Vingard (Solution) Instructions for Use

Marketing Authorization Holder

R-Pharm JSC (Russia)

Manufactured By

Nang Kuang Pharmaceutical, Co. Ltd. (China)

Or

Pharmland SP, LLC (Republic of Belarus)

Packaging and Quality Control Release

ORTAT, JSC (Russia)

ATC Code

J01MB08 (Nemonoxacin)

Active Substance

Nemonoxacin (Rec.INN registered by WHO)

Dosage Form

Vingard

Solution for infusion 2 mg/1 ml: bag 250 ml 1 pc.

Dosage Form, Packaging, and Composition

Solution for infusion in the form of a transparent liquid from yellow to greenish-yellow in color.

* 2.7704 mg of nemonoxacin malate hemihydrate is equivalent to 2 mg of nemonoxacin free base.

Excipients: sodium chloride – 9 mg, sodium hydroxide – to adjust pH to 3.8-6.0, water for injections – to 1 ml.

250 ml – polymeric bags^× (1) with a connecting port and cap – secondary polymeric bags (1) – consumer bags made of polymeric materials^×.

^× a self-adhesive label is affixed to the bag.

Clinical-Pharmacological Group

Antibacterial drug of the quinoline group

Pharmacotherapeutic Group

Antibacterial agent – quinolone derivative

Pharmacological Action

Antimicrobial agent from the quinolone group, does not contain fluorine. In vitro studies have shown that Nemonoxacin is effective against many species of gram-negative and gram-positive bacteria. The mechanism of action of nemonoxacin is based on the inhibition of DNA gyrase and topoisomerase IV, which are necessary for the replication, transcription, repair, and recombination of bacterial DNA.

Streptococcus pneumoniae strains with mutant DNA gyrase and topoisomerase (double mutation) are resistant to most fluoroquinolone antibiotics. In vitro studies have shown that Nemonoxacin can be used to treat infections caused by Streptococcus pneumoniae when an appropriate concentration of the active substance sufficient to inhibit these two enzyme systems is achieved.

The minimum inhibitory concentration of nemonoxacin in vitro for bacterial strains with a double mutation is still within the concentration range effective against common bacteria.

The main mechanism of resistance to fluoroquinolones is due to mutations in DNA gyrase and/or type IV topoisomerase. The mechanism of resistance to nemonoxacin is similar to the mechanism of resistance to fluoroquinolone antibiotics and involves the development of multi-step mutations and changes in the active efflux system.

The frequency of spontaneous mutation development is very low (from < 10^-10 to 10^–6). However, since the binding site of nemonoxacin on the target enzymes differs from that of fluorinated quinolone antibiotics, currently, based on the available limited data, there is no information on the presence of cross-resistance between nemonoxacin and antibiotics of the fluoroquinolone group.

Further observational studies under conditions of clinical use are necessary to clarify the possibility of cross-resistance occurrence.

The mechanism of action of antibiotics of the quinolone group (including Nemonoxacin) differs from the mechanism of action of antibiotics of the macrolide group, beta-lactam antibiotics, aminoglycoside antibiotics, or tetracycline antibiotics, therefore microorganisms resistant to these types of antibiotics may be sensitive to nemonoxacin and other antibiotics of the quinolone group.

Currently, there is no information on cross-resistance between nemonoxacin and the aforementioned classes of antibiotics. In in vitro studies, Nemonoxacin has shown efficacy against some strains resistant to macrolides and penicillin.

Nemonoxacin is active against gram-positive bacteria: Streptococcus pneumoniae (including penicillin-sensitive, intermediate, and resistant strains), Staphylococcus aureus (including methicillin-sensitive and resistant strains), Streptococcus pyogenes; gram-negative bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Moraxella catarrhalis; atypical bacteria: Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila.

Pharmacokinetics

After IV infusion of nemonoxacin to healthy volunteers, the concentration increases with increasing dose. C_max in blood plasma is reached 1-2 hours after administration. C_ss is achieved when nemonoxacin is applied once/day for 3-5 days. With a single administration of nemonoxacin at a dose of 500 mg or 750 mg, the average V_d is about 200 L, indicating that the active substance is well distributed in various body tissues.

In vitro, the binding of nemonoxacin to plasma proteins is 44-48%. Nemonoxacin in the human body undergoes slow metabolism with the formation of glucuronic acid conjugates. After oral administration or IV administration, less than 2% of nemonoxacin glucuronide is detected in the urine. Nemonoxacin is excreted mainly by the kidneys.

After a single oral intake or IV infusion of nemonoxacin to healthy volunteers, 70% of the dose is excreted in the urine and 6% in the feces unchanged. T_1/2 is about 11 hours. Renal clearance is 8 L/h.

Indications

Treatment of community-acquired pneumonia in adults (over 18 years of age) caused by microorganisms sensitive to nemonoxacin.

ICD codes

Dosage Regimen

Administer intravenously as a slow infusion over a duration of at least 90 minutes.

The standard dose is 500 mg administered once daily.

Determine the total duration of therapy based on the severity of the infection and the patient’s clinical response.

The recommended treatment course is 7 to 14 days.

Do not use in patients with moderate or severe renal impairment (CrCl < 60 ml/min).

No dose adjustment is required for patients with mild renal impairment or for elderly patients (60-79 years).

Initiate therapy based on susceptibility testing; adjust regimen when results become available.

Adverse Reactions

Blood and lymphatic system disorders common – decrease in the number of leukocytes in the blood, neutropenia.

Nervous system disorders common – dizziness; frequency unknown – headache.

Digestive system disorders common – nausea, increased activity of ALT, AST, GGT; frequency unknown – abdominal discomfort, diarrhea.

Cardiovascular system disorders common – QT interval prolongation on ECG.

Contraindications

Hypersensitivity to nemonoxacin; history of tendon lesions associated with the use of quinolones/fluoroquinolones; pseudoparalytic myasthenia; moderate and severe renal failure and end-stage renal disease (CrCl < 60 ml/min); epilepsy; impaired liver function; pregnancy, breastfeeding period; children and adolescents under 18 years of age.

With caution

Increased risk of developing tendinitis and tendon rupture (patients over 60 years of age, patients receiving corticosteroids, patients after organ transplantation); history of psychosis or mental illness; predisposition to the development of seizures or history of seizures; concomitant use of drugs that lower the seizure threshold of the brain, such as theophylline; neuropathy; presence of risk factors for QT interval prolongation; uncorrected electrolyte disturbances (with hypokalemia and with hypomagnesemia); heart disease (heart failure, myocardial infarction, bradycardia); congenital long QT syndrome; concomitant use of drugs that can prolong the QT interval (class I A antiarrhythmic drugs (quinidine and procainamide) and class III; elderly patients; female patients.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Throughout the period of nemonoxacin use, women of childbearing potential and men should use highly effective methods of contraception.

Use in Hepatic Impairment

Contraindicated for use in impaired liver function.

Use in Renal Impairment

There is no need to adjust the dose of nemonoxacin for patients with mild renal failure. Patients with moderate to severe renal failure and patients with end-stage renal failure are not recommended to use Nemonoxacin.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Dose adjustment in elderly patients (60-79 years) is not required.

Special Precautions

To reduce the risk of drug-resistant bacterial strains and ensure treatment efficacy, Nemonoxacin is indicated for the treatment of infections caused by bacteria only with confirmed or suspected sensitivity to it. Before starting treatment, it is necessary to isolate and identify the causative agents of the infection, and determine their sensitivity to antibacterial drugs (including Nemonoxacin).

Treatment with nemonoxacin can be started before obtaining the results of the above studies, with subsequent correction if necessary. If data from such studies are not available, empirical treatment should be carried out in accordance with local epidemiological data and information on the sensitivity of pathogens.

In addition, treatment with nemonoxacin requires regular bacteriological studies to timely detect the development of resistance. In the absence of evidence confirming the presence of a bacterial infection, the prescription of nemonoxacin will not benefit the patient and may increase the risk of developing bacterial resistance to this agent.

During the use of drugs from the quinolone group, tendinitis and tendon ruptures (especially the Achilles tendon) may develop. This complication can occur very quickly – within 48 hours from the start of taking the drug, or may occur several months after stopping the drug.

The risk of tendinitis and tendon ruptures increases in the elderly, as well as in individuals with impaired renal function, in patients after transplantation of various organs, and in patients simultaneously taking corticosteroids. Therefore, during therapy with nemonoxacin, the concomitant use of corticosteroids should be avoided.

No cases of tendinitis and tendon rupture after the use of nemonoxacin have been registered. Patients should be advised to rest if they complain of pain, swelling, inflammation, or if a tendon rupture is diagnosed, and to consult a doctor. If tendinitis or tendon rupture is suspected, treatment with nemonoxacin should be stopped immediately and appropriate treatment of the affected tendon should be started, for example, by ensuring sufficient immobilization.

Although psychotic reactions during the use of nemonoxacin have not been recorded, careful monitoring is required. If these symptoms occur, the patient should consult a doctor, it is recommended to discontinue Nemonoxacin and start appropriate treatment.

Diarrhea that develops during or after treatment with nemonoxacin, especially severe, persistent and/or bloody, may be a symptom of pseudomembranous colitis caused by Clostridium difficile. If pseudomembranous colitis is suspected, treatment with nemonoxacin should be stopped immediately and specific antibiotic therapy should be started immediately. Drugs that inhibit intestinal peristalsis are contraindicated.

No cases of peripheral neuropathy after the use of nemonoxacin have been noted. In patients receiving fluoroquinolone therapy, cases of sensory and sensorimotor peripheral neuropathy have been reported, the onset of which can be rapid. If a patient develops symptoms of neuropathy, the use of nemonoxacin should be discontinued. This minimizes the possible risk of irreversible changes. Patients should be informed of the need to report any symptoms of neuropathy to their healthcare provider. Fluoroquinolones should not be prescribed to patients with a history of clinical cases indicating peripheral neuropathy.

According to epidemiological studies, an increased risk of aortic aneurysm and aortic dissection after the use of fluoroquinolones has been reported, especially in elderly patients. In this regard, these drugs should be used only after a careful assessment of the benefit-risk ratio and consideration of other treatment options in patients with a family history of aortic aneurysm or congenital heart valve defect, or in patients with a diagnosed aortic aneurysm.

No cases of hyperglycemia and hypoglycemia after the use of nemonoxacin have been noted. However, cases of hyperglycemia and hypoglycemia have been observed with the use of fluoroquinolones, more often in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (e.g., glibenclamide) or insulin. When using the drug in such patients, the risk of developing hypoglycemia, up to hypoglycemic coma, increases. Patients should be informed about the symptoms of hypoglycemia (confusion, dizziness, increased appetite, headache, nervousness, palpitations or rapid pulse, pale skin, sweating, tremors, weakness). If a patient develops hypoglycemia, it is necessary to immediately stop treatment with nemonoxacin and begin appropriate therapy. In these cases, it is recommended to switch to therapy with another antibiotic, if possible. When conducting treatment with nemonoxacin in elderly patients and in patients with diabetes mellitus, careful monitoring of blood glucose concentration is recommended.

To prevent the development of photosensitivity, patients are not recommended to be exposed to strong sunlight or artificial ultraviolet radiation (for example, visiting a solarium) during treatment and for 48 hours after the end of treatment with nemonoxacin.

As with the use of other antibiotics, the use of nemonoxacin, especially for a long time, can lead to increased proliferation of microorganisms (bacteria and fungi) resistant to it, which can cause changes in the normal human microflora. As a result, there is an increased risk of developing superinfection. Therefore, during treatment, it is necessary to conduct a repeated assessment of the patient’s condition and, in case of superinfection development during treatment, appropriate measures should be taken.

Effect on ability to drive vehicles and operate machinery

Such side effects of nemonoxacin as dizziness, insomnia may reduce psychomotor reactions and the ability to concentrate. Patients who experience these adverse reactions are not recommended to drive vehicles and engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

In vitro studies have shown that Nemonoxacin is a substrate of P-glycoprotein.

According to data on the use of fluoroquinolones, potentiation of the action of the indirect anticoagulant warfarin is possible. Therefore, with the simultaneous use of warfarin or its derivatives and nemonoxacin, regular monitoring of blood coagulation parameters is necessary.

In clinical studies investigating the simultaneous use of nemonoxacin and hypoglycemic drugs (insulin, sitagliptin, pioglitazone, acarbose, glipizide, glimepiride, glibenclamide, gliclazide, rosiglitazone, repaglinide and metformin), no adverse reactions associated with changes in blood glucose levels occurred. It has been reported that in patients simultaneously receiving quinolones and hypoglycemic agents, hyperglycemia and hypoglycemia may be noted. With simultaneous use, blood glucose levels should be monitored.

If symptomatic hyperglycemia or hypoglycemia occurs, the drug should be discontinued immediately and appropriate treatment should be started immediately.

According to available data, the combined use of NSAIDs and fluoroquinolones may increase the risk of CNS stimulation and convulsive seizures.

It has been shown that Nemonoxacin has a slight effect on the pharmacokinetics of theophylline. Theophylline had a slight effect on the pharmacokinetics of nemonoxacin. The concentration or exposure of nemonoxacin in blood plasma did not change significantly. Thus, the concentration of theophylline should be monitored and its dose adjusted when used concomitantly with nemonoxacin.

Concomitant use of fluoroquinolones with cyclosporine increases the concentration of cyclosporine in blood plasma. Since relevant studies of nemonoxacin have not been conducted, it is not recommended to use it simultaneously with cyclosporine.

During clinical studies, healthy volunteers took probenecid 1 hour before, 12 and 24 hours after taking nemonoxacin. The renal clearance of nemonoxacin decreased by approximately 23.7%, AUC increased by approximately 25.4%. Caution is required when used concomitantly with probenecid and monitoring of the patient’s condition.

It has been reported that the use of fluoroquinolones can lead to a false-positive result of a urine screening test for opiates. More specific methods should be used to confirm positive opiate tests. Relevant studies of nemonoxacin have not been conducted, but it is recommended to take these data into account.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.