Hileflox (Tablets) Instructions for Use

Marketing Authorization Holder

Higlance Laboratories Pvt. Ltd. (India)

Contact Information

HIGLANCE LABORATORIES (India)

ATC Code

J01MA12 (Levofloxacin)

Active Substance

Levofloxacin (Rec.INN registered by WHO)

Dosage Forms

	Hileflox	Film-coated tablets, 250 mg: 3, 5, 10, 30, 50, 100, 500 or 1000 pcs.
		Film-coated tablets, 500 mg: 5, 10, 50, 100, 500 or 1000 pcs.
		Film-coated tablets, 750 mg: 5, 10, 50, 100, 500 or 1000 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets from light orange to orange in color, round, biconvex; on the break – a core from white with a yellowish tint to yellow.

Excipients: corn starch, microcrystalline cellulose, povidone K30, methylparaben, propylparaben, purified talc, magnesium stearate, sodium carboxymethyl starch.

Film coating composition: hypromellose, purified talc, macrogol 6000, titanium dioxide, sunset yellow FCF dye.

3 pcs. – blisters (1) – cardboard packs.
3 pcs. – blisters (10) – cardboard packs.
5 pcs. – blisters (1) – cardboard packs.
5 pcs. – blisters (2) – cardboard packs.
5 pcs. – blisters (10) – cardboard packs.
10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.
100 pcs. – polymer bags (1) – plastic jars.
500 pcs. – polymer bags (1) – plastic jars.
1000 pcs. – polymer bags (1) – plastic jars.

Film-coated tablets from light orange to orange in color, oval, biconvex, with a score on one side; on the break – a core from white with a yellowish tint to yellow.

Excipients: corn starch, microcrystalline cellulose, povidone K30, methylparaben, propylparaben, purified talc, magnesium stearate, sodium carboxymethyl starch.

Film coating composition: hypromellose, purified talc, macrogol 6000, titanium dioxide, sunset yellow FCF dye.

5 pcs. – blisters (1) – cardboard packs.
5 pcs. – blisters (10) – cardboard packs.
10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.
100 pcs. – polymer bags (1) – plastic jars.
500 pcs. – polymer bags (1) – plastic jars.
1000 pcs. – polymer bags (1) – plastic jars.

Film-coated tablets from light orange to orange in color, oval, biconvex, with a score on one side; on the break – a core from white with a yellowish tint to yellow.

Excipients: corn starch, microcrystalline cellulose, povidone K30, methylparaben, propylparaben, purified talc, magnesium stearate, sodium carboxymethyl starch.

Film coating composition: hypromellose, purified talc, macrogol 6000, titanium dioxide, sunset yellow FCF dye.

5 pcs. – blisters (1) – cardboard packs.
5 pcs. – blisters (10) – cardboard packs.
10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.
100 pcs. – polymer bags (1) – plastic jars.
500 pcs. – polymer bags (1) – plastic jars.
1000 pcs. – polymer bags (1) – plastic jars.

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Systemic antibacterial agents; quinolone derivatives; fluoroquinolones

Pharmacological Action

Levofloxacin is a synthetic broad-spectrum fluoroquinolone. It inhibits DNA gyrase (topoisomerase II) and topoisomerase IV, disrupts DNA supercoiling and cross-linking of breaks, suppresses DNA synthesis, and causes profound morphological changes in the cytoplasm, cell wall, and membranes of susceptible microorganisms.

Levofloxacin is active against 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 methicillin-sensitive strains of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus spp. (including strains of Staphylococcus groups C and G, Streptococcus agalactiae, Streptococcus pyogenes, penicillin-sensitive/moderately sensitive/resistant strains of Streptococcus pneumoniae, penicillin-sensitive/resistant strains of Streptococcus group viridans); 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 spp. (including Haemophilus ducreyi, Haemophilus parainfluenzae, ampicillin-sensitive/resistant strains of Haemophilus influenzae), Helicobacter pylori, Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae), Moraxella catarrhalis (β-lactamase-producing and non-producing strains), Morganella morganii, Neisseria spp. (including Neisseria meningitidis, penicillinase-producing and non-producing strains of Neisseria gonorrhoeae), Pasteurella spp. (including Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida), Proteus spp. (including 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., Veillonella spp.; other microorganisms: Bartonella spp., Chlamydia spp. (including Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis), Legionella pneumophila, Mycobacterium spp. (including Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma spp. (including Mycoplasma hominis, Mycoplasma pneumoniae), Rickettsia spp., Ureaplasma urealyticum.

The following are resistant to the drug: aerobic gram-positive microorganisms: Corynebacterium jeikeium, Staphylococcus spp. (coagulase-negative methicillin-resistant strains, including methicillin-resistant strains of Staphylococcus aureus); aerobic gram-negative microorganisms: Alcaligenes xylosoxidans; other microorganisms: Mycobacterium avium.

Pharmacokinetics

Absorption

After oral administration, Levofloxacin is rapidly and almost completely absorbed from the gastrointestinal tract. Food intake has little effect on the rate and extent of absorption. Bioavailability is 99%. C_max in plasma is reached in 1-2 hours and for levofloxacin in doses of 250 mg, 500 mg and 750 mg is 2.8 µg/ml, 5.2 µg/ml and 8 µg/ml, respectively.

Distribution

After a single or multiple dose, the amount of drug absorbed is directly proportional to the dose taken. C_ss in plasma is reached after 48 hours. The mean V_d of levofloxacin ranges from 74 to 112 L. Plasma protein binding is 30-40%. It penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, alveolar macrophages (concentration in lung tissues is 2-5 times higher than in plasma), genitourinary system organs, polymorphonuclear leukocytes.

Metabolism

Levofloxacin undergoes limited metabolism in the liver (oxidation and/or deacetylation).

Excretion

It is excreted from the body mainly by the kidneys via glomerular filtration and tubular secretion. T_1/2 of levofloxacin is 6-8 hours. Less than 5% of the administered dose is excreted as desmethyl and N-oxide metabolites. 70% of the orally administered dose is excreted unchanged by the kidneys within 24 hours and 87% within 48 hours. 4% of the orally administered dose is excreted via the intestines within 72 hours.

Indications

Mild to moderate infectious and inflammatory diseases caused by microorganisms sensitive to the drug:

• Lower respiratory tract infections (pneumonia, exacerbation of chronic bronchitis);
• Acute bacterial sinusitis;
• Urinary tract and kidney infections (including acute pyelonephritis);
• Skin and soft tissue infections (suppurated atheromas, abscess, furuncles);
• Chronic bacterial prostatitis;
• Intra-abdominal infection (in combination with antibacterial drugs active against anaerobic flora);
• Tuberculosis (as part of combination therapy for drug-resistant forms).

ICD codes

Dosage Regimen

Orally, before meals or between meals, without chewing, with a sufficient amount of water.

For adult patients with normal renal function (CrCl > 50 ml/min) use according to the regimens presented in the table.

* This regimen is indicated for the treatment of community-acquired pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae.

** This regimen is indicated for the treatment of urinary tract infections caused by Enterococcus faecalis, Enterobacter cloacae, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and acute pyelonephritis caused by Escherichia coli.

*** This regimen is indicated for the treatment of urinary tract infections caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and acute pyelonephritis caused by Escherichia coli, including cases with concomitant bacteremia.

Dosage adjustment of levofloxacin in adult patients with impaired renal function (CrCl < 50 ml/min).

In case of hepatic impairment, dosage adjustment is not required, because the extent of levofloxacin metabolism in the liver is limited.

Adverse Reactions

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

From the senses visual, hearing, smell, taste and tactile sensitivity disorders.

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

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

From metabolism hypoglycemia (increased appetite, increased sweating, trembling, nervousness).

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

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

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

Contraindications

• Epilepsy;
• Tendon damage associated with previous quinolone use;
• Childhood and adolescence under 18 years;
• Pregnancy;
• Lactation period;
• Hypersensitivity to levofloxacin, other fluoroquinolones or other components of the drug in the history.

With caution the drug should be prescribed to elderly patients (high probability of concomitant decreased renal function), in case of glucose-6-phosphate dehydrogenase deficiency.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

In case of hepatic impairment, dosage adjustment is not required, because the extent of levofloxacin metabolism in the liver is limited.

Use in Renal Impairment

Dosage adjustment of levofloxacin in adult patients with impaired renal function (CrCl < 50 ml/min).

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

With caution the drug should be prescribed to elderly patients (high probability of concomitant decreased renal function).

Special Precautions

After normalization of body temperature, it is recommended to continue treatment for at least 48-72 hours.

Levofloxacin should be taken at least 2 hours before or 2 hours after taking magnesium/aluminum antacids, or sucralfate, or other drugs containing calcium, iron, or zinc.

Due to possible photosensitivity, during treatment and for 5 days after completion of treatment with levofloxacin, exposure to sunlight and artificial ultraviolet radiation should be avoided. If phototoxicity develops, treatment with the drug should be discontinued.

If signs of tendinitis and pseudomembranous colitis appear, Levofloxacin should be immediately discontinued.

It should be borne in mind that in patients with a history of brain lesions (stroke, severe trauma), the development of seizures is possible.

In case of glucose-6-phosphate dehydrogenase deficiency, there is a risk of hemolytic reactions.

In patients with diabetes mellitus, blood glucose levels should be carefully monitored during treatment with levofloxacin.

With the simultaneous use of levofloxacin and warfarin, monitoring of prothrombin time, INR or other coagulation parameters, as well as monitoring for signs of bleeding, is indicated.

Data on the use of the drug Hileflox (750 mg) during radical or minimally invasive sinusotomy surgery in patients with chronic odontogenic perforating maxillary sinusitis indicate high clinical efficacy. Microbiological control of the drug use showed that the use of the drug at a dose of 750 mg once a day for 10 days suppresses a number of aggressive bacteria capable of causing infectious complications. The obtained results allow recommending the drug Hileflox (750 mg) for the prevention of inflammatory complications of minimally invasive sinusotomy surgery with plastic closure of the oroantral communication.

Effect on the ability to drive vehicles and mechanisms

While taking levofloxacin, the patient’s ability to concentrate and the speed of psychomotor reactions may be impaired. In this regard, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities.

Overdose

Symptoms nausea, erosive lesions of the gastrointestinal mucosa, QT interval prolongation, confusion, dizziness, convulsions.

Treatment gastric lavage, if necessary – symptomatic therapy. There is no specific antidote, dialysis is ineffective.

Drug Interactions

Levofloxacin increases the T_1/2 of cyclosporine.

The effect of levofloxacin is reduced by drugs that inhibit intestinal motility, sucralfate, aluminum- or magnesium-containing antacid drugs, and iron preparations.

NSAIDs and theophylline, when used concomitantly with levofloxacin, increase the risk of seizures in predisposed patients, and corticosteroids increase the risk of tendon rupture.

When levofloxacin is taken concomitantly with hypoglycemic drugs, changes in blood glucose levels, including hyperglycemia and hypoglycemia, are possible.

Levofloxacin enhances the effect of warfarin.

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

Storage Conditions

The drug should be stored out of the reach of children, in a dry, light-protected place, at a temperature from 8°C (46.4°F) to 25°C (77°F).

Shelf Life

The shelf life is 3 years.

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.