Forcox - instructions for use, dose, side effects, contraindications

Excipients: For dosing 75/150/400/275: shellac - 7.00 mg, povidone - 2.00 mg, talc purified - 20.00 mg, disodium edetate - 0.50 mg, silicon dioxide colloid - 5.00 mg, starch corn - 7,00 mg, croscarmellose sodium - 30,00 mg, crospovidone - 13.50 mg, calcium stearate - 7.50 mg; purified 9.75 mg, hypromellose 12.00 mg, castor oil 4.875 mg, diethyl phthalate 1.50 mg, titanium dioxide 7.50 mg, magnesium stearate 0.375 mg, dye sunset yellow 0.22 mg . For the dosage of 150/225/750/400: shellac - 10.00 mg, povidone - 2.50 mg, talc purified - 27.50 mg, silicon colloidal dioxide - 7.50 mg, corn starch - 12.00 mg , crospovidone - 35.00 mg, magnesium stearate -12.00 mg;

composition of the shell: Talcum purified - 8.29 mg, hypromellose - 10.52 mg, castor oil - 3.91 mg, diethyl phthalate - 1.52 mg, titanium dioxide - 6.38 mg, magnesium stearate - 1.28 mg, dye sunset yellow - 0.20 mg.

Description:

The tablets are biconvex, capsular, covered with a film coat from yellowish pink to a beige-pink color.

Pharmacotherapeutic group:Anti-tuberculosis drug combined

ATX: & nbsp

J.04.A.M.06 Isoniazid in combination with pyrazinamide, rifampicin and ethambutol

Pharmacodynamics:FORKOX® is a combined preparation containing fixed amounts of rifampicin, isoniazid, pyrazinamide, and ethambutol. Combined use of the active substances included in the drug reduces the risk of developing resistance, which develops with monotherapy of tuberculosis.

Pharmacokinetics:

Rifampicin.

After taking FORKOX® in healthy adults, the maximum concentration of rifampicin in plasma reaches 7.84 μg / ml. In the case of reception with absorption of food rifampicin, reduced by 30%. The maximum concentration of rifampicin in plasma is reached after 2 hours. Rifampicin widely distributed in the body, quickly penetrating into organs and tissues (the highest concentration is created in the liver and kidneys), also penetrates into bone tissue. Concentration in the saliva is 20% of the plasma. Rifampicin penetrates the blood-brain barrier (BBB) only in case of inflammation of the meninges. Penetrates through the placenta (plasma concentration in the fetus is 33% of the concentration in the mother's plasma) and in breast milk (breast-fed children receive no more than 1% of the therapeutic dose of the drug). Approximately 80% of the dose is associated with plasma proteins. The half-life of rifampicin is, on average, 3.35 ± 0.66 h. Rifampicin metabolized in the liver to pharmacologically active deacetyltrifampicin, excreted from the body by the kidneys (up to 30% of the dose taken).

Isoniazid.

After taking FORKOX® in healthy adults, the maximum concentration of isoniazid in plasma reaches 4.75 μg / ml after 2 hours. The half-life of isoniazid from plasma is 2-6 hours. Isoniazid is subjected to a pronounced pre-systemic metabolism in the wall of the small intestine and liver, as a result of which its plasma concentration in patients with a fast acetylation process is half the concentration in patients with a slow acetylation process. The apparent volume of isoniazid distribution is 61% of body weight. Isoniazid is present in effective concentrations in many tissues and biological fluids, including cerebrospinal fluid (CSF). Up to 95% of the dose of isoniazid is excreted by the kidneys within 24 hours, the rest is excreted through the intestine. The main products of urinary excretion are N-acetylisosodium and isonicotinic acid.

Pyrazinamide.

After taking FORKOX in healthy adults, the maximum concentration of pyrazinamide in plasma reaches 24.13 μg / ml after 3 hours. The half-life of pyrazinamide is 10-24 hours. The drug is widely distributed in the body, it penetrates well into tissues and biological fluids, including cerebrospinal fluid. Its concentrations in the cerebrospinal fluid are almost identical to those in the blood. In the liver pyrazinamide turns into the main active metabolite - pyrazinic acid. Approximately 30-40% of the accepted dose is excreted by the kidneys in the form of pyrazinic acid and 3.4% in the form of unchanged pyrazinamide.

Ethambutol.

After taking FORKOX in healthy adults, the maximum concentration of ethambutol in plasma reaches 3.45 μg / ml after 2 hours. Further, the concentration decreases in a two-phase manner: at the beginning, the elimination half-life is 4 hours and then 10 hours. Ethambutol well penetrates into tissues and organs (into the cerebrospinal fluid only with meningitis). Approximately 50-70% of the dose is excreted by the kidneys unchanged, and the rest - in the form of aldehyde and carboxyl metabolites. The average volume of distribution is 3.89 l / kg. About 10-40% of the drug binds to plasma proteins. A small portion of the dose taken is metabolized in the liver and, possibly, in other tissues. Metabolite is excreted by the kidneys. In patients with impaired renal function, ethambutol elimination is slowed down.

Indications:The initial stage of pulmonary tuberculosis and extrapulmonary tuberculosis.

Contraindications:

- hypersensitivity to any ingredient in this drug,

- visual impairment (diabetic retinopathy, optic nerve damage, inflammatory eye diseases),

- epilepsy and a penchant for seizures, previous poliomyelitis,

- violations of the liver and kidneys, gout, jaundice, acute hepatitis.

- thrombophlebitis, severe atherosclerosis.

Carefully:

- during pregnancy and lactation,

- children under 13 years,

- elderly people,

- at a psychosis, a gout.

Pregnancy and lactation:Carefully

Dosing and Administration:

Each film-coated tablet containing: Izoniazid 75 mg, Rifampicin 150 mg, Pyrazinamide 400 mg, Etambutolum 275 mg is ingested 1-2 hours before meals, 4 tablets per day, single patients whose body weight does not exceed 50 kg. The course of treatment - 2 months.

Each film-coated tablet containing: Isoniazidum 150 mg, Rifampicin 225 mg, Pyrazinamide 750 mg, Etambutolum 400 mg is ingested 1-2 hours before meals with 2 tablets per day with single patients whose body weight is not less than 60 kg. The course of treatment - 2 months.

It is possible to use the drug in combination with other anti-tuberculosis drugs, such as streptomycin and etc.

Side effects:

Side effects in the treatment with FORKOS® are determined by the active ingredients included in its composition.

Rifampicin.

Rifampicin can cause side effects on the part of the digestive system, such as heartburn, epigastric discomfort, anorexia, vomiting, intestinal colic and diarrhea, erosive gastritis, pseudomembranous enterocolitis. Men occasionally experience toxic liver damage, which usually develops in the first two weeks after the start of treatment.From the nervous system: pain, drowsiness, weakness, ataxia, dizziness, confusion, visual disorders, disorientation.

From the urinary system: nephronecrosis, interstitial nephritis. Allergic reactions: Quincke's edema, bronchospasm, arthralgia, fever, skin rashes and eosinophilia Other: leukopenia, dysmenorrhea, induction of porphyria, muscle weakness, hyperuricemia, exacerbation of gout. With irregular therapy or with the resumption of treatment after a break, flu-like syndrome (fever, chills, headache, dizziness, sore throat and soreness of the tongue, myalgia), skin reactions, hemolytic anemia, thrombocytopenic purpura, acute renal failure are possible.

Isoniazid

Long-term use of isoniazid causes peripheral neuropathy in 3.5-17% of patients. When taking isoniazid possible headache, dizziness, nausea, vomiting, the development of medicinal hepatitis. Gynecomastia in men and menorrhagia in women. Prophylactic and therapeutic use of isoniazid in the form of monotherapy or in combination with anti-tuberculosis drugs is associated with a significant risk of toxiclesions of the liver.

Pyrazinamide.

Pyrazinamide can cause liver damage and fulminant hepatitis. The likelihood of toxic damage to the liver increases with increasing dose and duration of treatment. At a dose of 3 g per day, signs of liver damage are observed in about 15% of patients. The abolition of pyrazinamide leads to a rapid normalization of liver enzyme levels.

Ethambutol.

The most serious side effects of ethambutol are retrobulbar neuritis, which is manifested by decreased visual acuity, narrowing of the field of vision, central or peripheral scotoma, and impaired color perception, especially the ability to distinguish between green and red. Other side effects include confusion, disorientation, hallucinations, headache, dizziness, general malaise, jaundice or transient liver dysfunction, peripheral neuropathy, and such gastrointestinal disturbances such as metallic taste in the mouth, nausea, vomiting, anorexia and abdominal pain.

Overdose:

Symptoms: pulmonary edema, confusion, convulsions, peripheral neuropathy, impaired liver function, nausea, vomiting, impaired vision and hearing, slurred speech, respiratory depression, stupor, coma.

Treatment: gastric lavage, the appointment of activated charcoal; symptomatic therapy, forced diuresis, artificial ventilation, intravenous - barbiturates of short action, pyridoxine, osmotic diuretics, sodium bicarbonate in the development of metabolic acidosis.

Interaction:

Rifampicin.

Rifampicin accelerates the metabolism of phenytoin, quinidine, oral anticoagulants and antifungal drugs.

Antacids, opiates reduce the bioavailability of rifampicin.

Rifampicin reduces the activity of oral hypoglycemic drugs, oral hormonal contraceptives, digitalis preparations, antiarrhythmics (disopyramide, mexiletine), glucocorticosteroids, dapsone, hydantoins (phenytoin), hexobarbital, nortriptyline, benzodiazepines, sex hormones, theophylline, chloramphenicol, ketoconazole, introconazole, cyclosporin A, beta adrenoblockers, enalapril and cimetidine.

Isoniazid.

Isoniazid enhances the effects of phenytoin, such as drowsiness and ataxia.

Prednisolone can significantly reduce the concentration of isoniazid in the blood plasma in slower and faster acetylators, but this effect is more pronounced in slow acetylators. Isoniazid increases the frequency and severity of liver function disorders in combination with rifampicin in patients with previous liver disease.

PASK preparations containing bentonite (aluminum hydrosilicate) are administered four hours after taking isoniazid. Antacids reduce the absorption of isoniazid.

Isoniazid reduces the effectiveness of oral contraceptives, oral hypoglycemic drugs, theophylline, tolazomide, vitamin B1 (enhances its excretion); reduces the excretion of triazolam; reduces the content of Zn2 + in the blood (increases its excretion).

Ethambutol.

Aluminum hydroxide disrupts the absorption of ethambutol, and therefore it is necessary to use alternative antacids.

When combined with neurotoxic agents, neurotoxic

the action of ethambutol.

Pyrazinamide.

Pyrazinamide slightly reduces the concentration of isoniazid in the blood serum, especially in the case of copper acetylators.

Special instructions:

Before the beginning of treatment it is recommended to conduct a complete ophthalmological examination of the patient, which includes the determination of visual acuity, color vision, visual fields and ophthalmoscopy.If corrective glasses were used before the treatment, they should be worn during the assessment of visual acuity. During 1-2 years of therapy, a refractive error may develop, which must be corrected to obtain accurate results of the study. The study of visual acuity through the stenopathic opening eliminates the error of refraction. Progressive deterioration of vision during treatment should be considered as a side effect of taking FORKOX. Such a violation on the part of the organ of vision is mainly reversible after discontinuation of the drug. In rare cases, recovery may be delayed for 1 year or more and may be irreversible. Therefore, patients should be advised to immediately inform the doctor of any change in visual acuity.

When prescribing the drug, it should be borne in mind that urine, faeces, saliva and tears can be painted in orange. In the last trimester of pregnancy FORKOS® should be prescribed with vitamin K, tk. rifampicin can cause postnatal hemorrhages in the mother and fetus. Do not interrupt (accidentally or intentionally) taking the drug without consulting a doctor.Women during the treatment period are recommended to use non-hormonal methods of contraception.

During the treatment should not be used microbiological methods to determine the concentration of folic acid and cyanocobalamin in the blood serum. Caution should be used when using in elderly patients, due to the increased risk of developing toxic effects.

To avoid the development of a hepatotoxic effect during treatment, ethanol should be avoided.

Eating during the treatment of certain types of cheese (Swiss, Cheshire) or fish (tuna, sardines) can lead to itching of the skin, palpitation, chills and headache (inhibition of MAO and di-amino-oxidase plasma isoniazid, which affects metabolism of the amine and histamine found in fish and cheese).

Pyrazinamide worsens the course of gout and diabetes, requires monitoring of kidney function, uric acid. In the case of a persistent increase in the level of acid and exacerbation of gouty arthritis, treatment is canceled.

Form release / dosage:Film coated tablets.

Packaging:6 or 10 tablets in an aluminum foil strip. 10 strips with instructions for use are placed in a cardboard box.When packing 6 or 10 tablets in a strip of aluminum foil in a Russian company (ZAO Rafarma), 10 strips with instructions for use are placed in a cardboard box.

Storage conditions:

List B.

In dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012904 / 01

Date of registration:21.11.2007

The owner of the registration certificate:McLeodz Pharmaceuticals Co., Ltd. McLeodz Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

MACLEODS PHARMACEUTICALS, Ltd. India

Representation: & nbspAdvansd Trading, OOOAdvansd Trading, OOO

Information update date: & nbsp26.12.2014

Illustrated instructions

Instructions

Forcox (Forcox)