Composition, form of production and packaging
A set of tablets of three types:
Tablets of pink color, flat-cylindrical, with a facet and a risk; on a break - pink color (1 piece in a blister).
fluconazole 150 mg
[PRING] microcrystalline cellulose - 153 mg, calcium hydrophosphate - 14.5 mg, croscarmellose sodium - 5 mg, magnesium stearate - 4 mg, silicon dioxide colloid - 1 mg, dye crimson (Ponso 4R) (E124) 2.5 mg.
The tablets covered with a cover of pink color, capsular, biconcave, with risk; on the fracture - the core is white or almost white (1 piece in the blister).
azithromycin dihydrate 1048 mg,
which corresponds to the content of azithromycin 1000 mg
[PRING] sodium lauryl sulfate - 12 mg, croscarmellose sodium - 37.24 mg, povidone K30 - 40 mg, magnesium stearate - 16 mg, silicon dioxide colloid - 2 mg.
Sheath composition: hypromellose (hydroxypropylmethylcellulose) - 24.5 mg, diethyl phthalate - 3.8 mg, talc - 5.2 mg, titanium dioxide - 6 mg, macroline 4000 - 4.2 mg, dye crimson (Ponso 4R) (E124) - 1.06 mg.
Tablets covered with a coat of white or almost white, capsular, biconvex, with a risk; on a break - white or almost white color (2 pieces in a blister).
secnidazole 1000 mg
[PRING] 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.
Sheath composition: hypromellose (hydroxypropylmethylcellulose) - 27.1 mg, diethyl phthalate - 4 mg, talc - 5.7 mg, titanium dioxide - 11.2 mg, macroline 4000 - 4.6 mg.
4 things. - blisters (1) - packs of cardboard.
4 things. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
A combination kit containing an antifungal drug, an antibiotic and an antibacterial drug with antiprotozoal activity.
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 less inhibits oxidative processes dependent on cytochrome P450 in human liver microsomes). Does not have anti-androgenic activity.
Active with opportunistic fungal infections , incl. caused by Candida spp. (including generalized forms of candidiasis on the background of immunodepression), Cryptococcus neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp .; with endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulation (including with immunodepression).
Antibacterial agent of a wide spectrum of action, azalide, acts bacteriostatically. Linking to the 50S subunit of ribosomes, inhibits peptidranslokase at the stage of translation, suppresses protein synthesis, slows the growth and multiplication of bacteria, at high concentrations has a bactericidal effect. It is active against extracellular and intracellular pathogens.
Azithromycin susceptible microorganisms: aerobic Gram-positive microorganisms - Staphylococcus aureus (methicillin susceptible strains), Streptococcus pneumoniae (penicillin susceptible 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 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 (group A beta-hemolytic streptococcus), Enterococcus faecalis and Staphylococcus aureus, including Staphylococcus aureus (methicillin-resistant strains) to erythromycin, azithromycin, other macrolides and lincosamides are described.
Antimicrobial bactericide 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. Not active against aerobic bacteria.
Interacts with the DNA of a microbial cell, causes a violation of the spiral structure, rupture of threads, suppression of the synthesis of nucleic acids and cell death.Causes sensitization to alcohol (tetur-like action).
Suction and distribution
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 Tmax 0.5-1.5 h, C max fluconazole in plasma 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. It penetrates well into the cerebrospinal fluid, with fungal meningitis, the concentration in the cerebrospinal fluid is about 85% of that in the plasma. In the fluid, epidermis and stratum corneum (selective accumulation), concentrations exceeding serum levels are achieved. V d approaches the total water content in the body.
Metabolism and excretion
T 1/2 fluconazole is about 30 hours. It is an inhibitor of the 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 creatinine clearance.
Pharmacokinetics in special clinical cases
The pharmacokinetics of fluconazole significantly depends on the functional state of the kidneys, and there is an inverse relationship between T 1/2 and KK. After hemodialysis for 3 hours the concentration of fluconazole in plasma is reduced by 50%.
Suction and distribution
Azithromycin is rapidly absorbed from the digestive tract, which is due to its resistance to acidic environment and lipophilicity. Bioavailability after a single dose of 500 mg - 37% (the effect of "first passage" through the liver). After oral administration, 500 mg of C max is 0.4 mg / l, and T max is 2.5-2.9 hours.
In tissues and cells, the concentration is 10-50 times higher than in serum. V d - 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).
Metabolism and excretion
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: T 1/2 is 14-20 hours in the range from 8 to 24 hours after taking the drug and 41 hours in the interval from 24 to 72 hours. It is excreted in bile in unchanged form (50% ) and kidneys (6%).
Pharmacokinetics in special clinical cases
Eating changes the pharmacokinetics: when taking azithromycin in the dosage form of the tablet, C max is increased by 31%, while the AUC does not change.
In elderly men (65-85 years) pharmacokinetic parameters do not change, in women C max increases (by 30-50%).
Suction and distribution
Absorption is high, bioavailability is 80%. After a single oral dose of 2 grams, T max is 4 hours.
Penetrates through the placental barrier, excreted in breast milk.
Metabolism and excretion
Metabolised in the liver.
It is excreted in the urine for 72 hours (16% of the dose).
Combined infections of the genitourinary tract, transmitted sexually:
- bacterial vaginosis;
- fungal infections;
- concomitant specific and nonspecific cystitis, urethritis, vulvovaginitis, cervicitis.
The drug should be taken orally - at the same time all 4 tab. (1 table fluconazole, 1 table azithromycin and 2 tablets per day), included in the blister, taking into account the intake of food (because the absorption of azithromycin varies with simultaneous meals, it is better to take it 1 hour before meals or 2 h after eating), once.
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 "liver" enzymes, Hepatitis, hepatocellular necrosis), incl. with a lethal 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).
From the hematopoiesis: leukopenia, thrombocytopenia, neutropenia, agranulocytosis.
From the cardiovascular system: an increase in the duration of the QT interval, fibrillation / flutter of the ventricles, arrhythmia ventricular tachysystolic type of "pirouette" (torsade de pointes).
Other: renal dysfunction, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia, increased sweating, myalgia, asthenia, weakness, fever.
From 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 of the tongue, 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.
On the part of the reproductive system: vaginal candidiasis, vaginitis.
From the side of the urinary system: interstitial nephritis, acute renal failure, an increase in the concentration of urea and creatinine in the blood plasma.
From the cardiovascular system: palpitations, chest pain, arrhythmia, decreased blood pressure, ventricular tachycardia, increased QT interval, bidirectional ventricular tachycardia.
From the nervous system: dizziness, headache, vertigo, drowsiness, convulsions, paresthesia, hypoesthesia, insomnia, hyperactivity, aggressiveness, anxiety, anxiety, nervousness, fainting.
From the hemopoietic 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.
Possible side effects noted when taking imidazole derivatives:
On the part of 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, impaired coordination of movements, ataxia, paresthesia, polyneuropathy.
Allergic reactions: urticaria.
- simultaneous administration of astemizole, erythromycin, pimozide, quinidine, cisapride, ergotamine, dihydroergotamine;
- simultaneous reception of other drugs that extend the QT interval;
- organic diseases of the central nervous system;
severe hepatic impairment;
- renal insufficiency with CC less than 40 ml / min;
- blood diseases (including in the anamnesis);
- lactation period;
- children's age till 18 years;
- hypersensitivity to fluconazole and other azole compounds;
- hypersensitivity to fluconazole (including other azole antifungal drugs in history), azithromycin (including macrolides), secnidazole (including other nitroimidazoles);
- Hypersensitivity to other components of the tablets that make up the kit.
Caution should be used at the same time as rifabutin or other drugs metabolized by the cytochrome P450 system; simultaneously with warfarin, digoxin, terfenadine;with potentially proaritmogenic states in patients with multiple risk factors (organic heart disease, electrolyte balance disorders); simultaneously with drugs that extend the QT interval (antiarrhythmic drugs IA and III class), with arrhythmia (risk of ventricular arrhythmias and prolongation of the QT interval), with moderate violations of the liver and kidneys, with myasthenia.
PREGNANCY AND LACTATION
Safocid is contraindicated for use in pregnancy and lactation (breastfeeding).
APPLICATION FOR FUNCTIONS OF THE LIVER
The drug is contraindicated in severe renal failure (CC less than 40 ml / min); with moderate renal dysfunction should be prescribed with caution
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in severe hepatic insufficiency; with moderate violations of the liver should be prescribed with caution
APPLICATION FOR CHILDREN
Contraindication: children under 18 years.
With simultaneous use of antacids, a break of 2 hours should be observed before taking azithromycin.
Due to the fact that when a joint use of secnidazole with alcohol can develop a disulfiram-like reaction (abdominal cramps, nausea, vomiting, headache, rush of blood to the face), during treatment 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).
Influence on ability to drive vehicles, mechanisms
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.
Cases of overdose of a set of Tabocid tablets are not described. In case of overdose, immediately consult a doctor.
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%.
Symptoms: nausea, temporary loss of hearing, vomiting, diarrhea.
Treatment: symptomatic; reception of activated carbon, control of vital functions.
In case of suspected overdose, supportive and symptomatic treatment should be performed; gastric lavage, reception of activated carbon.
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 prolongation of the QT interval and the development of ventricular arrhythmia such as pirouette.
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 prolongation of the QT interval and the development of ventricular arrhythmia such as pirouette.
With the simultaneous use of quinidine with fluconazole, inhibition of quinidine metabolism is possible. The use of quinidine is associated with prolongation of the QT interval and rare cases of ventricular arrhythmia such as pirouette.
With the simultaneous use of fluconazole and erythromycin, an increased risk of cardiotoxicity (prolongation of the QT interval, development of ventricular arrhythmia of the "pirouette" type), up to sudden cardiac arrest is possible.
With the 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 / day), a significant increase in the plasma cisapride concentration and an increase in the QT interval were observed.
Benzodiazepines (short-acting): fluconazole increases the concentration of midazolam after ingestion of the latter, which can lead to an increased risk of psychomotor effects. Fluconazole increases AUC and T 1/2 of triazolam after ingestion of the latter, so that an increase in the effect and an increase in the duration of the action of triazolam are possible. With simultaneous use of short-acting benzodiazepines fluconazole and may require dose reduction benzodiazepines and careful monitoring of patients.
Rifampicin Fluconazole increases metabolism, whereby T 1/2 and fluconazole concentration in plasma decreased by 20% and 25%), respectively. May require higher doses of fluconazole.
Fluconazole may increase tacrolimus concentration in serum after the last inward due to inhibition of gut metabolism of tacrolimus isoenzyme CYP3A4. After the on / in the Tacrolimus pharmacokinetic parameters significant changes were observed. When the concentration of tacrolimus increased risk of nephrotoxicity. It is necessary to control the concentration of tacrolimus and conduct dose correction if necessary.
Fluconazole increases the C max and AUC zidovudine respectively 84% and 74%, due to a decrease its clearance by about 45%. Therefore, may increase the risk of side effects of zidovudine. Patients should be carefully monitored for the development of zidovudine-related adverse reactions.
Some azoles in combination with terfenadine associated with the occurrence of serious arrhythmias including paroxysmal ventricular tachycardia (torsade de pointes), due to increased duration of QT interval on the electrocardiogram. Studies conducted with fluconazole showed that at a daily dose of 200 mg fluconazole was not observed lengthening of the QT interval. In applying fluconazole 400 or 800 mg there was a significant increase in the plasma concentration of terfenadine. Receiving fluconazole 400 mg or more in combination with terfenadine contraindicated. Patients should be carefully observed while receiving terfenadine and fluconazole less than 400 mg / cut.
Hydrochlorothiazide, increases the concentration of fluconazole in the plasma by 40% (clinical significance is unlikely).
Fluconazole increases the concentration in plasma and T 1/2 hypoglycemic drugs for oral administration, sulfonylurea derivatives: chlorpropamide, glibenclamide, tolbutamide and glipizide. It should periodically monitor the concentration of glucose in the blood (hypoglycaemia) and, if necessary, correct the dose of oral hypoglycemic drugs.
When simultaneous administration of fluconazole during treatment coumarin derivatives (warfarin), an increase in prothrombin time. In patients concomitantly receiving oral anticoagulants, coumarin derivatives, requires careful monitoring of the prothrombin time.
The simultaneous use of fluconazole and rifabutin can lead to an increase in plasma concentration of the latter; while the application of uveitis cases are described.
Fluconazole reduces theophylline clearance and increases its plasma concentration. Patients who are receiving high doses of theophylline or who have a chance of developing theophylline toxicity should be kept under observation for early detection of the symptoms of theophylline overdose.
Fluconazole clinically significant increases in the concentration of phenytoin plasma. With simultaneous application to be monitored phenytoin plasma concentration and, if necessary, to carry out dose correction.
Fluconazole increases the AUC of cyclosporin. With simultaneous application of fluconazole (200 mg / day) and cyclosporine (2.7 mg / kg / day) for patients with kidney transplantation Cyclosporine AUC value was increased 1.8 times.
With simultaneous use of fluconazole at 50 mg and oral contraceptives there were no significant changes in plasma concentrations of ethinyl estradiol and levonorgestrel, but using 200 mg of fluconazole increase in AUC was observed for 40% of ethinyl estradiol and levonorgestrel - 24%. So do not expect the effect of fluconazole on the effectiveness of combined oral contraceptives.
Antacids (aluminum and magnesium-containing), ethanol and food slow down and reduce the absorption of azithromycin.
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 has no clinically significant impact on the blood concentration of carbamazepine, cimetidine, didanosine, efavirenz, fluconazole, indinavir, midazolam, theophylline, triazolam, trimethoprim / sulfamethoxazole, cetirizine, sildenafil, atorvastatin, rifabutin and methylprednisolone, while the application.
Care must be taken with co-administration of terfenadine and azithromycin, since it has been found that simultaneous reception of terfenadine and various types of arrhythmia and antibiotics causes lengthening of the interval QT. On this basis, we can not exclude the above-mentioned complications during coadministration of terfenadine and azithromycin.
Ergotamine and dihydroergotamine: increased toxic effect (vasospasm, dysesthesia).
Macrolides slow excretion, increased plasma concentrations and toxicity of cycloserine, anticoagulants, methylprednisolone, felodipine, as well as medicaments suffer from microsomal oxidation (carbamazepine, terfenadine, cyclosporine, hexobarbital, ergot alkaloids, valproate, disopyramide, bromocriptine, phenytoin, oral hypoglycemic drugs), but when used azalides (azithromycin including) this type of interaction was observed.
Lincosamides weaken, and tetracycline and chloramphenicol enhance the efficacy of azithromycin.
When co-administered azithromycin and digoxin is necessary to control the concentration of digoxin in the blood, because Many macrolides enhance absorption of digoxin in the gut, thereby increasing its concentration in blood plasma.
If necessary, concomitant use of azithromycin with cyclosporine cyclosporine recommended to control blood due to a significant increase in AUC.
While the use of zidovudine, azithromycin does not affect the pharmacokinetic parameters of zidovudine in the blood plasma or renal excretion of zidovudine and its metabolite glyukuronirovannogo. However, increasing the concentration of the active metabolite - phosphorylated zidovudine in monocytes. The clinical significance of this fact is not known.
In an application with nelfinavir may increase the concentration of azithromycin in plasma is not accompanied by a significant increase in side reactions and not requiring correction dose preparations.
increases the effects of anticoagulants. It is not recommended to combine with nondepolarizing muscle relaxants (vecuronium bromide). Together with the admission drugs lithium increases its concentration in plasma.
It enhances the hypoglycemic effect of insulin and oral hypoglycemic agents.
Similarly, disulfiram causes intolerance to ethanol.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be kept out of the reach of children, the dark from light and moisture at a temperature of not higher than 30 В° C. Shelf life - 3 years.