Macox

Makox is an antibiotic with anti-tuberculosis properties.

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Indications Macox

The indication for the use of the drug is the complex treatment of the following diseases:

• tuberculosis of any localization, atypical forms of mycobacteriosis, as well as tuberculous meningitis;
• inflammations and infections of non-tuberculous origin – provoked by pathogens sensitive to the drug (including severe forms of leprosy, legionella infection, as well as staphylococcal infection and Bang's disease);
• asymptomatic carriage of meningococcus - to eliminate it from the nasopharynx, and also as a preventive measure against meningococcal meningitis.

Release form

Available in capsules of 150 or 300 mg. One blister contains 10 capsules. One pack contains 10 blister strips.

Pharmacodynamics

Rifampicin is a semi-synthetic antibiotic, part of the rifamycin group. It is a first-line anti-tuberculosis drug. It has bactericidal properties - it slows down the active activity of RNA polymerase, which depends on DNA. This occurs as a result of creating complexes with it - as a result, the process of RNA synthesis of microbes decreases.

The drug actively affects atypical fungi of various types (except M. fortuitum), gram-positive cocci (these are strepto- and staphylococci), clostridia, and in addition, anthrax bacilli, etc. Cocci from the gram-negative group (these are meningococci and gonococci (among them β-lactamases)) are affected by the drug, but quickly acquire immunity to it.

It has an active effect on hemophilic rods (among them ampicillin with chloramphenicol), Ducrey rods, whooping cough rods, anthrax bacilli, listeria monocytogenes, F. tularensis, legionella pneumophila, rickettsia prowaszekii, and also Hansen's bacillus. Rifampicin has a virucidal effect on the rabies virus, and in addition prevents the development of rabies encephalitis.

Microorganisms of the genus Enterobacteriaceae, as well as gram-negative microbes of the non-fermenting type (such as pseudomonads, acinetobacter, and also Stenothrophomonas spp., etc.) are not sensitive to the drug. It also has no effect on anaerobes.

Pharmacokinetics

Rifampicin is rapidly absorbed from the gastrointestinal tract, and its bioavailability is 95% (when taken on an empty stomach). This indicator decreases when taken with food. Effective concentrations of the drug are formed in saliva, sputum, and in addition to the lungs, eosinophils, peritoneal and pleural exudate of the liver with kidneys. In addition, the active substance penetrates well into cells, as well as through the blood-brain barrier, breast milk and placenta. During the treatment of tuberculous meningitis, it penetrates the spinal cord fluid.

Plasma protein binding is 60-90%, dissolution occurs in lipids. The peak concentration in the blood is reached 2 hours after use on an empty stomach, or 4 hours after eating. The therapeutic concentration of the substance in the body is maintained for approximately 8-12 hours (if microbes have increased sensitivity to it, then 24 hours). The active component can concentrate in the lung tissue and accumulate in the caverns for a long time.

Metabolism occurs in the liver, as a result of this process, active decay products are formed. The half-life is about 3-5 hours. Excretion occurs mainly with urine and bile. A small part is excreted with feces.

Dosing and administration

Rifampicin is taken orally half an hour before meals or 2 hours after meals. It must be washed down with water.

For tuberculosis: for adults, the daily dosage is 8-12 mg/kg. For patients weighing less than 50 kg – 450 mg; for those weighing 50+ kg – 600 mg. For children aged 6-12, the dosage is 10-20 mg/kg, with the maximum permissible daily limit not exceeding 600 mg.

The duration of tuberculosis treatment is determined individually, depending on its effectiveness (it can last 1+ years). To prevent pathogenic microbes from developing resistance to rifampicin, the medicine must be taken together with other first- or second-line anti-tuberculosis drugs (in standard dosage).

Infectious and inflammatory pathologies (non-tuberculous origin), provoked by microorganisms sensitive to the drug - such as brucellosis or legionellosis, as well as severe staphylococcal infections (in combination with another antibiotic to prevent the development of resistant strains): the daily dosage is 900-1200 mg in 2-3 doses (maximum per day - 1200 mg). After eliminating the signs of the disease, the drug should be taken for another 2-3 days.

For leprosy: oral administration (together with immune-stimulating drugs) at a daily dosage of 600 mg in 1-2 doses for 3-6 months (repeated courses can be carried out, making intervals of 1 month). With another scheme (together with combined anti-leprosy treatment), the daily dosage is 450 mg in 3 doses for 2-3 weeks. The treatment course lasts 1-2 years with intervals of 2-3 months.

For meningococci: prescribed for 4 days. For adults – daily dosage is 600 mg, and for children – 10-12 mg/kg.

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Use Macox during pregnancy

The use of the drug during pregnancy is permitted only if there are vital indications, and when the potential benefit to the woman outweighs the development of possible negative consequences for the fetus.

When rifampicin is used in the later stages of pregnancy, the risk of bleeding in the postpartum period increases for both mother and baby.

Contraindications

Among the contraindications:

• intolerance to rifampicin and other components of the drug;
• severe kidney or liver dysfunction;
• jaundice (also mechanical);
• infectious hepatitis suffered less than 1 year ago;
• severe pulmonary heart failure;
• combination with substances such as ritonavir or saquinavir.

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Side effects Macox

Side effects include:

• gastrointestinal tract: vomiting with nausea, diarrhea, loss of appetite, abdominal pain, discomfort, anorexia, erosive gastritis, and in addition pseudomembranous colitis;
• digestive system organs: development of hepatitis or hyperbilirubinemia, and in addition, discomfort in the right hypochondrium and increased activity of liver transaminases;
• skin: rashes and itching, development of urticaria, exfoliative dermatitis, exanthema. In addition, vasculitis, vesicular reaction, malignant exudative, as well as erythema multiforme, and toxic epidermal necrolysis;
• immune reactions: hypersensitivity (including Quincke's edema), anaphylaxis and bronchospasm;
• other: fever, joint pain, severe lacrimation and herpes;
• hematopoietic system: leukopenia, as well as neutropenia and thrombocytopenia (with or without purpura; most often develops as a result of intermittent treatment), hemolytic anemia and eosinophilia. In rare situations, DIC syndrome or agranulocytosis may develop. If the first signs of purpura occur, the drug should be discontinued immediately. This is necessary because there are data on cerebral hemorrhage and fatal outcomes as a result of continued treatment or its resumption of the appearance of these symptoms;
• nervous system organs: dizziness with headaches, visual impairment, disorientation, development of ataxia or psychosis;
• endocrine system organs: adrenal insufficiency (patients with dysfunction), as well as menstrual cycle disorders;
• organs of the urinary system: renal necrosis or interstitial nephritis, as well as acute renal failure (in reversible form) and hyperuricemia;
• other: urine/feces/mucus/sweating/salivation/sputum are colored orange-red. In addition, muscle weakness, induction of porphyria, as well as myopathy, exacerbated gout, dyspnea with wheezing, decreased blood pressure and cerebral hemorrhage.

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Overdose

Overdose symptoms: vomiting with nausea, diarrhea and abdominal pain. In addition, the development of jaundice, drowsiness, increased fatigue. In addition, the level of liver transamines and bilirubin increases in the blood plasma. The skin (and along with it the mucous membrane in the mouth, saliva, sweat, urine, mucus, feces and sclera) becomes orange or brown-red (in relation to the dose of the drug used). In addition, allergies, increased temperature, fever, dyspnea, acute hemolytic anemia, thrombocytopenia and leukopenia, swelling of the face, lungs and eyes, renal failure, and in addition convulsions, confusion and skin itching are observed.

As a treatment, you need to stop taking the drug and eliminate the symptoms of overdose. If the case is severe, forced diuresis is required. There is no specific antidote for this drug.

Interactions with other drugs

When rifampicin is combined with drugs metabolized by the same enzyme system, the rate of metabolism of these drugs may increase, and their activity may decrease. Therefore, it is necessary to maintain the correct drug concentration of these drugs in the blood - change their dose at the beginning of rifampicin use, as well as after stopping treatment with it.

Rifampicin increases the rate of metabolism of the following drugs: antiarrhythmics (such as mexiletine, disopyramide, and also propafenone, quinidine and tocainide), β-blockers (such as bisoprolol or propranolol), Ca2+ channel blockers (such as verapamil, diltiazem, nimodipine, and also nifedipine, nicardipine, isradipine and nisolpidine) and CGs (digoxin and digitoxin), as well as anticonvulsants (carbamazepine and phenytoin), psychotropic drugs (such as aripiprazole or haloperidol), tricyclics (nortriptyline and amitriptyline), hypnotics, anxiolytics (benzodiazepine, zolipidem, as well as diazepam and zopiclone) and barbiturates.

In addition, it has a similar effect on thrombolytics (vitamin K antagonists) and indirect anticoagulants. It is necessary to monitor prothrombin time every day or at intervals sufficient to determine the optimal dosage of the anticoagulant.

A similar effect is exerted on antifungal drugs (fluconazole, ketoconazole, as well as terbinafine, voriconazole and itraconazole), antiviral drugs (including indinavir, amprenavir, saquinavir and nelfinavir, as well as efavirenz, lopinavir, atazanavir and nevirapine) and antibacterial drugs (such as dapsone, teliromycin, doxylamine, as well as chloramphenicol, fluoroquinolones and clarithromycin), as well as corticosteroids (systemic use).

It also acts in this way on antiestrogens (toremifene, tamoxifen and gestrinone), estrogens, hormonal contraceptives and gestagens. Women using oral contraceptives are advised to use non-hormonal contraceptives when treated with rifampicin. In addition, it also acts on thyroid hormones (such as levothyroxine), clofibrate, oral antidiabetic drugs (such as tolbutamide, chloropamide and thiazolidinediones).

The effect also affects immunosuppressants (sirolimus and cyclosporine with tacrolimus), cytostatic drugs (erlotinib and imatinib with irinotecan), losartan, opioid analgesics, and also methadone, quinine, praziquantel, and riluzole.

The same activity is observed in relation to selective serotonin receptor antagonists (ondansetron), theophylline, diuretics (eplerenone), and also statins, the metabolism of which occurs through CYP 3A4 (this may be simvastatin).

As a result of the combination of atovaquone with rifampicin, the concentration of the former in the blood serum decreases, but the concentration of the latter increases. In the case of a combination with ketoconazole, the concentration of both drugs decreases.

Combination with enalapril reduces the concentration of its active decay product (enalaprilat) in the blood. Therefore, depending on the patient's condition, a dosage adjustment of the drug may be required.

Combination with antacid drugs can cause a delay in the absorption of rifampicin, so it is recommended to take it at least 1 hour before taking antacids.

In combination with Biseptol and probenecid, the concentration of rifampicin in the blood increases.

Due to the combination with saquinavir or ritonavir, the risk of hepatotoxicity increases, so combining them with rifampicin is prohibited. In addition, hepatotoxicity can develop when combined with isoniazid and halothane. Combining rifampicin with the latter is not recommended, and when used simultaneously with isoniazid, liver function should be carefully monitored.

When combined with sulfasalazine, the concentration of sulfapyridine in plasma decreases. This is usually due to the fact that the balance of intestinal microflora is disturbed, where the transformation of sulfasalazine into the substances sulfapyridine with mesalamine occurs.

Due to the combination with pyrazinamide (daily intake for 2 months) severe liver dysfunction may occur (there are reports of fatal outcome). Such a combination is permitted only under the condition of careful monitoring of the condition and if the possible benefit is higher than the risk of developing hepatotoxicity and fatal outcome.

Concomitant use with clozapine or flecainide increases the toxic effect on bone marrow.

When combined with para-aminosalicylic acid drugs that contain bentonite, in order to obtain the required concentration of drugs in the blood, it is necessary to observe an interval between their use (at least 4 hours).

As a result of combination with ciprofloxacin or clarithromycin, the concentration of rifampicin may increase.

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Storage conditions

Keep in a place protected from sunlight and moisture, and out of reach of children. Temperature conditions – no more than 25°C.

Shelf life

Makox is approved for use for 3 years from the date of manufacture of the medicine.