Cefidant

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CEFIDANT (CEFIDANT)

Composition:

Active substance: cefixime;

One film-coated tablet contains cefixime (as cefixime trihydrate) 400 mg;

Excipients: microcrystalline cellulose, pregelatinized starch, calcium hydrogen phosphate dihydrate, colloidal anhydrous silicon dioxide, magnesium stearate, Opadry® 03F180011 white film coating: hypromellose, titanium dioxide (E 171), macrogol.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: oval, biconvex, film-coated tablets, white to almost white, with a score line on one side.

Pharmacotherapeutic group

Antibacterials for systemic use. Other beta-lactam antibiotics. Third-generation cephalosporins. ATC code J01D D08.

Pharmacological Properties

Pharmacodynamics

Cefixime is an oral cephalosporin characterized by a broad spectrum of bactericidal activity and high resistance to the hydrolytic activity of beta-lactamases.

The bactericidal action of cefixime is due to inhibition of bacterial cell wall synthesis.

In vitro, it demonstrates significant bactericidal activity against a wide range of Gram-positive and Gram-negative microorganisms.

Clinically effective in the treatment of infections caused by the most common pathogenic microorganisms, including Streptococcus (except enterococci), Haemophilus, Branhamella, Neisseria, Escherichia, Klebsiella, Proteus, Enterobacter, Pasteurella, Providencia, Salmonella, Shigella, Citrobacter, Serratia.

Conversely, the following are mainly resistant to cefixime: Pseudomonas spp., Staphylococcus spp., Listeria monocytogenes, Bacteroides fragilis, and Clostridium spp.

Pharmacokinetics

After a single 200 mg oral dose, the maximum serum concentration of cefixime is 3 µg/mL, achieved within 3 to 4 hours.

After a single 400 mg oral dose, the maximum serum concentration is higher (3.5 to 4 µg/mL), although a direct proportional relationship with the administered dose is not observed.

Following repeated administration of cefixime at a dose of 400 mg/day orally (once or twice daily) for 15 days, serum levels and bioavailability remain unchanged, indicating no drug accumulation in the body.

Absorption. Absolute bioavailability after oral administration of cefixime is approximately 50% and is not affected by food. In this case, the time required to reach peak concentration is delayed by approximately 1 hour.

Distribution. The apparent volume of distribution is 17 liters. In animals, cefixime distributes into most tissues (except the brain), with tissue concentrations exceeding the MIC of susceptible strains (0.20 µg/mL).

Elimination. The drug is excreted unchanged via the renal route (16 to 25%). Extrarenal elimination occurs primarily via bile. No serum or urinary metabolites of cefixime have been detected in humans or animals.

Pharmacokinetic parameters are slightly altered in elderly individuals. A slight increase in serum concentrations, bioavailability, and amount of drug excreted (by 15 to 25%) does not require dose adjustment in this population.

In cases of severe renal impairment (creatinine clearance <20 mL/min), increased plasma elimination, prolonged elimination half-life, and elevated peak serum concentrations necessitate dose reduction from 400 mg/day to 200 mg/day.

In hepatic impairment, elimination is prolonged (t½ = 6.4 hours), but dose adjustment is not required.

Protein binding is approximately 70%, primarily to albumin, and is independent of concentration (within therapeutic dose ranges).

Clinical Characteristics

Indications

Infections caused by cefixime-susceptible microorganisms:

• upper respiratory tract infections (pharyngitis);
• ENT infections (otitis, tonsillitis);
• lower respiratory tract infections (pneumonia, bronchitis);
• kidney and urinary tract infections.

Contraindications

Hypersensitivity to the active substance or to any of the excipients. Hypersensitivity to penicillins and other cephalosporins.

Interaction with other medicinal products and other forms of interaction

Coumarin anticoagulants

Cefixime should be used with caution in patients receiving coumarin-type anticoagulants, such as potassium warfarin. Since cefixime may potentiate the effects of anticoagulants, an increase in prothrombin time with or without clinical signs of bleeding is possible.

Nifedipine—a calcium antagonist—may increase the bioavailability of cefixime by up to 70%.

Cefixime may reduce the efficacy of oral contraceptives.

The use of additional non-hormonal contraceptive methods is recommended.

Other forms of interaction

The use of cephalosporins, such as cefixime, may interfere with certain laboratory tests, causing false-positive results for glucosuria when using Benedict's, Fehling's, or Clinitest methods (but not with enzymatic methods). The glucose oxidase test is recommended for determining glucose in urine. Positive Coombs' test results have been reported during treatment with cephalosporins (sometimes false-positive).

Special precautions for use

Severe skin adverse reactions

Serious skin adverse reactions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) have been reported in some patients treated with cefixime. If severe adverse reactions occur, cefixime therapy should be discontinued and appropriate treatment and/or preventive measures should be initiated.

Hypersensitivity

A careful medical history should be obtained before initiating treatment with CEFDANT to identify any previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.

CEFDANT should be administered with caution to patients with allergic reactions to penicillins. Partial cross-allergenicity between penicillins and cephalosporins has been demonstrated both in vivo (in humans) and in vitro. Although rare, cases of anaphylactic-type reactions have been reported, particularly after parenteral administration.

Antibiotics should be prescribed with caution to all patients with a history of allergy, especially to drugs. The occurrence of an allergic-type reaction requires discontinuation of treatment.

Alterations in intestinal bacterial flora

Treatment with broad-spectrum antibiotics may alter the normal flora of the colon and promote overgrowth of Clostridia, leading to pseudomembranous colitis. Mild cases of pseudomembranous colitis may resolve upon discontinuation of therapy. If colitis does not resolve after these measures, oral vancomycin—the antibiotic of choice for pseudomembranous colitis—should be administered. Moderate to severe cases require additional treatment with electrolyte and protein solutions. Concomitant use of agents 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.

Laboratory tests

Rarely, minor and reversible changes in liver and kidney function and blood coagulation parameters (thrombocytopenia, leukopenia, and eosinophilia) have been observed during treatment with CEFDANT.

Renal impairment

The dose of CEFDANT should be appropriately reduced in patients with severe renal impairment undergoing hemodialysis or peritoneal dialysis (see section "Dosage and administration").

Acute renal failure

As with other cephalosporins, cefixime may lead to acute renal failure, including tubulointerstitial nephritis. If acute renal failure occurs, cefixime should be discontinued and appropriate therapy and/or measures should be initiated.

Seizures in patients with renal dysfunction

Many cephalosporins have been associated with seizure development, particularly when dose adjustment is not performed in patients with impaired renal function. If seizures occur, cefixime should be discontinued and appropriate treatment and/or measures should be initiated.

Antimicrobial resistance

Treatment with cefixime may increase the risk of bacterial resistance development—both with clinically evident superinfection and without.

Superinfection

Prolonged use of antibiotics may occasionally lead to overgrowth of resistant microorganisms. If superinfection occurs, appropriate therapy should be initiated.

Hemolytic anemia

Cases of hemolytic anemia, including severe cases with fatal outcomes, have been reported following treatment with cephalosporin-class drugs. Recurrences of hemolytic anemia after re-administration of cephalosporins have also been reported in patients who previously experienced hemolytic anemia after initial cephalosporin use (including cefixime).

Use in children

The safety of cefixime use in premature infants or newborns has not been established (see section "Dosage and administration").

Use during pregnancy or breastfeeding

The use of CEFDANT during pregnancy and breastfeeding should be considered only if the expected benefit to the mother outweighs the potential risk to the fetus or infant.

Pregnancy

In particular, although no embryotoxic effects have been observed, CEFDANT should be avoided during the first trimester of pregnancy as a precautionary measure.

Breastfeeding

There are no data on the passage of the drug into breast milk.

Ability to affect reaction speed when driving or operating machinery

CEFDANT does not impair the ability to drive or operate machinery.

Dosage and Administration

Adults. The recommended dose is 400 mg once daily as a single daily dose.

The tablet should be swallowed whole.

The usual course of treatment is 7 days. If necessary, it may be extended up to 14 days.

The tablet can be divided into two parts.

Dosage

Adults and children aged 12 years and older with body weight over 50 kg: the recommended dose is 200–400 mg daily depending on the severity of the infection.

Children under 12 years of age

The medicinal product CEFDANT is not recommended for use in children under 12 years of age. The safety and efficacy of cefixime in children under 6 months of age have not been established.

Special patient populations

For patients with creatinine clearance < 20 mL/min who are undergoing continuous ambulatory peritoneal dialysis or hemodialysis, the recommended dose is 200 mg once daily. Dose adjustment is not required for patients with creatinine clearance > 20 mL/min, elderly patients, or patients with hepatic impairment.

Administration

For oral use. Food intake does not significantly affect the absorption of cefixime.

Children

In children under 12 years of age, it is recommended to use the drug in another pharmaceutical form.

Overdose

Adverse reactions observed following administration of doses up to 2 g in healthy volunteers did not differ from those reported in patients receiving the drug at recommended doses.

Cefixime is not substantially removed from systemic circulation by dialysis.

There is no specific antidote. General supportive measures are recommended.

Adverse Reactions

When cephalosporins are used, adverse effects are mainly limited to gastrointestinal disturbances and, rarely, hypersensitivity reactions. The likelihood of such reactions is higher in individuals who have previously exhibited hypersensitivity reactions, as well as in those with a history of allergies, hay fever, urticaria, or allergic bronchial asthma. The following reactions have been observed rarely during cefixime therapy:

Infections and infestations: pseudomembranous colitis, pathogen resistance.

Gastrointestinal disorders: glossitis, nausea, vomiting, heartburn, abdominal pain, diarrhea, and dyspepsia, flatulence. Switching to a twice-daily regimen (200 mg twice daily) may help resolve diarrhea. The development of severe and prolonged diarrhea has been associated with the use of various classes of antibiotics. In case of severe and prolonged diarrhea induced by antibiotics, pseudomembranous colitis should be considered. If stool analysis and colonoscopy confirm the diagnosis, antibiotic use should be discontinued and oral vancomycin therapy initiated. Medicinal products that inhibit peristalsis are contraindicated.

Immune system disorders: anaphylactic reaction, serum sickness-like reactions, angioneurotic edema, arthralgia, drug fever, and facial swelling.

Blood and lymphatic system disorders: changes in certain laboratory parameters: transient neutropenia, granulocytopenia, thrombocytopenia, and eosinophilia, agranulocytosis, leukopenia, thrombocytosis, blood coagulation disorders. Cases of hemolytic anemia have been reported after treatment with cephalosporins.

Hepatobiliary disorders: jaundice, hepatitis.

Renal and urinary disorders: acute renal failure, including tubulointerstitial nephritis as the main pathological condition.

Respiratory, thoracic and mediastinal disorders: dyspnea.

Skin and subcutaneous tissue disorders: urticaria, skin rashes, pruritus, drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, genital pruritus.

Nervous system disorders: headache, dizziness.

General disorders and administration site conditions: fever, anorexia, candidal vaginitis.

Investigations: increased aspartate aminotransferase, increased alanine aminotransferase, increased alkaline phosphatase, increased blood bilirubin, increased blood urea, increased serum creatinine.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after drug registration is important. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life

3 years.

Storage conditions

Store at temperatures not exceeding 25 °C, in the original packaging, in a place inaccessible to children.

Packaging

5 film-coated tablets in a blister; 1 or 2 blisters per cardboard box.

Prescription status

Prescription only.

Manufacturer

PharmaVision San. ve Tic. A.S.

Manufacturer's address and place of business

Davutpasa Cad. No.145 Zeytinburnu Istanbul, Turkey