Emend kit, 125 mg+80 mg capsules 3 pcs

Name: Emend kit, 125 mg+80 mg capsules 3 pcs
SKU: 208366
Availability: InStock

€145.67

EAN: 8711141875007 SKU: 208366 Categories: Medicine, Neurology and Psychiatry, Vomiting and nausea

Description

Pharmacodynamics

An anti-emetic drug, a selective high-affinity neurokinin-1 (NK₁ receptor antagonist of Substance P. The selectivity of aprepitant binding to NK₁ receptors is at least 3,000 times higher than for other enzymes, ion channel transporters and receptor sites, including dopamine and serotonin receptors, which are the targets of currently available drugs used to treat chemotherapy-related nausea and vomiting.

In preclinical studies, NK₁ receptor antagonists have been shown to prevent the development of vomiting caused by chemotherapy drugs (such as cisplatin) through a central mechanism of action.

The aprepitant penetrates the brain and binds to brain NK₁ receptors. With its long-lasting central action, aprepitant inhibits both the acute and delayed phases of cisplatin-induced vomiting and enhances the antiemetic effects of ondansetron and dexamethasone.

Pharmacokinetics

Intake

After oral administration, C_max in plasma is reached after approximately 4 h. Absolute bioavailability on average is about 60-65%. Taking the capsule simultaneously with meals has no clinically significant effect on the bioavailability of aprepitant.

The pharmacokinetics of aprepitant in the clinical dose range is nonlinear.

After oral administration of Emend® at a dose of 125 mg on day 1 and then at a dose of 80 mg/day on days 2 and 3, the 24-hour AUC was approximately 19.5 µg×h/mL on day 1 and 20.1 µg×h/mL on day 3. C_max was 1.5 µg/mL and 1.4 µg/mL on days 1 and 3, respectively, and was reached approximately 4 h after drug administration.

Distribution

The binding to plasma proteins is more than 95%. V_d in equilibrium is approximately 66 l.

In experimental studies, aprepitant has been shown to penetrate the placental barrier in rats and through the HEB in rats and ferrets.

In humans, aprepitant penetrates through the GEB.

Metabolism

. Aprepitant undergoes intensive metabolism in the liver through oxidation in the morpholine ring and its side chains mainly by CYP3A4 and only a small part of the drug is metabolized with the participation of CYP1A2 and CYP2C19 (CYP2D6, CYP2C9 or CYP2E1 are not involved in aprepitant metabolism).

Elevation

The estimated T_1/2 is approximately 9 to 13 h.

The aprepitant is excreted primarily as metabolites through the intestine (86%) and the kidneys (5%).

The apparent plasma clearance of aprepitant is approximately 60 to 84 ml/min.

Pharmacokinetics in special clinical cases

The pharmacokinetics of Emend® in children and adolescents under 18 years of age have not been studied.

In patients 65 years of age and older, after oral administration of Emend® at a single dose of 125 mg on day 1 and then at a dose of 80 mg/day on days 2 and 5, the 24-hour AUC was 21% greater on day 1 and 36% greater on day 5 than in those younger than 65 years. C_max was 10% higher on day 1 and 24% higher on day 5. These differences were not clinically significant.

In patients with mild hepatic impairment (5-6 points on the Child-Pugh scale) after oral administration of Emend® at a dose of 125 mg on day 1 and then at a dose of 80 mg/day on days 2 and 3, AUC within 24 hours was 11% lower on day 1 and 36% lower on day 3 than in healthy volunteers who received the same doses of the drug. In patients with moderate hepatic impairment (7-9 Child-Pugh scores), the 24-hour AUC was 10% greater on day 1 and 18% greater on day 3 than in healthy volunteers who received the same doses. These differences were not found to be clinically significant.

Patients with severe renal impairment (CK < 30 ml/min) and terminal renal failure patients requiring hemodialysis received Emend® once at a dose of 240 mg. In patients with severe renal failure, the AUC for total aprepitant (both protein bound and unbound) was reduced by 21% and C_max was reduced by 32% compared to healthy volunteers. In patients with terminal renal failure who were on hemodialysis, the AUC for total aprepitant was 42% lower and C_max was 32% lower. Because of the slight decrease in binding of aprepitant to plasma proteins in patients with renal failure, the AUC values of the pharmacologically active unbound drug were not significantly different in these patients and in healthy subjects. Hemodialysis performed 4 and 48 h after drug administration had no significant effect on the pharmacokinetics of aprepitant. Less than 0.2% of the aprepitant dose was detected in the dialysate.

The AUC_0-24 and C_max of the drug were 9% and 17% higher in women than in men after a single oral dose of Emend®, respectively. T_1/2 aprepitant in women was 25% less than in men, and there were no significant differences in time to reach C_max between women and men. These differences in pharmacokinetic parameters have no clinical significance. There is no need to adjust the dose of Emend® depending on the race. Body mass index has no effect on the pharmacokinetics of Emend®.

Indications

Nausea, Vomiting, Cancer

For the prevention of acute and delayed nausea and vomiting caused by highly or moderately emetogenic anticancer drugs (in combination with other anti-emetic drugs).

Active ingredient

Aprepitant

Composition

1 capsule contains:

Active substances:

Prepitant 125 mg.

Auxiliary substances:

Hydroxypropylcellulose,

sodium lauryl sulfate,

p> sucrose,

Microcrystalline cellulose;

Capsule composition:

Titanium dioxide, gelatin; 125 mg capsules also contain iron oxide yellow and iron oxide red.

There are 3 capsules in the blister.

There is 1 blister in the carton pack.

How to take, the dosage
How to take, the dosage
The drug is taken orally regardless of meals.
Emend® is given for 3 days in combination with GCS and serotonin 5-HT₃ receptor antagonists.
Before starting treatment, read the instructions for use for the serotonin 5-HT₃ receptor antagonist prescribed concomitantly with Emend®. The recommended dose of Emend® in a three-day regimen is 125 mg 1 hour before chemotherapy drugs on day 1 and 80 mg once daily in the morning on days 2 and 3.
The tables show the drug regimen according to the degree of emetogenicity of the antitumor therapy.
Highly emetogenic chemotherapy
80 mg (morning)
Medication
Day 1
Day 2
Day 3
Day 4
Emend^®
125 mg orally 1 h before chemotherapy
80 mg (morning)

– <
Dexamethasone
12 mg orally 30 minutes before chemotherapy
8 mg orally (morning)
/p>
8 mg orally (morning)
8 mg orally (morning)
Serotonin 5-NT₃ receptor antagonists
see appropriate instructions for medical use
–
–
–
Moderately emetogenic chemotherapy
Day 2
Emend^®
–
Medication
Day 1

Day 3 <
125 mg orally 1 h before chemotherapy
80 mg (morning)
80 mg (morning)
Dexamethasone
12 mg orally 30 min before chemotherapy
–
–
Serotonin 5-NT₃ receptor antagonists
see appropriate instructions for medical use

–
In patients with mild to moderate hepatic impairment (5 to 9 points on the Child-Pugh scale), no dose adjustment is required. There are no clinical data on the use of the drug in patients with severe hepatic impairment ( > 9 points on the Child-Pugh scale).
In patients with severe renal failure (CK < 30 ml/min) and in patients in terminal renal failure who are on hemodialysis, no dose adjustment is required.
Dose adjustment according to sex, age, race, or body mass index is not required.

Interaction
Interaction
Aprepitant is a substrate, moderate inhibitor and inducer of CYP3A4 isoenzyme, as well as inducer of CYP2C9 isoenzyme.
When used concomitantly, aprepitant may increase plasma concentrations of drugs metabolized with the participation of CYP3A4 isoenzyme. Emend® should not be used concomitantly with pimozide, terfenadine, astemizole, cisapride, ergot alkaloid derivatives. Inhibition of CYP3A4 isoenzyme by aprepitant may increase the plasma concentrations of these drugs and lead to potentially serious and life-threatening reactions.
Prepitant induces metabolism of warfarin and tolbutamide. Simultaneous use of Emend® preparation with these or other drugs, which are metabolized with the participation of CYP2C9 isoenzyme (for example, with phenytoin) may lead to the reduction of their concentrations in plasma. No effect of Emend® preparation on AUC of R(+)- or S(-)-warfarin was observed, but in case of concomitant use of Emend® there was decreased minimal concentration of S(-)-warfarin that was accompanied with INR decreased by 14% in 5 days after the end of Emend® use.
In patients receiving long-term warfarin therapy, INR levels should be monitored closely for 2 weeks, and especially on days 7-10 after starting Emend® on a 3-day regimen, during each cycle of chemotherapy.
Emend® reduces the AUC of tolbutamide, a substrate of the CYP2C9 isoenzyme, by 23% at day 4, by 28% at day 8 and by 15% at day 15. At the same time, tolbutamide in a single dose of 500 mg was administered before the start of 3-day therapy with Emend® on days 4, 8 and 15.
The interaction of Emend® with drugs that are substrates of P-glycoprotein transporter is unlikely (no interaction of Emend® with digoxin). Aprepitant does not cause clinically significant changes in pharmacokinetics of serotonin 5HT₃ receptor antagonists – ondansetron, granisetron and hydrodolasetron (active metabolite of dolasetron).
When using Emend® together with chemotherapeutic agents whose metabolism mainly or partially occurs with the participation of CYP3A4 isoenzyme (etoposide, vinorelbine, docetaxel and paclitaxel) the doses of these drugs can not be corrected. However, it is recommended to exercise caution when using in patients receiving these drugs and provide additional monitoring. Post-registration studies have reported cases of neurotoxicity, which may be considered a possible side effect of ifosfamide used in conjunction with aprepitant.
The effect of Emend® on the pharmacokinetics of docetaxel has not been identified.
The efficacy of hormonal contraceptives may be reduced while taking Emend® and for 28 days after completion of treatment with Emend® (alternative or back-up contraceptive methods should be used during treatment with Emend® and for 1 month after the last dose of Emend®).
In concomitant oral administration of midazolam and Emend® there was an increase in AUC of midazolam. Possible increase of concentrations in plasma of midazolam or other benzodiazepines, metabolized with participation of CYP3A4 isoenzyme (alprazolam, triazolam) should be taken into consideration when prescribing these drugs with Emend®.
The concomitant use of Emend® with the drugs that inhibit the activity of CYP3A4 isoenzyme may increase the blood plasma concentration of aprepitant. Therefore, Emend® should be used with caution in combination with strong CYP3A4 isoenzyme inhibitors (e.g., ketoconazole). However, concomitant use of Emend® with moderate CYP3A4 isoenzyme inhibitors (e.g., diltiazem, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin and protease inhibitors) does not cause clinically significant changes of aprepitant plasma concentration.
Concomitant use of the drug Emend® with drugs that are strong inducers of CYP3A4 isoenzyme (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital) may lead to decreased plasma concentration of aprepitant and, thus, to decrease the effectiveness of the drug Emend®. Also concomitant use of aprepitant with preparations of St. John’s wort is not recommended.
In patients with mild to moderate arterial hypertension, administration of 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 of aprepitant and a simultaneous 1.7-fold increase in AUC of diltiazem. These pharmacokinetic effects did not result in clinically significant changes in ECG, HR, or BP compared with changes in these parameters when taking diltiazem alone.
Concomitant administration of aprepitant once daily in tablet form at a dose comparable to 85 mg or 170 mg of the drug in capsules and paroxetine at a dose of 20 mg once daily resulted in a decrease in AUC of approximately 25% and C_max of approximately 20% for both aprepitant and paroxetine.

Special Instructions
Special Instructions
Inhibition of CYP3A4 by the aprepitant may lead to increased plasma concentrations of drugs that are metabolized mainly with the participation of CYP3A4 isoenzyme (including some chemotherapeutic drugs).
Pediatric use
The safety and effectiveness of Emend® in children has not been established.
Impact on ability to drive vehicles and other mechanisms requiring high concentration
There have been no studies of the effect of the drug Emend® on the ability to drive vehicles or operate mechanisms. However, it is necessary to consider the profile of side effects of the drug, which may affect the ability of patients to operate mechanisms. Patients may have different reactions to Emend®.

Contraindications
Contraindications
Severe hepatic impairment ( > 9 points on the Child-Pugh scale);
concomitant use with pimozide, terfenadine, astemizole and cisapride;
high sensitivity to the drug components.
With caution: Emend® should be used in patients simultaneously receiving drugs which are metabolized mainly with the participation of CYP3A4 isoenzyme. Simultaneous use of Emend® with warfarin may lead to clinically significant decrease in INR. INR should be carefully monitored for 2 weeks in patients receiving long-term therapy with warfarin during each chemotherapy cycle and especially 7-10 days after the beginning of Emend® usage on 3-day regimen. The effectiveness of hormonal contraceptives may decrease during and for 28 days after treatment with Emend®. During treatment with Emend® and for 1 month after the last dose of Emend® , alternative and backup contraceptive methods should be used.

Side effects
Side effects
The safety of aprepitant was evaluated in approximately 6,500 patients.
Prevention of chemotherapy-induced nausea and vomiting
Highly emetogenic therapy
The clinical trial included 544 patients who received high emetogenic therapy and aprepitant in the first cycle. 413 patients from this group continued therapy (maximum number of chemotherapy courses was 6). The three-day regimen of Emend® in combination with ondansetron and dexamethasone was well tolerated by patients. Most adverse reactions reported in the clinical trials were defined as mild to moderate severity reactions.
The most common adverse reactions during high-emetogenic chemotherapy in patients receiving aprepitant in combination with serotonin 5-HT3-receptor antagonists and dexamethasone (observed with greater frequency than with therapy with serotonin 5-HT₃-receptor antagonists 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 trial in 1,169 patients who received various types of highly emetogenic chemotherapy and regimens to prevent nausea and vomiting using aprepitant and serotonin 5-HT antagonists₃-receptor and dexamethasone or serotonin 5-HT₃-receptor antagonists and dexamethasone alone, the adverse reaction profile was similar.
Moderately emetogenic therapy
In a clinical trial involving 868 patients, the most common adverse reaction during moderately emetogenic chemotherapy in patients who received aprepitant in combination with 5-HT₃ receptor antagonists and dexamethasone (observed with higher frequency than therapy with 5-HT₃ receptor antagonists and dexamethasone) was fatigue (1.4%).
In a pooled analysis of studies of highly emetogenic and moderately emetogenic chemotherapy, the following drug-related side effects were observed in patients treated with aprepitant, and with a higher frequency than with standard therapy:
frequent (≥1/100 to < 1/10);
infrequent (≥1/1000 to < 1/100);
infrequent (≥1/10,000 to < 1/1000).
Infectious and parasitic diseases: rare – candidiasis, staphylococcal infection.
Hematopoietic system: infrequent anemia and febrile neutropenia.
Metabolism and nutrition: often – decreased appetite; rarely – polydipsia.
Psychiatric disorders: infrequent – anxiety; rarely – disorientation and euphoria.
Nervous system disorders: infrequent – dizziness, somnolence; rare – cognitive disorders, lethargy, perversion of taste.
Sensory system disorders: rarely – conjunctivitis, tinnitus.
Cardiovascular system: infrequent – palpitations, hot flashes (“hot flashes”); rare – bradycardia, cardiovascular disorders.
Respiratory system: often – hiccups; rarely – sore throat, sneezing, cough, postnasal syndrome, irritation of the throat.
The digestive system: frequently – dyspepsia; infrequently – belching, nausea, gastroesophageal reflux, vomiting, abdominal pain, dry mouth, flatulence; rarely – hard feces, perforative duodenal ulcer, neutropenic colitis, stomatitis, bloating.
Skin and subcutaneous fatty tissue: infrequent – rash, acne; rarely – photosensitization, increased sweating, seborrhea, increased skin oiliness, itching rash.
Muscular system: rare – muscle cramps and muscle weakness.
The urinary system: infrequent dysuria; rarely – pollakiuria.
Changes of laboratory parameters: often – increased ALT activity; infrequent – increased AST activity, increased ALP activity; rarely – increased diuresis, the presence of red blood cells in urine, hyponatremia, weight loss, glucosuria, neutropenia.
General disorders: frequently – fatigue; infrequently – asthenia, malaise; rarely – edema, feeling of discomfort in the chest area, impaired gait.
The profile of adverse effects in patients receiving highly emetogenic and moderately emetogenic chemotherapy when repeated courses (maximum number of courses is 6) with aprepitant was comparable to that during the 1st cycle of chemotherapy.
In another study of the use of aprepitant to prevent chemotherapy-induced nausea and vomiting, serious side effects such as Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome) were reported.
Post-registration data
Because the reports came from volunteers from populations of uncertain size, it is not possible to reliably determine the expected incidence or causal relationship to taking the drug.
Skin and skin appendages: itching, rash, urticaria, rarely Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).
Immune system disorders: hypersensitivity reactions, including anaphylactic reactions.

Overdose
Overdose
Symptoms: available data on the use of aprepitant at high doses without chemotherapy (once up to 600 mg or 375 mg daily for 42 days) indicate good tolerance of the drug. One patient who took 1,440 mg of aprepitant experienced drowsiness and headache.
Treatment: therapy with Emend® should be discontinued and patient’s condition should be controlled. If necessary symptomatic therapy is carried out. Due to the antiemetic action of aprepitant the drugs, causing vomiting are unlikely to be effective. The antidote to the drug is unknown. Hemodialysis is not effective.

Pregnancy use
Pregnancy use
If adequate and strictly controlled clinical safety studies of the drug in pregnancy have not been conducted, therefore, the use of Emend® in pregnancy is not recommended.
It is unknown whether aprepitant is excreted with the breast milk in humans.
If it is necessary to use the drug during lactation, discontinuation of breastfeeding should be considered due to the risk of adverse effects on the infant.

Additional information
Weight 0.034 kg
Shelf life
4 years
Conditions of storage
At a temperature not exceeding 30 °C
Manufacturer
Merck Sharp & Doum B.V., The Netherlands
Medication form
capsules
Brand
Merck Sharp & Doum B.V.