Orcepol VM, 500 mg+500 mg 10 pcs

Indications

Mixed bacterial infections caused by sensitive gram-positive and gram-negative microorganisms, in combination with anaerobic microorganisms and/or protozoa: infectious and inflammatory diseases of the abdominal organs and biliary tract, kidneys (pyelonephritis) and/or complicated infections of the urinary tract, genitals and pelvic organs (adnexitis, prostatitis, epididymitis).

When using the drug Orcepol VM, official national recommendations on the proper use of antibacterial drugs, as well as the sensitivity of pathogenic microorganisms in a particular region, should be taken into account.

Pharmacological effect

Pharmacotherapeutic group: combined antimicrobial agent.

ATX code: J01RA

Pharmacological action

Pharmacodynamics

Orcepol VM is a combined antimicrobial and antiprotozoal drug, the pharmacological action of which is determined by the properties of its active ingredients: ornidazole (5-nitroimidazole derivative) and ciprofloxacin (second generation fluoroquinolone derivative).

Antimicrobial and antiprotozoal drug. Ornidazole is effective against Trichomonas vaginalis, Entamoeba histolytica, Giardia lamblia (Giardia intestinalis), as well as some anaerobic bacteria such as Bacteroides spp. and Clostridium spp., Fusobacterium spp., and anaerobic cocci: Peptostreptococcus spp., Peptococcus spp. Ciprofloxacin is a synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones.

Ciprofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. The bactericidal effect of ciprofloxacin is carried out through the inhibition of bacterial type II topoisomerases (topoisomerase II (DNA gyrase) and topoisomerase IV), which are necessary for the replication, transcription, repair and recombination of bacterial DNA.

Mechanisms of resistance

In vitro resistance to ciprofloxacin is often caused by point mutations in bacterial topoisomerases and DNA gyrase and develops slowly through multistep mutations. Single mutations may result in decreased susceptibility rather than the development of clinical resistance, but multiple mutations generally lead to the development of clinical resistance to ciprofloxacin and cross-resistance to quinolone drugs. Resistance to ciprofloxacin, as to many other antibiotics, can develop as a result of decreased permeability of the bacterial cell wall (as often occurs in the case of Pseudomonas aeruginosa) and/or activation of elimination from the microbial cell (efflux). The development of resistance caused by the Qnr coding gene localized on plasmids has been reported. Resistance mechanisms that lead to inactivation of penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not likely interfere with the antibacterial activity of ciprofloxacin. Microorganisms resistant to these drugs may be sensitive to ciprofloxacin. The minimum bactericidal concentration (MBC) usually does not exceed the minimum inhibitory concentration (MIC) by more than 2 times.

In vitro activity of ciprofloxacin has been demonstrated against the following sensitive strains of microorganisms:

Aerobic gram-positive microorganisms:

Bacillus anthracis, Staphylococcus aureus (methicillin-sensitive), Staphylococcus saprophyticus, Streptococcus spp.

Aerobic gram-negative microorganisms:

Aeromonas spp., Moraxella catarrhalis, Brucella spp., Neisseria meningitidis, Citrobacter koseri, Pasteurella spp., Francisella tularensis, Salmonella spp.,

Haemophilus ducreyi, Shigella spp., Haemophilus influenzae, Vibrio spp., Legionella spp., Yersinia pestis.

Anaerobic microorganisms: Mobiluncus spp.

Other microorganisms: Chlamydia trachomatis, Chlamydia pneumoniae, Mycoplasma hominis, Mycoplasma pneumoniae.

Varying degrees of sensitivity to ciprofloxadine have been demonstrated for the following microorganisms: Acinetobacter baumannii, Burkholderia cepacia. Campylobacter spp., Citrobacter freundii, Enterococcus faecalis, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Morganella morganii, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Serratia marcescens, Streptococcus pneumoniae, Peptostreptococcus spp., Propiоnibacterium acnes.

It is believed that Staphylococcus aureus (methicillin-resistant), Stenotrophomonas maltophilia, Actinomyces spp., Enteroccus faecium, Listeria monocytogenes, Mycoplasma genitalium, Ureaplasma urealitycum, anaerobic microorganisms (with the exception of Mobiluncus spp., Peptostreptococcus) are naturally resistant to ciprofloxadine spp., Propionibacterium acnes).

Pharmacokinetics

Ornidazole

Suction

After oral administration, ornidazole is rapidly absorbed from the gastrointestinal tract (GIT), absorption averages 90%. The maximum concentration (Cmax) of ornidazole in the blood plasma is observed 3 hours after taking the drug.

Distribution

The binding of ornidazole to plasma proteins is about 13%. Ornidazole penetrates into breast milk and most tissues, cerebrospinal fluid, other body fluids, passes through the blood-brain barrier and the placenta. Ornidazole concentrations in blood plasma are in the range of 6-36 mg/l, that is, at a level considered optimal for various indications for the use of the drug. After repeated administration of 500 mg or 1000 mg of the drug to healthy volunteers every 12 hours, the accumulation coefficient was 1.5-2.5.

Metabolism

Metabolized in the liver by hydroxylation, oxidation and pnocuronidation with the formation of mainly 2-hydroxymethyl and alpha-hydroxymethyl metabolites. Both metabolites are less active against Trichomonas vaginalis and anaerobic bacteria than unchanged ornidazole.

Removal

The half-life (T1/2) is about 13 hours. After a single use of the drug, 85% of the dose taken is excreted during the first 5 days, mainly in the form of metabolites: 60-70% by the kidneys and 20-25% by the intestines. Excreted unchanged by the kidneys (4%). Cumulates.

Pharmacokinetics in special groups of patients

Patients with liver dysfunction

In patients with cirrhosis, the half-life is longer (22 versus 14 hours) and clearance is lower (35 versus 51 ml/min) compared to healthy individuals. The dosing interval in patients with severe hepatic impairment should be doubled.

Patients with impaired renal function

In case of renal dysfunction, the pharmacokinetics of ornidazole does not change, so no dose adjustment is required. Ornidazole is eliminated during hemodialysis. Before starting hemodialysis, you must take additional ornidazole (50% of the prescribed dose).”

Ciprofloxacin

Suction

After oral administration, ciprofloxacin is rapidly absorbed mainly in the small intestine. Cmax of ciprofloxacin in blood plasma is achieved after 1-2 hours. Bioavailability is about 70-80%. The values ​​of Cmax in blood plasma and the area under the concentration-time curve (AUC) increase in proportion to the dose.

Distribution

The binding of ciprofloxacin to plasma proteins is 20-30%; the active substance is present in blood plasma mainly in non-ionized form. Ciprofloxacin is freely distributed in tissues and body fluids.

The volume of distribution in the body is 2-3 l/kg. The concentration of ciprofloxacin in tissues significantly exceeds the concentration in serum.

Metabolism

Biotransformed in the liver. Four metabolites of ciprofloxacin can be detected in the blood in small concentrations: diethylciprofloxacin (Ml), sulfociprofloxacin (M2), oxociprofloxacin (MZ), formylciprofloxacin (M4), three of which (M1-M3) exhibit antibacterial activity in vitro comparable to the antibacterial activity of nalidixic acid. The in vitro antibacterial activity of the M4 metabolite, present in smaller quantities, is more consistent with the activity of norfloxacin.

Removal

Ciprofloxacin is excreted from the body primarily by the kidneys by glomerular filtration and tubular secretion; a small amount – through the gastrointestinal tract. Renal clearance is 0.18-0.3 l/h/kg, total clearance –
0.48-0.60 l/h/kg. Approximately 1% of the administered dose is excreted in bile. Ciprofloxacin is present in bile in high concentrations. In patients with unchanged renal function, the elimination half-life is usually 3-5 hours.

If renal function is impaired, the half-life increases.

Special instructions

When treated with high doses of ornidazole or treatment duration beyond 10 days, regular laboratory and clinical monitoring is recommended.

When treating trichomoniasis, sexual partners should be treated simultaneously.

Caution should be exercised in patients with central nervous system diseases, such as multiple sclerosis.

In patients receiving lithium therapy, it is necessary to monitor the concentration of lithium, electrolytes and creatinine in the blood plasma during treatment with ornidazole.

There is a certain risk in patients with liver and brain damage who abuse alcohol.

In hemodialysis patients, a reduction in half-life is observed. A dose adjustment of the drug may be required (additional dose of ornidazole before or after hemodialysis).

The effect of other medicines may be enhanced or weakened during the period of use of the drug.

In patients with diseases caused by Candida spp. the course of this disease may worsen.

Severe infections, staphylococcal infections and infections caused by gram-positive and anaerobic bacteria

When treating severe infections, staphylococcal infections and infections caused by anaerobic bacteria, ciprofloxacin should be used in combination with appropriate antibacterial agents.

Infections caused by Streptococcus pneumoniae

Ciprofloxacin is not recommended for the treatment of infections caused by Streptococcus pneumoniae due to its limited effectiveness against the pathogen.

Genital tract infections

For genital infections suspected of being caused by strains of Neisseria gonorrhoeae resistant to fluoroquinolones, information about local resistance to ciprofloxacin should be taken into account and the sensitivity of the pathogen should be confirmed by laboratory tests.

Urinary tract infections

Resistance to fluoroquinolones in Escherichia coli, the most common pathogen causing urinary tract infections, varies depending on the region of the Russian Federation. When prescribing, it is recommended to take into account the local prevalence of Escherichia coli resistance to fluoroquinolones.

Heart disorders

Ciprofloxacin has an effect on prolonging the QT interval. Given that women have a longer average QT interval compared to men, they are more sensitive to drugs that cause QT prolongation. Elderly patients also have increased sensitivity to the effects of drugs that prolong the QT interval. Use the drug with caution in combination with drugs that prolong the QT interval (e.g., Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, and antipsychotics) or in patients at increased risk for QT prolongation or torsade de pointes (TdP) (e.g., congenital long QT syndrome, uncorrelated electrolyte imbalances such as hypokalemia or hypomagnesemia, as well as with heart diseases such as heart failure, myocardial infarction, bradycardia).

Use in children

It was found that ciprofloxacin, like other drugs of this class, causes arthropathy of large joints in animals. The use of the drug in children under 18 years of age is contraindicated, since the risk of damage to the cartilaginous growth zones of the child’s bones cannot be completely excluded.

Hypersensitivity

Sometimes, after taking the first dose, hypersensitivity to the drug, including allergic reactions, may develop, which should be reported to your doctor immediately. In rare cases, after the first use, anaphylactic reactions up to anaphylactic shock may occur. In these cases, the use of the drug should be stopped immediately and appropriate treatment should be carried out.

Gastrointestinal tract

If severe and prolonged diarrhea occurs during or after treatment with ciprofloxacin, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and the appointment of appropriate treatment (vancomycin orally at a dose of 250 mg 4 times a day). In this situation, the use of drugs that suppress intestinal motility is contraindicated.

Hepatobiliary system

Cases of liver necrosis and life-threatening liver failure have been reported with the use of ciprofloxacin. If you have the following signs of liver disease, such as anorexia, jaundice, dark urine, itching, painful abdomen, you should stop taking the drug.

Patients taking ciprofloxacin who have had liver disease may experience a temporary increase in the activity of liver transaminases and alkaline phosphatase or cholestatic jaundice.

Musculoskeletal system

Patients with myasthenia gravis should use diprofloxacin with caution, as exacerbation of symptoms may occur. At the first signs of tendinitis (painful swelling in the joint area, inflammation), use of the drug should be stopped and physical activity should be avoided, as There is a risk of tendon rupture, and consult a doctor.

When taking ciprofloxacin, cases of tendinitis and tendon rupture (mainly the Achilles tendon), sometimes bilaterally, may occur within the first 48 hours after the start of therapy. Inflammation and rupture of the tendon may occur even several months after stopping treatment with ciprofloxacin. Elderly patients and patients with tendon diseases who are simultaneously treated with glucocorticosteroids have an increased risk of tendinopathy.

The drug should be used with caution in patients with a history of tendon diseases associated with quinolones.

Nervous system

Ciprofloxacin, like other fluoroquinolones, can provoke seizures and lower the seizure threshold. In patients with epilepsy and a history of central nervous system diseases (for example, a decrease in the seizure threshold, a history of seizures, cerebrovascular accidents, organic brain lesions or stroke) due to the risk of developing adverse reactions from the central nervous system, ciprofloxacin should be used only in cases where the expected clinical effect outweighs the possible risk of developing side effects of the drug.

Cases of status epilepticus have been reported with the use of ciprofloxacin. If seizures occur, use of the drug should be discontinued.

Psychiatric reactions may occur even after the first use of fluoroquinolones, including ciprofloxacin. In rare cases, depression or psychotic reactions may progress to suicidal thoughts and suicide attempts, including completion. In the event of the development of any side effects from the central nervous system, including mental disorders, it is necessary to immediately discontinue the drug Orcepol VM and begin appropriate therapy. In these cases, it is recommended to switch to therapy with an antibiotic other than a fluoroquinolone, if possible.

Cases of sensory or sensorimotor polyneuropathy, hypoesthesia, dysesthesia, or weakness have been reported in patients taking fluoroquinolones, including ciprofloxacin. If symptoms such as pain, burning, tingling, numbness, or weakness occur, patients should inform their doctor before continuing to use the drug.

Dysglycemia

As with other fluoroquinolones, changes in blood glucose concentrations, including hypo- and hyperglycemia, are possible when using ciprofloxacin. During therapy with ciprofloxacin, dysglycemia may occur more often in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylureas) or insulin. When using ciprofloxacin in such patients, the risk of developing hypoglycemia, including hypoglycemic coma, increases. It is necessary to inform patients about the symptoms of hypoglycemia (confusion, dizziness, ravenous appetite, headache, nervousness, palpitations or increased heart rate, pale skin, perspiration, trembling, weakness). If the patient develops hypoglycemia, treatment with ciprofloxacin should be stopped immediately and appropriate therapy should be initiated. In these cases, it is recommended to switch to therapy with an antibiotic other than a fluoroquinolone, if possible. When treating with ciprofloxacin in elderly patients and patients with diabetes mellitus, careful monitoring of blood glucose concentrations is recommended.

Skin

Photosensitivity reactions may occur when taking ciprofloxacin, so patients should avoid contact with direct sunlight and UV light. Treatment should be discontinued if symptoms of photosensitivity are observed (for example, changes in the skin reminiscent of sunburn).

Cytochrome P450

Ciprofloxacin is known to be a moderate inhibitor of CYP450 1A2 isoenzymes. Caution should be exercised during the simultaneous use of ciprofloxacin and drugs metabolized by these enzymes, such as theophylline, methylxanthine, caffeine, duloxetine, ropinirole, clozapine, olanzapine, agomelatine, since an increase in the concentration of these drugs in the blood plasma, due to inhibition of their metabolism by ciprofloxacin, may cause specific adverse reactions. To avoid the development of crystalluria, it is unacceptable to exceed the recommended daily dose; it is also necessary to have sufficient fluid intake and maintain an acidic urine reaction.

In vitro, ciprofloxacin may interfere with the bacteriological study of Mycobacterium tuberculosis, inhibiting its growth, which can lead to false negative results when diagnosing this pathogen in patients taking ciprofloxacin.

Impact on the ability to drive vehicles and machinery

During the treatment period, it is not recommended to drive vehicles or engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Active ingredient

Ornidazole, Ciprofloxacin

Composition

Active ingredients: ciprofloxacin hydrochloride – 554.92 mg in terms of ciprofloxacin 500.00 mg, ornidazole – 500.00 mg;

Excipients: sodium carboxymethyl starch – 141.44 mg, croscarmellose sodium – 50.00 mg, povidone K29/32 – 17.40 mg, magnesium stearate – 7.80 mg, colloidal silicon dioxide – 16.60 mg, talc – 9.30 mg, corn starch – up to 1420.00 mg;

Film coating: opadry II yellow 02F22025 – 42.00 mg, consisting of: hypromellose – 26.25 mg, titanium dioxide – 11.23 mg, macrogol – 2.625 mg, iron dye yellow oxide – 1.47 mg, talc – 0.42 mg.

Pregnancy

Pregnancy

The safety of ciprofloxacin in pregnant women has not been established. However, based on the results of animal studies, the possibility of adverse effects on the articular cartilage of newborns cannot be completely excluded, and therefore the drug is contraindicated for use during pregnancy.

Breastfeeding period

The use of the drug is contraindicated during breastfeeding.

Ornidazole and ciprofloxacin pass into breast milk. Due to the potential risk of damage to the articular cartilage of newborns, the use of the drug is contraindicated during breastfeeding. If it is necessary to use the drug during breastfeeding, breastfeeding should be stopped. Resumption of breastfeeding is possible no earlier than 48 hours after taking the last dose of the drug.

Contraindications

– Increased individual sensitivity to ornidazole or other nitroimidazole derivatives, to ciprofloxacin and other drugs from the fluoroquinolone group, as well as to the excipients of the drug;

– pregnancy, breastfeeding period;

– children under 18 years of age;

– organic diseases of the central nervous system (CNS);

– pathological changes in the blood and blood cell abnormalities;

– simultaneous use with tizanidine due to clinically significant side effects (hypotension, drowsiness) associated with an increase in the concentration of tizanidine in the blood plasma;

– severe liver failure, renal failure (creatinine clearance less than 60 ml/min).

With caution

– For diseases of the central nervous system: epilepsy; decreased seizure threshold (or history of seizures); severe cerebral atherosclerosis; cerebrovascular accident; multiple sclerosis;

– mental illness (depression, psychosis);

– liver failure of moderate and mild severity;

– tendon damage due to previous treatment with quinolones;

– increased risk of prolongation of the QT interval or the development of torsade de pointes (for example, congenital long QT syndrome, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (for example, hypokalemia, hypomagnesemia));

– simultaneous use of drugs that prolong the QT interval (including class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics);

– simultaneous use with inhibitors of the CYP450 1A2 isoenzyme (including theophylline, methylxanthine, caffeine, duloxetine, clozapine, ropinirole, olanzapine, agomelatine);

– simultaneous use of lithium preparations.

– myasthenia gravis;

– deficiency of glucose-6-phosphate dehydrogenase;

– use in elderly patients;

– alcoholism;

– in patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylureas) or insulin.

Side Effects

The frequency of side effects listed below was determined according to the World Health Organization classification: very often (more than 10%); often (more than 1% and less than 10%); uncommon (more than 0.1% and less than 1%); rare (more than 0.01% and less than 0.1%); very rarely (less than 0.01%), including isolated reports; frequency unknown (cannot be estimated from available data).

Ornidazole-induced

Blood and lymphatic system disorders

uncommon: suppression of bone marrow hematopoiesis, neutropenia.

Nervous system disorders

often: dizziness, drowsiness, fatigue, headache;

rarely: tremor, muscle rigidity, incoordination, convulsions, temporary loss of consciousness, sensory or mixed peripheral neuropathy.

Gastrointestinal disorders

often: gastrointestinal dysfunction, including nausea, vomiting, diarrhea, “metallic” taste in the mouth.

Disorders of the liver and biliary tract

frequency unknown: changes in alanine aminotransferase and aspartate aminotransferase activity, jaundice.

Immune system disorders

uncommon: manifestations of skin reactions and hypersensitivity reactions (rash, itching, urticaria, Quincke’s edema).

Caused by ciprofloxacin

Infectious and parasitic diseases

uncommon: mycotic superinfections; rare: pseudomembranous colitis (in very rare cases with possible death).

Blood and lymphatic system disorders

uncommon: eosinophilia; rarely: leukopenia, anemia, neutropenia, leukocytosis, thrombocytopenia, thrombocythemia; very rare: hemolytic anemia, agranulocytosis, pancytopenia (life-threatening), bone marrow suppression (life-threatening). Immune system disorders

rarely: allergic reactions, allergic edema/angioedema;

very rare: anaphylactic reactions, anaphylactic shock (life-threatening), serum sickness.

Metabolic and nutritional disorders

uncommon: decreased appetite and amount of food taken;

rarely: hyperglycemia, hypoglycemia;

frequency unknown: severe hypoglycemia, up to the development of hypoglycemic coma, especially in elderly patients, patients with diabetes mellitus, taking oral hypoglycemic drugs or insulin.

Mental disorders

uncommon: psychomotor hyperactivity/agitation;

rare: confusion and disorientation, anxiety, dream disturbance (nightmares), depression (increased self-harm behavior such as suicidal thoughts/thoughts, attempted or successful suicide), hallucinations;

very rarely: psychotic reactions (increased behavior with the aim of self-harm, such as suicidal acts/thoughts, as well as attempted or successful suicide);

frequency unknown: attention disorders, nervousness, memory impairment, delirium.

Nervous system disorders

uncommon: headache, dizziness, sleep disturbance, taste disturbance; rarely: paresthesia and dysesthesia, hypoesthesia, tremor, convulsions (including epileptic seizures), vertigo; very rarely: migraine, impaired coordination of movements, impaired sense of smell, hyperesthesia, intracranial hypertension (cerebral pseudotumor symptoms); frequency unknown: peripheral neuropathy and polyneuropathy.

Visual disorders

rarely: visual disturbances; very rare: impaired color perception.

Hearing and labyrinth disorders

rarely: tinnitus, hearing loss; very rare: hearing impairment.

Heart disorders

rarely: tachycardia; frequency unknown: QT interval prolongation, ventricular arrhythmias (including pirouette type)*.

Vascular disorders

rarely: vasodilation, decreased blood pressure, fainting; very rare: vasculitis.

Respiratory, thoracic and mediastinal disorders

rarely: respiratory distress (including bronchospasm).

Gastrointestinal disorders

often: nausea, diarrhea;

uncommon: vomiting, abdominal pain, dyspepsia, flatulence; very rare: pancreatitis.

Disorders of the liver and biliary tract

infrequently: increased activity of liver transaminases, increased bilirubin concentration;

rarely: liver dysfunction, jaundice, hepatitis (non-infectious);

very rare: necrosis of liver tissue (in extremely rare cases, progressing to life-threatening liver failure).

Skin and subcutaneous tissue disorders

uncommon: rash, itching, urticaria; rarely: photosensitivity, blistering; very rarely: petechiae, erythema momoforma minor, erythema nodosum, Stevens-Johnson syndrome (malignant exudative erythema), including potentially life-threatening Lyell’s syndrome (toxic epidermal necrolysis);

frequency unknown: acute generalized pustular exanthema.

Musculoskeletal and connective tissue disorders

uncommon: arthralgia;

rarely: myalgia, arthritis, increased muscle tone, muscle cramps;

very rarely: muscle weakness, tendinitis, tendon rupture (mainly Achilles), exacerbation of myasthenia gravis symptoms.

Renal and urinary tract disorders

uncommon: renal dysfunction;

rarely: renal failure, hematuria, crystalluria, tubulointerstitial nephritis.

General disorders and disorders together with introduction

often: reactions at the injection site; uncommon: pain syndrome of nonspecific etiology, general malaise, fever;

rarely: swelling, increased sweating (hyperhidrosis); very rare: gait disturbance.

Influence on the results of laboratory and instrumental studies

uncommon: increased alkaline phosphatase activity in the blood;

rarely: changes in prothrombin content, increased amylase activity;

frequency unknown: increased MHO (in patients receiving vitamin K antagonists).

*more often in patients who are predisposed to developing prolongation of the QT interval.

The incidence of the following adverse reactions when administered intravenously and when using stepwise therapy with ciprofloxacin (with intravenous administration of the drug followed by oral administration) is higher than when taking the drug orally:

often – vomiting, increased activity of “liver” transaminases, rash;

uncommon – thrombocytopenia, thrombocythemia, confusion and disorientation, hallucinations, paresthesia and dysesthesia, convulsions, vertigo, visual impairment, hearing loss, tachycardia, vasodilation, decreased blood pressure, reversible liver dysfunction, jaundice, renal failure, edema;

rarely – pancytopenia, bone marrow depression, anaphylactic shock, psychotic reactions, migraine, olfactory impairment, hearing impairment, vasculitis, pancreatitis, liver tissue necrosis, petechiae, tendon rupture.

Children

Arthropathy has been frequently reported in children.

The incidence of arthropathy (arthralgia, arthritis) listed above is based on clinical studies in adult patients. In children, the incidence of arthropathy is assessed as frequent.

Interaction

Ornidazole

Unlike other nitroimidazole derivatives, ornidazole does not inhibit acetaldehyde dehydrogenase and is therefore not incompatible with alcohol.

Ornidazole enhances the effect of indirect coumarin anticoagulants, which requires appropriate adjustment of their dose.

Simultaneous use with phenobarbital and other inducers of microsomal liver enzymes reduces the half-life of ornidazole from blood plasma.

When used together with ornidazole with inhibitors of microsomal liver enzymes (for example, cimetidine), the half-life of ornidazole from blood plasma is reduced.

Ciprofloxacin

Drugs that cause QT prolongation

Caution should be exercised when ciprofloxacin, like other fluoroquinolones, is used concomitantly in patients receiving drugs known to prolong the QT interval (for example, class IA or class III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics).

Chelation formation

Simultaneous use of tablet forms of ciprofloxacin and cation-containing drugs; mineral supplements containing calcium, magnesium, aluminum, iron; sucralfate, antacids, polymeric phosphate compounds (such as sevelamer, lanthanum carbonate) and drugs with a large buffer capacity (such as didanosine tablets) containing magnesium, aluminum or calcium reduce the absorption of ciprofloxacin. In such cases, the drug should be taken either 1-2 hours before or 4 hours after taking these drugs.

This restriction does not apply to drugs belonging to the class of H2-histamine receptor blockers.

Eating food and dairy products

The simultaneous use of ciprofloxacin and dairy products or drinks fortified with minerals (for example, milk, yogurt, calcium-fortified orange juice) should be avoided as the absorption of ciprofloxacin may be reduced. However, calcium contained in other foods does not significantly affect the absorption of ciprofloxacin.

Omeprazole

With the combined use of ciprofloxacin and drugs containing omeprazole, a slight decrease in the maximum concentration of ciprofloxacin in plasma and a decrease in the area under the concentration-time pharmacokinetic curve may be observed.

Theophylline

The simultaneous use of ciprofloxacin and drugs containing theophylline may cause an undesirable increase in the concentration of theophylline in the blood plasma and, accordingly, the occurrence of theophylline-induced adverse events; in very rare cases, these adverse events can be life-threatening for the patient. If the simultaneous use of these two drugs is unavoidable, it is recommended to constantly monitor the concentration of theophylline in the blood plasma and, if necessary, reduce the dose of theophylline.

Other xanthine derivatives

The simultaneous use of ciprofloxacin and caffeine or pentoxifylline (oxpentifylline) may lead to an increase in the concentration of xanthine derivatives in the blood plasma.

Nonsteroidal anti-inflammatory drugs

The combination of very high doses of quinolones (DNA gyrase inhibitors) and some non-steroidal anti-inflammatory drugs (except acetylsalicylic acid) can provoke seizures.

Cyclosporine

With the simultaneous use of ciprofloxacin and drugs containing cyclosporine, a short-term transient increase in plasma creatinine concentration was observed. In such cases, it is necessary to determine the concentration of creatinine in the blood 2 times a week.

Oral hypoglycemic agents

With the simultaneous use of ciprofloxacin and oral hypoglycemic agents, mainly sulfonylureas (for example, glibenclamide, glimepiride), the development of hypoglycemia is presumably due to an increased effect of oral hypoglycemic agents.

Probenecid

Probenecid slows down the rate of excretion of ciprofloxacin by the kidneys. The simultaneous use of ciprofloxacin and drugs containing probenecid leads to an increase in the concentration of ciprofloxacin in the blood plasma.

Phenytoin

With the simultaneous use of ciprofloxacin and phenytoin, a change (increase or decrease) in the content of phenytoin in the blood plasma was observed. To avoid weakening of the anticonvulsant effect of phenytoin due to a decrease in its concentration, as well as to prevent adverse events associated with phenytoin overdose when discontinuing ciprofloxacin, it is recommended to monitor phenytoin therapy in patients taking both drugs, including determination of phenytoin plasma levels during the entire period of simultaneous use of both drugs and for a short time after completion of combination therapy.

Methotrexate

With the simultaneous use of methotrexate and ciprofloxacin, the renal tubular transport of methotrexate may slow down, which may be accompanied by an increase in the concentration of methotrexate in the blood plasma. This may increase the likelihood of developing side effects of methotrexate. In this regard, patients receiving concomitant therapy with methotrexate and ciprofloxacin should be closely monitored.

Tizanidine

As a result of a clinical study involving healthy volunteers, the simultaneous use of ciprofloxacin and drugs containing tizanidine revealed an increase in the concentration of tizanidine in the blood plasma: an increase in Cmax by 7 times (from 4 to 21 times), an increase in AUC by 10 times (from 6 to 24 times). An increase in tizanidine plasma concentrations may cause a decrease in blood pressure and drowsiness. Therefore, the simultaneous use of ciprofloxacin and drugs containing tizanidine is contraindicated.

Duloxetine

Clinical studies have shown that the simultaneous use of duloxetine and potent inhibitors of the CYP450 1A2 isoenzyme (such as fluvoxamine) may lead to an increase in the AUC and Cmax of duloxetine. Although there is no clinical data on possible interactions with ciprofloxacin, the likelihood of such an interaction can be anticipated when ciprofloxacin and duloxetine are used concomitantly.

Ropinirole

The simultaneous use of ropinirole and ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isoenzyme, leads to an increase in the Cmax and AUC of ropinirole by 60 and 84%, respectively. Monitor for adverse effects of ropinirole during co-administration with ciprofloxacin and for a short time after completion of combination therapy.

Lidocaine

In a study on healthy volunteers, it was found that the simultaneous use of drugs containing lidocaine and ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isoenzyme, leads to a 22% decrease in the clearance of lidocaine when administered intravenously. Despite the good tolerance of lidocaine when used simultaneously with ciprofloxacin, increased side effects due to interaction are possible.

Clozapine

With simultaneous use of clozapine and ciprofloxacin at a dose of 250 mg for 7 days, an increase in plasma concentrations of clozapine and N-desmethylclozapine by 29% and 31%, respectively, was observed. The patient’s condition should be monitored and, if necessary, the dosage regimen of clozapine should be adjusted during its combined use with ciprofloxacin and for a short time after completion of combination therapy.

Sildenafil

With simultaneous use of ciprofloxacin at a dose of 500 mg and sildenafil at a dose of 50 mg in healthy volunteers, there was a 2-fold increase in Cmax and AUC of sildenafil. In this regard, the use of this combination is possible only after assessing the benefit/risk ratio.

Vitamin K antagonists

The combined use of ciprofloxacin and vitamin K antagonists (for example, warfarin, acenocoumarol, phenprocoumon, fluindione) may lead to an increase in their anticoagulant effect. The magnitude of this effect may vary depending on concomitant infections, age and general condition of the patient, so it is difficult to assess the effect of ciprofloxacin on increasing INR (international normalized ratio). MHO should be monitored frequently during concomitant use of ciprofloxacin and vitamin K antagonists, as well as for a short time after completion of combination therapy.

Agomelatine

In clinical studies, fluvoxamine, as a strong inhibitor of the CYP450 1A2 isoenzyme, has been shown to markedly inhibit the metabolism of agomelatine, resulting in a 60-fold increase in agomelatine exposure. Although there is no clinical data on possible interaction with ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isoenzyme, similar effects can be expected with the simultaneous use of agomelatine and ciprofloxacin.

Zolpidem

Concomitant use of ciprofloxacin and zolpidem is not recommended as it may lead to increased plasma concentrations of zolpidem.

Overdose

Symptoms caused by ornidazole: loss of consciousness, headache, dizziness, trembling, convulsions, dyspeptic disorders and the occurrence of other dose-dependent symptoms, but in a more pronounced form.

Symptoms associated with ciprofloxacin: reversible toxic effects on the renal parenchyma.

Treatment: in case of overdose, in addition to standard measures (gastric lavage, after which you should take activated charcoal; administering large amounts of fluid; creating an acidic urine reaction to prevent crystalluria), it is also recommended to monitor renal function (including urine pH and acidity) and take magnesium- and calcium-containing antacids, which reduce the absorption of ciprofloxacin. Using hemo- or peritoneal dialysis, only a small amount of ciprofloxacin is removed (less than 10%). Symptomatic therapy is indicated. There is no specific antidote. If seizures develop, diazepam is prescribed.

Storage conditions

Store at a temperature not exceeding 25 °C.
Keep out of the reach of children!

Shelf life

3 years.
Do not use after expiration date.

Manufacturer

World Medicine Ilac San ve Tij A.Ş., Türkiye