Instructions for use Ciprolet A film-coated tablets 500 mg + 600 mg No. 10
Composition
active ingredients: ciprofloxacin, tinidazole;
1 film-coated tablet contains ciprofloxacin hydrochloride equivalent to ciprofloxacin 500 mg and tinidazole 600 mg;
excipients: corn starch, microcrystalline cellulose, croscarmellose sodium, sodium starch glycolate (type A), colloidal anhydrous silica, talc, magnesium stearate, hydroxypropylmethylcellulose, sorbic acid, titanium dioxide (E 171), polyethylene glycol 6000, polysorbate 80, dimethicone, Opadry 13 F80003 white.
Dosage form
Film-coated tablets.
Main physicochemical properties: white or almost white film-coated tablets, oval in shape, with a score on one side and a smooth surface on the other.
Pharmacotherapeutic group
Combined antibacterial agents. Fluoroquinolones in combination with other antibacterial agents. ATX code J01R A04.
Pharmacological properties
Pharmacodynamics
Pharmacological properties of the drug Ciprolet®A are due to the pharmacological properties of each of its substances. The mechanism of action of ciprofloxacin is due to the inhibition of the bacterial enzyme DNA gyrase of bacteria. The result of such inhibition is a disruption of the bulk structure of bacterial DNA and makes further division of bacterial cells impossible. Ciprofloxacin is active against gram-positive and gram-negative bacteria.
The spectrum of action of ciprofloxacin covers the following microorganisms:
aerobic gram-negative bacteria – Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Рroteus mirabilis, Proteus vulgaris, Shigella sonnei, Shigella boydii, Shigella dysenteriae, Shigella flexneri, Enterobacter cloacae, Morganella morganii, Providencia rettgeri, Providencia stuartii, Citrobacter diversus, Citrobacter freundii, Serratia marcescens, Campylobacter jejuni, Pseudomonas aeruginosa, Neisseria gonorrhoeae, Haemophilus influenzae, Haemophilus parainfluenzae, Bacillus anthracis, Moraxella catarrhalis;
aerobic gram-positive bacteria - staphylococci, including strains producing penicillinase and strains resistant to methicillin, streptococci, including Streptococcus pneumoniae, Listeria monocytogenes, Corynebacterium spp.
Tinidazole is a 5-nitroimidazole derivative with a substituted imidazole moiety, which is able to act against anaerobic bacteria and protozoa. The mechanism of action of tinidazole on anaerobic bacteria and protozoa is associated with the penetration of the drug into the cells of microorganisms and with damage to DNA or inhibition of its synthesis.
Tinidazole is active against both protozoa and obligate anaerobic bacteria. Protozoa susceptible to tinidazole include Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia.
Tinidazole is active against Gardnerella vaginalis and against most anaerobic bacteria, including Bacteroides fragilis, Bacteroides melaninogenicus, Bacteroides spp., Clostridium spp., Eubacterium spp., Fusobacterium spp., Peptococcus spp., Peptostreptococcus spp. and Veillonella spp.
Pharmacokinetics
Ciprofloxacin is rapidly absorbed after oral administration. Bioavailability is approximately 70%. Food does not affect the extent of absorption of ciprofloxacin, but may slow down the rate of absorption. The maximum concentration of ciprofloxacin in the blood plasma is reached after 1-2 hours. Ciprofloxacin reaches therapeutic concentrations in almost all tissues and body fluids. Binding to plasma proteins is insignificant - 20-40%. The half-life is 3-5 hours. Tinidazole is rapidly and completely absorbed when administered orally.
After oral administration of tinidazole at a dose of 2 g, serum concentrations peaked at
40-51 μg/ml within 2 hours and decreased to 11-19 μg/ml after 24 hours. The half-life of tinidazole from blood plasma is 12-14 hours. Tinidazole is actively distributed to all tissues of the body and penetrates the blood-brain barrier. Almost 12% of tinidazole in plasma is bound to blood proteins. Tinidazole is excreted by the liver and kidneys. Within 5 days, 60-65% of the administered dose is excreted by the kidneys, with 20-25% excreted unchanged. Approximately 12% of the dose is excreted in the feces.
Indication
Infections caused by microorganisms sensitive to the drug, including mixed aerobic-anaerobic infections, protozoal infections: respiratory tract - pleurisy, pleural empyema, lung abscess; ENT organs - chronic sinusitis, mastoiditis; skin and soft tissues - infected ulcers, abscesses, cellulitis, soft tissue infections in patients with diabetes mellitus; gastrointestinal tract - bacterial diarrhea, dysentery, amebiasis, other mixed gastrointestinal tract infections; intra-abdominal infections; gynecological infections; bone infections - chronic osteomyelitis; dental infections.
Contraindication
Hypersensitivity to ciprofloxacin or other fluoroquinolones, hypersensitivity to tinidazole or other 5-nitroimidazole derivatives, organic neurological disorders, history of blood diseases, pregnancy or breastfeeding, children. The simultaneous use of ciprofloxacin and tizanidine is contraindicated (see section "Interaction with other medicinal products and other types of interactions").
Interaction with other medicinal products and other types of interactions
Simultaneous use of Ciprolet®A with iron preparations, sucralfate and antacids containing magnesium, aluminum, calcium, and drugs with a high buffer capacity (e.g., antiretrovirals) reduces the absorption of ciprofloxacin. In this regard, Ciprolet®A should be administered 1-2 hours before or 4 hours after taking these drugs. This restriction does not apply to the class of H2-receptor blockers.
Theophylline
The simultaneous use of theophylline and ciprofloxacin leads to an increase in theophylline plasma concentration and a prolongation of its half-life, which in turn may lead to the development of adverse reactions. In isolated cases, such adverse reactions may be life-threatening or fatal. If the simultaneous use of these drugs cannot be avoided, theophylline serum concentration should be monitored and the dose of theophylline should be reduced appropriately (see section "Special instructions").
Cyclosporine
When used simultaneously with cyclosporine, an increase in serum creatinine has been observed in some cases. Therefore, frequent (2 times a week) monitoring of plasma creatinine concentration is necessary for these patients.
Indirect anticoagulants
Ciprolet®A may increase the concentration and prolong the half-life of indirect anticoagulants.
Concomitant use of ciprofloxacin and vitamin K antagonists may potentiate the anticoagulant effect of the vitamin K antagonist. The degree of risk may vary depending on the underlying type of infection, age, and general condition of the patient, so it is difficult to accurately assess the effect of ciprofloxacin on the increase in the International Normalized Ratio (INR). Frequent monitoring of INR should be performed during and immediately after concomitant use of ciprofloxacin and a vitamin K antagonist (e.g. warfarin, acenocoumarol, phenprocoumon, or fluindione).
Tizanidine
Tizanidine should not be administered concomitantly with ciprofloxacin (see section "Contraindications"). In a clinical study in healthy volunteers, concomitant administration of ciprofloxacin and tizanidine resulted in an increase in plasma tizanidine concentrations (7-fold increase in Cmax, range 4-21-fold; 10-fold increase in AUC, range 6-24-fold). Hypotensive and sedative adverse reactions are associated with increased serum tizanidine concentrations.
Methotrexate
Concomitant administration of ciprofloxacin may slow down the tubular transport (renal metabolism) of methotrexate, which may lead to an increase in the concentration of methotrexate in the blood plasma. This may increase the likelihood of adverse toxic reactions caused by methotrexate. Concomitant administration is not recommended.
Ropinirole.
In clinical studies, it was found that concomitant use of ropinirole with ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isoenzyme, resulted in an increase in ropinirole AUC and Cmax by 60% and 84%, respectively. Monitoring of ropinirole side effects and appropriate dose adjustment are recommended during and immediately after co-administration with ciprofloxacin (see section 4.4).
Clozapine.
After concomitant administration of 250 mg of ciprofloxacin with clozapine for
After 7 days, serum concentrations of clozapine and N-desmethylclozapine were increased by 29% and 31%, respectively. Clinical monitoring and appropriate dose adjustment of clozapine are recommended during and immediately after concomitant administration with ciprofloxacin (see section 4.4).
Drugs that prolong the QT interval.
Ciprolet®A, like other fluoroquinolone-containing drugs, should be prescribed with caution to patients receiving drugs that prolong the QT interval (e.g. class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see section "Special instructions").
Metoclopramide.
Metoclopramide accelerates the absorption of ciprofloxacin, resulting in a faster peak plasma concentration. No effect on the bioavailability of ciprofloxacin was observed.
Omeprazole.
Concomitant use of ciprofloxacin and medicinal products containing omeprazole leads to a slight decrease in Cmax and AUC of ciprofloxacin.
Lidocaine.
Concomitant use of ciprofloxacin, a moderate inhibitor of cytochrome P450 1A2, and lidocaine-containing medicinal products has been shown to reduce the clearance of intravenous lidocaine by 22% in healthy subjects. Despite the normal tolerability of lidocaine treatment, an interaction with ciprofloxacin associated with adverse reactions may occur with concomitant use of these medicinal products.
Sildenafil.
Cmax and AUC of sildenafil increased approximately 2-fold in healthy volunteers after oral administration of 50 mg sildenafil and concomitant administration of 500 mg ciprofloxacin. Therefore, caution should be exercised when co-administering Ciprolet®A with sildenafil and the risk/benefit ratio should be considered.
Ciprolet®A may increase the concentration and prolong the half-life of oral hypoglycemic agents. With the concomitant administration of ciprofloxacin and oral antidiabetic drugs, especially sulfonylureas (e.g. glibenclamide, glimepiride), hypoglycemia has been reported, which is probably due to the potentiation of the action of oral antidiabetic drugs by ciprofloxacin (see section "Adverse reactions"). Therefore, frequent monitoring of blood glucose levels is necessary in such patients.
Duloxetine.
Clinical studies have shown that concomitant use of duloxetine with strong CYP450 1A2 inhibitors, such as fluvoxamine, may result in increased AUC and Cmax of duloxetine. Although there are no clinical data on a possible interaction with ciprofloxacin, similar effects can be expected when these drugs are used concomitantly (see section 4.4).
Nonsteroidal anti-inflammatory drugs.
Animal studies have shown that the combination of very high doses of quinolones (gyrase inhibitors) and certain nonsteroidal anti-inflammatory drugs (except acetylsalicylic acid) can provoke seizures.
Ciprofloxacin affects the metabolism of caffeine, causing a prolongation of its half-life. With the simultaneous use of ciprofloxacin and phenytoin, changes in the level of phenytoin in the blood serum (increase or decrease) have been reported. The combined use of the drug Ciprolet®A and probenecid is accompanied by an increase in the concentration of ciprofloxacin in the blood plasma. Metoclopramide accelerates the absorption of the drug Ciprolet®A, as a result of which the period to achieve the maximum concentration of ciprofloxacin in the blood plasma is shortened (this does not affect the bioavailability of the latter).
Application features
Ciprofloxacin should be avoided in patients who have experienced serious adverse reactions to fluoroquinolones in the past. Ciprofloxacin should only be initiated in such patients if no alternative treatment options are available and after a careful benefit-risk assessment (see section 4.3).
During treatment with the drug, alcoholic beverages should not be consumed due to the possible development of a disulfiram-like reaction (hot flashes, abdominal cramps, vomiting, tachycardia). Alcohol should not be consumed within 72 hours after stopping the drug.
Patients with epilepsy, with a history of seizures, with vascular diseases and organic brain lesions due to the risk of developing adverse reactions from the central nervous system, Ciprolet®A should be prescribed only for vital indications. If adverse reactions from the central nervous system occur during treatment, the drug should be discontinued. If severe and prolonged diarrhea occurs during or after treatment with Ciprolet®A, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and the appointment of appropriate therapy.
In patients with impaired liver and/or kidney function, monitoring of ciprofloxacin plasma concentrations is recommended. No dose adjustment is required for elderly patients. In some cases, hypersensitivity and allergic reactions are observed after the first dose of ciprofloxacin. In very rare cases, anaphylactic reactions may progress, threatening the patient's life. In these cases, ciprofloxacin should be discontinued and medical treatment should be initiated immediately. If any signs of tendinitis (e.g., painful swelling, inflammation) occur, treatment with the drug should be discontinued immediately and physical activity should be avoided. Ciprofloxacin may cause photosensitivity reactions, therefore direct sunlight should be avoided during treatment. If photosensitivity reactions occur, ciprofloxacin therapy should be discontinued. Patients taking Ciprolet®A should drink sufficient fluids to avoid crystalluria.
Severe infections and/or mixed infections caused by Gram-positive or anaerobic bacteria
For the treatment of severe infections, infections caused by staphylococci or anaerobic bacteria, ciprofloxacin should be used in combination with appropriate antibacterial agents according to approved protocols.
Streptococcal infections (including Streptococcus pneumoniae)
Ciprofloxacin is not recommended for the treatment of streptococcal infections due to insufficient efficacy.
Urinary tract infections
Epididymo-orchitis and pelvic inflammatory disease may be caused by fluoroquinolone-resistant Neisseria gonorrhoeae. Ciprofloxacin should be administered concomitantly with other appropriate antibacterial agents, except in clinical situations where the presence of ciprofloxacin-resistant Neisseria gonorrhoeae has been excluded. If clinical improvement does not occur after 3 days, therapy should be reviewed.
Intra-abdominal infections
Data on the efficacy of ciprofloxacin in the treatment of postoperative intra-abdominal infections are limited.
Traveler's diarrhea
When choosing a drug, information on the resistance to ciprofloxacin of relevant microorganisms in the countries visited by the patient should be taken into account.
Bone and joint infections
Pulmonary form of anthrax
Use in humans is based on in vitro susceptibility data, animal studies and limited human data. The physician should follow national and/or international protocols for the treatment of anthrax.
Antibiotic-associated diarrhea
There are known cases of antibiotic-associated diarrhea during the use of antibacterial drugs, which can vary in severity from mild diarrhea to severe forms. The most common cause of antibiotic-associated diarrhea is usually Clostridium Difficile. The composition of the drug Ciprolet A includes tinidazole, which, in most cases, is active against Clostridium difficile, therefore the likelihood of antibiotic-associated diarrhea during the use of Ciprolet A is minimal, but not excluded (in the case of Clostridium difficile resistance to tinidazole). The doctor should carefully analyze the patient's clinical data and, if necessary, correct the water and electrolyte balance, consider the need for additional administration of protein drugs, the use of antibacterial drugs to which Clostridium difficile is sensitive.
Complicated urinary tract infections and pyelonephritis
Treatment of urinary tract infections with ciprofloxacin should be considered when other treatments are not possible. Treatment should be based on microbiological results.
Other specific severe infections
The use of ciprofloxacin may be justified on the basis of microbiological evidence in other infections in accordance with official guidelines or after a careful benefit-risk assessment when other treatments are not appropriate or when standard treatment has failed. The use of ciprofloxacin in specific severe infections other than those mentioned above has not been evaluated in clinical trials and clinical experience is limited. Therefore, caution is advised in treating patients with such infections.
Hypersensitivity to the drug
In some cases, hypersensitivity and allergic reactions may occur after the first dose of ciprofloxacin (see section "Adverse reactions"), which should be reported to the doctor immediately. In rare cases, anaphylactic/anaphylactoid reactions may progress to a state of shock, which is life-threatening for the patient. In some cases, they are observed after the first dose of ciprofloxacin. In such cases, the drug should be discontinued and medical treatment (treatment of anaphylactic shock) should be immediately initiated.
Musculoskeletal system
In general, ciprofloxacin should not be used in patients with a history of tendon diseases/disorders associated with the use of quinolones. However, in rare cases, after microbiological investigation of the pathogen and an assessment of the benefit/risk ratio, ciprofloxacin may be prescribed to these patients for the treatment of certain severe infections, namely in cases of failure of standard therapy or bacterial resistance, when the results of microbiological investigations justify the use of ciprofloxacin. Tendinitis or tendon rupture (especially of the Achilles tendon), sometimes bilateral, may occur with the use of ciprofloxacin, which may occur in the first
48 hours of treatment. There have been reports of tendon ruptures occurring several months after discontinuation of treatment with the drug. The risk of tendinopathy may be increased in elderly patients, in patients with impaired renal function, in patients who have undergone organ transplantation and in those taking corticosteroids concomitantly, therefore the concomitant use of corticosteroids with this drug should be avoided (see section "Adverse reactions"). If any signs of tendinitis (such as painful swelling, inflammation) occur, ciprofloxacin should be discontinued and alternative treatments should be considered. The affected limb should be rested and corticosteroids should not be used if there are signs of tendinopathy.
Ciprofloxacin should be used with caution in patients with myasthenia gravis (see section "Adverse reactions").
Photosensitivity
Ciprofloxacin has been shown to cause photosensitivity reactions. Patients taking ciprofloxacin are advised to avoid direct sunlight or
UV radiation (see section "Adverse reactions").
Central nervous system
Quinolones may cause convulsions or lower the seizure threshold. Ciprofloxacin should be used with caution in patients with CNS disorders who may be predisposed to seizures. If seizures occur, the drug should be discontinued (see section "Adverse Reactions"). Psychotic reactions may occur even after the first dose of ciprofloxacin. In rare cases, depression or psychosis may progress to suicidal thoughts and actions, such as suicide or attempted suicide. In these cases, the drug should be discontinued and appropriate measures should be taken in the clinical situation.
Cases of sensory or sensorimotor polyneuropathy, manifested by paresthesia, hypesthesia, dysesthesia or weakness (based on neurological symptoms such as pain, burning, sensory disturbances or muscle weakness, alone or in combination), have been reported in patients taking ciprofloxacin. Ciprofloxacin should be discontinued in patients who experience symptoms of neuropathy, including pain, burning, tingling, numbness and/or weakness, and a physician should be consulted before continuing treatment with the drug, in order to prevent the development of irreversible conditions (see section "Adverse reactions").
Heart disorders
The use of ciprofloxacin has been associated with cases of QT prolongation (see section "Adverse reactions").
Since women generally have a longer QT interval than men, they may be more sensitive to drugs that prolong the QT interval. Elderly patients may also be more sensitive to the effects of drugs on the QT interval. Caution should be exercised when ciprofloxacin is administered concomitantly with drugs that may prolong the QT interval (such as class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see section 4.5) or in patients with risk factors for QT prolongation or for the development of bidirectional ventricular spindle tachycardia (e.g. congenital long QT syndrome, uncorrected electrolyte disturbances such as hypokalaemia or hypomagnesaemia and cardiac disease, including heart failure, myocardial infarction or bradycardia).
Gastrointestinal tract
If severe and persistent diarrhoea occurs during or after treatment (even several weeks after treatment), the doctor should be informed, as this symptom may mask a serious gastrointestinal disease (e.g. pseudomembranous colitis, which may be fatal) that requires immediate treatment (see section "Adverse reactions"). In such cases, the drug should be discontinued and appropriate therapy should be initiated (e.g. vancomycin, 4 x 250 mg/day orally). Medicinal products that inhibit peristalsis are contraindicated.
Kidneys and urinary system
During therapy with Ciprolet®A, patients should monitor renal function, in particular serum creatinine levels (twice a week). Crystalluria has been reported in association with the use of ciprofloxacin (see section "Adverse reactions"). Patients taking ciprofloxacin should be adequately hydrated. Excessive alkalinity of the urine should be avoided.
Hepatobiliary system
Cases of hepatic necrosis and life-threatening hepatic failure have been reported with ciprofloxacin (see section 4.8). If any signs and symptoms of liver disease (such as anorexia, jaundice, dark urine, pruritus or abdominal tenderness) occur, treatment should be discontinued. Transient increases in transaminases, alkaline phosphatase and cholestatic jaundice may also occur, especially in patients with pre-existing liver damage who have received ciprofloxacin (see section 4.8).
Glucose-6-phosphate dehydrogenase deficiency
Hemolytic reactions have been reported with ciprofloxacin in patients with glucose-6-phosphate dehydrogenase deficiency. Ciprofloxacin should be avoided in such patients unless the potential benefit outweighs the potential risk. In such cases, hemolysis should be observed.
Resistance
During or after a course of ciprofloxacin treatment, resistant bacteria may be isolated with or without clinically apparent superinfection. There may be a certain risk of isolation of ciprofloxacin-resistant bacteria during long courses of treatment and when treating nosocomial infections and/or infections caused by Staphylococcus and Pseudomonas species.
Cytochrome P450
Ciprofloxacin moderately inhibits CYP450 1A2 and may therefore lead to increased serum concentrations of concomitantly administered substances that are also metabolised by this enzyme (e.g. theophylline, methylxanthines, caffeine, duloxetine, clozapine, olanzapine, ropinirole, tizanidine). Concomitant administration of ciprofloxacin and tizanidine is contraindicated. The increase in plasma concentrations associated with drug-specific adverse reactions is due to inhibition of their metabolic clearance by ciprofloxacin. Therefore, patients taking these substances concomitantly with ciprofloxacin should be closely monitored for clinical signs of overdose. Serum concentrations (e.g. theophylline) may also need to be determined (see section 4.5).
Methotrexate
The simultaneous administration of ciprofloxacin and methotrexate is not recommended (see section "Interaction with other medicinal products and other types of interactions").
Ciprofloxacin may interfere with culture results for Mycobacterium spp. in vitro by inhibiting the growth of mycobacterial cultures, which may lead to false-negative culture results in patients taking ciprofloxacin.
Risk of aortic aneurysm and dissection after taking fluoroquinolones
Epidemiological studies have reported an increased risk of aortic aneurysm and dissection after the use of fluoroquinolones, especially in elderly patients. Therefore, fluoroquinolones should be used only after careful benefit-risk assessment and after consideration of other treatment options in patients with a positive family history of aneurysm, in patients with a diagnosis of aortic aneurysm and/or dissection, or in the presence of other risk factors or conditions predisposing to aortic aneurysm and dissection (e.g. Marfan syndrome, Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behçet's disease, hypertension, atherosclerosis).
Patients should seek immediate medical attention in the emergency department if they experience sudden abdominal, chest, or back pain.
Fluctuations in blood glucose levels
Fluoroquinolones may cause disturbances in blood glucose levels, including hyperglycemia and hypoglycemia (see section "Adverse reactions"), usually in diabetic patients receiving concomitant treatment with oral hypoglycemic agents (e.g. glibenclamide) or insulin. Severe cases of hypoglycemia, leading to coma, have been reported. Close monitoring of blood glucose levels is recommended in such patients.
Ciprofloxacin should be avoided in patients who have had a history of serious adverse reactions to fluoroquinolones. Ciprofloxacin should only be initiated in such patients if no alternative treatment options are available and after a careful benefit-risk assessment (see section 4.3).
Long-term, disabling, potentially irreversible serious adverse reactions.
Very rarely, long-lasting (several months to years), disabling, potentially irreversible serious adverse reactions affecting various, sometimes simultaneously, organ systems (musculoskeletal, nervous, mental and sensory) have been reported in patients treated with quinolones and fluoroquinolones, regardless of age or previously identified risk factors. Ciprofloxacin should be discontinued immediately at the first signs or symptoms of any serious adverse reactions and a doctor should be consulted immediately.
Use during pregnancy or breastfeeding
The drug is contraindicated during pregnancy or breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
During treatment, you should refrain from driving vehicles and/or other mechanisms that require increased concentration and speed of psychomotor reactions.
Method of administration and doses
The usual dose of Ciprolet®A for adults is 1 tablet 2 times a day. Adults should take it orally 1 hour before or 2 hours after a meal. The tablets should be swallowed without chewing and washed down with a small amount of liquid. For patients with creatinine clearance from 31 to 60 ml/min, the maximum daily dose of the drug should be 2 tablets per day, for patients with creatinine clearance of 30 ml/min or less - 1 tablet per day. For severe infections of the abdominal cavity, respiratory tract, and chronic osteomyelitis, the maximum daily dose of the drug is 3 tablets per day. The course of treatment depends on the severity of the infection and the results of bacteriological studies. The usual course of treatment for acute infections is 5-7 days, but in the case of treatment of chronic recurrent infections, the course of treatment is 10-14 days. It is recommended to continue taking the drug for at least 3 days after the temperature normalizes or the symptoms of the infectious process disappear.
Children
The efficacy and safety of the drug in pediatric practice have not been established, therefore it should not be used in children.
Overdose
Symptoms of overdose may include dizziness, tremor, headache, fatigue, convulsions, hallucinations, confusion, abdominal discomfort, renal and hepatic failure, as well as crystalluria and hematuria. In case of acute overdose, renal toxicity has been reported. There is no specific antidote known. In case of overdose, gastric lavage should be performed. The patient should be closely observed and supportive treatment should be given, including monitoring of renal function and the use of antacids containing magnesium, aluminum or calcium, which may reduce the absorption of ciprofloxacin. Adequate hydration should be maintained. Tinidazole is readily removed by dialysis. Ciprofloxacin is only slightly removed by hemodialysis or peritoneal dialysis (less than 10%).
Adverse reactions
Gastrointestinal: nausea, diarrhea, increased liver enzymes (ALT, AST), alkaline phosphatase, vomiting, dyspeptic phenomena, heartburn, abnormal liver function tests, anorexia, constipation, flatulence, bilirubinemia, jaundice, cholestatic jaundice, pseudomembranous colitis, liver necrosis (which very rarely progresses to life-threatening liver failure), pancreatitis, hepatitis (non-infectious), metallic taste in the mouth, abdominal pain, coated tongue, glossitis, stomatitis.
*On the part of the nervous system: dizziness, sleep disorders, agitation, confusion, migraine, hallucinations, increased sweating, paresthesias, dysesthesias, hypesthesias, emotional disturbances (restlessness, fear, anxiety), sleep disorders, convulsions, increased drowsiness, insomnia, pathological/terrible dreams, lethargy, intracranial hyperesthesia, depression, tremor, unsteady gait, psychosis, increased intracranial pressure, ataxia, twitching, headache, sensory disturbances, peripheral neuropathy and polyneuropathy.
Cardiovascular system: arrhythmia (including extrasystole, atrial flutter, ventricular arrhythmia, tachycardia, palpitations, bidirectional ventricular tachycardia), syncope (fainting), vasodilation, flushing, decreased/increased blood pressure, vasculitis, QT interval prolongation.
From the side of the hematopoietic and lymphatic systems: eosinophilia, leukopenia, anemia, neutropenia, leukocytosis, altered prothrombin levels, thrombocytopenia, thrombocythemia, thrombocytosis, hemolytic anemia, petechiae, agranulocytosis, pancytopenia (life-threatening), bleeding, methemoglobinemia, monocytosis, bone marrow depression (life-threatening).
*Psychiatric disorders: psychomotor agitation/anxiety, restlessness, agitation, anxiety, abnormal dreams, confusion and disorientation, depression, hallucinations, psychoses, psychotic reactions (maniacal, phobic, depersonalization), delirium, irritability.
*Musculoskeletal and connective tissue disorders: pain in the extremities, arthralgia, joint dysfunction, myalgia, joint swelling, myasthenia gravis, exacerbation of myasthenia gravis symptoms, myoclonus, tendon damage, tendinitis, tendon ruptures (mainly Achilles), tendon damage, gout attack, back, neck, and chest pain.
From the genitourinary system: increased creatinine levels, increased urea nitrogen levels, renal failure, renal dysfunction, vaginal candidiasis, hematuria, crystalluria, polyuria, urinary retention, urethral bleeding, candiduria, cylindruria, albuminuria, exacerbation of urolithiasis, tubulointerstitial nephritis, darkening of urine.
Reproductive disorders: breast discomfort, gynecomastia.
Endocrine disorders: hyperglycemia, hypoglycemia, hypoglycemic coma, syndrome of inappropriate antidiuretic hormone secretion (SADH).
Respiratory system: dyspnea (including asthmatic conditions), laryngeal edema.
Hypersensitivity reactions. Skin and subcutaneous tissue disorders: skin rash, itching, maculopapular rash, skin redness, urticaria, photosensitivity reactions, nonspecific blistering, allergic reactions, drug fever, anaphylactoid/anaphylactic reactions (including anaphylactic shock), serum sickness-like reaction, petechiae, erythema multiforme, erythema nodosum, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, hyperpigmentation, angioedema (including swelling of the face, lips, neck, conjunctiva, hands).
*On the part of the organs of vision: visual impairment, impaired color perception, blurred vision, achromatopsia.
*From the sense organs and balance: taste disturbance, tinnitus/noise in the ears, temporary deafness, hearing and vision disturbances, diplopia, chromatopsia, parosmia, olfactory disturbance/smell disturbance.
*On the part of the body as a whole: abdominal pain, candidiasis, asthenia, pain in the extremities,
