Loprax

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LOPRAX (Loprax®)

Composition:

Active substance: cefixime;

5 ml of suspension contains: cefixime trihydrate equivalent to cefixime 100 mg;

Excipients: sucrose, xanthan gum, sodium benzoate (E 211), orange flavor.

Pharmaceutical form. Powder for oral suspension.

Main physicochemical properties: powder and suspension are cream-colored with an orange odor.

Pharmacotherapeutic group. Antimicrobial agents for systemic use.

Other β-lactam antibiotics. Third-generation cephalosporins. Cefixime.

ATC code J01D D08.

Pharmacological properties.

Pharmacodynamics.

Cefixime is an oral, semi-synthetic third-generation cephalosporin that demonstrates in vitro bactericidal activity against a wide variety of gram-positive and gram-negative microorganisms. Clinical efficacy has been demonstrated against infections caused by common pathogenic microorganisms, including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Klebsiella species, Haemophilus influenzae (β-lactamase-positive and β-lactamase-negative strains), Branhamella catarrhalis (beta-lactamase-positive and beta-lactamase-negative strains), and Enterobacter species. Cefixime is highly stable in the presence of β-lactamase.

Most strains of enterococci (Streptococcus faecalis, group D streptococci) and staphylococci (including coagulase-positive and coagulase-negative strains, as well as methicillin-resistant strains) are resistant to cefixime. In addition, most strains of Pseudomonas, Bacteroides fragilis, Listeria monocytogenes, and Clostridia are resistant to cefixime.

Pharmacokinetics.

Rapidly absorbed in the gastrointestinal tract. Bioavailability is 30–50%. Cmax (maximum serum concentration) is reached within 2–6 hours. Plasma protein binding (mainly to albumins) is 65%. T1/2 (elimination half-life) is 2.4–4 hours. Excreted primarily unchanged in the urine.

Clinical characteristics.

Indications.

• Acute and chronic bronchitis.
• Bacterial exacerbation of bronchitis.
• Otitis media.
• Pharyngitis and tonsillitis of bacterial etiology.
• Bacterial urinary tract infections: cystitis, urethritis, pyelonephritis, cervicitis.

Contraindications.

Loprax is contraindicated in patients with known hypersensitivity to any component of the drug, other cephalosporins, or penicillins, and in patients with porphyria.

Interaction with other medicinal products and other forms of interaction.

Probenecid (and other tubular secretion blockers) increases the maximum blood concentration of cefixime by slowing renal excretion of cefixime, which may lead to symptoms of overdose.

Salicylic acid increases the concentration of free cefixime by 50% due to displacement of cefixime from protein-binding sites; this effect is concentration-dependent.

Carbamazepine may cause an increase in cefixime plasma concentration; therefore, monitoring of its plasma levels is advisable.

Nifedipine increases the bioavailability of cefixime.

Furosemide and aminoglycosides increase the nephrotoxicity of the drug.

Potentially, similar to other antibiotics, cefixime may reduce reabsorption of estrogens and decrease the effectiveness of combined oral contraceptives.

Coumarin-type anticoagulants.

Cefixime should be used with caution in patients receiving anticoagulant therapy, e.g., warfarin. Since cefixime may potentiate the effect of anticoagulants, prolongation of prothrombin time with or without clinical signs of bleeding may occur.

Other forms of interactions: the use of cephalosporins may lead to false-positive reactions when testing for glucose in urine using Benedict's or Fehling's solutions, or with Clinitest tablets. During cefixime therapy, a false-positive direct Coombs test may occur.

Special precautions for use.

Severe skin reactions
Serious skin adverse reactions, including toxic epidermal necrolysis, Stevens-Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported in some patients receiving cefixime. In the event of serious skin adverse reactions, cefixime should be discontinued immediately and appropriate therapy initiated and/or necessary preventive measures taken.

Hypersensitivity reactions

Prior to initiating cefixime therapy, careful evaluation of the patient’s history of hypersensitivity reactions to penicillins, cephalosporins, or other drugs is essential.

Evidence of cross-allergic reactions between penicillins and cephalosporins has been demonstrated both in vivo (in the human body) and in vitro. Such cases are rare but may occur in an anaphylactic manner, particularly following parenteral administration.

Antibiotics should be administered with caution to patients with a history of any type of hypersensitivity reaction, especially following drug administration. If an allergic reaction occurs, the drug should be discontinued immediately and appropriate therapy initiated.

Alterations in intestinal flora

Prolonged use of antibacterial agents may lead to overgrowth of non-susceptible microorganisms and disruption of normal intestinal flora, potentially resulting in overgrowth of Clostridium difficile and development of pseudomembranous colitis. In mild cases of pseudomembranous colitis associated with antibiotic use, discontinuation of the drug may be sufficient. If colitis symptoms persist after discontinuation, oral vancomycin — the antibiotic of choice for pseudomembranous colitis — should be prescribed.

In moderate to severe colitis, treatment should include electrolyte and protein solutions. Concomitant use of drugs that reduce intestinal motility should be avoided. Broad-spectrum antibiotics should be prescribed with caution in patients with a history of gastrointestinal disorders, particularly colitis.

Prolonged cefixime therapy may lead to overgrowth of Candida albicans and result in oral mucosal candidiasis. Caution should be exercised when prescribing the drug to patients with a history of bleeding disorders, gastrointestinal diseases — particularly ulcerative colitis, regional enteritis, or antibiotic-associated colitis — as well as hepatic dysfunction.

Laboratory test data

Reversible changes in liver, kidney, and blood parameters (thrombocytopenia, leukopenia, and eosinophilia) may occur during treatment with the medicinal product Loprax. During prolonged therapy, blood counts, as well as liver and kidney function, should be monitored. It should be noted that cefixime may cause false-positive urine glucose test results and a positive Coombs test reaction.

Renal impairment

The drug should be administered with caution in patients with renal impairment. Dose adjustment should be based on creatinine clearance.

In children with renal disease, the dose should be 1.5–3 mg of the drug per kg of body weight per day.

Anemia

Cases of hemolytic anemia, including severe cases with fatal outcomes, have been reported following cephalosporin use. Recurrent episodes of hemolytic anemia have also been reported in patients previously diagnosed with hemolytic anemia after initial administration of cephalosporins, including cefixime.

For group A β-hemolytic streptococcal infections, the treatment course should last at least 10 days to prevent acute rheumatic fever or glomerulonephritis.

The drug may increase prothrombin time; therefore, it should be used with caution in patients receiving anticoagulant therapy.

If a patient has known intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

Use during pregnancy or breastfeeding

Controlled clinical studies in pregnant women have not been conducted. Cefixime may be used during pregnancy only if clearly needed and if the potential benefit to the mother outweighs the potential risk to the fetus. The use of cefixime during breastfeeding is not recommended. Breastfeeding should be discontinued for the duration of treatment.

Ability to affect reaction speed when driving or operating machinery
This drug is intended for use in pediatrics.

There are no data on the effect of cefixime on the ability to drive or operate machinery. Patients should be informed about possible adverse reactions such as headache, increased fatigue, and dizziness when using cefixime.

Dosage and Administration.

The suspension is intended for use in pediatrics. For children aged 6 months to 12 years with body weight up to 50 kg, the recommended daily dose should be administered at 8 mg/kg as a single dose or 4 mg/kg given in two divided doses every 12 hours. For children aged 6 months to 12 years, the duration of treatment depends on the severity of the infection and is determined individually. The treatment course ranges from 3 days (for uncomplicated infections) to 10–14 days.

The usual dose of cefixime for children aged 12 years and older with body weight exceeding 50 kg is 400 mg once daily or 200 mg twice daily, administered at 12-hour intervals.

Preparation of the suspension. Before preparation, invert and shake the bottle to loosen the powder. Add boiled cold water up to the mark indicated on the bottle. Shake well immediately after adding water. Then add more boiled cold water to the same mark and shake thoroughly again to form a uniform suspension.

The suspension should not be taken earlier than 5 minutes after preparation.

The prepared suspension should be shaken well before each dose.

Children.

The drug is indicated for children aged 6 months to 18 years. The efficacy and safety of cefixime in children under 6 months of age have not been established; therefore, cefixime is not recommended for use in this patient population.

Overdose.

In case of overdose, symptoms such as dizziness, nausea, vomiting, and diarrhea may occur. There are no specific antidotes available for the treatment of overdose. Symptomatic and supportive therapy should be administered (e.g., gastric lavage to reduce drug absorption, detoxification therapy, enteral sorbents). Hemodialysis or peritoneal dialysis only slightly enhances the elimination of cefixime from the body.

Side effects

When cephalosporins are used, gastrointestinal disturbances are most commonly observed, while hypersensitivity reactions occur less frequently.

Hypersensitivity reactions are more commonly observed in patients who have previously experienced such reactions, as well as in patients with a history of allergies, hay fever, urticaria, or bronchial asthma with an allergic component.

The following adverse reactions have rarely occurred during cefixime administration:

Gastrointestinal system: dry mouth, glossitis, nausea, vomiting, heartburn, abdominal pain, diarrhea, digestive disturbances, candidiasis of the oral and gastrointestinal mucosa, stomatitis, flatulence, stomach spasms, intestinal spasms, dysbacteriosis. Switching to a dosage of 200 mg twice daily may alleviate diarrhea. Severe and prolonged diarrhea has been associated with the use of certain classes of antibiotics. In such cases, pseudomembranous colitis should be ruled out. If the diagnosis is confirmed by colonoscopy, any antibiotic therapy must be discontinued immediately and oral vancomycin should be initiated. Medicinal products that reduce intestinal peristalsis are contraindicated.

Immune system: hypersensitivity reactions, serum sickness-like reactions, anaphylaxis, airway obstruction due to laryngeal edema, arthralgia, drug fever, interstitial nephritis.

Hematological system: transient leukopenia, agranulocytosis, pancytopenia, transient neutropenia, granulocytopenia, thrombocytopenia, eosinophilia, thrombophlebitis, purpura. Hemolytic anemia has also been reported in patients receiving cephalosporins. Isolated cases of impaired blood coagulation have been observed.

Hepatic system: jaundice, transient elevation of transaminases (AST, ALT), alkaline phosphatase, total bilirubin, isolated cases of hepatitis, cholestasis.

Urinary system: transient increase in serum urea and creatinine levels, renal function impairment, hematuria.

Respiratory system: dyspnea.

Skin: urticaria, skin rashes (erythema, exanthema), pruritus, skin hyperemia, multiform erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).

Nervous system: headache, dizziness, dysphoria.

Auditory and vestibular system: hearing loss.

General disorders: increased body temperature, facial swelling, palpitations, increased fatigue, hyperactivity, weakness, mucosal inflammation, elevated blood pressure.

Other: anorexia; Candida-induced vaginitis; genital pruritus.

Shelf life. 3 years.

Storage conditions. Store at a temperature not exceeding 30 °C in the original packaging. The prepared suspension should be stored for up to 7 days at a temperature not exceeding 25 °C or for up to 14 days in a refrigerator (at 2–8 °C). Do not freeze.

Packaging. One vial with a plastic measuring cup in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Exir Pharmaceutical Company, Iran.

Manufacturer's address and place of business.

2nd km Ring Road, Boroujerd 69189, Iran.