Cedoxim®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT CEDOXIM® (CEDOXIM®)

Composition:

Active substance: cefpodoxime;

One film-coated tablet contains 100 mg or 200 mg of cefpodoxime proxetil calculated as cefpodoxime;

Excipients:

Tablets of 100 mg: calcium carboxymethylcellulose, lactose monohydrate, low-substituted hydroxypropylcellulose, sodium lauryl sulfate, crospovidone, corn starch, magnesium stearate; coating Opadry Orange 03H53703: hypromellose, titanium dioxide (E 171), iron oxide yellow (E 172), polyethylene glycol, yellow sunset FCF (E 110);

Tablets of 200 mg: calcium carboxymethylcellulose, lactose monohydrate, low-substituted hydroxypropylcellulose, sodium lauryl sulfate, crospovidone, corn starch, magnesium stearate; coating Opadry Red 03H55305: hypromellose, yellow sunset FCF (E 110), special red AG, titanium dioxide (E 171), polyethylene glycol.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

Tablets of 100 mg: film-coated, oval-shaped tablets, yellow-orange in color, with "C" imprinted on one side and "61" on the other;

Tablets of 200 mg: film-coated, oval-shaped tablets, red in color, with "C" imprinted on one side and "62" on the other.

Pharmacotherapeutic group.

Antibacterials for systemic use. Third-generation cephalosporins. ATC code J01D D13.

Pharmacological properties.

Pharmacodynamics.

Cefpodoxime is active against many gram-positive and gram-negative microorganisms: Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus spp. (groups C, F, G), Escherichia coli, Haemophilus influenzae (including beta-lactamase-producing strains), Klebsiella pneumoniae, Neisseria gonorrhoeae (including penicillinase-producing strains), Proteus mirabilis, Citrobacter diversus, Haemophilus parainfluenzae, Klebsiella oxytoca, Proteus vulgaris, Corynebacterium diphtheriae, Branhamella catarrhalis, Neisseria meningitidis, Neisseria gonorrhoeae, Escherichia coli.

Pharmacokinetics.

It is absorbed from the gastrointestinal tract and de-esterified to form cefpodoxime. After oral administration of 100 mg, 50% is absorbed; maximum plasma concentration (Cmax) is 1.4 μg/mL. Food intake increases Cmax but does not alter the time to reach peak concentration (Tmax) when tablets are administered, whereas with suspension administration, Tmax is altered but not Cmax. Protein binding is 20–30%. Tmax is 2–3 hours. The drug penetrates into tissues, including tonsils and lungs, and into fluids, achieving concentrations exceeding the minimum inhibitory concentration (MIC50) for most microorganisms. Elimination half-life (T½) is 2.09–2.84 hours. Approximately 30–35% of the administered dose is excreted unchanged in urine within 12 hours.

In renal impairment, excretion is reduced: when creatinine clearance is 50–80 mL/min, T½ is 3.5 hours; 30–49 mL/min – 5.9 hours; 5–29 mL/min – 9.8 hours.

Clinical characteristics.

Indications.

Treatment of mild to moderate infections caused by susceptible microorganisms:

• infections of the ear, nose, and throat (sinusitis, tonsillitis, and pharyngitis);
• community-acquired pneumonia;
• exacerbations of chronic infectious bronchitis;
• uncomplicated skin and soft tissue infections;
• uncomplicated urinary tract infections, including acute pyelonephritis and cystitis;
• acute uncomplicated cervical and urethral gonorrhea.

Contraindications.

Hypersensitivity to cefpodoxime, cephalosporins, penicillins, or any other component of the drug. Hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Interaction with other medicinal products and other types of interactions.

Concomitant administration of high doses of antacids (sodium bicarbonate and aluminum hydroxide) or histamine H2-receptor blockers reduces the extent of absorption by 27–32% and Cmax by 24–42%. Oral anticholinesterase agents increase Tmax by 47%, but do not affect the extent of absorption.

The drug should be taken 2–3 hours after administration of ranitidine.

Probenecid slows excretion, promotes accumulation, and prolongs elevated drug concentrations in blood. Although nephrotoxicity has not been established when cefpodoxime is used as monotherapy, careful monitoring of renal function is recommended when Cedoxim® is used concomitantly with drugs known to be nephrotoxic.

Like other antibiotics, Cedoxim® may affect intestinal flora, leading to reduced reabsorption of estrogens and decreased efficacy of combined oral contraceptives.

Special precautions for use.

Cross-reactivity with cephalosporins occurs in approximately 5–10% of patients with confirmed penicillin allergy. This medicinal product is contraindicated in patients hypersensitive to penicillin. In patients with a history of allergic reactions, continuous medical supervision is required from the first day of treatment; appropriate medical support and monitoring must be readily available in case of any anaphylactic episode following administration of the drug.

When treating patients with known allergy to other cephalosporins, cross-allergenicity with cefpodoxime should be considered.

Allergic reactions (especially anaphylaxis) associated with the use of β-lactam antibiotics may be severe and, in rare cases, fatal.

At the first signs of hypersensitivity during treatment with this medicinal product, administration should be discontinued immediately and medical advice should be sought.

Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported with an incidence of "not known" in association with cefpodoxime therapy.

Patients should be informed about the signs and symptoms of these skin reactions, and careful monitoring for skin reactions is required.

If signs or symptoms suggestive of these reactions occur, cefpodoxime should be discontinued immediately and alternative therapy should be considered.

If a patient develops a serious reaction such as SJS, TEN, DRESS, or AGEP during cefpodoxime treatment, re-administration of cefpodoxime is absolutely contraindicated.

Cedoksim® is not an antibiotic for the treatment of staphylococcal pneumonia and should not be used for the treatment of atypical pneumonia caused by Legionella, Mycoplasma, and Chlamydia microorganisms.

Dosage adjustment is required in patients with renal impairment based on creatinine clearance values. Gastrointestinal adverse reactions (e.g., vomiting, nausea, abdominal pain) may occur during treatment; therefore, cefpodoxime should be administered with caution in patients with a history of gastrointestinal disorders, particularly colitis. The development of severe diarrhea during treatment may indicate pseudomembranous colitis caused by Clostridium difficile toxin. These adverse reactions may occur more frequently in patients receiving prolonged therapy and should therefore be considered potentially serious. Clostridium difficile infection should be investigated. In such cases, the drug should be discontinued and appropriate diagnostic evaluation initiated.

If colitis develops, treatment with the drug should be stopped immediately, and sigmoidoscopy and rectomanoscopy should be performed. If further treatment is needed, alternative therapy (e.g., vancomycin) should be initiated. Constipating foods should be avoided. Although any antibiotic may cause pseudomembranous colitis, the risk may be higher with broad-spectrum agents such as cephalosporins.

Neutropenia and agranulocytosis may occur during treatment with β-lactam antibiotics, particularly with prolonged therapy. Blood counts should be monitored if treatment exceeds 10 days, and cefpodoxime therapy should be discontinued if neutropenia develops.

Positive Coombs' test reactions may occur during treatment with Cedoksim® and, very rarely, hemolytic anemia.

Concomitant use with potentially nephrotoxic drugs (e.g., aminoglycosides, furosemide) may impair renal function. Prolonged use of cefpodoxime may lead to overgrowth of resistant microorganisms.

The medicinal product contains the excipient sunset yellow FCF, which may cause allergic reactions.

Use during pregnancy or breastfeeding.

Data on the safety of cefpodoxime use during pregnancy are lacking. Therefore, the drug should be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus, especially during the first trimester.

Cefpodoxime is excreted in breast milk. If treatment is necessary, breastfeeding should be discontinued.

Effect on ability to drive and use machines.

During treatment with this medicinal product, patients should refrain from driving or operating machinery.

Administration and dosage.

The medication should be administered orally during meals to enhance absorption due to the food effect, which increases the bioavailability of cefpodoxime proxetil.

Elderly patients. Dose adjustment in elderly patients without renal impairment is not required.

Hepatic impairment. Dose adjustment in patients with hepatic impairment is not required.

Renal impairment. In patients with severe renal impairment (creatinine clearance < 40 mL/min), the interval between doses should be increased to 24 hours. For patients undergoing hemodialysis, the drug should be administered 3 times a week after hemodialysis sessions. Pharmacokinetic studies indicate an increased elimination half-life and lower peak plasma concentration. Dosage of the drug in patients with renal insufficiency should be adjusted according to creatinine clearance.

There is no need to modify the dose in patients with impaired renal function if creatinine clearance is greater than 40 mL/min.

1. Single dose – 100 mg or 200 mg depending on the type of infection.

Children.

The drug is not intended for children under 12 years of age in the form of coated tablets.

For children under 12 years of age, the drug should be used in the form of a suspension.

Overdose.

Symptoms: nausea, vomiting, epigastric discomfort, diarrhea; encephalopathy may develop in patients with renal insufficiency.

Treatment: gastric lavage. Hemodialysis or peritoneal dialysis, especially in case of impaired renal function.

Adverse Reactions.

Infections and infestations: superinfection caused by some species of the genus Candida resistant to cefpodoxime; antibiotic-associated colitis.

General disorders: malaise, fatigue, asthenia, drug fever, fever, chest pain, back pain, chills, generalized pain, abnormal microbiological tests, abscesses, allergic reactions, facial swelling, bacterial infections; infections due to parasites; localized swelling, localized pain, candidiasis, vaginal fungal infections, vulvovaginal infections, discomfort, breast pain (pain may radiate to the back).

Cardiovascular system: congestive and chronic heart failure, migraine, palpitations, tachycardia, vasodilation, hematomas, arterial hypertension or hypotension.

Gastrointestinal tract: nausea, vomiting, dyspepsia, abdominal pain, dry mouth, bloating, decreased appetite, constipation, diarrhea, anorexia, belching, oral ulcers, gastritis, oral mucosal ulcers, tenesmus, disorders of the rectum, tongue, teeth, thirst, toothache, colitis (antibiotic-induced), candidal stomatitis, dehydration, gout, peripheral edema, weight gain, pseudomembranous colitis.

Hepatobiliary system: cholestatic liver injury.

Blood and lymphatic system: hemolytic anemia, eosinophilia, leukocytosis, lymphocytosis, agranulocytosis, basophilia, monocytosis, thrombocytosis, decreased hemoglobin and hematocrit levels, hemolytic anemia, leukopenia, neutropenia, lymphopenia, thrombocytopenia, thrombocytosis, prolonged thrombin and prothrombin time.

Musculoskeletal system: myalgia.

Nervous system: headache, vertigo, dizziness, headache, sleep disturbances, insomnia, somnolence, anxiety, unsteady gait, irritability, nervousness, cerebral hemorrhage, dream alteration, nightmares, night terrors, paresthesia, confusion.

Respiratory system: asthma, cough, epistaxis, rhinitis, sneezing, wheezing, bronchitis, dyspnea, pleural effusion, pneumonitis, sinusitis, bronchospasm.

Skin: rash, urticaria, pruritus, increased sweating, macular rash, vesicular rash, solar erythema, hyperhidrosis, maculopapular and vesiculobullous rashes, fungal dermatitis, epidermal exfoliation, dry skin, alopecia, sunburn, mucosal candidiasis, bullous reactions (Stevens–Johnson syndrome), toxic epidermal necrolysis, erythema multiforme, acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS).

Hypersensitivity reactions: anaphylactic reactions, angioedema, serum sickness, purpura, arthralgia, fever.

Sensory organs: altered or loss of taste, eye irritation, tinnitus, visual disturbances.

Urinary and reproductive system: hematuria, urinary tract infections, uterine bleeding, dysuria, nocturia, genital infections in males, proteinuria, vaginal pain, vaginal candidiasis, metrorrhagia, frequent urination, proteinuria.

Laboratory findings: most laboratory changes are transient and clinically insignificant; false-positive Coombs test.

Liver: transient increase in AST, ALT, GGT, alkaline phosphatase, bilirubin; cholestatic jaundice.

Biochemical tests: hyper- or hypoglycemia, hypoalbuminemia, hypoproteinemia, hyperkalemia, hyponatremia.

Urinary and reproductive system: increased bilirubin, urea, and creatinine in urine; in isolated cases, renal function impairment, particularly when cefpodoxime is used concomitantly with aminoglycosides and/or potent diuretics.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 30 °C in the original packaging.

Keep out of reach of children.

Packaging.

10 film-coated tablets in a blister; 1 blister per cardboard pack.

Prescription status. Prescription only.

Manufacturer.

Aurobindo Pharma Ltd. Unit VI, Block D.

Manufacturer's address and location of operations.

Survey No. 329/39 and 329/47, Chitkul Village, Patancheru Mandal, Sangareddy District, Telangana State, 502307, India.