3-dinir capsules 300 mg blister No. 10

Instructions 3-dinir capsules 300 mg blister No. 10

Composition

active ingredient: cefdinir;

1 capsule contains: cefdinir in terms of dry matter – 300 mg;

Excipients: calcium carboxymethylcellulose, polyethylene glycol (macrogol) stearate, colloidal anhydrous silicon dioxide, magnesium stearate.

Capsule shell composition: black iron oxide (E 172), titanium dioxide (E 171), gelatin.

Dosage form

Capsules.

Main physicochemical properties: hard gelatin capsules with a gray body and a black cap.

Pharmacotherapeutic group

Antibacterials for systemic use. Other beta-lactam antibacterials. Third-generation cephalosporins. Cefdinir.

ATX code J01D D15.

Pharmacological properties

Pharmacodynamics

As with other cephalosporins, the bactericidal activity of cefdinir is due to inhibition of cell wall synthesis. Cefdinir is resistant to some, but not all, β-lactamase enzymes. This property renders many organisms resistant to penicillins and some cephalosporins susceptible to cefdinir. Cefdinir has been shown to be active against most strains of these organisms both in vitro and in clinical infections.

The spectrum of action of cefdinir includes:

Aerobic gram-positive microorganisms:

Staphylococcus aureus (including strains producing β-lactamases, but inactive against methicillin-resistant staphylococci);

Streptococcus pneumoniae (penicillin-sensitive strains only);

Streptococcus pyogenes.

Aerobic Gram-negative microorganisms:

Haemophilus influenzae (including β-lactamase-producing strains);

Haemophilus parainfluenzae (including β-lactamase-producing strains);

Moraxella catarrhalis (including β-lactamase-producing strains).

The data listed below were obtained in vitro, but their clinical relevance is unknown.

The minimum inhibitory concentration (MIC) of cefdinir in vitro is 1 μg/mL or less against strains (> 90%) of the following microorganisms, however, the safety and efficacy of cefdinir in the treatment of infections caused by the following microorganisms have not been demonstrated in clinical studies.

Aerobic gram-positive microorganisms:

Staphylococcus epidermidis (methicillin-sensitive strains only);

Streptococcus agalactiae;

Streptococcus viridans group.

Note: Cefdinir is inactive against Enterococcus, methicillin-resistant Staphylococcus species.

Aerobic Gram-negative microorganisms:

Citrobacter diversus;

Escherichia coli;

Klebsiella pneumoniae;

Proteus mirabilis.

Note: Cefdinir is inactive against Pseudomonas and Enterobacter species.

Sensitivity tests

The following minimum MIC values were determined by serial dilution method:

For organisms other than Haemophilus spp. and Streptococcus spp.:

For Haemophilus spp.:a

a - these interpretation standards are applicable only to broth dilution susceptibility testing of Haemophilus spp. strains using Haemophilus Test Medium (HTM) (1);

The absence of data on the presence of resistant strains precludes the determination of results other than “susceptible.” Strains that give MIS results indicating the “unsuitability” category should be sent to a reference laboratory for further testing.

For Streptococcus spp.:

Streptococcus pneumoniae susceptible to penicillin (MIC ≤ 0.06 μg/mL) or streptococci other than S. pneumoniae susceptible to penicillin (MIC ≤ 0.12 μg/mL) may be considered susceptible to cefdinir. Testing of cefdinir against isolates that are moderately susceptible or resistant to penicillin is not recommended. Reliable interpretative criteria for cefdinir are not available.

A result of “susceptible” indicates that the organism is likely to be inhibited when the blood concentration of the antimicrobial agent reaches its usual values. A result of “intermediately susceptible” indicates that the result obtained should be considered equivocal and that the organism is not fully susceptible to alternative, clinically equivalent drugs. Such a test should be repeated. The category of “intermediately susceptible” implies possible clinical utility in body sites where the drug is physiologically concentrated or in situations where a high dose of the drug may be used. This category also provides a buffer zone that prevents minor uncontrolled technical factors from causing serious discrepancies in interpretation. A result of “resistant” indicates that the organism is likely not to be inhibited when the blood concentration of the antimicrobial agent reaches its usual values. In such cases, alternative therapy should be considered.

Standardized susceptibility testing procedures include the use of test cultures (to monitor technical aspects of the procedure). Standard cefdinir powder should provide the following MIC values:

c - This quality control range is only applicable to Haemophilus influenzae ATCC 49766, which was tested by the broth dilution method using HTM.

The following MIC values were determined by the agar diffusion method:

d - Since some strains of Citrobacter, Providencia and Enterobacter spp. give unreliable susceptibility results when using the cefdinir disk, strains of these genera should not be tested and interpreted with this disk.

For Haemophilus spp.:e

e - the specified zone diameter standards are only applicable to tests with Haemophilus spp. using HTM(2);

f - the absence of data on the presence of resistant strains precludes the determination of results other than “susceptible”. Strains that give MIS results indicating the “unsuitability” category should be transferred to the reference laboratory for further testing.

For Streptococcus spp.:

Streptococcus pneumoniae isolates should be tested on 1 μg oxacillin disks. Isolates with oxacillin zone sizes ≥ 20 mm are susceptible to penicillin and may be considered susceptible to cefdinir. Streptococci (except S. pneumoniae) should be tested on 10 U penicillin disks. Isolates with penicillin zone sizes ≥ 28 mm are susceptible to penicillin and may be considered susceptible to cefdinir.

As with standardized serial dilution methods, agar diffusion methods require the use of test organisms to control the technical aspects of the laboratory procedures. For the 5 μg cefdinir disk diffusion method, the following zone diameters should be achieved:

g - This quality control range is only applicable to Haemophilus influenzae ATCC 49766 using HTM.

Pharmacokinetics

Absorption

Oral bioavailability

The maximum plasma concentration of cefdinir (Cmax) is reached 2–4 hours after administration of the drug. Plasma concentration of cefdinir increases with dose, but the increase becomes less proportional in the dose range from 300 (7 mg/kg) to 600 mg (14 mg/kg). The expected bioavailability of cefdinir capsules is 21% after administration of 300 mg and 16% after administration of 600 mg of the drug.

The impact of food

Cmax and AUC of cefdinir are decreased by 16% and 10%, respectively, when a high-fat meal is consumed. The percentage decrease in these values is probably not clinically significant. Therefore, cefdinir can be taken without regard to food intake.

The plasma concentrations and pharmacokinetic parameters of cefdinir following single oral doses of 300–600 mg to healthy adult volunteers are shown in the following table:

Mean (± SD) values of cefdinir pharmacokinetic parameters in blood plasma after drug administration

Multiple reception

Cefdinir does not accumulate in plasma after once or twice daily dosing in patients with normal renal function.

Distribution

The mean volume of distribution (Vd) of cefdinir in adults is 0.35 l/kg (± 0.29), and in children (aged 6 months to 12 years) the Vd of cefdinir is 0.67 l/kg (± 0.38). 60–70% of cefdinir is bound to plasma proteins in both adults and children, and binding is independent of concentration.

Skin blisters

In adult patients, median (range) cefdinir concentrations in blister fluid of 0.65 (0.33-1.1) and 1.1 (0.49-1.9) mg/mL were observed 4-5 hours after administration of 300 and 600 mg doses, respectively. The mean (± SD) Cmax and AUC(0-∞) values in blister fluid were 48% (± 13) and 91% (± 18) of those in plasma, respectively.

Tonsil tissues

In adult patients who underwent selective tonsillectomy, the mean concentration of cefdinir in tonsillar tissue 4 hours after administration of single doses of 300 and 600 mg of the drug was 0.25 (0.22-0.46) and 0.36 (0.22-0.80) μg/g, respectively. The mean concentration of the drug in tonsillar tissue was 24% (± 8) of the plasma concentration values.

Nasal sinuses

In adult patients undergoing maxillary and ethmoidal sinus surgery, the mean sinus tissue concentration of cefdinir 4 hours after administration of 300 and 600 mg doses was <0.12 (<0.12-0.46) and 0.21 (<0.12-2.0) mcg/g, respectively. The mean sinus cefdinir concentration was 16% (± 20) of plasma concentrations.

Lung tissues

In adult patients undergoing diagnostic bronchoscopy, mean bronchial mucosal cefdinir concentrations 4 hours after administration of 300 and 600 mg cefdinir were 0.78 (<0.06–1.33) and 1.14 (<0.06–1.92) μg/mL, respectively, and 31% (± 18) of plasma concentrations. Corresponding lung concentrations were 0.29 (<0.3–4.73) and 0.49 (<0.3–0.59) μg/mL, respectively, and 35% (± 83) of plasma concentrations.

In pediatric patients with acute bacterial otitis media, the mean concentration of cefdinir in middle ear fluid was 0.21 (<0.09-0.94) and 0.72 (0.14-1.42) μg/mL 3 hours after single doses of 7 and 14 mg/kg, respectively. The mean concentration of the drug in middle ear fluid was 15% (± 15) of the plasma concentration values.

Cerebrospinal fluid

There are no data on the penetration of cefdinir into the cerebrospinal fluid.

Metabolism and excretion

Cefdinir is not metabolized. It is excreted primarily by the kidneys, with a mean elimination half-life (t½) of 1.7 (± 0.6) hours. In healthy volunteers (with normal renal function), the renal clearance of cefdinir is 2.0 (± 1.0) ml/min/kg, and the apparent oral clearance is 11.6 (± 6.0) and 15.5 (± 5.4) ml/min/kg at doses of 300 and 600 mg, respectively. The mean percentage of the dose excreted unchanged in the urine at doses of 300 and 600 mg is 18.4% (± 6.4) and 11.6% (± 4.6) of the administered dose, respectively. Cefdinir clearance is reduced in patients with renal dysfunction (see section "Special warnings and precautions for use" - "Patients with renal insufficiency").

Since renal excretion is the predominant route of elimination, the dosage of the drug should be adjusted accordingly in patients with severe renal impairment or in those undergoing hemodialysis (see section "Method of administration and dosage").

Special patient groups

Patients with renal failure

In patients with creatinine clearance (CLcr) between 30 and 60 ml/min, Cmax and t1/2 increased approximately 2-fold, AUC approximately 3-fold. In patients with CLcr <30 ml/min, Cmax increased approximately 2-fold, t1/2 approximately 5-fold, and AUC approximately 6-fold. In patients with severe renal impairment (CLcr <30 ml/min), a change in dosing regimen is recommended (see section 4.2).

Hemodialysis

Dialysis (4 hours) removes 63% of cefdinir from the body; t1/2 decreases from 16 (± 3.5) to 3.2 (± 1.2) hours. A change in the dosage regimen is recommended for this category of patients (see section "Method of administration and dosage").

Liver failure

Since cefdinir is excreted primarily by the kidneys and is not metabolized, studies in patients with hepatic impairment have not been conducted. No dosage adjustment is necessary in this patient population.

Elderly patients

No dosage adjustment is required for elderly patients with normal renal function.

Gender and race

These factors do not affect the pharmacokinetics of cefdinir.

Indication

For the treatment of mild to moderate infections caused by cefdinir-susceptible strains of 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. Cefdinir is effective in treating oropharyngeal S. pyogenes. However, there are no data on the use of cefdinir for the prevention of rheumatic fever after pharyngitis/tonsillitis caused by S. pyogenes.

Uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (including β-lactamase-producing strains) and Streptococcus pyogenes.

Contraindication

Hypersensitivity to cefdinir or to any other cephalosporin antibiotic.

Interaction with other medicinal products and other types of interactions

Aluminum- and magnesium-containing antacids

Concomitant use of cefdinir and antacids results in a decrease in Cmax and AUC of cefdinir by approximately 40%. The time to reach Cmax is increased by 1 hour. There is no significant effect on the pharmacokinetics of cefdinir if the antacid is administered 2 hours before or 2 hours after taking cefdinir. If antacids are required during treatment with 3-Dinir, it should be taken at least 2 hours before or after taking the antacid.

Probenecid

As with other β-lactam antibiotics, probenecid impairs the renal excretion of cefdinir when administered concomitantly, resulting in an approximately two-fold increase in AUC, a 54% increase in Cmax of cefdinir, and a 50% prolongation of t½.

Iron-containing medicines and iron-fortified products

When cefdinir is taken simultaneously with iron preparations containing 60 mg of elemental iron (in the form of FeSO4) or vitamin preparations containing 10 mg of iron, the absorption of cefdinir is reduced by 80% and 31%, respectively. If the patient requires iron preparations during cefdinir therapy, 3-Dinir should be taken at least 2 hours before or after taking iron preparations.

Cases of reddish discoloration of the stools have been reported in patients taking cefdinir. In many cases, these patients were also taking iron-fortified foods. The red discoloration may be due to the formation of unabsorbed complexes of cefdinir or its degradation products with iron in the gastrointestinal tract.

False-positive urine ketones may occur with nitroprusside tests, but not with nitroferricyanide. Cefdinir may cause false-positive urine glucose tests with Clinitest®, Benedict's solution, Fehling's reagent. Enzymatic methods are recommended for urine glucose determination. Cephalosporins may cause false-positive Coombs' test results.

Application features

Before prescribing 3-Dinir, it is necessary to establish whether the patient has had a history of hypersensitivity reactions to cefdinir, other cephalosporins, penicillins and other drugs. Cefdinir should be prescribed with caution to patients with sensitivity to penicillin due to the possibility of cross-hypersensitivity between β-lactam antibiotics. If allergic reactions to cefdinir occur, the drug should be discontinued. Serious acute hypersensitivity reactions may require the administration of epinephrine (adrenaline) and other emergency measures according to the situation.

Clostridium difficile associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including cefdinir, and has ranged in severity from mild diarrhea to fatal colitis. Antibacterial therapy disrupts the normal flora of the large intestine, leading to overgrowth of C. difficile.

C. difficile produces toxins A and B, which cause CDAD. C. difficile strains with overproduction of toxins are associated with increased morbidity and mortality because the infections they cause may be resistant to antimicrobial therapy and may require colectomy. CDAD should be suspected in all patients who present with diarrhea after antibiotic use. A careful history is necessary, as CDAD has been reported to occur more than 2 months after antibiotic administration.

3-Dinir, like other broad-spectrum antimicrobial drugs, should be prescribed with caution to individuals with a history of colitis.

As with other broad-spectrum antibiotics, prolonged treatment may result in the emergence and increase in the number of resistant organisms. Close patient monitoring is essential. If superinfection occurs during therapy, appropriate alternative therapy should be instituted.

In patients with transient or persistent renal insufficiency (CLcr <30 ml/min), the daily dose of cefdinir should be reduced, since the use of the drug at recommended doses may lead to a significant increase in plasma concentrations and t1/2 of cefdinir (see section "Method of administration and dosage").

The safety and efficacy of cefdinir in neonates and infants under 6 months of age have not been established. The use of cefdinir for the treatment of acute sinusitis in children 6 months to 12 years of age is supported by clinical trial data in adults and adolescents, the similar pathophysiology of acute sinusitis in adults and children, and comparative pharmacokinetic data in the pediatric population.

The efficacy of cefdinir in elderly patients and in younger adults is comparable. Although cefdinir is well tolerated in all age groups, in clinical trials, elderly patients had a lower rate of adverse events (including diarrhea) than younger adults. No dose adjustment is necessary in elderly patients with normal renal function.

Use during pregnancy or breastfeeding

Pregnancy: In preclinical studies, cefdinir was not teratogenic when administered orally to rats at doses up to 1000 mg/kg/day (70 times the recommended maximum therapeutic dose on a mg/kg/day basis, 11 times the recommended maximum therapeutic dose on a mg/m2/day basis) or to rabbits at doses up to 10 mg/kg/day (0.7 times the recommended maximum therapeutic dose on a mg/kg/day basis, 0.23 times the recommended maximum therapeutic dose on a mg/m2/day basis). Cefdinir did not affect female reproductive performance, survival of offspring, or developmental, behavioral, or reproductive parameters. However, clinical data on the effects of cefdinir on pregnant women are not available. Because animal reproduction studies are not always predictive of human outcomes, cefdinir should be used during pregnancy only if clinically necessary. The effects of cefdinir on parturition have not been studied.

Breastfeeding: Cefdinir was not detected in human breast milk when administered at a dose of 600 mg.

Ability to influence reaction speed when driving vehicles or other mechanisms

Experience with the use of cefdinir has not revealed any adverse effects on the ability to drive and use machines.

The drug in capsule form is intended for use in adults and adolescents aged 13 and over.

The recommended dose and duration of treatment for infections in adults and adolescents are described in the table below. The total daily dose for all infections is 600 mg. Dosing once daily for 10 days is as effective as dosing twice daily. Dosing once daily has not been studied in pneumonia and skin infections. Therefore, in these infections, 3-Dinir should be taken twice daily. The drug can be used regardless of food intake.

Patients with renal insufficiency

In adult patients with CLcr <30 mL/min, the dose of cefdinir should be 300 mg once daily.

Patients on hemodialysis

Hemodialysis helps to remove cefdinir from the body. For patients on continuous hemodialysis, the initial dose is 7 mg/kg (not to exceed 300 mg) on each subsequent day. At the end of each hemodialysis session, a dose of 7 mg/kg (not to exceed 300 mg) of cefdinir should be administered. Subsequent doses of 7 mg/kg (not to exceed 300 mg) are then administered on each subsequent day (i.e., every 48 hours).

Children

3-Dinir in capsule form is not intended for the treatment of children under 13 years of age.

Overdose

There are no data on overdose of cefdinir in humans. In acute toxicity studies in rodents, a single oral dose of 5600 mg/kg of cefdinir did not produce any adverse reactions. Signs and symptoms of overdose with other β-lactam antibiotics include nausea, vomiting, epigastric distress, diarrhea, and convulsions. Cefdinir is removed from the body by hemodialysis, which may be useful in severe toxic reactions caused by overdose, especially in patients with impaired renal function.

Side effects

Gastrointestinal: dry mouth, stomatitis, flatulence, abdominal pain, nausea, diarrhea, bowel disorders, dyspepsia, pseudomembranous colitis, acute enterocolitis, hemorrhagic colitis, hemorrhagic diarrhea, intestinal obstruction, constipation, anorexia, peptic ulcer, melena.

Respiratory system: feeling of suffocation, acute respiratory failure, induced pneumonia, asthma attack, eosinophilic pneumonia, idiopathic interstitial pneumonia.

Central nervous system: headache, insomnia, drowsiness, dizziness, loss of consciousness, convulsions, hyperkinesia, involuntary movements and rhabdomyolysis.

From the blood and lymphatic system: blood clotting disorders (disseminated intravascular coagulation syndrome), granulocytopenia, neutropenia, transient leukopenia, thrombocytopenia, pancytopenia and agranulocytosis, aplastic anemia, idiopathic thrombocytopenic purpura, hemolytic anemia, hemorrhage.

On the part of the immune system: serum sickness syndrome, anaphylaxis (in rare cases - fatal).

Hepatobiliary system: hepatic failure, acute hepatitis, fulminant hepatitis, liver dysfunction, including cholestasis, jaundice.

From the urinary system: renal dysfunction, toxic nephropathy, acute renal failure, nephropathy.

Allergic reactions: rash, skin itching, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylactic reactions, maculopapular rashes, allergic vasculitis, exfoliative dermatitis, erythema nodosum, toxic epidermal necrolysis, laryngeal and facial edema, shock, conjunctivitis, fever.

Biochemical parameters: increased ACT, increased amylase in the blood, pseudopositive test for glucose in the urine.

Effects due to biological action: itching, leucorrhoea, cutaneous candidiasis, vaginal candidiasis, vaginitis.

Others: bleeding tendency, bleeding and hemorrhages, chest pain, arterial hypertension, asthenia.

Expiration date

3 years from the date of manufacture in bulk.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging

10 capsules in a blister. 1 blister is placed in a pack.

Vacation category

According to the recipe.

Producer

PJSC "Kyivmedpreparat" (packaging from in bulk by the manufacturer PharmaVision Sanayi ve Tikaret A.S., Turkey).

Applicant

LLC "ARTERIUM LTD", Ukraine.

Address

Ukraine, 01032, Kyiv, Saksaganskoho St., 139.