Instructions for Safocid
Active ingredients Safocid:
- Azithromycin
- Secnidazole
- Fluconazole
Release form Safocid:
pills set
Owner / Registrar Safocid:
NIZHFARM, JSC
- International Classification of Diseases (ICD-10) A54
- Gonococcal infection A56.0
- Chlamydial infections of the lower urinary tract A56.1
- Chlamydial infections of the pelvic organs and others A59
- Trichomoniasis B37.3
- Vulvar and vaginal candidiasis (N77.1 *) B37.4
- Candidiasis of other urogenital sites N30
- Cystitis N34
- Urethritis and urethral syndrome N72
- Inflammatory disease of the cervix N76
Other inflammatory diseases of the vagina and vulva
Indications Safocid:
Sexually transmitted infections of the genitourinary tract:
gonorrhea and trichomoniasis
chlamydia and bacterial vaginosis
fungal infections and concomitant specific and non-specific cystitis, urethritis, vulvovaginitis, cervicitis.
Pharmacological group Safocid:
Combined drug with antiprotozoal, antifungal and antibacterial action
pharmachologic effect Safocid:
A combined set containing an antifungal agent Safocid, an antibiotic and an antibacterial agent with antiprotozoal activity.
Fluconazole
Antifungal agent Safocid, has a highly specific effect, inhibiting the activity of fungal enzymes, dependent on cytochrome P450. Blocks the transformation of fungal lanosterol into ergosterol; increases the permeability of the cell membrane, disrupts its growth and replication. Fluconazole, being highly selective for cytochrome P450 of 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 possess antiandrogenic activity.
Active in opportunistic mycoses, incl. caused by Candida spp. (including generalized forms of candidiasis against the background of immunosuppression), Cryptococcus neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp .; with endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulation (including with immunosuppression). Safocid
Azithromycin
A broad-spectrum antibacterial agent, azalide, acts bacteriostatically. By binding to the 50S ribosome subunit, it inhibits peptide translocase at the stage of translation, inhibits protein synthesis, slows down the growth and reproduction of bacteria, and has a bactericidal effect in high concentrations. It is active against extra- and intracellular pathogens.
Azithromycin-sensitive 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 medium sensitivity to penicillin). Safocid
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 have been reported between Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococcus), Enterococcus faecalis and Staphylococcus aureus, including Staphylococcus aureus (methicillin-resistant strains) to erythromycinamycin, other azithromycinamycin, and other
Secnidazole
Antimicrobial bactericidal agent Safocid - a synthetic derivative of nitroimidazole. It is active against obligate anaerobic bacteria (spore and non-spore-forming), causative agents of some protozoal infections: Trichomonas spp., Giardia lamblia, Entamoeba histolytica. Not active against aerobic bacteria.
It interacts with the DNA of a microbial cell, causes a violation of the spiral structure, breaking of threads, suppression of the synthesis of nucleic acids and cell death. It causes sensitization to alcohol (teturam-like action).
Pharmacokinetics Safocid:
Fluconazole
Absorption and distribution of Safocid
Absorption - high, bioavailability - 90%. Simultaneous food intake does not affect the absorption of the drug taken orally. After oral administration on an empty stomach, 150 mg T max - 0.5-1.5 h, C max of fluconazole in plasma is 90% of its plasma concentration when administered intravenously in the same dose.
The connection with plasma proteins is 11-12%. Plasma concentration is directly dose dependent. Fluconazole penetrates well into all body fluids. The concentration of the active substance in breast milk, joint 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 plasma. In sweat fluid, epidermis and stratum corneum (selective accumulation), concentrations exceeding serum are achieved. V d approaches the total body water content.
Metabolism and excretion Safocid:
T 1/2 of 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). Fluconazole/Safocid clearance is proportional to creatinine clearance.
Pharmacokinetics in special clinical situations Safocid:
The pharmacokinetics of fluconazole significantly depends on the functional state of the kidneys, while there is an inverse relationship between T 1/2 and CC. After hemodialysis for 3 hours, the plasma concentration of fluconazole decreases by 50%.
Azithromycin
Absorption and distribution:
Azithromycin is rapidly absorbed from the gastrointestinal tract, which is due to stability in an acidic environment and lipophilicity. Bioavailability after a single dose of 500 mg - 37% (the effect of "first pass" through the liver).
After oral administration of 500 mg, C max is 0.4 mg / l, T max is 2.5-2.9 hours.
In tissues and cells, the concentration is 10-50 times higher than in blood serum. V d- 31.1 l / kg. Easily passes histohematogenous barriers. It penetrates well into the respiratory tract, genitourinary organs and tissues, into the prostate gland, into the skin and soft tissues; accumulates in an environment 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).
Safocid Penetrates through cell membranes 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 inflammatory edema. In the focus of inflammation, it remains in effective concentrations for 5-7 days after taking the last dose. Communication with plasma proteins - 7-50% (inversely proportional to the concentration in the blood).
Metabolism and excretion
It is demethylated in the liver, the resulting metabolites are inactive. Plasma clearance - 630 ml / min.
The elimination of azithromycin from 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 range from 24 to 72 hours. It is excreted in the bile unchanged (50% ) and kidneys (6%).
Pharmacokinetics in special clinical situations Safocid:
Food intake changes the pharmacokinetics: when taking azithromycin in the dosage form of a tablet, C max increases by 31%, while the AUC does not change.
In elderly men (65-85 years old), pharmacokinetic parameters do not change, in women, C max increases (by 30-50%).
Secnidazole
Absorption and distribution
Absorption is high, bioavailability is 80%. After a single oral dose of 2 g, T max is 4 hours.
Penetrates through the placental barrier, excreted in breast milk.
Metabolism and excretion
Metabolized in the liver.
It is excreted in the urine within 72 hours (16% of the dose).
Fluconazole
The drug Safocid is usually very well tolerated.
From the central and peripheral nervous system: headache, dizziness, convulsions, insomnia, drowsiness, tremors.
From the digestive system: abdominal pain, diarrhea, flatulence, nausea, taste change, dyspepsia, vomiting, dryness of the oral mucosa, liver dysfunction (jaundice, hyperbilirubinemia, increased concentration of alkaline phosphatase, cholestasis, increased activity of "liver" enzymes, hepatitis, hepatocellular necrosis), incl. with a lethal outcome.
Allergic reactions: skin rash, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactic reactions (including angioedema, facial edema, urticaria, itching of the skin).
From the side of hematopoiesis: leukopenia, thrombocytopenia, neutropenia, agranulocytosis.
On the part of the cardiovascular system: an increase in the duration of the QT interval, fibrillation / flutter of the ventricles, ventricular tachysystolic arrhythmia of the "pirouette" type (torsade de pointes).
Others: impaired renal function, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia, increased sweating, myalgia, asthenia, weakness, fever.
Azithromycin
From the digestive system: flatulence, nausea, vomiting, constipation, abdominal pain, decreased appetite, gastritis, melena, cholestatic jaundice, increased activity of "hepatic" transaminases, candidiasis of the oral mucosa, diarrhea, indigestion, discoloration of the tongue, pseudomembranous colitis, pancreatitis, hepatitis, liver dysfunction, increased bilirubin concentration, liver failure, liver necrosis (possibly fatal), fulminant hepatitis.
Allergic reactions: skin rash, itching, angioedema, urticaria, anaphylactic reaction, including edema (in rare cases fatal), erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
From the reproductive system: vaginal candidomycosis, vaginitis.
From the urinary system: interstitial nephritis, acute renal failure, increased 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, hypesthesia, insomnia, hyperactivity, aggressiveness, anxiety, anxiety, nervousness, fainting. Safocid
From the hematopoietic system: lymphopenia, leukopenia, neutropenia, thrombocytopenia, hemolytic anemia, neutrophilia.
From the senses: tinnitus, reversible hearing impairment up to deafness, impaired perception of taste and smell.
Others: asthenia, photosensitivity, conjunctivitis, blurred vision, eosinophilia, myasthenia gravis, arthralgia, peripheral edema, malaise, changes in potassium concentration. Safocid
Secnidazole
Possible side effects noted when taking Safocid derivatives:
From the digestive system: nausea, vomiting, abdominal pain, "metallic" taste in the mouth, glossitis, stomatitis.
From the hematopoietic system: leukopenia.
From the side of the central and peripheral nervous system: dizziness, impaired coordination of movements, ataxia, paresthesia, polyneuropathy.
Allergic reactions Safocid: urticaria.
Overdose Safocid:
Cases of overdose of the Safocid set of tablets have not been described. In case of overdose, consult a doctor immediately.
Fluconazole
Symptoms: hallucinations, paranoid behavior.
Treatment: symptomatic; gastric lavage (if necessary), forced diuresis. Hemodialysis for 3 hours reduces the plasma concentration of fluconazole by approximately 50%.
Azithromycin
Symptoms: nausea, temporary hearing loss, vomiting, diarrhea.
Treatment: symptomatic; reception of activated carbon, control of vital functions.
Secnidazole
If an overdose is suspected, supportive and symptomatic treatment should be carried out; gastric lavage, intake of activated carbon.
Special instructions Safocid:
With the simultaneous use of antacids, it is necessary to observe a break of 2 hours before taking azithromycin.
Due to the fact that the combined use of secnidazole with alcohol may develop a disulfiram-like reaction (abdominal cramps, nausea, vomiting, headache, flushing), during the treatment period, it is necessary to avoid the use of ethanol.
Secnidazole can cause treponema immobilization, which leads to a false positive Nelson's test (treponema pallidum immobilization reaction, RIBT).
Influence on the ability to drive vehicles, mechanisms
The use of a set of tablets Safocid, as a rule, does not affect the ability to drive a car and perform work that requires a high speed of mental and physical reactions, however, when taken, dizziness and other side effects that may affect the above abilities may develop.
With renal failure
The drug is contraindicated in severe renal failure (CC less than 40 ml / min); with moderate impairment of renal function, the drug should be prescribed with caution
In case of liver dysfunction
The drug Safocid is contraindicated in severe hepatic impairment; with moderate liver dysfunction, the drug should be prescribed with caution
Application during pregnancy and lactation
Safocid is contraindicated for use during pregnancy and lactation (breastfeeding).
Drug Safocid interactions
Fluconazole
With the simultaneous use of astemizole with fluconazole, a decrease in the clearance of astemizole and an increase in its concentration in plasma may occur, which can cause an extension of the QT interval and the development of ventricular arrhythmias of the "pirouette" type.
With the simultaneous use of pimozide with fluconazole/Safocid, inhibition of the metabolism of pimozide is possible. An increase in the concentration of pimozide in blood plasma can cause prolongation of the QT interval and the development of ventricular arrhythmias 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 prolongation of the QT interval and rare cases of pirouette-type ventricular arrhythmias.
With the simultaneous use of fluconazole/Safocid and erythromycin, an increase in the risk of cardiotoxicity (prolongation of the QT interval, development of ventricular arrhythmias 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 heart disorders, 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 concentration of cisapride in plasma and an increase in the duration of the QT interval were observed.
Benzodiazepines (short-acting): fluconazole increases the concentration of midazolam after oral administration, which may lead to an increased risk of psychomotor effects. Fluconazole/Safocid increases the AUC and T 1/2 of triazolam after oral administration of the latter, which may increase the effect and increase the duration of action of triazolam. With the simultaneous use of short-acting benzodiazepines and fluconazole, it may be necessary to reduce the dose of benzodiazepines and carefully monitor the patient's condition.
Rifampicin increases the metabolism of fluconazole, as a result of which T 1/2 and plasma concentration of fluconazole decrease by 20% and 25%), respectively. Increasing the dose of fluconazole may be required.
Fluconazole can increase the concentration of tacrolimus in serum after oral administration, due to inhibition of the metabolism of tacrolimus in the intestine by the isoenzyme CYP3A4. No significant changes in pharmacokinetic parameters were observed after intravenous administration of tacrolimus. As the concentration of tacrolimus increases, the risk of nephrotoxicity increases. It is necessary to monitor the concentration of tacrolimus and, if necessary, adjust the dose.
Fluconazole increases the C max and AUC of zidovudine by 84% and 74%, respectively, due to a decrease in its clearance by approximately 45%. Therefore, the risk of side effects of zidovudine may be increased. Patients should be closely monitored for the development of zidovudine-related adverse reactions.
Some azoles in combination with terfenadine have been associated with the occurrence of serious rhythm disturbances, including paroxysms of ventricular tachycardia (torsade de pointes), due to an increase in the duration of the QT interval on the ECG. Studies carried out with fluconazole have shown that no prolongation of the QT interval was observed with a daily dose of 200 mg of fluconazole. When using fluconazole at a dose of 400 or 800 mg, a significant increase in the plasma concentration of terfenadine was observed. Taking fluconazole 400 mg or more in combination with terfenadine is contraindicated. Patients should be closely monitored while taking terfenadine and fluconazole at a dose of less than 400 mg / day. Safocid
Hydrochlorothiazide increases the plasma concentration of fluconazole by 40% (clinical significance is unlikely).
Fluconazole increases the plasma concentration and T 1/2 of hypoglycemic drugs for oral administration, sulfonylurea derivatives: chlorpropamide, glibenclamide, glipizide and tolbutamide. You should periodically monitor the concentration of glucose in the blood (risk of hypoglycemia) and, if necessary, adjust the dose of oral hypoglycemic drugs Safocid.
With the simultaneous administration of fluconazole during treatment with coumarin derivatives (warfarin), an increase in prothrombin time was observed. In patients who are simultaneously receiving indirect anticoagulants, coumarin derivatives, careful monitoring of prothrombin time is required.
The simultaneous use of fluconazole and rifabutin may lead to an increase in the concentration of the latter in plasma; with simultaneous use, cases of uveitis have been described.
Fluconazole reduces theophylline clearance and increases its plasma concentration. Patients who receive high doses of theophylline or who are likely to develop theophylline intoxication should be monitored for early detection of symptoms of theophylline overdose.
Fluconazole clinically significantly increases the plasma concentration of phenytoin. With simultaneous use, it is necessary to monitor the concentration of phenytoin in plasma and, if necessary, adjust the dose.
Fluconazole increases the AUC of cyclosporine. With the simultaneous use of fluconazole (200 mg / day) and cyclosporine (2.7 mg / kg / day) in patients with kidney transplantation, the AUC value of cyclosporin was increased by 1.8 times. Safocid
With the simultaneous use of fluconazole at a dose of 50 mg and oral contraceptives, no significant changes in plasma concentrations of ethinyl estradiol and levonorgestrel were observed, but with the use of 200 mg of fluconazole, an increase in the AUC of ethinylestradiol by 40% and levonorgestrel was observed by 24%. Therefore, the effect of fluconazole on the efficacy of combined oral contraceptives is not expected.
Azithromycin
Antacids (aluminum and magnesium), ethanol and food slow down and reduce the absorption of azithromycin.
With the joint appointment of warfarin and azithromycin (in usual doses), no change in prothrombin time was detected, however, given that the interaction of macrolides and warfarin may increase the anticoagulant effect, patients need careful control of prothrombin time.
Azithromycin does not have a clinically significant effect on the blood concentration of carbamazepine, cimetidine, didanosine, efavirenz, fluconazole, indinavir, midazolam, theophylline, triazolam, trimethoprim / sulfamethoxazole, cetirizine, the simultaneous use of sildenafil, atorfabnizuastatin, and the simultaneous use of sildenafil, atorfabnizustatin, Safocid
Care must be taken when concomitant administration of terfenadine and azithromycin, since it has been found that the simultaneous administration of terfenadine and various types of antibiotics causes arrhythmia and prolongation of the QT interval. Based on this, the above complications cannot be ruled out when taking terfenadine and azithromycin together.
Ergotamine and dihydroergotamine: increased toxic effects (vasospasm, dysesthesia).
Macrolides slow down excretion, increase the plasma concentration and toxicity of cycloserine, indirect anticoagulants, methylprednisolone, felodipine, as well as drugs that undergo microsomal oxidation (carbamazepine, terfenadine, cyclosporine, hexobarbital, ergot alkaloids, dysoproemic acid, drugs), however, when using azalides (including azithromycin), this type of interaction was not observed.
Lincosamides weaken, and tetracycline and chloramphenicol increase the effectiveness of azithromycin.
When taking digoxin and azithromycin together, it is necessary to control the concentration of digoxin in the blood, because many macrolides increase digoxin absorption in the intestine, thereby increasing its concentration in blood plasma.
If it is necessary to jointly use azithromycin with cyclosporine, it is recommended to control the content of cyclosporine in the blood due to a significant increase in AUC.
When used simultaneously with zidovudine, azithromycin does not affect the pharmacokinetic parameters of zidovudine in blood plasma or the renal excretion of zidovudine and its glucuronidated metabolite. However, the concentration of the active metabolite, phosphorylated zidovudine, increases in monocytes. The clinical significance of this fact is not known. Safocid
With simultaneous use with nelfinavir, an increase in the concentration of azithromycin in the blood plasma is possible, which is not accompanied by a significant increase in adverse reactions and does not require dose adjustment.
Secnidazole/Safocid
Enhances the action of indirect anticoagulants. It is not recommended to combine with non-depolarizing muscle relaxants (vecuronium bromide). When taken simultaneously with lithium preparations, it increases its concentration in plasma.
Enhances the hypoglycemic effect of insulin and oral hypoglycemic agents.
Similarly to disulfiram, it causes intolerance to ethanol.
How to take Safocid:
The drug Safocid should be taken orally - all 4 tablets at the same time. (1 tablet of fluconazole, 1 tablet of azithromycin and 2 tablets of secnidazole), which are part of the blister, taking into account the meal (since the absorption of azithromycin changes with the simultaneous intake of food, it is better to take it 1 hour before meals or after 2 h after meals), once.
Storage conditions and shelf life
The drug Safocid should be stored out of the reach of children, protected from light and moisture, at a temperature not exceeding 30 ° C. The shelf life is 3 years.
Dispensing from pharmacies
The drug Safocid
