Emend
Emend: 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: Emend
ATX code: A04AD12
Active ingredient: aprepitant (Aprepitant)
Manufacturer: Merck Sharp & Dome, Bldg. (Merck Sharp & Dohme, Corp.) (USA); Alkermes Pharma Ireland, Ltd. (Alkermes Pharma Ireland, Ltd.) (Ireland)
Description and photo update: 2019-09-07
Prices in pharmacies: from 3900 rubles.
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Emend is an antiemetic drug.
Release form and composition
Emend is available in capsule form:
- dosage 80 mg: hard gelatinous, with an opaque body and white cap, with the words "461" and "80mg" in black ink;
- dosage 125 mg: hard gelatinous, with an opaque white body and an opaque pink lid, with the words "462" and "125mg" in black ink.
The contents of the capsules of both dosages are almost white or white granules.
In a cardboard box put 1 blister with 2 capsules of 80 mg and 1 blister with 1 capsule of 125 mg, packed in a cardboard cover, and instructions for use of Emend.
Composition of 1 capsule:
- active substance: aprepitant - 80 or 125 mg;
- auxiliary components: sodium lauryl sulfate, sodium lauryl sulfate micronized, microcrystalline cellulose (in granules), sucrose, hydroxypropyl cellulose;
- capsule shell: 80 mg capsules - gelatin, titanium dioxide, black ink SW-9008/9009 (used for inscription); 125 mg capsules - gelatin, titanium dioxide, iron oxide red, iron oxide yellow, black ink SW-9008/9009 (used for inscription).
Pharmacological properties
Pharmacodynamics
The active ingredient of Emend capsules - aprepitant - is a selective high-affinity antagonist of neurokinin-1 (NK 1) receptors of substance P. The selectivity of drug binding to NK 1 receptors is at least 3000 times higher than with other enzymes, carriers of ion channels and receptor sites (in t including dopamine and serotonin), which are the targets of currently existing drugs for the treatment of nausea and vomiting during chemotherapy (for example, cisplatin).
In preclinical studies, NK 1 receptor antagonists inhibit the development of chemotherapy-induced vomiting through a central mechanism of action.
Aprepitant binds to NK 1 receptors in the brain, penetrating into the brain.
Thanks to the central mechanism of action, Emend suppresses both acute and delayed vomiting. It also enhances the antiemetic effect of ondansetron and dexamethasone.
Pharmacokinetics
Main pharmacokinetic parameters of aprepitant:
- absorption: the maximum plasma concentration (C max) is observed approximately 4 hours after administration. The average absolute bioavailability is 60–65%. Simultaneous food intake has no significant effect on the bioavailability of the drug. Pharmacokinetics is non-linear over the clinical dose range. After taking Emend on the 1st day at a dose of 125 mg, on the 2nd and 3rd days, 80 mg AUC (area under the concentration-time curve) for 24 hours was approximately 19.5 μg × h / ml on the 1st day and 20.1 μg × h / ml on the 3rd day. C max on the 1st day was 1.5 μg / ml, on the 3rd - 1.4 μg / ml;
- distribution: more than 95% of the taken dose of the drug binds to plasma proteins. The geometric mean of the volume of distribution (V d) in equilibrium is about 66 liters. In experimental studies on animals, it was found that aprepitant penetrates the blood-brain barrier (BBB) in ferrets and rats, and through the placental barrier in rats. In humans, the drug penetrates the BBB;
- metabolism: aprepitant is extensively metabolized in the liver by oxidation in the morpholine ring and its side chains, mainly with the participation of CYP3A4. Only a small amount of the drug is metabolized by CYP1A2 and CYP2C19 (CYP2E1, CYP2C9 and CYP2D6 are not involved in aprepitant metabolism);
- excretion: aprepitant is excreted mainly in the form of metabolites (86% - through the intestines, 5% - by the kidneys). Its apparent plasma clearance is approximately 60–84 ml / min. The final half-life (T 1/2) is approximately 9-13 hours.
Pharmacokinetics in special clinical situations:
- race: no changes in pharmacokinetic parameters were detected;
- gender: in women after a single dose of Emend, C max and AUC of aprepitant were higher by 17% and 9%, respectively, than in men. T 1/2 is about 25% lower than that of men. The time to reach C max did not change significantly. These changes have no clinical significance, therefore, dose adjustment depending on gender is not required;
- body mass index: in patients with different body weights, the characteristics of Emenda do not change, so there is no need to adjust the dose;
- children's age: in children and adolescents under 18 years of age, the pharmacokinetics of the drug has not been studied;
- elderly age: after taking Emend on the 1st day at a dose of 125 mg, on the 2nd and 5th days at 80 mg in patients aged ≥ 65 years, compared with patients <65 years old, the AUC for 24 hours was more by 21% on the 1st day, by 35% - on the 5th day. C max was 10% and 24% higher, respectively, on the 1st and 5th day. These differences were not of significant clinical significance, therefore, dose adjustment for elderly patients is not required;
- liver function: with mild and moderate disorders, there is a decrease in the AUC of aprepitant, but this does not require a dose adjustment of Emend. There is no experience of drug treatment in patients with severe hepatic impairment (> 9 points on the Child-Pugh scale);
- renal function: with impaired renal function from mild to severe, including end-stage renal failure in patients on hemodialysis, there is a decrease in AUC and C max of aprepitant, however, these changes do not require Emend dose adjustment. Carrying out hemodialysis 4 and 48 hours after taking the drug did not have a significant effect on the pharmacokinetics of aprepitant. Less than 0.2% of the drug dose was found in the dialysate.
Indications for use
Emend is prescribed to prevent nausea and vomiting (including delayed) in patients receiving moderate and highly emetogenic anticancer drugs (together with other antiemetic drugs).
Contraindications
- severe hepatic impairment (> 9 points on the Child-Pugh scale);
- treatment with pimozide, cisapride, astemizole, or terfenadine;
- children and adolescents under 18 years of age;
- the period of pregnancy and breastfeeding;
- hypersensitivity to any component of the drug.
Emend is used with caution in conjunction with drugs that are metabolized mainly by the CYP3A4 isoenzyme; with warfarin; with hormonal contraceptives.
Emend, instructions for use: method and dosage
Emend capsules should be taken orally. Meal timing doesn't matter.
Duration of application is 3 days. The drug is prescribed in combination with glucocorticosteroids (GCS) and antagonists of serotonin 5-HT 3 receptors.
Recommended drug regimen for highly emetogenic chemotherapy:
- 1st day: Emend - 125 mg 1 hour before the start of chemotherapy, dexamethasone - 12 mg orally 30 minutes before chemotherapy, antagonists of serotonin 5-HT 3 receptors (for example, ondansetron) - in accordance with their instructions for medical use;
- 2nd and 3rd day: Emend - 80 mg once a day (in the morning), dexamethasone - 8 mg once a day (in the morning);
- 4th day: dexamethasone - 8 mg once a day (in the morning).
Recommended drug regimen for moderately emetogenic chemotherapy:
- 1st day: Emend - 125 mg 1 hour before the start of chemotherapy, dexamethasone - 12 mg orally 30 minutes before chemotherapy, antagonists of serotonin 5-HT 3 receptors - in accordance with their instructions for medical use;
- 2nd and 3rd day: Emend - 80 mg once a day (in the morning).
Side effects
Highly emetogenic therapy
The main clinical study involved 544 patients who received highly emetogenic therapy and aprepitant in the first cycle. 413 patients continued their treatment (up to 6 courses of chemotherapy). The three-day combination therapy with Emend, dexamethasone and ondansetron was well tolerated. The reported side effects were generally mild to moderate. More often than with dexamethasone and antagonists of serotonin 5-HT 3 receptors, the following adverse reactions were noted: hiccups (4.6%), increased alanine aminotransferase activity (2.8%), dyspeptic disorders (2.6%), constipation (2.4%), decreased appetite (2%), headache (2%).
An additional clinical study involved 1169 patients who received different types of highly emetogenic chemotherapy and different regimens of nausea / vomiting therapy using aprepitant, dexamethasone and serotonin 5-HT 3 receptor antagonists or only dexamethasone and serotonin 5-HT 3 receptor antagonists. The profile of observed side effects was the same.
Moderately emetogenic therapy
In a clinical study, 868 patients were followed. Fatigue was observed more frequently than with dexamethasone and serotonin 5-HT 3 receptor antagonists (1.4%).
Pooled Analysis of High and Moderate Emetogenic Chemotherapy Studies
In patients receiving aprepitant, the following side effects were observed with a higher frequency than with standard therapy (classified as follows: often - from? 1/100 to <1/10, infrequently - from? 1/1000 to <1/100, rarely - from ≥ 1/10 000 to <1/1000):
- from the digestive system: often - dyspeptic disorders; infrequently - dry mouth, abdominal pain, belching, flatulence, nausea, vomiting, gastroesophageal reflux; rarely - stomatitis, bloating, hard feces, neutropenic colitis, perforated duodenal ulcer;
- on the part of hematopoietic organs: infrequently - febrile neutropenia, anemia;
- on the part of metabolic processes: often - loss of appetite; rarely, polydipsia;
- on the part of the heart and blood vessels: infrequently - paroxysmal fever, palpitations; rarely - bradycardia, cardiovascular disorders;
- from the nervous system and psyche: infrequently - drowsiness, dizziness, anxiety; rarely - taste perversion, lethargy, cognitive impairment, euphoria, disorientation;
- from the respiratory system: often - hiccups; rarely - throat irritation, sneezing, sore throat, cough, postnasal syndrome;
- from the urinary system: infrequently - dysuria; rarely - pollakiuria;
- on the part of the musculoskeletal system: rarely - muscle spasms, muscle weakness;
- from the senses: rarely - tinnitus, conjunctivitis;
- on the part of the skin and subcutaneous fat: infrequently - skin rashes, acne; rarely - an itchy rash, increased oily skin, increased sweating, photosensitivity, seborrhea;
- infections and invasions: rarely - candidiasis, staphylococcal infection;
- changes in laboratory parameters: often - an increase in the activity of alanine aminotransferase (ALT); infrequently - an increase in the activity of aspartate aminotransferase (AST) and alkaline phosphatase (ALP); rarely - a decrease in body weight, the presence of erythrocytes in the urine, an increase in urine output, glucosuria, hyponatremia, neutropenia;
- general disorders: often - fatigue; infrequently - malaise, asthenia; rarely - a violation of gait, a feeling of discomfort in the chest area, edema.
The profile of adverse reactions during repeated courses of highly and moderately emetogenic chemotherapy (up to 6 courses) using Emend was comparable to that during the first cycle of chemotherapy.
Post-registration data
- from the skin and subcutaneous fat: urticaria, rash, itching; rarely, Lyell's syndrome (toxic epidermal necrolysis), Stevens-Johnson syndrome;
- from the immune system: hypersensitivity reactions, including anaphylactic reactions.
The reported occurrence of the described phenomena came from volunteers from groups of the population with an undetermined number, therefore it is not possible to accurately establish the relationship of their development with the use of Emend.
Overdose
There is information about taking high doses of aprepitant (up to 600 mg once or for 42 days at 375 mg daily) without chemotherapy. The drug was well tolerated. One patient who took 1440 mg of aprepitant developed headache and drowsiness.
The antidote is unknown. Hemodialysis is not effective. Drugs that induce vomiting are likely to be ineffective due to the antiemetic effect of aprepitant. In case of an overdose, Emend is canceled and the patient is closely monitored. If necessary, symptomatic therapy is indicated.
special instructions
Aprepitant inhibits CYP3A4, which may lead to an increase in the plasma concentration of some drugs metabolized primarily by this isoenzyme, including some chemotherapeutic agents.
Influence on the ability to drive vehicles and complex mechanisms
The effect of Emend on reaction speed and ability to concentrate has not been studied. The degree of restrictions should be considered individually, depending on the presence and severity of side effects, for example, drowsiness and dizziness.
Application during pregnancy and lactation
The use of Emenda during pregnancy has not been studied in adequate and strictly controlled clinical trials, therefore the drug is not recommended for pregnant women.
It has not been established whether aprepitant penetrates into breast milk. If the appointment of antiemetic therapy is required during lactation, it is recommended to consider discontinuing breastfeeding.
Pediatric use
In children, the safety and effectiveness of Emend have not been established.
With impaired renal function
There is no need to adjust the dosage regimen of Emend for patients with severe renal failure (creatinine clearance <30 ml / min), as well as for patients on hemodialysis.
For violations of liver function
With mild and moderate hepatic impairment (5-9 points on the Child-Pugh scale), dose adjustment of Emend is not required.
There is no experience of using the drug in severe liver failure (> 9 points on the Child-Pugh scale).
Use in the elderly
It is not necessary to change the dosage regimen of Emend for elderly patients (over 65 years old).
Drug interactions
Aprepitant is an inducer of the CYP2C9 isoenzyme, as well as an inducer, a moderate inhibitor and a substrate of the CYP3A4 isoenzyme.
Emend can increase plasma concentrations of drugs that are metabolized with the participation of the CYP3A4 isoenzyme, which is fraught with the development of serious and potentially life-threatening reactions. Ergot alkaloid derivatives, astemizole, terfenadine, cisapride, pimozide should not be used simultaneously.
When Emend is prescribed in conjunction with chemotherapeutic agents that are partially or predominantly metabolized with the participation of the CYP3A4 isoenzyme (with docetaxel, vinorelbine, paclitaxel, etoposide), there is no need to adjust their doses. However, close observation of the patient should be ensured. In post-registration studies, cases of neurotoxicity have been reported, which can be considered as a possible side effect of ifosfamide used simultaneously with aprepitant.
Strong inducers of the CYP3A4 isoenzyme (for example, phenobarbital, rifampicin, carbamazepine, phenytoin) can reduce the plasma concentration of aprepitant and, as a result, reduce its effect. The simultaneous administration of drugs that are strong inducers of the indicated isoenzyme, as well as St. John's wort is not recommended.
Strong inhibitors of the isoenzyme CYP3A4 can increase the content of aprepitant in the blood plasma, and therefore such drugs (for example, ketoconazole) in combination with Emend should be used with caution.
There was no clinically significant effect on the pharmacokinetics of aprepitant of moderate inhibitors of the isoenzyme CYP3A4 (such as itraconazole, clarithromycin, posaconazole, voriconazole, diltiazem, telithromycin, protease inhibitors).
Aprepitant increases the metabolism of warfarin. With the joint appointment of these or other drugs that are metabolized with the participation of CYP2C9 (for example, phenytoin), their plasma concentrations may decrease. There is no effect of Emend on the AUC of the R (+) - and S (-) - isomers of warfarin, however, a decrease in the minimum concentration of S (-) - warfarin was noted, which was accompanied by a decrease in the International Normalized Ratio (INR) by about 14% 5 days after cancellation Emenda. In this regard, with long-term therapy with warfarin, it is necessary to carefully monitor the INR index within 2 weeks of each cycle of chemotherapy with aprepitant, especially on the 7-10th days after the start of Emend's administration according to the 3-day regimen.
Aprepitant increased the metabolism of tolbutamide (a substrate of the isoenzyme CYP2C9), and also reduced its AUC: on the 4th day - by 23%, on the 8th day - by 28%, on the 15th day - by 15%. Tolbutamide was used in a single dose of 500 mg before starting a 3-day therapy with aprepitant on days 4, 8 and 15.
Emend increases the AUC of GCS. With the simultaneous use of dexamethasone inside, this indicator increased 2.2 times, methylprednisolone inside - 2.5 times, methylprednisolone intravenously - 1.3 times. To achieve the desired effect with such a combination, the standard dose of dexamethasone inside and the dose of methylprednisolone inside is reduced by 50%, the dose of methylprednisolone intravenously - by 25%.
Aprepitant, when used simultaneously and within 28 days after the last dose, reduces the effect of hormonal contraceptives. In this regard, during the period of therapy with Emend and within 1 month after its end, it is recommended to use alternative or additional contraceptive methods.
Aprepitant increases the AUC of oral midazolam. With the joint appointment of benzodiazepines, the likelihood of an increase in their plasma concentrations should be taken into account.
With the simultaneous use of aprepitant 1 time per day in the form of tablets at a dose comparable to 85 mg or 170 mg of aprepitant in capsules, and paroxetine 1 time per day at a dose of 20 mg, a decrease in C max ~ 20% and AUC ~ 25% was observed in both drugs.
Co-administration for 5 days of aprepitant tablets at a dose comparable to 230 mg of the drug in capsules and diltiazem 3 times a day at a dose of 120 mg in patients with mild to moderate arterial hypertension led to a 2-fold increase in aprepitant AUC and diltiazem AUC 1.7 times. There were no clinically significant changes in blood pressure, heart rate, and electrocardiogram values compared with diltiazem alone.
Interaction of Emend with drugs that are substrates of the P-glycoprotein transporter is unlikely.
Aprepitant does not interact with digoxin. Does not significantly affect the pharmacokinetics of serotonin 5HT 3 receptor antagonists, for example, granisetron, ondansetron and hydrodolasetron (the active metabolite of dolasetron).
Analogs
The analogues of Emend are Emend V / V, Zofran, Yunorm, Emeton, Zofetron, Ondem, Emesetron-Health, Emeset, Latran, Ondasetron, etc.
Terms and conditions of storage
Keep out of the reach of children at a temperature not exceeding 30 ° C.
Shelf life is 4 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Emenda
According to reviews, Emend is an effective antiemetic drug used against the background of chemotherapy. Patients note its good efficacy and tolerability, but complain about its high cost.
Price for Emend in pharmacies
Depending on the region of sale and the pharmacy network, the price for Emend for 1 set (1 capsule 125 mg and 2 capsules 80 mg each) can range from 3200 to 5500 rubles.
Emend: prices in online pharmacies
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Drug name Price Pharmacy |
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Emend IV 150 mg lyophilisate for preparation of solution for infusion 1 pc. 3900 RUB Buy |
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Emend bl. (125mg.1caps.) + Bl. (80mg2caps.) Set of capsules 3 pcs. RUB 4132 Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, 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!
