Cipronat

Ciprofloxacin.

1 mL of the solution contains ciprofloxacin 2 mg.
Excipients/Inactive Ingredients: sodium chloride, disodium edetate, 0,1M hydrochloric acid, lactic acid, water for injections.

Pharmacotherapeutic group: Antibacterial drugs for systemic use. Fluoroquinolones. Ciprofloxacin. ATC code: J01M А02.
Pharmacology: Pharmacodynamics: Cipronat has a wide antibacterial range, including strains resistant to many antibiotics and sulfanilamides. It is highly active primarily against aerobic gram-negative bacteria, and active against some gram-positive and intracellular microorganisms: E. Coli, Salmonella spp., Shigella spp., Klebsiella spp., Proteus spp., Pseudomonas spp., Enterobacter spp., Serratia spp., Citrobacter spp., Hafnia spp., Yersinia spp., Staphylococcus spp., Streptococcus spp., Mycobacterium tuberculosis, Mycobacterium fortuitum, Neisseria spp., Haemophilus influenzae, Brucella spp., Vibrio spp., Providencia spp., Chlamydia spp., Campylobacter spp., Aeromonas spp., Plesiomonas spp.
Cipronat is also effective against beta-lactamase producing bacteria.
Treponema pallidum is not sensitive to ciprofloxacin.
The drug has a bactericidal effect. The mechanism of the bactericidal effect of Cipronat is associated with inhibition of bacterial DNA-gyrase, leading to their death. Ciprofloxacin also damages the bacterial cell membrane, causing expulsion of the cellular content. It is effective both in bacteria division stage and in steady stage. No cross-resistance with antibiotics and other antibacterial drugs, except for fluoroquinolones, is seen.
Pharmacokinetics: Ciprofloxacin easily penetrates into organs and tissues, forming high concentrations in saliva, phlegm, bronchial fluid, lungs, bile, gall bladder, prostate, urine, skin and bones. Peak blood plasma concentration of ciprofloxacin (after intravenous infusion of 200 mg at 30 minutes) is achieved immediately. Half-life of the drug is 3 to 5 hours. The drug is metabolized in liver, forming low-active metabolites. 75-90% of the drug is eliminated with urine; the drug is found in the urine within 20-24 hours even after a single dose.

Treatment of noncomplicated and complicated infections caused by pathogens sensitive to ciprofloxacin: middle ear and sinus infections; respiratory infections; abdominal infections; urinary tract infections; small pelvis infections; skin and soft tissue infections; bone and joint infections; sepsis.
Prevention and treatment of infections in patients with impaired immune function (including those associated with immunosuppressive drugs therapy and neutropenia).

Dosing regimen is determined individually depending on infection localization and severity and also on infection agent sensitivity. Drug solution can be administered undiluted or mixed with other infusion solutions.
Before starting Cipronat therapy the possibility of patient's hypersensitivity should be ruled out by skin test.
In adults, Cipronat is administered by intravenous drop infusion; the doses are between 200 mg and 400 mg (100-200 mL) depending on infection severity, two times a day, with average therapy duration of 7 to 10 days. In patients with chronic bronchitis in the acute stage the drug dose is 200 mg (100 mL) once daily, for 7-10 days. In patients with acute sinusitis the drug dose is 200 mg (100 mL) once daily, for 10 days. In patients with community-acquired pneumonia, the drug dose is 200 mg (100 ml) 1-2 times daily for 7-14 days. In patients with noncomplicated urinary infections the drug dose is 200 mg in a single dose or 100 mg for 3 days; for complicated urinary infections: 200 mg once daily for 7-10 days. For treatment of skin and soft tissue infections the recommended dose is 100 mg once daily for 5-7 days. For treatment of noncomplicated gonorrhea 100 mg should be administered twice daily for 1 day. The infusion time for Cipronat is 60 minutes.
In patients with severe infections, at recurring infections in patients with cystic fibrosis, abdominal, bone and joint infections caused by Pseudomonas or staphylococci, peritonitis, septicemia and acute pneumonias caused by Streptococcus pneumoniae the dose should be increased to 400 mg three times a day. The maximal daily dose is 1200 mg.
Dosing regimen in elderly patients: Elderly patients require lower Cipronat doses basing on the disease severity and creatinine clearance.
Dosing regimen for adult patients with renal or hepatic impairments: Renal function impairments: For patients with creatinine clearance from 31 to 60 mL/min/1.73 m² or blood plasma creatinine concentration from 1.4 to 1.9 mg/100 mL the maximal Cipronat dose for
intravenous administration is 800 mg per day.
For patients with creatinine clearance 30 mL/min/1.73 m² or lower, or blood plasma creatinine concentration 2/100 mL or higher the maximal Cipronat dose for intravenous administration is 400 mg per day.
Renal function impairments + hemodialysis: The maximal Cipronat dose for intravenous administration is 400 mg per day; at hemodialysis days Cipronat should be administered after hemodialysis.
Renal function impairments + outpatient peritoneal dialysis: Cipronat solution for infusions is added to dialysate (peritoneal administration): 50 mg Cipronat per 1 liter of dialysate is administered 4 times daily at 6-hour intervals.
Hepatic function impairments: Dose adjustment is not required.
The therapy duration depends on the infection severity, clinical course and bacteriological test results.
The drug therapy should be continued for at least three days after the body temperature normalizes or clinical symptoms resolve. The therapy duration for patients with acute noncomplicated gonorrhea and cystitis is 1 day. For patients with urinary and abdominal infections, the therapy duration is 7 days.
For patients with other infections the therapy duration is usually 7 to 10 days. In patients with impaired immunity, the therapy is continued throughout the entire neutropenia period.
In patients with infections caused by streptococci and chlamydia the minimal treatment duration is 10 days.

Overdose symptoms are manifested as nausea, vomiting, tachycardia, headache, hyperkinesia and convulsions. In case of acute overdose cancel the drug administration, ensure adequate hydration and ECG monitoring and prescribe symptomatic therapy.
No specific antidote is available. Hemodialysis and peritoneal dialysis can eliminate only a limited amount of Cipronat from the body (under 10%).

Hypersensitivity to ciprofloxacin and other quinolone drugs or to any of preparation components; pregnancy, lactation. Simultaneous administration of ciprofloxacin and tizanidine, due to clinically significant side effects (arterial hypotension, drowsiness) associated with increased blood plasma tizanidine concentration. As the drug administration leads to the development of chondropathies and arthropathies, it should not be prescribed in children.

Administration particulars: Caution must be exercised if the drug is prescribed in patients with pronounced cerebral atherosclerosis, cerebral circulation disorders and renal function impairment.
In case of allergic reactions, which may be manifested as early as the first dose, the drug therapy must be cancelled immediately. UV radiation is contraindicated during Cipronat treatment. In patients with epilepsy, history of convulsions, vascular diseases and organic brain lesions, Cipronat can only be prescribed by vital indications due to central nervous system risk of side effects. If heavy and protracted diarrhea develops during or after Cipronat treatment it should be ruled out the possibility of pseudomembrane colitis which requires immediate cancellation of the drug and prescription of appropriate treatment. During Cipronat treatment patients should cut down activities that require concentration and rapid reactions. Certain laboratory parameters may change during Cipronat treatment: urine hypostasis, temporary increase of blood serum carbamide, creatinine, bilirubin and liver transaminase concentrations; individual cases of hyperglycemia, crystalluria or erythuria; and change of prothrombin parameters. In patients with impaired hepatic and/or renal functions monitoring of blood Cipronat concentrations should be recommended. Cipronat is not recommended for treatment of acute tonsillitis (tonsillar quinsy).
Gastrointestinal tract: In case severe and persistent diarrhea develops during or after drug therapy medical attention should be sought, as these symptoms may conceal severe gastrointestinal condition (such as potentially lethal pseudomembrane colitis) requiring immediate treatment. In such cases administration of Cipronat must be stopped immediately and appropriate therapy initiated.
Peristalsis-inhibiting drugs are contraindicated.
Transitory increase in transaminase and alkaline phosphatase activity or cholestatic jaundice may be observed, especially in patients with history of liver disease.
Nervous system: Patients with epilepsy and history of central nervous system disorders (such as low convulsive threshold, history of convulsive fits, reduced cerebral circulation, brain structure alterations, and stroke) may use Cipronat only if the expected benefit exceeds the potential risk.
In some cases, central nervous system side effects are observed as early as after the first dose of Cipronat. In individual cases depression or psychosis may manifest and progress. In such cases administration of Cipronat must be stopped.
Increased hypersensitivity to the drug: In some cases, hypersensitivity and allergic reactions are observed as early as after the first Cipronat administration. In such cases patient's physician must be informed immediately. In individual cases anaphylactic/anaphylactoid reactions may progress, up to life-threatening shock. In separate cases they are observed as early as the first Cipronat administration. In such cases administration of Cipronat must be stopped, and appropriate therapy initiated immediately.
Musculoskeletal system: At any signs of tendinitis (such as painful swelling) Cipronat administration must be stopped.
The patient should avoid physical load and should seek medical attention.
Tendon rupture (especially heel tendon) was observed primarily in elderly patients or patients with history of glucocorticoid treatment.
Skin: Cipronat was shown to cause photosensitivity reactions. Patients receiving Cipronat treatment must avoid intense ultraviolet irradiation. In case of photosensitivity reactions (e.g. similar to sunburns) Cipronat therapy must be stopped.
Cytochrome P450: Ciprofloxacin is a known moderate inhibitor of cytochrome P40 1A2 enzymes. Caution must be exercised if Cipronat is administered concurrently with drugs that are metabolized by such enzymes as theophylline, methylxanthine, caffeine, duloxetine and others since increase in blood serum concentration of these drugs may cause specific side effects.
Effect on ability to drive and operate other machines: The use of Cipronat has a negative impact on work requiring quick psychomotor reactions (participation in traffic, driving and machinery operating).
Use in Children: The drug is contraindicated for administration in children.
As other drugs of this class Cipronat was shown to cause joint arthropy in impuberal animals.
Analysis of available safety data on administration of Cipronat in patients under 18 years of age showed no evidence of cartilage or joint damage associated with drug treatment.

Administration during pregnancy or lactation is contraindicated.

Gastrointestinal disorders: nausea, diarrhea, vomiting, abdominal pain, flatulence, decreased appetite, anorexia, jaundice, cholestatic jaundice (especially in patients with history of liver diseases), hepatitis, hepatonecrosis, candidosis (oral), pancreatitis.
Nervous system disorders: vertigo, headaches, increased fatigability, anxiety, tremor, insomnia, nightmares, peripheral paralgesia (pain perception anomaly), increased perspiration, increased intracranial pressure, confused consciousness, depression, hallucinations, other psychotic reaction symptoms (that in rare cases progress into potentially self-harming conditions), migraine, unconsciousness, cerebral artery thrombosis, convulsions, hyperesthesia, uncertain gait, psychosis, ataxia, tic.
Sensory organ disorders: taste and smell disruptions, sight impairment (diplopy, change in color perception), sonitus, hearing impairment, temporary deafness, chromatopsia.
Cardiovascular system disorders: tachycardia, heart rhythm disorder, arterial hypotension, apsychia, vasodilatation.
Blood and lymph system disorders: leucopenia, granulocytopenia, anemia, thrombocytopenia, thrombocytosis, leucocytosis, hemolytic anemia, prothrombin index changes, agranulocytosis, pancytopenia, bone marrow function inhibition.
Laboratory parameters deviations: hypoprothrombinemia, increased liver aminase and alkaline phosphatase activity, increased amylase and lipase activity, hypercreatinemia, hyperbilirubinemia, hyperglycemia.
Urinary system disorders: acute renal failure, renal function impairment, vaginal candidosis, erythruria, crystalluria (primarily in patients with alkaline urine and low diuresis), glomerulonephritis, dysuria, polyuria, urine retention, albuminuria, urethral hemorrhages, lowered renal nitrogen clearance function, interstitial nephritis, increased urine creatinine and carbamide nitrogen.
Allergic reactions: itching, skin rashes, nettle rush, hydrocysts accompanied with hemorrhages, small scab-forming nodes, ague, maculopapular eruptions, punctuate hemorrhages (petechia), facial or laryngeal edema, shortness of breath, labored breathing, eosinophilia, increased light sensitivity, vasculitis, erythema nodosum, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), serum disease, anaphylactoid (anaphylactic) reactions.
Other side effects: arthralgia, arthritis, joint edema, tendon rupture, asthenia, myalgia, superinfections (candidosis, pseudomembrane colitis), facial flushing, pathologic reactions in administration sites (edema, inflammation, pain, thrombophlebitis), limb, back or chest pain; myasthenia.

Concurrent administration of Cipronat and theophylline may cause undesired increase of blood plasma concentration of the latter and development of side effects. Accordingly, blood plasma theophylline concentration must be monitored, and its dose appropriately adjusted downwards.
Combined administration of very large doses of quinolones (gyrase inhibitors) and certain non-steroid anti-inflammatory drugs (including acetylsalicylic acid) may cause convulsions.
Concurrent administration of Cipronat and cyclosporine has in some cases caused increase of serum creatinine; in such patients, this parameter must be monitored frequently (twice per week).
In case of concurrent administration of Cipronat and warfarin, the latter's effect may be intensified. The interaction of Ciprofloxacin and glibenclamide may intensify the effect of the latter, causing hypoglycemia.
Concurrent administration of Cipronat and probenecid increases blood plasma ciprofloxacin concentrations.
Concurrent administration of Cipronat and methotrexate may slow down tubular transport (renal metabolism) of the latter which may cause increased blood plasma methotrexate concentrations and increase the probability of methotrexate-related side effects. Due to this,
patients, receiving combined therapy of methotrexate and Cipronat, require close monitoring.
Metoclopramide accelerates ciprofloxacin absorption, therefore shortening the time required to reach maximal blood plasma ciprofloxacin concentration (this does not impact the bioavailability of the latter).
Clinical trial with healthy volunteers receiving Cipronat and tizanidine simultaneously demonstrated increase of blood plasma tizanidine concentration (Cmax increasing 7 times, the range-4-21 times; concentration-time AUC-10 times, the range-6-24 times).
Increase of blood serum tizanidine concentration is associated with hypotensive and sedative side effects. Therefore, concurrent administration of Cipronat and tizanidine is contraindicated.
Clinical trials showed that concurrent administration of duloxetine and powerful CYP450 1A2 enzyme inhibitors (such as fluvoxamine) may cause increase of duloxetine AUC and Cmax. Despite the lack of clinical data on interaction with Cipronat, the possibility of interaction is anticipated in case of ciprofloxacin and duloxetine concurrent administration.
Cipronat may be used in combination with azlocillin and ceftazidime against infections caused by Pseudomonas; with mezlocillin, azlocillin and other effective beta-lactam antibiotics against streptococcal infections; with isoxazole penicillins and vancomycin against staphylococcal infections; with metronidazole and clindamycin against anaerobic infections.

Compatibility with other solutions: Cipronat infusion solution is compatible with 0.9% sodium chloride solution, Ringer's solution, Ringer's lactate solution, 5% and 10% glucose solution, 10% fructose solution and 5% glucose solution with 0.225% NaCl or 0.45% NaCl.
Incompatibilities: Incompatible with solutions with pH under 7.
If the compatibility with another infusion drug is not confirmed, Cipronat infusion solution should be administered separately.

Store in a dark place below 30°C.
Shelf life: 2 years.

Quinolones

J01MA02 - ciprofloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.

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