Cefdinir

Cefdinir belongs to the pharmacological class of Third-generation cephalosporin antibiotics.

Cefdinir has been approved to relieve symptoms and also for the treatment and maintenance of Chronic obstructive pulmonary disease, Odontogenic soft tissue infection, Otitis media, Rhinosinusitis, Streptococcal pharyngitis, and Urinary tract infection.

Cefdinir after oral administration is rapidly absorbed from the gastrointestinal tract, with a bioavailability of approximately 16-21%. Cefdinir exhibits linear pharmacokinetics, with a maximum concentration (Cmax) of roughly 1.5 μg/mL and a time to maximum concentration (Tmax) of 2-4 hours. The half-life of Cefdinir is approximately 1.7-1.8 hours, and it is primarily eliminated unchanged in the urine, with approximately 20% of the dose excreted in the feces. The pharmacokinetics of Cefdinir are not affected by food, and it does not significantly bind to plasma proteins. No dosage adjustments are required for patients with renal impairment, but caution should be exercised in patients with hepatic impairment.

The common side effects involved in using Cefdinir are nausea, headache, vomiting, rashes or itching at the site of injection, itching, diarrhea, headache, upset stomach, etc.

Cefdinir is available in the form of Oral Suspension, Capsules, and Tablets.

Cefdinir is approved in Germany, Japan, Malaysia, India, U.K., U.S., and China.

Cefdinir belongs to the pharmacological class of Third-generation cephalosporin antibiotics.

Cefdinir is a cephalosporin antibiotic that has a six-member dihydrothiazine ring, replacing the five-member thiazolidine rings in penicillins, which makes it more effective against bacteria. It works by inhibiting the synthesis of the bacterial cell wall by binding to penicillin-binding proteins (PBPs) in a similar mechanism to other beta-lactam antibiotics. Cefdinir can penetrate the bacterial cell wall, resist beta-lactamase enzymes, inactivate PBPs, and ultimately cause cell lysis, leading to the death of susceptible bacteria. It has been shown to have a high affinity for PBPs 2 and 3 and to inhibit transpeptidase enzymes of various bacteria, which contribute to its bactericidal action. Cefdinir may also inhibit myeloperoxidase release extracellularly, but the significance of this mechanism in relation to its overall mechanism of action is unclear.

Cefdinir has been approved to relieve symptoms and also for the treatment and maintenance of Chronic obstructive pulmonary disease, Odontogenic soft tissue infection, Otitis media, Rhinosinusitis, Streptococcal pharyngitis, Urinary tract infection.

The maximum plasma concentration (Cmax) of Cefdinir is achieved within 2 to 4 hours after oral administration. The time to reach maximum concentration (Tmax) varies, with a median of 2.5 hours. Cefdinir has an elimination half-life of approximately 1.7 hours in healthy adults.

The onset of action of Cefdinir is not clearly defined, but it is believed to begin as soon as the drug reaches the site of infection. The duration of action of Cefdinir is about 12 hours, which allows for twice-daily dosing.

Cefdinir is found to be available in the form of Oral suspension, Capsules.

Cefdinir can be used in the following treatment:

• Chronic obstructive pulmonary disease
• Odontogenic soft tissue infection
• Otitis media
• Rhinosinusitis
• Streptococcal pharyngitis
• Urinary tract infection

Cefdinir can help to relieve symptoms and also for the treatment and maintenance of Chronic obstructive pulmonary disease, Odontogenic soft tissue infection, Otitis media, Rhinosinusitis, Streptococcal pharyngitis, Urinary tract infection.

Cefdinir is approved for use in the following clinical indications:

• Chronic obstructive pulmonary disease
• Odontogenic soft tissue infection
• Otitis media
• Rhinosinusitis
• Streptococcal pharyngitis
• Urinary tract infection

• Chronic obstructive pulmonary disease, acute exacerbation:

Chronic obstructive pulmonary disease, acute exacerbation (COPD-AE) is a medical condition that requires careful consideration of patient risk factors before treatment. Patients with risk factors for Pseudomonas infection or poor outcomes, such as being 65 years or older with major comorbidities, having a forced expiratory volume in one second (FEV1) below 50% of predicted, or experiencing frequent exacerbations, should avoid treatment with certain medications .

• Odontogenic soft tissue infection, pyogenic:

In cases of pyogenic odontogenic soft tissue infection, Cefdinir may be used as an alternative agent for mild infections or as step-down therapy after parenteral treatment. Cefdinir should only be used for patients who are unable to take penicillin. The recommended oral dosage of Cefdinir is 300 mg twice daily in combination with metronidazole until clinical resolution, typically for 7 to 14 days. It should be used in addition to appropriate surgical management, such as drainage and/or extraction.

• Otitis media: Cefdinir may also be used as an alternative agent for acute otitis media in patients with mild nonanaphylactic penicillin allergy. The recommended dosage for oral treatment is 300 mg twice daily or about 600 mg once daily for a duration of 5 to 7 days for mild to moderate infection or 10 days for severe infection .

• Rhinosinusitis, acute bacterial: For acute bacterial rhinosinusitis in patients with penicillin allergy who are able to tolerate cephalosporins, Cefdinir may be used in conjunction with clindamycin for 5 to 7 days. Some experts may use Cefdinir as a monotherapy when the risk of drug-resistant Streptococcus pneumoniae is low. Initial observation and symptom management without antibiotic therapy is appropriate for most patients with uncomplicated acute bacterial rhinosinusitis, with antibiotic therapy reserved for poor follow-up or lack of improvement over the observation period .

• Streptococcal pharyngitis, group A: For patients with mild, nonanaphylactic penicillin allergy who require treatment for group A streptococcal pharyngitis, Cefdinir may be used at a dosage of 300 mg twice daily for 5 to 10 days or about 600 mg once daily for 10 days. Cephalosporin selection should be based on the type of hypersensitivity reaction to penicillin, with narrower spectrum cephalosporins preferred when possible to avoid resistance development .

• Urinary Tract Infection: Cefdinir may be used as an alternative agent for urinary tract infection in cases where preferred agents cannot be used. However, evidence suggests inferior efficacy of oral beta-lactams, and they should only be used when necessary. For acute uncomplicated cystitis, the recommended oral dosage of Cefdinir is 300 mg twice daily for 5 to 7 days. For complicated urinary tract infection, including pyelonephritis, the recommended oral dosage of Cefdinir is 300 mg twice daily for 10 to 14 days. If symptomatic improvement is seen within the first 48 to 72 hours of therapy, some experts may recommend shorter courses of 7 to 10 days. Oral beta-lactam therapy should generally follow appropriate parenteral therapy .

Capsules: 300 mg

Oral suspension: 125 mg/5 mL, 250 mg/5 mL

Oral suspension, Capsules.

Dosage Adjustments in Kidney Patients:

• Altered kidney function can affect the dosing of the medication. In patients with a creatinine clearance (CrCl) of 30 mL/minute or higher, no dosage adjustment is necessary. For those with a CrCl less than 30 mL/minute, a 300 mg once-daily dose is recommended.

• For patients undergoing hemodialysis, the medication is dialyzable, with about 63% of the dose being removed. However, limited pharmacokinetic data have shown prolonged half-lives and increased serum concentrations in these patients. To achieve pharmacokinetic/pharmacodynamic goals, a 300 mg initial dose should be followed by 300 mg three times per week postdialysis on dialysis days, along with an additional 300 mg dose 48 hours into each 72-hour interdialytic period. Alternatively, pharmacokinetic parameters suggest that 300 mg initially, followed by 300 mg three times per week after hemodialysis sessions, may be sufficient.

• In patients undergoing peritoneal dialysis, the medication is slightly dialyzable, and pharmacokinetic data have shown prolonged half-lives and increased serum concentrations. A 300 mg dose every 48 hours is recommended.

• For patients receiving continuous renal replacement therapy (CRRT), drug clearance depends on the effluent flow rate, filter type, and method of renal replacement. High-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) are recommended unless otherwise noted. Close monitoring of response and adverse reactions due to drug accumulation is important, and dosing should be adjusted accordingly. A 300 mg dose every 12 hours is recommended for oral administration. However, in general, the use of intravenous antimicrobial therapy or alternative oral therapies with greater bioavailability may be preferred in patients receiving CRRT.

• For patients receiving sustained, low-efficiency diafiltration (PIRRT), drug clearance depends on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations, and close monitoring of response and adverse reactions due to drug accumulation is important. A 300 mg dose every 12 hours is recommended on PIRRT days, and a 300 mg dose every 24 hours is recommended on non-PIRRT days, according to expert opinion. However, in general, the use of intravenous antimicrobial therapy or alternative oral therapies with greater bioavailability may be preferred in patients receiving PIRRT.

Dosage Adjustments in Pediatric Patients:

• Chronic and acute bacterial exacerbation of bronchitis in adolescents: Oral: 300 mg every 12 hours for 5 to 10 days or about 600 mg every 24 hours for 10 days.

• Acute otitis media in infants (≥6 months) and children: Oral: 14 mg/kg/day which is divided doses every 12 to 24 hours; maximum daily dose: 600 mg/day. For severe or recurrent AOM, tympanic membrane perforation, or children <2 years of age, treat for 10 days. For mild to moderate, nonrecurrent disease without tympanic membrane perforation in patients ≥2 years of age, shorter durations of 5 to 7 days may be sufficient. Twice-daily dosing is preferred, especially if shorter durations (i.e., 5 days) are used.

• Community-acquired pneumonia in adolescents: Oral: 300 mg every 12 hours for 10 days. Durations as short as 5 days, depending on patient response, are recommended in adult community-acquired pneumonia guidelines for patients who are improving clinically.

• Acute bacterial rhinosinusitis in infants (≥6 months) and children: Oral: 14 mg/kg/day which is divided doses every 12 to 24 hours for 10 days; maximum daily dose: 600 mg/day. In adolescents, oral Cefdinir is recommended at 300 mg every 12 hours or 600 mg for every 24 hours for 10 days.

• Uncomplicated skin and soft tissue infections: Infants (≥6 months) and children should take oral Cefdinir at 7 mg/kg/dose every 12 hours for 10 days with a maximum dose of 300 mg/dose. Adolescents should take 300 mg every 12 hours for 10 days.
• Pharyngitis/tonsillitis caused by Group A Streptococcus in infants (≥6 months) and children: Oral: 14 mg/kg/day in divided doses for every 12 to 24 hours; maximum daily dose: 600 mg/day. Preferred treatment duration is 10 days, though 5 days may be adequate if Cefdinir is dosed twice daily. In adolescents, oral Cefdinir is recommended at 300 mg every 12 hours or 600 mg for every 24 hours for 10 days. Narrow-spectrum cephalosporins (such as cephalexin) are preferred over broad-spectrum cephalosporins such as Cefdinir for non anaphylactic penicillin allergy.

There are found to be no specific dietary restrictions associated with the use of Cefdinir. However, it is generally recommended to take Cefdinir with food to help increase its absorption and reduce the risk of gastrointestinal side effects such as nausea, vomiting, and diarrhea. It is important to follow any dietary advice provided by your healthcare provider, particularly if you have any underlying medical conditions or take other medications that may interact with Cefdinir. Additionally, it is recommended to avoid alcohol while taking Cefdinir as it may increase the risk of certain side effects.

Cefdinir may be contraindicated under the following conditions:

• In patients with a known allergy to Cefdinir or other cephalosporins.
• In patients who have a history of allergic reactions to penicillins or other drugs.
• Additionally, Cefdinir should not be given to patients with severe renal impairment or a history of colitis.
• It should be used cautiously in patients with a history of gastrointestinal disease, particularly colitis.

The physician should closely monitor the patients and keep pharmacovigilance as follows:

Prior to initiating therapy with Cefdinir (Cefdinir), it is important to inquire about the patient's medical history to determine if they have experienced any hypersensitivity reactions to Cefdinir, other cephalosporins, penicillins, or any other medications. For patients who are sensitive to penicillin and are being treated with Cefdinir, caution should be exercised due to the possibility of cross-hypersensitivity reactions among beta-lactam antibiotics, which can occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to Cefdinir is experienced, the medication should be discontinued. Severe acute hypersensitivity reactions may require emergency treatment with epinephrine, as well as other interventions such as oxygen, IV fluids, IV antihistamines, corticosteroids, pressor amines, and airway management, as deemed necessary by clinical judgement.

Nearly all antibacterial agents, including Cefdinir, have been associated with cases of pseudomembranous colitis ranging in severity from mild to life-threatening. Therefore, patients who develop diarrhea after taking antibacterial agents should be evaluated for this condition. The administration of antibacterial agents can disrupt the normal flora of the colon and promote the growth of clostridia, which produce a toxin that causes "antibiotic-associated colitis." Once the diagnosis of pseudomembranous colitis has been confirmed, appropriate measures should be taken. Mild cases can often be treated by discontinuing the drug. For moderate to severe cases, management may include fluid and electrolyte replacement, protein supplementation, and an antibacterial agent effective against Clostridium difficile.

Cefdinir is a cephalosporin antibiotic that may cause certain side effects if taken with alcohol. It is recommended that patients taking Cefdinir should avoid consuming alcohol during treatment. This is because alcohol can increase the risk of certain side effects such as gastrointestinal upset, dizziness, and drowsiness. Alcohol may also reduce the effectiveness of Cefdinir in treating infections.

After the administration of a single 600-mg dose, Cefdinir was not found in human breast milk.

Pregnancy Category B

Cefdinir has been found to be non-teratogenic in rats as well as rabbits at oral doses up to 1000 mg/kg/day and 10 mg/kg/day, respectively. However, maternal toxicity had observed in rabbits at the maximum tolerated dose of 10 mg/kg/day. Decreased body weight was observed in rat fetuses at doses of 100 mg/kg/day or higher and in rat offspring at doses of 32 mg/kg/day or higher. No adverse effects were observed on offspring survival, development, behavior, or reproductive function, and no cefdinir was detected in human breast milk after single 600-mg dose.

There are no known food warnings related to the use of Cefdinir. However, taking the medication with food may help to reduce stomach upset.

The adverse reactions related to Cefdinir can be categorized as follows:

Common

• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Headache
• Rash
• Vaginal yeast infection
• Stomach upset

Less Common

• Dizziness
• Fatigue
• Itching
• Joint pain
• Muscle pain
• Difficulty breathing or swallowing
• Hives or welts
• Swelling of the face, lips, or tongue
• Rapid heartbeat

Rare

• Severe allergic reactions such as anaphylaxis
• Stevens-Johnson syndrome
• Hemolytic anemia
• Pseudomembranous colitis

The clinically relevant drug interactions of Cefdinir are briefly summarized here:

Antacids: When taking 300-mg cefdinir capsules, the absorption rate and extent may be reduced by approximately 40% when taken with antacids that contain aluminum or magnesium, such as Maalox® TC suspension. Taking Cefdinir at least 2 hours before or after an antacid is recommended.

Probenecid: Probenecid, a medication used to treat gout, may inhibit the renal excretion of Cefdinir, resulting in an approximate doubling in an AUC, a 54% increase in peak cefdinir plasma levels, as well as a 50% prolongation in the apparent elimination half-life.

Iron supplements: Taking Cefdinir with iron supplements or foods fortified with iron may reduce the extent of absorption by 80% and 31%, respectively. If iron supplements are necessary during cefdinir therapy, they should be taken at least 2 hours before or after Cefdinir. There have been rare reports of reddish stools in Japanese patients taking Cefdinir due to the formation of a nonabsorbable complex between Cefdinir or its breakdown products as well as iron in the gastrointestinal tract. The effect of highly fortified iron-rich foods, such as iron-fortified breakfast cereals, on cefdinir absorption has not been studied. Iron-fortified infant formula (2.2 mg elemental iron/6 oz) does not significantly affect cefdinir pharmacokinetics, and therefore, Cefdinir for Oral Suspension can be administered with iron-fortified infant formula.

The following are the side effects involving Cefdinir:

● Diarrhea

● Nausea

● Vomiting

● Abdominal pain

● Headache

● Dizziness

● Rash

● Itching

● Vaginal yeast infection

● Gas

● Loss of appetite

● Fatigue

● Fever

Pregnancy:

Pregnancy Category B

Cefdinir has been found to be non-teratogenic been in rats and rabbits at oral doses up to 1000 mg/kg/day and 10 mg/kg/day, respectively. However, maternal toxicity had been observed in rabbits at the maximum tolerated dose of 10 mg/kg/day. Decreased body weight was observed in rat fetuses at doses of 100 mg/kg/day or higher and in rat offspring at doses of 32 mg/kg/day or higher. No adverse effects were observed on offspring survival, development, behavior, or reproductive function, and no cefdinir was detected in human breast milk after single 600-mg doses.

Nursing Mothers:

After the administration of a single 600-mg dose, Cefdinir was not found in human breast milk.

Pediatric:

The safety and efficacy of Cefdinir in neonates and infants under six months of age have not been established. However, the use of Cefdinir for acute maxillary sinusitis in pediatric patients aged six months to 12 years is supported by evidence from adequate and well-controlled studies in adults and adolescents.

Geriatric:

Efficacy is similar in geriatric patients and younger adults, and Cefdinir has been well-tolerated in all age groups. In clinical trials, geriatric patients experienced a lower rate of adverse events, including diarrhea, than younger adults. Dose adjustment in elderly patients is not necessary unless renal function is markedly compromised.

Physicians should be knowledgeable and vigilant about the treatment and identification of overdosage of Cefdinir.

Overdosage of Cefdinir may cause adverse effects such as seizures, encephalopathy, and neuromuscular excitability. If an overdose is been suspected, immediate medical attention should be sought. Treatment may involve supportive measures such as monitoring vital signs, providing respiratory support, and managing symptoms.

There is no specific antidote for cefdinir overdose, and dialysis is not effective in removing the drug from the body. However, hemodialysis may be considered in patients with renal impairment or those on dialysis.

Pharmacodynamics

Cefdinir is an antibacterial drug that acts by disrupting cell wall synthesis and exhibits a bactericidal effect. It has broad-spectrum activity against various gram-positive and gram-negative bacterial infections and is effective against beta-lactamase enzyme-producing bacteria. Hence, Cefdinir can combat several resistant organisms that are not susceptible to other cephalosporins.

Pharmacokinetics

• Absorption:

Maximal plasma concentration of Cefdinir is achieved between 2-4 hours after ingestion, with bioavailability depending on the formulation used. The capsule form has an estimated bioavailability of 16%-21%, while absolute bioavailability after suspension administration is 25%. The Cmax of Cefdinir ranges from 1.60 μg/mL to 2.87 μg/mL, depending on the dose. While a high-fat meal may reduce absorption by up to 15%, this is not clinically significant. However, cefdinir absorption may decrease when given with aluminum or magnesium-containing antacids or iron, so it is recommended to allow a 2-hour gap between administrations.

• Distribution:

The average volume of distribution of Cefdinir is 0.35 L/kg in adults and 0.67 L/kg in children, although another resource estimates it at 1.56–2.09 L/kg in adults. Cefdinir is distributed in various tissues at effective concentrations, including the cerebrospinal fluid, allowing it to treat infections throughout the body. Cefdinir is also protein-bound, with plasma protein binding ranging from 60% to 70%.

• Metabolism:

Cefdinir is not significantly metabolized, and its pharmacological actions are mainly attributed to the parent drug.

• Excretion:

Cefdinir is mainly excreted by the kidneys, with approximately 18.4% of a 300 mg dose found unchanged in the urine during a pharmacokinetic study of 21 individuals. Dose adjustments may be necessary for patients with renal impairment or those on dialysis, as a large proportion of the administered dose is excreted in the feces.

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