Pharmacodynamics and pharmacokinetics
Pharmacodynamics
fluoroquinolone group (2nd generation monofluoroquinolones), which has a wide spectrum of action. Highly active against gram-negative and some gram-positive microorganisms .
Streptococcuspneumoniae , Enterococcusfaecalis , Pseudomonaspp are moderately sensitive to it , but anaerobic bacteria . Ofloxacin is resistant to β-lactamases .
Pharmacokinetics
Rapidly absorbed from the gastrointestinal tract. Eating slightly slows down the rate of absorption. Cmax in the blood is determined after 2 hours. It is widely distributed in the organs of the urinary and reproductive systems, lungs, gall bladder, ENT organs, skin and bones. Within 24 hours, 80% of the active substance is excreted unchanged in the urine, a small part is excreted in the feces. Half-life 6 hours.
Pharmacological properties of the drug Zanotsin
Pharmacodynamics. Ofloxacin ((±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3]-de-1 ,4-benzoxazine-6-carboxylic acid) is an antimicrobial agent of the fluoroquinolone group. The bactericidal effect of ofloxacin, like other fluorinated quinolones, is due to its ability to block the bacterial enzyme DNA gyrase. The antibacterial spectrum of the drug covers microorganisms resistant to penicillins, aminoglycosides, cephalosporins, as well as microorganisms with multiple resistance. Zanocin OD is a drug with prolonged release of the active substance - ofloxacin. The drug is taken 1 time per day. 1 tablet of Zanocin OD 400 or 800 mg, taken 1 time per day, provides a therapeutic effect equivalent to taking 2 regular tablets of ofloxacin 200 and 400 mg, respectively, taken 2 times a day. Zanocin in tablet form is active against a wide range of bacteria. Aerobic gram-negative bacteria: E. coli, Klebsiella spp., Salmonella spp., Proteus spp., Shigella spp., Yersinia spp., Enterobacter spp., Morganella morganii, Providencia spp., Vibrio spp., Citrobacter spp., Serratia spp. , Campylobacter spp., Pseudomonas aeruginosa, P. cepacia, Neisseria gonorrhoeae, N. meningitidis, Haemophilus influenzae, H. ducreyi, Acinetobacter spp., Moraxella catarrhalis, Gardnerella vaginalis, Pasteurella multocida, Helicobacter pylori. Brucella melitensis have varying sensitivity to the drug . Aerobic gram-positive bacteria: staphylococci, including penicillinase-producing and methicillin-resistant strains, streptococci (especially Streptococcus pneumoniae ), Listeria monocytogenes, Corynebacterium spp. Ofloxacin is more active than ciprofloxacin against Chlamydia trachomatis . Also active against Mycobacterium leprae and Mycobacterium tuberculosis and some other Mycobacterium . There are reports of the synergistic effect of ofloxacin and rifabutin against M. leprae . Treponema pallidum , viruses, fungi and protozoa are not susceptible to ofloxacin. Pharmacokinetics. The drug is quickly and almost completely absorbed in the digestive tract. The absolute bioavailability of ofloxacin is 96% after oral administration. Plasma concentrations reach 3–4 mcg/ml 1–2 hours after administration of a dose of 400 mg. Eating food does not reduce the absorption of ofloxacin, but may slightly slow down the rate of absorption. The half-life of the drug is 5–8 hours. Since ofloxacin is mainly excreted by the kidneys, its pharmacokinetics changes significantly in patients with impaired renal function (creatinine clearance ≤50 ml/min) and therefore they require dose adjustment. Hemodialysis slightly reduces the plasma concentration of ofloxacin. Ofloxacin is widely distributed in tissues and body fluids, including CSF; volume of distribution - from 1 to 2.5 l/kg. About 25% of the drug binds to blood plasma proteins. Ofloxacin crosses the placenta and into breast milk. Reaches high concentrations in most tissues and biological fluids of the body, including ascitic fluid, bile, saliva, bronchial secretions, gallbladder, lungs, prostate gland, bone tissue. Ofloxacin has a pyridobenzoxazine ring, which reduces the rate of metabolism of the parent compound. The drug is primarily excreted unchanged in the urine, with 65–80% excreted within 24–48 hours. Less than 5% of the dose is excreted in the urine as dimethyl or N-oxide metabolites. 4–8% of the dose taken is excreted in the feces. A small amount of ofloxacin is excreted in the bile. There were no differences in the volume of distribution of the drug in elderly people; the drug is excreted from the body primarily by the kidneys in unchanged form, although in a smaller volume. Since ofloxacin is excreted primarily by the kidneys, and elderly patients are more likely to have impaired renal function, the dose of the drug is adjusted if renal function is impaired, as recommended for all patients. The pharmacokinetic features of Zanocin OD facilitate its systemic use. Food does not affect the degree of absorption of the drug. Extended-release ofloxacin tablets are absorbed more quickly and have a greater degree of absorption compared to regular ofloxacin tablets taken 2 times a day. After oral administration of Zanocin OD 400 mg, the maximum concentration of ofloxacin in the blood plasma is achieved after 6.778 ± 3.154 hours and is 1.9088 μg/ml ± 0.46588 μg/ml. AUC0–1 is 21.9907±4.60537 µg•g/ml. After oral administration of Zanocin OD at a dose of 800 mg, the maximum concentration of the drug in the blood plasma is reached after 7.792 ± 3.0357 hours and is 5.22 ± 1.24 μg/ml. The AUC0-t level is 55.64±11.72 µg•g/ml. In vitro , the drug binds to plasma proteins by approximately 32%. The equilibrium concentration of the drug in the blood plasma is achieved after 4 doses of the drug, and the AUC is approximately 40% greater than that after a single dose. The elimination of ofloxacin from the body is two-phase. With repeated oral administration, the half-life of the drug is about 4-5 hours and 20-25 hours. Total clearance and volume of distribution are approximately similar for single or repeated use.
Indications for use
Infections:
- ENT organs ( otitis , sinusitis , tonsillitis );
- respiratory tract (infected bronchiectasis, pleurisy , empyema , abscess , community-acquired pneumonia); bones, skin and soft tissues;
- genitourinary system ( cystitis , urethritis , pyelonephritis , prostatitis , gonorrhea , epididymitis , mixed urethral infections);
- inflammation of the pelvic organs;
- typhoid fever , shigellosis , salmonellosis .
Side effects
- nausea, vomiting, stool upset, abdominal pain, loss of appetite, bloating, in rare cases - hepatitis , liver necrosis , pseudomembranous colitis and intestinal bleeding ;
- dizziness, insomnia or drowsiness, irritability, rarely - convulsions, depression , hallucinations , disturbing dreams, suicidal thoughts, phobias , peripheral neuropathy, coordination and speech disorders;
- rash, itching, angioedema , urticaria , anaphylactic shock , allergic pneumonitis, conjunctivitis , erythema nodosum , epidermal necrolysis ;
- vaginitis , dysmenorrhea , metrorrhagia , vaginal discharge and itching, vaginal candidiasis ;
- very rarely observed: edema, arterial hypertension or hypotension , tachycardia , urinary retention, polyuria or anuria , arthralgia , tendinitis , exacerbation of myasthenia gravis, hyper- or hypoglycemia, bronchospasm, stridor , epistaxis, anemia , agranulocytosis and leukopenia .
Side effects of the drug Zanocin
As a result of clinical studies, the most commonly observed events with repeated use of ofloxacin were: nausea (3%), headache (1%), dizziness (1%), diarrhea (1%), vomiting (1%), rash (1%), itching skin (1%), itching of the external genitalia in women (1%), vaginitis (1%), dysgeusia (1%). In clinical studies, the most common side effects that occurred regardless of the duration of use of the drug were nausea (10%), headache (9%), dyssomnia (7%), itching of the external genitalia in women (6%), dizziness (5). %), vaginitis (5%), diarrhea (4%), vomiting (4%). In clinical studies, the most common side effects, which occurred regardless of the duration of drug use and were observed in 1-3% of patients, were abdominal pain and colic, chest pain, decreased appetite, dry lips, dysgeusia, fatigue, flatulence, and mental disorders. Gastrointestinal tract, nervousness, pharyngitis, itching, fever, rash, dyssomnia, drowsiness, body pain, vaginal discharge, blurred vision, constipation. Side effects that were noted in clinical studies in less than 1% of cases, regardless of the duration of use of the drug: general disorders: asthenia, chilliness, malaise, pain in the extremities, nosebleeds; from the cardiovascular system: cardiac arrest, edema, hypertension, arterial hypotension, feeling of increased heartbeat, vasodilation; from the gastrointestinal tract: dyspepsia; from the genitourinary system: sensation of heat, irritation, pain and rash in the genital area in women, dysmenorrhea, metrorrhagia; from the musculoskeletal system: arthralgia, myalgia; from the central nervous system: convulsions, anxiety, impaired cognitive function, depression, abnormal dreams, euphoria, hallucinations, paresthesia, disturbances of consciousness, vertigo, tremor; from the metabolic side: thirst, weight loss; from the respiratory system: respiratory arrest, cough, rhinorrhea; allergic and skin reactions: angioedema, hyperhidrosis, urticarial rash, vasculitis; from the senses: decreased hearing acuity, ringing in the ears, photophobia; from the urinary system: dysuria, frequent urination, urinary retention. Changes in laboratory parameters were detected in ≥1% of patients with repeated use of ofloxacin. These changes are caused both by taking the drug and by the underlying disease: from the blood system: anemia, leukopenia, leukocytosis, neutropenia, neutrophilia, band neutrophyllosis, lymphocytopenia, eosinophilia, lymphocytosis, thrombocytopenia, thrombocytosis, increased ESR; from the hepatobiliary system: increased levels of alkaline phosphatase, AST, ALT; laboratory parameters: hyperglycemia, hypoglycemia, hypercreatininemia, increased urea levels, glucosuria, proteinuria, alkalinuria, hyposthenuria, hematuria, pyuria. Post-marketing experience Additional side effects that occurred regardless of the duration of use of the drug were noted as a result of marketing studies of quinolones, including ofloxacin. From the cardiovascular system: cerebral thrombosis, pulmonary edema, tachycardia, arterial hypotension/shock, fainting, ventricular tachycardia of the pirouette type. From the endocrine system and metabolism: hyper- or hypoglycemia, especially in patients with diabetes using insulin therapy or oral hypoglycemic drugs. From the gastrointestinal tract: hepatonecrosis, jaundice (cholestatic or hepatocellular), hepatitis, intestinal perforation, liver failure (including fatal cases), pseudomembranous colitis (symptoms of pseudomembranous colitis can occur both during and after the end of antibacterial therapy), bleeding from the gastrointestinal tract, hiccups, soreness of the oral mucosa, heartburn. From the genitourinary system: vaginal candidiasis. From the blood system: anemia (including hemolytic and aplastic), hemorrhage, pancytopenia, agranulocytosis, leukopenia, reversible depression of bone marrow function, thrombocytopenia, thrombocytopenic purpura, petechiae, subcutaneous hemorrhage/bruising. From the musculoskeletal system: tendinitis, tendon ruptures, weakness, acute necrosis of skeletal muscles. From the central nervous system: nightmares, suicidal thoughts or actions, disorientation, psychotic reactions, paranoia, phobia, agitation, anxiety, aggressiveness/hostility, mania, emotional lability, peripheral neuropathy, ataxia, loss of coordination, possible exacerbation of myasthenia gravis and extrapyramidal disorders; dysphasia, dizziness. From the respiratory system: dyspnea, bronchospasm, allergic pneumonitis, wheezing. Allergic and skin reactions: anaphylactic/anaphylactoid reaction/shock, purpura, serum sickness, erythema multimorpha/Stevens-Johnson syndrome, erythema nodosum, exfoliative dermatitis, hyperpigmentation, toxic epidermal necrolysis, conjunctivitis, photosensitivity/phototoxicity reactions, vesiculobullous rash. From the senses: diplopia, nystagmus, blurred vision, dysgeusia, impaired smell, hearing and balance, which usually disappear after stopping the drug. From the urinary system: anuria, polyuria, kidney stones, renal failure, interstitial nephritis, hematuria. Laboratory indicators: prolongation of prothrombin time, acidosis, hypertriglyceridemia, increased cholesterol, potassium, liver function tests, including gamma-glutamyl transpeptidase, LDH, bilirubin, albuminuria, candiduria. In clinical trials, repeated use of quinolones has been associated with ophthalmic abnormalities, including cataracts and pinpoint opacities of the lens. The connection between taking the drug and the appearance of these disorders has not yet been established. Crystalluria and cylindruria have been reported with other quinolones.
Zanotsin, instructions for use (Method and dosage)
The tablets are taken orally whole (do not break or chew) after meals with water.
The dose depends on the severity of the disease, age, body weight, kidney function and is determined by the doctor. Most often, the dose is 400 mg/day, divided into 2 doses (or in one dose in the morning), and the course of treatment is 7-10 days. For severe infections, therapy is prolonged.
Zanocin OD is a film-coated tablet of prolonged action, 400 mg and 800 mg, taken once a day and is equivalent in therapeutic effect to 2 tablets of 200 mg and 400 mg, taken twice a day. For some diseases, the daily dose is 800 mg and it is more advisable to take the drug Zanotsin OD.
Special instructions for the use of the drug Zanotsin
Convulsions, increased intracranial pressure and toxic psychosis have been reported in patients taking quinolone drugs, including ofloxacin. Quinolones, including ofloxacin, may also have a stimulant effect on the central nervous system, which may lead to tremor, restlessness/agitation, nervousness/anxiety, dizziness, confusion, hallucinations, paranoia and depression, nightmares, dyssomnia, and rarely, suicidal thoughts and actions. Such reactions may occur after taking the first dose. If such symptoms occur in patients taking ofloxacin, the drug should be discontinued and appropriate measures taken. Dyssomnia is the most common disorder with ofloxacin than with other quinolone drugs. Like all quinolones, ofloxacin is used with caution in cases of established/suspected disorders of the nervous system, since these drugs can provoke convulsions or a decrease in the threshold of convulsive readiness (severe cerebral atherosclerosis, epilepsy), or with other risk factors (on the background of continuous therapy, impaired renal function), which can provoke seizures or a decrease in the seizure threshold. Severe and fatal (rare) hypersensitivity reactions and/or anaphylactic reactions have been reported in patients receiving quinolones, including ofloxacin. Such reactions were often noted after taking the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension/shock, seizures, loss of consciousness, tinnitus, angioedema (including swelling of the tongue, larynx, pharynx or face), airway obstruction (including bronchospasm, dyspnea and acute respiratory failure), dyspnea, urticarial rash, itching and other severe skin reactions. The drug is immediately discontinued at the first sign of skin rash or other hypersensitivity reactions. In severe acute hypersensitivity reactions, epinephrine therapy and other resuscitation measures may be necessary, including oxygen therapy, fluid resuscitation, antihistamines, corticosteroids, vasopressor amines, and airway management. Other severe and sometimes fatal cases associated with hypersensitivity reactions or unknown etiologies have been reported rarely during therapy with quinolones, including ofloxacin. Such cases could be severe and generally occurred after repeated doses of the drug. The drug is immediately discontinued at the first manifestation of a skin rash, jaundice or other symptoms of hypersensitivity and symptomatic therapy is prescribed. During treatment with quinolones, including ofloxacin, isolated cases of sensory or sensorimotor neuronal polyneuropathy involving small and/or large neurons, manifested by paresthesia, hypoesthesia, dysesthesia and weakness, have been reported. To prevent the development of irreversible conditions, treatment with ofloxacin is discontinued if symptoms of neuropathy (pain, burning sensation, tingling, numbness and/or weakness) or other disturbances in tactile, pain, temperature, positional, vibration sensitivity develop. Diarrhea associated with Clostridium difficile with almost all antibacterial agents, including ofloxacin; The disease can range from mild diarrhea to fatal colitis. Treatment with antibacterial drugs affects the normal intestinal microflora and leads to increased growth of Clostridium difficile. Clostridium difficile- associated diarrhea should be considered in all cases of diarrhea occurring after taking antibacterial drugs. Clostridium difficile- associated diarrhea have been reported 2 months after stopping antibiotic use. If diarrhea associated with Clostridium difficile , antibacterial drugs whose action is not directed at Clostridium difficile are discontinued. Tendon ruptures of the upper (shoulder tendon), lower (Achilles tendon), and other tendons requiring surgery or causing long-term disability have been reported in patients treated with quinolones, including ofloxacin. Post-marketing studies indicate that the risk of musculoskeletal disorders increases with the combined use of GCS, especially in elderly patients. Ofloxacin is discontinued if pain, inflammation or tendon rupture occurs. The patient is recommended to rest in bed and limit movement until tendonitis or tendon rupture is confirmed/excluded. Tendon ruptures can occur both during and after treatment with quinolone drugs, including ofloxacin. Ofloxacin is not effective against syphilis. Antibacterial therapy, prescribed in high doses and for a short period for the treatment of gonorrhea, can mask or delay the manifestations of the incubation period of syphilis. All patients with gonorrhea undergo a serologic test for syphilis during the diagnostic workup. When using ofloxacin to treat gonorrhea, perform a serological test for syphilis 3 months after treatment and prescribe appropriate antibiotic therapy if the test result is positive. If ofloxacin is prescribed in the absence of data regarding the confirmed or most likely causative agent of the disease, or for prophylactic treatment, the benefit to the patient is unlikely; this increases the risk of developing bacterial resistance to the drug. To prevent the development of crystalluria, ensure adequate fluid intake. After taking quinolone antibacterial drugs and subsequent exposure to solar or ultraviolet irradiation, moderate to severe photosensitivity/phototoxicity reactions may occur, which are manifested by sunburn (redness, erythema, exudation, vesicles, edema) on exposed skin areas (face, anterior neck , extensor surface of the forearm, dorsal surface of the upper limbs). Therefore, during the treatment period, sun exposure should be avoided. Some quinolones, including ofloxacin, may cause prolongation of the QT on the ECG and rarely arrhythmia. Isolated cases of torsade de pointes (TdP) in patients taking quinolones, including ofloxacin, have been reported during post-marketing studies. Ofloxacin should not be prescribed in cases of established prolongation of the QT , uncorrected hypokalemia, and in patients taking class IA (quinidine, procainamide) or class III antiarrhythmic drugs (amiodarone, sotalol). During pregnancy and breastfeeding . Reliable and controlled studies of the use of the drug during pregnancy have not been conducted. The safety and effectiveness of the use of ofloxacin during pregnancy have not been established, therefore the drug is not prescribed during this period. When taking ofloxacin during breastfeeding in a single dose of 200 mg, the level of drug concentration in breast milk corresponded to a similar level in blood plasma. Since there is a risk of severe adverse reactions in infants, breastfeeding should be stopped or the drug should be discontinued (depending on the clinical significance of taking the drug for the woman). Children . Ofloxacin is not indicated for the treatment of children and adolescents under 18 years of age. The ability to influence reaction speed when driving vehicles or working with machinery. Since isolated cases of drowsiness, dizziness and visual impairment associated with taking the drug have been reported, you should not drive or operate other machinery during the treatment period.
Interaction
The absorption of quinolones decreases and their concentration in the blood decreases when used simultaneously with Sucralfate , antacids , iron supplements , and multivitamins with zinc . These medications are taken at intervals of 2 hours.
When ofloxacin and NSAIDs , there is a risk of seizures. of theophylline in the blood , which is associated with increased adverse reactions of the latter.
When used simultaneously with aminoglycosides , beta-lactam antibiotics , Metronidazole , the effectiveness of the action is cumulative.
Drug interactions Zanocin
Antacids, sucralfate, metal cations, multivitamins . Quinolones form chelates with alkaline agents and metal cation transporters. The use of quinolones in combination with antacids containing calcium, magnesium or aluminum, sucralfate, di- or trivalent cations (iron), multivitamin preparations containing zinc, didanosine can significantly reduce the absorption of quinolones, thereby reducing their systemic concentrations. The above drugs are taken 2 hours before or after taking ofloxacin. Caffeine. No interaction detected. Cyclosporins . There are no reports of increased plasma levels of cyclosporine when combined with quinolones. Potential interactions between quinolones and cyclosporines have not been studied. Cimetidine caused a violation of the elimination of some quinolones, namely, it led to an increase in the half-life of the drug and AUC. The possible interaction between ofloxacin and cimetidine has not been studied. Drugs that are metabolized by cytochrome P450 enzymes . Most quinolone drugs inhibit the enzyme activity of cytochrome P450. This may lead to a prolongation of the half-life of drugs that are metabolized by the same system (cyclosporine, theophylline/methylxanthines, warfarin) when used in combination with quinolones. NSAIDs. The combined use of NSAIDs and quinolones, including ofloxacin, may lead to an increased risk of CNS stimulant effects and seizures. Probenecid . The combined use of probenecid and quinolones may affect renal tubular excretion. The effect of probenecid on the excretion of ofloxacin has not been studied. Theophylline. Plasma levels of theophylline may increase when combined with ofloxacin. Like other quinolones, ofloxacin may prolong the half-life of theophylline, increase plasma theophylline levels and the risk of theophylline side effects. Plasma theophylline levels should be regularly determined and the dose adjusted when coadministered with ofloxacin. Side effects (including seizures) may occur with or without an increase in plasma theophylline levels. Warfarin. Some quinolones may enhance the effects of oral administration of warfarin or its derivatives. Therefore, when quinolones are combined with warfarin or its derivatives, prothrombin time and other blood coagulation parameters are regularly monitored. Antidiabetic agents (insulin, glyburide/glibenclamide) . Changes in blood glucose levels, including hyper- and hypoglycemia, have been reported during concomitant use of quinolone drugs and antidiabetic agents; therefore, glycemia should be closely monitored when the above drugs are used in combination. Drugs affecting renal tubular excretion (furosemide, methotrexate). With the simultaneous administration of quinolones and drugs that affect renal tubular excretion, excretion disturbances and an increase in the level of quinolones in the blood plasma may occur. Interference with laboratory or diagnostic tests . Some quinolones, including ofloxacin, may produce false-positive results for urinary opiates when administered with oral immunoassays. In the absence of data on the compatibility of the solution with other infusion solutions or drugs, Zanocin in the form of solution for infusion must be used separately. The drug is compatible with isotonic sodium chloride solution, Ringer's solution, 5% glucose or fructose solution.
Zanotsin's analogs
Level 4 ATX code matches:
Siflox
Hyleflox
Leflobakt
Lefoccin
Gatifloxacin
Ofloxacin
Faktiv
Tigeron
Lebel
Lomefloxacin
Eleflox
Lomflox
Pefloxacin
Tsiprobay
Sparflo
Tariwid
Zoflox
Abaktal
Moxifloxacin
Levofloxacin
Dancil , Zoflox , Ofloxacin , Ofloxin , Floxal , Tarivid , Uniflox .
Reviews about Zanotsin
Quinolones are widely used in the treatment of gynecological and urological diseases, as evidenced by reviews. Many patients were prescribed this drug for the treatment of salpingo-oophoritis , perimetritis , metroendometritis on an outpatient basis. The treatment was highly effective and rational, since according to gynecologists, ofloxacin is the most effective drug for the treatment of these diseases. The treatment was well tolerated. Only a few experienced minor nausea, anorexia and diarrhea . Manifestations of photosensitivity during treatment in the summer.
Ofloxacin is excreted in the urine by the kidneys, which makes it possible to successfully treat urological diseases of an inflammatory nature. Already on days 5-7 bacteriuria and overall health improved. The treatment was carried out with a low level of side effects.
Norbactin and Zanocin are effective against pseudomonas and Escherichia coli , which makes it possible to use these drugs for the treatment of purulent-inflammatory diseases. The drug Zanocin, in addition to a wide spectrum of bactericidal action has an immunomodulatory effect , which makes it the drug of choice for the treatment of diseases in patients with weakened immune systems ( AIDS , cancer patients ).
Overdose of the drug Zanotin, symptoms and treatment
Data on overdose with ofloxacin are limited. Symptoms: confusion, drowsiness, lethargy, disorientation, dizziness, nausea, vomiting. Treatment: there is no specific antidote. In case of overdose, the stomach is washed, adsorbents and sodium sulfate are prescribed (if possible, during the first 30 minutes), and antacids are used to protect the gastric mucosa. The patient is examined and, if necessary, hydrated. Forced diuresis accelerates the elimination of ofloxacin from the body. Hemodialysis or peritoneal dialysis are ineffective.
