Properties
What is it?
Trade name: Ornitsin. International Nonproprietary Name: Ciprofloxacin + Ornidazole. Dosage form: Film-coated tablets. Composition: Each film-coated tablet contains: Active substances: Ciprofloxacin 500 mg (as Ciprofloxacin Hydrochloride USP) Ornidazole 500 mg Excipients: Colloidal anhydrous silica, Povidone, Microcrystalline cellulose, Corn starch, Purified water, Purified talc, Magnesium stearate, Sodium starch glycolate (Type A), Hypromellose (Hydroxypropyl methylcellulose), Macrogol (PEG-6000), Titanium dioxide, Iron oxide yellow. Also see: Ciprofloxacin - Ciprofloxacin 500mg 14 tablets Pharmacotherapeutic group: Combined antimicrobial agent. ATC code: J01RA12 Pharmacological properties: Pharmacodynamics: A combined antimicrobial and antiprotozoal drug whose pharmacological action is due to the properties of its constituent components - ciprofloxacin (2nd generation fluoroquinolone) and ornidazole (5-nitroimidazole derivative). Ciprofloxacin inhibits the bacterial enzyme DNA gyrase and/or topoisomerase IV (catalysts of DNA duplication, transcription, repair), and inhibits bacterial DNA synthesis; causes morphological changes in the bacterial cell wall, which is characterized by a dual effect against microorganisms and leads to rapid cell death. Affects bacteria during growth and rest. It has a broad spectrum of antimicrobial activity, is active against a number of aerobic gram-positive and gram-negative microorganisms: Staphylococcus spp. (including penicillinase-producing and non-producing strains, 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., Vibrio cholerae, Campylobacter spp, Citrobacter, Yersinia enterocolitica, E. coli; and others - Mycobacterium tuberculosis, Chlamydia trachomatis and Mycoplasma hominis. Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. Resistant to ciprofloxacin. Its action against Treponema pallidum is not sufficiently studied. It has a bactericidal effect on bacteria in both reproductive and resting phases. Ornidazole is a medicinal agent with antibacterial and antiprotozoal activity. The mechanism of action of the drug is based on the ability of the nitro group of the ornidazole molecule to be reduced under the influence of microbial enzymes. The reduced nitro group forms complex compounds with bacterial DNA, resulting in disruption of DNA replication and transcription processes. In addition, ornidazole has a cytotoxic effect and disrupts the cellular respiration processes of microorganisms. Thus, the drug has a bactericidal and bacteriostatic effect. The drug is effective in various infectious diseases caused by Trichomonas vaginalis, Entamoeba histolytica, Lamblia intestinalis (Giardia intestinalis), Gardnerella vaginalis, Bacteroides, Clostridium spp., Fusobacterium spp. and anaerobic cocci. Activity against some strains of Helicobacter pylori has been noted. Pharmacokinetics: Ciprofloxacin is rapidly absorbed from the gastrointestinal tract, Cmax in blood serum is reached 1-2 hours after oral administration and is 2.5 mg/ml. Bioavailability - 70-80%. It crosses the placenta and is excreted in breast milk. Maximum concentration in blood is reached 60-90 minutes after oral administration. The half-life of ciprofloxacin ranges from 3 to 5 hours. Ciprofloxacin reaches the highest concentrations at the sites of infection, for example, in fluid environments and tissues. After oral administration, ornidazole is well absorbed from the gastrointestinal tract. The bioavailability of the drug reaches 90%, ornidazole is characterized by a low degree of binding to plasma proteins (not more than 13%). The peak concentration of active substances in blood plasma is observed 3 hours after administration of the drug. Ornidazole penetrates well into all biological fluids and body tissues. It has the ability to cross the blood-brain and placental barriers and is excreted in breast milk. It is metabolized in the liver with the formation of pharmacologically active metabolites (the antimicrobial and antiprotozoal activity of the metabolites is slightly lower than that of unchanged ornidazole). 85% of the dose administered after a single use is excreted within 5 days. The half-life of ornidazole is 12-14 hours, it is mainly excreted by the kidneys (about 70%) and intestines, both unchanged and as metabolites. Indications for use: Treatment of associated infections caused by the combined action of 2 or more pathogens sensitive to the components of the drug: · Kidney and/or urinary tract infections: acute and chronic pyelonephritis, cystitis, urethritis, bacterial prostatitis, epididymitis, including complicated and recurrent; · Sexually transmitted diseases caused by penicillin-resistant gonococci, chlamydia, trichomonads (agent causing trichomoniasis) and other microorganisms (mixed infections); · Lower respiratory tract infections; · Bone and joint infections; · Prevention of anaerobic infections during large bowel surgery and gynecological interventions; Official guidelines for the use of antibacterial agents should be taken into account. Dosage and administration: Ornitsin is taken orally, before or 2 hours after meals, without chewing. The course of treatment for acute infections is 5 days, and for chronic recurrent infections: 10 days, 1 tablet 2 times a day. It is necessary to continue taking the drug for 2 days after the disappearance of disease symptoms. For patients with creatinine clearance of 20 ml/min or less, elderly patients, and patients with low body weight, half of the usual dose is prescribed. Contraindications: · Hypersensitivity to ciprofloxacin or ornidazole; · Children under 18 years of age. Use during pregnancy and lactation: Contraindicated during pregnancy and lactation (breastfeeding). Dosage and administration: Ornitsin is taken orally, before or 2 hours after meals, without chewing. The course of treatment for acute infections is 5 days, and for chronic recurrent infections: 10 days, 1 tablet 2 times a day. It is necessary to continue taking the drug for 2 days after the disappearance of disease symptoms. For patients with creatinine clearance of 20 ml/min or less, elderly patients, and patients with low body weight, half of the usual dose is prescribed. Side effects: Caused by ciprofloxacin. From the digestive system: nausea, vomiting, diarrhea, abdominal pain, increased activity of liver transaminases, alkaline phosphatase, LDH, bilirubin, pseudomembranous colitis. From the central nervous system: headache, dizziness, fatigue, sleep disturbances, nightmares, hallucinations, weakness, visual disturbances. From the urinary system: crystalluria, glomerulonephritis, dysuria, polyuria, albuminuria, hematuria, transient increase in serum creatinine. From the hematopoietic system: eosinophilia, leukopenia, neutropenia, changes in platelet count. From the cardiovascular system: tachycardia, cardiac rhythm disturbances, arterial hypotension. Allergic reactions: skin itching, urticaria, Quincke's edema, Stevens-Johnson syndrome, arthralgia. Side effects related to chemotherapeutic action: candidiasis. Other: vasculitis. Diseases of the musculoskeletal system and connective tissue* Diseases of the nervous system* General disorders and administration site conditions* Mental disorders* Disorders of the visual organ* Disorders of the vestibular system and balance organs* * Information was provided on the development of very rare, long-term (lasting one month or a year), disabling, potentially irreversible serious adverse reactions affecting various, sometimes multiple systems and sensory organs of the human body (including adverse reactions such as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbance, neuropathy associated with paresthesia, depression, weakness, decreased memory, sleep, hearing, vision, taste, and smell) associated with the use of quinolones and fluoroquinolones, in some cases, even in the absence of risk factors. Reports of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal), regurgitation/heart valve insufficiency in patients taking fluoroquinolones have been received. Caused by ornidazole. Side effects of ornidazole are dose-dependent. From the blood and lymphatic system: manifestations of bone marrow effects and neutropenia. From the immune system: hypersensitivity reactions, angioneurotic edema. From the skin and subcutaneous tissue: skin rash, urticaria, itching. From the nervous system: dizziness, drowsiness, headache, tremor, muscle rigidity, impaired coordination, convulsions, temporary loss of consciousness, signs of sensory or mixed peripheral neuropathy, excitability, confusion. From the gastrointestinal 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. Overdose: Ciprofloxacin. Reports have been received that overdose due to intake of 12 g of the drug causes symptoms of moderate toxicity. Acute overdose of 16 g caused the development of ARF (acute renal failure). Symptoms of overdose included dizziness, tremor, headache, excessive fatigue, convulsions, hallucinations, confusion, abdominal discomfort, kidney and liver failure, as well as crystalluria and hematuria. Reversible renal toxicity was also noted. Due to the possible prolongation of the Q-T interval, ECG monitoring is also recommended. In case of overdose, in addition to the usual emergency measures taken, monitoring of kidney function is recommended, in particular, determination of urine pH and, if necessary, increasing its acidity to prevent crystalluria. Patients should drink enough fluids. Only a small amount of ciprofloxacin (<10%) is excreted with the help of hemodialysis or peritoneal dialysis. Ornidazole. Symptoms mentioned in the "Side Effects" section, but in a more pronounced form. Treatment is symptomatic, no specific antidote is known. To remove ornidazole from the body, gastric lavage or hemodialysis is recommended. In case of convulsions, diazepam administration is recommended. Drug interactions: Ciprofloxacin. Effect of other drugs on ciprofloxacin. Chelate complex formation. Simultaneous use of oral ciprofloxacin with medicinal products containing polyvalent cations, mineral supplements (e.g., calcium, magnesium, aluminum, iron), phosphate binders (e.g., sevelamer), sucralfate or antacids, as well as with drugs with high buffering capacity (such as didanosine) containing magnesium, aluminum or calcium, reduces the absorption of ciprofloxacin. In this regard, ciprofloxacin should be taken 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 H2 receptor blockers. Food and dairy products. Calcium in food has little effect on absorption. However, simultaneous use of ciprofloxacin and milk or mineral-enriched products (such as milk, yogurt, calcium-rich orange juice) should be avoided, as ciprofloxacin absorption may be reduced. Probenecid. Probenecid affects the renal secretion of ciprofloxacin. Simultaneous use of medicinal products containing probenecid and ciprofloxacin leads to an increase in the concentration of ciprofloxacin in blood plasma. Effect of ciprofloxacin on other drugs. Tizanidine. Tizanidine should not be prescribed with ciprofloxacin. In a clinical study involving healthy volunteers, simultaneous administration of ciprofloxacin and tizanidine resulted in an increase in tizanidine concentration in blood plasma (7-fold increase in Cmax, range - 4-21-fold; 10-fold increase in AUC values, range - 6-24-fold). Increased tizanidine concentration in blood plasma is associated with hypotensive and sedative side effects. Methotrexate. Simultaneous administration of ciprofloxacin may slow down the tubular transport (renal metabolism) of methotrexate, which can lead to an increase in methotrexate concentration in blood plasma. At the same time, the probability of side toxic reactions caused by methotrexate may increase. Simultaneous administration is not recommended. Theophylline. Simultaneous use of ciprofloxacin and medicinal products containing theophylline may lead to an undesirable increase in the concentration of theophylline in blood plasma, which, in turn, may lead to the development of side effects. These side effects may, in rare cases, be fatal. If simultaneous use of these drugs cannot be avoided, it is necessary to monitor the concentration of theophylline in blood plasma and adjust the dose accordingly. Other xanthine derivatives. After simultaneous use of ciprofloxacin and preparations containing caffeine or pentoxifylline (oxypentifylline), an increase in the concentration of these xanthines in blood plasma was observed. Phenytoin. Simultaneous use of ciprofloxacin and phenytoin may lead to an increase or decrease in plasma concentration of phenytoin, so monitoring of drug levels is recommended. Vitamin K antagonists. Simultaneous use of ciprofloxacin and vitamin K antagonists may enhance their anticoagulant effect. In patients taking antibacterial drugs, particularly fluoroquinolones, an increase in the activity of oral anticoagulants has been observed. The degree of risk can vary depending on the type of underlying infection, age, and general condition of the patient, so it is difficult to accurately assess the effect of ciprofloxacin on the increase in INR (International Normalized Ratio) values. Regular monitoring of INR should be performed during and immediately after the simultaneous use of ciprofloxacin and vitamin K antagonists (e.g., warfarin, acenocoumarol, phenprocoumon, fluindione). Ropinirole. Clinical studies have shown that simultaneous administration of ropinirole with ciprofloxacin, a moderate inhibitor of the CYP 450 1A2 isoenzyme, leads to an increase in ropinirole AUC and Cmax by 60% and 84%, respectively. Monitoring of ropinirole side effects and appropriate dose adjustment is recommended during and immediately after co-administration with ciprofloxacin. Clozapine. After taking 250 mg of ciprofloxacin with clozapine for 7 days, plasma concentrations of clozapine and N-desmethylclozapine increased by 29% and 31%, respectively. Clinical monitoring of clozapine and dose adjustment as needed is recommended during and immediately after co-administration with ciprofloxacin. Drugs that prolong the Q-T interval. Ornitsin, like other fluoroquinolones, should be prescribed with caution in patients taking drugs that prolong the Q-T interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics). Metoclopramide. Metoclopramide accelerates the absorption of ciprofloxacin, leading to a faster achievement of Cmax in blood plasma. No effect on the bioavailability of ciprofloxacin was observed. Omeprazole. Simultaneous use of ciprofloxacin and medicinal products containing omeprazole leads to a slight decrease in Cmax and AUC of ciprofloxacin. Lidocaine. It has been shown that in healthy volunteers, simultaneous use of ciprofloxacin, a moderate inhibitor of cytochrome P450 1A2 isoenzymes, and medicinal products containing lidocaine reduces the clearance of intravenous lidocaine by 22%. Despite normal tolerance of lidocaine treatment, interaction with ciprofloxacin is possible, associated with adverse reactions, and may develop with simultaneous use of these drugs. Sildenafil. Sildenafil Cmax and AUC increased approximately 2-fold in healthy volunteers after oral administration of 50 mg sildenafil and simultaneous administration of 500 mg ciprofloxacin. Therefore, caution should be exercised when co-administering Ornitsin with sildenafil, and the risk/benefit ratio should be considered. Oral hypoglycemic agents. Hypoglycemia has been reported with the simultaneous administration of ornidazole and oral antidiabetic drugs, especially sulfonylureas (e.g., glibenclamide, glimepiride), likely associated with the potentiation of the effect of oral antidiabetic drugs by ciprofloxacin. Duloxetine. Clinical studies have shown that simultaneous use of duloxetine with strong inhibitors of CYP 450 1A2, such as fluvoxamine, can lead to an increase in duloxetine AUC and Cmax. Despite the lack of clinical data on possible interaction with ciprofloxacin, similar effects are expected with simultaneous use of the mentioned drugs. NSAIDs. Animal studies have shown that a combination of high doses of quinolones (gyrase inhibitors) and certain NSAIDs (except acetylsalicylic acid) can cause seizures. Cyclosporine. A transient increase in serum creatinine levels has been determined with simultaneous administration of ciprofloxacin and medicinal products containing cyclosporine. Therefore, frequent (twice a week) monitoring of plasma creatinine concentration is necessary in these patients. Ornidazole. Unlike other nitroimidazole derivatives, ornidazole does not inhibit aldehyde dehydrogenase and is therefore compatible with alcohol. However, ornidazole enhances the effect of oral anticoagulants of the coumarin series, requiring appropriate dose adjustment. Ornidazole prolongs the muscle relaxant effect of vecuronium bromide. Combined use of phenobarbital and other enzyme inducers reduces the circulation period of ornidazole in blood plasma, while enzyme inhibitors (e.g., cimetidine) increase it. Special instructions: Ciprofloxacin. The use of ciprofloxacin should be avoided in patients with a history of serious adverse reactions associated with the intake of medicinal products containing quinolone or fluoroquinolone. Treatment of such patients with ciprofloxacin should only be initiated if alternative treatment options are not available and the benefit/risk ratio is thoroughly assessed. Long-term, disabling, potentially irreversible serious adverse reactions: Very rare, long-term, disabling, potentially irreversible serious adverse reactions affecting various, sometimes multiple systems of the human body (musculoskeletal, nervous, and mental systems, sensory organs) have been reported in patients taking quinolones or fluoroquinolones, regardless of their age and pre-existing risk factors. At the first signs and symptoms of any serious adverse reaction, ciprofloxacin intake should be immediately discontinued and a doctor should be consulted. Tendinitis and tendon rupture: Tendinitis and tendon rupture (especially Achilles tendon), sometimes bilateral, can occur within 48 hours of starting treatment with quinolones and fluoroquinolones and for several months after discontinuation of treatment. The risk of developing tendinitis and tendon rupture increases in elderly patients, patients with renal insufficiency, patients who have undergone organ transplantation and are simultaneously receiving corticosteroid therapy. Simultaneous use of corticosteroids and fluoroquinolones should be avoided. In case of the first signs of tendinitis (e.g., painful swelling, inflammation), ciprofloxacin intake should be discontinued and alternative treatment considered. The affected limb(s) should be treated appropriately. Corticosteroids should not be used in case of signs of tendinopathy. Peripheral neuropathy: Cases of sensory or sensorimotor polyneuropathy, leading to paresthesia, hypoesthesia (decreased sensation), dysesthesia, or weakness, have been reported in patients taking quinolones and fluoroquinolones. Patients using ciprofloxacin should be advised to inform their doctor if symptoms of neuropathy, such as pain, burning, tingling, numbness, or weakness, develop before continuing treatment, to prevent the development of potentially irreversible conditions. Aortic dissection and aneurysm, regurgitation/heart valve insufficiency. According to epidemiological studies, an increased risk of aortic aneurysm and aortic dissection, especially in elderly patients, and aortic and mitral valve regurgitation has been observed after the use of fluoroquinolones. Reports of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal), in patients with heart valve insufficiency/regurgitation taking fluoroquinolones have been received. Fluoroquinolones should only be used after careful assessment of the benefit-risk ratio and consideration of other treatment options in patients with a history of aneurysm or congenital heart valve defect, or who have an aneurysm and/or aortic dissection or conditions that predispose to their development: - simultaneously both aortic aneurysm and dissection, as well as heart valve regurgitation/insufficiency (e.g., connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, hypertension, rheumatoid arthritis), or - aortic aneurysm and dissection (e.g., vascular diseases such as Takayasu's arteritis or giant cell arteritis, or known atherosclerosis, or Sjögren's syndrome), or - heart valve regurgitation/insufficiency (e.g., infectious endocarditis). The risk of developing aortic aneurysm and dissection and its rupture may increase in patients simultaneously taking systemic corticosteroids. In case of sudden pain in the abdomen, chest, or back, patients should immediately seek emergency medical attention. Patients should be advised to seek immediate medical attention in case of acute shortness of breath, new onset of palpitations, swelling of the abdomen or lower extremities. The use of ciprofloxacin is not recommended in children for the treatment of diseases other than complications of pulmonary mucoviscidosis (in children aged 5 to 17 years) associated with Pseudomonas aeruginosa, and for the treatment and prophylaxis of pulmonary anthrax (Bacillus anthracis) after suspected or confirmed infection. Since ciprofloxacin can stimulate the CNS, it should be prescribed with caution in patients with CNS diseases such as severe cerebral atherosclerosis or epilepsy. To prevent crystalluria, patients taking this drug should drink enough fluids. Excessive urine alkalization should be avoided. The dose should be reduced in patients with renal insufficiency. Avoid direct sunlight exposure during ciprofloxacin treatment. Ornidazole. When using high doses of the drug and for treatment longer than 10 days, clinical and laboratory monitoring is recommended. In patients with a history of blood disorders, monitoring of leukocyte levels is recommended, especially during repeated courses of treatment. Exacerbation of central or peripheral nervous system disorders may occur during treatment with the drug. In case of peripheral neuropathy, impaired coordination of movements (ataxia), dizziness, or clouded consciousness, treatment should be discontinued. Exacerbation of candidomycosis may occur, requiring appropriate treatment. In case of hemodialysis, it is necessary to consider the reduction of T½ and administer additional doses of ornidazole before or after hemodialysis. Monitoring of lithium salts, creatinine, and electrolyte concentrations is necessary when using lithium therapy. The effectiveness of other drugs may increase or decrease during ornidazole treatment. Effect on ability to drive and operate machinery: Patients taking Ornitsin should exercise caution when driving and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions (especially when consuming alcohol simultaneously). Dosage form: 10 tablets in a PVC blister. One blister in a cardboard box with instructions for use. Storage conditions: Store in a dry place at a temperature not exceeding 25°C. Keep out of reach of children. Shelf life: Indicated on the packaging. Do not use after the expiry date. Dispensing conditions: By prescription only.