Ental

Ental contains a substance capecitabine, which is a derivative of the carbamate fluoropyrimidine. It is an ingested cytostatic that is activated inside the tumor tissue and demonstrates its selective cytotoxic effect in its relation. At the same time, capecitabine itself does not possess cytotoxic activity, but fluorouracil (5-FU) is transformed into a cytotoxic element.

The formation of the 5-FU component inside the tumor tissue is realized under the influence of the angiogenic element thymidine phosphorylase of the neoplasm, due to which the total effect of 5-FU on healthy tissues is minimized.

Indications Ental

It is used in such situations:

• breast carcinoma : metastatic or common local carcinoma (in combination with docetaxel if chemotherapy with taxanes and anthracyclines was ineffective or with contraindications to their use in a patient);
• colorectal carcinoma or colon carcinoma: adjuvant treatment or 1st line substance in the treatment of metastatic colorectal carcinoma;
• carcinoma of the stomach and esophagus: medicine of the 1st line in the common form of carcinoma.

[1], [2], [3], [4], [5], [6], [7]

Release form

The release of the drug substance is made in tablets - with a volume of 0.15 g in 10 pieces inside a cell bundle, 6 packs in a package; with a volume of 0.5 g - 10 pieces inside the packaging plate, 12 plates inside the box.

Pharmacodynamics

The sequential enzymatic conversion of capecitabine to the 5-FU component forms higher values inside the neoplasm cells than inside healthy tissues. When drugs are used by persons with colon carcinoma, the level of 5-FU inside the tumor tissue is 3.2 times higher than the indices inside healthy tissues. The proportion of 5-FU values inside the neoplasm tissues and plasma is 21.4, while the ratio of indicators inside healthy tissues and plasma is 8.9.

The effectiveness of thymidine phosphorylase inside the primary colorectal neoplasm is four times higher than its activity inside healthy tissues.

Inside the cells of the neoplasm in individuals with carcinoma of the breast, colon, stomach, ovaries and uterine cervix, a greater amount of thymidine phosphorylase is detected, which is able to transform 5'-DFUR into a component in 5-FU than inside healthy tissues.

[8]

Pharmacokinetics

The drug at high speed, fully absorbed inside the gastrointestinal tract (eating food reduces the rate of absorption). Inside the liver, the drug, together with the carboxy esterases, undergoes transformation, forming the element 5-DFCT, which deaminates under the influence of cytidine deaminase (inside the tissue of the neoplasm and liver), after which it becomes a component of 5-DFUR. Synthesis with capecitabine protein, as well as components of 5-DFTC, 5-FU and 5-DFUR are, respectively, 54%, 10%, 10% and 62%.

The Cmax values of capecitabine are determined after 90 minutes, and 5-DFCT with 5-DFUR - after 2 hours; their half-life is 0.7-1.14 hours. Cmax α-fluoro-β-alanine, which is a metabolic element of 5-FU, is determined after 3 hours; the term of its half-life is in the range of 3-4 hours.

Excretion is mainly carried out in the urine (at 95.5% of the dosage), while 57% is excreted in the form of α-fluoro-β-alanine.

In individuals with kidney function deficiency, a 50% decrease in the QA values of α-fluoro-β-alanine is observed by 114%.

[9], [10], [11]

Dosing and administration

The medication is taken orally, for a maximum of half an hour after a meal.

When monotherapy is usually used such portions: in the case of carcinoma of the breast or colon, as well as colorectal carcinoma - the introduction of 2.5 g / m ² per day (in 2 uses, in the morning, and then in the evening). Therapy is conducted weekly courses - daily intake of drugs in the period of 14 days, and then a 7-day break.

In the case of complex breast carcinoma treatment, the drug is usually used together with docetaxel - in a dose of 1.25 g / m ³ 2 times a day, for a period of 2 weeks, after which it is necessary to make a 7-day period. For people with carcinoma of the stomach, colon or esophagus, as well as with colorectal carcinoma, in combination therapy, first reduce the dose of capecitabine to 0.8-1 g / m ², 2 times a day (for a period of 14 days, after which they make 7 - daily break) or up to 625 mg / m ² 2-fold per day in case of continuous administration.

[19], [20], [21],

Use Ental during pregnancy

Do not use Ental during pregnancy or breastfeeding, because the drug is considered a teratogen.

Contraindications

The main contraindications:

• strong sensitivity to the elements of drugs;
• diagnosed lack of an element of the DPD;
• severe stage of thrombocyto-, leuko- or neutropenia;
• severe hepatic dysfunction;
• renal dysfunction, having a severe character (CC values are below 30 ml per minute);
• use in combination with sovarudin or its analogs.

[12], [13], [14], [15], [16]

Side effects Ental

Among the adverse events:

• disorders of the neurological type: fatigue, asthenia, eye irritation, paresthesias, polyneuropathy and weakness, as well as taste disorders, dizziness, potentiation of tearing, headaches, and confusion. Drowsiness, cerebellar signs (ataxia with dysarthria, as well as coordination and balance problems), insomnia, encephalopathy and conjunctivitis are also possible;
• problems cardiovascular character angina, infarction or myocardial ischemia, anemia, heart failure, false angina, tachycardia and cardiomyopathy as well as phlebitis, pancytopenia, arrhythmia supraventricular type extrasystoles ventricular thrombophlebitis, increase or decrease blood pressure values, bone marrow suppression operation and sudden death;
• disorders of respiratory function: cough, dyspnea, RDS syndrome, pain in the throat, embolism affecting the blood vessels of the lungs, and bronchial spasm;
• digestive disorders: diarrhea, bloating, stomatitis, loss of appetite, anorexia, constipation, xerostomia, nausea, abdominal pain and changes in the consistency of feces. In addition, liver failure, hyperbilirubinemia, oral candidiasis, cholestatic type hepatitis and lesions with an ulcer-inflammatory nature (duodenitis, colitis with gastritis, bleeding inside the gastrointestinal tract and esophagitis) may be observed;
• ODA lesions: pain in the limbs or lower back, arthralgia, leg swelling, or myalgia;
• epidermal symptoms: alopecia, epidermal dryness, redness, LPS (peeling, numbness, blistering, tingling, sharp pain, paresthesia and swelling), as well as dermatitis, hyperpigmentation and epidermal cracks. In addition, there are erythematous rashes, infection of the nails, itching, peeling of the focal type, photosensitivity, onycholysis, as well as discoloration, dystrophy and brittle nails;
• others: hyperglycemia, sepsis, bleeding from the nose, infections associated with myelosuppression, weight loss, stenosis affecting the lacrimal-nasal tract, sternum pain, changes in AST or ALT, and dehydration.

[17], [18]

Overdose

Signs of poisoning: mucositis, bleeding, vomiting, suppression of bone marrow function, irritation in the gastrointestinal tract and diarrhea.

Symptomatic actions are performed.

[22]

Interactions with other drugs

Use with coumarin anticoagulants (for example, fenprokumon or warfarin) leads to disruption of the processes of bleeding and blood coagulation. Similar signs appeared in the range of several days / months since the start of treatment; once such a violation developed after 1 month after the end of therapy.

Magnesium or aluminum-containing antacids lead to a slight increase in plasma indicators of capecitabine and the first of the metabolic elements (5'-DFCR).

An introduction in combination with sovarudine or its analogs can lead to a clinically significant interaction (with the 5-FU component), which develops in connection with the inhibition of DPD under the influence of soirudine. As a result, the toxic properties of fluoropyrimidines are potentiated, which can even be fatal. Because of this, Ental is not used together with sorivudin or chemical analogues of this substance (for example, with brivudine).

It is forbidden to use the combination therapy capecitabine-docetaxel or capecitabine-cisplatin in situations where the last drugs are contraindicated to the patient.

[23], [24], [25], [26], [27], [28], [29], [30]

Storage conditions

Enthal must be maintained at temperature values in the range of 15-25 ° C.

Shelf life

Enthal can be used within a 36-month term from the time the therapeutic substance is realized.

[31], [32], [33]

Application for children

There is no information regarding the safety and drug efficacy of the drug in persons under the age of 18 years.

Analogs

Analogues of drugs are drugs Xeloda, Capecibex with Apsibin, Tsitin and Kapetero with Capecitabine, as well as Newcapibin and Caponco.