Cifracid (Solution) Instructions for Use

Marketing Authorization Holder

Edge Pharma Private Limited (India)

ATC Code

J01MA02 (Ciprofloxacin)

Active Substance

Ciprofloxacin (Rec.INN registered by WHO)

Dosage Form

Cifracid

Solution for infusion 2 mg/ml: bottle 100 ml

Dosage Form, Packaging, and Composition

100 ml – infusion bottles (1) with polymer suspension – cardboard packs.

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Antimicrobial agent – fluoroquinolone

Pharmacological Action

A broad-spectrum antimicrobial agent, a fluoroquinolone derivative.

It inhibits bacterial DNA gyrase (topoisomerases II and IV, responsible for the supercoiling process of chromosomal DNA around nuclear RNA, which is necessary for reading genetic information), disrupts DNA synthesis, growth, and division of bacteria; causes pronounced morphological changes (including of the cell wall and membranes) and rapid death of the bacterial cell.

It acts bactericidally on gram-negative organisms during both the resting and division phases (as it affects not only DNA gyrase but also causes lysis of the cell wall), and on gram-positive microorganisms only during the division phase.

Low toxicity to the cells of the macroorganism is explained by the absence of DNA gyrase in them. During the administration of ciprofloxacin, no parallel development of resistance to other antibiotics not belonging to the group of gyrase inhibitors occurs, which makes it highly effective against bacteria that are resistant, for example, to aminoglycosides, penicillins, cephalosporins, tetracyclines, and many other antibiotics.

The following are sensitive to ciprofloxacin: gram-negative aerobic bacteria enterobacteria (Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Hafnia alvei, Edwardsiella tarda, Providencia spp., Morganella morganii, Vibrio spp., Yersinia spp.), other gram-negative bacteria (Haemophilus spp., Pseudomonas aeruginosa, Moraxella catarrhalis, Aeromonas spp., Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejuni, Neisseria spp.), some intracellular pathogens (Legionella pneumophila, Brucella spp., Chlamydia trachomatis, Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii, Corynebacterium diphtheriae); gram-positive aerobic bacteria Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).

Most staphylococci resistant to methicillin are also resistant to ciprofloxacin. The sensitivity of Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) is moderate (high concentrations are required for their suppression).

The following are resistant to ciprofloxacin: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. It is ineffective against Treponema pallidum.

Resistance develops extremely slowly because, on the one hand, practically no persisting microorganisms remain after the action of ciprofloxacin, and on the other hand, bacterial cells lack enzymes that inactivate it.

Pharmacokinetics

After IV administration, C_max of ciprofloxacin is reached at the end of the infusion. The pharmacokinetics of ciprofloxacin is linear in the dose range up to 400 mg. When administered IV 2-3 times/day, no accumulation of ciprofloxacin and its metabolites was noted.

The binding of ciprofloxacin to plasma proteins is 20-30%; the active substance is present in the plasma mainly in a non-ionized form. Ciprofloxacin is freely distributed in body tissues and fluids. V_d in the body is 2-3 L/kg. The concentration of ciprofloxacin in tissues significantly exceeds the concentration in blood serum. It is metabolized in the liver. Four metabolites of ciprofloxacin can be detected in the blood in small concentrations: diethylciprofloxacin (M1), sulfociprofloxacin (M2), oxociprofloxacin (M3), 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 metabolite M4, present in smaller quantities, more closely corresponds to the activity of norfloxacin. Ciprofloxacin is eliminated from the body mainly by the kidneys through glomerular filtration and tubular secretion; a small amount is eliminated through the gastrointestinal tract. Renal clearance is 0.18-0.3 L/h/kg, total clearance is 0.48-0.60 L/h/kg. Approximately 1% of the administered dose is excreted in the bile. Ciprofloxacin is present in bile in high concentrations. In patients with unchanged renal function, T_1/2 is usually 3-5 hours. In case of impaired renal function, T_1/2 increases.

Indications

Uncomplicated and complicated infections caused by microorganisms sensitive to ciprofloxacin.

Adults

Infections of the respiratory tract – pneumonias caused by Klebsiella spp., Enterobacter spp., Proteus spp., Escherichia coli, Pseudomonas aeruginosa, Haemophilus spp., Moraxella catarrhalis, Legionella spp., Staphylococcus spp.; middle ear infections (otitis media), especially if these infections are caused by Staphylococcus spp. and gram-negative microorganisms, including Pseudomonas aeruginosa; eye infections; kidney infections and/or complicated urinary tract infections; genital infections, including adnexitis, gonorrhea, prostatitis; abdominal infections (bacterial infections of the gastrointestinal tract, biliary tract, peritonitis); skin and soft tissue infections; bone and joint infections; sepsis; infections or prevention of infections in patients with reduced immunity (patients taking immunosuppressants or patients with neutropenia); selective intestinal decontamination in patients with reduced immunity; prevention and treatment of the pulmonary form of anthrax (infection with Bacillus anthracis).

For the treatment of the following infectious and inflammatory diseases, Ciprofloxacin may be used only as an alternative to other antimicrobial drugs: acute sinusitis; uncomplicated urinary tract infections.

Children

Treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years; prevention and treatment of the pulmonary form of anthrax (infection with Bacillus anthracis).

The use of ciprofloxacin in children should be initiated only after assessing the benefit/risk ratio due to the possible adverse effect on joints and periarticular tissues.

ICD codes

Dosage Regimen

Determine the dosage individually based on the infection’s severity, causative pathogen, and the patient’s renal function, age, and clinical status.

For adults, administer a single dose of 200 mg to 400 mg by intravenous infusion. Administer the total daily dose twice daily (every 12 hours).

For urinary tract infections, a dose of 200 mg twice daily is often sufficient. For more severe or complicated infections, including bone, joint, and respiratory infections, a dose of 400 mg twice daily is recommended.

For pediatric patients (5-17 years) with cystic fibrosis, administer 10 mg per kg of body weight intravenously. The maximum single dose should not exceed 400 mg. Administer the dose every 8 hours (three times daily).

For renal impairment, adjust the dosage based on creatinine clearance (CrCl). For CrCl 30-60 mL/min, administer the standard dose every 12 hours. For CrCl 5-29 mL/min, administer half the standard dose every 18-24 hours. For patients on hemodialysis, administer the standard dose after each dialysis session.

Infuse each 200 mg dose over at least 30 minutes. Infuse each 400 mg dose over at least 60 minutes. Do not administer by rapid IV bolus.

The duration of therapy depends on the clinical response. Generally, continue treatment for at least 3 days after signs and symptoms have disappeared. For anthrax, a treatment course of 60 days is recommended.

Adverse Reactions

Infectious and parasitic diseases uncommon – mycotic superinfections; rare – pseudomembranous colitis (in very rare cases with possible fatal outcome).

From the hematopoietic system: uncommon – eosinophilia; rare – leukopenia, anemia, neutropenia, leukocytosis, thrombocytopenia, thrombocythemia. Very rare: hemolytic anemia, agranulocytosis, pancytopenia (life-threatening), bone marrow depression (life-threatening).

Allergic reactions uncommon – urticaria; rare – allergic edema/angioedema; very rare – anaphylactic reactions, anaphylactic shock (life-threatening), serum sickness.

From the endocrine system frequency unknown – syndrome of inappropriate ADH secretion.

From metabolism uncommon – decreased appetite and food intake; rare – 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, nightmares, depression, hallucinations; very rare – psychotic reactions (increase in self-injurious behavior such as suicidal acts/thoughts, as well as suicide attempt or successful suicide); frequency unknown – attention disturbances, nervousness, memory impairment, delirium.

From the nervous system uncommon – headache, dizziness, sleep disorder, taste disturbances; rare – paresthesia and dysesthesia, hypoesthesia, tremor, convulsions (including epileptic seizures), vertigo; very rare – migraine, impaired coordination, impaired sense of smell, hyperesthesia, intracranial hypertension (cerebral pseudotumor symptoms); frequency unknown – peripheral neuropathy and polyneuropathy.

From the organ of vision rare – visual disturbances; very rare – impaired color perception.

From the organ of hearing and labyrinthine disorders rare – tinnitus, hearing loss; very rare – hearing disorders.

From the cardiovascular system rare – tachycardia, vasodilation, decreased blood pressure, fainting; very rare – vasculitis; frequency unknown – QT interval prolongation, ventricular arrhythmias (including torsades de pointes, more often in patients predisposed to QT interval prolongation).

From the respiratory system rare – breathing disorders (including bronchospasm).

From the digestive system common – nausea, diarrhea; uncommon – vomiting, abdominal pain, dyspepsia, flatulence; very rare – pancreatitis.

From the liver and biliary tract uncommon – increased activity of hepatic transaminases, increased bilirubin concentration; rare – liver function disorders, jaundice, hepatitis (non-infectious); very rare – liver tissue necrosis (in extremely rare cases progressing to life-threatening liver failure).

From the skin and subcutaneous tissues uncommon – rash, itching, urticaria; rare – photosensitivity, blistering; very rare – petechiae, erythema multiforme minor, erythema nodosum, Stevens-Johnson syndrome (malignant exudative erythema), including potentially life-threatening; Lyell’s syndrome (toxic epidermal necrolysis), including potentially life-threatening; frequency unknown – acute generalized exanthematous pustulosis.

From the musculoskeletal system uncommon – arthralgia; rare – myalgia, arthritis, increased muscle tone, muscle cramps; very rare – muscle weakness, tendinitis, tendon rupture (primarily Achilles), exacerbation of myasthenia gravis symptoms.

From the kidneys and urinary tract uncommon – renal function disorders; rare – renal failure, hematuria, crystalluria, tubulointerstitial nephritis.

General reactions uncommon – pain syndrome of nonspecific etiology, general malaise, fever; rare – edema, hyperhidrosis; very rare – gait disturbance.

From laboratory parameters uncommon – increased alkaline phosphatase activity; rare – change in prothrombin content, increased amylase activity; frequency unknown – increased INR (in patients receiving vitamin K antagonists).

The frequency of the following adverse reactions with IV administration and with the use of step-down therapy with ciprofloxacin (IV administration followed by oral administration) is higher than with oral administration common – vomiting, increased activity of hepatic transaminases, rash; uncommon – thrombocytopenia, thrombocythemia, confusion and disorientation, hallucinations, paresthesia and dysesthesia, convulsions, vertigo, visual disturbances, hearing loss, tachycardia, vasodilation, decreased blood pressure, reversible liver function disorders, jaundice, renal failure, edema; rare – pancytopenia, bone marrow depression, anaphylactic shock, psychotic reactions, migraine, olfactory disturbances, hearing disorders, vasculitis, pancreatitis, liver tissue necrosis, petechiae, tendon rupture.

In children common – arthropathies. The frequency of arthropathy (arthralgia, arthritis) mentioned above is based on clinical studies in adult patients.

Contraindications

Hypersensitivity to ciprofloxacin or other drugs from the fluoroquinolone group; concomitant use of ciprofloxacin and tizanidine due to clinically significant side effects (arterial hypotension, drowsiness) associated with an increase in tizanidine plasma concentration; pregnancy, breastfeeding period; childhood and adolescence under 18 years of age – until the completion of the skeletal formation process for all indications (except for therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs up to 5 years of age; prophylaxis and treatment of the pulmonary form of anthrax).

With caution

Epilepsy, lowered seizure threshold (or history of seizures), severe cerebral atherosclerosis, cerebrovascular accident, organic brain lesions or stroke; mental illnesses (depression, psychosis); severe renal and/or hepatic insufficiency; tendon disorders during previous treatment with quinolones; increased risk of QT interval prolongation or development of torsades de pointes arrhythmia (for example, congenital long QT syndrome, heart diseases (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (for example, in hypokalemia, hypomagnesemia); concomitant use of drugs that prolong the QT interval (including class IA and III antiarrhythmic agents, tricyclic antidepressants, macrolides, antipsychotics); concomitant use with inhibitors of the CYP1A2 isoenzyme (including theophylline, methylxanthine, caffeine, duloxetine, clozapine, ropinirole, olanzapine, agomelatine); myasthenia gravis; use in elderly patients, in patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylurea drugs) or insulin.

Use in Pregnancy and Lactation

Use is contraindicated during pregnancy and the breastfeeding period.

Use in Hepatic Impairment

Use with caution in severe hepatic insufficiency.

Use in Renal Impairment

Patients with impaired renal function require dosage regimen adjustment.

Pediatric Use

Intravenous administration is contraindicated in children and adolescents under 18 years of age – until the completion of the skeletal formation process for all indications (except for therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs up to 5 years of age; prophylaxis and treatment of the pulmonary form of anthrax).

Geriatric Use

In elderly patients, Ciprofloxacin should be used in lower doses, depending on the severity of the disease and creatinine clearance.

Special Precautions

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

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

For genital infections presumably caused by fluoroquinolone-resistant Neisseria gonorrhoeae strains, information on local resistance to ciprofloxacin should be considered and the susceptibility of the pathogen should be confirmed by laboratory tests.

Resistance of Escherichia coli, the most common pathogenic microorganism causing urinary tract infections, to fluoroquinolones 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.

Ciprofloxacin has an effect on QT interval prolongation. Given that women have a greater average QT interval duration compared to men, they are more sensitive to drugs that cause QT interval prolongation. Elderly patients also have increased sensitivity to the action of drugs that cause QT interval prolongation. Ciprofloxacin should be used with caution in combination with drugs that prolong the QT interval (for example, class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, and antipsychotic drugs) or in patients with an increased risk of QT interval prolongation or development of torsades de pointes arrhythmia (for example, with congenital long QT syndrome, corrected electrolyte imbalance such as hypokalemia or hypomagnesemia, as well as with heart diseases such as heart failure, myocardial infarction, bradycardia).

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

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 prescription of appropriate treatment (vancomycin orally at a dose of 250 mg 4 times/day). In this situation, the use of drugs that suppress intestinal peristalsis is contraindicated.

Cases of liver necrosis and life-threatening liver failure have been reported with the use of ciprofloxacin. If signs of liver disease such as anorexia, jaundice, dark urine, itching, abdominal pain are present, ciprofloxacin should be discontinued. In patients taking Ciprofloxacin and who have had liver disease, a temporary increase in the activity of liver transaminases and alkaline phosphatase or cholestatic jaundice may be observed.

Ciprofloxacin should be used with caution in patients with severe myasthenia gravis, as exacerbation of symptoms is possible.

At the first signs of tendinitis (painful swelling in the joint area, inflammation), the use of ciprofloxacin should be discontinued, physical activity should be avoided because there is a risk of tendon rupture, and a doctor should be consulted. When taking ciprofloxacin, cases of tendinitis and tendon ruptures (mainly the Achilles tendon), sometimes bilateral, may occur even within the first 48 hours after the start of therapy. Inflammation and tendon rupture may occur even several months after discontinuation of ciprofloxacin treatment. In elderly patients, patients with renal failure, patients after organ transplantation, simultaneously receiving corticosteroid treatment, there is an increased risk of tendinopathy. Ciprofloxacin should be used with caution in patients with a history of tendon disorders associated with quinolone use.

Ciprofloxacin, like other fluoroquinolones, can provoke convulsions and lower the seizure threshold. In patients with epilepsy and those who have had CNS diseases (for example, lowered seizure threshold, history of seizures, cerebrovascular accidents, organic brain lesions or stroke) due to the threat of developing CNS side effects, Ciprofloxacin should be used only in cases where the expected clinical benefit outweighs the possible risk of side effects. If convulsions occur, the use of ciprofloxacin should be discontinued.

Mental reactions can occur even after the first use of fluoroquinolones, including Ciprofloxacin. In rare cases, depression or psychotic reactions may progress to suicidal thoughts and suicidal attempts, including completed ones. If any CNS side effects develop, including mental disorders, Ciprofloxacin should be discontinued immediately and appropriate therapy initiated. In these cases, it is recommended to switch to therapy with another antibiotic, other than fluoroquinolones, if possible.

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

A photosensitivity reaction may occur with the use of ciprofloxacin, so patients should avoid contact with direct sunlight and UV light. Treatment should be discontinued if symptoms of photosensitivity are observed (for example, skin changes resembling sunburn).

It is known that Ciprofloxacin is a moderate inhibitor of CYP1A2 isoenzymes. Caution should be exercised when using ciprofloxacin concomitantly with drugs metabolized by these enzymes, such as theophylline, methylxanthine, caffeine, duloxetine, ropinirole, clozapine, olanzapine, agomelatine – because an increase in the serum concentration of these drugs due to inhibition of their metabolism by ciprofloxacin can cause specific adverse reactions. Concomitant use of ciprofloxacin and tizanidine is contraindicated.

To avoid the development of crystalluria, exceeding the recommended daily dose is unacceptable, sufficient fluid intake and maintenance of acidic urine reaction are also necessary.

Under in vitro conditions, Ciprofloxacin may interfere with the bacteriological examination of Mycobacterium tuberculosis, inhibiting its growth, which may lead to false-negative results when diagnosing this pathogen in patients taking Ciprofloxacin.

As with other fluoroquinolones, changes in blood glucose concentration, including hypo- and hyperglycemia, are possible with the use of ciprofloxacin. During therapy with ciprofloxacin, dysglycemia may occur more frequently in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylurea drugs) or insulin. When using ciprofloxacin in such patients, the risk of hypoglycemia increases, up to hypoglycemic coma. Patients should be informed about the symptoms of hypoglycemia (confusion, dizziness, increased appetite, headache, nervousness, palpitations or rapid pulse, pale skin, sweating, tremors, weakness). If a patient develops hypoglycemia, treatment with ciprofloxacin should be stopped immediately and appropriate therapy initiated. In these cases, it is recommended to switch to therapy with another antibiotic, other than fluoroquinolones, if possible. When conducting treatment with ciprofloxacin in elderly patients, in patients with diabetes mellitus, careful monitoring of blood glucose concentration is recommended.

According to epidemiological studies, an increased risk of aortic aneurysm and aortic dissection has been reported after taking fluoroquinolones, especially in elderly patients.

In this regard, fluoroquinolones should be used only after a careful benefit/risk assessment and consideration of other treatment options in patients with a family history of aortic aneurysm or in patients with diagnosed aortic aneurysm and/or aortic dissection or in the presence of other risk factors or conditions predisposing to the development of aortic aneurysm or aortic dissection (for example, Marfan syndrome, vascular type Ehlers-Danlos syndrome, Takayasu’s arteritis, giant cell arteritis, Behçet’s disease, arterial hypertension, atherosclerosis).

In case of sudden abdominal, chest, or back pain, patients should immediately consult a doctor in the emergency department.

Effect on ability to drive vehicles and operate machinery

Fluoroquinolones, including Ciprofloxacin, may impair patients’ ability to drive a car and engage in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions due to the effect on the CNS.

Drug Interactions

Caution should be exercised when using ciprofloxacin concomitantly, as with other fluoroquinolones, in patients receiving drugs that cause QT interval prolongation (for example, class I A or class III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotic drugs).

Concomitant oral intake 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 high buffering capacity (such as didanosine tablets), containing magnesium, aluminum or calcium, reduces the absorption of ciprofloxacin. In such cases, Ciprofloxacin should be taken either 1-2 hours before or 4 hours after taking these drugs.

This restriction does not apply to histamine H₂-receptor blockers.

With concomitant use of ciprofloxacin and omeprazole, a slight decrease in C_max in plasma and a decrease in AUC may be noted.

Concomitant use of ciprofloxacin and theophylline may cause an undesirable increase in the plasma concentration of theophylline and, accordingly, the occurrence of theophylline-induced adverse events; in very rare cases, these adverse events may be life-threatening to the patient. If concomitant use of these two drugs is unavoidable, then continuous monitoring of the plasma concentration of theophylline is recommended and, if necessary, the dose of theophylline should be reduced.

Concomitant use of ciprofloxacin and caffeine or pentoxifylline (oxpentifylline) may lead to an increase in the serum concentration of xanthine derivatives.

The combination of very high doses of quinolones (DNA gyrase inhibitors) and some NSAIDs (excluding acetylsalicylic acid) may provoke convulsions.

With concomitant 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 blood creatinine concentration twice a week.

With concomitant use of ciprofloxacin and oral hypoglycemic agents, mainly sulfonylurea derivatives (for example, glibenclamide, glimepiride), the development of hypoglycemia is presumably due to the enhancement of the action of oral hypoglycemic agents.

Probenecid slows down the rate of renal excretion of ciprofloxacin. Concomitant use of ciprofloxacin and drugs containing probenecid leads to an increase in the plasma concentration of ciprofloxacin.

With concomitant use of ciprofloxacin and phenytoin, a change (increase or decrease) in the plasma concentration of phenytoin was observed. To avoid a 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 upon discontinuation of ciprofloxacin, it is recommended to monitor phenytoin therapy in patients taking both drugs, including determining the plasma concentration of phenytoin throughout the entire period of concomitant use of both drugs and for a short time after the end of combination therapy.

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

With concomitant use of ciprofloxacin and tizanidine, an increase in the serum concentration of tizanidine was observed: an increase in C_max by 7 times (from 4 to 21 times), an increase in AUC by 10 times (from 6 to 24 times). An increase in the serum concentration of tizanidine may cause a decrease in blood pressure and drowsiness. Thus, concomitant use of ciprofloxacin and drugs containing tizanidine is contraindicated.

Clinical studies have shown that concomitant use of duloxetine and potent inhibitors of the CYP1A2 isoenzyme (such as fluvoxamine), may lead to an increase in the AUC and C_max of duloxetine. Despite the lack of clinical data on possible interaction with ciprofloxacin, the possibility of such an interaction can be anticipated with concomitant use of ciprofloxacin and duloxetine.

Concomitant use of ropinirole and ciprofloxacin, a moderate inhibitor of the CYP1A2 isoenzyme, leads to an increase in C_max and AUC of ropinirole by 60% and 84%, respectively. Adverse effects of ropinirole should be monitored during its concomitant use with ciprofloxacin and for a short time after the end of combination therapy.

A study in healthy volunteers established that concomitant use of drugs containing lidocaine, and ciprofloxacin, a moderate inhibitor of the CYP1A2 isoenzyme, leads to a 22% decrease in the clearance of lidocaine when administered intravenously. Despite the good tolerability of lidocaine when used concomitantly with ciprofloxacin, an increase in side effects due to interaction is possible.

With concomitant use of clozapine and ciprofloxacin at a dose of 250 mg for 7 days, an increase in serum 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 concomitant use with ciprofloxacin and for a short time after the end of combination therapy.

With concomitant use in healthy volunteers of ciprofloxacin at a dose of 500 mg and sildenafil at a dose of 50 mg, a 2-fold increase in C_max and AUC of sildenafil was noted. In this regard, the use of this combination is possible only after a benefit/risk assessment.

With concomitant use of agomelatine and ciprofloxacin, similar effects can be expected.

With concomitant use of zolpidem and ciprofloxacin, an increase in the plasma concentration of zolpidem is possible. Concomitant use of drugs containing these substances is not recommended.

Concomitant use of ciprofloxacin and vitamin K antagonists (for example, warfarin, acenocoumarol, phenprocoumon) may lead to an enhancement of 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 the increase in INR. INR should be monitored sufficiently frequently during concomitant use of ciprofloxacin and vitamin K antagonists, as well as for a short time after the end of combination therapy.

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

Storage Conditions

Store at 8°C (46°F) to 15°C (59°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.