Ciprobay^® (Tablets, Solution) 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

A broad-spectrum antimicrobial agent, a derivative of fluoroquinolone.

It inhibits bacterial DNA gyrase (topoisomerases II and IV, responsible for the process of supercoiling 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), on gram-positive microorganisms – only during the division phase.

Low toxicity for 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.

Sensitive to ciprofloxacin are 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, since 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 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 excreted 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 – pneumonia 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 can 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 started only after assessing the benefit/risk ratio due to the possible side effect on the joints and periarticular tissues.

ICD codes

Dosage Regimen

Tablets

Individual, depending on the indications, clinical situation and age of the patient.

Adults are prescribed 250-750 mg 2 times/day; children – 15-20 mg/kg 2 times/day.

Solution

Individual, depending on the indications, clinical situation and age of the patient.

A single dose for adults is 200-400 mg, frequency of administration is 2 times/day; for children – 10 mg/kg, frequency of administration is 2-3 times/day.

Adverse Reactions

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

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

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

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

From metabolism infrequently – decreased appetite and amount of food intake; rarely – 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 infrequently – psychomotor hyperactivity/agitation; rarely – confusion and disorientation, anxiety, nightmares, depression, hallucinations; very rarely – psychotic reactions (increased 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 infrequently – headache, dizziness, sleep disturbance, taste disturbances; rarely – paresthesia and dysesthesia, hypoesthesia, tremor, convulsions (including epileptic seizures), vertigo; very rarely – migraine, impaired coordination of movements, impaired sense of smell, hyperesthesia, intracranial hypertension (cerebral pseudotumor symptoms); frequency unknown – peripheral neuropathy and polyneuropathy.

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

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

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

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

From the digestive system often – nausea, diarrhea; infrequently – vomiting, abdominal pain, dyspepsia, flatulence; very rarely – pancreatitis.

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

From the skin and subcutaneous tissues infrequently – rash, itching, urticaria; rarely – photosensitivity, blistering; very rarely – 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 infrequently – arthralgia; rarely – myalgia, arthritis, increased muscle tone, muscle cramps; very rarely – muscle weakness, tendinitis, tendon rupture (mainly Achilles), exacerbation of myasthenia gravis symptoms.

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

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

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

The frequency of development of the following adverse reactions with IV administration and with the use of stepwise therapy with ciprofloxacin (with IV administration followed by oral administration) is higher than with oral administration often – vomiting, increased activity of liver transaminases, rash; infrequently – 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; rarely – 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 often – arthropathies. The frequency of arthropathy (arthralgia, arthritis) indicated 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 the concentration of tizanidine in the blood plasma; 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).

Use with caution

Epilepsy, lowered seizure threshold (or history of convulsions), severe cerebral atherosclerosis, cerebrovascular accident, organic brain lesions or stroke; mental illness (depression, psychosis); severe renal and/or hepatic impairment; tendon disorders associated with previous quinolone treatment; increased risk of QT interval prolongation or development of torsades de pointes arrhythmia (e.g., congenital long QT syndrome, cardiac disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (e.g., 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 (e.g., sulfonylureas) or insulin.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use with caution in severe hepatic impairment.

Use in Renal Impairment

Patients with impaired renal function require dosage adjustment.

Pediatric Use

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

Geriatric Use

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

Special Precautions

For the treatment of 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 (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 development of torsades de pointes arrhythmia (e.g., with congenital long QT syndrome, corrected electrolyte imbalance such as hypokalemia or hypomagnesemia, and with cardiac 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 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 occur, 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 of the risk of tendon rupture, and a doctor should be consulted. Cases of tendinitis and tendon rupture (mainly the Achilles tendon), sometimes bilateral, may occur during treatment with ciprofloxacin, sometimes 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, may provoke convulsions and lower the seizure threshold. In patients with epilepsy and those who have had CNS diseases (e.g., lowered seizure threshold, history of convulsions, cerebrovascular accident, 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 suicidal attempts, including completed suicides. In case of any CNS side effects, including mental disorders, Ciprofloxacin should be discontinued immediately and appropriate therapy should be 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 (e.g., skin changes resembling sunburn).

Ciprofloxacin is known to be a moderate inhibitor of CYP1A2 isoenzymes. Caution should be exercised when ciprofloxacin is used 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 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 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 in the diagnosis of 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 therapy with ciprofloxacin, dysglycemia may occur more frequently in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (e.g., sulfonylureas) or insulin. When ciprofloxacin is used 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 discontinued immediately and appropriate therapy should be initiated. In these cases, it is recommended to switch to therapy with another antibiotic, other than fluoroquinolones, if possible. When treating 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 (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 the ability of patients 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 ciprofloxacin, like other fluoroquinolones, is used concomitantly 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 administration 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.

When ciprofloxacin and omeprazole are used concomitantly, 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, it is recommended to continuously monitor the plasma concentration of theophylline and, if necessary, reduce the dose of theophylline.

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.

When ciprofloxacin and drugs containing cyclosporine were used concomitantly, 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.

When ciprofloxacin and oral hypoglycemic agents , mainly sulfonylurea derivatives (e.g., glibenclamide, glimepiride), are used concomitantly, 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. Concomitant use of ciprofloxacin and drugs containing probenecid leads to an increase in the plasma concentration of ciprofloxacin.

When ciprofloxacin and phenytoin were used concomitantly, 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.

When methotrexate and ciprofloxacin are used concomitantly, 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 methotrexate side effects. In this regard, patients receiving concomitant therapy with methotrexate and ciprofloxacin should be carefully monitored.

When ciprofloxacin and tizanidine were used concomitantly, 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 when ciprofloxacin and duloxetine are used concomitantly.

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 found 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.

When clozapine and ciprofloxacin at a dose of 250 mg were used concomitantly 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.

When ciprofloxacin at a dose of 500 mg and sildenafil at a dose of 50 mg were used concomitantly in healthy volunteers, 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.

When agomelatine and ciprofloxacin are taken concomitantly, similar effects can be expected.

When zolpidem and ciprofloxacin are used concomitantly, 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 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.

Concomitant use of ciprofloxacin and dairy products or mineral-fortified drinks (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.