Amikacid

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT AMIKACID (AMIKACID)

Composition:

Active substance: amikacin sulfate;

1 ml of solution contains amikacin sulfate equivalent to amikacin 250 mg;

Excipients: sodium citrate, sodium metabisulfite (E 223), sulfuric acid, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless or slightly yellowish solution.

Pharmacotherapeutic group. Antibacterials for systemic use. Aminoglycoside antibacterials. Other aminoglycosides. Amikacin.

ATC code J01G B06.

Pharmacological properties.

Pharmacodynamics.

Amikacin is a semisynthetic antibiotic of the broad-spectrum aminoglycoside group.

Mechanism of action

Amikacin exerts a bactericidal effect. By binding to the 30S subunit of microbial ribosomes, it interferes with the formation of the complex between transfer RNA and messenger RNA, blocks protein synthesis, and also disrupts bacterial cytoplasmic membranes.

In vitro spectrum of activity

Amikacin is effective in vitro against a range of Gram-negative and Gram-positive pathogenic microorganisms. Minimum inhibitory concentrations (MICs) (in mcg/mL):

a) Microorganisms susceptible to amikacin:

Amikacin does not lose activity under the influence of enzymes that inactivate other aminoglycosides and may remain active against strains of Proteus rettgeri, Serratia marcescens, and Nocardia asteroides resistant to kanamycin, gentamicin, and tobramycin.

b) Microorganisms resistant to amikacin:

Haemophilus influenzae, Streptococcus, anaerobic microorganisms – are insensitive to amikacin.

Sensitivity to amikacin can be determined using standardized methods: serial dilution method and disk diffusion method.

The following susceptibility criteria are recommended:

Pharmacokinetics.

Amikacin can be administered either as a twice- or thrice-daily regimen or as a single daily dose. With both twice-daily administration and single-dose administration, a consistent linear correlation is observed between changes in kinetic parameters and serum concentrations of amikacin and the amount of amikacin administered.

Absorption

Intramuscular administration: amikacin is rapidly absorbed following intramuscular injection.

After injection of 250 mg (3.7 mg/kg), 375 mg (5 mg/kg), and 500 mg (7.5 mg/kg), serum concentrations of 12 µg/mL, 16 µg/mL, and 21 µg/mL are observed at 1 hour, respectively. At 10 hours, the corresponding serum levels are 0.3 µg/mL, 1.2 µg/mL, and 2.1 µg/mL.

Intravenous administration: when a single dose of 500 mg (7.5 mg/kg) is administered to adults by short infusion over 30 minutes, the blood level is 38 µg/mL at the end of the infusion and 24 µg/mL, 18 µg/mL, and 0.75 µg/mL at 30 minutes, 1 hour, and 10 hours after administration, respectively.

A 30-minute infusion with a single dose of 1000 mg (15 mg/kg) results in a blood level of 77 µg/mL at the end of the infusion, and 47 µg/mL and 1 µg/mL at 1 hour and 12 hours after infusion, respectively.

The area under the concentration-time curve (AUC) following administration of 15 mg/kg amikacin ranges from 137 mg·h/L to 193 mg·h/L in adult patients.

Distribution

The volume of distribution in adults is 24 liters, approximately 28% of body weight. Protein binding ranges from 0% to 11%.

After administration of the recommended dose, therapeutic concentrations are achieved in bone, heart, gallbladder, and lung tissues, and significant concentrations are observed in urine, bile, sputum, bronchial secretions, interstitial fluid, pleural, and synovial fluids.

Like other aminoglycoside antibiotics, amikacin generally achieves low and primarily unpredictable concentrations in cerebrospinal fluid (CSF), even in the presence of meningeal inflammation.

In young children, CSF levels are approximately 10–20% of serum concentrations and may increase up to 50% in cases of meningitis.

Amikacin crosses the placental barrier, and fetal serum levels may reach 16–50% of maternal serum concentrations.

It is not known whether amikacin is excreted in breast milk. However, small amounts of other aminoglycoside antibiotics have been detected in breast milk.

Metabolism

Not metabolized.

Elimination

Eliminated by the kidneys via glomerular filtration.

With normal renal function, approximately 92% of an intramuscular dose is excreted unchanged in urine within the first 8 hours and about 98% within 24 hours (Qo=0.02). Serum clearance is 100 mL/min, and renal clearance is 94 mL/min with normal renal function.

The mean elimination half-life of amikacin in healthy volunteers is 2 hours. Even with a single daily dose of 15 mg/kg, the half-life does not change; however, it may increase to 3–4 hours in patients with concomitant disease and up to 10 hours in elderly patients.

Pharmacokinetics in special clinical situations

Patients with impaired renal function. In patients with renal insufficiency or reduced glomerular filtration rate, amikacin is eliminated significantly more slowly. Therefore, renal function should be carefully monitored and dosage adjusted as necessary.

Amikacin should not be administered as a single daily dose to patients with impaired renal function (creatinine clearance <50 mL/min): a single dose of amikacin 15 mg/kg in patients with moderate or moderately reduced renal function results in plasma concentrations of 82–95 µg/mL. Elimination constant, elimination half-life, AUC, total plasma clearance, and accumulation rate are markedly altered depending on renal function. This means that in patients with creatinine clearance <50 mL/min, particularly in those with greater renal impairment (creatinine clearance <25 mL/min), changes in pharmacokinetic parameters are pronounced, leading to prolonged drug retention in the body. This issue is independent of dose, and reducing the dose results in loss of the beneficial effect of high blood levels.

Elderly patients. In elderly patients (mean creatinine clearance 64 mL/min), the blood level of 55 µg/mL after a 30-minute infusion of 15 mg/kg decreased to 5.4 µg/mL at 12 hours. AUC after administration of 15 mg/kg amikacin increases to 255 mg·h/L in elderly patients and possibly even higher in very elderly patients.

Preclinical data

Short-term animal studies on carcinogenicity are available. Mutagenicity studies have not been performed. Amikacin did not affect fertility in animals when administered to rats at a dose 10 times higher than the human daily dose. However, fetotoxic and/or teratogenic effects have been observed with the use of aminoglycosides.

Clinical characteristics.

Indications.

Infections caused by amikacin-susceptible strains of microorganisms resistant to other aminoglycosides.

Official recommendations on the appropriate use of antibacterial medicinal products should be followed.

Contraindications.

• Renal insufficiency;
• Auditory nerve neuritis;
• Hypersensitivity to amikacin or to any other aminoglycoside antibiotic and their derivatives;
• Hypersensitivity to any of the excipients contained in the medicinal product;
• Myasthenia gravis;
• Vestibular apparatus dysfunction;
• Azotemia (residual nitrogen above 150 mg%);
• Prior treatment with ototoxic or nephrotoxic agents.

Interaction with other medicinal products and other types of interactions.

Pharmaceutically incompatible with penicillins, heparin, cephalosporins, capreomycin, amphotericin B, hydrochlorothiazide, erythromycin, nitrofurantoin, vitamin B complex, vitamin C, and potassium chloride.

Concomitant or sequential use of amikacin with other neurotoxic, ototoxic, or nephrotoxic agents should be avoided, particularly bacitracin, cisplatin, amphotericin B, cyclosporine, tacrolimus, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglycosides, due to the potential for additive effects.

Amikacin exhibits synergy when used in combination with carbenicillin, benzylpenicillin, and cephalosporins (in patients with severe chronic renal insufficiency, concomitant use with beta-lactam antibiotics may reduce the efficacy of aminoglycosides).

The risk of nephrotoxic effects increases when amikacin is used concomitantly with penicillin, cephalosporins, sulfonamides, vancomycin, methoxyflurane, enflurane, nonsteroidal anti-inflammatory drugs (NSAIDs), radiographic contrast agents, cyclosporine, cisplatin, amphotericin B, cephalothin, polymyxin, and diuretics (especially with furosemide).

Increased nephrotoxicity has been reported after concomitant parenteral administration of aminoglycoside antibiotics and cephalosporins. Concomitant use of cephalosporins may lead to elevated serum creatinine levels.

The risk of ototoxicity increases when amikacin is used together with fast-acting diuretics (furosemide and ethacrynic acid), particularly when the diuretic is administered intravenously. Diuretics may enhance the toxicity of aminoglycosides by altering antibiotic concentrations in serum and tissues. Concomitant use of furosemide and ethacrynic acid, which also have ototoxic effects, may lead to irreversible deafness.

Nalidixic acid, polymyxin B, cisplatin, and vancomycin increase the risk of ototoxicity and nephrotoxicity.

Indomethacin, phenylbutazone, and other NSAIDs, which impair renal blood flow, may slow the elimination rate of amikacin. If amikacin is administered concomitantly with intravenous indomethacin in premature infants, plasma concentrations of the drug increase, raising the risk of toxicity. Parenteral administration of indomethacin increases the risk of toxic effects of aminoglycosides (prolonged T1/2 and reduced clearance).

There is an increased risk of hypocalcemia when aminoglycosides are used concomitantly with bisphosphonates.

There is an increased risk of nephrotoxicity and possibly ototoxicity when aminoglycosides are used with platinum compounds.

Concomitant use with ethyl ether and neuromuscular blocking agents increases the risk of respiratory depression.

Amikacin potentiates the muscle relaxant effect of curare-like agents.

Amikacin is not recommended for patients under the influence of anesthetics, muscle relaxants, or patients receiving large-volume blood transfusions preserved with citrate anticoagulants, due to the risk of neuromuscular blockade and increased risk of respiratory paralysis.

Amikacin reduces the effectiveness of drugs used in the treatment of myasthenia.

Simultaneous administration of thiamine (vitamin B1) with amikacin may lead to thiamine degradation due to the reactive sulfite component of amikacin.

The antibiotic combinations amikacin + ceftazidime and amikacin + cefoperazone show the greatest additive and synergistic effect against Pseudomonas aeruginosa.

When multiple antibiotics are used, amikacin must not be mixed in the same syringe or vial with other antibacterial medicinal products.

Special precautions for use.

Prior to administering the medicinal product, the susceptibility of isolated pathogens should be determined.

Amikacin must not be used in patients with hypersensitivity to other aminoglycosides due to the risk of cross-allergy.

Caution is required when administering the drug to patients with pre-existing renal insufficiency or existing hearing or vestibular function impairment. If audiometric tests yield unsatisfactory results, the dose should be reduced or treatment discontinued.

Patients with infectious-inflammatory diseases of the urinary tract are recommended to consume large amounts of fluid.

Patients receiving parenteral aminoglycosides must be under close clinical monitoring due to the potential ototoxicity and nephrotoxicity associated with their use. The safety of prolonged treatment (more than 14 days) has not been established. Precautions regarding dosing and adequate hydration must be observed.

During treatment, renal function, auditory nerve function, and vestibular function should be monitored at least once weekly.

If therapy is expected to last 7 days or longer in patients with impaired renal function, or 10 days or longer in patients with normal renal function, an audiogram should be performed before initiating treatment and repeated during therapy. Amikacin therapy should be discontinued if patients report tinnitus, subjective hearing loss, or if subsequent audiograms show significant high-frequency hearing loss.

Neuro-/Ototoxicity

The main toxic effect of the drug following parenteral administration is its action on the VIII cranial nerve, initially manifesting as hearing loss in the high-frequency range.

Neurotoxicity, presenting as vestibular and/or bilateral ototoxicity, may occur in patients receiving aminoglycosides. The risk of ototoxic complications is significantly higher in patients with impaired renal function and in those receiving high doses or prolonged therapy (5–7 days or longer). High-frequency hearing loss usually occurs first and may only be detected by audiometric testing. Dizziness may occur, indicating vestibular damage.

Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and seizures. The risk of ototoxicity due to aminoglycoside use increases with persistently high peak or trough serum concentrations. Patients developing vestibular or cochlear damage may have no initial symptoms warning of toxic injury to the VIII cranial nerve. Complete or partial irreversible bilateral hearing loss or dizziness may occur after completion of therapy. Aminoglycoside-induced ototoxicity is typically irreversible.

Amikacin use in patients with a history of allergic reactions to aminoglycosides, or in patients with subclinical kidney or VIII cranial nerve damage caused by prior use of nephrotoxic or ototoxic agents—such as streptomycin, dihydrostreptomycin, gentamicin, tobramycin, kanamycin, dibekacin, neomycin, polymyxin B, colistin, cephaloridine, or viomycin—should be considered with caution, as toxicity may be additive. Amikacin should be administered to such patients only under medical supervision when the expected benefit outweighs the potential risk.

Concomitant administration of amikacin sulfate and potent diuretics such as ethacrynic acid derivatives, furosemide, or mannitol (especially if the diuretic is administered intravenously) may lead to irreversible hearing loss.

Patients with mitochondrial DNA mutations (particularly the A1555G mutation in the 12S rRNA gene) are at increased risk of ototoxicity, even if serum aminoglycoside levels remain within the recommended range during treatment. Alternative treatment options should be considered for such patients.

Patients with a family history of mitochondrial DNA mutations or aminoglycoside-induced hearing loss should consider alternative treatment options or undergo genetic testing prior to drug administration.

Neuromuscular blockade

Neuromuscular blockade and respiratory paralysis have been reported following parenteral administration, local instillation (such as in orthopedic or abdominal irrigation or local treatment of empyema), and even after oral administration of aminoglycosides. The possibility of respiratory paralysis should be considered when aminoglycosides are administered by any route, particularly in patients receiving anesthetics, neuromuscular blocking agents, or massive transfusions of citrate-anticoagulated blood. In cases of neuromuscular blockade, calcium salts may reverse the effect, but artificial ventilation may be required. Neuromuscular blockade and muscle paralysis have been demonstrated in laboratory animals receiving high doses of amikacin.

Amikacin must not be used in patients with myasthenia gravis. The drug should be used with caution in patients with myasthenia, Parkinsonism, or botulism (aminoglycosides may impair neuromuscular transmission, leading to further skeletal muscle weakness), dehydration, renal insufficiency, neonates (especially premature infants), and elderly patients.

Nephrotoxicity

Aminoglycosides are potentially nephrotoxic. The risk of nephrotoxicity is higher in patients with impaired renal function and when the drug is administered at high doses or for prolonged periods (such patients require daily monitoring of renal function).

Fluid and electrolyte balance should be corrected in patients prior to initiating treatment. During amikacin sulfate therapy, patients should consume adequate fluids, serum creatinine concentrations should be frequently monitored, and dosing regimens adjusted as necessary. In patients with impaired renal function, the daily dose should be reduced and/or the dosing interval extended according to serum creatinine levels to prevent drug accumulation and minimize the risk of ototoxicity. Renal functional activity should be regularly assessed. Urinalysis is required before and during treatment.

Amikacin use may alter the following laboratory parameters: serum alanine aminotransferase, aspartate aminotransferase, bilirubin, lactate dehydrogenase, alkaline phosphatase, blood urea nitrogen, creatinine, and calcium, magnesium, potassium, and sodium ions.

If signs of renal irritation appear (presence of urinary casts, albuminuria, microhematuria, leukocyturia, decreased creatinine clearance, reduced urine specific gravity, increased blood urea nitrogen, serum creatinine, or oliguria), hydration should be increased and the dose reduced. These manifestations usually resolve after completion of therapy. Monitoring of renal function is particularly important in elderly patients during aminoglycoside treatment. Dose reduction of amikacin is required in elderly patients due to decreased renal function and possible reduction in body mass, which may not be detected by routine screening tests such as blood urea nitrogen or serum creatinine.

If signs of ototoxicity (e.g., dizziness, ringing or noise in the ears, or hearing loss) or nephrotoxicity (e.g., decreased creatinine clearance, oliguria) occur, amikacin use should be discontinued or the dose reduced. Treatment should be stopped if azotemia or worsening oliguria develops.

Concomitant and/or sequential systemic, oral, or topical use of other neurotoxic or nephrotoxic medicinal products—such as bacitracin, cisplatin, amphotericin B, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglycosides—should be avoided. Other factors that may increase the risk of toxicity include advanced age and dehydration.

Other

Two aminoglycosides must not be administered simultaneously, nor should one aminoglycoside be replaced by another if the first has been used for 7–10 days. A repeat course should not be initiated earlier than 4–6 weeks after the previous course.

In the absence of positive clinical response, the development of microbial resistance should be considered. In such cases, treatment should be discontinued and appropriate therapy initiated.

Aminoglycosides are rapidly and almost completely absorbed following local application, except in the urinary bladder, due to surgical procedures. Cases of irreversible hearing loss, renal failure, and fatal outcomes due to neuromuscular blockade have been reported following application of aminoglycoside preparations to both small and large surgical areas.

Aminoglycosides should be used with caution in premature and full-term neonates due to their immature renal function and, consequently, prolonged elimination half-life of these drugs.

Cases of macular infarction, potentially leading to complete vision loss, have been reported following intravitreal injection (injection into the eye) of amikacin.

The medicinal product contains sodium metabisulfite, which may cause allergic-type reactions, including anaphylactic symptoms and asthma attacks of varying severity, particularly in patients with bronchial asthma.

When used concomitantly with cephalosporins, administration at different sites (for intramuscular injection) with an interval of at least 1 hour is recommended.

2 mL of the medicinal product contains less than 1 mmol (23 mg) of sodium, i.e., it is practically sodium-free.

4 mL of the medicinal product contains less than 1.3 mmol (29.86 mg) of sodium; therefore, caution is advised when administering the drug to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Since amikacin crosses the placenta and may exert ototoxic and nephrotoxic effects on the fetus, the drug is contraindicated during pregnancy.

As amikacin passes into breast milk in low concentrations and may affect the intestinal flora of breastfed infants, breastfeeding should be discontinued during amikacin therapy.

Ability to affect reaction speed when driving or operating machinery.

The medicinal product generally does not affect reaction speed; however, the potential occurrence of adverse effects on the central nervous system and sensory organs—such as drowsiness, impaired neuromuscular transmission, motor incoordination, and dizziness—should be considered.

Administration and Dosage.

Administer amikacin intramuscularly or intravenously. The usual dose for children aged 12 years and older and adults is 5 mg/kg body weight every 8 hours or 7.5 mg/kg body weight every 12 hours. The maximum dose for adults is 15 mg/kg body weight per day. In severe cases and infections caused by Pseudomonas, the daily dose should be divided into 3 administrations. The maximum daily dose is 1.5 g. The maximum total dose for the entire course should not exceed 15 g. The duration of treatment is usually 3–7 days for intravenous administration and 7–10 days for intramuscular administration.

For premature newborns, administer an initial dose of 10 mg/kg body weight, followed by 7.5 mg/kg body weight every 18–24 hours for 7–10 days. For full-term newborns and children under 12 years of age, administer an initial dose of 10 mg/kg body weight, followed by 7.5 mg/kg body weight every 12 hours for 7–10 days.

In patients with impaired renal function, the daily dose should be reduced and/or the intervals between doses increased. The dose should be adjusted according to plasma creatinine levels and patient body weight. The dosing interval can be calculated by multiplying the plasma creatinine level by 9; for example: if the creatinine level is 2 mg/dL, the drug should be administered every 18 hours.

Amikacin should be administered to adults and children by intravenous infusion using a volume of fluid sufficient for a slow infusion over 60–90 minutes (at a rate of 50 drops per minute), and for newborns, over 1–2 hours. The concentration of amikacin solution for intravenous administration should not exceed 5 mg/mL. Intravenous injection of amikacin should be performed very slowly (over 2–7 minutes). The solution for parenteral administration should be prepared immediately before use and used promptly after preparation.

For intravenous administration, the following diluents may be used: 0.9% sodium chloride solution, 5% glucose solution, Ringer's lactate solution for injection containing glucose (5%).

Children.

The drug should be used with caution in premature and full-term infants due to the risk of prolonged elimination of aminoglycosides caused by immature excretory systems, which may lead to toxic effects.

Overdose.

Overdose may result in ototoxic and nephrotoxic effects of the drug and signs of neuromuscular blockade: tinnitus, hearing loss, auditory disturbances, skin rashes, headache, dizziness, chills, paresthesia, decreased kidney function (up to renal failure), respiratory depression or paralysis, and toxic reactions (ataxia, urinary disorders, thirst, loss of appetite, nausea, vomiting).

Treatment: to reverse neuromuscular blockade and its consequences—hemodialysis or peritoneal dialysis; anticholinesterase agents, calcium salts, artificial ventilation of the lungs, and other symptomatic and supportive therapy. Amikacin levels should be reduced by continuous arteriovenous hemofiltration.

Adverse Reactions

The list of adverse reactions is presented by organ system classes, using preferred MedDRA terms and frequency categories: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000), very rare (<1/10,000), and frequency not known (cannot be estimated based on available data).

Infections and infestations: uncommon – superinfection or colonization with resistant bacteria or yeasts.

Blood and lymphatic system disorders: rare – eosinophilia, anemia, leukopenia, granulocytopenia, thrombocytopenia.

Gastrointestinal disorders: rare – nausea, vomiting, diarrhea.

Endocrine and metabolic disorders: uncommon – hypomagnesemia.

Skin and subcutaneous tissue disorders: skin rashes, pruritus, urticaria, skin hyperemia, Quincke's edema.

Immune system disorders: frequency not known – anaphylactic shock, hypersensitivity reactions, anaphylactoid reactions, anaphylactic reactions.

Cardiovascular system disorders: rare – hypotension, tachycardia, myocarditis.

Nervous system disorders: headache, drowsiness, neurotoxic effects (muscle twitching, numbness, tingling, epileptic seizures), possible hearing loss, vestibular disorders, dizziness, paresthesia, tremor, convulsions, encephalopathy; in isolated cases – neuromuscular conduction disturbances, possible development of neuromuscular blockade (muscle paralysis, respiratory depression).

Sensory organ disorders: ototoxicity (deafness, hearing loss, tinnitus, vestibular labyrinthine disorders, partially reversible or irreversible deafness), toxic effects on the vestibular apparatus (movement incoordination, dizziness, nausea, vomiting).

Eye disorders: blindness, retinal infarction*.

Hepatobiliary disorders: liver function abnormalities (increased liver transaminase activity, hyperbilirubinemia), hepatomegaly, liver necrosis.

Renal and urinary disorders: renal function impairment (oliguria, proteinuria, microhematuria, albuminuria, cylindruria, hyperazotemia, hematuria, increased creatinine levels); rare – acute necrosis, interstitial nephritis, acute renal failure, toxic nephropathy, azotemia, altered erythrocytes in urine, presence of leukocytes in urine.

Respiratory, thoracic and mediastinal disorders: apnea, bronchospasm.

Musculoskeletal and connective tissue disorders: arthralgia, muscle cramps.

General disorders and administration site conditions: frequency not known – injection site pain and thrombophlebitis, splenomegaly; rare – hyperthermia.

*Amikacin is not intended for intravitreal use. Cases of blindness and retinal infarction following intravitreal administration (injection into the eye) of amikacin have been reported.

Sodium metabisulfite, an ingredient of the medicinal product, may cause severe hypersensitivity reactions and bronchospasm.

All aminoglycosides may cause ototoxicity, nephrotoxicity, and neuromuscular blockade. These toxic effects occur more frequently in patients with renal insufficiency, in patients receiving other ototoxic or nephrotoxic medicinal products, and in patients receiving treatment for longer durations and/or at higher doses than recommended.

Renal function impairment is usually reversible after discontinuation of the drug.

Toxic effects on the eighth cranial nerve may lead to hearing loss and impaired coordination. Amikacin primarily affects auditory function. Cochlear damage includes high-frequency hearing loss, which may be detected by audiometric testing and precedes clinical manifestations of hearing loss (see section "Special precautions").

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after medicinal product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions.

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze. Keep out of reach of children.

Incompatibilities

Amikacin sulfate solution should not be directly mixed with other aminoglycosides, penicillins, heparin, cephalosporins, capreomycin, amphotericin B, thiopental, hydrochlorothiazide, erythromycin, nitrofurantoin, vitamins B and C, or potassium chloride. If administration of two medicinal products is necessary, they should be given separately and sequentially. When multiple antibiotics are used, amikacin must not be mixed in the same syringe or vial with other antibacterial agents.

Packaging

2 ml or 4 ml in vials; 1 vial per cardboard box.

2 ml or 4 ml in vials; 5 vials in a blister pack; 2 blister packs per cardboard box.

Prescription status. Prescription only.

Manufacturer. Limited liability company "Novofarm-Biosyntez".

Manufacturer's address and place of business.

38 Zhитомirska Street, city of Zvyahel, Zvyahel district, Zhytomyr region, 11700, Ukraine.