Atrican 250

Release form, composition and packing

Enteric soft gelatin capsule, opaque, ovoid, yellow-brown, measuring about 7.5 mm x 14 mm; contents of capsules - gray-brown homogeneous oily mass.

1 capsule. tenonitrozol 250 mg.

Other ingredients: peanut butter, hydrogenated soybean oil, soy lecithin, gelatin, sorbitol and sorbitanov solution, glycerol, hypromellose phthalate, dibutyl phthalate, titanium dioxide (E171), iron oxide yellow (E172).

Clinico-pharmacological group: Protivoprotozoyny drug used for trichomoniasis.

Pharmacological action

Protivoprotozoyny drug. Active against Trichomonas vaginalis. Has also disulfiramopodobnoe action.

Pharmacokinetics

Absorption and excretion

Well absorbed from the gastrointestinal tract. Slowly excreted, thus maintaining the blood concentration trihomonatsidnuyu for many hours.

Statement
trichomoniasis of the urogenital system.

Dosing regimen

The drug was appointed interior, 250 mg 2 times a day (morning and evening) during the meal for 4 days. Do not exceed the recommended daily dose. In the case of pass the admission of one or more doses of the drug should be resumed in the usual dose.

Side effect
From the digestive system: sometimes - nausea, feeling of heaviness in the epigastrium, loss of appetite.

Other: allergic reactions.

Contraindications
acute and chronic liver failure;
Infancy;
Hypersensitivity to tenonitrozolu and other ingredients.

Pregnancy and lactation

It is advisable not to use the drug during pregnancy. Do not recommend to use the drug during lactation (breastfeeding) because tenonitrozol excreted in breast milk.

Use in hepatic dysfunction

Contraindicated in acute and chronic liver failure.

Cautions

The drug is used to treat trichomoniasis only in adults. During treatment you should avoid alcohol and drugs containing ethanol.

Should not be prescribed medication to persons who are not able to abstain from alcohol during treatment. Necessary to carry out the simultaneous treatment of sexual partners. Not recommended to wear contact lenses during treatment with Atrikan 250 (possibly penetration of the active substance in the eye fluid).

In applying Atrikana 250 possible color sclera and urine yellow. The patient should be informed about the need to tell the doctor about a history of episodes of change in the number of leukocytes in peripheral blood while taking other medicines.

Overdose

Currently, cases of drug overdose Atrikan 250 is not reported.

Drug Interactions

Keep in mind that during the period of the drug is contraindicated in receiving ethanol. Conditions and terms of List B. The drug should be stored in a dry place inaccessible to children at or above 30 ° C.

Shelf life - 3 years.

Atriance

Release form, composition and packing

Infusion solution is transparent, colorless, without any visible mechanical inclusions.

1 ml 1 vial. - Nelarabin 5 mg 250 mg

Excipients: sodium chloride, hydrochloric acid, sodium hydroxide, water, d / and.

Clinico-pharmacological group

Antitumor drug. Antimetabolite.

Pharmacological action

Antitumor drug. Antimetabolite. Nelarabin is a prodrug 9-β-D-arabinofuranozilguanina (ara-G), an analogue of deoxyguanosine. Under the action of adenosine deaminase nelarabin quickly transformed into Ara-G, and then, as a result of phosphorylation produced its 5-monophosphate and further - ara-guanosine triphosphate (ara-GTP). As a result of accumulation of ara-GTP in the blast cells in leukemia, he concurrently embedded in the DNA chain, causing inhibition of DNA synthesis and consequently cell death. In vitro it was shown that T-cells are more sensitive to cytotoxic effects nelarabina compared with B cells.

Pharmacokinetics

Suction

Cmax ara-G plasma levels achieved at the end of infusion nelarabina and on average, higher than the Cmax nelarabina, which involves rapid and intense transformation of the prodrug in medicine. After a two-hour infusion at a dose of nelarabina 1500 mg/m2 adult patients with average Cmax nelarabina and ara-G were 13.9 micromol and 115 micromol, respectively.

AUC nelarabina and ara-G were 5.13 mmol / h and 571 mmol / h, respectively, after infusion of 1500 mg/m2. Cmax for intracellular ara-GTP is achieved through a 3-25 h on the first day of a course of treatment. Mean values of intracellular Cmax and AUC of ara-GTP of 95.6 mmol and 2214 mmol / h for a given dose.

Distribution

Nelarabin and ara-G are characterized by a large Vd. Vd at steady state in adults and children were, respectively, 115 l / m 2 and 89.4 l / m 2. The apparent Vd ara-G is 44.8 l / m 2 and 32.1 l / m 2 in adults and children, respectively.

Linking nelarabina and ara-G to plasma proteins and only slightly less than 25% for both components it does not depend on the concentration in the range up to 600 micromoles. There was no accumulation of any nelarabina nor ara-G, including with the introduction of the scheme-1, 3, 5 day ".

Intracellular concentrations of ara-GTP in lymphoblasts were determined over a long period after the infusion nelarabina. Marked accumulation ara-GTP in the cells after repeated infusions nelarabina scheme "1, 3, 5, with increasing values of Cmax and AUC (0-t) on the third day of treatment by 50% and 30%, respectively, compared with similar indicators for first day of the course.

Metabolism

The main route of biotransformation nelarabina is O-demethylation of adenosine deaminase to form ara-G, further metabolized to guanine. In addition, nelarabin partially hydrolyzed to methylguanine, which then undergoes O-demethylation with the formation of guanine. At the next stage, N-deamination of guanine to form xanthine and its oxidation to uric acid.

Breeding

Nelarabin and ara-G are rapidly cleared from blood plasma, T1 / 2 are, respectively, 30 min and 3 h after infusion at a dose of 1500 mg/m2.

The average clearance nelarabina when administered in doses from 104 to 2900 mg / m 2 in adults and children were, respectively, 138 and 125 l/ch/m2 l/ch/m2 on day 1. The apparent clearance of ara-G is comparable in both age groups and is 9.5 l/ch/m2 adults and 10.8 l/ch/m2 children on day 1.

Nelarabin and ara-G are derived in part by the kidneys. Average number printed by the kidneys is to nelarabina and ara-G, respectively, 5.3% and 23.2% of the administered dose within 24 h after infusion nelarabina on day 1. Renal clearance averaged 16.4 L / h for nelarabina and 4.9 l / h - for ara-G.

Pharmacokinetics in special clinical situations

The main pharmacokinetic parameters in children are similar to those in adults.

No differences in key pharmacokinetic parameters in older patients.

In clinical studies included patients with CC more than 80 ml / min, with impaired renal function Mild (CC 50-80 ml / min) and moderate (creatinine clearance below 50 ml / min) degrees. Mean apparent clearance of ara-G to 7% lower in patients with moderate renal impairment. Differences in efficacy and safety were observed.

For patients with abnormal liver function No data.

Clinical efficacy and safety

Nelarabin demonstrated clinical efficacy at the recommended dose of adult and child patients in two independent clinical studies - CALGB 19801 and COG R9673. In adults with acute T-cell lymphoblastic leukemia or T-cell lymphoma after two or more courses of induction nelarabinom monotherapy resulted in complete remission (PR) in 18% of cases (95% CI: 6-37%) for the duration of complete remission from 15 to 195 + weeks, survival at 1 year was 29%, which confirms the clinical efficacy in this group of patients who had previously conducted an intensive treatment. Close results were obtained in children and patients are not over 21 years old with relapsed or refractory T-cell acute lymphoblastic leukemia or T-cell lymphoma after two or more courses of induction (group 02): monotherapy nelarabinom caused complete remission in 13% (95% CI : 4-27%) for the duration of PR from 4.7 to 36.4 weeks, survival at 1 year was 14%.

In some patients, after two or more ineffective courses of induction, during the period reached on monotherapy nelarabinom complete remission was transplanted blood stem cells. At the time of transplantation duration of complete remission was 1.6-9.3 weeks in children and 6.3-195.4 + weeks in adults. The study PGAA2001 data recovery hematological parameters were obtained from 21 of the 27 patients who after treatment nelarabinom performed transplantation of hematopoietic stem cells. Of these, 20 patients (95%) was confirmed by recovery in neutrophils. The study PGAA2002 data recovery hematological parameters were obtained in 6 of 7 patients who, after therapy nelarabinom performed transplantation of hematopoietic stem cells. In 3 of them (50%) had recovery levels of neutrophils.

In refractory patients, after the inefficient exchange induction therapy nelarabinom secured an impressive rate of complete remission - 18% in adults and children, after two or more previous courses of induction and 44% in children after one year preceding the induction. In addition to the patients who achieved complete remission, one adult patient and in three children with refractory disease achieved complete remission with an optional normalization of hematological parameters.

Indications for use of the drug

Patients with refractory to chemotherapy or relapsed disease:
T-cell acute lymphoblastic leukemia;
T-cell lymphoblastic lymphoma.

Dosing regimen

The course of treatment nelarabinom could only be a specialist with experience in the application of anticancer drugs.

The drug is intended for intravenous infusion in undiluted form.

Adult (16 years and over) the recommended dose of 1500 mg/m2 for 2 h on days 1, 3 and 5 every 21 days.

For children (under 16 years) the recommended dose is 650 mg/m2, iv, for 1 hour, consistently 5 days (days 1-5) every 21 days.

Not enough data to generate specific recommendations to correct dosing regimen in renal impairment (creatinine clearance below 50 ml / min). Given the partial removal of the kidney, requires careful monitoring of clinical condition.

Not enough data to generate specific recommendations to correct dosing regimen for patients with impaired liver function.

Application nelarabina should be discontinued at the first sign of neurotoxicity grade 2 severity or higher on the toxicity criteria of the National Cancer Institute. Increased intervals between dosing may be considered as an alternative for the development of other toxic manifestations, including hematologic toxicity.

Side effect

Safety nelarabina estimated for the general population of patients enrolled in clinical studies. The overall safety assessment was conducted for 103 adults and 84 children enrolled in controlled clinical studies. Most private adverse events: fatigue, gastrointestinal disorders, hematopoietic disorders, disorders of the respiratory system and increase body temperature. Neurotoxicity is dose related.

The incidence of adverse events was classified as follows: very common (≥ 1 / 10), frequently (≥ 1 / 100, <1 / 10), sometimes (≥ 1 / 1000, <1 / 100), rare (≥ 1 / 10 000 , <1 / 1000), very rare (<1 / 10, 000), including individual cases.

Infections and infestations: very often - infections, including sepsis, bacteremia, pneumonia, fungal infections. There are some reports on the development of fatal opportunistic infections. Registered one case of adult progressive multifocal leukoencephalopathy, confirmed by biopsy.

Atram

Release form, composition and packing

Tablets brownish-yellow, interspersed with, the risk of division on one side and engraved with the figure "12" - to another.

1 tab. carvedilol 12.5 mg

Excipients: sucrose, povidone 30, lactose monohydrate 200, colloidal anhydrous silica, sodium croscarmellose, magnesium stearate, iron oxide yellow, iron oxide red.

Tablets brownish-yellow, interspersed with, the risk of division on one side and engraved with the figure "25" - on the other.

1 tab. Carvedilol 25 mg

Excipients: sucrose, povidone 30, lactose monohydrate 200, colloidal anhydrous silica, sodium croscarmellose, magnesium stearate, iron oxide yellow, iron oxide red.

Pill yellow, interspersed with, the risk of dividing on one side and engraved with the figure "6" - on the other.

1 tab. Carvedilol 6.25 mg

Excipients: sucrose, povidone 30, lactose monohydrate 200, colloidal anhydrous silica, sodium croscarmellose, magnesium stearate, iron oxide yellow.

Clinico-pharmacological group

Beta1-, beta2-blocker. Alpha 1-blocker.

Pharmacological action

Carvedilol has a combined non-selective β1-β2-and α1-blocking action. The drug has its own sympathomimetic activity, has membrane stabilizing properties. Due to the blockade of β-adrenergic receptors of the heart may decrease blood pressure, cardiac output and slowed heart rate, carvedilol inhibits the renin-angiotensin-aldosterone system blockade by β-adrenergic receptors of kidneys, causing a decrease in plasma renin activity. Blocking α-adrenergic receptors, the drug can cause increased peripheral vascular disease, thereby reducing systemic vascular resistance.

The combination of β-adrenoceptor blockade and vasodilatation has the following effects: patients with arterial hypertension - blood pressure reduction, in patients with coronary artery disease - antiischemic and antianginal, in patients with left ventricular dysfunction and circulatory failure - beneficial effect on hemodynamic parameters, improves left ventricular ejection fraction and reduces its size.

Pharmacokinetics

Carvedilol is rapidly absorbed from the gastrointestinal tract. Has a high lipophilicity. Cmaxv blood is achieved by 1-1.5 h. T1 / 2 is 6-10 am bound to plasma proteins in the blood of 95-99%. Bioavailability - 24-28%. Food intake did not affect the bioavailability.

Metabolized in the liver to form several active metabolites. 60-75% of the adsorbed drug is metabolized during first passage through the liver. Metabolites have antioxidant and adrenoblokiruyuschee action.

Withdrawal from the body occurs through the gastrointestinal tract. Carvedilol crosses the placental barrier, excreted in breast milk.

If the kidney function pharmacokinetic parameters of carvedilol does not significantly change.

In patients with impaired liver function a systemic bioavailability of carvedilol is increased by reducing the metabolism of the first passage through the liver. When serious liver Carvedilol is contraindicated.

Indications for use of the drug
hypertension (as monotherapy and combination with a diuretic);
Chronic heart failure (as part of combination therapy);
Coronary heart disease;
stable angina.

Dosing regimen

Inside, regardless of the meal.

Arterial hypertension

The initial dose of 6.25-12.5 mg 1 time in the first 2 days of treatment. Then - 25 mg 1 time / When failure of antihypertensive effect after 2 weeks of therapy, the dose may be increased by a factor of 2. The maximum recommended daily dose is 50 mg 1 time (possibly divided into 2 doses).

Coronary artery disease

The initial dose of 12.5 mg of 2 in the first 2 days of treatment. Then - 25 mg of 2 When failure antianginal effect after 2 weeks of therapy, the dose may be increased by a factor of 2. The maximum recommended daily dose is 100 mg divided into 2 doses.

Chronic heart failure

Dose choose individually, under the close supervision of a physician. The recommended starting dose is 3.125 mg, 2 for 2 weeks. Good tolerability of dose increased at intervals of not less than 2 weeks to 6.25 mg of 2, then - up to 12.5 mg of 2, then - up to 25 mg of 2 dose should be increased to the maximum, which is well tolerated by patients. In patients weighing less than 85 kg target dose is 50 mg, in patients weighing over 85 kg target dose - 75-100 mg /

Side effect
CNS and peripheral nervous system: dizziness, headache (usually not severe and early treatment), loss of consciousness, myasthenia gravis (usually at the beginning of treatment), fatigue, depression, sleep disturbance, paresthesia.
Cardio-vascular system: bradycardia, orthostatic hypotension, AV-block ll-III degree, rarely - a violation of the peripheral circulation, the progression of heart failure (in the period increased doses), edema of the lower extremities, angina, marked reduction in blood pressure.
From the digestive system: dry mouth, nausea, diarrhea or constipation, vomiting, abdominal pain, anorexia, elevation of liver transaminases.
From the hematopoietic system: rarely - thrombocytopenia, leukopenia.
From a metabolism: weight gain, impaired carbohydrate metabolism.

Allergic reactions: allergic skin reactions, exacerbation of psoriasis, a stuffy nose.
With the respiratory system: dyspnea, and bronchospasm (in predisposed patients).

Other: blurred vision, reduced tearing, influenza-like syndrome, sneezing, myalgia, arthralgia, pain in the limbs, intermittent claudication, rarely - a violation of urination, impaired renal function.

Contraindications to the use of the drug
acute and chronic heart failure (in the decompensation stage);
severe hepatic impairment;
AV-block ll-lll degree;
marked bradycardia (less than 50 beats / min);
sick sinus syndrome;
hypotension (systolic blood pressure <85 mmHg. cent.);
cardiogenic shock;
chronic obstructive pulmonary disease;
age of 18 years (the efficacy and safety have not been established);
Hypersensitivity to carvedilol or other ingredients.

Precautions: Prinzmetal angina, thyrotoxicosis, peripheral vascular occlusive disease, pheochromocytoma, psoriasis, kidney failure, AV-block I degree, extensive surgery and general anesthesia, diabetes, hypoglycemia, depression, myasthenia gravis.

Pregnancy and lactation

Controlled trial of carvedilol in pregnant women has been conducted, so the drug in such patients is only possible in cases where the benefits to the mother outweighs the potential risk to the fetus.

Not recommended for breast-feeding during treatment with carvedilol.

Use in hepatic dysfunction

Contraindications: severe hepatic impairment.

Use in renal impairment

Precautions: renal impairment.

Cautions

Therapy should be prolonged and should not be abruptly stopped, especially in patients with CHD, as this may lead to a worsening of the underlying disease. If necessary, reduction in dose should be gradual, over 1-2 weeks.

At the beginning of carvedilol therapy, or at higher doses in patients, especially elderly, may show excessive BP reduction, mainly on rising. Necessary correction doses. In patients with chronic heart failure in the selection of the dose may increase the symptoms of heart failure, the appearance of edema. One should not increase the dose Atrama, recommended the appointment of high doses of diuretics until the stabilization of the patient.

Recommended constant monitoring of ECG and blood pressure while appointing Atrama and slow calcium channel blockers, derivatives fenilalkilamina (verapamil) and benzodiazepines (diltiazem), as well - with class I antiarrhythmics.

Recommended to monitor renal function in patients with chronic renal failure, hypotension and congestive heart failure. In the case of surgery using general anesthesia, the anesthesiologist should be warned about previous treatment with carvedilol.

Atram not affect the concentration of glucose in the blood and causes no changes in indicators glucose tolerance test in patients with insulin-dependent diabetes mellitus.

During treatment avoid using ethanol.