Emend capsules 125mg №1 + 80mg №2

Indications

- to prevent acute and delayed nausea and vomiting caused by high or moderately methogenic anticancer drugs (in combination with other antiemetic drugs).

Dosage and administration

The drug is taken orally, regardless of the meal.

Emend^® prescribed for 3 days in combination with corticosteroids and serotonin antagonists 5-HT₃-receptors.

Before starting treatment, you should read the instructions for use of the antagonist of serotonin 5-HT₃ receptors administered simultaneously with the drug Emend ^®. The recommended dose of the drug Emend^® with a three-day regimen, it is 125 mg 1 hour before taking chemotherapeutic drugs on the 1st day and 80 mg 1 time / day in the morning on the 2nd and 3rd days.

The tables show the regimen of medication, depending on the degree of emetogenicity of antitumor therapy.

High Effective Chemotherapy

Mild chemotherapy

Have patients with mild or moderate liver failure (from 5 to 9 points on the Child-Pugh scale) dose adjustment is not required. Clinical data on the use of the drug in patients with severe liver failure (> 9 points on the Child-Pugh scale) are missing.

Have patients with severe renal failure (CC <30 ml / min), and also in patients in end-stage renal disease on hemodialysis, dose adjustment is not required.

Dose adjustment depending on gender, age, race or body mass index not required.

Side effect

The safety of aprepitant was evaluated in approximately 6500 patients.

Prevention of nausea and vomiting caused by chemotherapy

High Effective Therapy

The clinical study involved 544 patients who received highly emethogenic therapy and aprepitant in the first cycle. 413 patients from this group continued therapy (the maximum number of chemotherapy courses was 6). Three-day regimen of drug Emend^® in combination with ondansetron and Dexamethasone, it was well tolerated by patients. Most of the adverse reactions reported in clinical studies were identified as mild to moderate.

Most frequent adverse reactions with highly edematous chemotherapy in patients who received aprepitant in combination with serotonin antagonists 5-HT₃-receptors and dexamethasone (observed with greater frequency than during therapy with serotonin antagonists 5-HT₃-receptors and dexamethasone): hiccups (4.6%), increased ALT activity (2.8%), dyspepsia (2.6%), constipation (2.4%), headache (2%) and decreased appetite (2%).

In an additional clinical study in 1169 patients who received various types of high-efficacy chemotherapy and regimens for the prevention of nausea and vomiting with the use of aprepitant and serotonin antagonists 5-HT₃receptors and dexamethasone or serotonin 5-HT antagonists only₃receptor and dexamethasone, the profile of adverse reactions was the same.

Moderately emetic therapy

In a clinical trial involving 868 patients, the most frequent adverse reaction against moderate emethogenic chemotherapy in patients who received aprepitant in combination with 5-HT antagonists₃receptors and dexamethasone (was observed with greater frequency than during therapy with 5-HT antagonists₃ receptor and dexamethasone), was fatigue (1.4%).

In the combined analysis of high-emittogenic and moderately emittogenic chemotherapy in patients treated with aprepitant, the following side effects were observed with administration of the drug, and more often than with standard therapy: often (from ≥1 / 100 to <1/10), infrequently (from ≥1 / 1000 to <1/100), rarely (from ≥1 / 10 000 to <1/1000).

Infection: rarely - candidiasis, a staph infection.

Hemic and lymphatic: infrequently - anemia, febrile neutropenia.

Metabolism and nutrition: often - loss of appetite; rarely polydipsia.

Psychological: infrequently - anxiety; rarely - disorientation, euphoria.

Nervous system: infrequently - dizziness, drowsiness; rarely - cognitive impairment, lethargy, taste perversion.

Special senses: rarely - conjunctivitis, tinnitus.

Since the cardiovascular system: infrequently - rapid heartbeat, paroxysmal sensations of heat ("hot flashes"); rarely - bradycardia, cardiovascular disorders.

Respiratory: often - hiccups; rarely - sore throat, sneezing, cough, post-nasal syndrome, pharyngeal irritation.

Gastrointestinal: often - dyspepsia; rarely — belching, nausea, gastroesophageal reflux, vomiting, abdominal pain, dry mouth, flatulence; rarely - solid feces, perforated duodenal ulcer, neutropenic colitis, stomatitis, bloating.

On the part of the skin and subcutaneous fat: infrequently - rash, acne; rarely - photosensitization, excessive sweating, seborrhea, increased oily skin, itchy rash.

Musculoskeletal system: rarely, muscle spasms, muscle weakness.

Urogenital: infrequently - dysuria; rarely, pollakiuria.

Changes from laboratory indicators: often - increased activity of ALT; infrequently - increased AST activity, increased activity of alkaline phosphatase; rarely - an increase in diuresis, the presence of red blood cells in the urine, hyponatremia, weight loss, glycosuria, neutropenia.

Common disorders: often - fatigue; infrequently - asthenia, malaise; rarely - swelling, discomfort in the chest, gait disturbance.

The side effect profile of patients receiving highly emittogenic and moderate emethogenic chemotherapy during the repeated courses (the maximum number of courses was 6) using aprepitant was comparable to that during the 1st cycle of chemotherapy.

In another study of the use of aprepitant for the prevention of nausea and vomiting induced by chemotherapy, a message was received about serious side effects - Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Post-registration data

Due to the fact that reports were received from volunteers from groups of the population with an undetermined number, it is impossible to reliably determine the expected frequency or causal relationship with taking the drug.

From the skin and skin appendages: itching, rash, urticaria, rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

On the part of the immune system: hypersensitivity reactions, including Anaphylactic reactions .

Contraindications

- severe liver failure (> 9 points on the Child-Pugh scale);

- simultaneous use with pimozide, terfenadine, astemizole and cisapride;

- hypersensitivity to the drug.

C caution should use Emend^® in patients simultaneously receiving drugs that are metabolized mainly with the participation of the isoenzyme CYP3A4 . The simultaneous appointment of the drug Emend^® with Warfarin can lead to a clinically significant reduction in INR. In patients receiving long-term warfarin therapy, the INR value should be carefully monitored for 2 weeks with each cycle of chemotherapy, and especially 7-10 days after starting Emend^® on a 3-day schedule. The effectiveness of hormonal contraceptives may decrease during and within 28 days after treatment with drug Emend^®. During treatment with drug Emend^® and within 1 month after taking the last dose of Emend^® alternative and backup methods of contraception should be used.

Use during pregnancy and lactation

Adequate and strictly controlled clinical studies of the safety of the drug during pregnancy was not conducted, therefore, the use of the drug Emend^® during pregnancy is not recommended.

It is not known whether aprepitant is excreted in human breast milk. If necessary, the use of the drug during lactation should decide on the termination of breastfeeding due to the risk of undesirable effects on the infant.

Application for violations of the liver

Have patients with mild or moderate liver failure (from 5 to 9 points on the Child-Pugh scale) dose adjustment is not required. Clinical data on the use of the drug in patients with severe liver failure (> 9 points on the Child-Pugh scale) are missing.

Application for violations of kidney function

Have patients with severe renal failure (CC less than 30 ml / min), and also in patients in end-stage renal disease on hemodialysis, dose adjustment is not required.

Use in children

Safety and efficacy of the drug Emend^® in children are not installed.

Use in elderly patients

Elderly patients (65 years and older) dose adjustment is not required.

special instructions

Inhibition of CYP3A4 with an aprepitant can lead to an increase in plasma concentrations of drugs that are metabolized mainly with the participation of the CYP3A4 isoenzyme (including some chemotherapeutic drugs).

Use in pediatrics

Safety and efficacy of the drug Emend^® in children are not installed.

Influence on ability to drive motor transport and control mechanisms

Studies on the effect of the drug Emend^® the ability to drive vehicles or work with mechanisms was not carried out. However, the side effects profile of the drug, which may affect the ability of patients to control the mechanisms, should be considered. Patients may have different reactions to Emend^®.

Overdose

Symptoms: available data on the use of aprepitant in high doses without chemotherapy (once up to 600 mg or 375 mg daily for 42 days) indicate good tolerability of the drug. In 1 patient, who took 1440 mg of aprepitant, drowsiness and headache were observed.

Treatment: drug therapy Emend^® discontinue and monitor the patient’s condition. If necessary, conduct symptomatic therapy. Due to the anti-emetic effect of aprepitant, drugs that induce vomiting are not likely to be effective. Antidote to the drug is unknown. Hemodialysis is not effective.

Drug interaction

Aprepitant is a substrate, a moderate inhibitor and inducer of the isoenzyme CYP3A4, as well as an inducer of the isoenzyme CYP2C9.

With the simultaneous appointment of aprepitant may increase the plasma concentration of drugs, the metabolism of which occurs with the participation of the isoenzyme CYP3A4. Emend^® should not be used simultaneously with pimozide, terfenadine, astemizole, cisapride, ergot alkaloid derivatives. Inhibition of CYP3A4 isoenzyme under the influence of aprepitant can lead to increased plasma concentrations of these drugs and to potentially serious and life-threatening reactions.

Aprepitant induces the metabolism of warfarin and tolbutamide. The simultaneous appointment of the drug Emend^® with these or other drugs that are metabolized with the participation of the CYP2C9 isoenzyme (for example, phenytoin), can lead to a decrease in their concentration in plasma. No effect of Emend drug is noted.^® on AUC R (+) - or S (-) - warfarin, however, when used together, a decrease in the minimum concentration of S (-) - warfarin was observed, which was accompanied by a decrease in INR by 14% 5 days after the end of taking Emend^®.

In patients receiving warfarin therapy for a long time, the level of INR should be carefully monitored for 2 weeks, and especially for 7-10 days after starting the drug Emend^® on a 3-day schedule, during each cycle of chemotherapy.

Emend^® reduces the AUC of tolbutamide, a substrate of CYP2C9 isoenzyme, by 23% on the 4th day, by 28% on the 8th day, and by 15% on the 15th day. In this case, tolbutamide in a single dose of 500 mg was prescribed before starting a 3-day regimen with drug Emend^® in the 4th, 8th and 15th days.

Drug interaction Emend^® with drugs that are substrates of the P-glycoprotein transporter, it is unlikely (lack of interaction of the drug Emend^® with digoxin). Aprepitant does not cause clinically significant changes in the pharmacokinetics of serotonin 5HT antagonists₃-receptors — ondansetron, granisetron, and hydrodolasetron (the active metabolite of dolasetron).

While taking the drug Emend^® and GKS marked increase in AUC of dexamethasone (by ingestion) by 2.2 times, methylprednisolone, introduced in / in - by 1.3 times and methylprednisolone ingested - by 2.5 times. In this regard, to achieve the desired effect, the standard dose of dexamethasone when taken orally in combination with aprepitant is reduced by 50%, methylprednisolone is reduced by approximately 25% when administered IV, and 50% when administered orally.

When using the drug Emend^® Together with chemotherapeutic drugs, the metabolism of which mainly or partially occurs with the participation of the CYP3A4 isoenzyme (etoposide, vinorelbine, docetaxel and paclitaxel), the doses of these drugs can not be adjusted.However, caution is advised when applying to patients receiving these drugs and to provide additional monitoring. In post-registration studies, there have been cases of neurotoxicity, which can be considered as a possible side effect of ifosfamide, used in conjunction with aprepitant.

Effect of drug Emend^® on the pharmacokinetics of docetaxel not detected.

The effectiveness of hormonal contraceptives in the period of admission and within 28 days after taking the drug Emend^® may be reduced (during treatment with drug Emend^® and within 1 month after taking the last dose of the drug Emend^® alternative or backup methods of contraception should be used).

With simultaneous oral administration of midazolam and drug Emend^® marked increase in midazolam AUC. A possible increase in plasma concentration of midazolam or other benzodiazepines, the metabolism of which is carried out with the participation of the CYP3A4 isoenzyme (alprazolam, triazolam), should be taken into account when co-administering these drugs with Emend^®.

Simultaneous administration of the drug Emend^® with drugs that inhibit the activity of CYP3A4 isoenzyme, can lead to an increase in the concentration of aprepitant in the blood plasma. Therefore, it is necessary to assign Emend with care.^® in combination with strong inhibitors of the CYP3A4 isoenzyme (for example, with ketoconazole). However, the simultaneous administration of the drug Emend^® with moderate inhibitors of the CYP3A4 isoenzyme (for example, with diltiazem, itraconazole, voriconazole, posaconazole, Clarithromycin, telithromycin and protease inhibitors) does not cause clinically significant changes in the concentration of aprepitant in the blood plasma.

Simultaneous administration of the drug Emend^® with drugs that are strong inducers of CYP3A4 isoenzyme (for example, with rifampicin, phenytoin, Carbamazepine, phenobarbital), can lead to a decrease in the concentration of aprepitant in the plasma and, thus, to a decrease in the effectiveness of the drug Emend^®. Also, the simultaneous use of aprepitant with preparations of Hypericum perforatum is not recommended.

In patients with mild and moderate arterial hypertension, taking an aprepitant tablet containing a dose comparable to 230 mg of the drug in capsules in combination with diltiazem at a dose of 120 mg 3 times / day for 5 days resulted in a 2-fold increase in AUC aprepitant and AUC diltiazem 1.7 times. These pharmacokinetic effects did not lead to clinically significant changes on the ECG, heart rate or blood pressure compared with changes in these indicators when taking only diltiazem.

The simultaneous administration of aprepitant 1 time / day in the form of tablets in a dose comparable to 85 mg or 170 mg of the drug in capsules, and paroxetine in a dose of 20 mg 1 time / day resulted in a decrease in AUC by approximately 25% and C_max approximately 20% for both aprepitant and paroxetine.

Terms and conditions of storage

The drug should be stored out of the reach of children at a temperature not higher than 30 ° C.