Rodinir

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

Composition:

Active substance: cefdinir;

5 ml of oral suspension contains cefdinir 250 mg;

Excipients: citric acid, anhydrous; sodium citrate dihydrate; sodium benzoate; xanthan gum; guar gum; colloidal hydrated silicon dioxide; magnesium stearate; strawberry flavor; cream flavor; sucrose.

Pharmaceutical form. Powder for oral suspension.

Main physicochemical properties:

Powder: homogeneous granular cream-yellow powder with a strawberry and cream odor;

Prepared suspension: homogeneous cream-yellow suspension with a strawberry and cream odor.

Pharmacotherapeutic group.

Antimicrobial agents for systemic use. Other beta-lactam antibiotics. Third-generation cephalosporins. ATC code J01D D15.

Pharmacological Properties.

Pharmacodynamics.

Cefdinir is a semi-synthetic, oral, broad-spectrum cephalosporin antibiotic of the third generation.

Like other antibiotics in the cephalosporin class, cefdinir exerts a bactericidal effect against susceptible microorganisms by inhibiting cell wall synthesis. It is resistant to the action of many, but not all, beta-lactamases. As a result, many microorganisms resistant to penicillins and some cephalosporins remain sensitive to cefdinir.

The antimicrobial spectrum of cefdinir includes:

• Aerobic gram-positive microorganisms: Staphylococcus aureus (only methicillin-susceptible strains), Streptococcus pneumoniae (only penicillin-susceptible strains), Streptococcus pyogenes;
• Aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis.

The minimum inhibitory concentration (MIC) of cefdinir in vitro is 1 mcg/mL or less against (>90%) of the strains of the following microorganisms; however, its safety and efficacy in treating infections caused by these microorganisms have not been established in adequate and well-controlled clinical trials.

Aerobic gram-positive microorganisms: Staphylococcus epidermidis, Streptococcus agalactiae, Streptococcus group viridans.

Aerobic gram-negative microorganisms: Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis.

Pharmacokinetics.

Absorption.

After oral administration, the time to reach maximum plasma concentration of cefdinir ranges from 2 to 4 hours. Plasma concentrations of cefdinir increase with increasing dose; however, the increase becomes less proportional within the dose range of 300 mg (7 mg/kg) to 600 mg (14 mg/kg).

When cefdinir is taken with a high-fat meal, the maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) decrease by 16% and 10%, respectively. This reduction is considered clinically insignificant. Therefore, cefdinir may be administered regardless of food intake.

With single or twice-daily dosing in patients with normal renal function, cefdinir does not accumulate in plasma.

Distribution.

The mean volume of distribution (Vdarea) of cefdinir in adult patients is 0.35 L/kg (±0.29); in pediatric patients (aged 6 months to 12 years), Vdarea is 0.67 L/kg (±0.38). The extent of binding of cefdinir to plasma proteins ranges from 60% to 70% in adults. In pediatric patients, the degree of binding is independent of cefdinir concentration.

Metabolism and Excretion.

Cefdinir undergoes no significant metabolism. It is primarily eliminated by the kidneys, with a mean elimination half-life (T1/2) of 1.7 (±0.6) hours. In healthy volunteers with normal renal function, creatinine clearance (CrCl) is 2.0 (±1.0) mL/min/kg, and oral clearance is 11.6 (±6.0) and 15.5 (±5.4) mL/min/kg after administration of 300 mg and 600 mg of cefdinir, respectively. The mean percentage of the administered dose excreted unchanged in urine is 18.4% (±6.4) and 11.6% (±4.6) after 300 mg and 600 mg doses, respectively. Cefdinir clearance is reduced in patients with impaired renal function.

Since renal excretion is the principal route of elimination of cefdinir, dosage adjustment is required in patients with severe renal impairment and in patients undergoing hemodialysis.

Elderly Patients.

Systemic exposure to cefdinir is significantly increased in elderly individuals: Cmax and AUC are increased by 44% and 86%, respectively. This is due to reduced clearance. The volume of distribution is also reduced. However, no significant change in mean T1/2 of cefdinir was observed (elderly patients: 2.2 ± 0.6 hours vs. younger patients: 1.8 ± 0.4 hours). Since cefdinir clearance is primarily related to changes in renal function rather than age, dosage adjustment is not necessary in elderly patients.

Patients with Hepatic Impairment.

Because cefdinir is primarily eliminated by the kidneys and undergoes negligible metabolism, studies in patients with hepatic impairment have not been conducted. Dosage adjustment is not anticipated in these patients.

Patients with Renal Impairment.

In patients with CrCl of 30 to 60 mL/min, Cmax and T1/2 are approximately doubled, and AUC is increased approximately threefold. In patients with CrCl <30 mL/min, Cmax is increased approximately twofold, T1/2 approximately fivefold, and AUC approximately sixfold. Dosage adjustment is required in patients with severe renal impairment (CrCl <30 mL/min).

Patients on Hemodialysis.

During dialysis (lasting 4 hours), 63% of cefdinir is removed from the body, and T1/2 decreases from 16 (±3.5) to 3.2 (±1.2) hours. Dosage adjustment is recommended for patients undergoing hemodialysis.

Clinical characteristics.

Indications.

Adults and children aged 13 years and older

Community-acquired pneumonia caused by:

• Haemophilus influenzae (including beta-lactamase-producing strains);
• Haemophilus parainfluenzae (including beta-lactamase-producing strains);
• Streptococcus pneumoniae (only penicillin-susceptible strains);
• Moraxella catarrhalis (including beta-lactamase-producing strains).

Acute exacerbation of chronic bronchitis caused by:

• Haemophilus influenzae (including beta-lactamase-producing strains);
• Haemophilus parainfluenzae (including beta-lactamase-producing strains);
• Streptococcus pneumoniae (only penicillin-susceptible strains);
• Moraxella catarrhalis (including beta-lactamase-producing strains).

Acute sinusitis caused by:

• Haemophilus influenzae (including beta-lactamase-producing strains);
• Streptococcus pneumoniae (only penicillin-susceptible strains);
• Moraxella catarrhalis (including beta-lactamase-producing strains).

Pharyngitis/tonsillitis caused by:

• Streptococcus pyogenes.

Uncomplicated skin and soft tissue infections caused by:

• Staphylococcus aureus (including beta-lactamase-producing strains);
• Streptococcus pyogenes.

Children with body weight of 18 kg or more

Acute otitis media caused by:

• Haemophilus influenzae (including beta-lactamase-producing strains);
• Streptococcus pneumoniae (only penicillin-susceptible strains);
• Moraxella catarrhalis (including beta-lactamase-producing strains).

Acute sinusitis caused by:

• Haemophilus influenzae (including beta-lactamase-producing strains);
• Streptococcus pneumoniae (only penicillin-susceptible strains);
• Moraxella catarrhalis (including beta-lactamase-producing strains).

Pharyngitis/tonsillitis caused by:

• Streptococcus pyogenes.

Uncomplicated skin and soft tissue infections caused by:

• Staphylococcus aureus (including beta-lactamase-producing strains);
• Streptococcus pyogenes.

Contraindications.

Hypersensitivity to cefdinir, other cephalosporins, or to any excipients of the medicinal product.

Interaction with other medicinal products and other types of interactions.

When cefdinir is used concomitantly with other medicinal products, the following interactions are possible:

With antacids (containing aluminum or magnesium) – reduction in Cmax and AUC of cefdinir by approximately 40%. When these medicinal products are used concomitantly, cefdinir should be taken at least 2 hours before or 2 hours after the antacid.

With iron-containing medicinal products (containing 60 mg of elemental iron), vitamin preparations (containing 10 mg of iron) – decreased absorption of cefdinir by 80% and 31%, respectively. When these medicinal products are used concomitantly, cefdinir should be taken at least 2 hours before or 2 hours after the iron-containing product.

Cases of reddish discoloration of stools have been reported in patients taking cefdinir. In many cases, patients were concurrently taking iron-fortified products. The red discoloration may be related to the formation in the gastrointestinal tract of a complex between cefdinir or its degradation products and unabsorbed iron.

With probenecid – impaired renal excretion of cefdinir (as with other cephalosporins), resulting in a doubling of AUC, an increase in Cmax by 54%, and prolongation of T1/2 by 50%.

Interaction with laboratory tests.

During cefdinir use, false-positive urine ketone tests may occur when using sodium nitroprusside, but not nitroferricyanide.

Cefdinir use may also cause false-positive urine glucose tests when using Benedict's solution or Fehling's reagent. Urine glucose should be tested using enzymatic methods only.

Cephalosporin use may occasionally lead to false-positive direct Coombs' test results.

Special Warnings and Precautions for Use

Administration of the medicinal product in the absence of proven or strongly suspected bacterial infection, or prophylactic use of cefdinir, is of questionable benefit to the patient and increases the risk of developing antimicrobial resistance.

Prior to initiating treatment with the medicinal product, it is essential to rule out a history of hypersensitivity reactions to cefdinir, other cephalosporins, penicillins, or other medicinal agents.

As with other broad-spectrum antibiotics, prolonged treatment with cefdinir may lead to overgrowth of non-susceptible microorganisms. Patients should be closely monitored. If superinfection occurs, appropriate alternative therapy should be instituted.

Effect on the Immune System

Extreme caution should be exercised when administering cefdinir to patients with known hypersensitivity to penicillins, as cross-hypersensitivity between beta-lactam antibiotics has been documented and may affect up to 10% of patients with a history of penicillin allergy.

If hypersensitivity reactions occur, the drug should be discontinued immediately. In the event of severe allergic reactions, administration of epinephrine and other emergency measures may be required, including oxygen administration, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway maintenance, as clinically indicated.

Effect on the Gastrointestinal Tract

Antibacterial agents alter the normal gut flora of the colon, which may lead to overgrowth of Clostridium difficile, subsequent release of toxins A and B, and development of antibiotic-associated diarrhea (AAD). Since C. difficile may be refractory to antimicrobial therapy, this condition is associated with increased morbidity and mortality and may require colectomy.

Antibiotic-associated diarrhea, ranging from mild diarrhea to fatal colitis, has been reported with nearly all antibacterial agents, including cefdinir. A diagnosis of AAD should be considered in any patient presenting with diarrhea during or following antibiotic therapy. A careful patient history is essential, as cases of delayed-onset AAD have been reported, including cases of pseudomembranous colitis occurring up to 2 months after completion of antimicrobial therapy.

If AAD is suspected or confirmed, the medicinal product should be discontinued. Depending on the clinical condition, management may include fluid and electrolyte replacement, amino acid solutions, specific antibiotic therapy directed against C. difficile, and surgical intervention.

Use in Patients with a History of Colitis

The medicinal product should be administered with caution to patients with a history of colitis.

Use in Patients with Renal Impairment

Patients with transient or persistent renal impairment (creatinine clearance < 30 mL/min) should receive a reduced daily dose of the medicinal product, as administration at the recommended doses may result in significantly increased plasma concentrations and prolonged elimination half-life of cefdinir.

Use During Pregnancy or Breastfeeding

Reproduction studies in animals have shown no teratogenic effects. However, data on the use of cefdinir in pregnant women are lacking. The medicinal product may be used during pregnancy only if clinically justified.

When administered at a dose of 600 mg, cefdinir is not detected in breast milk.

Ability to Affect Reaction Speed While Driving or Operating Machinery

The medicinal product does not affect the ability to drive or operate machinery.

Method of administration and dosage

The medicinal product is intended for oral administration.

The suspension is prepared immediately before first use. Shake the bottle to loosen the powder, then add 38 ml or 63 ml of boiled, cooled-to-room-temperature water in two portions (up to the mark), shaking vigorously each time. Then allow the suspension to stand for approximately 5 minutes to ensure complete dissolution. The suspension should be shaken well before each use. For accurate dosing, a 5 ml measuring spoon should be used, which must be thoroughly rinsed with water after each use. After reconstitution, the suspension should be stored for no longer than 10 days at room temperature. For ease of administration, the suspension may be diluted with water in a 1:2 ratio for children under 2 years of age. The medicinal product may be administered independently of food intake.

The dosage regimen should be determined individually, depending on the patient's age, body weight, renal function, and the severity of the infection.

Adults and children aged 13 years and older

The total daily dose for treatment of all infections is 14 mg/kg body weight. The maximum daily dose of the medicinal product is 600 mg. Administration once daily for 10 days is as effective as administration twice daily. However, once-daily administration of cefdinir has not been studied in the treatment of skin infections; therefore, in such cases, the medicinal product should be taken twice daily.

Children with body weight of 18 kg and above

The recommended dosage and duration of treatment for infections are indicated in the tables below.

Table 1

Type of infection	Dosage	Duration
Acute otitis media	7 mg/kg every 12 hours or 14 mg/kg every 24 hours	5-10 days or 10 days

Acute sinusitis	7 mg/kg every 12 hours or 14 mg/kg every 24 hours	10 days
Pharyngitis/tonsillitis	7 mg/kg every 12 hours or 14 mg/kg every 24 hours	5–10 days or 10 days
Uncomplicated skin and soft tissue infections	7 mg/kg every 12 hours or 14 mg/kg every 24 hours	10 days

Table 2

Body weight, kg	Dosage
18	2.5 ml every 12 hours or 5 ml once daily
27	3.75 ml every 12 hours or 7.5 ml once daily
36	5 ml every 12 hours or 10 ml once daily
≥ 431	6 ml every 12 hours or 12 ml once daily

1For children with body weight ≥ 43 kg, the medicinal product should be administered at the maximum daily dose of 600 mg.

Patients with renal impairment.

In adult patients with creatinine clearance < 30 ml/min, the medicinal product should be administered at a dose of 300 mg once daily; in children – 7 mg/kg once daily (up to 300 mg per day).

The following formula may be used to estimate creatinine clearance (CC) in adult patients. Plasma creatinine should reflect a steady state of kidney function.

[140 – age (in years)] × body weight (kg) 72 × plasma creatinine (mg/dL)

(× 0.85 for women)

CC (ml/min) =

To estimate CC in children, the following formula can be used.

K × height (cm)_________________ plasma creatinine (mg/dL)

CC (mL/min/1.73 m²) =

K = 0.55 for children with body weight ≥18 kg.

Patients on hemodialysis.

For patients on chronic hemodialysis, the recommended initial dose is 300 mg or 7 mg/kg every other day. Administer 300 mg (or 7 mg/kg) of cefdinir at the end of each hemodialysis session; subsequent doses (300 mg or 7 mg/kg) should be administered every other day.

Patients with hepatic impairment.

Dosage adjustment is not required for these patients.

Elderly patients.

No dosage adjustment is necessary for elderly patients.

Children.

The drug should be administered to children with body weight ≥18 kg.

Overdose.

There are no data regarding cefdinir overdose in humans. In acute toxicity studies in rodents, single oral doses of cefdinir up to 5600 mg/kg did not result in any adverse reactions. With overdose of other cephalosporins, symptoms and signs reported include nausea, vomiting, gastric discomfort, diarrhea, and seizures.

Cefdinir is removed by hemodialysis, which may be beneficial in the event of serious toxic reactions due to overdose, particularly in patients with impaired renal function.

Adverse reactions.

The following adverse reactions were observed during treatment with cefdinir at the following frequencies: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10000 and <1/1000), very rare (<1/10000), frequency not known (cannot be estimated from available data):

Common – diarrhea, vaginal candidiasis, nausea, headache, abdominal pain, vaginitis;

Uncommon – rash, dyspepsia, flatulence, vomiting, defecation disorder, anorexia, constipation, dizziness, dry mouth, asthenia, insomnia, leukorrhea, candidiasis, pruritus, somnolence.

The following adverse reactions have been reported with the use of cephalosporin-class antibiotics:

allergic reactions, anaphylaxis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, renal function disorders, toxic nephropathy, hepatic function disorders (including cholestasis), aplastic anemia, hemolytic anemia, hemorrhagic disorders, false-positive urine glucose test, neutropenia, pancytopenia, and agranulocytosis. Pseudomembranous colitis may develop during or after antibiotic therapy.

Seizures have been reported with some cephalosporins, particularly in patients with renal impairment who did not receive dose adjustment. If seizures occur, discontinue the drug. Anticonvulsant therapy may be initiated if clinically indicated.

Post-marketing experience with cefdinir has also revealed the following adverse reactions: shock, anaphylaxis (rarely with fatal outcome), facial and laryngeal edema, sensation of suffocation, serum sickness, conjunctivitis, stomatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, nodular erythema, acute hepatitis, cholestasis, fulminant hepatitis, hepatic failure, jaundice, elevated amylase levels, acute enterocolitis, hemorrhagic diarrhea, hemorrhagic colitis, melena, pseudomembranous colitis, pancytopenia, granulocytopenia, leukopenia, thrombocytopenia, idiopathic thrombocytopenic purpura, hemolytic anemia, acute respiratory failure, asthma attack, drug-induced pneumonia, eosinophilic pneumonia, idiopathic interstitial pneumonia, collapse, acute renal failure, nephropathy, tendency to bleeding, coagulation disorders, generalized thrombohemorrhagic syndrome, upper gastrointestinal bleeding, peptic ulcer, intestinal obstruction, loss of consciousness, allergic vasculitis, possible cefdinir-diclofenac interaction, heart failure, chest pain, myocardial infarction, hypertension, involuntary movements, rhabdomyolysis.

Reporting suspected adverse reactions.

Reporting of suspected adverse reactions after drug registration is very important. This allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national pharmacovigilance system.

Shelf life. 3 years.

The prepared suspension can be stored for up to 10 days.

Storage conditions.

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

Packaging.

60 ml or 100 ml in a bottle with a cap; 1 bottle with a measuring spoon in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

PharmaVision San. ve Tic. A.S.

Manufacturer's address and location of operations.

Davutpasa Cad. No:145 Zeytinburnu Istanbul, Turkey.

Marketing authorization holder.

WORLD MEDICINE, LLC, Ukraine.