Protub-5 (Protub-5)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceLomefloxacin + Pyrazinamide + Prothionamide + Etambutol + PyridoxineLomefloxacin + Pyrazinamide + Prothionamide + Etambutol + Pyridoxine
Similar drugsTo uncover
  • Prothiocomb®
    pills inwards 
    AKRIKHIN HFK, JSC     Russia
  • Protub-5
    pills inwards 
    FARMASINTEZ, JSC (Irkutsk)     Russia
    • Dosage form: & nbspFilm-coated tablets.
    Composition:Each film-coated tablet contains:
    Active substances:

    Lomefloxacin

    - 200 mg

    - 200 mg

    hydrochloride in terms of



    lomefloxacin



    Pyrazinamide

    400 mg

    - 370 mg

    Prothionamide

    - 188 mg

    - 150 mg

    Ethambutol hydrochloride

    360 mg

    - 325 mg

    Pyridoxine hydrochloride

    - 20 mg

    - 20 mg
    Excipients.
    Core:     lactose (milky sugar), medium molecular weight polyvinyl pyrrolidone (povidone, kollidon 25), microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch (primogel), magnesium stearate, magnesium hydrosilicate (talc), aerosil (colloidal silicon dioxide), crosspovidone (collidine CL).
    Sheath: hydroxypropylmethylcellulose 15 (hypromelose E15), hydroxypropylmethylcellulose 5 (hypromelose E5), propylene glycol, macrogol 6000 (polyethylene glycol 6000), magnesium hydrosilicate (talc), titanium dioxide, iron dye oxide yellow, iron oxide red dye.
    Description:Tablets containing 200 mg of lomefloxacin, 400 mg of niazinamide, 188 mg of protionamide, 360 mg of ethameuol hydrochloride and 20 mg of pyridoxine hydrochloride are red-brown in color, capsular, with a risk on one side.On the cross-section the tablet is yellow. Tablets containing 200 mg of Lomefloxacin,; 70 mg of pyrazinamide, 150 mg of protionamide, 325 mg of ethambutol hydrochloride and 20 mg of pyridoxine hydrochloride: yellow, capsular, with a risk on one side. On the cross-section the tablet is yellow.
    Pharmacotherapeutic group:Antituberculous combined agent.
    ATX: & nbsp

    J.04.A.M   Combinations of antituberculous drugs

    Pharmacodynamics:Combined anti-tuberculosis drug.
    Lomefloxacin. Antimicrobial bactericide of broad spectrum of action from the group of fluoroquinolones. Affects the bacterial enzyme DNA-gyrase, which provides supercoiling, forms a complex with its tetramer (subunit of gyrase A2B2) and disrupts transcription and replication of DNA, leads to the death of the microbial cell. Beta-lactamases, produced by pathogens, do not affect the activity of lomefloxacin. Highly active against gram-negative aerobic microorganisms: Neisseria gonorrhoeae, Neisseria meningitidis, Escherichia coli, Citrobacter diversus, Klebsiella pneumoniae, Enterobacter cloacae, Proteus vulgaris, Salmonella spp., Shigella spp., Moraxella catarrhalis, Morganella morganii, Haemophilus influenzae and parainfmenzae, Legionella pneumophila , Pseudomonas aeruginosa. Moderately sensitive to the drug Staphylococcus aureus, Staphylococcus epidermidis, Serratia liguifaciens and marcescens, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Chlamydia trachomatis, Hafnia alvei, Citrobacter freundii, Aeromonas hydrophila, Proteus mirabilis and Proteus stuartii, Providencia rettgeri and Providencia alcalifaciens, Klebsiella oxytoca, Klebsiella ozaenae , Enterobacter aerogenes, Enterobacter agglomerans.Resistant to the drug Streptococcus spp., Pseudomonas cepacia, Ureaplasma urealyticum, Treponema pallidum, Mycoplasma hominis and anaerobic bacteria. It acts on both extracellular and intracellularly located Mycobacterium tuberculosis, shortens the time of their isolation from the body, provides a faster resolution of infiltrates. Most microorganisms act at low concentrations (the concentration necessary to control the growth of 90% of strains, usually not more than 1 μg / ml). Resistance is rare.
    Pyrazinamide. Pyrazinamide has a bactericidal action at acidic pH values. Well penetrates into the tuberculosis foci. Its activity is high in caseous-necrotic processes, caseous lymphadenitis, tuberculomas. It is subjected to enzymatic conversion into the active form - pyrazinic acid. At acidic pH values, the minimum inhibitory concentration of pyrazinamide in vitro is 20 mg / l. On non-tuberculosis pathogens does not work.
    Prothionamide. It blocks the synthesis of mycolic acids, which are an important structural component of the Mycobacterium tuberculosis cell wall, a nicotinic acid antagonist. In high concentrations, bactericidal disruption of the protein synthesis of the microbial cell acts.Effective against mycobacteria resistant to anti-tuberculosis drugs of the first series. Affects both extracellular and intracellularly located mycobacteria. It is not very active against mycobacteria of bovine tuberculosis, atypical mycobacteria and acid-resistant saprophytes (the minimum suppressing concentration is 20-30 μg / ml). The pathogenic nonspecific flora does not work. Penetrates into cells, in particular macrophages. Has a bactericidal effect in an acidic environment. The development of resistance of mycobacterium tuberculosis to protionamide with monotherapy develops rapidly (at 2 months in 32%, 4 months in 82%). With combined therapy, resistance can develop by 6 months (up to 15%).
    Ethambutol. Bacteriostatic drug, effective against typical and atypical mycobacteria tuberculosis. The mechanism of action of the drug is associated with a violation of the synthesis of RNA in bacterial cells, it suppresses the synthesis of the cell wall, blocking the inclusion of mycolic acids in it. Ethambutol Active against rapidly and slowly growing atypical mycobacteria. The minimum concentration of ethambutol is 0.78-2.0 mg / l.On non-tubercular pathogens ethambutol It does not work.
    Pyridoxine. Vitamin product. Participates in the metabolism. It is necessary for the normal functioning of the central and peripheral nervous system. With tuberculosis infection, there is a deficiency of pyridoxine. With the simultaneous administration of pyridoxine inwards with lomefloxacin, pyrazinamide and ethambutol, no interaction of these drugs is observed at the pharmacokinetic and microbiological levels. Reduces the neurotoxicity of anti-tuberculosis drugs.
    Pharmacokinetics:Lomefloxacin. The active components that make up Proteb-5, do not affect the rate of absorption of Lomefloxacin from the gastrointestinal tract. Bioavailability of Lomefloxacin is more than 90%. The drug after intake is rapidly absorbed from the gastrointestinal tract. The maximum concentration is 5.1 mg / l, the time to reach is 1-1.5 hours. The body circulates for a long time: the half-life is 8-9 hours. The connection with blood proteins is insignificant - 10%. It penetrates well into various organs and tissues, where concentrations are created that are 9-13 times higher than serum concentrations.In small amounts, biotransfrmtsiya in the liver is exposed with the formation of 5 metabolites, which have little antimicrobial activity. In 80% is excreted by the kidneys, in 20% with feces, then with saliva. Hepatic failure does not affect the biotransformation of lomefloxacin.
    Pyrazinamide. Quickly and completely absorbed in the gastrointestinal tract. The connection with plasma proteins is 10-20%. TCmax - 1-2 hours. It penetrates well into tissues and organs.
    Metabolised in the liver, where the active metabolite-pyrazinic acid is first formed, which later becomes an inactive metabolite-5-hydroxypyrazinic acid. T1/2 - 8-9 hours.
    It is excreted by the kidneys: unchanged, 3%, pyrazinic acid 33%, other metabolites 36%. It escapes with hemodialysis.
    Prothionamide. Absorption in the gastrointestinal tract is rapid. TCmax - 2-3 hours. Easily penetrates into healthy and pathologically altered tissues (tubercular foci, caverns in the lungs, serous and purulent pleural effusion, spinal fluid with meningitis).
    Metabolised in the liver (one of the metabolites - sulfoxide, has tuberculostatic activity).It is excreted by the kidneys and with bile (15-20% unchanged).
    Ethambutol. Absorption is high; bioavailability is 75-80%. After oral administration of a dose of 25 mg TCmax - 2-4 hours, the maximum concentration of the drug in the blood Cmax - 1-5 μg / ml. Connection with plasma proteins - 20-30%.
    It penetrates well into tissues and organs, as well as into biological fluids, with the exception of ascitic and pleural (in spinal fluid only with meningitis). The greatest concentrations are created in the kidneys, lungs, saliva, urine. Penetrates into breast milk. Do not pass through the intact blood-brain barrier.
    Partially metabolized in the liver (15%) with the formation of inactive metabolites. T1/2 - 3-4 hours, with renal dysfunction -8 hours. It is excreted by the kidneys - 80-90% (50% - unchanged, 15% - in the form of inactive metabolites) and with the calves - 10-20% (unchanged ). It is excreted in hemodialysis and peritoneal dialysis.
    Pyridoxine. Absorbed rapidly throughout the small intestine, a larger amount is absorbed in the jejunum. Metabolised in the liver with the formation of pharmacologically active metabolites (pyridoxal phosphate and pyridoxamine phosphate). Pyridoxal phosphate with plasma proteins binds to 90%.It penetrates well into all tissues; accumulates mainly in the liver, less - in the muscles and central nervous system. Penetrates through the placenta, is secreted with breast milk. The half-life is 15-20 days. It is excreted by the kidneys.
    Indications:- drug-resistant tuberculosis with moderate resistance of mycobacterium tuberculosis (isoniazid - to 10, rifampicin - up to 40, ethambutol - up to 2 μg / ml,).
    - acutely progressive course of tuberculosis;
    - tuberculosis with concomitant inflammatory diseases caused by non-specific pathogenic flora, sensitive to lomefloxacin.
    Contraindications:- hypersensitivity to lomefloxacin, protionamide gshrazinamide, ethambutol, pyridoxine;
    - pregnancy, lactation period;
    - Children's age under 18 years (the period of formation and growth of the skeleton).
    - Stomach ulcer and 12 duodenal ulcer;
    - ulcerative colitis;
    - Acute hepatitis, cirrhosis of the liver;
    - diseases of the central nervous system (epilepsy and other diseases with a tendency to convulsive seizures);
    - Diseases of the organs of vision (inflammation of the optic nerve, cataracts, diabetic retinopathy, inflammatory diseases of the eyes);
    - kidney failure;
    - gouty arthritis;
    - Thrombophlebitis.
    Dosing and Administration:Inside.The drug is taken 1 time per day after meals with a full glass of water, preferably in the morning. Dosage is carried out by lomefloxacin - 13.2 mg / kg, but not more than 5 tablets. The course of treatment - 3 months. If necessary, it can be combined with streptomycin or kanamycim IM / m - 16 mg / kg 1 time per day for 3 months.
    Side effects:Lomefloxacin
    From the digestive system: nausea, vomiting, dry mouth, gastralgia, abdominal pain, diarrhea or constipation, flatulence, pseudomembranous enterocolitis, dysphagia, discoloration of the tongue, loss of appetite or bulimia, taste distortion, dysbiosis, increased activity of "liver" transaminases (alanine aminotransferase (ALT) ), aspartate aminotransferase (ACT), alkaline phosphatase).
    From the nervous system: fatigue, malaise, asthenia, headache, dizziness, fainting, insomnia, hallucinations, convulsions, hyperkinesia, tremor, paresthesia, nervousness, anxiety, depression, agitation.
    From the genitourinary system: glomerulonephritis, dysuria, polyuria, anuria, albuminuria, urethral bleeding, crystalluria, hematuria, urinary retention,edema; in women - vaginitis, leukorrhea, intermenstrual bleeding, pain in the perineum, vaginal candidiasis; in men - orchitis, epididymitis.
    From the side of metabolism: hypoglycemia, gout.
    From the musculoskeletal system: arthralgia, vasculitis, calf muscle cramps, pain in the back and chest.
    On the part of the organs of hematopoiesis and the system of hemostasis: bleeding from the digestive tract, thrombocytopenia, purpura, increased fibrinolysis, epistaxis, lymphadenopathy.
    From the respiratory system: dyspnoea, respiratory infections, bronchospasm, cough, hypersecretion of sputum, flu-like symptoms.
    From the sense organs: impaired vision, pain and noise in the ears, pain in the eyes.
    From the cardiovascular system: lowering of blood pressure, tachycardia, bradycardia, extrasystole, arrhythmias, progression of heart failure and angina pectoris, pulmonary embolism, myocardiopathy, phlebitis.
    Allergic reactions: skin itching, hives, photosensitivity, malignant exudative erythema (Stevens-Johnson syndrome).
    Influence on the fetus: the experiment described fetotoxic action (arthropathy).
    Other: Candidiasis, increased sweating, chills, thirst, superinfection.
    Pyrazinamide
    From the digestive system - nausea, vomiting, diarrhea, "metallic" taste in the mouth, impaired liver function (decreased appetite, liver tenderness, hepatomegaly, jaundice, yellow atrophy of the liver); exacerbation of peptic ulcer.
    From the nervous system: dizziness, headache, sleep disorders, increased excitability, depression. In some cases - hallucinations, convulsions, confusion.
    On the part of the organs of hematopoiesis and the system of hemostasis: thrombocytopenia, sideroblastic anemia, erythrocyte vacuolization, porphyria, hypercoagulation, splenomegaly.
    From the musculoskeletal system: arthralgia, myalgia.
    From the urinary system: dysuria, interstitial nephritis.
    Allergic reactions: skin rash, hives.
    Other: hyperthermia, acne, hyperuricemia, exacerbation of gout, photosensitivity, increased serum iron concentration.
    Prothionamide
    From the digestive system - nausea ,. vomiting, diarrhea, hypersalivation, "metallic" taste in the mouth, impaired liver function.
    From the nervous system:     insomnia, agitation, depression, anxiety, rarely - dizziness, drowsiness, headache, asthenia, in single cases - paresthesia, peripheral neuropathy, optic neuritis.
    From the cardiovascular system: tachycardia, weakness, orthostatic hypotension.
    From the endocrine system: hypoglycemia in patients with diabetes mellitus, gynecomastia, dysmenorrhea, hypothyroidism, decreased potency.
    Allergic reactions: skin rash.
    Ethambutol
    From the nervous system and sensory organs: weakness, headache, dizziness, impaired consciousness, disorientation, hallucinations, depression, peripheral neuritis (paresthesia in the limbs, numbness, paresis, pruritus), optic neuritis (decreased visual acuity, violation of color perception, mainly green and red, color blindness, scotoma).
    From the digestive system: decreased appetite, nausea, vomiting, gastralgia, impaired liver function - increased activity of "liver" transaminases (ALT, ACT, alkaline phosphatase).
    Allergic reactions: dermatitis, skin rash, itching, arthralgia, fever, anaphylaxis.
    Other: hyperuricemia, exacerbation of gout.
    Pyridoxine
    Allergic reactions, hypersecretion of hydrochloric acid, numbness, the appearance of a feeling of compression in the limbs - a symptom of "stocking" and "gloves", rarely a skin rash, itching of the skin.
    Overdose:Lomefloxacin - Treatment: induction of vomiting or gastric lavage, adequate hydration, symptomatic therapy. Hemo- and peritoneal dialysis with an overdose is ineffective (less than 3% is output).
    Pyrazinamide - Symptoms: a violation of the liver, increased severity of side effects from the central nervous.
    Treatment: symptomatic
    Prothionamide Symptoms: nausea, vomiting. Metallic taste in the mouth; rinse the stomach. There are no specific antidotes.
    Ethambutol - Symptoms: nausea, vomiting, hallucinations, polyneuritis.
    Treatment: symptomatic.
    Interaction:Lomefloxacin together with isoniazid, ethambutol and, especially, pyrazinamide significantly increases antimicrobial activity against sensitive and especially resistant mycobacteria tuberculosis. The combined use of the drug with probenecid slows the excretion of lomefloxacin; with rifampicin leads to a decrease in antimicrobialactivity of this combination against mycobacterium tuberculosis because of the antagonism existing between lomefloxacin and rifampicin at the microbial level. Sucralfate and antacid agents containing magnesium or aluminum ions form chelate-forming complexes with lomefloxacin. The interval between admission should be at least 2 hours before or after taking Lomefloxacin.
    Prothionamide in combination with lomefloxacin significantly increases antimicrobial activity against mycobacteria tuberculosis. Antacids reduce the absorption of protionamide. Reduces the effectiveness of antihypertensive drugs.
    Pyrazinamide increases the concentration of isoniazid in the serum, slowing its excretion. When taking rifampicin together with pyrazinamide, the risk of developing hepatoxic reactions increases. Aluminum hydroxide reduces the absorption of ethambutol. The administration of ethambutol with aminoglycosides, imipenem, carbamazepine, lithium salts, quinine increases the risk of neurotoxic action of the drug, and also increases the antimicrobial activity of other antituberculous drugs. Pyridoxine weakens the action of levodopa when combined.Reduces the risk of toxic effects of antituberculosis drugs on the central and peripheral nervous system. Pyridoxine does not affect the antimicrobial activity of the preparations that make up Protub-5.
    Special instructions:With cirrhosis of the liver, there is no need for correction of the dosing regimen (with normal kidney function).
    During the treatment period, prolonged exposure to sunlight and the use of artificial ultraviolet light should be avoided (evening reception reduces the risk of reaction to ultraviolet radiation). At the first signs of photosensitivity arising from the lomefloxacin (increased skin sensitivity, burn, hyperemia, edema, blistering, rash, itching, dermatitis) or allergic reactions, neurotoxicity (excitation, convulsions, tremor, photophobia, confusion, toxic psychoses, hallucinations) therapy should be discontinued.
    At the beginning of treatment, it is possible to increase cough, increase the amount of sputum. It is necessary to monitor the function of the liver and kidneys every month, the function of the organ of vision, the picture of peripheral blood,activity of alanine aminotransferase (ALT) and the concentration of uric acid in the blood.
    In patients with diabetes, the risk of hypoglycemia increases. When determining urobilinogen using Ehrlich's reagent, the results may be distorted.
    Effect on the ability to drive transp. cf. and fur:During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
    Form release / dosage:Tablets, film-coated 200 mg + 370 mg + 150 mg + 325 mg + 20 mg; 200 mg + 400 mg + 188 mg + 360 mg + 20 mg.
    Packaging:For 100, 500 or 1000 tablets (for hospitals) in a jar of polypropylene or low-density polyethylene, sealed with a lid of polypropylene or high-pressure polyethylene or a can of polyethylene terephthalate for pharmaceuticals with a screw cap or with a control of the first opening. The space free from tablets is filled with cotton absorbent cotton.
    Banks, together with an equal number of instructions for use, are placed in a group package.
    Storage conditions:List B.In a dry, protected from light place, at a temperature of no higher than 25 ° C. Keep away from children.
    Shelf life:2 years. Do not use after the expiration date indicated on the package.
    Terms of leave from pharmacies:For hospitals
    Registration number:LSR-004062/09
    Date of registration:25.05.2009
    The owner of the registration certificate:FARMASINTEZ, JSC (Irkutsk) FARMASINTEZ, JSC (Irkutsk) Russia
    Manufacturer: & nbsp
    Information update date: & nbsp2016-10-18
    Illustrated instructions
      Instructions
      Up