Enthal

Ental contains the substance capecitabine, which is a derivative of fluoropyrimidine carbamate. It is an orally administered cytostatic that is activated within the tumor tissue and exhibits a selective cytotoxic effect on it. Capecitabine itself does not have cytotoxic activity, but is transformed into the cytotoxic element fluorouracil (5-FU).

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

Indications Entala

It is used in the following situations:

• breast carcinoma: metastatic or locally advanced carcinoma (in combination with docetaxel if chemotherapy using taxanes and anthracyclines was ineffective or if the patient has contraindications to their use);
• colorectal carcinoma or colon carcinoma: adjuvant treatment or first-line agent in the treatment of metastatic colorectal carcinoma;
• carcinoma in the stomach and esophagus: first-line drug for widespread carcinoma.

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Release form

The medicinal substance is released in tablets - with a volume of 0.15 g, 10 pieces inside a blister pack, 6 packs inside a package; with a volume of 0.5 g - 10 pieces inside a packaging plate, 12 plates inside a box.

Pharmacodynamics

Sequential enzymatic conversion of capecitabine to the 5-FU component forms higher values inside tumor cells than inside healthy tissues. When using the drug by people with colon carcinoma, the level of 5-FU inside tumor tissue is 3.2 times higher than the values inside healthy tissues. The proportion of 5-FU values inside tumor tissues and plasma is 21.4, and the ratio of values inside healthy tissues and plasma is 8.9.

The activity of thymidine phosphorylase inside primary colorectal neoplasms is four times greater than its activity inside healthy tissues.

Within the cells of neoplasms in individuals with carcinoma of the breast, colon, stomach, ovaries and cervix, a greater volume of thymidine phosphorylase capable of transforming 5'-DFUR into a component of 5-FU is determined than within healthy tissues.

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Pharmacokinetics

The drug is fully absorbed in the gastrointestinal tract at high speed (eating food reduces the absorption rate). In the liver, the drug is transformed together with carboxylesterases, forming the element 5-DFCT, which is deaminated under the influence of cytidine deaminase (inside the tissues of the tumor and liver), after which it is converted into the component 5-DFUR. The synthesis rates with the protein of capecitabine, as well as the components 5-DFCT, 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. The Cmax indicator of α-fluoro-β-alanine, which is a metabolic element of 5-FU, is determined after 3 hours; its half-life is in the range of 3-4 hours.

Excretion occurs mainly in urine (95.5% of the dose), with 57% excreted in the form of α-fluoro-β-alanine.

In individuals with renal failure, with a 50% decrease in CC values, an increase in the level of α-fluoro-β-alanine by 114% is observed.

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Dosing and administration

The medication is taken orally, within a maximum of half an hour after eating.

In monotherapy, the following doses are usually used: in the case of breast or colon carcinoma, as well as colorectal carcinoma - the introduction of 2.5 g / m ² per day (in 2 doses, in the morning and then in the evening). Therapy is carried out in weekly courses - daily intake of drugs for a period of 14 days, and then a 7-day break.

In case of complex treatment of breast carcinoma, 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 break. For people with carcinoma of the stomach, colon or esophagus, as well as with colorectal carcinoma in combination therapy, the dosage of capecitabine is first reduced to 0.8-1 g / m ², 2 times a day (for a period of 14 days, after which a 7-day break is made) or to 625 mg / m ² 2 times a day in case of continuous administration.

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Use Entala during pregnancy

Enthal should not be used during pregnancy or breastfeeding because the drug is considered a teratogen.

Contraindications

Main contraindications:

• severe sensitivity to drug elements;
• diagnosed deficiency of the DPD element;
• severe stage of thrombocyto-, leuko- or neutropenia;
• severe liver dysfunction;
• renal dysfunction of a severe nature (CC values are below 30 ml per minute);
• use in combination with sorivudine or its analogues.

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Side effects Entala

Side effects include:

• neurological disorders: fatigue, asthenia, ocular irritation, paresthesia, polyneuropathy and weakness, as well as taste disturbances, dizziness, increased lacrimation, headaches and confusion. Drowsiness, cerebellar signs (ataxia with dysarthria, as well as problems with coordination and balance), insomnia, encephalopathy and conjunctivitis are also possible;
• cardiovascular problems: angina pectoris, myocardial infarction or ischemia, anemia, heart failure, cardialgia, tachycardia and cardiomyopathy, as well as phlebitis, pancytopenia, supraventricular arrhythmia, ventricular extrasystole, thrombophlebitis, increased or decreased blood pressure, suppression of bone marrow function and sudden death;
• respiratory disorders: cough, dyspnea, RDS syndrome, sore throat, embolism affecting the pulmonary vessels, and bronchial spasm;
• digestive disorders: diarrhea, bloating, stomatitis, loss of appetite, anorexia, constipation, xerostomia, nausea, abdominal pain and changes in fecal consistency. In addition, liver failure, hyperbilirubinemia, oral candidiasis, cholestatic hepatitis and ulcerative-inflammatory lesions (duodenitis, colitis with gastritis, bleeding inside the gastrointestinal tract and esophagitis) may be observed;
• musculoskeletal disorders: pain in the limbs or lower back, arthralgia, swelling of the legs or myalgia;
• Epidermal symptoms: alopecia, epidermal dryness, redness, flaking (scaling, numbness, blistering, tingling, sharp pain, paresthesia and swelling), as well as dermatitis, hyperpigmentation and epidermal cracks. In addition, erythematous rashes, nail infections, itching, focal flaking, photosensitivity, onycholysis, as well as discoloration, dystrophy and brittleness of the nails are noted;
• others: hyperglycemia, sepsis, epistaxis, infections associated with myelosuppression, weight loss, stenosis affecting the nasolacrimal tract, chest pain, changes in AST or ALT levels, and dehydration.

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Overdose

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

Symptomatic actions are performed.

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Interactions with other drugs

Use with coumarin anticoagulants (e.g. phenprocoumon or warfarin) leads to a violation of bleeding and blood clotting processes. Such signs appeared within a range of several days/months from 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 levels of capecitabine and 1 of the metabolic elements (5'-DPCR).

Administration in combination with sorivudine or its analogues may lead to a clinically significant interaction (with the 5-FU component), which develops due to the suppression of DPD under the influence of sorivudine. As a result, the toxic properties of fluoropyrimidines are potentiated, which can even be fatal. For this reason, Enthal is not used together with sorivudine or chemical analogues of this substance (for example, with brivudine).

Combination therapy with capecitabine-docetaxel or capecitabine-cisplatin should not be used in situations where the patient is contraindicated for the latter drugs.

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Storage conditions

Enthal should be stored at temperatures in the range of 15-25°C.

Shelf life

Enthal can be used within a 36-month period from the date of sale of the therapeutic substance.

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Application for children

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

Analogues

Analogues of the drug are Xeloda, Capecibex with Apsibin, Cytin and Capetero with Capecitabine, as well as Newcapibine and Kaponco.