Prevention of early and delayed nausea and vomiting associated with anti-cancer chemotherapy in adults, using Cisplatin, a high-risk vomiting drug. Prevention of nausea and vomiting associated with anti-cancer chemotherapy with moderate risk of vomiting in adults. The 125 mg / 80 mg preparation is used in combination therapy.
Composition:
The package contains 3 capsules: 2 capsules contain 80 mg of aprepitant, 1 capsule contains 125 mg of aprepitant. The capsules contain sucrose.
Action:
An anti-emetic and anti-nausea medicine. Aprepitant is a selective high affinity antagonist that acts on the human neurokinin P-receptors. Bioavailability is 59-67%. Cmax occurs after about 4 hours. It binds to proteins on average in 97%. The drug is extensively metabolised, mainly mediated by CYP4A4, to a lesser extent involving CYP1A2 and CYP2C19. Metabolism occurs through the oxidation of the morpholine ring and its side chains, and the metabolites that are formed have a weak pharmacological effect. Metabolites are excreted in urine and faeces. T0,5 in the final phase is 9-13 hours.
Contraindications:
Hypersensitivity to the active substance or to any of the excipients. Co-administration with pimozide, terfenadine, astemizole or cisapride.
Precautions:
There are limited data on use in patients with moderate hepatic impairment and no data available in patients with severe hepatic impairment. Caution should be exercised when using the drug in these patients. The drug should be used with caution in patients receiving concomitant oral active substances mainly metabolised by CYP3A4 and active substances with a narrow therapeutic range, such as: cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, ergotamine, fentanyl and quinidine. Special care should be taken when using the product in combination with irinotecan. Caution should be exercised when using the preparation with derivatives of ergot alkaloids. Co-administration with strong CYP3A4 activators (eg rifampicin, phenytoin, carbamazepine, phenobarbital) should be avoided. Co-administration of herbal products containing St John's wort is not recommended. Caution should be exercised when co-administered with CYP3A4 inhibitors (eg ketoconazole, Itraconazole, voriconazole, posaconazole, Clarithromycin, telithromycin, nefazodone and protease inhibitors). In patients taking long-term Warfarin, the INR should be closely monitored during treatment with the product and for 14 days after each 3-day treatment. The safety and efficacy of the preparation has not yet been established in children and adolescents under 18 years of age. The product contains sucrose - should not be used in patients with rare inherited disorders associated with fructose intolerance, malabsorption of Glucose and galactose or sucrase-isomaltase deficiency.
Pregnancy and lactation:
There are no data available on the use of aprepitant during pregnancy. The preparation should not be used during pregnancy unless clearly necessary. During and 28 days after administration, the effectiveness of hormonal contraceptives may be reduced. During treatment with the preparation and for 2 months after the last dose, alternative non-hormonal additional methods of contraception should be used. Breastfeeding during the use period is not recommended.
Side effects:
Common: reduced appetite, headache, hiccups, constipation, indigestion, tiredness, increased ALT. Uncommon: febrile neutropenia, anemia, dizziness, drowsiness, palpitations, hot flushes, acid reflux, nausea, vomiting, gastro-oesophageal reflux, abdominal pain, dry mouth, bloating, rash, acne, difficulty urinating , asthenia, malaise, increased AST, increased alkaline phosphatase.Rarely: yeast infection, staph infections, excessive thirst, confusion, euphoria, cognitive impairment, lethargy, taste disorders, conjunctivitis, tinnitus, bradycardia, cardiovascular disorders, mouth and throat pain, sneezing, coughing, discharge of secretions on the back of the throat, throat irritation, perforating duodenal ulcer, stomatitis, abdominal distension, hard stools, neutropenic colitis, photosensitivity, hyperhidrosis, seborrhea, skin changes, itchy rash, Stevens-Johnson syndrome / toxic necrosis -difficultaneous epidermis, muscle weakness, muscle spasms, pollakiuria, edema, chest discomfort, gait disturbance, presence of red blood cells in the urine, decrease in blood sodium concentration, weight loss, decreased neutrophil count, urine Glucose, increased excretion urine. Not known: hypersensitivity reactions (including anaphylactic reactions), pruritus, urticaria. In patients treated with aprepitant during nausea and vomiting after surgical procedures (PONV), additional side effects were observed with a greater frequency than ondansetron: epigastric pain, abnormal bowel sounds, constipation, speech impairment, dyspnoea, hypoaesthesia, insomnia, miosis, nausea, disturbances in the senses, discomfort in the stomach, permeable obstruction, reduced visual acuity, wheezing.
Dosage:
Orally. Adults. The preparation should be taken for 3 days in combination with a corticosteroid and a 5-HT receptor antagonist3. The recommended dose is 125 mg once a day for 1 hour before the first day of chemotherapy and the dose of 80 mg once a day on the 2nd and 3rd day. No dose adjustment is necessary in the elderly, in patients with renal impairment or in hemodialysis of ESRD patients, and in patients with mild hepatic impairment. There are limited data in patients with moderate hepatic impairment and no data in patients with severe hepatic impairment. Caution should be used in these patients when using aprepitant. Kaps. should be swallowed whole, taken regardless of meals.
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