM) (Russia); GlaxoSmithKline Inc (Canada); GlaxoSmithKline Trading, CJSC (Russia)

Description and photo update: 2019-09-07

Tafinlar is an antineoplastic drug, a protein kinase inhibitor.

Release form and composition

Tafinlar is produced in the form of capsules: hard, opaque, inside the capsules there is a powder from almost white to white:

dosage of 50 mg: size No. 2, dark red, GS TEW inscription on the lid in black ink, 50 mg on the body;
dosage 75 mg: size No. 1, dark pink color, the inscription GS LHF is applied on the lid on the lid, on the body - 75 mg.

Packaging: 28 pcs. or 120 pcs. in polyethylene bottles, in a cardboard box 1 bottle and instructions for use of Tafinlar.

1 capsule contains:

active substance: micronized dabrafenib mesylate - 59.25 mg or 88.88 mg, which corresponds to the content of 50 mg or 75 mg of dabrafenib;
auxiliary components: microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide;
capsule shell size 1: Opaque Pink, hypromellose, titanium dioxide, iron oxide red;
capsule shell size # 2: Swedish Orange, hypromellose, titanium dioxide, iron oxide red;
S-1-17822 or S-1-17823 ink: shellac, propylene glycol, butanol, isopropanol, iron dye black oxide, aqueous ammonia.

Pharmacological properties

Pharmacodynamics

Tafinlar is an antineoplastic drug. Its active ingredient, dabrafenib, is a potent selective inhibitor of RAF kinases that competes with ATP (adenosine triphosphoric acid).

Pharmacodynamics of dabrafenib in monotherapy

When monotherapy with Tafinlar, the inhibitory concentration IC ₅₀ (the concentration of half-maximal inhibition) of dabrafenib for isoenzymes is: BRAF ^V600E - 0.65 nmol / l; BRAF ^V600K - 0.5 nmol / l; BRAF ^V600D - 1.84 nmol / L.

Oncogenic mutations of the BRAF gene encoding the protein cause constitutive activation of the RAS / RAF / MEK / ERK pathway and stimulation of tumor cell growth. A high frequency of mutations in the BRAF gene is detected in melanoma (about 50% of cases) and other specific neoplasms. Most often, cancer patients have a mutation in the BRAF ^V600E and BRAF ^{V600K genes}, which accounts for 95% of the BRAF gene mutations. Mutations BRAF ^V600D, BRAF ^V600G and BRAF ^V600R are rare. The inhibitory activity of dabrafenib is manifested against wild-type CRAF and BRAF isoenzymes, its IC ₅₀is 5 nmol / l and 3.2 nmol / l, respectively. Tafinlar inhibits the growth of non-small cell lung cancer cells that carry the BRAF ^V600 gene mutation in vitro and in vivo in xenograft models of melanoma.

Pharmacodynamics of dabrafenib in combination with trametinib

Trametinib is a highly selective, reversible allosteric inhibitor of the activation of mitogen-activated kinases 1 and 2 (MEK1 and MEK2), which are regulated by extracellular signaling. MEK proteins are components of the extracellular signaling kinase (ERK) signaling pathway.

The use of Tafinlar in combination with trametinib causes simultaneous inhibition of BRAF and MEK, two kinases of this signaling pathway. This allows to achieve duplicated suppression of proliferative signal transmission and additive synergistic effect of drugs in melanoma cell lines, as well as non-small cell lung cancer with BRAF mutation. In addition, the formation of resistance in melanoma xenografts carrying the BRAF ^V600 gene mutation slows down in combination with trametinib therapy.

According to the results of in vitro studies and in animal experiments, it was revealed that dabrafenib inhibits phosphorylated ERK kinase (an underlying pharmacodynamic marker) in melanoma cells that carry the BRAF ^V600 mutation. In patients with melanoma, the BRAF ^V600 mutation, dabrafenib inhibits the activity of phosphorylated ERK kinase in relation to the initial value.

Prolongation of the QT interval

Specialized studies have been conducted to evaluate the potential effect of repeated dabrafenib administration on QT prolongation. 32 patients with tumors with the BRAF ^V600 gene mutation took dabrafenib at a dose of 300 mg twice a day (exceeding the therapeutic dose). At the same time, there was no clinically significant effect of dabrafenib or its metabolites on lengthening the QTc interval - the QT interval corrected relative to the heart rate (HR).

In 3% of patients receiving dabrafenib, a maximum, more than 60 ms, QTc interval lengthening was observed, including one episode with an increase of more than 500 ms from the total indication in the population.

During the phase III study of MEK115306 in patients taking trametinib in combination therapy with dabrafenib, not a single case of QT interval lengthening, corrected by QTc (B) (Bazett's formula), more than 500 ms was recorded. An extension of QTc (B) above 60 ms from baseline was observed in less than 1% of cases (in 3 patients out of 209).

When studying the effect of trametinib in combination with dabrafenib on patients with phase III MEK116513, 4 of them (1%) had QTc lengthening (B) of grade 3 - more than 500 ms, 2 (0.5%) had QTc lengthening (B) Grade 3 - more than 500 ms, which was also an elongation of more than 60 ms from the initial indicator.

Pharmacokinetics

When taken orally, dabrafenib is actively absorbed. Its maximum concentration (C _max) in plasma is reached on average after 2 hours. The absolute bioavailability can average 95%. Against the background of regular use 2 times a day, an increase in the exposure of dabrafenib AUC (area under the pharmacokinetic curve "concentration - time") and, to a lesser extent, C _max depend on the dose taken. It is believed that some reduction in exposure with repeated use may be due to the induction of its own metabolism. The average AUC cumulation ratio after 18 days of therapy was 0.73. After taking Tafinlar at a dose of 150 mg 2 times a day, the geometric mean C _max was 1478 ng / ml, AUC _{0 – τ}- 4341 ng × h / ml, the concentration of the substance before the dose (Cτ) - 26 ng / ml. With the simultaneous intake of food, its bioavailability decreases, absorption slows down, decreases by 51% C _max and 31% AUC (compared with fasting).

Plasma protein binding is 99.7%, the apparent volume of distribution (V _d) is 70.3 liters.

In vitro, dabrafenib is a substrate for human P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP1). When administered orally, the bioavailability and elimination of dabrafenib is slightly affected by these vectors, so the risk of drug interactions is minimal.

Dabrafenib is metabolized in several stages. At the first stage, with the participation of CYP2C8 and CYP3A4 isoenzymes, hydroxydabrafenib is formed, which is oxidized to carboxydabrafenib using the CYP3A4 isoenzyme. Carboxydabrafenib, as a result of non-enzymatic decarboxylation, is biotransformed into desmethyldabrafenib, which is oxidized by the CYP3A4 isoenzyme. Carboxydabrafenib is excreted in bile and urine. The formation and reabsorption of desmethyldabrafenib can also occur in the intestine.

The terminal half-life (T _1/2) of hydroxydabrafenib is 10 hours, carboxydabrafenib and desmethyldabrafenib is from 21 to 22 hours. The activity of hydroxydabrafenib and desmethyldabrafenib plays an important role in the realization of the clinical efficacy of dabrafenib, the role of carboxydabrafenib is insignificant.

Due to the lengthening of the terminal phase, the final T _{1/2 of} dabrafenib is 8 hours, its clearance after a single use is 17 l / h, after 14 days of taking 2 times a day - 34.4 l / h. Dabrafenib is excreted mainly through the intestines (71% of the dose taken), through the kidneys - 23%.

With a mild degree of liver dysfunction due to oral administration of dabrafenib, its clearance does not differ significantly from that in patients with normal liver function. In addition, mild liver dysfunction does not significantly affect the plasma concentration of dabrafenib metabolites. In case of moderate to severe liver dysfunction, Tafinlar should be used with caution.

When the drug is taken orally, mild and moderate renal dysfunction with creatinine clearance (CC) from 30 to 89 ml / min has a weak and clinically insignificant effect on the clearance of dabrafenib, as well as on the plasma concentrations of hydroxydabrafenib, carboxydabrafenib and desmethyldabrafenib. The influence of Tafinlar on the condition of patients with severe renal impairment has not been established.

The results of the population pharmacokinetic analysis indicate the absence of a significant effect of the patient's age on the pharmacokinetics of dabrafenib. In patients aged 75 years and older, higher plasma concentrations of carboxydabrafenib and desmethyldabrafenib are predicted (40% increase in exposure). The safety and efficacy of Tafinlar in persons under 18 years of age has not been established.

When administered orally, the effect of body weight and gender of the patient on pharmacokinetic parameters such as dabrafenib clearance, volume of distribution and distribution clearance are not considered clinically significant.

The effect of race on the pharmacokinetics of dabrafenib has not been established.

As a result of the combined repeated administration of dabrafenib at a dose of 150 mg 2 times a day and trametinib at a dose of 2 mg once a day, the C _{max of} dabrafenib increased by 16% and AUC - by 23%. The bioavailability of trametinib decreases slightly, its AUC becomes 12% lower. These changes are not clinically significant.

Indications for use

The use of Tafinlar is indicated in the treatment of the following cancers caused by the BRAF ^V600 gene mutation:

unresectable or metastatic melanoma (monotherapy / combination with trametinib);
adjuvant therapy after total resection of stage III melanoma (combination with trametinib);
advanced non-small cell lung cancer (monotherapy / combination with trametinib).

Contraindications

Absolute:

melanoma or non-small cell lung cancer with a wild-type BRAF gene mutation;
period of pregnancy;
breast-feeding;
age up to 18 years;
hypersensitivity to the components of the drug.

It is recommended to use Tafinlar capsules with caution for the treatment of patients with severe renal impairment, moderate and severe liver dysfunction, with concomitant therapy with drugs that are inducers or inhibitors of CYP3A4 and CYP2C8 isoenzymes or substrates of polypeptide carriers of organic anions OATP1B1 and OATP1B3.

Tafinlar, instructions for use: method and dosage

Tafinlar should be treated by a doctor with experience in the use of antineoplastic agents.

Capsules are taken orally 1 hour before meals or 2 hours after meals. An interval of 12 hours should be observed between each dose. If you accidentally skip taking the next dose, you can take the missed dose only if there are more than 6 hours before the next dose. When treating with the drug in combination with trametinib, a single daily dose of trametinib should be taken regularly at the same time as the morning or evening dose of dabrafenib.

The use of Tafinlar should only be started after appropriate confirmation of the BRAF ^V600 gene mutation in each patient by an approved or validated test.

Recommended dosage: monotherapy or in combination with trametinib - 150 mg of dabrafenib 2 times a day (total daily dose 300 mg). The duration of treatment is determined by the clinical efficacy of Tafinlar.

If a toxic reaction or other side effects occur, other than squamous cell skin cancer (SCRC) or a new focus of primary melanoma, a dose reduction, interruption of therapy, or complete cessation of drug treatment may be required.

When decreasing the daily dose of dabrafenib, the following scheme should be followed:

initial dose: 300 mg (150 mg 2 times / day);
first dose reduction: 200 mg (100 mg 2 times / day);
second dose reduction: 150 mg (75 mg 2 times / day);
third dose reduction: 100 mg (50 mg 2 times / day).

A dose reduction of less than 100 mg (50 mg 2 times / day) is not recommended.

The need for dose adjustment of Tafinlar is determined by assessing the severity of adverse reactions using the CTC-AE scale (Standard criteria for assessing adverse reactions), version 4.

Recommended dabrafenib dose adjustment regimen:

unwanted toxic reactions of 1 or 2 degrees of severity (tolerable): treatment is continued, monitoring the patient's condition in accordance with clinical indications;
adverse toxic reactions of 2 (intolerable) or 3 degrees of severity: a break in the use of the drug is indicated for the period until the adverse events correspond to 0-1 degrees. The therapy should be resumed with a dose reduced by 1 level;
undesirable toxic reactions of 4 degrees of severity: Tafinlar is discontinued or interrupted for a period until the patient's condition recovers and will correspond to 0-1 degrees of severity of toxic reactions. After a forced break, therapy is started with a dose reduced by 1 level.

After successfully overcoming the undesirable phenomenon, a gradual increase in the dose is possible, which is carried out in the reverse order of the decrease in the dose.

If during therapy with dabrafenib in combination with trametinib, adverse reactions such as fever and uveitis occur, appropriate measures should be taken:

fever (an increase in body temperature above 38.5 ° C): if it appears during monotherapy with Tafinlar or treatment in combination with trametinib, the drug should be interrupted, and therapy with trametinib should be continued at the same dose. The patient is prescribed antipyretics (ibuprofen, acetaminophen, or paracetamol) and is examined for signs and symptoms of infection. After normalization of body temperature, taking the drug in the same dose can be resumed in combination with the prophylactic intake of antipyretics. Reducing the dose of Tafinlar by one level is indicated in cases where the development of fever is repeated and / or it is accompanied by such severe symptoms as dehydration, arterial hypotension, renal failure. With the ineffectiveness of antipyretics, the appointment of oral glucocorticosteroids is indicated;
uveitis: with its development, the dose of Tafinlar is not adjusted if it is possible to control the symptoms of the inflammatory process by using ophthalmic drugs for topical use. Taking capsules is interrupted in the absence of a clinical response to the ongoing therapy of uveitis for the period of relief of the inflammatory process. Antineoplastic therapy was resumed with a reduced dose of dabrafenib by one level; no change in the trametinib dose was required.

If any other toxic reactions occur during combination therapy with trametinib, given the severity of the patient's condition, it is necessary to reduce the dose of two drugs at once, interrupt or completely stop the combined treatment.

For patients over the age of 65, with mild to moderate renal dysfunction or mild liver dysfunction, dose adjustment is not required.

Particular care should be taken when treating patients with severe renal impairment and / or moderate to severe liver dysfunction.

Side effects

Adverse reactions established in a clinical study involving 578 people with melanoma taking Tafinlar as monotherapy for more than 6 months:

neoplasms (including cysts and polyps), benign, malignant and unspecified: very often - papilloma; often - a soft wart (acrochordon), seborrheic keratosis, squamous cell skin cancer, basal cell carcinoma; infrequently - the formation of a new focus of primary melanoma;
from the immune system: infrequently - hypersensitivity reactions;
infectious and parasitic pathologies: often - nasopharyngitis;
on the part of metabolism and nutrition: very often - decreased appetite; often - hyperglycemia, hypophosphatemia;
from the nervous system: very often - headache;
on the part of the organ of vision: infrequently - uveitis;
from the respiratory system, chest and mediastinal organs: very often - cough;
from the gastrointestinal tract: very often - diarrhea, nausea, vomiting; often constipation; infrequently - pancreatitis;
on the part of the skin and subcutaneous tissues: very often - skin rash, hyperkeratosis, palmar-plantar erythrodysesthesia, alopecia; often - dry skin, itching, erythema, skin lesions, photosensitivity reactions, actinic keratosis; infrequently - panniculitis;
from the musculoskeletal system: very often - pain in the limbs, arthralgia, myalgia;
from the urinary system: infrequently - nephritis, renal failure, acute renal failure;
general disorders: very often - increased fatigue, fever, asthenia, chills; often - flu-like syndrome.

Side effects established in a clinical study involving 1076 patients (of which 82 patients with advanced non-small cell lung cancer), taking Tafinlar as a combination therapy with trametinib:

infections and invasions: very often - nasopharyngitis; often - urinary tract infection, folliculitis, cellulitis, pustular rash, paronychia;
neoplasms (including cysts and polyps) of benign, malignant and unspecified nature: often - squamous cell skin cancer (including Bowen's disease / dermatosis, keratoacanthoma), papilloma (including skin papilloma), seborrheic keratosis; infrequently - acrochordon, a new focus of primary melanoma (including malignant melanoma, metastatic malignant melanoma, superficial spreading stage III melanoma);
from the skin and subcutaneous tissue: very often - itching, rash, dry skin, erythema; often - actinic keratosis, acneform dermatitis, night sweats, alopecia, palmar-plantar erythrodysesthesia syndrome, hyperkeratosis, skin lesions, panniculitis, hyperhidrosis, photosensitivity reactions, superficial cracks in the skin;
on the part of the blood and lymphatic system: often - neutropenia, leukopenia, anemia, thrombocytopenia;
from the immune system: infrequently - hypersensitivity reactions;
on the part of metabolism and nutrition: very often - decreased appetite; often - hyponatremia, hyperglycemia, hypophosphatemia, dehydration;
from the nervous system: very often - dizziness, headache;
on the part of the organ of vision: often - visual impairment, uveitis, blurred vision; infrequently - retinal detachment, chorioretinopathy, periorbital edema;
from the side of the heart: often - a decrease in the ejection fraction; infrequently - bradycardia; frequency not established - myocarditis;
on the vascular side: very often - hemorrhages of various localization (including intracranial hemorrhage, fatal bleeding), arterial hypertension; often - lymphatic edema, arterial hypotension;
from the respiratory system, chest and mediastinum: very often - cough; often - shortness of breath; infrequently - pneumonitis;
from the gastrointestinal tract: very often - constipation, diarrhea, pain in the upper and lower abdomen, nausea, vomiting; often - stomatitis, dry mouth; infrequently - colitis, pancreatitis; rarely - perforation of the gastrointestinal tract;
from the musculoskeletal system: very often - pain in the limbs, muscle spasms, muscle stiffness, arthralgia, myalgia;
from the urinary system: infrequently - nephritis, renal failure;
general disorders: very often - chills, fever, increased fatigue, asthenia, peripheral edema, flu-like pathologies; often - swelling of the face, inflammation of the mucous membranes;
laboratory indicators: very often - an increase in the activity of alanine aminotransferase, aspartate aminotransferase; often - an increase in the activity of gamma-glutamyltransferase, alkaline phosphatase, creatine phosphokinase.

Overdose

To date, data on overdose of dabrafenib are limited, the maximum dose received by patients in clinical trials is 600 mg (300 mg 2 times / day). Overdose symptoms have not been established.

Treatment: there is no specific antidote. In the event of the development of adverse events, symptomatic and supportive therapy is prescribed, corresponding to the clinical manifestations. Immediate withdrawal of the drug is required.

special instructions

Before starting the use of the drug Tafinlar in combination with trametinib, you should also read the full instructions for the medical use of the latter.

On the background of monotherapy with Tafinlar or in combination with trametinib, fever and severe non-infectious febrile fever may occur. The most common cases of fever were observed during the treatment of unresectable or metastatic melanoma in patients receiving Tafinlar in combination with trametinib. The first episodes of fever usually occur at the beginning of therapy (the first month), and may be accompanied by severe tremors, arterial hypotension, dehydration, and in rare cases, the development of acute renal failure. In patients who have experienced severe episodes of fever, renal function parameters, including serum creatinine concentration, should be monitored. To relieve these conditions, it is recommended to adjust the dose of dabrafenib and / or to suspend treatment while prescribing maintenance therapy.

The likelihood of developing squamous cell skin cancer (SCRC) in patients with unresectable or metastatic melanoma is higher when the drug is used as monotherapy. In the course of clinical studies, it was found that after the start of monotherapy with Tafinlar, the first signs of SCRC can appear after 2 months and be noted in 10% of patients. Whereas, in combination therapy with trametinib, SCRC is observed only in 3% of patients and the period before the appearance of its first signs is 5–8 months. In the treatment of non-small cell lung cancer, SCRC was observed in 18% of patients on monotherapy with the drug, and in 2% of patients receiving dabrafenib in combination with trametinib. When SCRC appeared on the background of the drug use, treatment in more than 90% of patients was continued without changing the dose.

The condition of the skin should be examined both before starting treatment, and regularly throughout the entire course of therapy with an interval of 2 months. It is necessary to continue monitoring the condition of the skin after the end of drug therapy with an interval of 2-3 months for the next 6 months. A diagnosed SCRC requires surgery on the affected area without stopping dabrafenib therapy. The patient should be informed about the need to immediately contact the attending physician if new lesions appear on the skin.

Due to the existing risk of developing malignant neoplasms of other localization, carrying the mutation of the RAS genes, during the period of Tafinlar use and within 6 months after its withdrawal, patients should be provided with appropriate observation. When malignant neoplasms of a different localization appear, the question of continuing therapy with the drug is decided individually.

In the case of abdominal pain of unknown etiology, it is necessary to conduct an examination to determine the activity of amylase and lipase in the blood serum. If the development of pancreatitis is confirmed, therapy should be suspended, and the patient should be closely monitored after resuming dabrafenib treatment.

Before starting the use of Tafinlar, after one month of therapy and at each dose adjustment, it is necessary to conduct an electrocardiographic study (ECG) and determine the content of plasma electrolytes (including magnesium). It is not recommended to start taking Tafinlar in case of amenable to correction of imbalance in water and electrolyte balance, prolongation of the QT interval syndrome and patients taking drugs that can cause prolongation of the QT interval. Dabrafenib should not be initiated or continued with a QTc interval of more than 500 ms. The therapy can be resumed at a reduced dose if the QTc value is less than 500 ms, achieved after restoration of water-electrolyte balance and correction of cardiac risk factors affecting QT interval prolongation (including congestive heart failure and bradycardia). Treatment with the drug should be discontinued completely when the QTc interval is more than 500 ms, as well as in the case of an increase from the initial value of more than 60 ms.

When prescribing Tafinlar, patients should be informed of the need for immediate medical attention in case of any symptoms of adverse reactions.

Persons with already diagnosed hyperglycemia or diabetes mellitus should be warned about the need to carefully monitor the concentration of glucose in the blood serum, and immediately consult a doctor in case of excessive thirst, increased volume and frequency of urination. The results of laboratory studies indicate that the incidence of grade 3 hyperglycemia with the use of dabrafenib is 6%.

It is recommended to use Tafinlar with caution and under close medical supervision in patients with glucose-6-phosphate dehydrogenase deficiency. This is associated with an increased risk of developing hemolytic anemia in this category of patients, accompanied by general weakness, fatigue, muscle cramps, and shortness of breath.

Influence on the ability to drive vehicles and complex mechanisms

During the period of treatment with Tafinlar, the patient's ability to drive vehicles and perform other work requiring a high speed of psychomotor reactions is determined individually, taking into account the general condition of the patient and the toxicity profile of the drug.

Application during pregnancy and lactation

The use of Tafinlar is contraindicated during the period of gestation and breastfeeding.

In the course of scientific studies of the effect of the drug on fetal development in animals, dabrafenib demonstrated embryotoxic and teratogenic efficacy. Upon reaching an exposure that exceeded 0.5 times that during the use in humans of the maximum recommended dose of 150 mg 2 times / day, at birth, the offspring showed a lag in skeletal development and a decrease in body weight. In the case of an exposure exceeding that when using the maximum recommended dose in humans three times, in addition, the fetus was observed to have defects in the interventricular septum, variations in the shape of the thymus gland and embryoletality. The doctor must necessarily inform the pregnant patient about the possible risk to the development of the fetus.

There is no reliable data on the effect of dabrafenib on breastfed babies, as well as on milk production during lactation. The risk of a negative effect of Tafinlar on children receiving breast milk cannot be ruled out. In this connection, it is necessary to warn nursing women about the potential risks to the child. When prescribing the drug during lactation, the benefits of breastfeeding for the child and the importance of therapy for the mother should be carefully evaluated. If the latter prevails, breastfeeding is stopped.

Patients of reproductive age are advised to use reliable barrier methods of contraception during the entire period of treatment and for at least 4 months after its termination. The use of hormonal contraception at the same time as dabrafenib is ineffective.

Pediatric use

It is contraindicated to prescribe Tafinlar capsules for the treatment of children and adolescents due to the lack of data on the safety and efficacy of the drug under the age of 18 years.

With impaired renal function

Tafinlar should be used with caution in severe renal impairment.

No dose adjustment is required for mild to moderate renal impairment.

Special care should be taken when treating patients with severe renal impairment.

For violations of liver function

Tafinlar should be used with caution in case of moderate and severe liver dysfunction.

In case of mild liver dysfunction, dose adjustment is not required.

Take capsules with extreme caution in case of moderate to severe liver dysfunction.

Use in the elderly

Dabrafenib dose adjustment is not required for patients over the age of 65.

Drug interactions

With the simultaneous use of Tafinlar:

ketoconazole, gemfibrozil, ritonavir, saquinavir, nefazodone, clarithromycin, telithromycin, itraconazole, atazanavir, voriconazole, posaconazole and other drugs that are strong inhibitors of the CYP2C8 and CYP3A4 enzymes: these drugs can cause an increase in concentration;
rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort preparations (inducers of CYP2C8 or CYP3A4 isoenzymes): combined use leads to a decrease in the level of dabrafenib in the blood;
OATP1B1 and OATP1B3 substrates, including rosuvastatin: a possible increase in C _max and AUC of OATP1B1 and OATP1B3 substrates with a narrow therapeutic index should be taken into account;
rabeprazole and other drugs that increase the acidity of gastric juice: do not cause clinically significant disturbances in the pharmacokinetics of dabrafenib;
drugs sensitive to the induction of CYP3A4 or CYP2C9 isoenzymes (including warfarin, dexamethasone, hormonal contraceptives): their concentration may decrease and clinical efficacy is lost, therefore, caution should be exercised if concomitant therapy with such drugs is required or alternative treatment should be prescribed

In addition, the interaction of dabrafenib and its metabolites with the following drugs is expected, but its intensity may have significant differences: fentanyl, methadone and other analgesics; clarithromycin, doxycycline, and other antibiotics; antineoplastic agents including cabazitaxel; anticoagulants, including acenocoumarol, warfarin; antiepileptic drugs, including carbamazepine, valproic acid, phenytoin, primidone; antipsychotics such as haloperidol; calcium channel blockers such as diltiazem, nicardipine, nifedipine, felodipine, verapamil; dexamethasone, methylprednisolone, and other corticosteroids; cardiac glycosides such as digoxin; antiviral agents for the treatment of HIV (human immunodeficiency virus) infection, including amprenavir, atazanavir, delavirdine, efavirenz, darunavir, fosamprenavir,indinavir, saquinavir, tipranavir, lopinavir, nelfinavir; diazepam, zolpidem, midazolam and other hypnotics; atorvastatin, simvastatin and other statins metabolized by CYP3A4; immunosuppressants including tacrolimus, sirolimus, cyclosporine.

When combined therapy with Tafinlar and trametinib, it is also necessary to take into account the interaction of trametinib with other drugs used simultaneously.

Analogs

The analogue of Tafinlar is Ervoy, Mekinist, Zelboraf, Keytruda, Opdivo, Rafinlar, etc.

Terms and conditions of storage

Keep out of the reach of children.

Store at temperatures up to 30 ° C.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Tafinlar

Tafinlar, according to experts, is a promising drug for targeted (targeted) therapy in an adjuvant environment for melanoma caused by a mutation in the BRAF ^V600 gene. Since this type of mutation occurs in about half of melanoma patients, improving progression-free survival and overall survival with drug therapy is very important.

Since 2016, Tafinlar, together with Mekinist, have been included in the treatment protocol for stage III and IV melanoma.

Combined targeted adjuvant therapy with dabrafenib and trametinib doubles relapse-free survival, according to the COMBI-AD study presented in Madrid at ESMO 2017 and published in the most widely read, cited and influential periodical in general medicine, the New England Journal of Medicine. in patients with stage III BRAF mutant melanoma.

Patients and their relatives also note that the use of Tafinlar provides a positive trend in the reduction and destruction of metastases.

Price for Tafinlar in pharmacies

The price of Tafinlar for a package containing 120 capsules, at a dosage of 50 mg, can range from 251 thousand rubles, in a dosage of 75 mg - from 268 thousand rubles.

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!