Grandazol solution for infusion 2.5 mg + 5 mg bottle 200 ml

Instructions Grandazol solution for infusion 2.5 mg + 5 mg bottle 200 ml

Composition

active ingredients: ornidazole; levofloxacin;

1 ml of solution contains ornidazole 5 mg, levofloxacin 2.5 mg;

Excipients: disodium edetate, sodium chloride, water for injections.

Dosage form

Solution for infusion.

Main physicochemical properties: transparent colorless or light yellow liquid.

Pharmacotherapeutic group

Antimicrobials for systemic use. Levofloxacin, combinations with other antibacterial agents.

ATX code J01R A05.

Pharmacological properties

Levofloxacin

Pharmacodynamics.

Levofloxacin is a synthetic antibacterial agent of the fluoroquinolone group, the S-enantiomer of the racemic mixture of the drug ofloxacin.

Mechanism of action

As an antibacterial drug from the fluoroquinolone group, levofloxacin acts on the DNA-DNA gyrase complex and topoisomerase IV.

Pharmacokinetics/pharmacodynamics relationship

The degree of bactericidal activity of levofloxacin depends on the ratio of the maximum serum concentration (Cmax) or the area under the pharmacokinetic curve (AUC) and the minimum inhibitory concentration (MIC).

Mechanism of resistance

The main mechanism of resistance is due to mutations in the gyr-A genes. In vitro, there is cross-resistance between levofloxacin and other fluoroquinolones.

Due to its mechanism of action, there is usually no cross-resistance between levofloxacin and antibacterial agents of other classes.

Antibacterial spectrum

The prevalence of resistance may vary geographically and over time for individual species. It is advisable to obtain local information on the resistance of microorganisms, especially when treating severe infections. Specialist advice should be sought when the local prevalence of resistance is such that the benefit of the agent, at least in some types of infections, is questionable.

Other data

Hospital-acquired infections caused by P. aeruginosa may require combination therapy.

Pharmacokinetics.

Absorption

There is no significant difference in the pharmacokinetics of levofloxacin after intravenous and oral administration.

After intravenous administration, the drug accumulates in the bronchial mucosa and bronchial secretions of lung tissue (concentration in the lungs exceeds that in blood plasma), urine. Levofloxacin penetrates poorly into the cerebrospinal fluid.

Distribution

Approximately 30-40% of levofloxacin is bound to serum proteins. There is virtually no accumulation of levofloxacin with repeated administration of 500 mg once daily. There is a small but predictable cumulative effect after administration of 500 mg twice daily. Steady state is achieved within 3 days.

Penetration into body tissues and fluids

Penetration into the bronchial mucosa, bronchial secretions of lung tissues

The maximum concentration of levofloxacin in the bronchial mucosa and bronchial secretions of the lungs after oral administration of 500 mg was 8.3 μg/g and 10.8 μg/ml, respectively. These values were achieved within one hour after administration of the drug.

Penetration into lung tissue

The maximum concentration of levofloxacin in lung tissue after oral administration of 500 mg was approximately 11.3 μg/g and was reached 4–6 hours after administration. The concentration in the lungs exceeds that in blood plasma.

Penetration into the bladder contents

The maximum concentration of levofloxacin of 4-6.7 μg/ml in the bladder contents was reached 2-4 hours after application of the drug after 3 days of use of the drug at doses of 500 mg once or twice a day, respectively.

Penetration into cerebrospinal fluid

Levofloxacin penetrates poorly into the cerebrospinal fluid.

Penetration into prostate tissue

After administration of 500 mg levofloxacin once daily for 3 days, mean prostate tissue concentrations reached 8.7 μg/g, 8.2 μg/g, and 2 μg/g at 2 hours, 6 hours, and 24 hours, respectively; the mean prostate/plasma concentration ratio was 1.84.

Concentration in urine

The mean urinary concentrations 8–12 hours after single oral doses of 150 mg, 300 mg, and 500 mg of levofloxacin were 44 mg/L, 91 mg/L, and 200 mg/L, respectively.

Levofloxacin is metabolized to a very small extent, the metabolites being desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for less than 5% of the drug excreted in the urine. Levofloxacin is stereochemically stable and does not undergo inversion of the choral structure.

Breeding

After oral and intravenous administration, levofloxacin is eliminated from the blood plasma relatively slowly (half-life 6-8 hours). Excretion occurs mainly by the kidneys (more than 85% of the administered dose).

There is no significant difference in the pharmacokinetics of levofloxacin after intravenous and oral administration, indicating the interchangeability of these routes of administration (oral and intravenous).

Linearity

Levofloxacin has linear pharmacokinetics in the range of 50–600 mg.

Patients with renal failure

The pharmacokinetics of levofloxacin are affected by renal insufficiency. With decreased renal function, renal excretion and clearance are reduced, and half-lives are increased.

Elderly patients

There are no significant differences in the pharmacokinetics of levofloxacin in young and elderly patients, except for differences related to creatinine clearance.

Gender differences

Separate analyses of male and female patients demonstrated slight gender differences in the pharmacokinetics of levofloxacin. There is no evidence that these gender differences are clinically relevant.

Ornidazole

Pharmacodynamics.

The mechanism of action of ornidazole is associated with disruption of the DNA structure in susceptible microorganisms. Ornidazole is active against Trichomonas vaginalis, Entamoeba histolytica, Giardia lamblia (Giardia intestinalis), as well as some anaerobic bacteria, such as Bacteroides, Fusobacterium spp.; anaerobic gram-positive bacteria Clostridium spp., sensitive strains of Eubacterium spp.; anaerobic gram-positive cocci Peptococcus spp., Peptostreptococcus spp.

It easily penetrates the microbial cell and, by binding to DNA, disrupts the replication process.

Pharmacokinetics.

Ornidazole penetrates well through the blood-brain and placental barriers, enters the cerebrospinal fluid, bile; is excreted in breast milk. With intravenous administration at a dose of 15 mg/kg and subsequent administration at a dose of 7.5 mg per 1 kg of body weight every 6 hours, the equilibrium concentration is 18-26 μg/ml. Approximately 30-60% of the drug is metabolized in the body by hydroxylation, oxidation and glucuronidation.

Excretion: Ornidazole is excreted mainly in the urine (60-80%), almost 20% in unchanged form, 6-15% in the feces.

Indication

Treatment of mixed infections of the genitourinary tract caused by pathogens (microorganisms and protozoa) sensitive to the components of the drug.

Treatment of acute respiratory infections.

Prevention of purulent-inflammatory complications after surgical interventions on the abdominal organs.

Prevention of purulent-inflammatory complications after gynecological surgeries.

Contraindication

Hypersensitivity to levofloxacin or other fluoroquinolones, ornidazole or other nitroimidazole derivatives and other components of the drug;

glucose-6-phosphate dehydrogenase deficiency;

organic diseases of the central nervous system, epilepsy, multiple sclerosis;

complaints of adverse reactions from the tendons after previous use of quinolones;

circulatory disorders, pathological blood lesions or other hematological abnormalities;

chronic alcoholism;

childhood (up to 18 years old);

pregnancy;

breastfeeding period.

Interaction with other medicinal products and other types of interactions

Levofloxacin.

Theophylline, fenbufen or similar nonsteroidal anti-inflammatory drugs

No pharmacokinetic interaction of levofloxacin with theophylline was found. However, a significant decrease in the seizure threshold may occur when quinolones are used concomitantly with theophylline, nonsteroidal anti-inflammatory drugs, and other agents that lower the seizure threshold. The concentration of levofloxacin in the presence of fenbufen was approximately 13% higher than when levofloxacin was administered alone.

Probenecid and cimetidine

Probenecid and cimetidine have a statistically significant effect on the elimination of levofloxacin. The renal clearance of levofloxacin is reduced by 24% in the presence of cimetidine and by 34% in the presence of probenecid. This is because both drugs are able to block the tubular secretion of levofloxacin. However, at the doses tested in the study, it is unlikely that the statistically significant kinetic differences are of clinical relevance. Caution should be exercised when levofloxacin is co-administered with drugs that affect tubular secretion, such as probenecid and cimetidine, especially in patients with renal insufficiency.

Other information

In clinical pharmacology studies, it was demonstrated that no clinically significant effect was caused on the pharmacokinetics of levofloxacin when levofloxacin was taken together with calcium carbonate, digoxin, glibenclamide, ranitidine.

Cyclosporine

The half-life of cyclosporine is increased by 33% when co-administered with levofloxacin.

When used concomitantly with vitamin K antagonists (e.g. warfarin), increases in coagulation tests (prothrombin time/international normalized ratio) and/or bleeding, which may be severe, have been reported. Therefore, coagulation parameters should be monitored in patients receiving concomitant vitamin K antagonists (see section 4.4).

Drugs that prolong the QT interval

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving medicinal products known to prolong the QT interval (e.g. antiarrhythmics of classes IA and III, tricyclic antidepressants, macrolides, neuroleptics) [see section "Special warnings and precautions for use. QT interval prolongation"].

Other information

Levofloxacin does not affect the pharmacokinetics of theophylline, which is predominantly metabolized by CYP1A2, therefore it can be assumed that levofloxacin is not a CYP1A2 inhibitor.

Ornidazole.

When used simultaneously with indirect anticoagulants, ornidazole potentiates the effect of coumarin anticoagulants (warfarin, etc.), which requires appropriate adjustment of their dose. Ornidazole prolongs the muscle relaxant effect of vecuronium bromide.

The concentration of the drug decreases with simultaneous use with inducers of microsomal enzymes (phenobarbital, rifampicin) and increases with simultaneous use with inhibitors of liver microsomal systems, in particular with H2-receptor blockers (cimetidine).

When used with other 5-nitroimidazole derivatives, isolated cases of peripheral neuritis, mental depression, and seizures similar to epilepsy have been reported.

Unlike other nitroimidazole derivatives, ornidazole does not inhibit aldehyde dehydrogenase and is therefore compatible with alcohol.

Application features

Use with caution and only if there are direct indications in patients with severe liver dysfunction and elderly patients.

Throughout the course of treatment, it is necessary to monitor kidney and liver function.

When using the drug, you should refrain from drinking alcohol.

During the period of use of the drug, patients should receive sufficient fluid to prevent crystalluria.

Levofloxacin should be avoided in patients with a history of serious adverse reactions to quinolones and fluoroquinolones (see section 4.8). Levofloxacin should only be used in such patients if there are no alternative treatment options and after a careful benefit/risk assessment (see also section 4.8).

Risk of resistance

Methicillin-resistant Staphylococcus aureus (MRSA) has a very high potential for co-resistance to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of infections known or suspected to be caused by MRSA, unless laboratory tests have confirmed susceptibility to levofloxacin (and usually when the use of antibacterial agents recommended for the treatment of MRSA infections is considered inappropriate).

Resistance of Escherichia coli, the most common cause of urinary tract infections, to fluoroquinolones varies across the European Union. When prescribing levofloxacin, physicians should take into account the local prevalence of fluoroquinolone resistance in Escherichia coli.

Prolonged, disabling and potentially irreversible serious adverse reactions

Very rare, long-lasting (several months or years), disabling, potentially irreversible serious adverse reactions affecting various body systems (musculoskeletal, nervous and mental systems, sensory organs) have been reported in patients receiving quinolones or fluoroquinolones, regardless of their age and the presence of risk factors. At the first signs and/or symptoms of any serious adverse reaction, levofloxacin should be discontinued immediately and a doctor should be consulted.

Tendinitis and tendon rupture

Tendinitis and tendon rupture (especially Achilles tendon), sometimes bilateral, may occur within 48 hours of starting treatment with quinolones and fluoroquinolones, sometimes even within several months after stopping the drug. The risk of developing tendonitis and tendon rupture is increased in patients receiving levofloxacin at a daily dose of 1000 mg, elderly patients, patients with renal insufficiency, patients after solid organ transplantation and in patients receiving concomitant corticosteroids. Concomitant use of corticosteroids and fluoroquinolones should be avoided. At the first signs of tendinitis (e.g. painful swelling or inflammation of the joints), levofloxacin treatment should be discontinued immediately and alternative treatment should be considered. The affected limb should be treated appropriately (e.g. immobilization). Corticosteroids should not be used if signs of tendinopathy appear.

Diarrhea, especially (in severe cases) persistent and/or hemorrhagic, during or after treatment with Grandazol® (including within several weeks after treatment) may be a symptom of Clostridium difficile-associated disease (CDAD). The severity of CDAD varies from mild to life-threatening. The most severe form of this disease is pseudomembranous colitis (see section "Adverse reactions"). It is therefore important to consider this diagnosis in patients who develop severe diarrhea during or after treatment with levofloxacin. If pseudomembranous colitis is suspected, the Grandazol® infusion should be stopped immediately and appropriate treatment should be initiated immediately (e.g. oral vancomycin). Agents that inhibit intestinal motility are contraindicated in this clinical situation.

Patients prone to seizures

Quinolones can lower the seizure threshold and provoke the development of seizures.

The drug is contraindicated in patients with a history of epilepsy (see section "Contraindications"). As with other quinolones, it should be used with extreme caution in patients prone to seizures (e.g. patients with central nervous system lesions), with concomitant therapy with fenbufen and similar non-steroidal anti-inflammatory drugs or drugs that increase seizure readiness (lower the seizure threshold), such as theophylline. If seizures occur, treatment with the drug should be discontinued.

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or existing defects in glucose-6-phosphate dehydrogenase activity may be prone to hemolytic reactions when treated with quinolone antibacterial agents, therefore levofloxacin should be used with caution and the risk of hemolysis should be constantly monitored.

Patients with renal insufficiency

Since levofloxacin is excreted mainly by the kidneys, dose adjustment is required for patients with impaired renal function (renal failure) (see section "Method of administration and dosage").

Hypersensitivity reactions

Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (e.g. angioedema up to anaphylactic shock), in some cases after the first dose (see section "Adverse reactions"). If hypersensitivity reactions occur, the drug should be discontinued, a doctor should be consulted and appropriate treatment should be initiated.

Severe skin adverse reactions

Severe cutaneous adverse reactions, which may be fatal, including toxic epidermal necrolysis (also known as Lyell's syndrome), Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported in patients receiving levofloxacin (see section 4.8). Patients should be advised of the signs and symptoms of severe cutaneous reactions and monitored closely when levofloxacin is prescribed. At the first appearance of signs and symptoms suggestive of these reactions, levofloxacin should be discontinued immediately and alternative treatment should be considered. If a patient develops a serious reaction such as Stevens-Johnson syndrome, toxic epidermal necrolysis or DRESS with levofloxacin, levofloxacin should not be restarted in this patient under any circumstances.

Blood glucose fluctuations

As with other quinolones, fluctuations in blood glucose levels, including cases of hyperglycemia and hypoglycemia, have been reported, more frequently in the elderly, especially in diabetic patients receiving concomitant therapy with oral hypoglycemic agents (e.g. glibenclamide) or insulin. Cases of hypoglycemic coma have been reported. Close monitoring of blood glucose levels is recommended in diabetic patients (see section 4.8).

If the patient reports fluctuations in blood glucose levels, the drug should be discontinued immediately and alternative treatment with an antibacterial drug that does not belong to the fluoroquinolone class should be considered.

Prevention of photosensitivity

Photosensitivity has been reported with levofloxacin (see section 4.8). To avoid photosensitivity, patients are advised not to unnecessarily expose themselves to strong sunlight or artificial UV sources (e.g., sunlamps, tanning beds) during treatment and for 48 hours after stopping levofloxacin.

Patients receiving vitamin K antagonists

Due to the possible increase in coagulation test values (prothrombin time/international normalized ratio) and/or bleeding in patients taking Grandazol® in combination with a vitamin K antagonist (e.g. warfarin), coagulation test values should be monitored if these medicinal products are used concomitantly (see section “Interaction with other medicinal products and other types of interactions”).

Psychotic reactions have been reported in patients taking quinolones, including levofloxacin. In rare cases, these have progressed to suicidal ideation and self-harm, sometimes after only a single dose of levofloxacin (see section 4.8). At the first sign or symptom of such reactions, the patient should immediately discontinue levofloxacin and contact their treating physician. The physician should consider alternative treatment with a non-fluoroquinolone antibacterial agent and take appropriate measures. Levofloxacin should be used with caution in patients with psychotic disorders or in patients with a history of psychiatric illness.

QT interval prolongation

Fluoroquinolones, including levofloxacin, should be used with caution in patients with known risk factors for QT prolongation, such as:

congenital long QT syndrome;

concomitant use of drugs known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, neuroleptics);

uncorrected electrolyte imbalance (e.g., hypokalemia, hypomagnesemia);

heart disease (e.g., heart failure, myocardial infarction, bradycardia).

Elderly patients and women may be more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones, including levofloxacin, should be used with caution in these groups of patients [see sections "Dosage and administration. Elderly patients", "Interaction with other medicinal products and other forms of interaction", "Overdose", "Adverse reactions"].

Peripheral neuropathy

Cases of sensory or sensorimotor peripheral polyneuropathy have been reported in patients receiving quinolones or fluoroquinolones, resulting in paraesthesia, hypoesthesia, dysesthesia or weakness. Patients receiving levofloxacin should inform their physician before continuing treatment if they experience symptoms of neuropathy, including pain, burning, tingling, numbness and/or weakness, in order to prevent the development of potentially irreversible conditions (see section 4.8).

Aggravation of central or peripheral nervous system disorders may occur during treatment with ornidazole. In the event of the development of peripheral neuropathy, impaired coordination of movements (ataxia), dizziness or clouding of consciousness, treatment should be discontinued.

Hepatobiliary disorders

Cases of necrotizing hepatitis, up to life-threatening hepatic failure, have been reported, predominantly in patients with severe underlying diseases such as sepsis (see section 4.8). Patients should be advised to discontinue treatment and seek medical advice if signs and symptoms of liver disease such as anorexia, jaundice, dark urine, pruritus or abdominal pain occur.

Exacerbation of myasthenia gravis

Fluoroquinolones, including levofloxacin, have neuromuscular blocking effects and may exacerbate muscle weakness in patients with myasthenia gravis. In the post-marketing period, serious adverse reactions, including fatalities and conditions requiring respiratory support, have been associated with the use of fluoroquinolones in patients with myasthenia gravis. Levofloxacin is not recommended for use in patients with a history of myasthenia gravis.

Vision impairment

If any visual disturbances or adverse reactions from the visual organs occur while taking levofloxacin, you should immediately consult an ophthalmologist (see sections “Ability to affect the speed of reactions when driving vehicles or using other mechanisms” and “Adverse reactions”).

Superinfection

The use of levofloxacin, especially for prolonged periods, may lead to overgrowth of non-susceptible microorganisms. If superinfection occurs during therapy, appropriate measures should be taken.

Exacerbation of candidiasis may occur, which will require appropriate treatment.

Impact on laboratory test results

In patients treated with levofloxacin, urine opiates may give false-positive results. Positive opiates from screening tests may need to be confirmed by more specific methods.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and therefore cause false-negative results in bacteriological diagnosis of tuberculosis.

Aortic aneurysm and aortic dissection and heart valve regurgitation/insufficiency

Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other treatment options in patients with a strong family history (presence of aneurysm or congenital heart valve disease), in patients with a diagnosed aortic aneurysm and/or aortic dissection, or in patients with valvular heart disease, or in the presence of other risk factors, such as:

Risk factors for the development of both aortic aneurysm and aortic wall dissection, as well as regurgitation/valve insufficiency: connective tissue diseases such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, arterial hypertension, rheumatoid arthritis;

Risk factors for developing aortic aneurysm and aortic wall dissection: vascular diseases such as Takayasu arteritis or giant cell arteritis, atherosclerosis, Sjögren's syndrome;

Risk factors for the development of regurgitation/valve insufficiency: infective endocarditis.

The risk of aortic aneurysm and aortic wall dissection and rupture is increased in patients receiving concomitant systemic corticosteroids.

Patients should seek immediate medical attention in the emergency department if they experience sudden abdominal, chest, or back pain.

Patients should be advised to seek immediate medical attention if they experience shortness of breath, palpitations, or swelling of the abdomen or lower extremities.

Blood system disorders

If the patient has a history of blood system disorders, monitoring of leukocytes is recommended, especially when conducting repeated courses of treatment.

Hemodialysis

In case of hemodialysis, it is necessary to take into account the reduction in the half-life and prescribe additional doses of the drug before or after hemodialysis.

Lithium

The concentration of lithium salts, creatinine, and electrolytes must be monitored during lithium therapy.

The effect of other medicines may be enhanced or weakened during treatment with ornidazole.

Sodium content

This medicine contains:

15.4 mmol (or 355 mg) of sodium per 100 ml dose;

30.8 mmol (or 710 mg) of sodium per 200 ml dose.

Caution should be exercised when used in patients on a controlled sodium diet.

Use during pregnancy or breastfeeding

Use is contraindicated.

Ability to influence reaction speed when driving vehicles or other mechanisms

Some adverse reactions (e.g. dizziness/vertigo, muscle rigidity, tremor, convulsions, impaired coordination, including when walking, temporary loss of consciousness, drowsiness, confusion, visual and hearing disturbances) may impair the patient's ability to concentrate and react quickly and thus lead to an increased risk in situations where these qualities are of particular importance (e.g. when driving a car or operating other machinery).

Method of administration and doses

The drug is administered intravenously by drip.

The daily dose of Grandazol® is 100 ml (500 mg ornidazole and 250 mg levofloxacin) - 200 ml (1000 mg ornidazole and 500 mg levofloxacin) for 1-2 injections. The duration of use and dosage depends on the course of the disease and is determined by the doctor. After the condition has stabilized, you should switch to oral administration of levofloxacin and ornidazole. Treatment should be continued for 48-72 hours after the disappearance of clinical symptoms of the disease or obtaining laboratory confirmation of the disappearance of the pathogen.

The maximum daily dose of Grandazol® is 200 ml (1000 mg of ornidazole and 500 mg of levofloxacin) in 1–2 injections per day.

Dosage for adult patients with impaired renal function whose creatinine clearance is less than 50 ml/min (dose is calculated based on levofloxacin)

1 No additional doses are required after hemodialysis or chronic ambulatory peritoneal dialysis (CHAP).

Dosage for patients with impaired liver function: No dose adjustment is required since levofloxacin is metabolized to a minor extent in the liver.

Depending on the patient's condition, a transition from intravenous administration to oral administration at the same dosage may be possible after a few days.

The duration of treatment depends on the course of the disease. As with other antibacterial agents, it is recommended to continue treatment with Grandazol® for at least 48-72 hours after normalization of body temperature or confirmed destruction of pathogens by microbiological tests.

Children

Use is contraindicated.

Overdose

Levofloxacin: Based on animal toxicity studies or clinical pharmacology studies conducted at doses higher than therapeutic, the most serious signs to be expected after acute overdose of levofloxacin are central nervous system symptoms such as confusion, dizziness, impaired consciousness and seizures, and QT prolongation.

During post-marketing studies, central nervous system adverse reactions such as confusion, seizures, hallucinations, and tremor were observed.

Ornidazole. Overdose may cause loss of consciousness, headache, dizziness, tremors, convulsions, peripheral neuritis, dyspeptic disorders, and increased symptoms of other adverse reactions.

Treatment. In case of overdose, symptomatic treatment is carried out. ECG monitoring is necessary, since there is a possibility of prolongation of the QT interval. Hemodialysis, including peritoneal dialysis and chronic ambulatory peritoneal dialysis, are not effective in removing levofloxacin from the body.

There are no specific antidotes. In case of convulsions, diazepam should be used.

Side effects

Adverse reactions are described by MedDRA system organ class.

The frequency is defined as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000), frequency unknown (frequency cannot be estimated from the available data).

Organ systems	Often	Infrequently	Rarely	Frequency unknown
Infections and infestations		fungal infections, including infections caused by fungi of the genus Candida; resistance of pathogenic microorganisms
Blood and lymphatic system disorders		leukopenia, eosinophilia	thrombocytopenia, neutropenia	pancytopenia, agranulocytosis, hemolytic anemia, bone marrow effects
Immune system disorders			Quincke's edema, hypersensitivity reactions (see section "Special instructions for use")	anaphylactic shock1 with symptoms such as urticaria, bronchospasm and severe wheezing; anaphylactoid shock1; angioedema (see section "Special warnings and precautions for use")
Endocrine disorders			syndrome of inappropriate antidiuretic hormone secretion (SADH)
Metabolic disorders, metabolism		anorexia	hypoglycemia, especially in patients with diabetes mellitus; hypoglycemic coma (see section "Special warnings and precautions for use")	hyperglycemia (see section "Special warnings and precautions for use")
Mental disorders*	insomnia	anxiety, confusion, nervousness	psychotic reactions (e.g. with hallucinations, paranoia), depression, agitation, sleep disturbances, nightmares, delirium	psychotic disorders with behavior threatening to the patient, including suicidal thoughts or suicide attempts (see section "Special warnings and precautions for use")
Neurological disorders*	headache, dizziness	drowsiness, tremor, dysgeusia (subjective taste disturbance)	Convulsions (see section "Special warnings and precautions for use"), paresthesia, memory impairment	sensory or sensorimotor peripheral neuropathy (see p Specifications Characteristics Active ingredient Ornidazole, Levofloxacin hemihydrate Adults Can ATC code J ANTIMIBRICANTS FOR SYSTEMIC USE; J01 ANTIBACTERIALS FOR SYSTEMIC USE; J01R COMBINED ANTIBACTERIALS; J01R A Combined antibacterials; J01R A05 Levofloxacin and ornidazole Country of manufacture Ukraine Diabetics Can Drivers It is impossible. For allergies With caution For children It is impossible. Form Infusions Method of application Injections Nursing It is impossible. Pregnant It is impossible. Producer Yuria-Pharm LLC Quantity per package 200 ml Trade name Grandazole Vacation conditions By prescription Reviews There are no reviews for this product. + Add review Write a review Grandazol solution for infusion 2.5 mg + 5 mg bottle 200 ml My mark: Continue There are no reviews for this product, be the first to leave your review. Answers & questions Add your question and we will answer as soon as possible. + Ask a question Ask a question Add your question and we will answer as soon as possible. * Your question Continue No questions about this product, be the first and ask your question. You are watched new Hit Symbicort Turbuhaler inhalation powder dosed 80 mcg/dose + 4.5 mcg/dose turbuhaler 120 doses In stock 0 1 225.50 грн. Add to Cart 851.64 грн. Add to Cart