Ornidazole, Ofloxacin

Pharmacological properties

The pharmacological effect of ofloxacin is antibacterial (bactericidal). inhibits dna gyrase (topoisomerases ii and iv), disrupts the process of supercoiling and crosslinking of DNA breaks, inhibits cell division, causes structural changes in the cytoplasm and death of microorganisms.

It has a wide spectrum of action. It mainly affects gram-negative and some gram-positive microorganisms: Citrobacter diversus, Entrobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Citrobacter diversus, Neisseria gonorrhoeae, Chlamydia trachococomatus, Stlamatocomphus Stlamata. Effective against microorganisms that are resistant to most antibiotics and sulfa drugs.

The pharmacological effect of ornidazole is antibacterial and antiprotozoal. It is active against Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia (Giardia intestinalis), as well as some anaerobic bacteria (Clostridium spp., Bacteroides spp., Fusobacterium) and anaerobic cocci. According to the mechanism of action, ornidazole is a DNA-tropic drug with selective activity against microorganisms with enzyme systems capable of reducing the nitro group and catalyzing the interaction of proteins of the feredoxin group with nitro compounds. After the drug penetrates into the cell of the microorganism, its mechanism of action is due to the restoration of the nitro group under the influence of nitroreductases of the microorganism and the activity of the already reduced nitroimidazole. Recovery products form complexes with DNA, causing its degradation, disrupt DNA replication and transcription. In addition, the metabolic products of the drug have cytotoxic properties and disrupt the processes of cellular respiration.

Pharmacokinetics Not investigated.

Indications

• Treatment for 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

Ofor should be taken orally, without chewing, washed down with water. allowed to take the drug both before and after meals.

The dose and duration of treatment depend on the sensitivity of microorganisms, the severity and type of infection. Dose for adults - 1 tablet 2 times a day for 5 days, then continue with therapy for another 2-5 days with ofloxacin in the form of tablets. Treatment should be continued for at least 3 days after the disappearance of the clinical symptoms of the disease.

Contraindications

Hypersensitivity to ofloxacin, ornidazole, other derivatives of fluoroquinolones, derivatives of nitroimidazole or other components of the drug. damage to the central nervous system with a reduced convulsive threshold (after traumatic brain injury, stroke, inflammatory processes of the brain and meninges); multiple sclerosis, epilepsy, glucose-6-phosphate dehydrogenase deficiency; a history of tendonitis, pathological lesions of the blood, or other hematological abnormalities; lengthening the q – t interval; decompensated hypoglycemia.

The drug is contraindicated in patients taking class IA antiarrhythmic drugs (quinidine, procainamide) or class III (amiodarone, sotalol), tricyclic antidepressants, macrolides; patients with tendon ruptures after a history of fluoroquinolones.

Side effects

On the part of the skin: itching, rash, urticaria, the appearance of blisters, hyperhidrosis, pustular rashes; erythema multiforme, vascular purpura, Stevens-Johnson syndrome, Lyell syndrome, acute generalized exanthematous pustulosis, photosensitivity, hypersensitivity (in the form of solar erythema), discoloration of the skin or exfoliation of nails.

On the part of the immune system: hypersensitivity reactions, including anaphylactic / anaphylactoid reactions, angioedema (including swelling of the tongue, larynx, pharynx, swelling / swelling of the face), anaphylactic / anaphylactoid shock.Anaphylactic / anaphylactoid reactions may develop immediately after the administration of ofloxacin, including signs of anaphylaxis, tachycardia, fever, shortness of breath, shock, angioedema, vasculitis (which in exceptional cases can lead to skin necrosis), eosinophilia. In this case, the use of the drug should be discontinued and alternative therapy should be started. In rare cases, pneumonitis may occur.

On the part of the cardiovascular system: hot flashes, tachycardia, short-term arterial hypotension, collapse (in the event of severe arterial hypotension, the drug should be discontinued), ventricular arrhythmia, flutter-ventricular fibrillation (reported mainly for patients with risk factors for prolonging the Q – T interval) on an ECG, prolongation of the Q – T interval, cerebral thrombosis, pulmonary edema, torsades de pointes.

From the side of the central nervous system: headache, dizziness, depression, sleep disturbances, insomnia, drowsiness, anxiety, agitation, convulsions, confusion, temporary loss of consciousness, nightmares, slowing down the reaction rate, increased intracranial pressure, paresthesia, sensory or sensorimotor neuropathy, tremor and other extrapyramidal disorders, impaired muscle coordination (imbalance, unstable gait), psychotic reactions, suicidal thoughts / actions, hallucinations, salivation, anxiety oyeya, rigidity, violation of peripheral sensitivity (violation of taste, smell, vision); photophobia, exacerbation of myasthenia gravis, dysphasia.

From the digestive tract: anorexia, nausea, vomiting, heartburn, gastralgia, abdominal pain or pain, diarrhea, enterocolitis, diarrhea (sometimes it can be a symptom of enterocolitis, which in some cases can be hemorrhagic), flatulence, dysbiosis; pseudomembranous colitis, metallic taste in the mouth, dysgeusia, frequent loose stools, gastrointestinal distress, constipation, dry mouth, hypoglycemia in patients with diabetes mellitus receiving hypoglycemic drugs.

On the part of the liver: increased activity of hepatic enzymes (AlAT, AsAT, LDH, ALP, gamma-glutamyltransferase), bilirubin, cholestatic jaundice, increased levels of TG, cholesterol, in some cases hepatitis, up to a very severe degree.

A specific form of enterocolitis, which is possible with antibiotics, is pseudomembranous colitis (in most cases caused by Clostridiu difficile). If colitis caused by Clostridium difficile is suspected, the use of the drug should be stopped immediately and adequate therapy should be started. Medicines that reduce peristalsis should not be used in such cases.

From the genitourinary system: impaired renal function, acute interstitial nephritis or an increase in plasma creatinine, which can lead to acute renal failure, anuria, polyuria, kidney stones, hematuria, itching of the genital organs in women, vaginitis, vaginal candidiasis.

From the musculoskeletal system: crystalluria (especially in the elderly), muscle cramps, myalgia, arthralgia; muscle rupture, tendon rupture (including the Achilles tendon), which can occur 48 hours after the start of the use of ofloxacin and can be bilateral; rhabdomyolysis and / or myopathy, muscle weakness. If there are signs of tendon inflammation, drug therapy should be stopped immediately and appropriate treatment for the affected tendon should be prescribed.

On the part of the blood: neutropenia, leukopenia, anemia, hemolytic anemia, eosinophilia, thrombocytopenia, pancytopenia agranulocytosis, inhibition of bone marrow hematopoiesis, blood dysrasia according to the type of medullary aplasia, petechia, ecchymosis / bruising, prothrombotic prolongation of thrombotic time.

From the sensory organs: eye irritation, vertigo, tinnitus, hearing loss.

From the respiratory system: cough, nasopharyngitis, pharyngitis, bronchospasm, allergic pneumonitis, severe suffocation, shortness of breath, stridor.

Metabolic disorders: hypoglycemia or hyperglycemia (in patients with diabetes mellitus).

Infections: fungal infections, candidiasis, resistance to pathogenic microorganisms.

Others: fatigue, chest pain, fever, nose pain, weakness, fever, malaise, excessive increase or decrease in blood glucose, weakness.

It is possible that Ofor may cause an attack of porphyria in susceptible patients.

In addition, in some cases, side effects, such as impaired smell, taste, and hearing, disappeared after discontinuation of Ofor therapy.

Hiccups, soreness of the oral mucosa are also possible.

special instructions

Before starting treatment, it is necessary to conduct tests: culture on microflora and determination of sensitivity to ofloxacin.

When using the drug Ofor, it is required to maintain adequate hydration. In patients with impaired renal and hepatic function, the drug should be prescribed with caution and monitor laboratory parameters of liver and kidney function. For patients with impaired renal function, the prescribed dose of ofloxacin must be adjusted, given the slow release.

In case of impaired liver function, the drug is used carefully because of the possibility of impaired liver function. For fluoroquinolones, cases of fulminant hepatitis, which could cause liver failure (up to death), have been reported. It is necessary to stop treatment and consult a doctor in case of signs and symptoms of liver disease, such as anorexia, jaundice, dark urine, itching and abdominal pain.

Diseases caused by Clostridium difficile. Diarrhea, especially severe, persistent or mixed with blood, during or after treatment with the drug may be a symptom of pseudomembranous colitis.

If pseudomembranous colitis is suspected, ofloxacin should be discontinued immediately and appropriate symptomatic antibiotic therapy (eg, vancomycin, teicoplanin, or metronidazole) should be started. In this situation, drugs that inhibit intestinal motility are contraindicated.

Hypersensitivity and allergic reactions to fluoroquinolones have been reported after the first use. Anaphylactic and anaphylactoid reactions can go into shock, which is life-threatening, even after the first use. In this case, the drug should be discontinued and appropriate treatment should begin.

Patients taking Ofor should avoid sun exposure and UV rays (tanning beds) due to possible photosensitization. If photosensitivity reactions occur (for example, like sunburn), ofloxacin therapy should be discontinued.

Cases of sensory or sensorimotor peripheral neuropathy have been reported in patients taking fluoroquinolones, including ofloxacin. With the development of neuropathy, ofloxacin should be discontinued.

In case of severe arterial hypotension, the use of the drug should be discontinued.

Extension of the Q – T interval. When taking fluoroquinolones, very rare cases of lengthening of the Q – T interval have been reported. Caution should be exercised when using fluoroquinolones, including ofloxacin, in patients with known risk factors for prolonging the Q – T interval, elderly people, in case of electrolyte imbalance (hypokalemia, hypomagnesemia), congenital or acquired prolongation of the Q – T interval, heart disease (cardiac insufficiency, myocardial infarction, bradycardia).

Tendonitis. In rare cases, with quinolone treatment, tendonitis may occur, which can lead to rupture of tendons, including Achilles.The most susceptible to the development of tendonitis are elderly patients. The risk of tendon rupture is enhanced by treatment with glucocorticoids. If tendinitis is suspected or the first symptoms of pain or inflammation appear, treatment should be stopped immediately and appropriate measures taken (for example, to ensure immobilization).

Patients with impaired central nervous system function, with cerebral arteriosclerosis, in people with mental illness at present or in a history of the drug should be prescribed with caution.

In patients with diabetes, ofloxacin can cause potentiation of the hypoglycemic effect of insulin, oral hypoglycemic drugs (including glibenclamide). In these patients, it is necessary to control the level of glucose in the blood.

With prolonged or repeated antibiotic treatment, opportunistic infections and the growth of resistant microorganisms are possible. With the development of a secondary infection, appropriate measures must be taken.

During treatment with the drug, like other drugs of this group, the resistance of some strains of Pseudomonas aeruginosa can develop quite quickly.

Ophor is not the drug of choice for treatment of pneumonia caused by pneumococci or mycoplasmas, or tonsillar tonsillitis caused by β-hemolytic streptococcus.

During treatment should not drink alcoholic beverages.

In patients with a history of myasthenia gravis, the drug is prescribed with caution.

In patients taking vitamin K antagonists, blood coagulation should be monitored while taking the drug and vitamin K antagonists (warfarin) because of the potential risk of increased blood coagulation (prothrombin time) and / or bleeding.

The drug contains lactose, therefore, in patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome, the drug should not be used.

Laboratory research. During treatment with the drug, false-positive results may occur when determining opiates or porphyrins in urine. Therefore, it is necessary to use more specific methods.

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

If there is a history of abnormalities from the blood system, it is recommended to control the number of leukocytes, especially during repeated courses of treatment.

During the treatment period, an increase in the severity of disorders of the central nervous system or peripheral nervous system may be noted. In the event of peripheral neuropathy, impaired coordination of movements (ataxia), dizziness, or impaired consciousness, treatment with the drug should be discontinued.

Possible exacerbation of candidomycosis, requiring appropriate treatment.

During hemodialysis, a decrease in T_½ and prescribe additional doses of the drug before or after hemodialysis.

The concentration of lithium salts, creatinine and electrolytes must be controlled when using lithium therapy.

The severity of the effect of other drugs may increase or decrease during treatment.

Use during pregnancy and lactation. The drug is contraindicated during pregnancy and lactation.

When using the drug for the period of therapy, breast-feeding should be discontinued.

Children. The drug is contraindicated in children (under the age of 18 years) until the growth of the skeleton is completed.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. When using the drug, undesirable manifestations from the nervous system are possible.The possibility of such manifestations must be considered by persons who drive vehicles or work with mechanisms.

Interactions

With the simultaneous administration of ofloxacin with antihypertensive drugs, a sudden decrease in hell is possible. in such cases, or if ofloxacin is used for anesthesia with barbiturates, it is necessary to monitor the function of the cardiovascular system.

It is contraindicated to use ofloxacin simultaneously with drugs that extend the Q – T interval (class IA antiarrhythmic drugs - quinidine, procainamide and class III - amiodarone, sotalol, tricyclic antidepressants, macrolides).

With the simultaneous use of ofloxacin with NSAIDs (including derivatives of propionic acid), derivatives of nitroimidazole and methylxanthines, the risk of developing a nephrotoxic effect increases, a decrease in the seizure threshold can lead to the development of seizures.

The concomitant use of ofloxacin in high doses with drugs that are released by tubular secretion can lead to increased plasma concentrations due to a decrease in their excretion.

Since most quinolones, including ofloxacin, inhibit the enzymatic activity of cytochrome P450, the simultaneous use of ofloxacin with drugs that are metabolized by this system (cyclosporine, theophylline, methylxanthine, caffeine, warfarin) prolongs T_½ specified medicines.

With the simultaneous administration of ofloxacin and vitamin K antagonists, it is necessary to constantly monitor the blood coagulation system.

The simultaneous use of the drug with antacids containing calcium, magnesium or aluminum, with sucralfate, with ferrous or trivalent iron, with multivitamins containing zinc, reduces the absorption of ofloxacin. Therefore, the interval between taking these drugs should be at least 2 hours.

With the simultaneous use of ofloxacin with oral antidiabetic agents and insulin, hypoglycemia or hyperglycemia is possible. Therefore, it is necessary to monitor the parameters to compensate for these conditions. With simultaneous use with glibenclamide, an increase in the level of glibenclamide in blood plasma is possible.

When used with drugs that alkalize urine (carbonic anhydrase inhibitors, citrates, sodium bicarbonate), the risk of crystalluria and nephrotic manifestations increases.

The simultaneous use of ofloxacin with probenecid, cimetidine, furosemide, methotrexate leads to an increase in the concentration of ofloxacin in the blood plasma.

Ofloxacin can inhibit the growth of Mycobacterium tuberculosis, which leads to false negative results in a bacteriological study to diagnose tuberculosis.

Unlike other nitroimidazoles, ornidazole does not inhibit alcohol dehydrogenase, however, like other imidazoles, Ofor should not be taken simultaneously with alcohol.

Concomitant use with oral anticoagulants may increase the risk of hemorrhage.

The equilibrium concentration of theophylline in blood plasma, T_½ and the risk of theophylline-dependent adverse reactions may increase while taking Ofor. Plasma theophylline levels must be carefully monitored and theophylline dosage adjusted as necessary while taking Ofor. Adverse reactions (including seizures) can occur with or without increased plasma theophylline levels.

If Ofor is taken together with warfarin or its derivatives, it is necessary to carefully monitor the prothrombin time or conduct an appropriate coagulation test.

Ornidazole prolongs the muscle relaxant effect of vecuronium bromide.

Laboratory research.During treatment with ofloxacin, false-positive results may be noted in the determination of opiates or porphyrins in urine. Therefore, it is necessary to use more specific methods.

Overdose

Symptoms: dizziness, agitation, headache, confusion, lethargy, abdominal pain, diarrhea, nausea, vomiting, cramps, erosive damage to the mucous membrane, interstitial nephritis or increased manifestations of other adverse reactions may develop.

Treatment: gastric lavage, enhanced hydration, detoxification, desensitizing and symptomatic therapy, which should be aimed at correcting disorders of the internal organs. The specific antidote is unknown. ECG monitoring is necessary because of the risk of lengthening the Q – T interval. Hemodialysis and peritoneal dialysis slightly reduce the concentration of the drug in the blood. When seizures appear diazepam is indicated.

Storage conditions

In the original packaging at a temperature not exceeding 30 ° C.