The instruction "Emenda" is necessary for everyone who plans to use this drug. Recently, it is considered one of the most effective drugs to prevent or prevent vomiting or nausea caused by anticancer drugs. You should know that you should take it in combination with other antiemetic drugs, only in this way you can achieve the maximum effect. In this article, we will provide detailed instructions for use, we will talk about the composition, as well as about the feedback of patients who have already used this tool.
Structure
According to the instructions, Emend contains 80 mg of the active substance aprepitant in each capsule. There are also auxiliary substances that contribute to the absorption of the drug and achieve a greater effect. Here is an exhaustive list of them:
- hydroxypropyl cellulose (16 mg);
- sodium lauryl sulfate (0.3097 mg);
- sucrose (80 mg);
- microcrystalline cellulose in granules (39.16 mg);
- micronized sodium lauryl sulfate (0.3097 mg).
The amount of each substance in the composition of Emenda is given per capsule. In most cases, it is available in the form of capsules enclosed in a hard gelatin from directly gelatin and titanium dioxide.
It is worth noting that the medicine is available in two dosages. According to the instructions of the Emenda tablets, the main active substance can be 80 mg, as in the already described example, or 125 mg. In the second case, exactly the same auxiliary substances are used. At a dosage of "Emenda" 125 mg, the capsule itself contains, in addition to gelatin and titanium dioxide, red and yellow iron oxides.
The drug is sold in pharmacies in cardboard packaging, in which there is one blister. In each blister, there are one, three or five capsules.
Pharmacodynamics
Now we dwell in more detail on the instructions for the use of Emenda. Pharmacists position this drug as an antiemetic drug, which is a high-affinity selective antagonist of neurokinin receptors. This is a very effective tool, since the selectivity of binding to receptors is at least three thousand times higher than for other similar enzymes, which can also be carriers of receptor sites and ion channels. In a specific case, we can talk about serotonin and dopamine receptors. They are the main targets of most existing drugs that are used to treat vomiting and nausea during intensive chemotherapy courses.
During preclinical studies, it was possible to establish that existing receptor antagonists prevent the development of vomiting caused by chemotherapeutic drugs. In particular, the very common "Cisplatin". This is due to the central mechanism of action.
An active substance called aprepitant, which is used in Emend tablets, penetrates the brain, directly binding to brain receptors. Possessing a rather long and long central action, this substance inhibits not only the acute, but also the delayed phase of vomiting, which can be caused by cisplatin. At the same time, the antiemetic effect of both Dexamethasone and Ondansetron is enhanced.
Pharmacokinetics
According to the instructions for use of Emenda, the body's assimilation of this drug is divided into several stages. The first is absorption.
Its maximum concentration in the blood is reached approximately four hours after direct ingestion. Moreover, the absolute bioavailability is approximately 60-65 percent. It is worth noting that taking the Emenda capsule at the same time as eating does not have a significant clinical effect on the bioavailability of the active substance of aprepitant.
It should be noted that the pharmacokinetics in the range of clinical doses is nonlinear.
After direct ingestion of the drug in 125 mg on the first day, a dose of 80 mg of Emenda on the second and third day should be to maximize the effect. At the same time, its highest concentration in the body on the first and third days will be achieved in about four hours.
After absorption, distribution occurs. Binding to plasma proteins occurs. During experimental studies, scientists were able to find out that aprepitant penetrates the blood-brain barrier in ferrets and rats, and only in rats through the placental barrier. In humans, the penetration of the active substance occurs through the blood-brain barrier.
In the process of metabolism, the aprepitant of the Emenda capsule begins to undergo intensive metabolism in the liver due to oxidation in the morpholine ring, as well as its side chains.
Withdrawal takes place from nine to thirteen hours. The active substance of the Emend tablets is excreted through the kidneys by five percent, and the intestine takes over the bulk. About 86 percent is displayed through it. Plasma clearance reaches an indicator of 60 to 84 ml / minute.
The antiemetic Emend is relatively recent in the pharmaceutical market. With special care, it should be given to children and adolescents. In most cases, doctors do not prescribe Emend medicine at all to minor patients, since its pharmacokinetics on them has not been fully studied.
For patients over the age of 65, when taking this medication by mouth on the first day, it is recommended to limit themselves to a single dose of 125 mg. Then on the second and fifth days with a dose of 80 mg Emenda. In this case, the maximum concentration of the active substance in the body will be ten percent higher on the first day and almost a quarter on the fifth. The differences obtained by most experts are considered clinically insignificant.
It is necessary to observe certain rules for the administration of the antiemetic Emend, depending on the presence of concomitant diseases in patients. For example, patients with severe renal failure and patients who needed hemodialysis received a single dose of 240 ml. In severe renal failure, the total exposure to the active substance is reduced by more than 30 percent than in healthy volunteers. If the patient has a thermal stage of renal failure, while he is on hemodialysis, then these indicators can be even higher. Due to the decrease in the binding of aprepitant to plasma proteins in a patient with renal insufficiency, the concentration of the drug in the blood plasma practically did not differ from that in a healthy individual. Moreover, if hemodialysis is performed four hours after taking the drug, and then another two days later, there is no significant effect on its pharmacokinetics. In the dialysis itself, no more than two tenths of a percent of the dose of the active substance of the Emend drug was detected.
After a single oral administration, the maximum concentration of the substance and the concentration of the drug in the blood plasma in women was higher than in men. Nine and seventeen percent, respectively. But the half-life of the aprepitant of the fairer sex turned out to be a quarter less. In this case, no significant differences in the time to reach the maximum concentration of a substance in the body between men and women were noted.
From the foregoing, we can conclude that the existing differences in pharmacokinetic parameters do not have a significant clinical effect. Also, dose adjustment of the drug is not required depending on the patient's race or its mass index. This will not affect the pharmacokinetics of the active substance.
Indications and contraindications
According to the instructions, Emend is taken to delay and prevent acute vomiting and nausea, which can be caused by anticancer drugs. Both moderately and highly emetogenic. The use of Emenda is recommended to be combined with other antiemetic drugs.
Among the contraindications are the simultaneous use with "Terfenadine", "Pimozide", "Cisapride" and "Astemizole". This drug should not be prescribed in case of individual intolerance to its individual components, as well as in severe liver failure, if it is above nine points on the Child-Pugh scale.
With extreme caution, this drug should be used by patients who simultaneously receive drugs that are metabolized primarily with the participation of an isoenzyme. With the parallel appointment of Emenda with Warfarin, this can lead to a significant decrease in the international normalized blood ratio. If a patient receives Warfarin therapy for a long time, the value of the international normalized blood ratio must be carefully monitored for at least two weeks during each of the chemotherapy cycles. Especially close attention should be paid after the start of taking Emenda according to the instructions for three days.
It must be remembered that this drug can significantly reduce the effectiveness of hormonal contraceptives, this position will continue throughout the administration of this drug, as well as over the next month.
During the period of treatment with this drug, as well as four weeks after the completion of its administration, reserve and alternative methods of contraception should be used, since hormonal methods will demonstrate extremely low effectiveness.
Doses and methods of application
Emenda capsules and ampoules are taken orally, regardless of the time of eating. This drug is prescribed for three days in combination with glucocorticosteroids and serotonin receptor antagonists.
It is important that you carefully read the complete instructions for use of Emenda before starting therapy (photos of the drug are presented in the article), as well as antagonists of serotonin receptors, which will be prescribed in parallel.
With a three-day regimen of therapy, the recommended dose is 125 mg one hour before taking chemotherapy drugs on the first day. On the second and third days, 80 mg - once a day, in the morning.
Here is a more detailed drug regimen for highly emetogenic chemotherapy. On the first day, drink 125 mg of Emenda one hour before the start of chemotherapy. Half an hour before chemotherapy, you take Dexamethasone, as well as serotonin receptor antagonists according to the instructions.
On the second and third day, the patient drinks 80 mg of Emenda and 8 mg of Dexamethasone in the morning. On the fourth day in the morning you should drink 8 mg of "Dexamethasone".
If the patient has moderately emetogenic chemotherapy, then on the first day one hour before the start of chemotherapy should drink 125 mg of Emenda. 30 minutes before the start of chemotherapy - 12 mg of "Dexamethasone", and take the serotonin receptor antagonists in accordance with the instructions. On the second and third days, take only Emend - 80 mg in the morning.
Some features are prescribed for patients with concomitant diseases. In moderate or mild liver failure (with indicators from five to nine points on the Child-Pugh scale), dose adjustment is not required. There are no clinical data on the use of this drug in patients with severe hepatic insufficiency at a level above nine on the Child-Pugh scale.
It is also worth noting that with a terminal and severe stage of renal failure, even in hemodialysis, dose adjustment is not necessary.
During pregnancy and during breastfeeding, no strictly controlled and adequate safety studies of this drug have been conducted. In this regard, it should not be used during lactation or expectation of a child. At present, it has not been established whether the active substance aprepitant is secreted in a nursing mother with breast milk. If during the period of lactation the use of this drug appears to be necessary, the issue of stopping breastfeeding should be urgently resolved, since a newborn baby can be adversely affected. At least for a while it should be transferred to an artificial mixture.
Side effects
Like every powerful drug, Emenda has certain side effects. It should be noted that the safety of the main active substance was confirmed in the course of studies in which about six and a half thousand patients took part.
With highly emetogenic therapy, qualified studies were conducted on a group of 544 patients. They received highly emetogenic therapy with aprepitant in the first cycle. Of this number of sick subjects, 413 people continued therapy. The maximum number of courses that was held for them was six. The greatest effectiveness was shown by the three-day intake of Emenda in combination with Dexamethasone and Ondansetron. Almost all the side effects that were recorded at the stage of clinical trials were considered to be moderate to mild reactions. In most cases, in some patients, hiccups, an increase in the activity of analinaminotransferase in the blood, constipation, dyspepsia, loss of appetite, headache were observed.
During an additional clinical study, which involved more than one thousand patients who received various types of highly emetogenic therapy and drugs for the prevention of nausea, the adverse reactions were almost identical.
With moderately emetogenic therapy, a qualified study was conducted involving almost 900 patients. The most common clinical reaction was fatigue. This factor was manifested in almost one and a half percent of the subjects.
When conducting a combined analysis of studies of patients with moderately emetogenic and highly emetogenic therapy, it was found that in patients taking the active substance aprepitant as part of Emenda, the following side effects were observed:
- parasitic and infectious diseases (staphylococcal infection and candidiasis);
- problems with the hematopoietic system (febrile neutropenia, anemia);
- mental disorders (euphoria, anxiety, disorientation);
- from the sensory organs - tinnitus, conjunctivitis;
- from the respiratory system - sore throat, hiccups, coughing, sneezing, pharyngeal irritation, postnasal syndrome;
- from the side of nutrition and metabolism - polydipsia, decreased appetite;
- on the part of the cardiovascular system - paroxysmal sensations of heat (they are often called “hot flashes”), heart palpitations, cardiovascular disorders, bradycardia;
- from the nervous system - drowsiness, dizziness, lethargy, cognitive impairment, taste perversion;
- from the subcutaneous fat and skin - acne, rash, excessive sweating, photosensitivity, increased oily skin, seborrhea, itchy rash;
- from the urinary system - pollakiuria, dysuria;
- from the digestive system - belching, dyspepsia, gastroesophageal reflux, nausea, abdominal pain, vomiting, dry mouth, hard feces, flatulence, neutropenic colitis, perforated duodenal ulcer, bloating stomatitis;
- from the musculoskeletal system - muscle cramps, muscle weakness.
Compared with laboratory indicators, an increase in the activity of alanine aminotransferase was often observed, in some cases an increase in the activity of alkaline phosphatase, an increase in the activity of aspartate aminotransferase in the blood. In some cases, there was an entry of red blood cells into the urine, an increase in diuresis, a decrease in body weight, hyponatremia, neutropenia, glucosuria.
Common disorders that have occurred in patients taking this drug are asthenia, fatigue, swelling, malaise, gait disturbance, discomfort in the chest area.
It is important that when conducting repeated courses of chemotherapy (maximum six), the profile of side effects was comparable to that manifested in the first course of chemotherapy.
In one of the alternative studies when using this drug to prevent vomiting and nausea, more serious side effects were discovered - the development of Stevens-Johnson syndrome, as well as Lyell syndrome, i.e. toxic epidermal necrolysis.
The data of post-registration studies cannot be considered reliable, since the reports in these cases came from volunteers from population groups whose total number was impossible to establish. Therefore, it is not possible to reliably determine the causal frequency and the expected relationship of a side effect with taking the drug.
It should also be noted that from the side of the immune system hypersensitivity reactions appeared, in particular, anaphylactic ones, and from the side of skin appendages and skin - rash, itching, urticaria. Serious side effects such as Lyell and Stevens-Johnson syndromes also fall into the latter category.
. , . , .
, . "" . , . , .
Overdose
. , , . , .
, "" . , 1 440 , .
"" , . , .
It must be understood that due to the antiemetic effect of the main substance of aprepitant, drugs that cause vomiting, which are usually used for overdoses, will be ineffective in this case. Hemodialysis is considered ineffective, the antidode is unknown.
Alternative remedies
It is worth noting that the analogues of Emenda, the instructions to which we have considered, have not yet been developed in modern pharmacology. The active substance used in this drug is not used in other drugs with the same concentration and for the same purpose.
It is not yet possible to find Emenda analogues on either the domestic or foreign markets.
Reviews
You can find quite conflicting opinions about this drug. In reviews of Emenda, some patients and relatives of those who took it admitted that the drug did not help at all.
The most amazing thing is that not all oncologists know how to use this product effectively, that is, with Dexamethasone and Ondansetron. In chemotherapy reviews of Emenda, one has to deal with situations where only this drug is prescribed without complex therapy. In this case, the patient has nothing to rely on at least for some positive effect. The reaction to chemotherapy will be exactly the same as without Emenda. But if you follow the instructions for the use of Emenda, the reviews say that you can count on a positive effect. In this case, the patient's condition should be much easier.
In reviews of Emenda, patients and their relatives often note that for many, this drug becomes a real salvation, although it costs a lot of money. For example, if you receive a disability pension, then for one package you will have to pay almost half of this money - about five thousand rubles. As a rule, there are three capsules in one package, as it is designed for one course of chemotherapy. The main thing is not to confuse in what order to take the tablets, since the first of them is much more than the other two. As a result, chemotherapy is much easier to tolerate. Exhausting vomiting and nausea fade into the background. Many are strongly advised to follow the Emenda instructions. Reviews in this case leave mostly positive.
This is a great and effective tool, but very expensive. However, its importance cannot be underestimated. Indeed, especially in elderly patients, vomiting during chemotherapy should not be allowed. Some useful substances remain in their bodies, and if they are also washed intensively, then treatment will do more harm than good.
The small capsules contained in the package do work. Chemotherapy does not vomit. But to avoid lethargy and apathy, most likely, will not succeed.
Interaction
The aprepitant used in this medicine as the main active substance is an isoenzyme inducer and a moderate inhibitor. With its appointment, you can encounter a significant increase in the concentration of drugs in the plasma.
In this regard, it is strongly not recommended to use this drug simultaneously with Terfenadine, Pimozide, Cisapride, Astemizole, as well as ergot alkaloids derivatives. Under the influence of aprepitant, inhibition of the isoenzyme can provoke a significant increase in the concentration of these drugs in human plasma. This threatens dangerous reactions, not only for health, but even for the life of the patient.
The simultaneous appointment of Emenda with Tolbutamide and Warfarin can also lead to undesirable consequences, since the aprepitant in this case will begin to metabolize them with the participation of certain isoenzymes. This, on the contrary, will lead to a significant reduction in human plasma.
Emend significantly reduces the effectiveness of Tolbutamide. But the interaction of this drug with substrates that are carriers of P-glycoprotein is unlikely. In this case, no clinically significant changes should be expected.
It is noteworthy that you can not adjust the dose of chemotherapeutic drugs, the metabolism of which mainly develops with the participation of certain isoenzymes (vinorelbine, etoposide, paclitaxel, docetaxel). However, some care should be taken to maintain the health of patients receiving these drugs. They should always be closely monitored by doctors.
To reduce the concentration of the active substance of aprepitant in plasma leads to the use of "Emenda" in conjunction with drugs that are inducers of certain isoenzymes. In particular, it can be phenytoin, rifampicin, phenobarbital, carbamazepine. Because of this, the effectiveness of the Emenda itself is reduced many times, which, of course, cannot be allowed. After all, this is an important component of treatment with chemotherapy, in addition, we should not forget that the drug is very expensive. So it is impossible that it actually disappeared in vain.
Also, the simultaneous administration of Emenda with medicines based on such a component as St. John's wort perforated is not recommended. This is fraught with a mutual decrease in the effectiveness of important and useful components, which largely neutralizes the benefits of the therapy, actually reducing it to zero.
Summing up, we can say that this is a new, fairly effective, but expensive tool with a minimum set of side effects. It is able to provide significant assistance with chemotherapy to patients who should not be allowed to have nausea and severe vomiting during this period. The drug is able to successfully neutralize these manifestations, so that the course of therapy passes with maximum benefit and effectiveness.