Dabrafenib (Dabrafenibum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Antineoplastic agents - inhibitors of protein kinases

Included in the formulation
  • Tafinlar
    capsules inwards 
    GlaxoSmithKline Trading, ZAO     Russia
    • АТХ:

    L.01.X.E.23   Dabrafenib

    Pharmacodynamics:

    The drug is a selective inhibitor RAF-Kinase, also inhibits isoenzymes CRAF and BRAF wild type. Due to these properties, the drug inhibits the growth of melanoma cells that carry a gene mutation BRAF V600.

    Pharmacokinetics:

    Are taken orally, the absorption is complete. The maximum concentration in blood plasma is achieved on average after 2 hours. The average bioavailability is 95%. If the drug is taken with food, the bioavailability is reduced to 50-30%. The drug binds well to blood plasma proteins, is metabolized in several stages: first forms hydroxydabrafenib, then carboxydabrafenib, which is excreted with bile and urine, or metabolized to desmethydabrafenib. The elimination half-life is 10 hours. Through the gastrointestinal tract 7% are eliminated, through the kidneys - 23%.

    Indications:

    Unresectable or metastatic melanoma with a gene mutation BRAF V600.

    ICD-10

    II.C43-C44   Melanoma and other malignant neoplasms of the skin

    Contraindications:

    - Age to 18 years;

    - Pregnancy and lactation.

    Carefully:

    Chronic liver and / or kidney disease.

    Pregnancy and lactation:

    Category FDA - D. Adequate and well-controlled studies on humans have not been conducted.

    Dosing and Administration:

    Reception of the drug inwards. The recommended adult dose is 150 mg 2 times a day on an empty stomach. Between receptions it is necessary to maintain a break of 12 hours. Reception of the drug is continued until the development of signs of toxicity or to the progression of the disease. In case of side effects, a break in taking dabrafenib is possible. If there is a dose skipping, and before taking the next dose remains less than 6 hours, then the missed dose is not taken.

    Side effects:

    From the nervous system: headache.

    From the immune system: hypersensitivity, bullous rash.

    From the side of the organ of vision: uveitis, iritis.

    From the respiratory system: nasopharyngitis, cough.

    From the gastrointestinal tract: pancreatitis, constipation, nausea, diarrhea, vomiting.

    From the skin: rash, actinic keratosis, dry skin, erythema, hyperkeratosis, alopecia.

    From the side of the urinary system: renal dysfunction, nephritis, acute renal failure.

    From the musculoskeletal system: pain in the back, pain in the extremities, myalgia, arthralgia.

    Other: increased activity of alkaline phosphatase, hyponatremia, flu-like syndrome, chills, asthenia, hyperthermia, decreased appetite, hypophosphatemia.

    Overdose:

    Clinical studies to study the conditions of drug overdose have not been conducted, there is no specific antidote. Treatment is symptomatic, taking the drug is temporarily canceled.

    Interaction:

    Drugs that are inhibitors or inducers CYP2C8 or CYP3C4, respectively, increase or decrease the concentration of dabrafenib.

    The combined use of dabrafenib and warfarin, sensitive to the induction of these enzymes, can lead to a decrease in the concentration of warfarin and the loss of its effectiveness. If the use of warfarin is necessary, it should be monitored for its effectiveness.

    Dabrafenib strengthens CYP3A4-mediated metabolism. The combined use of dabrafenib and dexamethasone, which is sensitive to the induction of these enzymes, can lead to a decrease in the concentration of dexamethasone and loss of its effectiveness. If dexamethasone is needed, its effectiveness should be monitored.

    Joint use of ketoconazole - a strong inhibitor CYP3A4 - increases the bioavailability of dabrafenib. If simultaneous use of dabrafenib and ketoconazole can not be avoided, care must be taken and careful monitoring of patients to identify side reactions of dabrafenib.

    Ritonavir and clarithromycin, which are strong inhibitors CYP3A4, can increase the concentration of dabrafenib. Care should be taken when using dabrafenib in conjunction with ritonavir and clarithromycin.

    Rifampicin, carbamazepine, phenobarbital and phenytoin, which are strong inducers CYP3A4, can reduce the concentration of dabrafenib.

    Drugs that change pH in the gastrointestinal tract, can affect the absorption of the drug.

    Special instructions:

    Does not affect the ability to drive vehicles and mechanisms. The drug can develop hyperglycemia, so the doctor in charge should monitor the blood glucose level during treatment. It is also necessary to monitor the condition of patients who are being treated with this drug in advance to detect signs of developing hemolytic anemia. And also the general control of a condition of the patient is necessary,since the drug has many severe systemic side effects.

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