Clinical and pharmacological group: & nbsp

Ansamycins

Included in the formulation
  • Pentacox®
    pills inwards 
  • Ripafex
    pills inwards 
    Lupine Co., Ltd.     India
  • АТХ:

    J.04.A.B   Antibiotics

    J.04.A.B.05   Rifapentin

    Pharmacodynamics:

    Anti-tuberculosis antibiotic of the rifamycin group. In therapeutic doses rifapentin shows bactericidal activity against intracellular and extracellular forms of Mycobacterium tuberculosis.

    Pharmacokinetics:

    After oral administration in a dose of 600 mg Cmax, rifapentin in blood plasma is reached after 4-6 hours. With the intake of rifapentin with fatty foods, AUC and Cmax increased by 43% and 44%, respectively.

    The binding of rifapentin to plasma proteins (mainly with albumins) is 97.7%. The half-life is 13.19 ± 1.38 hours. It is excreted with feces (70%) and with urine (17%). Within 7 days, 80% of the active substance is excreted from the body.

    Indications:

    Treatment of pulmonary tuberculosis caused by Mycobacterium tuberculosis in combination with one or more anti-tuberculosis drugs.

    I.A15-A19.A15   Tuberculosis of respiratory organs, confirmed bacteriologically and histologically

    Contraindications:

    Hypersensitivity to rifamycins

    Diseases of the liver and gastrointestinal tract

    Pregnancy, lactation

    Thrombophlebitis

    Children under 12 years old

    Carefully:

    Use with caution in elderly patients, given the possible worsening of the function of the liver, kidneys, cardiovascular system,the presence of concomitant diseases and simultaneous use of other drugs. With the carrier of hepatitis B and C.

    Pregnancy and lactation:

    FDA recommendation category X.

    Contraindicated during pregnancy and lactation.

    Dosing and Administration:

    Rifapentin is intended for admission inwards in a dose of 600 mg 1-2 times a week with an interval of at least 3 consecutive days (72 hours) in combination with other antituberculous agents (ethambutol, pyrazinamide, isoniazid, streptomycin).

    Treatment is carried out according to a special scheme consisting of an initial phase of therapy, lasting 2 months and a subsequent phase, lasting 4 months. The choice of an antituberculous agent for a combination is based on the sensitivity of the pathogen. The effectiveness of rifapentin in combination with ethambutol, pyrazinamide, isoniazid or streptomycin is shown.

    Treatment is carried out under strict clinical control.

    Side effects:

    From the urinary system: pyuria, proteinuria, hematuria, urinary tract infections, incontinence episodes, cystitis, urethral diseases, pyelonephritis.

    From the side of metabolism: Hyperglycemia, hyperkalemia, hypoglycemia, increase in the content of non-protein nitrogen, hyperglycemia, increased LDH, hyperphosphatemia, weight loss, increased residual urea nitrogen, diabetes mellitus, increased activity of AP, hypophosphatemia, hypercalcemia, hypovolemia, weight gain, porphyria.

    On the part of the hematopoiesis system: anemia, lymphopenia, neutropenia, leukocytosis, neutrophilia, thrombocytosis, thrombocytopenia, polycythemia, lymphadenopathy, lymphocytosis, hematoma, purpura, thrombosis.

    On the part of the body as a whole: pain in the back, pain all over the body, chest pain, trauma, abdominal pain, fever, weakness, propensity for puffiness, asthenia, abscesses.

    Dermatological reactions: rash, increased sweating, itching, acne, skin diseases, maculopapular rash, eczema, ulcerative skin lesions, urticaria, dry skin, furunculosis, skin pigmentation disorder, fungal dermatitis, nail diseases, erythematous rash, alopecia.

    From the respiratory system: hemoptysis, cough, upper respiratory tract infections, bronchitis, pharyngitis, dyspnea, pleurisy, loud breathing, pneumothorax, pneumonia,rhinitis, dyspnea, pleural effusion, pneumonia, sinusitis, increasing the amount of sputum, pulmonary fibrosis, upper airway congestion, asthma, bronchospasm, laryngeal edema.

    From the digestive system: anorexia, dyspepsia, vomiting, nausea, constipation, diarrhea, hemorrhoids, increased activity of ALT and AST, gastroenteritis, gastritis, esophagitis, cheilitis, the deterioration of the teeth, pancreatitis, proctitis, an increase in the salivary glands, tenesmus, nonspecific gastrointestinal symptoms, bilirubinemia , hepatomegaly, jaundice, hepatotoxicity, hyperbilirubinemia, porphyria, diarrhea due to Clostridium difficile.

    Infections: influenza, tuberculosis infection, other infections, shingles, infection with parasites and protozoa.

    From the side of the central nervous system: insomnia, drowsiness, convulsions nonspecific, dysphonia, hypoesthesia, torticollis, hyporeflexia, meningitis, stupor, headache, anxiety, impaired consciousness, stupor.

    From the musculoskeletal system: arthralgia, arthritis, arthrosis, gout, myalgia, myositis, fracture of bones, muscle weakness, muscle spasm.

    From the cardiovascular system: arterial hypertension, syncope, tachycardia, palpitation, orthostatic hypotension, pericarditis, deep vein thrombophlebitis, vascular disorders, vasodilation.

    On the part of the reproductive system: diseases of the penis, vaginitis, vaginal bleeding, leukorrhea, mastitis of the breast in men, prostate disease.

    From the sense organs: conjunctivitis, nonspecific hearing disorders, otitis media, ear pain, otitis externa, perforation of the tympanic membrane, eye pain, eye disorders, loss of taste sensations.

    Malignant neoplasms: pulmonary carcinoma, nonspecific neoplasm, carcinoma, lipoma.

    Other: change in the color of body fluids.

    Overdose:No data.
    Interaction:

    Rifapentin is the inducer of cytochrome P450 isoenzymes, so when used concurrently with drugs metabolized by this enzyme system, such as protease inhibitors, reverse transcriptase inhibitors, can cause a significant decrease in the concentration of these drugs in the blood plasma and the loss of their therapeutic effect.

    Rifapentin can reduce the effectiveness of hormonal contraceptives (during treatment, patients should use reliable non-hormonal contraception).

    Rifapentin is an inducer of the isoenzymes CYP3A4 and CYP2C8 / 9, so when used simultaneously with drugs metabolized by these isoenzymes, it is possible to increase their metabolism. Induction of isoenzymes caused by rifapentin is observed for 4 days after the first dose and returns to the baseline level 14 days after rifapentin cancellation. In addition, the degree of induction of enzymes rifapentin depends on its dose and frequency of use: less pronounced activity is observed at an oral dose of 600 mg at an interval of 72 hours, compared with daily intake.

    When used simultaneously with rifapentin, dose adjustment of the following drugs metabolized with the participation of CYP3A4 and CYP2C8 / 9 isoenzymes may be required: warfarin, phenytoin, quinidine, fluconazole, itraconazole, ketoconazole, haloperidol, phenobarbital, diazepam, propranolol, diltiazem, nifedipine, verapamil, digoxin, prednisone, clofibrate, hypoglycemic agents (sulfonylureas derivatives), ethinyl estradiol, levonorgestrel, ciclosporin, tacrolimus, theophylline, methadone, sildenafil, levothyroxine, amitriptyline, nortriptyline.

    Special instructions:

    Should not be used as a weekly prolonged therapy (4 months) in combination with isoniazid in HIV-seropositive patients with pulmonary tuberculosis because of higher degree of treatment failure and / or recurrence of tuberculosis in the presence of rifampin-resistant strains.

    Rifapentin has not been studied as part of the initial therapy (within 2 months) in HIV-seropositive patients with pulmonary tuberculosis.

    Do not use rifapentin as a monotherapy.

    Caution should be applied rifapentin cavernous patients with pulmonary tuberculosis and / or presence of agent in the sputum after the initial treatment phase, or in the presence of bilateral lung damage due to a high risk of relapse.

    In HIV seropositive patients receiving rifapentin therapy in the long-term phase of treatment (within 4 months), there is a higher incidence of tuberculosis recurrence. Factor in the risk of relapse is the presence, along with damage to the lungs, extrapulmonary tuberculosis, the low level of CD4-cells, the use of antifungal azole derivative and the younger age of the patient.

    It is impossible to exclude the appearance of hyperbilirubinemia due to competition for the way of excretion between rifapentin and bilirubin. between rifampin and bilirubin this competition is observed. During the treatment period, the level of bilirubin in the blood should be monitored.

    In patients with diseases or conditions predisposing to the development of neuropathy (including malnutrition, HIV infection, kidney failure, alcoholism, as well as pregnancy and the period of breastfeeding) in order to avoid the development of peripheral neuropathy should be simultaneously applied pyridoxine (vitamin B6).

    Against the background of rifapentin application, red-orange staining of tissues and / or body fluids (eg, skin, teeth, tongue, urine, feces, saliva, sputum, tears, sweat, cerebrospinal fluid) is possible.

    Do not use rifapentin in patients with porphyria, given that rifampin causes an exacerbation of the disease.

    In case of development against the background of treatment of diarrhea caused by Clostridium difficile, appropriate therapy should be started immediately.

    Use with caution in elderly patients, given the possible worsening of the function of the liver, kidneys, cardiovascular system,the presence of concomitant diseases and simultaneous use of other drugs.

    The safety and efficacy of rifapentin in patients younger than 12 years of age have not been studied.

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