Ivacyn (Solution) Instructions for Use

Marketing Authorization Holder

Claris Lifesciences, Ltd. (India)

ATC Code

J01MA12 (Levofloxacin)

Active Substance

Levofloxacin (Rec.INN WHO registered)

Dosage Form

Ivacyn

Solution for infusion 500 mg/100 ml: bottle 1 pc.

Dosage Form, Packaging, and Composition

100 ml – polyethylene bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Antimicrobial agent – fluoroquinolone

Pharmacological Action

Fluoroquinolone, a broad-spectrum antimicrobial bactericidal agent. It blocks DNA gyrase (topoisomerase II) and topoisomerase IV, disrupts DNA supercoiling and cross-linking of breaks, inhibits DNA synthesis, and causes profound morphological changes in the cytoplasm, cell wall, and membranes of bacteria.

Levofloxacin is active in vivo and in vitro against the following microorganisms.

Aerobic gram-positive microorganisms: Corynebacterium diphtheriae, Enterococcus spp. (including Enterococcus faecalis), Listeria monocytogenes, Staphylococcus spp. (leukotoxin-containing and coagulase-negative methicillin-sensitive / moderately sensitive strains), including Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains); Streptococcus spp. groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-sensitive/moderately sensitive/resistant strains), Streptococcus pyogenes, Streptococcus spp. viridans group (penicillin-sensitive/resistant strains).

Aerobic gram-negative microorganisms: Acinetobacter spp. (including Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp. (including Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampicillin-sensitive/resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae), Moraxella catarrhalis (beta-lactamase-producing and non-producing strains), Morganella morganii, Neisseria gonorrhoeae (penicillinase-producing and non-producing strains), Neisseria meningitidis, Pasteurella spp. (including Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa), Serratia spp. (including Serratia marcescens), Salmonella spp.

Anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterium spp., Veilonella spp.

Other microorganisms: Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Mycobacterium spp. (including Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

Moderately sensitive microorganisms (minimum inhibitory concentration more than 4 mg/l)

Aerobic gram-positive microorganisms: Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis (methicillin-resistant strains), Staphylococcus haemolyticus (methicillin-resistant strains).

Aerobic gram-negative microorganisms: Burkholderia cepacia, Campylobacter jejuni, Campylobacter coli.

Anaerobic microorganisms: Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.

Resistant microorganisms (minimum inhibitory concentration more than 8 mg/l)

Aerobic gram-positive microorganisms: Corynebacterium jeikeium, Staphylococcus aureus (methicillin-resistant strains), other Staphylococcus spp. (coagulase-negative methicillin-resistant strains).

Aerobic gram-negative microorganisms: Alcaligenes xylosoxidans.

Other microorganisms: Mycobacterium avium.

Pharmacokinetics

After IV infusion of 500 mg over 60 min, C_max is about 6 µg/ml. With single and multiple IV administration, the apparent V_d after administration of the same dose is 89-112 L.

Plasma protein binding is 30-40%. It penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, genitourinary system organs, polymorphonuclear leukocytes, alveolar macrophages.

A small part is oxidized and/or deacetylated in the liver.

Renal clearance is 70% of total clearance. T_1/2 is 6-8 hours. It is excreted from the body mainly by the kidneys through glomerular filtration and tubular secretion. Less than 5% of levofloxacin is excreted as metabolites. 70% is excreted unchanged by the kidneys within 24 hours and 87% within 48 hours.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to levofloxacin.

• Lower respiratory tract infections (exacerbations of chronic bronchitis, community-acquired pneumonia);
• Acute maxillary sinusitis;
• Uncomplicated urinary tract infections;
• Complicated urinary tract infections (including acute pyelonephritis);
• Skin and soft tissue infections (suppurated atheromas, abscess, boils);
• Septicemia/bacteremia;
• Chronic bacterial prostatitis;
• Intra-abdominal infection;
• Complex therapy of drug-resistant forms of tuberculosis.

ICD codes

Dosage Regimen

The solution for infusion is administered intravenously by drip. The duration of IV infusion of 500 mg of levofloxacin (100 ml of infusion solution) should be at least 60 minutes. Doses are determined by the nature and severity of the infection, as well as the sensitivity of the suspected pathogen.

For patients with normal renal function (creatinine clearance > 50 ml/min) the following dosing regimen is recommended.

Exacerbation of chronic bronchitis: 250-500 mg of levofloxacin once a day for 7-10 days;

Community-acquired pneumonia: 500 mg of levofloxacin 1-2 times a day for 7-14 days;

Acute maxillary sinusitis: 500 mg of levofloxacin once a day for 10-14 days;

Uncomplicated urinary tract infections: 250 mg of levofloxacin once a day for 3 days;

Complicated urinary tract infections (including acute pyelonephritis): 250 mg of levofloxacin once a day for 7-10 days;

Skin and soft tissue infections: 500 mg of levofloxacin twice a day for 7-14 days;

Septicemia/bacteremia: 500 mg of levofloxacin 1-2 times a day for 10-14 days;

Chronic bacterial prostatitis: 500 mg of levofloxacin once a day for 28 days;

Intra-abdominal infection: 500 mg of levofloxacin once a day for 7-14 days (in combination with antibacterial drugs acting on anaerobic flora);

Complex therapy of drug-resistant forms of tuberculosis: 500 mg of levofloxacin 1-2 times a day for up to 3 months.

For patients with impaired renal function (creatinine clearance < 50 ml/min) the following dosing regimen is recommended.

No additional doses are required after hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

No dose adjustment is required in case of hepatic impairment, since Levofloxacin is metabolized in the liver to a small extent.

Depending on the patient’s condition, after several days of treatment, it is possible to switch from IV drip administration to oral administration of the same dose of the drug in the form intended for oral administration.

Adverse Reactions

From the digestive system: nausea, vomiting, diarrhea (including bloody), indigestion, decreased appetite, abdominal pain, pseudomembranous colitis, increased activity of “liver” transaminases, hyperbilirubinemia, hepatitis, dysbacteriosis.

From the cardiovascular system: decreased blood pressure, vascular collapse, tachycardia, QT interval prolongation, atrial fibrillation.

From the metabolism: hypoglycemia (increased appetite, increased sweating, tremors, nervousness), hyperglycemia.

From the nervous system: headache, dizziness, weakness, drowsiness, insomnia, anxiety, paresthesia, fear, hallucinations, confusion, depression, movement disorders, convulsions.

From the sensory organs: visual, hearing, smell, taste and tactile sensitivity disorders.

From the musculoskeletal system: arthralgia, muscle weakness, myalgia, tendon rupture, tendinitis, rhabdomyolysis.

From the urinary system: hypercreatininemia, interstitial nephritis, acute renal failure.

From the hematopoietic organs: eosinophilia, hemolytic anemia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, pancytopenia, hemorrhages.

Allergic reactions: itching and redness of the skin, swelling of the skin and mucous membranes, urticaria, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), bronchospasm, anaphylactic shock, allergic pneumonitis, vasculitis.

Other: asthenia, exacerbation of porphyria, photosensitivity, persistent fever, development of superinfection.

Local reactions: pain, redness at the injection site, phlebitis.

Contraindications

Hypersensitivity to levofloxacin, any other component of the drug or other drugs from the fluoroquinolone group, epilepsy, tendon damage during previous treatment with quinolones, pregnancy, lactation, childhood and adolescence (under 18 years).

With caution: in elderly persons due to the high probability of concomitant renal function impairment, in glucose-6-phosphate dehydrogenase deficiency.

Use in Pregnancy and Lactation

Contraindicated: pregnancy, lactation period.

Use in Hepatic Impairment

No dose adjustment is required in case of hepatic impairment, since Levofloxacin is metabolized in the liver to a small extent.

Use in Renal Impairment

Dose adjustment is recommended for patients with impaired renal function (creatinine clearance < 50 ml/min).

Pediatric Use

Contraindicated: childhood and adolescence (under 18 years).

Geriatric Use

With caution: in elderly persons due to the high probability of concomitant renal function impairment.

Special Precautions

After normalization of body temperature, it is recommended to continue treatment for at least 48-72 hours. During treatment, it is necessary to avoid solar and artificial UV radiation to avoid skin damage (photosensitivity).

If signs of tendinitis, pseudomembranous colitis, or allergic reactions appear, Levofloxacin should be discontinued immediately.

It should be borne in mind that in patients with a history of brain damage (stroke, severe trauma), seizures may develop, and in glucose-6-phosphate dehydrogenase deficiency, there is a risk of hemolysis.

Effect on ability to drive vehicles and mechanisms. During the treatment period, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: manifest mainly from the central nervous system (confusion, dizziness, impaired consciousness and convulsions of the epileptic type). In addition, gastrointestinal disorders (for example, nausea) and erosive lesions of the mucous membranes of the gastrointestinal tract, QT interval prolongation may be noted.

Treatment: symptomatic. Dialysis is ineffective. A specific antidote is unknown.

Drug Interactions

Levofloxacin increases the T_1/2 of cyclosporine.

Non-steroidal anti-inflammatory drugs, theophylline increase the risk of seizures.

Taking glucocorticosteroids increases the risk of tendon rupture.

Cimetidine and drugs that block tubular secretion slow down the excretion of levofloxacin.

The solution for infusion is compatible with 0.9% sodium chloride solution, 5% dextrose solution, 2.5% Ringer’s solution with dextrose, combined solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).

It should not be mixed with heparin and solutions with an alkaline reaction (for example, sodium bicarbonate solution).

In patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, hypo- and hyperglycemic conditions are possible during the use of levofloxacin, so it is recommended to monitor blood glucose concentration. Levofloxacin enhances the anticoagulant activity of warfarin.

Storage Conditions

In a dry place protected from light at a temperature not exceeding 25°C (77°F). Do not freeze. Keep out of reach of children.

Shelf Life

Shelf life. 2 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

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.