Properties
What is it?
DAZOLAX Composition Each film-coated tablet contains: Ciprofloxacin Hydrochloride BP equivalent to Ciprofloxacin 500 mg Ornidazole 500 mg Excipients q.s. Color: Titanium Dioxide BP Excipients: PVP K 30, Corn Starch, Microcrystalline Cellulose Powder, Isopropyl Alcohol, Talc, Aerosil, Sodium Starch Glycolate, Magnesium Stearate, Base Granules for coating, Hydroxypropyl Methylcellulose, Titanium Dioxide, Methylene Dichloride. Description Dazolax is a combination drug containing Ciprofloxacin (a 2nd generation fluoroquinolone derivative) and Ornidazole (a 5-nitroimidazole derivative) and acts as antimicrobial and antiprotozoal agents. Pharmacological Properties Pharmacodynamics Ciprofloxacin Mechanism of Action The mechanism of action of fluoroquinolones, including ciprofloxacin, differs from that of penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines; therefore, microorganisms resistant to these drug classes may be susceptible to ciprofloxacin. Resistance to fluoroquinolones primarily occurs through mutations in DNA gyrases, decreased outer membrane permeability, or reduced drug efficacy. Cross-resistance There are no reports of cross-resistance between ciprofloxacin and other classes of antimicrobials. Ciprofloxacin is active against the following bacterial strains, both in vitro and in clinical infections. Gram-positive bacteria Bacillus anthracis, Enterococcus faecalis, Staphylococcus aureus (methicillin-susceptible strains only), Staphylococcus epidermidis (methicillin-susceptible strains only), Staphylococcus saprophyticus, Streptococcus pneumoniae, Streptococcus pyogenes. Gram-negative bacteria Campylobacter jejuni, Citrobacter koseri, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella, Moraxella catarrhalis, Morganella morganii, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Salmonella typhi, Serratia marcescens, Shigella lloydii, Shigella flexneri, Shigella sonnei, Yersinia pestis. Ornidazole Ornidazole is a 5-nitroimidazole derivative with antiprotozoal and anaerobic antibacterial activity. In the body, it is converted into a product that interacts with the DNA of susceptible microorganisms, causing its structure to break down, inhibiting protein synthesis, and leading to cell death. Ornidazole is effective against Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia (Giardia intestinalis), as well as certain anaerobic bacteria such as Bacteroides and Clostridium spp., Fusobacterium spp., and anaerobic cocci. Pharmacokinetics Ciprofloxacin Following oral administration of single doses of 250 mg, 500 mg, and 750 mg of ciprofloxacin, it is rapidly and extensively absorbed, primarily from the small intestine, reaching maximum serum concentrations 1-2 hours later. Absolute bioavailability is approximately 70-80%. Ciprofloxacin is excreted unchanged, mainly by the kidneys, with a small portion via feces. The half-life in patients with normal renal function is approximately 4-7 hours. Ornidazole Following oral administration, ornidazole is rapidly absorbed. Bioavailability is on average 90%. Plasma concentration peak is reached in 3 hours. The half-life is approximately 13 hours. 85% of a single dose is excreted within the first 5 days. Most of the administered dose is metabolized, and 4% is excreted unchanged in the urine. Indications for Use Dazolax is indicated for the treatment of the following infections caused by strains susceptible to the ciprofloxacin/ornidazole combination: - Sexually transmitted infections, including chlamydia, mycoplasmosis, gonorrhea, trichomoniasis, as well as mixed infections; - Infections of the kidneys and/or urinary tract; - Lower respiratory tract infections; - Chronic infections of the ENT organs; - Skin and soft tissue infections; - Bone and joint infections; - Gastrointestinal tract infections; It can be used for the treatment and prophylaxis of infections during major bowel surgery and gynecological procedures, including abortions. Dosage Take orally, 1-2 hours before or 2 hours after meals. For acute infections, the course of treatment is 5-7 days, and for chronic recurrent infections – 1 tablet twice daily for 10-14 days; or as prescribed by a doctor. After the symptoms of the disease subside, the drug should be continued for 2 days. In patients with creatinine clearance of 20 ml/min or less, as well as in elderly and underweight patients, half of the usual dose is prescribed. Contraindications - Hypersensitivity to ciprofloxacin, ornidazole, imidazole derivatives, quinolones, or any of the excipients in the preparation; - Concomitant use of fluoroquinolones and tizanidine; - Diseases of the central nervous system; - Blood formation disorders. Side Effects Fluoroquinolone drugs, such as ciprofloxacin, can cause side effects affecting tendons, muscles, joints, and the nervous system. Characteristic are tendon inflammation and strain, muscle pain or swelling, difficulty walking, numbness and tingling sensations, severe pain, fatigue, depression, memory problems, sleep, vision, and hearing disturbances, changes in taste and smell. Tendon swelling and damage can occur within 2 days of starting fluoroquinolone treatment, or several months after discontinuing treatment. Contact your doctor in the following cases: - At the first sign of tendon damage, such as tendon pain or swelling. Rest the affected area; - If you feel pain, numbness or tingling, itching, burning, weakness, especially in your legs or hands; - If you have swelling of your shoulders, arms or legs, difficulty walking, feel tired or depressed, or have problems with memory, sleep, or notice changes in hearing, vision, or smell. Serious side effects include tendon inflammation, tendon strain, joint pain, limb pain, pain during walking, neuropathies associated with paresthesia, depression, fatigue, memory impairment, sleep, hearing, vision, taste, and smell disturbances. Tendon strain (especially Achilles tendon and other tendons) can occur within 48 hours of starting fluoroquinolone treatment, or later, several months after discontinuing treatment. Patients over 60 years of age with renal insufficiency or organ transplant recipients treated with corticosteroids (drugs such as hydrocortisone and prednisolone) are at higher risk of tendon damage. Therefore, concomitant use of fluoroquinolones with corticosteroids should be avoided. To prevent the development of potentially irreversible conditions, if the first signs of tendon pain or inflammation appear, fluoroquinolone use should be discontinued. In case of neuropathy symptoms, such as pain, burning, tingling, numbness, or weakness, fluoroquinolone treatment should be discontinued and a doctor consulted. Fluoroquinolones should generally not be used in patients who have developed serious side effects when using quinolone or fluoroquinolone drugs. Frequency parameters of adverse reactions are defined as follows: very common (≥1/10); common (≥1/100 but <1/10); uncommon (≥1/1000 but <1/100); rare (≥1/10000 but <1/1000); very rare (<1/10000); frequency unknown (cannot be estimated from available data). Ciprofloxacin The most common side effects of ciprofloxacin are nausea and diarrhea. The following are the adverse reactions of ciprofloxacin established by clinical studies, by frequency category. Frequency analysis considers data for both oral and intravenous use of ciprofloxacin. - Infections and parasitic diseases: Uncommon - fungal superinfections. - Blood and lymphatic system disorders: Uncommon - eosinophilia; Rare - leukopenia, anemia, neutropenia, leukocytosis, thrombocytopenia, thrombocythemia; Very rare - hemolytic anemia, agranulocytosis, pancytopenia (risk of death), bone marrow function suppression (risk of death). - Immune system disorders: Rare - allergic reaction, edema/allergic angioneurotic edema; Very rare - anaphylactic reactions, anaphylactic shock (risk of death), serum sickness-like reaction. - Endocrine disorders: Frequency unknown - syndrome of inappropriate secretion of antidiuretic hormone. - Metabolism and nutrition disorders: Uncommon - decreased appetite; Rare - hyperglycemia, hypoglycemia; Frequency unknown - hypoglycemic coma. - Psychiatric disorders: Uncommon - psychomotor hyperactivity/agitation; Rare - disturbance of consciousness and disorientation, anxiety reaction, nightmares; Depression (potentially progressing to suicidal ideation/behavior or suicide attempt and suicide), hallucinations; Very rare - psychotic reactions (potentially progressing to suicidal ideation/behavior or suicide attempt and suicide); Frequency unknown - mania, including hypomania. - Nervous system disorders: Uncommon - headache, dizziness, sleep disturbances, taste disturbances; Rare - paresthesia and dysesthesia, hypoesthesia, tremor, convulsions (including status epilepticus), vertigo; Very rare - migraine, coordination disorder, gait disturbance, olfactory nerve disorders, intracranial hypertension and pseudotumor cerebri; Frequency unknown - peripheral neuropathy and polyneuropathy. - Eye disorders: Rare - visual disturbances (e.g., diplopia); Very rare - color vision disturbances. - Ear and labyrinth disorders: Rare - tinnitus, hearing loss/changes. - Cardiac disorders: Rare - tachycardia; Frequency unknown - ventricular arrhythmia and torsades de pointes type tachycardia (mainly observed in patients with risk factors for QT interval prolongation), QT interval prolongation on ECG. - Vascular disorders: Rare - vasodilation, hypotension, syncope; Very rare - vasculitis. - Respiratory, thoracic and mediastinal disorders: Rare - dyspnea (including asthma). - Gastrointestinal disorders: Common - nausea, diarrhea; Uncommon - vomiting, abdominal and stomach pain, dyspepsia, flatulence; Rare - colitis associated with antibiotic use (in very rare cases, potentially fatal); Very rare - pancreatitis. - Hepato-biliary disorders: Uncommon - increased transaminase levels, increased bilirubin levels; Rare - liver dysfunction, cholestatic jaundice, hepatitis; Very rare - liver necrosis (in very rare cases, may progress to liver failure, risk of death). - Skin and subcutaneous tissue disorders: Uncommon - exanthema, pruritus, urticaria; Rare - photosensitivity reactions; Very rare - petechiae, erythema multiforme, erythema nodosum, Stevens-Johnson syndrome (risk of death), toxic epidermal necrolysis (risk of death); Frequency unknown - acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS). - Musculoskeletal and connective tissue disorders: Uncommon - musculoskeletal pain (e.g., limb pain, back pain, chest pain), arthralgia; Rare - myalgia, arthritis, increased muscle tone, spasms; Very rare - muscle weakness, tendinitis, tendon rupture (primarily Achilles tendon), exacerbation of symptoms of severe myasthenia gravis. - Renal and urinary disorders: Uncommon - renal impairment; Rare - renal failure, hematuria, crystalluria, tubulointerstitial nephritis. - General disorders and administration site conditions: Uncommon - asthenia, fever; Rare - edema, sweating (hyperhidrosis). - Additional investigations: Uncommon - increased serum alkaline phosphatase; Rare - increased amylase levels. Ornidazole Adverse reactions of ornidazole are usually dose-dependent. - Blood and lymphatic system disorders: Uncommon - bone marrow suppression and neutropenia. - Immune system disorders: Uncommon - allergic reactions. - Nervous system disorders: Rare - tremor, rigidity, coordination disorder, convulsions, disturbance of consciousness and signs of sensory or mixed peripheral neuropathy. Mild side effects such as dizziness and drowsiness may occur. - Gastrointestinal disorders: Common - nausea, vomiting, unpleasant metallic taste. Special Precautions Should not be used: - For the treatment of infections that may improve without treatment or are not severe (e.g., throat infections); - For the treatment of non-bacterial infections, e.g., non-bacterial (chronic) prostatitis; - To prevent traveler's diarrhea or recurrent lower urinary tract infections (urinary infections that do not extend beyond the bladder); - For the treatment of mild or moderate bacterial infections, except when other antibacterial drugs are usually recommended for these infections. Should be used with particular caution in the elderly, patients with kidney disease, and organ transplant recipients due to the higher risk of tendon damage. Use with caution in elderly patients with atherosclerosis of the cerebrovascular system, impaired cerebral circulation, epilepsy, and convulsive syndrome of unclear etiology. It is recommended to refrain from alcohol consumption during treatment. Ciprofloxacin Caution is required in patients with a history of serious adverse reactions to quinolone or fluoroquinolone-containing drugs. Treatment of such patients with ciprofloxacin should only be initiated in the absence of alternative options and after careful assessment of the benefit/risk ratio. Severe and mixed infections caused by Gram-positive and anaerobic pathogens Ciprofloxacin monotherapy is not used to treat severe infections or infections that may be caused by Gram-positive or anaerobic pathogens. In such infections, ciprofloxacin should be used in combination with other appropriate antibacterial agents. Streptococcal infections (including Streptococcus pneumoniae) Ciprofloxacin is not recommended for the treatment of streptococcal infections due to insufficient efficacy. Genital tract infections Gonococcal urethritis, cervicitis, epididymo-orchitis, and pelvic inflammatory disease may be caused by fluoroquinolone-resistant strains of Neisseria gonorrhoeae. For this reason, ciprofloxacin may be used in the treatment of gonococcal urethritis or cervicitis only if infection caused by Neisseria gonorrhoeae strains resistant to ciprofloxacin is excluded. For epididymo-orchitis and pelvic inflammatory disease, empirical use of ciprofloxacin may be considered only in combination with other appropriate antibacterial agents (e.g., cephalosporins) if infection caused by Neisseria gonorrhoeae strains resistant to ciprofloxacin cannot be excluded. If clinical improvement is not achieved after 3 days of treatment, treatment should be reviewed. Urinary tract infections Resistance of the pathogen, which is the most common cause of urinary tract infections – Escherichia coli – to fluoroquinolones varies within the European Union. It is recommended that physicians study the local prevalence of resistance of Escherichia coli to fluoroquinolones before prescribing treatment. It is expected that a single dose of ciprofloxacin may be less effective for treating uncomplicated cystitis in premenopausal women compared to longer-term treatment. The increasing resistance of Escherichia coli to quinolones should be taken into account. Intra-abdominal infections Data on the efficacy of ciprofloxacin in the treatment of post-operative intra-abdominal infections are limited. Traveler's diarrhea When choosing ciprofloxacin, information on pathogen resistance to it must be considered. Bone and joint infections Ciprofloxacin should be used in combination with other antibacterial agents, based on microbiological study results. Pulmonary anthrax The basis for human use is the following data: in vitro susceptibility studies, animal experiments, and limited data on human use. The prescription of anthrax treatment by a physician should be in accordance with recognized national and/or international documents. Hypersensitivity Hypersensitivity reactions and allergic reactions, including anaphylaxis and anaphylactic reactions, which can be life-threatening, may occur after a single dose. In case of such a reaction, ciprofloxacin treatment should be discontinued and appropriate treatment administered. Long-term, disabling, and potentially irreversible serious adverse drug reactions There are reports of very rare, long-lasting (lasting several months or years), disabling, potentially irreversible serious adverse drug reactions affecting various, sometimes multiple, body systems (musculoskeletal, nervous, sensory organs) in patients taking quinolones and fluoroquinolones, regardless of 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 consulted. Tendinitis and tendon rupture In general, the use of ciprofloxacin is not recommended in patients with a history of tendon-related diseases or disorders during quinolone treatment. Nevertheless, in very rare cases, after microbiological identification of the causative microorganism and assessment of the benefit-risk ratio, ciprofloxacin may be prescribed to patients for the treatment of established severe infections, especially in cases of failure of standard treatment or bacterial resistance, when microbiological data justify the use of ciprofloxacin. Tendinitis and tendon rupture (especially Achilles tendon), sometimes bilateral, may develop within the first 48 hours of starting treatment with quinolones and fluoroquinolones, as well as several months after completion of treatment. The risk of developing tendinitis and tendon rupture is increased in the elderly, patients with renal insufficiency, parenchymal organ transplantation, and concomitant therapy with corticosteroids. In case of any signs of tendinitis (e.g., painful swelling, inflammation), ciprofloxacin treatment should be discontinued and alternative treatment considered. Appropriate treatment of the affected limb(s) should be carried out (e.g., limb immobilization). Corticosteroids should not be used when signs of tendinopathy appear. Patients with severe myasthenia gravis Caution should be exercised when using ciprofloxacin in patients with severe myasthenia gravis, as symptoms may be exacerbated. Aneurysm and aortic dissection Based on epidemiological studies, there are reports of an increased risk of aneurysm development and aortic dissection after the use of fluoroquinolones, especially in elderly patients. In patients with a history of aneurysm, or who have an aneurysm and/or aortic dissection, as well as other risk factors or conditions predisposing to aneurysm and aortic dissection (e.g., Marfan syndrome, Ehlers-Danlos syndrome vascular type, Takayasu arteritis, giant cell arteritis, Behçet's disease, arterial hypertension, atherosclerosis), fluoroquinolones should be used only after a proper benefit/risk assessment and consideration of other possible treatment options. In case of sudden abdominal, chest, or back pain, the patient should immediately seek emergency medical attention. Visual disturbances In case of visual disturbances or any effects on the eyes, immediate consultation is recommended. Photosensitivity It has been established that ciprofloxacin can cause photosensitivity reactions. Patients taking ciprofloxacin should be advised to avoid prolonged exposure to sunlight or UV radiation during treatment. Central nervous system Ciprofloxacin, like other quinolones, is known to cause seizures or lower the seizure threshold. There have been reports of status epilepticus. Ciprofloxacin should be used with caution in patients with central nervous system disorders who may be prone to seizures. If seizures occur, ciprofloxacin treatment should be discontinued. Mental reactions may occur even after the first use of ciprofloxacin. In rare cases, depression or psychosis may progress to suicidal ideation/behavior, suicide attempt, or suicide. If adverse reactions occur, ciprofloxacin treatment should be discontinued. Peripheral neuropathy There are reports of sensory or sensorimotor polyneuropathy in patients taking quinolones or fluoroquinolones, leading to paresthesia, hypoesthesia (reduced sensation), dysesthesia, or weakness. Patients using ciprofloxacin are recommended to inform their doctor about the development of neuropathy symptoms (such as pain, burning, tingling, numbness, or weakness) before continuing treatment, to prevent the development of potentially irreversible conditions. Cardiac disorders Caution should be exercised when using fluoroquinolones, including ciprofloxacin, in patients with risk factors for QT interval prolongation, such as: - Congenital long QT syndrome; - Concomitant use with drugs that prolong the QT interval (e.g., Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, and antipsychotics); - Uncorrected electrolyte imbalance (e.g., hypokalemia, hypomagnesemia); - Cardiac diseases (e.g., cardiac arrest, myocardial infarction, bradycardia). Elderly patients and women may be more susceptible to QT interval-prolonging drugs. Therefore, caution should be exercised when using fluoroquinolones, including ciprofloxacin, in these patient groups. Dysglycemia Like all quinolones, changes in blood glucose levels (including hyperglycemia and hypoglycemia) have been reported in diabetic patients treated with oral hypoglycemic agents (e.g., glibenclamide) or insulin. There have been reports of hypoglycemic coma. In diabetic patients, adequate blood glucose monitoring is recommended. Gastrointestinal tract Severe acute diarrhea (potentially fatal) during or after treatment (up to several weeks after completion of treatment) may indicate colitis associated with antimicrobial therapy, requiring immediate treatment. In such cases, ciprofloxacin treatment should be immediately discontinued and appropriate treatment initiated. The use of peristalsis-inhibiting drugs is contraindicated in similar situations. Kidneys and urinary tract Cases of crystalluria associated with the use of ciprofloxacin have been described. It is recommended to drink plenty of fluids during ciprofloxacin treatment, and to avoid excessive urine alkalinization. Renal impairment Since ciprofloxacin is mainly excreted unchanged by the kidneys, in patients with renal impairment, dose correction is necessary to avoid exacerbation of severe side effects due to ciprofloxacin accumulation, as described in the "Dosage and Administration" section. Liver and biliary tract Cases of liver necrosis and liver failure with risk of death have been described with the use of ciprofloxacin. In case of any signs or symptoms of hepatopathy (e.g., anorexia, jaundice, presence of yellow pigments in urine, itching, and pain on abdominal palpation), treatment should be discontinued. Glucose-6-phosphate dehydrogenase deficiency Hemolytic reactions have been observed in patients with glucose-6-phosphate dehydrogenase deficiency when using ciprofloxacin. In such patients, ciprofloxacin should only be used when the potential benefit outweighs the possible risk. In such cases, monitoring for possible hemolysis is necessary. Resistance During or after ciprofloxacin treatment, bacteria exhibiting resistance to ciprofloxacin may develop, with or without clinical signs of superinfection. There is a particular risk of developing ciprofloxacin-resistant bacteria with prolonged treatment, as well as in the treatment of nosocomial infections and/or infections caused by Staphylococcus and Pseudomonas species. Cytochrome P450 Ciprofloxacin inhibits CYP1A2, so when used with agents metabolized by this pathway (e.g., theophylline, clozapine, olanzapine, ropinirole, tizanidine, duloxetine, agomelatine), serum drug concentrations may increase. For this reason, adequate monitoring of patients is necessary when taking such drugs concomitantly with ciprofloxacin. Serum concentration determination may also be necessary to detect clinical signs of overdose (e.g., theophylline). Concomitant administration of ciprofloxacin and tizanidine is contraindicated. Methotrexate Concomitant administration of ciprofloxacin and methotrexate is not recommended. Effect on analyses The in vitro activity of ciprofloxacin against Mycobacterium tuberculosis may lead to false-negative results in bacteriological analyses of samples taken from patients receiving ciprofloxacin. Ornidazole With high doses or treatment longer than 10 days, regular laboratory and clinical monitoring is necessary. In patients with a history of blood dyscrasia, leukocyte count monitoring should be performed before and after treatment, especially during repeated therapy. Severe diseases of the central and peripheral nervous system may be exacerbated during treatment with the drug. If peripheral neuropathy, ataxia, dizziness, or confusion occurs, treatment should be discontinued. Treatment with ornidazole may exacerbate existing candidiasis. If necessary, appropriate measures should be taken. For patients undergoing hemodialysis, the reduced half-life should be taken into account. An additional dose may be needed before or after hemodialysis. For patients undergoing lithium therapy, monitoring of plasma lithium concentration, creatinine, and electrolytes is necessary when prescribing imidazoles. Effect on diagnostic test results Ornidazole affects the determination of serum glutamic oxaloacetic transaminase and alanine aminotransferase in blood serum. Values are usually very low. Effect on ability to drive and operate machinery When taking Dazolax, the ability to concentrate and the speed of psychomotor reactions may be reduced, which should be considered when using the drug in individuals whose activities are related to driving, operating machinery and mechanisms. Use during pregnancy and lactation The drug is not used during pregnancy and lactation. If it is necessary to take the drug during lactation, breastfeeding should be discontinued. Use in pediatrics The drug is not used in pediatric practice. Interactions with other medicinal products Ciprofloxacin Effects of other drugs on ciprofloxacin: Drugs that prolong the QT interval Ciprofloxacin, like other fluoroquinolones, should be used with caution in patients taking QT interval-prolonging drugs (e.g., Class I and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics). Formation of chelate complexes Concomitant oral administration of ciprofloxacin with medicinal products and mineral supplements containing polyvalent cations (e.g., calcium, magnesium, aluminum, iron), polymeric phosphate binders (e.g., sevelamer or lanthanum carbonate), sucralfate, or antacids, as well as with drugs coated with very hard shells (e.g., didanosine tablets) containing magnesium, aluminum, or calcium, reduces the absorption of ciprofloxacin. For this reason, ciprofloxacin intake is recommended 1-2 hours before or at least 4 hours after taking such drugs. This restriction does not apply to H2 receptor antagonist antacids. Food products and dairy products Calcium, which is part of the diet, does not significantly affect absorption. However, concomitant use of mineral-rich dairy products or beverages (e.g., milk, yogurt, calcium-fortified orange juice) and ciprofloxacin is not recommended, as ciprofloxacin absorption is reduced at this time. Probenecid Probenecid impairs the renal excretion of ciprofloxacin. Concomitant administration of probenecid and ciprofloxacin increases serum concentrations of ciprofloxacin. Metoclopramide Metoclopramide accelerates the absorption of ciprofloxacin (when used orally), resulting in a shorter time to reach maximum plasma concentrations. No effects on ciprofloxacin bioavailability have been observed. Omeprazole Concomitant use of medicinal products containing omeprazole and ciprofloxacin leads to a slight decrease in Cmax and AUC values of ciprofloxacin. Effects of ciprofloxacin on other medicinal products: Tizanidine Combined use of tizanidine with ciprofloxacin is not recommended. In clinical studies in healthy volunteers, an increase in tizanidine concentration in blood serum (Cmax increase: 7-fold, range: 4-21-fold; AUC increase: 10-fold, range: 6-24-fold) was observed with concomitant use with ciprofloxacin. Increased serum concentration of tizanidine is accompanied by enhanced hypotensive and sedative effects. Methotrexate Tubular transport of methotrexate may be inhibited when taken with ciprofloxacin, which can lead to increased plasma concentrations of methotrexate and increase the risk of developing methotrexate-related toxic reactions. Concomitant use of these drugs is not recommended. Theophylline Concomitant administration of ciprofloxacin and theophylline may lead to an undesirable increase in serum theophylline concentration. This may lead to theophylline-induced adverse reactions, which in very rare cases can be life-threatening or fatal. During concomitant use, monitoring of serum theophylline concentration and dose reduction as needed is necessary. Other xanthine derivatives Concomitant administration of ciprofloxacin with caffeine or pentoxifylline (oxypentifylline) has been associated with increased serum concentrations of xanthine derivatives. Phenytoin Concomitant use of ciprofloxacin and phenytoin may lead to increased or decreased phenytoin levels in blood serum, so monitoring of drug levels is recommended. Cyclosporine Concomitant use of medicinal products containing ciprofloxacin and cyclosporine has been associated with a transient increase in serum creatinine concentration. Therefore, frequent monitoring of serum creatinine concentration (twice weekly) is necessary in such patients. Vitamin K antagonists Concomitant use of ciprofloxacin with vitamin K antagonists may enhance their anticoagulant effects. The risk may vary depending on the underlying infection, age, and general health status of the patient, making it difficult to assess the degree of ciprofloxacin's influence on the increase in the international normalized ratio. During or immediately after concomitant use of ciprofloxacin and vitamin K antagonists (e.g., warfarin, acenocoumarol, phenprocoumon, or fluindione), frequent monitoring of the international normalized ratio is recommended. Duloxetine Clinical studies have shown that concomitant use of duloxetine with strong inhibitors of the CYP450 isoenzyme, such as fluvoxamine, can lead to an increase in AUC and Cmax values of duloxetine. There are also preclinical data on possible interaction with ciprofloxacin, so similar effects may be expected after concomitant use. Ropinirole Clinical studies have shown that concomitant use of ropinirole with ciprofloxacin, a moderate inhibitor of the CYP450 isoenzyme, leads to an increase in AUC and Cmax values of ropinirole by 60% and 84%, respectively. Clinical observation for treatment-related adverse reactions and corresponding dose adjustment is recommended during or immediately after concomitant use of ciprofloxacin. Lidocaine Concomitant use of medicinal products containing lidocaine and ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isoenzyme, in healthy volunteers reduces the clearance of intravenously administered lidocaine by 22%. Although lidocaine treatment was well tolerated, interaction with ciprofloxacin after use may occur, accompanied by adverse effects. Clozapine After concomitant administration of 250 mg ciprofloxacin with clozapine for 7 days, serum concentrations of clozapine and N-desmethylclozapine increased by 29% and 31%, respectively. Therefore, clinical observation and dose adjustment of clozapine are recommended during and immediately after concomitant use with ciprofloxacin. Sildenafil After a single oral dose of 50 mg sildenafil concomitantly with 500 mg ciprofloxacin, Cmax and AUC values increased approximately twofold in healthy volunteers. For this reason, caution should be exercised when co-administering ciprofloxacin with sildenafil, considering the risks and benefits. Agomelatine Clinical studies have shown that fluvoxamine, a potent inhibitor of the CYP450 1A2 isoenzyme, significantly inhibits the metabolism of agomelatine, leading to a 60-fold increase in agomelatine exposure. Despite the lack of clinical data on possible interaction with ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isoenzyme, similar effects may be expected after concomitant use. Zolpidem Concomitant use with ciprofloxacin may increase blood levels of zolpidem; concomitant use is not recommended. Ornidazole Unlike other nitroimidazoles, ornidazole does not inhibit aldehyde dehydrogenase and is therefore not incompatible with alcohol. On the other hand, ornidazole potentiates the anticoagulant effect of oral anticoagulants of the coumarin series. This circumstance should be taken into account when adjusting the dose of the anticoagulant. In addition, ornidazole prolongs the muscle relaxant effect of vecuronium bromide. Concomitant use of phenobarbital and other enzyme inducers reduces the half-life of ornidazole from serum. Enzyme inhibitors (e.g., cimetidine) increase the half-life of ornidazole. For determination of interaction with lithium therapy, see "Special Precautions". Overdose Symptoms: Dizziness, confusion and convulsions, vomiting, damage to mucous membranes. Treatment: Symptomatic therapy is carried out. There is no specific antidote. Storage Conditions Store at a temperature not exceeding 25°C, protected from moisture and light, in a place inaccessible to children. Dosage Form Blister 1X10 tablets. Dispensing Category Pharmaceutical Product Group II, dispensed with prescription N3. Manufactured by Adnova Healthcare Pvt. Ltd., 156/157A, Siddhi Industrial Infrastructure Park, Waghodia, Vadodara, Gujarat- 391760, India. Manufactured for Medior Life Care LLP, 172, Kedhar Crest, Nirvana Country I, Sector 50, Gurgaon- 122 018, India.