Orcipol® [Ornidazole, Ciprofloxacin]

Pharmacological properties

orcipole is a combined antimicrobial and antiprotozoal drug, the pharmacological action of which is due to the properties of its constituent components: ciprofloxacin (a derivative of fluoroquinolone of the second generation) and ornidazole (a derivative of 5-nitroimidazole).

Ciprofloxacin inhibits the bacterial DNA hydrase enzyme and inhibits the synthesis of bacterial DNA; causes morphological changes in the membrane and cell wall of bacteria, leading to rapid cell death. It acts on microorganisms in a state of growth and dormancy. It has a wide spectrum of antimicrobial activity, is active against a number of anaerobic gram-positive and gram-negative microorganisms: Staphylococcus spp. (including strains producing and not producing penicillinase, methicillin-resistant strains), Streptococcus spp. (including S. pneumoniae and S. pyogenes strains), Enterococcus spp., Listeria monocytogenes; Enterobacter spp., Haemophilus influenzae, Klebsiella spp., Legionella spp., Moraxella catarrhalis, Morganella morganii, Neisseria spp., Proteus spp., Pseudomonas aeruginosa, Salmonella spp., Shigella spp., Vibriochlopperebr. Yersinia enterocolitica, E. coli and others - Mycobacterium tuberculosis, Chlamydia trachomatis and Mycoplasma hominis. Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroids, Treponema pallidum are resistant to ciprofloxacin.

The mechanism of action of ornidazole is associated with a violation of the structure of DNA-sensitive microorganisms. It is active against Trichomonas vaginalis, Giardia lamblia, Entamoeba histolytica, as well as against some anaerobic bacteria (including Bacteroides spp., Clostridium spp., Fusobacterium spp. And anaerobic cocci).

Pharmacokinetics Ornidazole after oral administration is rapidly absorbed.

Absorption. After oral administration, ciprofloxacin is rapidly and well absorbed, mainly from the upper small intestine. Bioavailability - 70–80%, C_max in blood plasma is achieved after 1-2 hours

After oral administration, ornidazole is rapidly absorbed in the digestive tract. Bioavailability - 90%, C_max in blood plasma is reached within 3 hours

Distribution. The binding of ciprofloxacin with proteins is insignificant (20–30%), and the substance is in the blood plasma mainly in non-ionized form. Ciprofloxacin can freely diffuse into the extravascular space. The significant volume of distribution in a state of stable equilibrium, which reaches 2-3 l / kg of body weight, proves that ciprofloxacin penetrates tissues in concentrations that can be many times higher than the level of the drug in blood plasma.

The binding of ornidazole to plasma proteins is about 13%. The active substance penetrates the CSF, other body fluids and into tissues.

The concentration of ornidazole in blood plasma is in the range of 6–36 mg / L.

Metabolism. Small concentrations of the following 4 ciprofloxacin metabolites were recorded: diethylciprofloxacin (M₁), sulfociprofloxacin (M₂), oxociprofloxacin (M₃) and formylciprofloxacin (M₄) Metabolites M₁–M₃ detect in vitro antimicrobial activity similar to or below nalidixic acid activity. M₄ in a minimal amount is the equivalent of norfloxacin with respect to antimicrobial activity in vitro.

Ornidazole is metabolized in the liver to form mainly 2-hydroxymethyl and α-hydroxymethyl metabolites. Both metabolites are less active against Trichomonas vaginalis and anaerobic bacteria than unchanged ornidazole.

Ciprofloxacin is secreted for the most part unchanged both by the kidneys and through the digestive tract.

T_½ Orniazole is about 13 hours. After a single use, 85% of the dose is excreted during the first 5 days, mainly in the form of metabolites. About 4% of the dose taken is excreted by the kidneys unchanged.

Children. The pharmacokinetics of ciprofloxacin and ornidozole in children is similar to that in adults.

Indications

• Treatment of mixed infections caused by pathogens (microorganisms and protozoa) sensitive to the components of the drug; diseases of the genitourinary system: acute and chronic pyelonephritis, prostatitis, cystitis, epididymitis, complicated or recurrent urinary tract infections; sexually transmitted diseases.

Application

Orcipol should be used orally before meals or 2 hours after meals. tablets are taken intact, not halving and not chewing.

The course of treatment for acute infections is 5-7 days. The dose and duration of treatment depend on the sensitivity of microorganisms, the severity and type of infection. Adults take 1 tablet 2 times a day for 5 days, then continue to use ciprofloxacin for another 2–5 days. Treatment should be continued for at least 3 days after the disappearance of the clinical symptoms of the disease.

Unless otherwise prescribed, the following daily doses are recommended:

Adults

Urinary tract infections:

• acute, uncomplicated - 1 tablet 2 times a day for 3 days;
• cystitis in women (before menopause) - 1 tablet once;
• complicated - 1 tablet 2 times a day for 7 days.

Genital Infections:

• uncomplicated gonorrhea (including extragenital foci of infection) - 1 tablet once;
• adnexitis, prostatitis, orchoepididymitis - 1 tablet 2 times a day. The duration of the course of treatment is determined by the sensitivity of the pathogen to the drug and the clinical picture. Treatment with the drug should be continued for at least 3 days after the disappearance of the symptoms of the disease and until the normalization of body temperature.

Children. The daily dose of ciprofloxacin is 10–20 mg per 1 kg of body weight orally every 12 hours, but not more than the maximum dose of 750 mg; the daily dose of ornidazole is 20 mg per 1 kg of body weight orally every 12 hours.

Dosage regimen for elderly patients (65 years). In the treatment of elderly patients, the lowest possible doses should be used, depending on the severity of the disease and creatinine clearance.

Dosage regimen for impaired renal or hepatic function

Adults

Impaired renal function:

• with creatinine clearance of 30-60 ml / min / 1.73 m² (moderate renal failure) or its plasma concentration of 1.4–1.9 mg / 100 ml; the maximum daily dose of Orcipol is 2 tablets (1000 mg of ciprofloxacin per day);
• with creatinine clearance 30 ml / min / 1.73 m² (severe renal failure) or its plasma concentration ≥2 mg / 100 ml; the maximum daily dose of Orcipol is 1 tablet (500 mg of ciprofloxacin per day).

Impaired renal function and hemodialysis:

• with creatinine clearance of 30-60 ml / min / 1.73 m² (moderate renal failure) or its plasma concentration of 1.4–1.9 mg / 100 ml; the maximum daily dose of Orcipol is 2 tablets (1000 mg of ciprofloxacin per day);
• with creatinine clearance 30 ml / min / 1.73 m² (severe renal failure) or its plasma concentration ≥2 mg / 100 ml; the maximum daily dose of Orcipol is 1 tablet (500 mg of ciprofloxacin per day).

Impaired renal function and chronic peritoneal dialysis on an outpatient basis: 1 tablet of Orcipol per day.

Impaired liver function: dose adjustment not required.

Impaired renal and hepatic function:

• with creatinine clearance of 30-60 ml / min / 1.73 m² (moderate renal failure) or its plasma concentration of 1.4–1.9 mg / 100 ml; the maximum daily dose of Orcipol is 2 tablets (1000 mg of ciprofloxacin per day);
• with creatinine clearance 30 ml / min / 1.73 m² (severe renal failure) or its plasma concentration ≥2 mg / 100 ml; the maximum daily dose of Orcipol is 1 tablet (500 mg of ciprofloxacin per day).

There is no experience with the use of the drug in children with impaired renal or hepatic function.

Children. Use in children over the age of 15 years. The use of ciprofloxacin in children and adolescents should be carried out in accordance with current official recommendations.

Ciprofloxacin can be used in children as a second and third line drug for the treatment of complicated urinary tract infections and pyelonephritis caused by Escherichia coli.

However, treatment with ciprofloxacin in children and adolescents should only begin after a thorough assessment of the risk / benefit ratio because of the likelihood of side effects from the joints and / or adjacent tissues.

Clinical experience with ciprofloxacin in children for other indications is limited.

Contraindications

• Hypersensitivity to the components of the drug; hypersensitivity to fluoroquinolone derivatives and nitroimidazole derivatives; epilepsy, multiple sclerosis; damage to the central nervous system with a reduced convulsive threshold (after traumatic brain injury, stroke, inflammatory processes of the brain and meninges); the drug is not prescribed for patients with prolongation of the q – t interval, with uncompensated hypokalemia, for patients who are simultaneously taking antiarrhythmic drugs of class ia (zinidine, procainamide) or class iii (amiodarone, sotalol); pathological blood lesions or other hematological abnormalities; simultaneous use with tizanidine.

Side effects

Ciprofloxacin

The body as a whole: candidiasis, asthenia, candidiasis of the oral mucosa.

From the digestive system: nausea, vomiting, diarrhea, flatulence, pancreatitis, hyperbilirubinemia, hepatitis, increased liver transaminases: AlAT, AcAT, alkaline phosphatase, abnormal values ​​of liver function tests, pain in the stomach and intestines, abdominal pain, dyspeptic disorders, jaundice, cholestatic jaundice, pseudomembranous colitis, impaired liver function, liver necrosis (very rarely progressing to life-threatening liver failure).

On the part of the hematopoietic system and lymphatic system: eosinophilia, leukopenia, anemia, neutropenia, leukocytosis, thrombocytopenia, thrombocythemia, agranulocytosis, a change in the level of prothrombin, hemolytic anemia, petechiae (intermittent hemorrhage of the skin), pancytenia for life (urea) brain (life threatening).

From the nervous system: headache, dizziness, sleep disturbances, paresthesia, dysesthesia, hypesthesia, tremors, cramps (including status epilepticus), impaired gait, impaired coordination, migraine, severe cramping of large muscles, unstable gait, psychosis, intracranial (intracranial) hypertension, ataxia, startle, peripheral neuropathy and polyneuropathy.

From the musculoskeletal system and connective tissue: arthralgia (joint pain), musculoskeletal pain (e.g. pain in the limbs, lumbar region, chest), myalgia, joint swelling, arthritis, increased muscle tone, muscle weakness, exacerbation of symptoms myasthenia gravis, tendonitis, tendon ruptures (mainly Achilles).

From the cardiovascular system: tachycardia, syncope (fainting), vasodilation (hot flashes), arterial hypotension, ventricular arrhythmia, Q-T interval lengthening, pirouette type tachycardia (torsades de pointes), vascular thrombosis.

From the side of metabolism and nutrition: anorexia, increased creatinine and urea nitrogen, edema (peripheral, vascular, facial), hyperglycemia, increased activity of amylase, lipase.

From the kidneys and urinary system: impaired renal function, renal failure, vaginal candidiasis, hematuria, crystalluria, tubulointerstitial nephritis, hyperkalemia.

On the part of the skin and subcutaneous tissue: rash, itching, urticaria, photosensitivity reactions, petechiae, erythema multiforme, erythema nodosum, Stevens-Johnson syndrome (with potential life threatening), toxic epidermal necrolysis (with potential life threatening).

From the respiratory system: shortness of breath (including asthmatic conditions), laryngeal edema.

From the vessels: vasculitis, syncope.

From the side of the psyche: psychotic reactions and depression with possible suicidal ideas / thoughts or attempts / committing suicide, psychomotor excitability, confusion, disorientation, anxiety, pathological dreams, hallucinations.

From the side of the immune system: allergic reactions, allergic / angioedema, anaphylactic shock (life-threatening), anaphylactoid (anaphylactic) reaction, serum sickness.

Sensory organs: loss of taste (taste impairment), parosmia (violation of smell), loss of smell (usually reversible when the drug is canceled).

From the side of the organ of vision: visual impairment, diplopia, achromatopsia, violation of color perception.

On the part of the organ of hearing and the labyrinth: ringing in the ears, hearing loss / hearing loss.

Infections and infestations: fungal superinfection, antibiotic-associated colitis (very rarely - with possible mortality).

Common disorders: edema, fever, sweating (hyperhidrosis).

Laboratory indicators: increased activity of alkaline phosphatase, abnormal prothrombin levels, increased amylase activity.

Adverse reactions such as allergic edema, decreased appetite and decreased amount of food consumed, hypoglycemia, behavior disorders, hyperesthesia, vesicles, pseudotumors of the brain, acute generalized exanthematous pustulosis, asthenia, malaise, and an increase in the international normalized ratio (INR) in patients taking vitamin K antagonists, pain, palpitations, atrial flutter, ventricular ectopia, hypertension, angina pectoris, phlebitis, insomnia, drowsiness, weakness, phobia, deperso oralization, soreness of the mucous membrane of the oral cavity, dysphagia, lymphadenopathy, increased lipase levels, joint disorders, exacerbation of gout, nephritis, polyuria, urination disorders, bleeding from the urethra, vaginitis, acidosis, chest pain, nosebleeds, pulmonary edema, hiccups, hemoptysis, bronchospasm, pulmonary embolism, hot flashes, chills, swelling of the face, neck, lips, conjunctiva, hands, hyperpigmentation, decreased visual acuity, double vision, eye pain.

Adverse reactions such as agitation, exfoliative dermatitis, erythema, methemoglobinemia, nystagmus, polyneuropathy, an increase in the level of gamma-glutamyltransferase of blood, uric acid, a decrease in hemoglobin level, hemorrhagic diathesis, an increase in the level of monocytes, cylindruria have also been reported.

Ornidazole

Side effects of ornidazole are dose dependent.

On the part of the blood and lymphatic system: manifestations of the effect on bone marrow and neutropenia.

On the part of the immune system: hypersensitivity reactions, angioedema.

On the part of the skin and subcutaneous tissue: skin rash, urticaria, itching.

From the nervous system: dizziness, drowsiness, headache, tremors, muscle stiffness, impaired coordination, cramps, temporary loss of consciousness, signs of sensory or mixed peripheral neuropathy, agitation, confusion.

From the digestive tract: taste disturbance, nausea, vomiting, metallic taste in the mouth, dry mouth, dyspepsia.

From the liver and biliary tract: changes in liver function tests, hepatotoxicity.

General disorders: fever, fatigue, shortness of breath.

special instructions

Ciprofloxacin

Severe infections and / or mixed infections caused by gram-positive or anaerobic bacteria. For the treatment of severe infections and infections caused by gram-positive or anaerobic bacteria, as well as infections caused by staphylococci or anaerobic bacteria, ciprofloxacin should be used in combination with appropriate antibacterial agents.

Urinary tract infections. Orheoepididymitis and inflammatory diseases of the pelvic organs can be caused by fluoroquinolone-resistant Neisseria gonorrhoeae. Ciprofloxacin should be prescribed simultaneously with other appropriate antibacterial drugs, except in clinical situations where the presence of ciprofloxacin-resistant strains of Neisseria gonorrhoeae is excluded. If clinical improvement does not occur after 3 days, treatment should be reviewed.

In countries of the European Union, there is a different resistance to ciprofloxacin from Escherichia coli, the most common pathogen that causes urinary tract infections. When prescribing therapy, doctors are advised to consider the possible resistance of Escherichia coli to ciprofloxacin.

It is believed that single doses of ciprofloxacin, which can be used for uncomplicated cystitis in women with premenopausal women, are less effective than long-term therapy with ciprofloxacin. This fact must be taken into account, given the increasing level of resistance of Escherichia coli to ciprofloxacin.

Complicated urinary tract infections and pyelonephritis. Consideration should be given to treating urinary tract infections with ciprofloxacin when another treatment is not possible. Treatment should be based on the results of a microbiological examination.

Antibiotic-associated diarrhea caused by Clostridium difficile. Cases of antibiotic-associated diarrhea caused by Clostridium difficile are known, which can vary in severity from mild diarrhea to lethal colitis, with the use of almost all antibacterial drugs, including ciprofloxacin. Treatment with antibacterial drugs causes a change in the normal flora of the large intestine, which, in turn, leads to an excessive growth of Clostridium difficile.

Clostridium difficile produces toxins A and B, which contribute to the development of antibiotic-associated diarrhea. Clostridium difficile produces a large amount of toxin, causes an increase in morbidity and mortality due to the potential resistance of the pathogen to antimicrobial therapy and the need for colectomy. Keep in mind the possibility of the occurrence of antibiotic-associated diarrhea caused by Clostridium difficile in all patients with diarrhea after using antibiotics. A careful collection of medical history is necessary, since the development of antibiotic-associated diarrhea caused by Clostridium difficile is possible within 2 months after the introduction of antibacterial drugs. If the diagnosis of antibiotic-associated diarrhea caused by Clostridium difficile is being considered or already confirmed, the use of antibiotics that do not work on Clostridium difficile may be discontinued. Depending on the clinical data, it is necessary to correct the water-electrolyte balance, consider the need for additional administration of protein preparations, apply antibacterial drugs to which Clostridium difficile is sensitive. Surgical intervention may also be required.

Streptococcal infections. Ciprofloxacin is not recommended for the treatment of streptococcal infections due to lack of effectiveness.

Hypersensitivity to the drug. In some cases, hypersensitivity and allergic reactions may develop after the first dose of ciprofloxacin (see ADVERSE EFFECTS), which should be immediately reported to the doctor.

In rare cases, anaphylactic / anaphylactoid reactions can progress to a state of shock that threatens the patients life. Sometimes they occur after the first dose of ciprofloxacin. In this case, the use of ciprofloxacin should be stopped and drug treatment should be carried out immediately (treatment of anaphylactic shock).

Musculoskeletal system. In general, ciprofloxacin should not be used in patients with tendon diseases and medical history of quinolones. Despite this, in rare cases, after microbiological examination of the pathogen and assessment of the benefit / risk ratio, ciprofloxacin can be prescribed to these patients for the treatment of certain severe infectious processes, namely, in case of failure of standard therapy or bacterial resistance, when the results of microbiological studies justify the use of ciprofloxacin. When ciprofloxacin is used, tendonitis or tendon rupture (especially the Achilles tendon) may occur, sometimes bilateral, in the first 48 hours of treatment. The risk of tendinopathy may be increased in elderly patients or in patients who take corticosteroids at the same time (see ADVERSE EFFECTS).If there are any signs of tendonitis (such as painful swelling, inflammation), the use of ciprofloxacin should be discontinued. The affected limb should provide peace.

Use ciprofloxacin with caution in patients with myasthenia gravis (see ADVERSE EFFECTS).

Photosensitivity. Ciprofloxacin has been proven to cause photosensitivity reactions. Patients taking ciprofloxacin are advised to avoid direct sunlight and UV radiation during treatment.

CNS. Quinolones cause seizures or lower the seizure threshold. Ciprofloxacin is used with caution in patients with central nervous system disorders, which may be prone to seizures. With the development of seizures, ciprofloxacin should be discontinued (see ADVERSE EFFECTS). Even after the first dose of ciprofloxacin, psychotic reactions are possible. In rare cases, depression or psychosis can progress to suicidal thoughts and actions. In these cases, ciprofloxacin should be discontinued and the necessary measures taken in this clinical situation.

In patients taking ciprofloxacin, cases of polyneuropathy have been reported (based on neurological symptoms such as pain, burning, sensory disturbances, or muscle weakness, alone or in combination). Ciprofloxacin should be discontinued in patients who have symptoms of neuropathy, in particular pain, burning, discomfort, numbness and / or weakness, in order to prevent the development of irreversible conditions (see ADVERSE EFFECTS).

Heart disorders. The use of ciprofloxacin is associated with cases of prolongation of the Q – T interval (see ADVERSE EFFECTS).

Since women, as compared to men, tend to have a longer Q – Tc interval, they may be more sensitive to drugs that lead to a prolonged Q – Tc interval. Elderly patients may also be more sensitive to the effects of drugs on the duration of the Q – T interval. Caution should be exercised while prescribing ciprofloxacin and drugs that can lead to a prolonged Q-T interval (such as class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics) (see INTERACTIONS), or in patients with risk factors for elongation Q-T interval or the development of bidirectional ventricular spindle-shaped tachycardia (for example, congenital long Q-T syndrome, uncorrected electrolyte disorders such as hypokalemia or hypoma rotting, and heart disease, in particular cardiac insufficiency, myocardial infarction or bradycardia).

Gastrointestinal tract. If severe and persistent diarrhea occurs during or after treatment (even several weeks after treatment), you should inform your doctor, as this symptom can mask a serious gastrointestinal disease (for example, pseudomembranous colitis, which can be fatal), which requires immediate treatment (see ADVERSE EFFECTS). In such cases, ciprofloxacin should be discontinued and appropriate therapy initiated. Medicines that suppress peristalsis are contraindicated.

Kidneys and urinary system. Crystalluria associated with ciprofloxacin has been reported (see ADVERSE EFFECTS). Patients taking ciprofloxacin should receive a sufficient amount of fluid. Excessive alkalinity of urine should be avoided.

Impaired renal function. Since ciprofloxacin is excreted mainly unchanged by the kidneys, in patients with impaired renal function, it is necessary to carry out a dose adjustment according to the instructions given in the APPLICATION section to avoid an increase in the frequency of adverse reactions caused by the accumulation of ciprofloxacin.

Hypoglycemia.As with the use of other quinolones, most often hypoglycemia occurs in patients with diabetes, mainly in elderly patients. Careful monitoring of blood glucose levels in all patients with diabetes is recommended (see ADVERSE EFFECTS).

Hepatobiliary system. When taking ciprofloxacin, cases of the development of liver necrosis and liver failure have been reported with a threat to the patients life (see ADVERSE EFFECTS). In the event of any signs and symptoms of liver disease (such as anorexia, jaundice, dark urine, itching, or tension of the anterior abdominal wall), treatment should be discontinued. There may also be a temporary increase in the level of transaminases, alkaline phosphatase, the development of cholestatic jaundice, especially in patients with previous liver damage who received ciprofloxacin (see ADVERSE EFFECTS).

Glucose-6-phosphate dehydrogenase deficiency. When taking ciprofloxacin, hemolytic reactions were reported in patients with glucose-6-phosphate dehydrogenase deficiency. The use of ciprofloxacin in these patients should be avoided unless the potential benefit outweighs the potential risk. In this case, patients should be observed regarding the possible occurrence of hemolysis.

Resistance During or after a course of treatment with ciprofloxacin, resistant bacteria can be isolated with or without a clinically determined superinfection. There may be a certain risk of isolation of ciprofloxacin-resistant bacteria during long courses of treatment and in the treatment of nosocomial infections and / or infections caused by the species Staphylococcus and Pseudomonas.

Cytochrome P450. Ciprofloxacin moderately inhibits CYP 450 1A2 and therefore can cause an increase in plasma concentration of simultaneously prescribed substances that are also metabolized by this enzyme (for example, theophylline, methylxanthines, caffeine, duloxetine, clozapine, olanzapine, ropinirole, tizanidine). The simultaneous administration of ciprofloxacin and tizanidine is contraindicated. An increase in plasma concentration, associated with drug-specific adverse reactions, is determined by the inhibition of their metabolic clearance by ciprofloxacin. Therefore, patients who take these substances simultaneously with ciprofloxacin should be closely monitored regarding the possible occurrence of clinical signs of overdose. There may also be a need to determine plasma concentrations (for example, theophylline) (see INTERACTIONS).

Methotrexate. The simultaneous administration of ciprofloxacin and methotrexate is not recommended (see INTERACTIONS).

Influence on the results of laboratory tests. In vitro ciprofloxacin may affect inoculation results on Mycobacterium spp. by inhibiting the growth of the culture of mycobacteria, which can lead to false negative results of the analysis of seeding in patients taking ciprofloxacin.

Ornidazole When using the drug in high doses and during treatment for more than 10 days, clinical and laboratory monitoring is recommended.

In patients with a history of blood disorders, it is recommended to monitor the level of leukocytes, especially when conducting repeated courses of treatment.

An increase in disorders of the central or peripheral nervous system can be noted during treatment with the drug. In the case of peripheral neuropathy, impaired coordination of movements (ataxia), dizziness or blurred consciousness, treatment should be discontinued.

An exacerbation of candidomycosis may occur, which requires appropriate treatment.

In the case of hemodialysis, a decrease in T_½ and prescribe additional doses of ornidazole before or after hemodialysis. The concentration of lithium salts, creatinine and electrolytes must be controlled when using lithium therapy.

The effectiveness of other drugs can be increased or weakened with treatment with ornidazole.

Use during pregnancy and lactation. During pregnancy, the use of the drug is contraindicated.

Ciprofloxacin passes into breast milk. Due to the potential risk of damage to the articular cartilage in newborns, ciprofloxacin is not allowed during breastfeeding.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms

Ciprofloxacin. Fluoroquinolones, which include ciprofloxacin, may affect the patients ability to drive a car and work with other mechanisms due to reactions from the central nervous system, so the ability to drive vehicles and work with other mechanisms may be impaired.

Ornidazole When using the drug, such manifestations as drowsiness, stiffness, dizziness, tremors, convulsions, loss of coordination, temporary loss of consciousness are possible. The possibility of such manifestations must be considered for patients who drive vehicles or work with other mechanisms.

Interactions

The effect of other agents on ciprofloxacin

The formation of the chelate complex. With the simultaneous use of ciprofloxacin (oral) and drugs containing multivalent cations, mineral additives (e.g. calcium, magnesium, aluminum, iron), phosphate-binding polymers (e.g. Sevelamer), sucralfates or antacids, as well as drugs with a large buffer capacity (such as didanosine ) containing magnesium, aluminum or calcium, the absorption of ciprofloxacin is reduced. In this regard, ciprofloxacin should be taken either 1-2 hours before or at least 4 hours after taking these drugs.

This restriction does not apply to antacids belonging to the class of blockers H₂receptors.

Food and dairy products. Calcium in food products does not significantly affect absorption. However, concomitant use of ciprofloxacin and dairy or mineral-fortified products (such as milk, yogurt, orange juice with a high calcium content) should be avoided, since absorption of ciprofloxacin may be reduced.

Probenecid. Probenecid affects the renal secretion of ciprofloxacin. The simultaneous use of drugs containing probenecid and ciprofloxacin leads to an increase in the concentration of ciprofloxacin in the blood plasma.

The effect of ciprofloxacin on other drugs

Tizanidine. Tizanidine should not be prescribed simultaneously with ciprofloxacin (see CONTRAINDICATIONS). In a clinical study involving healthy volunteers with the simultaneous use of ciprofloxacin and tizanidine, an increase in the concentration of tizanidine in blood plasma was revealed (increase in C_max 7 times, range - 4-21 times; increase in AUC by 10 times, range - 6-24 times). With an increase in the concentration of tizanidine in blood plasma, hypotensive and sedative adverse reactions are associated.

Methotrexate. With the simultaneous administration of ciprofloxacin, it is possible to slow down the tubular transport (renal metabolism) of methotrexate, which can lead to an increase in the concentration of methotrexate in blood plasma. In this case, the likelihood of adverse toxic reactions caused by methotrexate may increase. Concomitant use is not recommended (see SPECIAL INSTRUCTIONS).

Theophylline. The simultaneous use of ciprofloxacin and drugs containing theophylline can lead to an undesirable increase in theophylline concentration in blood plasma, which, in turn, can lead to the development of adverse reactions. In rare cases, such adverse reactions can be fatal. E