Pentacoke

General characteristics. Structure:

Active ingredient: 150,0 mg of rifapentine.

Excipients: cellulose microcrystallic, starch prezhelatinizirovanny (LM 1500), a hypro rod, edetovy acid, sodium carboxymethylstarch (sodium glikolit starch), sodium lauryl sulfate, ascorbic acid, silicon dioxide colloid (aerosil the A-200 brand), a macrogoal 6000 (PEG-6000), croscarmellose sodium (primelloza), calcium stearate.

Structure of a film cover: ready mix of an inst коат 3370 (gipromelloza, diethyl phthalate, ethyl cellulose, talc, titanium dioxide, dye ferrous oxide red, dye ferrous oxide yellow).

Antitubercular antibiotic of group of Rifamycinum.

Pharmacological properties:

Pharmacodynamics. An antitubercular antibiotic of group of Rifamycinum - tsiklopentilny Rifamycinum. Inhibits a DNA-dependent RNA polymerase of sensitive strains of Mycobacterium tuberculosis, but not in cells of mammals. In therapeutic doses rifapentine shows bactericidal activity concerning the intracellular and extracellular Mycobacterium tuberculosis forms. Rifapentine and its active metabolite (25-dezatsetilrifapentin) collect in human monocytic macrophages with a ratio внутри-/extracellular contents about 24:1 and 7:1 respectively.

There is a cross resistance of strains of Mycobacterium tuberculosis between rifapentine and Rifamycinum. Cross resistance between rifapentine and other antituberculous remedies was not observed.

Pharmacokinetics. After intake in a dose of 600 mg of Cmax of rifapentine in a blood plasma it is reached in 4-6 h. At rifapentine reception by AUC and Cmax greasy food increased for 43% and 44% respectively.

Linkng of rifapentine with proteins of plasma (it is preferential with albumine) makes 97.7%.

Under the influence of esterases it is metabolized about formation of an active metabolite of a 25-dezatsetilrifapentin.

T1/2 makes 13.19±1.38 h. It is removed with a stake (70%) and with urine (17%). Within 7 days 80% of active agent are removed from an organism.

Indications to use:

Treatment of the pulmonary tuberculosis caused by Mycobacterium tuberculosis in a combination from one or more antituberculous remedies.

Route of administration and doses:

Apply only at sensitivity of the activator to this antibiotic.

Rifapentine is intended for intake in a dose of 600 mg 1-2 times week with an interval not less than 3 consecutive days (72 h) in a combination with other antituberculous remedies (этамбуол, Pyrazinamidum, an isoniazid, streptomycin).

Treatment is carried out according to the special scheme consisting of an initial phase of therapy lasting 2 months and the subsequent phase, lasting 4 months. The choice of an antituberculous remedy is made for a combination on the basis of definition of sensitivity of the activator. Efficiency of rifapentine in a combination with Ethambutolum, Pyrazinamidum, an isoniazid or streptomycin is shown.

Treatment is carried out under strict clinical control.

Features of use:

Adequate and strictly controlled researches of safety of use of rifapentine at pregnancy and in the period of a lactation (breastfeeding) were not conducted.

It is unknown whether rifapentine with breast milk at the person is emitted. It must be kept in mind that against the background of drug use breast milk can get reddish-orange coloring. In need of use of rifapentine in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

In pilot studies it is shown that rifapentine has embriofetotoksichesky effect at animals.

Use at renal failures. At patients with the diseases or states contributing to development of a neuropathy (including a renal failure) in order to avoid development of a peripheral neuropathy it is necessary to apply a pyridoxine (B6 vitamin) at the same time.

Use for children. Safety and efficiency of rifapentine at patients are younger than 12 years is not studied.

Use for elderly patients. With care to apply at patients of advanced age, considering possible deterioration in function of a liver, kidneys, cardiovascular system, existence of associated diseases and simultaneous use of other medicines.

It is not necessary to apply as weekly long therapy (within 4 months) in a combination with an isoniazid at HIV-seropositive patients with a pulmonary tuberculosis because of higher degree of inefficiency of treatment and/or development of a recurrence of tuberculosis at presence Rifampinum - resistant strains.

Rifapentine is not studied as a part of initial therapy (within 2 months) at HIV-seropositive patients with a pulmonary tuberculosis.

It is not necessary to apply rifapentine as monotherapy.

With care it is necessary to apply rifapentine at patients with a cavernous pulmonary tuberculosis and/or existence of the activator in a phlegm after an initial phase of therapy or in the presence of bilateral damage of lungs, in connection with higher risk of a recurrence.

At the HIV-seropositive patients receiving therapy by rifapentine in a long phase of treatment (within 4 months), higher frequency of a recurrence of tuberculosis is observed. Risk factor of a recurrence is existence, along with damage of lungs, extra pulmonary tuberculosis, the low level of CD4 cells, use of antifungal means of derivatives of an azol and younger age of the patient.

It is impossible to exclude emergence of a hyperbilirubinemia owing to the competition for ways of removal between rifapentine and bilirubin since between Rifampinum and bilirubin this competition is observed. During treatment it is necessary to control bilirubin level in blood.

At patients with the diseases or states contributing to development of a neuropathy (including deficit of food, HIV infection, a renal failure, alcoholism, and also pregnancy and the period of breastfeeding) in order to avoid development of a peripheral neuropathy it is necessary to apply a pyridoxine (B6 vitamin) at the same time.

Against the background of rifapentine use perhaps preferential red-orange coloring of fabrics and/or liquids of an organism (for example, skin, teeth, language, urine, calla, saliva, phlegm, tears, sweat, cerebrospinal fluid).

It is not necessary to apply rifapentine at patients with a porphyria, considering that Rifampinum causes an exacerbation of this disease.

In case of development against the background of treatment of diarrheas, the caused Clostridium difficile should begin the corresponding therapy immediately.

With care to apply at patients of advanced age, considering possible deterioration in function of a liver, kidneys, cardiovascular system, existence of associated diseases and simultaneous use of other medicines.

Safety and efficiency of rifapentine at patients are younger than 12 years is not studied.

Side effects:

The listed reactions were observed at use of rifapentine as a part of a combination therapy.

From an urinary system: pyuria, proteinuria, hamaturia, infections of urinary tract, urine incontience episodes, cystitis, urethra diseases, pyelonephritis.

From a metabolism: hyperuricemia, hyperpotassemia, hypoglycemia, increase in content of nonprotein nitrogen, hyperglycemia, increase in contents LDG, hyperphosphatemia, body degrowth, increase in content of residual nitrogen of urea, diabetes mellitus, increase in activity ShchF, hypophosphatemia, hypercalcemia, hypovolemia, increase in body weight, porphyria.

From system of a hemopoiesis: anemia, lymphopenia, neutropenia, leukocytosis, neutrophilia, thrombocytosis, thrombocytopenia, polycythemia, lymphadenopathy, lymphocytosis, hematoma, hematoma, purpura, thrombosis.

From an organism in general: dorsodynias, all body pains, stethalgia, traumatism, abdominal pains, fever, weakness, tendency to puffiness, adynamy, abscesses.

Dermatological reactions: rash, increase in sweating, itch, acne, skin diseases, makulo-papular rash, eczema, skin cankers, small tortoiseshell, xeroderma, furunculosis, disturbance of a xanthopathy, fungal dermatitis, diseases of nails, erythematic rash, alopecia.

From respiratory system: pneumorrhagia, cough, upper respiratory tract infections, bronchitis, pharyngitis, short wind, pleurisy, loud breath, pheumothorax, pneumonia, rhinitis, диспноэ, pleural exudate, pneumonitis, sinusitis, increase in quantity of a phlegm, pulmonary fibrosis, stagnation of upper respiratory tracts, asthma, bronchospasm, throat hypostasis.

From the alimentary system: anorexia, dyspepsia, vomiting, nausea, a lock, diarrhea, hemorrhoids, increase in activity of ALT and nuclear heating plant, a gastroenteritis, gastritis, an esophagitis, a cheilitis, an aggravation of symptoms of teeth, pancreatitis, a proctitis, increase in volume of sialadens, tenesmus, nonspecific gastrointestinal disturbances, a bilirubinemia, a hepatomegalia, jaundice, a hepatotoxic, a hyperbilirubinemia, a porphyria, the diarrhea caused by Clostridium difficile.

Infections: flu, tubercular infection, other infections, shingles, infection with parasites and protozoa.

From TsNS: sleeplessness, drowsiness, nonspecific spasms, dysphonia, hypesthesia, wryneck, hyporeflexia, meningitis, stupor, migraine, alarm, consciousness disturbance, stupor.

From a musculoskeletal system: arthralgia, arthritis, arthrosis, gout, mialgiya, miositis, fracture of bones, muscular weakness, muscular spasm.

From cardiovascular system: arterial hypertension, syncope, tachycardia, palpitation, orthostatic hypotension, pericardis, thrombophlebitis of deep veins, vascular disorders, vazodilatation.

From reproductive system: penis diseases, a vaginitis, vulval bleeding, a leukorrhea, mastitis of chest gland at men, prostate diseases.

From sense bodys: conjunctivitis, nonspecific hearing disorder, average otitis, ear pains, outside otitis, perforation of a tympanic membrane, eye pain, eye disturbances, loss of flavoring feelings.

Malignant new growths: pulmonary carcinoma, nonspecific neoplasm, carcinoma, lipoma.

Others: discoloration of fluid mediums of an organism.

Interaction with other medicines:

Rifapentine – the inductor of isoenzymes of P450 cytochrome therefore at simultaneous use with the drugs which are metabolized this fermental system such as protease inhibitors, inhibitors of the return transcriptase, can cause considerable reduction of concentration of these drugs in a blood plasma and loss of their therapeutic effect.

Rifapentine is capable to reduce efficiency of hormonal contraceptives (during treatment patients have to apply well-tried remedies of non-hormonal contraception).

Rifapentine is the inductor of isoenzymes of CYP3A4 and CYP2C8/9 therefore at simultaneous use with medicines, the metabolized these isoenzymes, strengthening of their metabolism is possible. The induction of isoenzymes caused by rifapentine is observed during 4 days after reception of the first dose and is returned to initial level in 14 days after rifapentine cancellation. Besides, extent of induction of enzymes rifapentine depends on its dose and frequency of use: less expressed activity is observed at a peroral dose of 600 mg with an interval of 72 h, in comparison with daily reception.

At simultaneous use with rifapentine dose adjustment of the following medicines which are metabolized with the participation of isoenzymes of CYP3A4 and CYP2C8/9 can be required: warfarin, Phenytoinum, quinidine, флуконазол, итраконазол, кетоконазол, a haloperidol, phenobarbital, diazepam, propranolol, diltiazem, nifedipine, verapamil, digoxin, Prednisonum, Clofibratum, hypoglycemic means derivative sulphonylurea, ethinylestradiol, levonorgestrel, cyclosporine, такролимус, theophylline, methadone, sildenafit, left thyroxine, amitriptyline, нортриптилин.

Contraindications:

Hypersensitivity to rifapentine and other antibiotics of group of Rifamycinum.

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children

Issue conditions:

According to the recipe

Packaging:

30 pieces - plastic bags (1) low density - banks.
50 pieces - plastic bags (1) low density - banks.
100 pieces - plastic bags (1) low density - banks.