Ciprex (Tablets) Instructions for Use

ATC Code

J01MA02 (Ciprofloxacin)

Active Substance

Ciprofloxacin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Antimicrobial agent – fluoroquinolone

Pharmacological Action

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).

Resistant to ciprofloxacin are: 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 oral administration, Ciprofloxacin is rapidly absorbed primarily from the small intestine. C_max in blood plasma is reached within 1-2 hours. Bioavailability is about 70-80%. The values of C_max in blood plasma and AUC increase proportionally to the dose.

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 freely distributes 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 excreted from the body primarily 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 unimpaired renal function, T_1/2 is usually 3-5 hours. In cases 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 aged 5 to 17 years; prevention and treatment of the pulmonary form of anthrax (infection with Bacillus anthracis) in children from 3 years of age.

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

ICD codes

Dosage Regimen

Determine the dosage individually based on the indication, severity of the infection, and the patient’s renal function and age.

For adults, administer 250 mg to 750 mg orally twice daily. The total daily dose typically should not exceed 1500 mg.

For most uncomplicated urinary tract infections, prescribe 250 mg twice daily. For complicated and severe infections, including pyelonephritis and hospital-acquired pneumonia, use 500 mg to 750 mg twice daily.

For children aged 3 to 17 years, calculate the dose as 15 mg/kg to 20 mg/kg orally, administered twice daily. The single dose must not exceed 750 mg, and the total daily dose must not exceed 1500 mg.

Use in children is generally restricted to complicated UTIs, pyelonephritis, exposure to inhalational anthrax, and pulmonary exacerbations in cystic fibrosis.

For geriatric patients, adjust the dose based on creatinine clearance and clinical status. Use a lower dose range for elderly patients, especially those with impaired renal function.

In patients with renal impairment, adjust the dose according to creatinine clearance (CrCl). For CrCl 30-50 mL/min, administer 250-500 mg every 12 hours. For CrCl 5-29 mL/min, administer 250-500 mg every 18 hours.

For patients on hemodialysis or peritoneal dialysis, administer 250-500 mg every 24 hours, dosing after the dialysis session.

Take tablets with a full glass of water. Maintain adequate hydration to prevent crystalluria.

Administer oral doses at least 2 hours before or 4 hours after taking antacids, sucralfate, or products containing calcium, magnesium, aluminum, or iron to avoid impaired absorption.

The duration of therapy depends on the severity and site of infection. Continue treatment for at least 48 to 72 hours after symptoms disappear or until bacteriological eradication is confirmed.

For acute uncomplicated cystitis, a 3-day course may be sufficient. For pyelonephritis or bone and joint infections, treatment may extend for 4 to 6 weeks or longer.

Do not exceed the recommended dosage or duration of therapy due to the risk of serious adverse reactions.

Adverse Reactions

Infections 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.

Psychiatric 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 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 disturbances; rare: paresthesia and dysesthesia, hypoesthesia, tremor, convulsions (including epileptic seizures), vertigo; very rare: migraine, impaired coordination, impaired sense of smell, hyperesthesia, intracranial hypertension (pseudotumor cerebri symptoms); frequency unknown: peripheral neuropathy and polyneuropathy.

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

From the ear and labyrinth disorders – rare: tinnitus, hearing loss; very rare: hearing impairment.

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 pustular exanthema.

From the musculoskeletal system – uncommon: arthralgia; rare: myalgia, arthritis, increased muscle tone, muscle cramps; very rare: muscle weakness, tendinitis, tendon rupture (primarily Achilles tendon), 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 intravenous administration and with the use of step-down therapy with ciprofloxacin (with intravenous 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, impaired sense of smell, hearing impairment, 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; 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; children under 3 years of age.

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 damage during previous treatment with quinolones; increased risk of QT interval prolongation or development of torsades de pointes arrhythmia (e.g., congenital long QT syndrome, heart diseases (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (e.g., in hypokalemia, hypomagnesemia); simultaneous use of drugs that prolong the QT interval (including class IA and III antiarrhythmics, 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 (e.g., 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

Use is contraindicated in children under 3 years of age.

Geriatric Use

In elderly patients, Ciprofloxacin should be used at 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.

In genital infections suspected to be caused by fluoroquinolone-resistant Neisseria gonorrhoeae strains, information on local resistance to ciprofloxacin should be considered and pathogen susceptibility 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 affects 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 (e.g., class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, and antipsychotic drugs) or in patients with an increased risk of QT interval prolongation or torsades de pointes arrhythmia (e.g., with congenital long QT syndrome, corrected electrolyte imbalance such as hypokalemia or hypomagnesemia, and with heart diseases such as heart failure, myocardial infarction, bradycardia).

Hypersensitivity reactions, including allergic reactions, may sometimes 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 discontinued immediately and appropriate treatment 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 occur, such as anorexia, jaundice, dark urine, itching, abdominal pain – ciprofloxacin should be discontinued. In patients taking Ciprofloxacin 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 due to the risk of tendon rupture, and a doctor should be consulted. Cases of tendinitis and tendon ruptures (primarily the Achilles tendon), sometimes bilateral, may occur during ciprofloxacin therapy, even within the first 48 hours after initiation. 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, concurrently 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, may provoke convulsions and lower the seizure threshold. In patients with epilepsy and those with a history of CNS diseases (e.g., lowered seizure threshold, history of convulsive seizures, cerebrovascular disorders, organic brain lesions, or stroke), due to the threat of developing CNS side reactions, 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 suicides. In case of any CNS side effects, including mental disorders, it is necessary to immediately discontinue Ciprofloxacin and initiate appropriate therapy. In these cases, it is recommended to switch to therapy with another antibiotic, not a fluoroquinolone, 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 when taking ciprofloxacin, so patients should avoid contact with direct sunlight and UV light. Treatment should be discontinued if symptoms of photosensitivity are observed (e.g., skin changes resembling sunburn).

Ciprofloxacin is known to be 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. Concomitant use of ciprofloxacin and tizanidine is contraindicated.

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

In vitro, 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, may occur with the use of ciprofloxacin. During ciprofloxacin therapy, dysglycemia may occur more frequently in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (e.g., 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, ciprofloxacin treatment should be discontinued immediately and appropriate therapy initiated. In these cases, it is recommended to switch to therapy with another antibiotic, not a fluoroquinolone, if possible. When conducting ciprofloxacin treatment in elderly patients and 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 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 (e.g., 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 the ability to drive vehicles and operate machinery

Fluoroquinolones, including Ciprofloxacin, may impair patients’ ability to drive cars and engage in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions due to their 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 (e.g., 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.

Metoclopramide accelerates the absorption of ciprofloxacin (when taken orally), leading to a shorter time to reach C_max of ciprofloxacin in plasma. No effect on the bioavailability of ciprofloxacin was found.

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 constant 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 (e.g., glibenclamide, glimepiride), the development of hypoglycemia is presumably due to the enhancement of the effect of oral hypoglycemic agents (see the “Adverse Reactions” section).

Probenecid slows 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, changes (increase or decrease) in the plasma phenytoin concentration were 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 phenytoin concentration 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, which may be accompanied by an increase in the plasma concentration of methotrexate. 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 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 the 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% reduction 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 (e.g., 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 the 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 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 beverages (e.g., milk, yogurt, calcium-fortified orange juice) should be avoided, as the absorption of ciprofloxacin may be reduced. However, calcium contained in other foods 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.