Ciprolet A, 600 mg+500 mg 10 pcs

Pharmacological action – antimicrobial, antiprotozoal.
Pharmacodynamics

A combined drug, the action of which is due to the components in its composition.

Tinidazole is an antiprotozoal and antimicrobial agent, imidazole derivative, effective against Trichomonas vaginalis, Entamoeba histolytica, Lamblia, as well as pathogens of anaerobic infections (Clostridium spp, Bacteroides fragilis, Bacteroides melaninogenicus, Eubacter spp., Fusobacterium spp., Peptococcus spp. and Peptostreptococcus spp.) Being a highly lipophilic drug, it penetrates inside trichomonads and anaerobic microorganisms, where it is reduced by nitroreductase, inhibits synthesis and damages DNA structure.

Ciprofloxacin is an antimicrobial agent of broad spectrum activity, derivative of fluoroquinolone, inhibits bacterial DNA-giase (topoisomerases II and IV, responsible for the process of superspiralization of chromosomal DNA around the nuclear RNA, which is required for reading genetic information), inhibits DNA synthesis, growth and division of bacteria, causes evident morphological changes (including cell wall and membrane membrane).cell wall and membranes) and rapid death of the bacterial cell.

It is bactericidal on Gram-negative organisms during resting and dividing (as it affects not only DNA-giase, but also causes lysis of cell wall), on Gram-positive microorganisms – only during dividing. Low toxicity for macroorganism cells is explained by the absence of DNA-gyrase in them. Against the background of ciprofloxacin use there is no parallel development of resistance to other antibiotics which do not belong to gyrase inhibitor group which makes it highly effective against bacteria resistant to aminoglycosides, penicillins, cephalosporins, tetracyclines and many other antibiotics.

Ciprofloxacin is sensitive to Gram-negative aerobic bacteria: Enterobacteriaceae (Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Hafnia alvei, Edwardsiella tarda, Providencia spp., Morganella morganii, Vibrio spp., Yersinia spp.), other Gram-negative bacteria (Haemophilus spp., Pseudomonas aeruginosa, Moraxella catarrhalis, Aeromonas spp, Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejuni, Neisseria spp.), some intracellular pathogens (Legionella pneumophila, Brucella spp, Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii); Gram-positive aerobic bacteria: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).

Most methicillin-resistant staphylococci are also resistant to ciprofloxacin. Resistance develops very slowly because, on the one hand, after the action of ciprofloxacin there are practically no persistent microorganisms, and on the other hand, bacterial cells have no enzymes that inactivate it. Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides are resistant to the drug. Ineffective against Treponema pallidum.

Pharmacokinetics

Intake

All ciprofloxacin and tinidazole are well absorbed in the GI tract after oral administration. Food intake slows absorption but does not change the maximum concentration and bioavailability.

Distribution

Tinidazole. Bioavailability – 100%, binding to plasma proteins – 12%, Tmax after oral administration – 2 hours, Cmax after 500 mg oral administration – 47,7 µg/ml.

Ciprofloxacin. Bioavailability – 50-85%, Vd – 2-3.5 l/kg, binding to plasma proteins – 20-40%, Tmax after oral administration – 60-90 min, Cmax after 500 mg – 0.2 µg/ml.

Metabolism and excretion

Tinidazole penetrates the cerebrospinal fluid at a concentration equal to that in plasma and is reabsorbed in the renal tubules. T1/2 is 12-14 h. Tinidazole is metabolized in the liver with participation of cytochrome P450 enzyme system (CYP3A4). About 50% is excreted in the bile, 25% – by the kidneys, 12% – as metabolites. It is reabsorbed in the renal tubules.

Ciprofloxacin penetrates well into the body fluids and tissues (excluding fat-rich tissue, such as nerve tissue). Concentrations in tissues are 2-12 times higher than in plasma. Therapeutic concentrations are achieved in saliva, tonsils, liver, gallbladder, bile, intestine, abdominal and pelvic organs, uterus, seminal fluid, prostatic tissue, endometrium, fallopian tubes and ovaries, kidneys and urinary tract, lung tissue, bronchial secretion, bone tissue, muscles, synovial fluid and joint cartilage, peritoneal fluid, skin. It penetrates into the cerebrospinal fluid in small amounts, where its concentration, in the absence of cerebral membrane inflammation, is 6-10% of serum fluid, and in the case of inflammation – 14-37%.

Ciprofloxacin also penetrates well into the ocular fluid, bronchial secretion, pleura, peritoneum, lymph, and through the placenta. The concentration of ciprofloxacin in neutrophils is 2-7 times higher than in blood plasma. Activity decreases slightly at pH values less than 6. It is metabolized in the liver (15-30%) to form inactive metabolites (diethylciprofloxacin, sulfociprofloxacin, oxociprofloxacin, formylciprofloxacin). T1/2 is about 4 hours. It is eliminated mainly by the kidneys by tubular filtration and tubular secretion unchanged (40-50%) and as metabolites (15%), the rest – through the gastrointestinal tract. A small amount is excreted with breast milk. Renal Cl is 3-5 ml/min/kg; total Cl is 8-10 ml/min/kg.

In special cases

The pharmacokinetic parameters of tinidazole in patients with CKD (creatinine Cl above 22 ml/min) do not differ from those in healthy subjects.

The T1/2 of ciprofloxacin in CPN is increased up to 12 hours. In CKD (creatinine Cl above 20 ml/min) the percentage excreted through the kidneys.

Indications

Mixed bacterial infections caused by sensitive gram-positive and gram-negative microorganisms, in association with anaerobic microorganisms and/or protozoa:

respiratory tract infections (acute and chronic (in the acute stage) bronchitis, pneumonia, bronchiectasis);
infections of the ENT organs (otitis media, sinusitis, frontal sinusitis, sinusitis, mastoiditis, tonsillitis, pharyngitis);
oral infections (acute ulcerative gingivitis, periodontitis, periostitis);
kidney and urinary tract infections (cystitis, pyelonephritis);
infections of the pelvic and genital organs (prostatitis, adnexitis, salpingitis, oophoritis, endometritis, tubular abscess, pelvioperitonitis);
intra-abdominal infections (infections of the gastrointestinal tract, biliary tract, intraperitoneal abscesses);
infections of the skin and soft tissues (infected ulcers, wounds, burns, abscesses, cellulitis, ulcerative skin lesions in diabetic foot syndrome, bedsores);
infections of bones and joints (osteomyelitis, septic arthritis);
postoperative infections.

Pharmacological effect

Pharmacological action – antimicrobial, antiprotozoal.
Pharmacodynamics

A combined drug whose effect is determined by the components included in its composition.

Tinidazole is an antiprotozoal and antimicrobial agent, an imidazole derivative, effective against Trichomonas vaginalis, Entamoeba histolytica, Lamblia, as well as pathogens of anaerobic infections (Clostridium spp., Bacteroides fragilis, Bacteroides melaninogenicus, Eubacter spp., Fusobacterium spp., Peptococcus spp. and Peptostreptococcus spp.). Being a highly lipophilic drug, it penetrates into Trichomonas and anaerobic microorganisms, where it is reduced by nitroreductase, inhibits synthesis and damages the DNA structure.

Ciprofloxacin is a broad-spectrum antimicrobial agent, a fluoroquinolone derivative, that inhibits bacterial DNA gyrase (topoisomerases II and IV, responsible for the process of supercoiling of chromosomal DNA around nuclear RNA, which is necessary for reading genetic information), disrupts DNA synthesis, growth and division of bacteria; causes pronounced morphological changes (including cell wall and membranes) and rapid death of the bacterial cell.

It has a bactericidal effect on gram-negative organisms during the period of rest and division (since it affects not only DNA gyrase, but also causes lysis of the cell wall), on gram-positive microorganisms – only during the period of division. Low toxicity for the cells of the macroorganism is explained by the absence of DNA gyrase in them. While taking ciprofloxacin, there is no parallel development of resistance to other antibiotics that do not belong to the group of gyrase inhibitors, which makes it highly effective against bacteria resistant to aminoglycosides, penicillins, cephalosporins, tetracyclines and many other antibiotics.

Gram-negative aerobic bacteria are sensitive to ciprofloxacin: enterobacteria (Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Hafnia alvei, Edwardsiella tarda, Providencia spp., Morganella morganii, Vibrio spp., Yersinia spp.), other gram-negative bacteria (Haemophilus spp., Pseudomonas aeruginosa, Moraxella catarrhalis, Aeromonas spp., Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejuni, Neisseria spp.), some intracellular pathogens (Legionella pneumophila, Brucella spp., Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii); gram-positive aerobic bacteria: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).

Most staphylococci resistant to methicillin are also resistant to ciprofloxacin. Resistance develops extremely slowly, since, on the one hand, after the action of ciprofloxacin there are practically no persistent microorganisms left, and on the other hand, bacterial cells do not have enzymes that inactivate it. The following are resistant to the drug: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. Ineffective against Treponema pallidum.

Pharmacokinetics

Suction

Both ciprofloxacin and tinidazole are well absorbed from the gastrointestinal tract after oral administration. Eating slows down absorption, but does not change the maximum concentration or bioavailability.

Distribution

Tinidazole. Bioavailability – 100%, plasma protein binding – 12%, Tmax after oral administration – 2 hours, Cmax after oral administration of 500 mg – 47.7 mcg/ml.

Ciprofloxacin. Bioavailability – 50-85%, Vd – 2-3.5 l/kg, plasma protein binding – 20-40%, Tmax after oral administration – 60-90 min, Cmax after oral administration 500 mg – 0.2 μg/ml.

Metabolism and excretion

Tinidazole penetrates the cerebrospinal fluid in a concentration equal to that in plasma and is reabsorbed in the renal tubules. T1/2 – 12-14 hours. Tinidazole is metabolized in the liver with the participation of the cytochrome P450 (CYP3A4) enzyme system. About 50% is excreted in bile, 25% in the kidneys, and 12% in the form of metabolites. It is reabsorbed in the renal tubules.

Ciprofloxacin penetrates well into body fluids and tissues (excluding fat-rich tissue, such as nervous tissue). Concentrations in tissues are 2–12 times higher than in plasma. Therapeutic concentrations are achieved in saliva, tonsils, liver, gall bladder, bile, intestines, abdominal and pelvic organs, uterus, seminal fluid, prostate tissue, endometrium, fallopian tubes and ovaries, kidneys and urinary organs, lung tissue, bronchial secretions, bone tissue, muscles, synovial fluid and articular cartilage, peritoneal liquids, skin. It penetrates into the cerebrospinal fluid in a small amount, where its concentration, in the absence of inflammation of the meninges, is 6–10% of the serum value, and with inflammation – 14–37%.

Ciprofloxacin also penetrates well into the ocular fluid, bronchial secretions, pleura, peritoneum, lymph, and through the placenta. The concentration of ciprofloxacin in blood neutrophils is 2–7 times higher than in blood plasma. Activity decreases slightly at pH values ​​less than 6. Metabolized in the liver (15–30%) with the formation of low-active metabolites (diethylciprofloxacin, sulfociprofloxacin, oxociprofloxacin, formylciprofloxacin). T1/2 – about 4 hours. It is excreted mainly by the kidneys by tubular filtration and tubular secretion in unchanged form (40-50%) and in the form of metabolites (15%), the rest – through the gastrointestinal tract. A small amount is excreted in breast milk. Renal Cl – 3–5 ml/min/kg; total Cl – 8–10 ml/min/kg.

In special cases

The pharmacokinetic parameters of tinidazole in patients with chronic renal failure (creatinine Cl above 22 ml/min) do not differ from those in healthy people.

For ciprofloxacin in chronic renal failure, T1/2 increases to 12 hours. In chronic renal failure (creatinine Cl above 20 ml/min), the percentage excreted through the kidneys.

Special instructions

The possibility of cross-allergic reactions should be taken into account. Patients with hypersensitivity to other imidazole derivatives may develop cross-sensitivity to tinidazole; the development of a cross-allergic reaction to ciprofloxacin is also possible in patients with hypersensitivity to other fluoroquinolone derivatives.

During treatment, it is recommended to avoid contact with direct sunlight. If photosensitivity reactions occur, you should immediately stop using the drug.

During the treatment period, it is not recommended to take ethanol (risk of developing disulfiram-like reactions against the background of tinidazole, which is part of the drug).

To avoid the development of crystalluria, the recommended daily dose should not be exceeded; sufficient fluid intake and maintaining an acidic urine reaction are also necessary. Causes dark coloration of urine, which has no clinical significance.

For patients with epilepsy, a history of seizures, vascular diseases and organic brain damage, due to the risk of developing adverse reactions from the central nervous system, the drug should be prescribed only for health reasons.

If severe and prolonged diarrhea occurs during or after treatment, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and the appointment of appropriate treatment.

If pain appears in the tendons or the first signs of tenosynovitis appear, treatment should be stopped.

When treating for more than 6 days, peripheral blood patterns should be monitored.

Impact on the ability to drive a car or perform work that requires increased speed of physical and mental reactions. During treatment, you should refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Active ingredient

Tinidazole, Ciprofloxacin

Composition

1 Film-coated tablet:

active substances:

ciprofloxacin hydrochloride monohydrate – 582.285 mg (equivalent to 500 mg ciprofloxacin),

tinidazole – 600.00 mg,

excipients: corn starch – 35 mg; croscarmellose sodium – 27.476 mg; MCC – 5 mg; sodium carboxymethyl starch (type A) – 5 mg; colloidal silicon dioxide – 3.952 mg; talc – 8.952 mg; magnesium stearate – 7 mg,

film shell: hypromellose (6 cps) – 21.21 mg; sorbic acid – 0.2095 mg; titanium dioxide – 1 mg; talc – 4.01 mg; macrogol 6000 – 4.01 mg; polysorbate 80 – 0.2095 mg; dimethicone – 0.295 mg; dye “Sunset” yellow (E110) – 9.047 mg.

Pregnancy

Since tinidazole and ciprofloxacin are excreted into breast milk, during treatment with the drug it is necessary to stop breastfeeding, since tinidazole can have a mutagenic and carcinogenic effect.

Contraindications

Hypersensitivity (including to fluoroquinolone or imidazole derivatives);
blood diseases (history);
inhibition of bone marrow hematopoiesis;
organic diseases of the central nervous system;
pregnancy;
lactation period;
simultaneous use with tizanidine (risk of a pronounced decrease in blood pressure, drowsiness);
acute porphyria;
children under 18 years of age.

With caution: severe cerebral atherosclerosis;

cerebrovascular accident;

mental illness; epilepsy; history of seizures;

severe renal and/or liver failure;

old age.

Side Effects

From the digestive system: loss of appetite, dryness of the oral mucosa, metallic taste in the mouth, nausea, vomiting, diarrhea, abdominal pain, flatulence, cholestatic jaundice (especially in patients with previous liver diseases), hepatitis, hepatonecrosis.

From the nervous system: headache, dizziness, increased fatigue, impaired coordination of movements (including locomotor ataxia), dysarthria, peripheral neuropathy; rarely – convulsions, weakness, anxiety, tremor, insomnia, nightmares, peripheral paralgesia (anomaly in the perception of pain), increased ICP, confusion, depression, hallucinations, as well as other manifestations of psychotic reactions, migraine, fainting, thrombosis of cerebral arteries, increased sweating.

From the senses: disturbances of taste and smell, visual impairment (diplopia, changes in color vision), tinnitus, hearing loss.

From the cardiovascular system: tachycardia, arrhythmia, decreased blood pressure.

From the hematopoietic organs: leukopenia, granulocytopenia, anemia (including hemolytic), thrombocytopenia, leukocytosis, thrombocytosis.

From the urinary system: hematuria, crystalluria (with an alkaline reaction of urine and decreased diuresis), glomerulonephritis, dysuria, polyuria, urinary retention, albuminuria, decreased nitrogen excretory function of the kidneys, interstitial nephritis.

Allergic reactions: skin itching, urticaria, skin rash, drug fever, petechiae, angioedema, shortness of breath, eosinophilia, photosensitivity, vasculitis, erythema nodosum, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

Laboratory indicators: hypoprothrombinemia, increased activity of liver transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, hyperglycemia.

Other: arthralgia, arthritis, tenosynovitis, tendon ruptures, asthenia, myalgia, superinfections (candidiasis, pseudomembranous colitis), flushing.

Interaction

Effects due to tinidazole. Enhances the effect of indirect anticoagulants. To reduce the risk of bleeding, the dose of Tsiprolet®A is reduced by 50%. Enhances the effect of ethanol (disulfiram-like reactions). Phenobarbital accelerates the metabolism of tinidazole. The drug Tsiprolet® A is not recommended to be prescribed with ethionamide.

Effects due to ciprofloxacin. Due to a decrease in the activity of microsomal oxidation processes in hepatocytes, it increases the concentration and lengthens T1/2 of theophylline and other xanthines, incl. caffeine, oral hypoglycemic drugs, indirect anticoagulants, helps reduce the prothrombin index. It enhances the nephrotoxic effect of cyclosporine, there is an increase in serum creatinine; in such patients it is necessary to monitor this indicator 2 times a week.

Oral administration together with iron-containing drugs, sucralfate and antacid drugs containing Mg2+, Ca2+, Al3+, didanosine leads to a decrease in the absorption of ciprofloxacin. Therefore, the drug Ciprolet®A is prescribed 1–2 hours before or 4 hours after taking the above drugs. NSAIDs (excluding acetylsalicylic acid) increase the risk of seizures. Metoclopramide accelerates absorption, which leads to a decrease in Tmax. Co-administration of uricosuric drugs leads to a slower elimination (up to 50%) and an increase in plasma concentrations of ciprofloxacin. Increases Cmax by 7 times (from 4 to 21 times) and AUC of tizanidine, which increases the risk of a pronounced decrease in blood pressure and drowsiness.

The drug Tsiprolet®A is compatible with sulfonamides and antibiotics (β-lactam antibiotics, aminoglycosides, erythromycin, rifampicin, cephalosporins), when combined with which synergism is usually observed.

Overdose

Symptoms: in cases of acute overdose, symptoms of reversible damage to the urinary system will prevail, and convulsions are possible.

Treatment: induction of vomiting, gastric lavage. Symptomatic, supportive therapy (including adequate hydration of the body). There is no specific antidote. With the help of hemo- or peritoneal dialysis, tinidazole can be completely eliminated from the body, and ciprofloxacin – only slightly (< 10%).

Storage conditions

At a temperature not higher than 25 C.
Keep out of the reach of children!

Shelf life

3 years.

Manufacturer

Dr. Reddy’s Laboratories Ltd, India