Instructions 3-Dinir powder for oral suspension 250 mg/5 ml bottle 60 ml
Composition
active ingredient: cefdinir;
5 ml of suspension contains cefdinir 250 mg;
excipients: sucrose, xanthan gum, colloidal anhydrous silicon dioxide, sodium citrate, anhydrous citric acid, Strawberry flavoring, quinoline yellow (E 104).
Dosage form
Powder for oral suspension.
Main physicochemical properties:
for dry powder: yellow granular powder with a characteristic odor;
for reconstituted suspension: light yellow suspension.
Pharmacotherapeutic group
Antibacterial agent for systemic use. Third generation cephalosporins.
ATX code J01D D15.
Pharmacological properties
Pharmacodynamics
Cefdinir is a third-generation cephalosporin with a broad spectrum of activity against enteric Gram-negative bacteria. Cefdinir is stable in the presence of some, but not all, β-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins are susceptible to cefdinir. Cephalosporins act in the same way as penicillins: they interfere with the synthesis of bacterial cell wall peptidoglycan by inhibiting terminal transpeptidation, which is necessary for cross-linking. This effect is bactericidal.
Mechanism of action
Cefdinir is a β-lactam antibiotic similar to the penicillins and is predominantly bactericidal. Cefdinir inhibits the third and final step of bacterial cell wall synthesis, primarily by binding to penicillin-binding proteins (PBPs), which are located within the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in cell wall synthesis. Thus, the intrinsic activity of cefdinir, like that of other cephalosporins and penicillins against a particular organism, depends on their ability to access and bind to the required PBPs. Like all β-lactam antibiotics, the ability of cefdinir to interfere with PBP-mediated cell wall synthesis ultimately results in cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins).
Mechanism of resistance
Resistance to cefdinir occurs primarily through hydrolysis by some β-lactamases, alteration of penicillin-binding proteins (PBPs), and decreased permeability. Cefdinir is inactive against most strains of Enterobacter spp., Pseudomonas spp., Enterococcus spp., penicillin-resistant streptococci, and methicillin-resistant staphylococci. β-lactamase-negative, ampicillin-resistant (BLNAR) strains of H. influenzae are generally not susceptible to cefdinir.
Cefdinir antimicrobial susceptibility test
| Microorganismsa | MIC (μg/ml) | Zone Diameter (mm) | | | | |
| S | I | R | S | I | R | |
| Haemophilus influenzae | ≤1 | | -- | ≥20 | | -- |
| Haemophilus parainfluenzae | ≤1 | | -- | ≥20 | | -- |
| Moraxella catarrhalis | ≤0.5 | 2 | ≥4 | ≥20 | 17 to 19 | ≤16 |
| Streptococcus pneumoniae | ≤0.5 | 1 | ≥2 | | -- | |
| Streptococcus pyogenes | ≤1 | 2 | ≥4 | ≥20 | 17 to 19 | ≤16 |
a Streptococci other than S. pneumoniae that are susceptible to penicillin (MIC 0.12 μg/mL) can be considered susceptible to cefdinir.
b S. pneumoniae susceptible to penicillin (MIC 0.06 μg/mL) can be considered susceptible to cefdinir. S. pneumoniae isolates tested against a 1 μg oxacillin disk with an oxacillin zone size of 20 mm are susceptible to penicillin and can be considered susceptible to cefdinir. Testing of cefdinir against penicillin-intermediate or penicillin-resistant isolates is not recommended. There are no reliable interpretative criteria for cefdinir.
Antimicrobial activity
Cefdinir has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections.
Gram-positive bacteria
Staphylococcus aureus (methicillin-susceptible strains only)
Streptococcus pneumoniae (penicillin-susceptible strains only)
Streptococcus pyogenes
Gram-negative bacteria
Haemophilus influenzae
Haemophilus parainfluenzae
Moraxella catarrhalis
The following in vitro data are available, but their clinical relevance is unknown.
Cefdinir exhibits in vitro minimum inhibitory concentrations (MICs) of 1 μg/mL or less against (≥ 90%) strains of the following microorganisms; however, the safety and efficacy of cefdinir in the treatment of clinical infections caused by these microorganisms have not been established in adequate and well-controlled clinical studies.
Gram-positive bacteria
Staphylococcus epidermidis (methicillin-susceptible strains only)
Streptococcus agalactiae
Viridans group streptococci
Gram-negative bacteria
Citrobacter koseri
Escherichia coli
Klebsiella pneumonia
Proteus mirabilis.
Cefdinir is administered orally. Once in the systemic circulation, cefdinir is 60–70% bound to plasma proteins in both adults and children; plasma protein binding is independent of concentration. Distribution occurs to various sites, including the lungs, middle ear fluid, sinuses, skin blisters, and tonsils. There is no data on the penetration of cefdinir into human cerebrospinal fluid (CSF). Cefdinir is not significantly metabolized, and its activity is mainly due to the parent drug. Elimination occurs primarily by renal excretion with a mean plasma half-life of approximately 1.7 hours.
Absorption
Oral bioavailability
Peak plasma concentrations of cefdinir occur 2–4 hours after dosing. Plasma concentrations of cefdinir increase with increasing doses, but the increase in concentration is less than dose-proportional from 300 mg (7 mg/kg) to 600 mg (14 mg/kg). Following administration of the suspension to healthy adults, the bioavailability of cefdinir is 120% relative to capsules. The estimated absolute bioavailability of cefdinir suspension is 25%. Cefdinir 250 mg/5 mL oral suspension has been shown to be bioequivalent to a 125 mg/5 mL dosage in healthy adults under fasting conditions.
The impact of food
In adults receiving 250 mg/5 mL of the high-fat oral suspension, the maximum concentration (Cmax) and area under the concentration-time curve (AUC) of cefdinir were reduced by 44% and 33%, respectively. The magnitude of these reductions is not clinically meaningful because safety and efficacy studies of the oral suspension in pediatric patients were conducted without regard to food intake. Therefore, cefdinir can be taken without regard to food.
Metabolism and excretion
Cefdinir is not metabolized significantly. The activity is mainly due to the active substance. Cefdinir is eliminated primarily by renal excretion, with a mean plasma elimination half-life (t½) of 1.7 (±0.6) hours. In healthy subjects with normal renal function, renal clearance is 2.0 (±1.0) ml/min/kg, and peripheral clearance is 11.6 (±6.0) and 15.5 (±5.4) ml/min/kg after 300 and 600 mg doses, respectively. The mean percentage of the dose excreted unchanged in the urine after 300 and 600 mg doses is 18.4% (±6.4) and 11.6% (±4.6), respectively. Renal clearance is reduced in patients with impaired renal function.
Since renal excretion is the major route of elimination, the dose should be adjusted in patients with marked renal impairment or those on hemodialysis.
Indication
Mild to moderate infections in children caused by susceptible strains of the following microorganisms:
community-acquired pneumonia caused by Haemophilus influenzae (including β-lactamase-producing strains), Haemophilus parainfluenzae (including β-lactamase-producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only) and Moraxella catarrhalis (including β-lactamase-producing strains);
exacerbation of chronic bronchitis caused by Haemophilus influenzae (including β-lactamase-producing strains), Haemophilus parainfluenzae (including β-lactamase-producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only) and Moraxella catarrhalis (including β-lactamase-producing strains);
acute sinusitis caused by Haemophilus influenzae (including β-lactamase-producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only) and Moraxella catarrhalis (including β-lactamase-producing strains);
pharyngitis/tonsillitis caused by Streptococcus pyogenes;
uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (including β-lactamase-producing strains) and Streptococcus pyogenes;
acute bacterial otitis media caused by Haemophilus influenzae (including β-lactamase-producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only) and Moraxella catarrhalis (including β-lactamase-producing strains).
Contraindication
The drug is contraindicated in patients with a known allergy to cephalosporin antibiotics.
Interaction with other medicinal products and other types of interactions
Antacids (aluminum or magnesium-containing)
Co-administration of 300 mg of cefdinir and 30 ml of aluminum hydroxide and magnesium hydroxide suspension resulted in a decrease in the rate of Cmax and the extent of AUC of absorption by approximately 40%. The time to reach Cmax is also prolonged by 1 hour. Antacids do not have a significant effect on the pharmacokinetics of cefdinir if they are administered 2 hours before or 2 hours after the administration of cefdinir. If the use of antacids during therapy with Cefdinir is necessary, the drug should be taken at least 2 hours before or 2 hours after taking the antacid.
Probenecid
As with other β-lactam antibiotics, probenecid inhibits the renal excretion of cefdinir, resulting in an approximately two-fold increase in AUC, a 54% increase in maximum plasma concentration, and a 50% prolongation of the elimination half-life (t½).
Concomitant administration of cefdinir with iron preparations containing 60 mg elemental iron (as FeSO4) or vitamin preparations containing 10 mg elemental iron reduced the absorption of cefdinir by 80% and 31%, respectively. If a patient requires iron supplements during cefdinir therapy, cefdinir should be taken at least 2 hours before or after taking the iron preparations. The effect of foods high in elemental iron (mainly iron-fortified breakfast cereals) on the absorption of cefdinir has not been studied.
Iron-fortified infant formula has no significant effect on the pharmacokinetics of cefdinir. Therefore, cefdinir oral suspension can be administered concomitantly with iron-fortified infant formula.
Cases of reddish stool discoloration have been reported in patients receiving the drug. In many cases, these patients were also receiving iron-fortified foods. The reddish color is due to the formation of a complex of cefdinir or its degradation products with iron, which is not absorbed in the gastrointestinal tract.
Application features
Warning
Before initiating therapy with cefdinir, careful inquiry should be made to determine whether the patient has had a previous hypersensitivity reaction to cefdinir, other cephalosporins, penicillins, or other drugs. Caution should be exercised when prescribing cefdinir to patients sensitive to penicillin, as cross-hypersensitivity among β-lactam antibiotics has been demonstrated, which may occur in up to 10% of patients with a history of allergic reactions to penicillin. If an allergic reaction occurs following administration of cefdinir, the drug should be discontinued. In the event of a serious hypersensitivity reaction, administration of epinephrine and other emergency measures may be necessary, including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids, pressor amines, and airway management as clinically indicated.
Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including cefdinir, and may range in severity from mild diarrhea to fatal colitis. Antibacterial therapy alters the normal flora of the colon, resulting in overgrowth of C. difficile strains. C. difficile produces toxins A and B, which contribute to the development of pseudomembranous colitis. Toxin-producing strains of C. difficile cause increased morbidity and mortality because these infections may be difficult to treat with antimicrobial therapy and may require colectomy. Patients who present with diarrhea following antibiotic therapy should be evaluated for pseudomembranous colitis. A careful medical history is necessary because symptoms of pseudomembranous colitis have been reported to occur within 2 months of antibiotic administration. In case of suspected or confirmed pseudomembranous colitis, discontinuation of antibiotics not directed against C. difficile is recommended. Based on the clinical condition, the patient may be shown to restore fluid and electrolyte balance, administer electrolyte and amino acid solutions, treat with Clostridium difficile antibiotics, or undergo surgery.
Safety measures
The general prescription of cefdinir in the absence of a proven or substantiated suspected bacterial infection, or a valid reason for prophylactic administration, is of questionable benefit to the patient and increases the risk of the development of antibiotic-resistant bacteria.
As with other broad-spectrum antibiotics, prolonged treatment with cefdinir may result in the emergence and overgrowth of drug-resistant microorganisms. The patient should be closely monitored. If superinfection develops during therapy, appropriate alternative therapy should be used. Cefdinir, as with other broad-spectrum antimicrobials (antibiotics), should be administered with caution to patients with a history of colitis. In patients with transient or persistent renal impairment (creatinine clearance <30 ml/min), the total daily dose of cefdinir should be reduced, since administration of the recommended doses may result in significant increases in plasma concentrations and half-life of cefdinir.
False-positive urine glucose tests have been observed in patients receiving cephalosporins such as cefdinir. Diabetic patients who test their urine for glucose should use glucose oxidase-based enzymatic glucose tests during treatment with cefdinir.
Important information about some of the components of the drug.
The suspension contains sucrose. This should be taken into account in patients with diabetes. A doctor's consultation is required.
Use during pregnancy or breastfeeding
The drug is intended for use in children. Adequate and well-controlled studies of the use of cefdinir in pregnant women have not been conducted. Cefdinir has not been detected in breast milk after administration of a single dose of 600 mg.
Ability to influence reaction speed when driving vehicles or other mechanisms
The drug is intended for use in children. Cefdinir may cause side effects that affect concentration and reaction speed.
Method of administration and doses
Route of administration: oral.
Dosage
The recommended dosage regimen and duration of treatment for infections in children are described in the table below; the total daily dose for all infections is 14 mg/kg, up to a maximum dose of 600 mg per day. Once daily administration for 10 days is as effective as twice daily administration. Once daily administration has not been studied in skin infections; therefore, cefdinir oral suspension should be administered twice daily in these infections. The suspension may be taken without regard to meals.
Children (under 12 years old)
| Type of infection | Dose | Duration of treatment |
| Acute otitis media | 7 mg/kg every 12 hours or 14 mg/kg once every 24 hours | 5–10 days 10 days |
| Acute upper sinusitis | 7 mg/kg every 12 hours or 14 mg/kg once every 24 hours | 10 days 10 days |
| Pharyngitis/Tonsillitis | 7 mg/kg every 12 hours or 14 mg/kg once every 24 hours | 5–10 days 10 days |
| Uncomplicated skin and soft tissue infections | 7 mg/kg every 12 hours | 10 days |
Approximate dosage schedule for cefdinir for children*
| Body weight | 1 time per 12 hours | 1 time per 24 hours | Body weight | 1 time per 12 hours | 1 time per 24 hours |
| 7–8 kg | 1 ml | 2 ml | 25–26 kg | 3.5 ml | 7 ml |
| 9–10 kg | 1.25 ml | 2.5 ml | 27–28 kg | 3.75 ml | 7.5 ml |
| 11–12 kg | 1.5 ml | 3 ml | 29–30 kg | 4 ml | 8 ml |
| 13–14 kg | 1.75 ml | 3.5 ml | 31–32 kg | 4.25 ml | 8.5 ml |
| 15–16 kg | 2 ml | 4 ml | 33–34 kg | 4.75 ml | 9.5 ml |
| 17–18 kg | 2.5 ml | 5 ml | 35–36 kg | 5 ml | 10 ml |
| 19–20 kg | 2.75 ml | 5.5 ml | 37–38 kg | 5.25 ml | 10.5 ml |
| 21–22 kg | 3 ml | 6 ml | 39–40 kg | 5.5 ml | 11 ml |
| 23–24 kg | 3.25 ml | 6.5 ml | 41–42 kg | 5.75 ml | 11.5 ml |
| ≥ 43** | 6 ml | 12 ml | | | |
* The dose is determined individually by the doctor depending on the age and body weight of the patient. For all patients aged 6 months to 12 years, a single dose of the drug is 7 mg/kg body weight, or 0.14 ml of suspension per 1 kg of body weight.
** For children weighing ≥ 43 kg, the drug is prescribed in a maximum daily dose of 600 mg.
Patients with renal impairment
The recommended dose for patients with creatinine clearance (CLcr) < 30 mL/min is 300 mg of cefdinir twice daily.
Creatinine clearance is difficult to measure on an outpatient basis.
The following formula can be used to determine CLcr in children:
where K=0.55 for children over 1 year of age and 0.45 for infants (under 1 year of age).
In both cases, CLcr is calculated in ml/min/1.73 m2, body length or height in centimeters, and serum creatinine in ml/dl.
Patients on hemodialysis
Cefdinir is removed from the body by hemodialysis.
In patients on chronic hemodialysis, the recommended initial dosage regimen is 300 mg or 7 mg/kg every other day. 300 mg (or 7 mg/kg) should be administered after each hemodialysis session. Subsequent doses (300 mg or 7 mg/kg) should be administered every other day.
Cefdinir dilution instructions for oral suspension
| Final concentration | Final volume (ml) | Amount of water | Instruction |
| 250 mg/5 ml | 60 | 38 ml | Tap the bottle to loosen the powder, then add water in two portions. Shake well after each addition of water. |
Children
The drug is prescribed for children aged 6 months (with a body weight of at least 7 kg) to 12 years.
The safety and efficacy of the drug in children under 6 months of age have not been studied.
Overdose
Information on overdose with cefdinir in humans is not available. Toxic signs and symptoms following overdose with other β-lactam antibiotics have included nausea, vomiting, epigastric discomfort, diarrhea, and convulsions. Cefdinir is removed from the body by hemodialysis. This information should be considered in cases of serious intoxication due to overdose, especially in cases of impaired renal function.
Side effects
Adverse reactions associated with the use of cefdinir in studies involving adult patients, adolescents and children:
| Frequency | Effects |
| Frequency ≥ 1% | Diarrhea Rash Vomiting |
| Frequency < 1% but > 0.1% | Soft tissue candidiasis Pain in the epigastric region Leukopenia Vaginal candidiasis Vaginitis Atypical bowel movements Dyspepsia Hyperkinesia (increased muscle activity) Increased AST levels Maculopapular rash Nausea |
The following adverse reactions and laboratory test abnormalities, regardless of their relationship to cefdinir use, have been reported during the long post-marketing period: Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, erythema nodosum, bloody diarrhea, hemorrhagic colitis, pseudomembranous colitis, pancytopenia, granulocytopenia, leukopenia, thrombocytopenia, idiopathic thrombocytopenic purpura, hemolytic anemia, bleeding tendency, coagulation disorders, disseminated intravascular coagulation syndrome, upper gastrointestinal bleeding, loss of consciousness, allergic vasculitis, hypertension, involuntary movements.
The following adverse reactions and laboratory abnormalities have been reported, which are generally typical of cephalosporin antibiotics:
allergic reactions, anaphylaxis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic disease, pancytopenia, and agranulocytosis. Symptoms of pseudomembranous colitis may occur during or after antibiotic treatment.
The use of some cephalosporins has been associated with the development of seizures, especially in patients with impaired renal function, for whom dose adjustment has not been performed. If seizures occur during therapy, the drug should be discontinued. If clinically indicated, anticonvulsant therapy may be prescribed.
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Store the prepared suspension for no more than 10 days at a temperature not exceeding 25 °C.
Packaging
1 bottle with powder for the preparation of 60 ml of suspension complete with a dosing syringe in a cardboard box.
Vacation category
According to the recipe.
Producer
Sense Laboratories Pvt. Ltd.
Address
VI/51B, P/O No. 2, Kojuvanal, Pala, Kottayam – 686 573, Kerala, India.
Applicant
LLC "ARTERIUM LTD".
