Safocid - instructions for use, doses, side effects, contraindications

Active substanceFluconazole + Azithromycin + SecnidazoleFluconazole + Azithromycin + Secnidazole

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Safocid

pills inwards

NIZHFARM, JSC Russia

Dosage form: & nbspTablets set.

Composition:

Fluconazole 1 tablet contains:

active substance: fluconazole - 150 mg;

Excipients: cellulose microcrystalline - 153 mg, calcium hydrophosphate - 14.5 mg, croscarmellose sodium - 5 mg, magnesium stearate - 4 mg, silicon dioxide colloid - 1 mg, dye crimson (Ponso 4R) (E 124) 2.5 mg.

Azithromycin

1 tablet, film-coated, contains:

active substance: azithromycin dihydrate - 1048 mg (in terms of azithromycin - 1000 mg);

Excipients: sodium lauryl sulfate - 12 mg, croscarmellose sodium - 37.24 mg, povidone-K30 - 40 mg, magnesium stearate - 16 mg, silicon dioxide colloid - 2 mg; composition of the shell: hypromellose (hydroxypropylmethylcellulose) - 24.5 mg, diethyl phthalate - 3.8 mg, talc - 5.2 mg, titanium dioxide - 6 mg, macrogol-4000 - 4.2 mg, dye crimson (Ponso 4R) (E 124) 1.06 mg.

Secnidazole

1 tablet, film-coated, contains:

active substance: secnidazole - 1000 mg;

Excipients: corn starch - 95 mg, microcrystalline cellulose - 130 mg, silicon dioxide colloid - 6 mg, sodium carboxymethyl starch - 20 mg, povidone (PVPK-30) - 2.5 mg, talc - 11.5 mg, magnesium stearate 10 mg; shell composition: hypromellose (hydroxypropylmethylcellulose) 27.1 mg, diethyl phthalate 4 mg, talc 5.7 mg, titanium dioxide 11.2 mg, macrogol 4000 4.6 mg.

Description:

Fluconazole

Tablets are flat-cylindrical pink with a facet and a risk. On the break the tablets are pink.

Azithromycin

The capsular biconvex tablets covered with a film membrane of pink color, with a risk. On the fracture, the core of the tablet is white or almost white in color.

Secnidazole

The capsule-shaped biconvex tablets covered with a film coat of white or almost white color, with a risk. On the break the tablets are white or almost white in color.

Pharmacotherapeutic group:Antimicrobial medication combined

ATX: & nbsp

J.01.R.A Combinations of antibacterial drugs

J.01.R.A.07 Azithromycin, fluconazole and secnidazole

Pharmacodynamics:

Fluconazole

Antifungal agent, has a highly specific effect, inhibiting the activity of enzymes of fungi, dependent on cytochrome P450. Blocking the conversion of lanosterol of fungal cells to ergosterol; increases the permeability of the cell membrane, disrupts its growth and replication. Fluconazole, being highly selective for cytochrome P450 fungi, practically does not inhibit these enzymes in the human body (in comparison with itraconazole, clotrimazole,econazole and ketoconazole to a lesser extent suppresses oxidative processes dependent on cytochrome P450 in human liver microsomes). Does not have anti-androgenic activity. Active with opportunistic mycoses, including those caused by Candida spp. (including generalized forms of candidiasis on the background of immunodepression), Cryplocaccus neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp.; with endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including immunosuppression).

Azithromycin

Antibacterial agent of a wide spectrum of action, azalide, acts bacteriostatically. Communicating with 50S subunit of ribosomes, inhibits peptidranslokase at the stage of translation, suppresses protein synthesis, slows the growth and multiplication of bacteria, has a bactericidal effect at high concentrations.

Effects on extracorporeal and intracellular pathogens.

Sensitive to azithromycin microorganisms: aerobic Gram-positive microorganisms - Staphylococcus aureus (methicillin-sensitive strains), Streptococcus pneumoniae (penicillin-sensitive strains), Streptococcus pyogenes; aerobic gram-negative microorganisms - Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae; anaerobic microorganisms - Clostridium perfringens, Fusobacterium spp., Prevotella spp., Porphyromonas spp.; other microorganisms - Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.

Microorganisms with acquired resistance to azithromycin: aerobic Gram-positive microorganisms - Streptococcus pneumoniae (penicillin-resistant strains and strains with an average sensitivity to penicillin).

Microorganisms with natural resistance: aerobic Gram-positive microorganisms - Enterococcus faecalis, Staphylococcus aureus (methicillin-resistant strains), Staphylococcus epidermidis (methicillin-resistant strains); anaerobic microorganisms - Bacteroides fragilis.

Cases of cross-resistance between Streptococcus pneumoniae, Streptococcus pyogenes (beta-hemolytic group streptococcus A), Enterococcus faecalis and Staphylococcus aureus, including Staphylococcus aureus (methicillin-resistant strains) to erythromycin, azithromycin, other macrolides and lincosamides.

Secnidazole

Antimicrobial bactericidal preparation is a synthetic derivative of nitroimidazole. It is active against obligate anaerobic bacteria (sporo- and non-spore forming), pathogens of some protozoal infections: Trichomonas spp., Giardia lamblia, Entamoeba histolytica. Inactive against aerobic bacteria. Interacts with the DNA of a microbial cell, causes a disruption in the spiral structure, rupture of filaments,suppression of the synthesis of nucleic acids and cell death. Causes sensitization to alcohol (tetur-like action).

Pharmacokinetics:

Fluconazole

Absorption is high, bioavailability is 90%. Simultaneous food intake does not affect the absorption of the drug taken internally. After oral administration of 150 mg, the time to reach the maximum concentration (Tcmax) 0.5-1.5 hours, the maximum concentration of fluconazole in plasma (C_m_Oh) is 90% of its plasma concentration when administered intravenously at the same dose. The connection with plasma proteins is 11-12%. The concentration in the plasma is in direct proportion to the dose. Fluconazole well penetrates into all body fluids. The concentration of the active substance in breast milk, articular fluid, saliva, sputum and peritoneal fluid is similar to that in plasma. Good penetrates into the cerebrospinal fluid (CSF), with fungal meningitis, the concentration in the CSF is about 85% of that in the plasma. In the fluid, epidermis and stratum corneum (selective accumulation), concentrations exceeding serum levels are achieved. The volume of distribution approximates the total water content in the body; half-life (Ti/₂) fluconazole is about 30 hours. Is an inhibitor of isoenzyme CYP2C9 in the liver. It is excreted mainly by the kidneys (80% - unchanged, 11% - in the form of metabolites). The clearance of fluconazole is proportional to the clearance of creatinine (CC). The pharmacokinetics of fluconazole significantly depends on the functional state of the kidneys, and there is an inverse relationship between T1 / 2 and KK. After hemodialysis for 3 hours the concentration of fluconazole in plasma is reduced by 50%.

Azithromycin

Azithromycin is rapidly absorbed from the gastrointestinal tract (GIT), which is due to its resistance to acidic environment and lipophilicity. Bioavailability after a single dose of 0.5 g - 37% (the effect of "first passage" through the liver). After oral administration, 0.5 g of C_m_Oh is 0.4 mg / l, Tc_m_a_x - 2,5-2,9 hours. In tissues and cells, the concentration is 10-50 times higher than in serum. The volume of distribution is 31.1 l / kg. Easily passes the histohematological barriers. It penetrates well into the respiratory tract, urino-genital organs and tissues, into the prostate gland, into the skin and soft tissues; accumulates in a medium with low pH, in lysosomes (which is especially important for the eradication of intracellular pathogens). It is also transported by phagocytes, polymorphonuclear leukocytes and macrophages (without significantly affecting their function).It penetrates the membranes of cells and creates high concentrations in them. The concentration in the foci of infection is significantly higher (by 24-34%) than in healthy tissues, and correlates with the severity of the inflammatory edema. In the focus of inflammation persists in effective concentrations within 5-7 days after taking the last dose. The connection with plasma proteins is 7-50% (inversely proportional to the concentration in the blood). In the liver demethylated, the metabolites formed are inactive. Plasma clearance - 630 ml / min. Excretion of azithromycin from the blood plasma takes place in 2 stages: T1/2 is 14-20 hours in the interval from 8 to 24 hours after taking the drug and 41 hours in the range of 24 to 72 hours.

It is excreted with bile in unchanged form (50%) and kidneys (6%). Eating changes the pharmacokinetics: when taking azithromycin in a tablet dosage form FROM_m_Ohincreases by 31%, while the area under the curve "concentration-time" (AUC) does not change. In elderly men (65-85 years) the pharmacokinetic parameters do not change, in women C increases_m_Oh (by 30-50%).

Secnidazole

Absorption is high, bioavailability is 80%. After a single oral intake of 2 g of T_FROM_m_Oh- 4 hours. Metabolised in the liver. It is excreted by the kidneys - 72 hours (16% of the dose taken).It is secreted into breast milk, it penetrates the placental barrier.

Indications:

Combined sexually transmitted infections of the genitourinary tract, such as gonorrhea, trichomoniasis, chlamydia, bacterial vaginosis, fungal infections, as well as specific and non-specific cystitis accompanying them, urethritis, vulvovaginitis and cervicitis.

Contraindications:

Hypersensitivity to fluconazole (including other azole antifungal drugs in history), azithromycin (including macrolides), secnidazole (including other nitroimidazoles); hypersensitivity to other components of the drugs that make up the set of tablets.

Simultaneous reception of astemizole, erythromycin, pimozide, quinidine, cisapride, ergotamine, dihydroergotamine; simultaneous reception of other drugs that extend the interval Q-T.

Organic diseases of the central nervous system, severe hepatic insufficiency, renal insufficiency with creatinine clearance less than 40 ml / min, blood diseases (including in anamnesis); pregnancy, lactation, children under 18 years of age.

Carefully:

Simultaneous administration of rifabutin or other drugs metabolized by the cytochrome P450 system; simultaneous administration of warfarin, digoxin, terfenadine; potentially proaritmogenic states in patients with multiple risk factors (organic heart disease, electrolyte balance disorders); simultaneous use of drugs that extend the interval Q-T (antiarrhythmic drugs IA and III class), arrhythmia (risk of ventricular arrhythmia and lengthening of the interval Q-T), moderate violations of the liver and kidneys, myasthenia gravis.

Pregnancy and lactation:

Application during pregnancy and during lactation is contraindicated.

Dosing and Administration:

Inside. Take all 4 tablets included in the blister at the same time, taking into account the intake of food (as the absorption of azithromycin varies with simultaneous intake of food, it is better to take it an hour before meals or 2 hours after eating), once.

Side effects:

Fluconazole

Drug tolerance is usually very good.

From the central and peripheral nervous system: headache, dizziness, convulsions, insomnia, drowsiness, tremor.

From the digestive system: abdominal pain, diarrhea, flatulence, nausea, taste change, indigestion, vomiting, dryness of the oral mucosa, impaired liver function (jaundice, hyperbilirubinemia, increased alkaline phosphatase concentration, cholestasis, increased activity of "hepatic" enzymes, hepatitis, hepatocellular necrosis ), including those with a fatal outcome.

Allergic reactions: skin rash, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactic reactions (including angioedema, face swelling, hives, itching of the skin).

On the part of the organs of hematopoiesis: leukopenia, thrombocytopenia, neutropenia, agranulocytosis.

From the cardiovascular system: increasing the duration of the interval Q-T, fibrillation / flutter of the ventricles, arrhythmia ventricular tachysystolic type "pirouette" (torsade de pointes).

Other: impaired renal function, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia, increased sweating, myalgia, asthenia, weakness, fever.

Azithromycin

From the side of the digestive system, flatulence, nausea, vomiting, constipation, abdominal pain, decreased appetite, gastritis, melena, cholestatic jaundice, increased activity of "liver" transaminases, candidiasis of the oral mucosa, diarrhea, indigestion, discoloration, pseudomembranous colitis, pancreatitis, hepatitis , liver dysfunction, increased bilirubin concentration, hepatic insufficiency, liver necrosis (possibly fatal), fulminant hepatitis.

Allergic reactions: skin rash, itching, angioedema, hives, anaphylactic reaction, including edema (in rare cases, fatal); erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the genitourinary system: vaginal candidiasis, vaginitis; interstitial nephritis, acute renal failure, an increase in the concentration of urea and creatinine in the blood plasma.

From the cardiovascular system: heart palpitations, chest pain, arrhythmia, lowering of arterial pressure, ventricular tachycardia, increased interval Q-T, bidirectional ventricular tachycardia.

From the nervous system: dizziness, headache, vertigo, drowsiness, convulsions, paresthesia, hypoesthesia, insomnia, hyperactivity, aggressiveness, anxiety, anxiety, nervousness, fainting.

From the side of the blood and lymphatic system: lymphopenia, leukopenia, neutropenia, thrombocytopenia, hemolytic anemia, neutrophilia.

From the sense organs: noise in the ears, reversible hearing loss down to deafness, a violation of the perception of taste and smell.

Other: asthenia, photosensitivity, conjunctivitis, impaired vision, eosinophilia, myasthenia gravis, arthralgia, peripheral edema, malaise, change in potassium concentration.

Secnidazole

Possible side effects noted when taking imidazole derivatives.

From the digestive system: nausea, vomiting, abdominal pain, "metallic" taste in the mouth, glossitis, stomatitis.

On the part of the hematopoiesis system: leukopenia.

From the central and peripheral nervous system, dizziness, incoordination, ataxia, paresthesia, polyneuropathy.

Allergic reactions: hives.

Overdose:

Cases of overdose of a set of Tabocid tablets are not described. In case of overdose, immediately consult a doctor.

Fluconazole

Symptoms: hallucinations, paranoid behavior.

Treatment: symptomatic; gastric lavage (if necessary), forced diuresis. Hemodialysis within 3 hours reduces the concentration of fluconazole in the blood plasma by approximately 50%.

Azithromycin

Symptoms: nausea, temporary loss of hearing, vomiting, diarrhea.

Treatment: symptomatic; reception of activated carbon, control of vital functions.

Secnidazole

In case of suspected overdose, supportive and symptomatic treatment should be performed; gastric lavage, reception of activated carbon.

Interaction:

Fluconazole

With the simultaneous use of astemizole with fluconazole, a decrease in the clearance of astemizole and an increase in its plasma concentration may occur, which may cause lengthening of the interval Q-T and the development of ventricular arrhythmia of the "pirouette" type.

With the simultaneous use of pimozide with fluconazole, inhibition of the metabolism of pimozide is possible. An increase in the concentration of pimozide in the blood plasma can cause lengthening of the interval Q-T and the development of ventricular arrhythmia of the "pirouette" type.

With the simultaneous use of quinidine with fluconazole, inhibition of quinidine metabolism is possible. The use of quinidine is associated with the lengthening of the interval Q-T and rare cases of development of ventricular arrhythmia of the "pirouette" type.

With the simultaneous use of fluconazole and erythromycin, an increased risk of cardiotoxicity (lengthening of the interval Q-T, the development of ventricular arrhythmia such as "pirouette"), until sudden cardiac arrest.

With simultaneous use of cisapride and fluconazole, there have been cases of serious cardiac abnormalities, including paroxysms of ventricular tachycardia (torsade de pointes). With the simultaneous administration of fluconazole (200 mg / day) and cisapride (20 mg 4 times a day), there was a significant increase in the concentration of cisapride in plasma and an increase interval duration Q-T.

Benzodiazepines (short-acting): fluconazole increases concentration midazolam after taking the latter inside, which can lead to an increased risk of psychomotor effects. Fluconazole enhances AUC and the half-life of triazolam after ingestion of the latter, as a result of which an increase in the effect and an increase in the duration of the action of triazolam are possible.With the simultaneous use of short-acting benzodiazepines and fluconazole, a dose reduction of benzodiazepines and careful monitoring of the patients' condition may be required. Rifampicin increases the metabolism of fluconazole, resulting in a half-life and a plasma concentration of fluconazole reduced by 20% and 25%, respectively. An increase in the dose of fluconazole may be required.

Fluconazole may increase the concentration of tacrolimus in the serum after ingestion of the latter, due to inhibition of the metabolism of tacrolimus in the intestine isoenzyme CYP3A4. After intravenous administration of tacrolimus, no significant changes in pharmacokinetic parameters were observed. When the concentration of tacrolimus increases, the risk of nephrotoxic action increases. It is necessary to monitor the concentration of tacrolimus and, if necessary, adjust the dose.

Fluconazole increases C_m_Oh and AUC zidovudine, respectively, by 84% and 74%, due to a decrease in its clearance by approximately 45%. Therefore, there may be an increased risk of side effects of zidovudine. Patients should be carefully monitored for the development of zidovudine-associated adverse reactions.

Some azoles in combination with terfenadine were associated with the occurrence of severe rhythm disturbances, including paroxysms of ventricular tachycardia (torsade de pointes), due to the increase in the duration of the interval Q-T on the ECG. Studies conducted with fluconazole showed that with a daily dose of fluconazole 200 mg, no lengthening of the interval was observed Q-T. With the use of fluconazole at a dose of 400 or 800 mg, a significant increase in the concentration of terfenadine in plasma was observed. The administration of fluconazole 400 mg or more in combination with terfenadine is contraindicated. Patients should be carefully observed while taking terfenadine and fluconazole at a dose of less than 400 mg per day.

Hydrochlorothiazide increases the concentration of fluconazole in the plasma by 40% (clinical significance is unlikely).

Fluconazole increases the plasma concentration and half-life of hypoglycemic medicines for oral use, sulfonylurea derivatives: chlorpropamide, glibenclamide, glipizide and tolbutamide. Periodically monitor the concentration of glucose in the blood (risk of hypoglycemia) and, if necessary, adjust the dose of oral hypoglycemic drugs.

With the simultaneous administration of fluconazole during treatment with coumarin derivatives (warfarin) there was an increase in prothrombin time. Patients who simultaneously receive indirect anticoagulants, coumarin derivatives, require careful monitoring of prothrombin time.

The simultaneous use of fluconazole and rifabutin can lead to an increase in plasma concentrations of plasma; with simultaneous application described cases of uveitis.

Fluconazole reduces the clearance of theophylline and increases its plasma concentration. Patients who receive high doses of theophylline or who are likely to develop theophylline intoxication should be monitored for the early detection of symptoms of theophylline overdose.

Fluconazole clinically significantly increases the concentration in the plasma of phenytoin. With simultaneous application it is necessary to monitor the concentration of phenytoin in the plasma and, if necessary, carry out dose adjustment.

Fluconazole increases AUC cyclosporine. With the simultaneous use of fluconazole (200 mg / day) and cyclosporine (2.7 mg / kg / day) in patients with kidney transplantation magnitude AUC cyclosporine was increased 1.8 times.

With the simultaneous use of fluconazole at a dose of 50 mg and oral contraceptives, there were no significant changes in plasma concentrations of ethinylestradiol and levonorgestrel, but with 200 mg of fluconazole an increase AUC ethinyl estradiol by 40% and levonorgestrel by 24%. Therefore, the effect of fluconazole on the efficacy of combined oral contraceptives is not expected.

Azithromycin

Antacids (aluminum and magnesium-containing), ethanol and food slows down and reduces absorption.

When co-administration of warfarin and azithromycin (in normal doses) changes in prothrombin time were found, however, given that the interaction of macrolides and warfarin may be increased anticoagulant effect, patients requires careful monitoring of the prothrombin time.

Azithromycin does not have a clinically significant effect on the concentration in the blood carbamazepine, cimetidine, didanosine, efavirenz, fluconazole, indinavir, midazolam, theophylline, triazolam, trimethoprim / sulfamethoxazole, cetirizine, sildenafil, atorvastatin, rifabutin and methylprednisolone.

Caution should be exercised in the joint administration of terfenadine and azithromycin, since it was found that the simultaneous use of terfenadine and various types of antibiotics causes arrhythmia and lengthening Q-T interval. Proceeding from this, it is impossible to exclude the aforementioned complications in the joint administration of terfenadine and azithromycin.

Ergotamine and dihydroergotamine: increased toxic effect (vasospasm, dysesthesia). Macrolides slow down excretion, increase plasma concentrations and toxicity of cycloserine, indirect anticoagulants, methylprednisolone, felodipine, and drugs that undergo microsomal oxidation (carbamazepine, terfenadine, ciclosporin, hexobarbital, ergot alkaloids, valproic acid, disopyramide, bromocriptine, phenytoin, oral hypoglycemic drugs), however, no such interaction was observed with the use of azalides (including azithromycin).

Lincosamides weaken, and tetracycline and chloramphenicol increase the effectiveness of azithromycin.

With the joint administration of digoxin and azithromycin, it is necessary to control the concentration of digoxin in the blood,since many macrolides increase absorption of digoxin in the intestine, thereby increasing its concentration in the blood plasma.

If a joint use of azithromycin with cyclosporin is required, it is recommended to monitor the content of cyclosporin in the blood because of a significant increase in the area under the concentration-time curve.

When combined with zidovudine azithromycin does not affect the pharmacokinetic parameters of zidovudine in blood plasma or the excretion of zidovudine and its glucuronated metabolite by the kidneys. Nevertheless, the concentration of the active metabolite - phosphorylated zidovudine in monocytes - increases. The clinical significance of this fact is not known.

With simultaneous application with nelfinavir, an increase in the concentration of azithromycin in the blood plasma is possible, not accompanied by a significant increase in adverse reactions and not requiring correction of the dose of drugs.

Secnidazole

Strengthens the effect of indirect anticoagulants. It is not recommended to combine non-depolarizing muscle relaxants (vecuronium bromide). At simultaneous reception with preparations of lithium raises its concentration in plasma.

Strengthens the hypoglycemic effect of insulin and oral hypoglycemic agents.

Similarly, disulfiram causes intolerance to ethanol.

Special instructions:

With simultaneous use of antacids, you must observe a break 2 hours before taking azithromycin.

Due to the fact that with the joint use of secnidazole with alcohol, a disulfiram-like reaction (abdominal cramps, nausea, vomiting, headache, flush to the face), during the treatment period, it is necessary to avoid the use of ethanol.

Secnidazole can cause immobilization by treponem, which leads to false positive Nelson's test (reaction of immobilization of pale treponemes, RIBT).

Effect on the ability to drive transp. cf. and fur:

The use of the Safocid tablet set does not generally affect the ability to drive and perform work that requires a high rate of mental and physical reactions, but it can lead to dizziness and other side effects that may affect the above abilities.

Form release / dosage:Tablets set.

Packaging:

Tablets set.For 4 tablets (one tablet - fluconazole, one tablet - azithromycin, two tablets - secnidazole) in a contour squamous packaging (blister) from a polyvinylchloride film and aluminum foil. 1 or 3 blisters together with instructions for use in a cardboard pack.

Storage conditions:

In a place protected from light and moisture at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-002448

Date of registration:11.09.2012

The owner of the registration certificate:NIZHFARM, JSC NIZHFARM, JSC Russia

Manufacturer: & nbsp

Laika Labs Limited India

Representation: & nbspNizhpharm, JSCNizhpharm, JSCRussia

Information update date: & nbsp05.10.2015

Illustrated instructions

Instructions

Safocid (Safocid)