Indications for use of the drug Emend:
Prevention of acute and delayed nausea and vomiting due to highly or moderately emetogenic-antitumor drugs (in combination with others. Antiemetics).
The active substance group:
Aprepitant (Aprepitant), antiemetic - neurokinin receptor blocker
Dosage Form:
capsules, capsules set
Contraindications:
Hypersensitivity, simultaneous reception with pimozide, terfenadine, astemizole, and cisapride; severe hepatic insufficiency (more than 9 points on the scale of Child-Pyuga), pregnancy, lactation, children's age (safety and efficacy not established).
Dosage and administration:
Inside, regardless of food intake, for 3 days in combination with corticosteroids and antagonists of 5-HT3 receptors. The recommended dose - 125 mg for 1 h before receiving chemotherapy drugs in 1 day and 80 mg day 1 morning isolator in the 2nd and 3rd days. No dose adjustment based on gender and race, in elderly patients with hepatic insufficiency of mild to moderate severity, with renal failure (including severe with CC less than 30 ml / min and in patients in end-stage renal failure hemodialysis) is not required.
Pharmacological action:
Selective high-affinity receptor antagonist of neurokinin-1 (NK), substance P; selective binding to NK-3 receptors is about thousand. times higher than for others. enzymes, ion channels and transporter sites of receptors including dopamine and serotonin receptors. Prevents the development of emesis induced by chemotherapeutic drugs (including, cisplatin) by a central mechanism of action: penetrates into the brain and associated with brain NK receptors, inhibit both acute and the delayed phases of cisplatin-induced emesis, and reinforces wherein the antiemetic effect of ondansetron and dexamethasone.
Side effects:
The most common side effects in highly emetogenic chemotherapy: hiccups (4.6%), weakness / fatigue (2.9%), increased ALT (2.8%), constipation (2.2%), headache (2.2%), anorexia (2.0%); with moderately emetogenic chemotherapy - fatigue (2.5%). Most (more than 1/100 and less than 1/10), rare (more than 7/7000 and less than 1/100). From the side of hematopoiesis: rarely - anemia, febrile neutropenia. From the nervous system: often - headache, dizziness; rarely - a violation of dreams, cognitive impairment, disorientation, euphoria, anxiety. From the sensory organs: rarely - conjunctivitis, tinnitus. From the CCC: rarely - bradycardia. The respiratory system: rarely - sore throat, sneezing, cough, postnasal syndrome, irritation of the throat. From the digestive system: often - anorexia, hiccups, constipation, diarrhea, indigestion, belching; rarely - nausea, acid reflux, dysgeusia, epigastric discomfort, obstipation, gastroesophageal reflux disease, perforated ulcer 12 duodenal ulcer, abdominal pain, dry mucous membranes of the mouth, enterocolitis, flatulence, stomatitis. For the skin: rarely - rash, acne, increased photosensitivity, increased sweating and sebum production, itching. From the musculoskeletal system: rarely - muscle cramps, myalgia. From the urinary system: rarely - polyuria, dysuria, pollakiuria. Laboratory tests: often - increased activity of ALT and ACT; rarely - increased activity of alkaline phosphatase, hyperglycemia, hyponatremia, microhematuria. Other: often - weakness / fatigue; rarely - swelling, hot flashes (<tides>), chest discomfort, lethargy, thirst, decreased or increased body weight, joining a staph or fungal (Candida) infections. In rare cases - Stevens-Johnson syndrome (chemotherapy), angioedema, and urticaria (monotherapy aprepitant).
Special instructions:
During treatment and for 1 month after the last dose of aprepitant should use alternative methods of contraception. Well-controlled studies in pregnant women has not been; during pregnancy is not recommended. Data on the allocation of aprepitant passes into breast milk in lactating women do not. During the period of lactation should decide to discontinue nursing or the drug discontinuation due to the potential adverse effect of the drug on infants.
Connectivity:
Co-administration with warfarin may result in a clinically significant reduction in the international normalized ratio (MHO). There was no effect of aprepitant on the AUC R (+) - or S (-) - warfarin, however, a joint application was observed reduction in the minimum concentration of S (-) - warfarin, which was accompanied by a decrease in MHO 14% in 5 days after receiving the aprepitant. In patients receiving long-term warfarin therapy should be carefully monitored MHO for 2 weeks during each cycle of chemotherapy, especially after 7-10 days after receiving the aprepitant 3-day scheme. Efficacy of oral hormonal contraceptives may be reduced during the reception and for 28 days after dosing. Aprepitant is a substrate, a moderate inhibitor and inducer of CYP3A4, CYP2C9 and inducer: can increase the concentration in plasma drug metabolism that occurs under the action of CYP3A4. Should not be used concurrently with pimozide, terfenadine, astemizole, and cisapride because Inhibition of CYP3A4 aprepitant increases the concentration of these drugs in the plasma and potentially serious and life-threatening side effects. Induces the metabolism of warfarin and tolbutamide. Simultaneous with the appointment of these or others. Drugs metabolized by CYP2C9 (including phenytoin), reducing their concentration in plasma. Decreases AUC tolbutamide (substrate CYP2C9), 23% at day 4, 28% in 8 days and 15% at day 15 (tolbutamide in a single dose of 500 mg taken before the 3-day regimen aprepitant on the 4th, 8th and 15th day). Interactions with drugs that are substrates of P-glycoprotein transporter, it is unlikely (no interaction with digoxin). Do not have a clinically meaningful effect on the pharmacokinetics receptor antagonists 5NTZ (ondansetron, granisetron and gidrodolasetrona - the active metabolite of dolasetron). Increases AUC of dexamethasone (inside) 2.2 times, metidprednizolona (w / w) - 1.3 times, and methylprednisolone (inside) - 2.5 times. In this regard, to achieve the desired effect of a standard dose of oral dexamethasone used in combination with aprepitant reduced by 50%, methylprednisolone at / in - 25%, when orally - 50% respectively. In an application with chemotherapeutic drugs metabolized primarily or in part, it is mediated by CYP3A4 (etoposide, vinorelbine, docetaxel and paclitaxel), dose adjustment of these drugs is not required, but recommended caution in patients receiving these drugs, and additional monitoring. Simultaneous oral midazolam observed increase in AUC of midazolam. Possible increase in plasma concentrations of midazolam or other. Benzodiazepines metabolized carried out with the participation of CYP3A4 (alprazolam, triazolam) should be taken into account while appointing these drugs. Simultaneous treatment with drugs that inhibit CYP3A4 activity, may lead to an increase in the plasma concentration of aprepitant; must be used with caution aprepitant in combination with potent inhibitors of CYP3A4 (including ketoconazole). Simultaneous treatment with moderate inhibitors of CYP3A4 (including with diltiazem) does not cause clinically significant changes in plasma concentrations of aprepitant. Simultaneous treatment with drugs that are potent inducers of CYP3A4 (including rifampicin) may reduce plasma concentrations of aprepitant in and thus reduce the effectiveness of aprepitant. Patients with mild to moderate hypertension receiving aprepitant in a dose of 230 mg in combination with diltiazem in a dose of 120 mg three times a day for 5 days increases AUC aprepitant 2 times and diltiazem 1.7 times that did not result in heart rate or arterial blood pressure compared with the changes in these indicators only when taking diltiazem. Simultaneous reception aprepitant 1 times a day in a dose of 85 mg or 170 mg of paroxetine at 20 mg per day resulted in a reduction in the AUC by 25% and 20% Cmax for aprepitant and paroxetine.
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