Cyphracid - instructions for use, doses, side effects, contraindications

100 ml of the preparation contain: active substance: ciprofloxacin lactate monohydrate - 254.4 mg, in terms of ciprofloxacin - 200 mg; Excipients: lactic acid - 11,00 mg, sodium chloride - 900,00 mg, disodium edetate - 5,00 mg, hydrochloric acid - 0,005 ml, water for injections - up to 100 ml.

Description:

Transparent, colorless or slightly yellowish liquid.

Pharmacotherapeutic group:Antimicrobial agent, fluoroquinolone.

ATX: & nbsp

J.01.M.A.02 Ciprofloxacin

Pharmacodynamics:

A broad-spectrum antimicrobial agent, a quinolone derivative, suppresses bacterial DNA gyrase (topoisomerases II and IV, responsible for the process of supercoiling the chromosomal DNA around the nuclear RNA, which is necessary for reading the genetic information), disrupts DNA synthesis, growth and division of bacteria; causes significant morphological changes (including the cell wall and membranes) and the rapid death of the bacterial cell.

It acts bactericidal on gram-negative organisms during rest and division (because it affects not only the DNA-gyrase, but also causes lysis of the cell wall), gram-positive microorganisms - only during the fission period.

Low toxicity for macroorganism cells is explained by the absence of DNA-gyrase in them. Against the background of taking ciprofloxacin, there is no parallel development of resistance to other antibiotics that do not belong to the group of inhibitors of gyrase, which makes it highly effective against bacteria that are resistant, for example, to aminoglycosides, penicillins, cephalosporins, tetracyclines.

Gram-negative aerobic bacteria are sensitive to ciprofloxacin:

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. Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii; Gram-positive aerobic bacteria: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).

The majority of staphylococci, resistant to methicillin, are resistant to ciprofloxacin. Sensitivity of Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) - moderate (high concentrations are required to repress). Bacillus anthracis is also sensitive to ciprofloxacin.

For drug resistant: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. Not effective against Treponema pallidum.

Resistance develops very slowly, because on the one hand, after the action of ciprofloxacin are left with persistent microorganisms, and on the other - the bacterial cells do not have the enzymes that inactivate it.

Pharmacokinetics:

After an intravenous infusion of 200 mg or 400 mg, the time required to reach the maximum concentration (TC_max) - 60 min, the maximum concentration (C_max) - 2,1 and 4,6 μg / ml, respectively, the connection with plasma proteins - 20-40%.

Well distributed in body tissues (excluding tissue, rich in fats, for example, nervous tissue). Concentration in tissues is 2-12 times higher than in plasma. Therapeutic concentrations are achieved in saliva, tonsils, liver, gall bladder, bile, intestine, abdominal and pelvic organs (endometrium, fallopian tubes and ovaries, uterus), seminal fluid, prostate tissue, kidney and urinary organs, lung tissue, bronchial secretion, bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, skin. The cerebrospinal fluid penetrates in a small amount, where its concentration in the absence of inflammation of the meninges is 6-10% of that in the serum, and when inflamed - 14-37%. Ciprofloxacin well penetrates also into the eye fluid, pleura, peritoneum, lymph, through the placenta. The concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in blood serum.

The activity is somewhat reduced at pH values less than 6.

Metabolised in the liver (15-30%) with the formation of low-activity metabolites (diethylciprofloxacin, sulfociprofloxacin, oxocycloploxacin, formyl ciprofloxacin).

Half-life (T1 / 2) - 5-6 hours - with intravenous administration, with chronic renal failure - up to 12 hours. It is excreted mainly by the kidneys by tubular filtration and tubular secretion in unchanged form (50-70%) and in the form of metabolites ( 10%), the rest - through the gastrointestinal tract (GIT). A small amount is excreted in breast milk. After intravenous administration, the concentration in the urine during the first 2 hours after administration is almost 100 times greater than in the serum, which significantly exceeds the minimum inhibitory concentration for most pathogens of urinary tract infections

Kidney clearance - 3-5 ml / min / kg; total clearance - 8-10 ml / min / kg.

In chronic renal failure (creatinine clearance (CK) above 20 ml / min), the percentage of drug released through the kidneys decreases,but cumulation in the body does not occur due to a compensatory increase in the metabolism of the drug and excretion through the gastrointestinal tract.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to ciprofloxacin
Diseases of the lower respiratory tract (acute and chronic (at the stage of exacerbation) bronchitis, pneumonia, bronchiectatic disease, infectious complications of cystic fibrosis);
Infections of ENT organs (acute sinusitis);
Infections of the kidneys and urinary tract (cystitis, pyelonephritis);
Complicated intra-abdominal infections (in combination with metronidazole), incl. peritonitis;
Chronic bacterial prostatitis;
Uncomplicated gonorrhea;
Typhoid fever, campylobacteriosis, shigellosis;
Infections of the skin and soft tissues (infected ulcers, wounds, burns, abscesses, phlegmon);
Infections of bones and joints (osteomyelitis, septic arthritis);
Septicemia; infection on the background of immunodeficiency (arising in the treatment of immunosuppressive drugs or in patients with neutropenia);
Prevention of infections during surgical interventions;
Prevention and treatment of pulmonary form of anthrax.
Children.Therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years;
Prevention and treatment of pulmonary form of anthrax (infection with Bacillus anthracis).

Contraindications:

Hypersensitivity to ciprofloxacin and other fluoroquinolones;
Simultaneous reception with tizanidine (risk of pronounced reduction in blood pressure, drowsiness);
Children's age (up to 18 years - before the completion of the skeletal process, except for the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years old, prevention and treatment of the pulmonary form of anthrax);
Pregnancy;
Lactation period.

Carefully:

Pronounced atherosclerosis of cerebral vessels,
With organic damage to the brain or stroke,
mental illness (depression, psychosis),
epilepsy, lowering the threshold of convulsive readiness (or convulsions in the anamnesis),
syndrome of congenital extension of the Q-T interval,
heart disease (heart failure, myocardial infarction, bradycardia),
electrolyte imbalance (eg, hypokalemia, hypomagnesemia),
marked renal and / or hepatic insufficiency,
simultaneous administration of drugs that extend the Q-T interval (including antiarrhythmic IA and III classes),
simultaneous application with inhibitors of isoenzymes CYP450 1A2, (including, theophylline, methylxanthine, caffeine, duloxetine, clozapine),
patients with a history of indications of tendon diseases associated with the administration of quinolones,
elderly age.

Pregnancy and lactation:

It should not be prescribed during pregnancy and lactation, given the lack of experience in its use in this category of patients. Possible damage to articular cartilage in newborns.

Dosing and Administration:

Intravenous infusion: duration of Infusion Cyphricide is 30 minutes at a dose of 200 mg and 60 minutes at a dose of 400 mg.

Infusion solutions Cyphracide are light-sensitive, so the vial should be removed from the box only before use.

When stored at low temperatures, a precipitate may form which dissolves at room temperature. Therefore, it is not recommended to store the infusion solution in the refrigerator.

In infections of the lower respiratory tract: 200-400 mg 2 times a day.

With infections of the urinary tract: acute uncomplicated - 100 mg 2 times a day; cystitis in women (before menopause) - once 100 mg; Complicated - 200 mg 2 times a day.

With uncomplicated gonorrhea: 100 mg once, with extragenital - 100 mg 2 times a day.

Infectious diarrhea - 200 mg 2 times, the course of treatment - 5-7 days.

Especially severe infections (streptococcal pneumonia, infectious complications of cystic fibrosis, infections of bones and joints, septicemia, peritonitis), especially caused by Pseudomonas aeruginosa, Staphylococcus spp .: 400 mg 3 times a day.

Pulmonary form of anthrax (treatment and prophylaxis): 400 mg 2 times a day.

For the prevention of infections during surgical interventions: 200-400 mg for 0.5-1 h before surgery; When the duration of the operation is more than 4 hours, re-enter in the same dose.

For other infections (depending on the severity of the course): 200-400 mg 2 times a day.

Older patients are prescribed lower doses, depending on the severity of the infection and the CC score.

In pediatrics:

In the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years: 10 mg / kg 3 times a day (maximum dose of 1200 mg). Duration of treatment is 10-14 days.

With a pulmonary form of anthrax (prevention and treatment): 10 mg / kg 2 times a day.

The maximum single dose of the drug Tsifratsid - 400 mg, daily - 800 mg. The total duration of the Cyphricide is 60 days.

Chronic renal failure (CRF): at a glomerular filtration rate (CK 31-60 ml / min / 1.73 m2 or serum creatinine concentration from 1.4 to 1.9 mg / 100 ml), the maximum daily dose is 800 mg. At a glomerular filtration rate (with QC below 30 ml / min / 1.73 m2 or serum creatinine concentration above 2 mg / 100 ml) and with hemodialysis the maximum daily dose is 400 mg; when hemodialysis tsiphratsid introduced after a session of hemodialysis.

With peritoneal dialysis, the infusion solution is added to dialysate (intraperitoneally) at a dose of 50 mg per liter of dialysate 4 times a day (every 6 hours).

The average course of treatment: 1 day - with acute uncomplicated gonorrhea and cystitis; up to 7 days - with infections of the kidneys, urinary tract and abdominal cavity; during the whole period of the neutropenic phase - in patients with weakened protective forces of the body, no more than 2 months - with osteomyelitis and 7-14 days - with all other infections. With streptococcal infections due to the danger of late complications, treatment should last at least 10 days.

Treatment should be carried out at least 3 days after the normalization of body temperature or the disappearance of clinical symptoms.

After intravenous administration, you can continue treatment orally.

Side effects:

On the part of the body as a whole: asthenia, pain in the back, chest, limbs,

From the digestive system: flatulence, nausea, diarrhea, vomiting, abdominal pain, anorexia, hyperbilirubinemia, oral cavity candidiasis, cholestatic jaundice (especially in patients with liver disease), pseudomembranous colitis, pancreatitis, hepatitis, and necrosis of liver tissue.

From the nervous system: dizziness, headache, sleep disorders, fatigue, anxiety, tremor, insomnia, nightmarish dreams, peripheral paralysis (anomaly of perception of pain), increased sweating, increased intracranial pressure, confusion, depression, hallucinations, and other manifestations psychotic reactions (occasionally progressing to conditions in which the patient can do harm to themselves), migraine, convulsions, fainting, thrombosis of the cerebral arteries, increased muscle tone, unstable gait, agitation, disorientation, paresthesia and dysesthesia, hypoesthesia, vertigo, hyperesthesia, peripheral neuropathy and polyneuropathy.

From the sense organs: impairment of taste and smell, visual impairment (diplopia, change in color perception), tinnitus, temporary hearing impairment, hearing loss, parosmia, anosmia.

From the cardiovascular system: tachycardia, symptoms of vasodilation, lowering blood pressure, lengthening the Q-T interval, ventricular arrhythmias (including pirouettes), fainting, vasculitis.

From the hematopoietic system: leukopenia, neutropenia, eosinophilia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, thrombocytopenia, an increase or decrease in prothrombin, oppression of bone marrow hematopoiesis, hemolytic anemia, pancytopenia, agranulocytosis.

Laboratory indicators: hypoprotrombinemia, increased activity of amylase, changes in the parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (APF), hypercreatininaemia, hyperglycemia.

From the urinary system: increased levels of creatinine and concentrations of nitrogen and urea, glomerulonephritis, acute renal failure, vaginal candidiasis, dysuria, polyuria, urinary retention, albuminuria, urethral bleeding, hematuria, crystalluria,interstitial nephritis, decreased renal nitrogen function,

Allergic reactions: skin itching, anaphylactic reactions, skin rashes, urticaria, the formation of blisters accompanied by bleeding, and the appearance of small nodules forming scabs, drug fever, pinpoint hemorrhages on the skin (petechiae), serum sickness, angioedema, anaphylactic shock, edema of the face or larynx, dyspnea, erythema nodosum, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

From the side of the musculoskeletal system: increased muscle tone, muscle weakness, muscle cramps, exacerbation of myasthenia symptoms, arthralgia, joint swelling, myalgia, arthritis, tendovaginitis, tendon ruptures (predominantly Achilles).

From the respiratory system: dyspnoea.

Other: violation of breathing (including bronchospasm), "tides" of blood to the face, increased photosensitivity, candidiasis.

Local reactions: pain, burning, redness, phlebitis.

Overdose:

Treatment: a specific antidote is unknown.With hemo - or peritoneal dialysis, only a small (less than 10%) amount of the drug can be excreted.

Interaction:

Due to a decrease in the activity of microsomal oxidation in hepatocytes, Cyphracid increases the concentration and lengthens T1 / 2 theophylline (and other xanthines, for example, caffeine), oral hypoglycemic drugs, indirect anticoagulants, and helps to reduce the prothrombin index.

When combined with other antifungal medicinal products (beta-lactam antibiotics, aminoglycosides, clindamycin, metronidazole) synergy is usually observed; can be successfully used in combination with azlocillin and ceftazidime in infections caused by Pseudomonas spp .; with mezlocillin, azlocillin, etc. beta-lactam antibiotics - with streptococcal infections; with isoxazolylpenicillins and vancomycin - with staphylococcal infections; with metronidazole and clindamycin - with anaerobic infections.

Preparation Tsifratsid strengthens the nephrotoxic effect of cyclosporine, there is an increase in serum creatinine, in such patients monitoring of this indicator is necessary 2 times a week.

Nonsteroidal anti-inflammatory drugs in combination with Cyphricide (excluding acetylsalicylic acid) increase the risk of seizures.

The joint administration of uricosuric medicines and Cyphracida leads to a delay in excretion (up to 50%) and an increase in the plasma concentration of ciprofloxacin.

Cyphracid increases C_max 7 times (4 to 21 times) and the area under the concentration-time curve is 10 times (6 to 24 times) of tizanidine, which increases the risk of pronounced reduction in blood pressure and drowsiness.

When used simultaneously with drugs that extend the Q-T interval (antiarrhythmic IA and III classes), the Q-T interval can be extended.

With the simultaneous use of ciprofloxacin and omeprazole, there may be a slight decrease in the maximum plasma concentration in the plasma and a decrease in the area under the concentration-time curve.

With the simultaneous use of ciprofloxacin, renal metabolism of methotrexate may be slowed, which may be accompanied by an increase in the concentration of methotrexate in the blood plasma (the probability of side effects of methotrexate increases).

The simultaneous use of duloxetine and potent inhibitors of the isoenzyme CYP450 1A2 (such as fluvoxamine) resulted in an increase in AUC and C_max duloxetine.Despite the lack of clinical data on the possible interaction with ciprofloxacin, it is possible to foresee the likelihood of such interaction with the simultaneous use of ciprofloxacin and duloxetine.

The simultaneous use of ropinirole and ciprofloxacin, a moderate inhibitor of the isoenzyme CYP450 1A2, leads to an increase in C_max and AUC of ropinirole by 60% and 84%, respectively. It is necessary to monitor the side effects of ropinirole during its combined use with ciprofloxacin and for a short time after completion of the combination therapy.

With the simultaneous use of clozapine and ciprofloxacin at a dose of 250 mg for 7 days, an increase in the serum concentrations of clozapine and N-desmethylclozapine by 29% and 31%, respectively (correction of the dosage regimen of clozapine during its simultaneous use with ciprofloxacin and for a short time after completion of combination therapy).

With the simultaneous use of ciprofloxacin in a dose of 500 mg and sildenafil at a dose of 50 mg, there was an increase in C_max and AUC of sildenafil in 2 times (application of this combination is possible only after evaluation of the benefit / risk ratio).

The solution for intravenous administration is compatible with 0.9% NaCl solution, 5% dextrose solution, 2.5% Ringer's solution with dextrose, combined solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).

The infusion solution is pharmaceutically incompatible with all infusion solutions and drugs that are physico-chemically unstable under acidic conditions (the pH of the infusion solution of ciprofloxacin is 3.9-4.5). Do not mix the IV solution with solutions that have a pH greater than 7. Do not mix with heparin.

Special instructions:

Cyphricide is not a drug of choice in suspected or established pneumonia caused by Streptococcus pneumonia.

In the treatment of severe infections, staphylococcal infections and infections caused by anaerobic bacteria, ciprofloxacin should be used in combination with appropriate antibacterial agents.

For infections suspected to be caused by Neisseria gonorrhoeae resistant to fluoroquinolones, local information on ciprofloxacin resistance should be taken into account and the sensitivity of the causative agent in laboratory tests should be confirmed.In rare cases, after the first application, anaphylactic reactions may occur up to anaphylactic shock. In these cases, the use of ciprofloxacin should be stopped immediately and appropriate treatment should be given.

In elderly patients with tendon diseases, or previously treated with glucocorticosteroids, there may be cases of rupture of tendons (mainly Achilles tendon).

Side effects from the CNS can occur after the first use of the drug. In very rare cases, psychosis may manifest as suicidal attempts.

In these cases, immediately stop taking ciprofloxacin and inform the doctor about it. Ciprofloxacin is a moderate inhibitor of CYP450 1A2 isoenzymes.

Caution should be exercised with the simultaneous use of ciprofloxacin and drugs metabolized by these enzymes (including theophylline, methylxanthine, caffeine, duloxetine, clozapine), since an increase in the concentration of these drugs in the blood serum, due to inhibition of their metabolism by ciprofloxacin, can cause specific undesirable reactions. In vitro in laboratory tests ciprofloxacin Suppress the growth of Mycobacterium spp., which can lead to false-negative results in the diagnosis of this pathogen in patients who are injected ciprofloxacin.

It is necessary to take into account the content of sodium chloride in the solution of ciprofloxacin in the treatment of patients in whom sodium intake is limited (heart failure, renal insufficiency, necrotic syndrome).

With simultaneous intravenous administration of Cyphricide and drugs for general anesthesia from the group of barbituric acid derivatives, continuous monitoring of the number of cardiac contractions, arterial pressure, and electrocardiograms is necessary.

To avoid the development of crystalluria, exceeding the recommended daily dose is inadmissible, adequate fluid intake and maintenance of acid urine reaction are also necessary.

Patients with epilepsy, episodes of seizures in history, vascular diseases and organic brain damage, in connection with the threat of development of adverse reactions from the central nervous system should be prescribed only for "vital" indications.

If a severe and prolonged diarrhea occurs during or after treatment, the diagnosis of pseudomembranous colitis should be deleted,which requires immediate withdrawal of the drug and the appointment of appropriate treatment.

When pain occurs in the tendons or the first signs of tendovaginitis treatment should be discontinued (individual cases of inflammation and even rupture of tendons during treatment with fluoroquinolones are described).

During the treatment should avoid UV-irradiation (including contact with direct sunlight).

Effect on the ability to drive transp. cf. and fur:

During treatment, Cyphricide should refrain from engaging in potentially dangerous activities that require increased attention and speed of mental and motor reactions.

Form release / dosage:Solution for infusion.

Packaging:

Infusion bottle with a polymer suspension of 100 ml capacity, with a tamper-proof cap.

For 1 bottle containing 100 ml of the drug is sealed in a cellophane bag, placed along with the instruction for medical use in a cardboard pack.

Storage conditions:

In the dark place at a temperature of 5 to 20 ° C.

Keep out of the reach of children.

Freezing is not allowed.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001748

Date of registration:02.07.2012

The owner of the registration certificate:Edge Pharma Private LimitedEdge Pharma Private Limited India

Manufacturer: & nbsp

EDGE PHARMA PRIVATE, Limited India

Representation: & nbspEdge Pharma Private Limited Edge Pharma Private Limited India

Information update date: & nbsp19.10.2015

Illustrated instructions

Instructions

Cyphricide (Cifracid)