Ciprofloxabol^® (Solution) Instructions for Use

Marketing Authorization Holder

Abolmed, LLC (Russia)

ATC Code

J01MA02 (Ciprofloxacin)

Active Substance

Ciprofloxacin (Rec.INN registered by WHO)

Dosage Form

Ciprofloxabol®

Solution for infusion 2 mg/1 ml: bottle 100 ml 1 pc., vial 100 ml 1 pc.

Dosage Form, Packaging, and Composition

Solution for infusion as a clear liquid with a yellowish or greenish tint.

Excipients: sodium chloride, 1M hydrochloric acid solution or 1M sodium hydroxide solution, lactic acid, water for injections.

100 ml – glass vials (1) – cardboard packs.
100 ml – glass bottles (1) – 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 the resting and division phases (because 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 macroorganism cells 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, after the action of ciprofloxacin, practically no persisting microorganisms remain, and on the other hand, bacterial cells do not have 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 low 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 – 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 decontamination of the intestine 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 regimen individually based on the indication, severity of infection, and patient-specific factors.

For adult patients, administer a single dose of 200 mg to 400 mg by intravenous infusion.

Infuse the solution slowly over 60 minutes.

Repeat the administration every 12 hours.

For pediatric patients (5-17 years with cystic fibrosis), administer a dose of 10 mg per kg body weight.

Do not exceed a maximum single dose of 400 mg in pediatric patients.

Administer the dose to pediatric patients every 8 hours.

Adjust the dosage in all patients with impaired renal function based on creatinine clearance.

For patients with a creatinine clearance of 30-60 mL/min, administer 200-400 mg every 12 hours.

For patients with a creatinine clearance of 5-29 mL/min, administer 200-400 mg every 18-24 hours.

In patients on hemodialysis or peritoneal dialysis, administer 200-400 mg every 24 hours after the dialysis session.

Use a lower dosage range for geriatric patients, guided by renal function assessment.

The duration of therapy depends on the clinical response; typically continue for at least 3 days after symptoms have resolved.

For anthrax exposure (post-exposure prophylaxis and treatment), administer 400 mg every 12 hours in adults.

For severe or complicated infections, initiate therapy with the higher end of the dosage range (400 mg).

Do not administer as a bolus or rapid intravenous injection.

Complete the full course of therapy as prescribed, even if symptoms improve.

Adverse Reactions

Infectious and parasitic diseases – uncommon: mycotic superinfections; rare: pseudomembranous colitis (in very rare cases with a 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-harming behavior, such as suicidal actions/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 disturbance, taste disorders; rare: paresthesia and dysesthesia, hypoesthesia, tremor, convulsions (including epileptic seizures), vertigo; very rare: migraine, coordination disturbance, smell disturbance, hyperesthesia, intracranial hypertension (pseudotumor cerebri symptomatology); frequency unknown: peripheral neuropathy and polyneuropathy.

From the organ of vision – rare: visual disturbances; very rare: color vision disturbance.

From the ear and labyrinth – 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 liver 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 (with IV administration followed by oral administration) is higher than with oral administration – common: vomiting, increased activity of liver 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, smell disturbances, hearing disorders, vasculitis, pancreatitis, liver tissue necrosis, petechiae, tendon rupture.

In children, arthropathies are common. 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; simultaneous 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 up to 18 years – 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; prevention 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 lesions 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); simultaneous use of drugs that prolong the QT interval (including class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics); simultaneous 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 breastfeeding.

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; prevention 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 pathogen causing urinary tract infections, to fluoroquinolones varies across regions 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 longer average QT interval 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 immediately discontinued and appropriate treatment should be initiated.

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 (oral vancomycin 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, as 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 diseases 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 may occur even after the first use of fluoroquinolones, including Ciprofloxacin. In rare cases, depression or psychotic reactions may progress to suicidal thoughts and suicide attempts, including completed ones. In case of any CNS side effects, including mental disorders, Ciprofloxacin should be immediately discontinued 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.

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 – as an increase in the serum concentration of these drugs due to inhibition of their metabolism by ciprofloxacin may cause specific adverse reactions. Simultaneous 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 in the diagnosis of 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, trembling, weakness). If a patient develops hypoglycemia, treatment with ciprofloxacin should be immediately discontinued 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 careful assessment of the benefit/risk ratio 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 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 mechanisms

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).

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

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

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

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

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

With simultaneous 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 effect of oral hypoglycemic agents.

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

With simultaneous use of ciprofloxacin and phenytoin, changes (increase or decrease) in phenytoin plasma concentration were observed. To avoid the 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 phenytoin plasma concentration throughout the entire period of simultaneous use of both drugs and for a short time after the end of combination therapy.

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

With simultaneous use of ciprofloxacin and tizanidine, an increase in tizanidine serum concentration 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 tizanidine serum concentration may cause a decrease in blood pressure and drowsiness. Thus, simultaneous use of ciprofloxacin and drugs containing tizanidine is contraindicated.

Clinical studies have shown that simultaneous 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 simultaneous use of ciprofloxacin and duloxetine.

Simultaneous 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 simultaneous use of drugs containing lidocaine and ciprofloxacin, a moderate inhibitor of the CYP1A2 isoenzyme, leads to a 22% decrease in lidocaine clearance upon its intravenous administration. Despite the good tolerability of lidocaine when used concomitantly with ciprofloxacin, an increase in side effects due to interaction is possible.

With simultaneous 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 simultaneous 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 assessing the benefit/risk ratio.

With simultaneous intake of agomelatine and ciprofloxacin, similar effects can be expected.

With simultaneous use of zolpidem and ciprofloxacin, an increase in zolpidem plasma concentration is possible. Simultaneous 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 frequently enough during concomitant use of ciprofloxacin and vitamin K antagonists, as well as for a short time after the end of combination therapy.

Simultaneous 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 food products does not significantly affect the absorption of ciprofloxacin.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°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.