Ceftibuten

Name: Ceftibuten

Ceftibuten Drug Class

Ceftibuten is part of the drug class:

  • Third generation cephalosporins

What happens if I miss a dose?

Take the medication as soon as you remember the missed dose. If it is almost time for your next dose, skip the missed dose and use the medicine at your next regularly scheduled time. Do not use extra medicine to make up the missed dose.

Uses for Ceftibuten

Acute Otitis Media (AOM)

Treatment of AOM caused by Haemophilus influenzae (including β-lactamase-producing strains), Moraxella catarrhalis (including β-lactamase-producing strains), or Streptococcus pyogenes (group A β-hemolytic streptococci).1 3 5 7 8 48 (See Acute Otitis Media under Cautions.)

When anti-infectives indicated, AAP recommends high-dose amoxicillin or amoxicillin and clavulanate as drugs of choice for initial treatment of AOM; certain cephalosporins (cefdinir, cefpodoxime, cefuroxime, ceftriaxone) recommended as alternatives for initial treatment in penicillin-allergic patients without a history of severe and/or recent penicillin-allergic reactions.37

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci).1 14 Generally effective in eradicating S. pyogenes from nasopharynx; efficacy in prevention of subsequent rheumatic fever not established to date.1

AAP, IDSA, AHA, and others recommend a penicillin regimen (10 days of oral penicillin V or oral amoxicillin or single dose of IM penicillin G benzathine) as treatment of choice for S. pyogenes pharyngitis and tonsillitis;10 16 17 other anti-infectives (oral cephalosporins, oral macrolides, oral clindamycin) recommended as alternatives in penicillin-allergic patients.10 11 16 17

If an oral cephalosporin used, 10-day regimen of first generation cephalosporin (cefadroxil, cephalexin) preferred instead of other cephalosporins with broader spectrums of activity (e.g., cefaclor, cefdinir, cefixime, cefpodoxime, cefuroxime).10 16 17

Respiratory Tract Infections

Treatment of acute bacterial exacerbations of chronic bronchitis caused by Streptococcus pneumoniae (penicillin-susceptible strains only), H. influenzae (including β-lactamase-producing strains), or M. catarrhalis (including β-lactamase-producing strains).1 9 12 26

Treatment of acute maxillary sinusitis† caused by susceptible S. pneumoniae, H. influenzae, or M. catarrhalis.3 45 Because of variable activity against S. pneumoniae and H. influenzae, IDSA no longer recommends second or third generation oral cephalosporins for empiric monotherapy of acute bacterial sinusitis.43 Oral amoxicillin or amoxicillin and clavulanate usually recommended for empiric treatment.43 44 If an oral cephalosporin used as an alternative in children (e.g., in penicillin-allergic individuals), combination regimen that includes a third generation cephalosporin (cefixime or cefpodoxime) and clindamycin (or linezolid) recommended.43 44

Treatment of acute bronchitis†,3 26 27 46 bronchiectasis†,47 or pneumonia†3 46 47 caused by susceptible bacteria.

Urinary Tract Infections (UTIs)

Treatment of uncomplicated UTIs† caused by susceptible Escherichia coli, Klebsiella, Proteus mirabilis, Enterobacter, or staphylococci.3 63 64

Treatment of complicated or recurrent UTIs† caused by susceptible E. coli, Klebsiella, P. mirabilis, Enterobacter, or staphylococci.3 63 64

Some clinicians suggest that certain oral third generation cephalosporins (cefdinir, cefpodoxime, ceftibuten) are one of several alternatives for outpatient treatment of recurrent UTIs or UTIs that occur in patients who have indwelling urinary catheters or acquired the infections in hospitals or nursing homes; these infections likely to be caused by multidrug-resistant gram-negative bacilli.11

Stability

Storage

Oral

Capsules

2–25°C in tight container.1

For Suspension

2–25°C.1 Following reconstitution, store suspension at 2–8°C; discard after 14 days.1

Indications and Usage for Ceftibuten

Ceftibuten is indicated for the treatment of individuals with mild-to-moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below (see DOSAGE AND ADMINISTRATION and CLINICAL STUDIES sections).

Acute Bacterial Exacerbations of Chronic Bronchitis due to Haemophilus influenzae (including β-lactamase-producing strains), Moraxella catarrhalis (including β-lactamase-producing strains), or Streptococcus pneumoniae (penicillin-susceptible strains only).

NOTE: In acute bacterial exacerbations of chronic bronchitis clinical trials where Moraxella catarrhalis was isolated from infected sputum at baseline, Ceftibuten clinical efficacy was 22% less than control.

Acute Bacterial Otitis Media due to Haemophilus influenzae (including β-lactamase-producing strains), Moraxella catarrhalis (including β-lactamase-producing strains), or Streptococcus pyogenes.

NOTE: Although Ceftibuten used empirically was equivalent to comparators in the treatment of clinically and/or microbiologically documented acute otitis media, the efficacy against Streptococcus pneumoniae was 23% less than control. Therefore, Ceftibuten should be given empirically only when adequate antimicrobial coverage against Streptococcus pneumoniae has been previously administered.

Pharyngitis and Tonsillitis due to Streptococcus pyogenes.

NOTE: Only penicillin by the intramuscular route of administration has been shown to be effective in the prophylaxis of rheumatic fever. Ceftibuten is generally effective in the eradication of Streptococcus pyogenes from the oropharynx; however, data establishing the efficacy of the Ceftibuten product for the prophylaxis of subsequent rheumatic fever are not available.

Warnings

BEFORE THERAPY WITH Ceftibuten IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO Ceftibuten, OTHER CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLERGIC REACTION TO THE Ceftibuten OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including Ceftibuten, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of "antibiotic-associated colitis".

After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile.

Precautions

General

As with other broad-spectrum antibiotics, prolonged treatment may result in the possible emergence and overgrowth of resistant organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

The dose of Ceftibuten may require adjustment in patients with varying degrees of renal insufficiency, particularly in patients with creatinine clearance less than 50 mL/min or undergoing hemodialysis (see DOSAGE AND ADMINISTRATION). Ceftibuten is readily dialyzable. Dialysis patients should be monitored carefully, and administration of Ceftibuten should occur immediately following dialysis.

Ceftibuten should be prescribed with caution to individuals with a history of gastrointestinal disease, particularly colitis.

Information to Patients

Patients should be informed that:

  • If the patient is diabetic, he/she should be informed that Ceftibuten Oral Suspension contains 1 gram sucrose per teaspoon of suspension.
  • Ceftibuten Oral Suspension should be taken at least 2 hours before a meal or at least 1 hour after a meal (see CLINICAL PHARMACOLOGY, Food Effect on Absorption).

Drug Interactions

Theophylline

Twelve healthy male volunteers were administered one 200-mg Ceftibuten capsule twice daily for 6 days. With the morning dose of Ceftibuten on day 6, each volunteer received a single intravenous infusion of theophylline (4 mg/kg). The pharmacokinetics of theophylline were not altered. The effect of Ceftibuten on the pharmacokinetics of theophylline administered orally has not been investigated.

Antacids or H2-receptor antagonists

The effect of increased gastric pH on the bioavailability of Ceftibuten was evaluated in 18 healthy adult volunteers. Each volunteer was administered one 400-mg Ceftibuten capsule. A single dose of liquid antacid did not affect the Cmax or AUC of Ceftibuten; however, 150 mg of ranitidine q12h for 3 days increased the Ceftibuten Cmax by 23% and Ceftibuten AUC by 16%. The clinical relevance of these increases is not known.

Drug/Laboratory Test Interactions

There have been no chemical or laboratory test interactions with Ceftibuten noted to date. False-positive direct Coombs' tests have been reported during treatment with other cephalosporins. Therefore, it should be recognized that a positive Coombs' test could be due to the drug. The results of assays using red cells from healthy subjects to determine whether Ceftibuten would cause direct Coombs' reactions in vitro showed no positive reaction at Ceftibuten concentrations as high as 40 µg/mL.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of Ceftibuten. No mutagenic effects were seen in the following studies: in vitro chromosome assay in human lymphocytes, in vivo chromosome assay in mouse bone marrow cells, Chinese Hamster Ovary (CHO) cell point mutation assay at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus, and in a bacterial reversion point mutation test (Ames). No impairment of fertility occurred when rats were administered Ceftibuten orally up to 2000 mg/kg/day (approximately 43 times the human dose based on mg/m2/day).

Pregnancy

Teratogenic effects

Pregnancy Category B

Ceftibuten was not teratogenic in the pregnant rat at oral doses up to 400 mg/kg/day (approximately 8.6 times the human dose based on mg/m2/day). Ceftibuten was not teratogenic in the pregnant rabbit at oral doses up to 40 mg/kg/day (approximately 1.5 times the human dose based on mg/m2/day) and has revealed no evidence of harm to the fetus. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Labor and Delivery

Ceftibuten has not been studied for use during labor and delivery. Its use during such clinical situations should be weighed in terms of potential risk and benefit to both mother and fetus.

Nursing Mothers

It is not known whether Ceftibuten (at recommended dosages) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Ceftibuten is administered to a nursing woman.

Pediatric Use

The safety and efficacy of Ceftibuten in infants less than 6 months of age has not been established.

Geriatric Patients

The usual adult dosage recommendation may be followed for patients in this age group. However, these patients should be monitored closely, particularly their renal function, as dosage adjustment may be required.

Clinical Studies

Acute Bacterial Exacerbations of Chronic Bronchitis

Three clinical trials (two domestic, the third abroad) have been conducted testing Ceftibuten in the treatment of acute exacerbations of chronic bronchitis (AECB). Overall, the clinical outcome among patients who had signs and symptoms of AECB, who had a gram stain showing a predominance of PMNs and few epithelial cells, and who were evaluated at approximately 1 to 2 weeks after completing therapy were equivalent to comparators. The bacterial eradication rates of specific pathogens are presented below.

BACTERIOLOGICAL OUTCOME ACUTE BACTERIAL EXACERBATIONS OF CHRONIC BRONCHITIS
Ceftibuten 400 mg QD Control
Bacteriological Eradication Rates
  Haemophilus influenzae 45/62 (73%) 26/36 (72%)
  H. parainfluenzae 10/10 4/6
  Moraxella catarrhalis 33/46 (72%) 32/34 (94%)
  Streptococcus pneumoniae 23/35 (66%) 14/20 (70%)

Acute Bacterial Otitis Media

Four clinical trials (three domestic, the fourth abroad) have been conducted testing Ceftibuten in the treatment of acute bacterial otitis media. Overall, the clinical outcome among patients who had signs and symptoms of acute bacterial otitis media and who were evaluated at approximately 1 to 2 weeks after completing therapy were equivalent to comparators. Tympanocentesis was performed on patients in three of the above-mentioned studies; the bacterial eradication rates of specific pathogens are presented below.

BACTERIOLOGICAL OUTCOME ACUTE BACTERIAL OTITIS MEDIA
Ceftibuten 9 mg/kg QD Control
Bacteriological Eradication Rates
  Haemophilus influenzae 56/67 (81%) 29/38 (76%)
  Moraxella catarrhalis 20/26 (77%) 13/17 (77%)
  Streptococcus pneumoniae 68/105 (65%) 35/40 (88%)
  Streptococcus pyogenes 13/15 (87%) 5/5

References

  1. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically – Third Edition. Approved Standard NCCLS Document M7-A3, Vol. 13, No. 25, NCCLS, Villanova, PA. December, 1993.
  2. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests – Fifth Edition. Approved Standard NCCLS Document M2-A5, Vol. 13, No. 24, NCCLS, Villanova, PA. December, 1993.

MACOVEN

PHARMACEUTICALS

For inquires call 1-877-622-6836

Manufactured by:

Merck Sharp & Dohme Corp., a subsidiary of

MERCK & CO., INC.

Whitehouse Station, NJ 08889, USA

Distributed by Macoven Phamaceuticals, LLC

Morristown, NJ 07960, USA

Rev. 03/15

35327908

PRINCIPAL DISPLAY PANEL - 400 mg Capsule Bottle Label

NDC 44183-400-22

Ceftibuten
Capsules

400 mg

For Oral Administration

Rx only
20 Capsules

MACOVEN
PHARMACEUTICALS

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Cedax: 400 mg [contains butylparaben, edetate calcium disodium, methylparaben, propylparaben]

Generic: 400 mg

Suspension Reconstituted, Oral:

Cedax: 90 mg/5 mL (60 mL [DSC], 90 mL [DSC], 120 mL [DSC]) [contains polysorbate 80, sodium benzoate]

Cedax: 180 mg/5 mL (30 mL, 60 mL) [contains sodium benzoate; cherry flavor]

Generic: 180 mg/5 mL (60 mL)

Use Labeled Indications

Acute bacterial exacerbations of chronic bronchitis: Treatment of mild to moderate acute bacterial exacerbations of chronic bronchitis due to Haemophilus influenzae (including beta-lactamase-producing strains), Moraxella catarrhalis (including beta-lactamase-producing strains), or Streptococcus pneumoniae (penicillin-susceptible strains only).

Limitations of use: In acute bacterial exacerbations of chronic bronchitis clinical trials where M. catarrhalis was isolated from infected sputum at baseline, ceftibuten clinical efficacy was 22% less than control.

Acute bacterial otitis media: Treatment of mild to moderate acute bacterial otitis media due to H. influenzae (including beta-lactamase-producing strains), M. catarrhalis (including beta-lactamase-producing strains), or Streptococcus pyogenes.

Limitations of use: Although ceftibuten used empirically was equivalent to comparators in the treatment of clinically and/or microbiologically documented acute otitis media, the efficacy against S. pneumoniae was 23% less than control. Therefore, ceftibuten should be given empirically only when adequate antimicrobial coverage against S. pneumoniae has been previously administered.

Pharyngitis/tonsillitis: Treatment of mild to moderate pharyngitis and tonsillitis due to S. pyogenes.

Reconstitution

Refer to manufacturer’s product labeling for reconstitution instructions. Shake well.

Dietary Considerations

Capsule: Take without regard to food.

Suspension: Take 2 hours before or 1 hour after meals.

Warnings/Precautions

Concerns related to adverse effects:

• Penicillin allergy: Use with caution in patients with a history of penicillin allergy; if a hypersensitivity reaction occurs, discontinue therapy and institute supportive emergency measures.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Colitis: Use with caution in patients with a history of colitis and other gastrointestinal diseases.

• Renal impairment: Use with caution in patients with renal impairment; modify dosage in moderate to severe impairment and in hemodialysis patients.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.

• Sucrose: Some formulations may contain sucrose.

Usual Pediatric Dose for Pneumonia

>12 years: 200 mg orally every 12 hours for 7 to 14 days

Liver Dose Adjustments

Data not available

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