Levofloxacin euro

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LEVOFLOXACIN EURO (LEVOFLOXACIN EURO)

Composition:

Active substance: levofloxacin;

One tablet contains levofloxacin hemihydrate equivalent to 500 mg of levofloxacin;

Excipients: microcrystalline cellulose, maize starch, sodium starch glycolate (type A), hypromellose, colloidal anhydrous silicon dioxide, povidone, magnesium stearate, titanium dioxide (E 171), talc, polyethylene glycol 6000, iron oxide red (E 172).

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties:

biconvex capsule-shaped tablets, film-coated, light pink to pink in colour, with a break line on one side and smooth on the other.

Pharmacotherapeutic group. Antibacterial agents of the quinolone group. Fluoroquinolones. Levofloxacin. ATC code J01MA12.

Pharmacological properties.

Pharmacodynamics.

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

Mechanism of action. Levofloxacin, as an antibacterial agent from the fluoroquinolone group, acts on the DNA gyrase and topoisomerase IV complex.

Pharmacokinetic/pharmacodynamic relationship. The degree of antibacterial activity of levofloxacin depends on the ratio between the maximum serum concentration (Cmax) or the area under the concentration-time curve (AUC) and the minimum inhibitory concentration (MIC).

Mechanism of resistance. The primary mechanism of resistance results from mutations in the gyr-A genes. In vitro, cross-resistance exists between levofloxacin and other fluoroquinolones. Due to its mechanism of action, cross-resistance between levofloxacin and other classes of antibacterial agents is generally not observed.

Breakpoints

The recommended breakpoints for levofloxacin MIC values established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), which distinguish susceptible microorganisms from moderately susceptible (intermediate) and resistant organisms, are presented in Table 1 (MIC testing, mg/L).

Table 1

Clinical breakpoints for levofloxacin (version 10.0, 2020-01-01):

1. Only uncomplicated urinary tract infections.

2. Susceptibility depends on sensitivity to ciprofloxacin.

The prevalence of resistance may vary geographically and over time for selected species; local information on resistance is desirable, especially when treating severe infections. When necessary, advice from a specialist should be sought if local resistance prevalence is such that the benefit of the drug is at least questionable in some types of infections.

Typically sensitive species

Aerobic Gram-positive bacteria

Bacillus anthracis, Staphylococcus aureus methicillin-susceptible, Staphylococcus saprophyticus, Streptococci, group C and G, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes.

Aerobic Gram-negative bacteria

Eikenella corrodens, Haemophilus influenzae, Haemophilus para-influenzae, Klebsiella oxytoca, Moraxella catarrhalis, Pasteurella multocida, Proteus vulgaris, Providencia rettgeri.

Anaerobic bacteria

Peptostreptococcus.

Others

Chlamydophila pneumoniae, Chlamydophila psittaci, Chlamydia trachomatis, Legionella pneumophila, Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum.

Species for which acquired (secondary) resistance may be problematic

Aerobic Gram-positive bacteria

Enterococcus faecalis, Staphylococcus aureus methicillin-resistant*

Coagulase-negative Staphylococcus spp.

Aerobic Gram-negative bacteria

Acinetobacter baumannii, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Providencia stuartii, Pseudomonas aeruginosa, Serratia marcescens.

Anaerobic bacteria

Bacteroides fragilis.

Significantly resistant strains

Aerobic Gram-positive bacteria

Enterococcus faecium.

* The resistance mechanism of Staphylococcus aureus is likely associated with cross-resistance to fluoroquinolones, including levofloxacin.

Pharmacokinetics.

Absorption

Levofloxacin is rapidly and almost completely absorbed after oral administration, with Cmax reached within 1–2 hours. Absolute bioavailability is approximately 99–100%.

Food has almost no effect on the absorption of levofloxacin.

Steady state is achieved within 48 hours with a dosing regimen of 500 mg once or twice daily.

Distribution

Approximately 30–40% of levofloxacin is protein-bound in plasma. The mean volume of distribution of levofloxacin is approximately 100 L after single and repeated 500 mg doses, indicating extensive tissue distribution throughout the body.

Penetration into tissues and body fluids

Levofloxacin has the ability to penetrate into bronchial mucosa, epithelial lining fluid, alveolar macrophages, lung tissue, skin (vesicle contents), prostate tissue, and urine. However, levofloxacin penetrates poorly into cerebrospinal fluid.

Biotransformation

Levofloxacin is metabolized to a very minor extent, with metabolites being desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for less than 5% of the administered dose excreted in urine. Levofloxacin is stereochemically stable and does not undergo chiral inversion.

Elimination

After oral administration and intravenous infusion, levofloxacin is eliminated from plasma relatively slowly (elimination half-life is 6–8 hours). Elimination occurs primarily via the kidneys (over 85% of the administered dose). Mean total systemic clearance of levofloxacin after a single 500 mg dose was 175 ± 29.2 mL/min. There is no significant difference in the pharmacokinetics of levofloxacin after oral administration and intravenous infusion, indicating interchangeability of these routes (oral and intravenous).

Linearity

Levofloxacin exhibits linear pharmacokinetics over the dose range of 50 to 1000 mg.

Special patient groups

Patients with renal impairment

Renal function impairment affects the pharmacokinetics of levofloxacin. In renal impairment, renal elimination is slowed, clearance is reduced, and elimination half-life is prolonged (see Table 2).

Table 2. Pharmacokinetics in renal impairment after a single oral 500 mg dose

Elderly patients

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

Gender differences

Separate analysis for male and female patients demonstrated minor differences in the pharmacokinetics of levofloxacin depending on gender. There is no evidence that these gender differences are clinically significant.

Clinical characteristics.

Indications.

Levofloxacin Euro is indicated for the treatment in adults of the following infections caused by microorganisms sensitive to levofloxacin:

• acute bacterial sinusitis;
• acute exacerbation of chronic obstructive pulmonary disease, including bronchitis;
• community-acquired pneumonia;
• complicated skin and soft tissue infections;
• uncomplicated cystitis;

(when treating the above-mentioned infections, the drug should be used only if other antibacterial agents, typically prescribed for initial treatment of these infections, cannot be used);

• acute pyelonephritis and complicated urinary tract infections;

• chronic bacterial prostatitis;

• pulmonary form of anthrax: post-exposure prophylaxis and treatment.

Levofloxacin in this pharmaceutical form (tablets) may be used to complete the course of therapy in patients who have shown improvement during initial treatment with levofloxacin infusion solution.

Official recommendations regarding appropriate use of antibacterial agents should be taken into account.

Contraindications.

Hypersensitivity to levofloxacin, to other fluoroquinolones, or to any component of the drug.

Epilepsy.

Tendon damage related to prior use of fluoroquinolones.

Pediatric age.

Pregnancy and lactation.

Interaction with other medicinal products and other types of interactions.

Antacids containing magnesium and aluminium: products containing iron salts, zinc, didanosine.

Absorption of levofloxacin is significantly reduced when administered concomitantly with antacids containing magnesium and aluminium, products containing iron salts, or with didanosine (didanosine in a buffered tablet with aluminium or magnesium). Concurrent administration of fluoroquinolones with multivitamins containing zinc leads to reduced absorption.

The recommended time interval between administration of levofloxacin and the mentioned products should be at least 2 hours.

Calcium salts have minimal effect on levofloxacin absorption.

Sucralfate.

Bioavailability of levofloxacin is significantly reduced when administered concomitantly with sucralfate. If a patient needs to receive both sucralfate and levofloxacin, the interval between administration of these drugs should be at least 2 hours.

Theophylline, fenbufen, or similar nonsteroidal anti-inflammatory drugs (NSAIDs).

No pharmacokinetic interaction between levofloxacin and theophylline has been observed. However, a significant decrease in seizure threshold may occur when quinolones are used concomitantly with theophylline, NSAIDs, and other substances that lower the seizure threshold. The concentration of levofloxacin when administered with fenbufen is approximately 13% higher than when levofloxacin is administered alone.

Probenecid and cimetidine.

Probenecid and cimetidine have a statistically significant effect on levofloxacin elimination. Renal clearance of levofloxacin decreases by 34% with probenecid and by 24% with cimetidine. Thus, both drugs can block tubular excretion of levofloxacin. However, in studies, statistically significant kinetic differences did not have clinical significance. Levofloxacin should be prescribed with caution concomitantly with medicinal products affecting tubular secretion, such as probenecid and cimetidine, especially in patients with renal impairment.

Other drugs.

The pharmacokinetics of levofloxacin are not altered when co-administered with the following drugs: calcium carbonate, digoxin, glyburide, ranitidine, warfarin.

Cyclosporine.

The elimination half-life of cyclosporine increases by 33% when administered concomitantly with levofloxacin.

Vitamin K antagonists.

When administered concomitantly with vitamin K antagonists (e.g., warfarin), coagulation tests (prothrombin time/international normalized ratio (INR)) and/or bleeding may increase, and such effects can be pronounced. Therefore, patients receiving vitamin K antagonists concurrently should be monitored for coagulation parameters.

MEDICINAL PRODUCTS THAT PROLONG THE QT INTERVAL.

Levofloxacin, as well as other fluoroquinolones, should be used with caution in patients receiving medicinal products that prolong the QT interval (including class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotic medicinal products), see section "Special warnings and precautions for use".

Levofloxacin does not affect the pharmacokinetics of theophylline, which is primarily metabolized via CYP1A2; therefore, levofloxacin is not considered an inhibitor of CYP1A2.

Food intake.

No interaction with food; may be taken independently of food intake.

Concomitant use of levofloxacin with alcohol is not recommended.

Special precautions for use.

The use of the drug should be avoided in patients who have previously experienced serious adverse reactions to quinolones or fluoroquinolones. Treatment of such patients with levofloxacin should be initiated only if there are no alternative treatment options and after careful benefit/risk assessment.

Prolonged, disabling, and potentially irreversible serious adverse reactions.

Very rarely, prolonged (lasting for months or years), disabling, and potentially irreversible serious adverse reactions affecting various, and sometimes multiple simultaneously, body systems (particularly musculoskeletal, nervous, psychiatric, and sensory organs) have been reported in patients receiving quinolones and fluoroquinolones, regardless of age or existing risk factors. The drug should be discontinued immediately upon the first signs or symptoms of any serious adverse reaction, and medical advice should be sought.

Aortic aneurysm and dissection, and heart valve regurgitation/insufficiency.

Epidemiological studies have reported an increased risk of aortic aneurysm and dissection, particularly in elderly patients, as well as aortic and mitral valve regurgitation following fluoroquinolone use. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any heart valve have been reported in patients receiving fluoroquinolones (see section "Adverse Reactions").

Therefore, fluoroquinolones should be used only after careful benefit/risk assessment and consideration of alternative therapeutic options in patients with a positive family history of aneurysm or congenital heart valve defects, or in patients with an existing diagnosis of aneurysm and/or aortic dissection, or with heart valve disease, or in the presence of other risk factors or predisposing conditions:

• for both aortic aneurysm and dissection and heart valve regurgitation/insufficiency (e.g., connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behçet’s disease, hypertension, rheumatoid arthritis), or additionally
• for aortic aneurysm and dissection (e.g., vascular disorders such as Takayasu arteritis or giant cell arteritis, known atherosclerosis, or Sjögren’s syndrome), or additionally
• for heart valve regurgitation/insufficiency (e.g., infective endocarditis). The risk of aortic aneurysm and dissection and their rupture may be increased in patients receiving systemic corticosteroids concomitantly.

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

Patients should be advised to seek immediate medical help if they develop acute shortness of breath, a new episode of palpitations, or develop abdominal or lower limb swelling.

Methicillin-resistant S. aureus (MRSA).

In very severe cases of pneumococcal pneumonia, levofloxacin may not exhibit optimal therapeutic efficacy.

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

Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to fluoroquinolones, including levofloxacin; therefore, levofloxacin is not recommended for treatment of MRSA infections except when microbial susceptibility to levofloxacin has been confirmed.

Levofloxacin may be prescribed for the treatment of acute bacterial sinusitis and acute exacerbation of chronic bronchitis when adequate diagnosis of these conditions has been established.

Escherichia coli resistant to levofloxacin may be the most common pathogen in urinary tract infections; this should be considered when prescribing levofloxacin for urinary tract infections. Local prevalence of fluoroquinolone resistance in Escherichia coli should be taken into account when prescribing fluoroquinolones.

The use of levofloxacin in pulmonary anthrax is based on in vitro susceptibility data for Bacillus anthracis, experimental animal data, and limited human data. Physicians should consider national and/or international consensus guidelines for the treatment of anthrax.

Tendinitis and tendon rupture.

Tendinitis and tendon rupture (not limited to the Achilles tendon), sometimes bilateral, may occur within 48 hours of initiating treatment with quinolones and fluoroquinolones and have been reported even several months after discontinuation of treatment in patients receiving daily doses of 1000 mg levofloxacin. The risk of tendinitis and tendon rupture is increased in elderly patients, patients with renal impairment, organ transplant recipients, and patients receiving concomitant corticosteroid therapy. Therefore, concomitant use of corticosteroids should be avoided.

If signs of tendinitis (e.g., painful swelling, inflammation) occur, treatment with the drug should be discontinued, and alternative therapy should be considered. The affected limb(s) should be appropriately managed (e.g., immobilization). Corticosteroids should not be used if signs of tendinopathy occur.

Myoclonus.

Cases of myoclonus have been reported in patients treated with levofloxacin (see section "Adverse Reactions"). The risk of myoclonus is increased in elderly patients and in patients with renal impairment if the levofloxacin dose is not adjusted according to creatinine clearance. Levofloxacin should be discontinued immediately at the first signs of myoclonus, and appropriate treatment should be initiated.

Clostridium difficile-associated disease.

Diarrhea, especially severe, persistent, or with blood, occurring during or after treatment (including several weeks after treatment) with levofloxacin, may be symptoms of Clostridium difficile-associated disease (CDAD). CDAD may range in severity from mild to life-threatening; the most severe form being pseudomembranous colitis. If pseudomembranous colitis is suspected, levofloxacin should be immediately discontinued and symptomatic and specific treatment (e.g., vancomycin) should be promptly initiated. In such cases, drugs that inhibit intestinal peristalsis are contraindicated.

Patients with seizure predisposition.

Quinolones may lower the seizure threshold and provoke seizures. Levofloxacin is contraindicated in patients with a history of epilepsy.

As with other quinolones, the drug should be used with extreme caution in patients predisposed to seizures, such as those with pre-existing central nervous system disorders, concomitant therapy with phenylbutazone and similar nonsteroidal anti-inflammatory drugs, or drugs that increase seizure susceptibility (lower seizure threshold), such as theophylline (see section "Interaction with other medicinal products and other forms of interaction"). If seizures occur, treatment with levofloxacin should be discontinued.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Patients with latent or manifest deficiency of glucose-6-phosphate dehydrogenase activity may be prone to hemolytic reactions when treated with quinolone antibacterial agents. Therefore, levofloxacin should be used with caution in such patients, and possible development of hemolysis should be monitored.

Renal impairment.

Levofloxacin is primarily eliminated via the kidneys; therefore, dose adjustment is required in patients with renal impairment (see section "Dosage and administration").

Hypersensitivity reactions.

Levofloxacin may occasionally cause serious, potentially fatal hypersensitivity reactions (including angioedema, anaphylactic shock), even after the first dose (see section "Ad游戏副本

Method of administration and dosage.

Take tablets 1-2 times daily. The dose depends on the type and severity of infection and the susceptibility of the likely causative organism. The duration of treatment depends on the course of the disease and should not exceed 14 days. It is recommended to continue treatment for at least 48–72 hours after normalization of body temperature or after microbiological tests have confirmed eradication of the pathogen.

Swallow the tablets whole, without chewing, with sufficient fluid. Administer independently of food intake. A dividing line is marked on the tablet to facilitate splitting into parts if necessary.

The drug should be administered at least 2 hours before or after administration of iron salts, zinc salts, antacids containing magnesium or aluminum, didanosine (only for formulations containing aluminum or magnesium in buffering agents), and sucralfate (see section "Interaction with other medicinal products and other forms of interaction").

Table 2

Recommended dosage for adult patients with normal renal function, in whom creatinine clearance is over 50 ml/min

Special populations

Table 3

Dosing for patients with renal impairment with creatinine clearance less than 50 ml/min

1 Additional doses are not required after hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

Dosing in patients with hepatic impairment. Dose adjustment is not necessary, since levofloxacin is minimally metabolized in the liver and is primarily excreted by the kidneys.

Dosing in elderly patients. If renal function is normal, dose adjustment is not required (see section "Special precautions": Tendinitis and tendon rupture, QT interval prolongation).

Children.

Levofloxacin is contraindicated in children, as damage to joint cartilage cannot be excluded (see section "Contraindications").

Overdose.

Symptoms: confusion, dizziness, disturbances of consciousness, seizures, myoclonus, hallucinations, tremor, nausea, erosion of mucous membranes, QT interval prolongation.

Treatment: symptomatic therapy. Due to the potential for QT interval prolongation, ECG monitoring is required. In cases of clear overdose, gastric lavage should be administered. Antacids may be used to protect the gastric mucosa. Hemodialysis, including peritoneal dialysis and continuous ambulatory peritoneal dialysis, is ineffective in removing levofloxacin from the body. There is no specific antidote.

Side effects

The frequency of adverse effects was determined using the following criteria: very common (>1/10), common (from >1/100 to <1/10), uncommon (from >1/1000 to <1/100), rare (from >1/10,000 to <1/1000), very rare (<1/10,000), frequency not known (cannot be estimated from available data).

Within each group, adverse reactions are listed in order of decreasing severity.

Infections and infestations:

Uncommon: fungal infections, including Candida species, proliferation of other resistant microorganisms, disruption of normal intestinal flora, and development of secondary infections.

Blood and lymphatic system disorders:

Uncommon: leukopenia, eosinophilia;
Rare: thrombocytopenia, neutropenia;
Frequency not known: bone marrow dysfunction, including aplastic anemia, pancytopenia, agranulocytosis, hemolytic anemia.

Immune system disorders:

Rare: angioedema, hypersensitivity (see section "Special precautions");
Frequency not known: anaphylactic/anaphylactoid shock (see section "Special precautions").

Metabolism and nutrition disorders:

Uncommon: anorexia;
Rare: hypoglycemia, mainly in diabetic patients (see section "Special precautions");
Frequency not known: hyperglycemia, hypoglycemic coma (see section "Special precautions").

Psychiatric disorders*:

Common: insomnia;
Uncommon: anxiety, restlessness, fear, confusion, nervousness;
Rare: psychotic reactions (including hallucinations, paranoia), depression, agitation, unusual dreams, nightmares, delirium;
Frequency not known: psychotic reactions with self-destructive behavior, including suicidal ideation or actions, mania (see section "Special precautions").

Nervous system disorders*:

Common: headache, dizziness;
Uncommon: drowsiness, tremor, dysgeusia (subjective taste disturbance);
Rare: seizures (see section "Contraindications" and "Special precautions"), paresthesia, memory impairment;
Frequency not known: peripheral sensory or sensorimotor neuropathy (see section "Special precautions"), olfactory disturbances (parosmia), including anosmia (loss of smell), dyskinesia (impaired movement coordination), extrapyramidal disorders, ageusia, syncope (fainting), benign intracranial hypertension, myoclonus.

Eye disorders*:

Rare: visual disturbances such as blurred vision, visual blurring (see section "Special precautions");
Frequency not known: temporary vision loss, uveitis (see section "Special precautions").

Ear and labyrinth disorders*:

Uncommon: vertigo;
Rare: tinnitus;
Frequency not known: hearing loss, hearing impairment.

Cardiac disorders**:

Rare: tachycardia, palpitations;
Frequency not known: ventricular tachycardia, which may lead to cardiac arrest; torsade de pointes ventricular arrhythmia (mainly in patients with risk factors for QT interval prolongation); QT interval prolongation on ECG (see sections "Special precautions": QT interval prolongation, and "Overdose").

Vascular disorders**:

Rare: arterial hypotension.

Respiratory system disorders:

Uncommon: dyspnea (shortness of breath);
Frequency not known: bronchospasm, allergic pneumonitis.

Gastrointestinal disorders:

Common: diarrhea, vomiting, nausea;
Uncommon: abdominal pain, dyspepsia, flatulence/bloating, constipation;
Frequency not known: hemorrhagic diarrhea, which may indicate enterocolitis, including pseudomembranous colitis (see section "Special precautions"); pancreatitis.

Hepatobiliary disorders:

Common: increased liver enzyme levels (ALT/AST, alkaline phosphatase, GGT);
Uncommon: increased blood bilirubin levels;
Frequency not known: jaundice and severe liver injury, including cases of acute liver failure (sometimes fatal), mainly in patients with severe underlying conditions (see section "Special precautions"); hepatitis.

Skin and subcutaneous tissue disorders:

Rare: drug rash with eosinophilia and systemic symptoms (DRESS syndrome), localized drug-induced skin eruptions;
Uncommon: rash, pruritus, urticaria, hyperhidrosis;
Frequency not known: toxic epidermal necrolysis (Lyell's syndrome), Stevens-Johnson syndrome, erythema multiforme, photosensitivity reactions (see section "Special precautions"); leukocytoclastic vasculitis, stomatitis, skin hyperpigmentation.

Musculoskeletal and connective tissue disorders*:

Uncommon: arthralgia, myalgia;
Rare: tendon disorders (see section "Special precautions"), including tendon inflammation (tendinitis) (e.g., Achilles tendon); muscle weakness, which may be particularly significant in patients with myasthenia gravis (see section "Special precautions");
Frequency not known: rhabdomyolysis, tendon rupture (e.g., Achilles tendon: see section "Special precautions"), ligament rupture, muscle rupture, arthritis.

Renal and urinary disorders:

Uncommon: elevated serum creatinine levels;
Rare: acute renal failure (e.g., due to interstitial nephritis).

Endocrine disorders:

Rare: syndrome of inappropriate antidiuretic hormone secretion (SIADH).

General disorders*:

Uncommon: asthenia;
Rare: increased body temperature (pyrexia);
Frequency not known: pain (including back, chest, and limb pain).

aAnaphylactic and anaphylactoid reactions may sometimes occur even after administration of the first dose.

bSkin and mucous membrane reactions may sometimes occur even after administration of the first dose.

Other adverse effects associated with fluorquinolone administration include:

• Acute attacks of porphyria in patients with porphyria.

*Very rare cases of long-term (up to months or years), disabling, and potentially irreversible serious adverse reactions affecting multiple, sometimes several, organ systems and sensory organs (including such reactions as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbances; in some cases, neuropathies associated with paresthesia, depression, fatigue, memory impairment, sleep disturbances, and disturbances of hearing, vision, taste, and smell) have been reported with quinolones and fluoroquinolones, regardless of pre-existing risk factors (see section "Special precautions"); anxiety, suicidal thoughts, panic attacks, neuralgia, and impaired concentration have also been reported as potential features of long-term, disabling adverse reactions caused by fluoroquinolones.

***Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any cardiac valve have been reported in patients receiving fluoroquinolones (see section "Special precautions").**

Shelf life. 2 years.

Storage conditions. Store at temperatures not exceeding 30 °C. Keep out of reach of children.

Packaging. 5 tablets per blister; 1 or 2 blisters per cardboard box.

Prescription category. Prescription only.

Manufacturer.

FDS Limited.

Manufacturer's address and location of business operations.

L-121B, Phase III/A, Verna Industrial Estate, Verna, Salcette, Goa - 403 722, India.