Loracarbef is a synthetic carbacephem antibiotic.
Carbacephems are b-lactam antibiotics structurally and pharmacologically related to cephalosporins; however, carbacephems contain a methylene group instead of sulfur in the dihydrothiazine ring of the cephalosporin nucleus, resulting in a tetrahydropyridine ring. This structural modification does not affect microbiologic activity, but substantially improves stability in aqueous solution and in serum, plasma, and other body fluids.
Loracarbef is the carba analog of cefaclor, a second generation cephalosporin. SumMon® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer’s labeling should be consulted.
It is essential that the labeling be consulted for detailed information on the usual cautions, precautions, and contraindications concerning potential drug interactions and/or laboratory test interferences and for information on acute toxicity.
Uses
Loracarbef is used orally for the treatment of mild to moderate respiratory tract infections (i.e., acute maxillary sinusitis, secondary bacterial infections of acute bronchitis, acute exacerbations of chronic bronchitis, pneumonia) caused by susceptible bacteria; acute otitis media caused by susceptible bacteria; and pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A b-hemolytic streptococci).
The drug also is used orally for the treatment of mild to moderate uncomplicated skin and skin structure infections and mild to moderate uncomplicated urinary tract infections (including uncomplicated cystitis or pyelonephritis) caused by susceptible bacteria.
Respiratory Tract Infections
Loracarbef is used in adults and adolescents 13 years of age and older for the treatment of secondary bacterial infections of acute bronchitis and acute bacterial exacerbations of chronic bronchitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae (including b-lactamase-producing strains), or Moraxella (formerly Branhamella) catarrhalis (including b-lactamase-producing strains).
Loracarbef is used in adults and adolescents 13 years of age and older for the treatment of mild to moderate pneumonia caused by susceptible S. pneumoniae or non-b-lactamase-producing H. influenzae when oral therapy is considered appropriate.
Because of a possible lack of efficacy, the American Thoracic Society (ATS) states that loracarbef should not be used for the empiric treatment of community-acquired pneumonia if multidrug-resistant S. pneumoniae are suspected. The manufacturer states that efficacy of the drug in the treatment of pneumonia caused by b-lactamase-producing H. influenzae remains to be established. Loracarbef also is used in adults and children 6 months of age and older for the treatment of mild to moderate acute maxillary sinusitis caused by susceptible strains of S. pneumoniae, non-b-lactamase-producing H. influenzae, or M. catarrhalis (including b-lactamase-producing strains).
Loracarbef has been associated with somewhat lower bacteriologic eradication and clinical cure rates in patient populations with significant numbers of b-lactamase-producing organisms than therapy with certain other anti-infectives (e.g., combined amoxicillin and clavulanate potassium). Therefore, when selecting an anti-infective for the treatment of acute maxillary sinusitis, the possibility of reduced overall efficacy should be weighed carefully against local susceptibility patterns for common pathogens encountered in these infections.
Otitis Media
Loracarbef is used in adults and children 6 months of age or older for the treatment of acute otitis media caused by S. pneumoniae, S. pyogenes, H. influenzae (including b-lactamase-producing strains), or M. catarrhalis (including b-lactamase-producing strains).
The manufacturer states that only loracarbef oral suspension should be used for the treatment of acute otitis media since this formulation is absorbed from the GI tract more rapidly than capsules and clinical studies evaluating the safety and efficacy of loracarbef for the treatment of these infections were conducted using the oral suspension.
Various anti-infectives, including oral amoxicillin, oral amoxicillin and clavulanate potassium, various oral cephalosporins (cefaclor, cefdinir, cefixime, cefpodoxime proxetil, cefprozil, ceftibuten, cefuroxime axetil, cephalexin), IM ceftriaxone, oral co-trimoxazole, oral erythromycin-sulfisoxazole, oral azithromycin, oral clarithromycin, and oral loracarbef, have been used in the treatment of AOM. The American Academy of Pediatrics (AAP), US Centers for Disease Control and Prevention (CDC), and other clinicians state that, despite the increasing prevalence of multidrug-resistant S. pneumoniae and presence of b-lactamase-producing H. influenzae or M. catarrhalis in many communities, amoxicillin remains the anti-infective of first choice for treatment of uncomplicated AOM since amoxicillin is highly effective, has a narrow spectrum of activity, is well distributed into middle ear fluid, and is well tolerated and inexpensive.
Because S. pneumoniae resistant to amoxicillin also frequently are resistant to co-trimoxazole, clarithromycin, and azithromycin, these drugs may not be effective in patients with AOM who fail to respond to amoxicillin. For additional information regarding treatment of AOM and information regarding prophylaxis of recurrent AOM, treatment of persistent or recurrent AOM, and treatment of otitis media with effusion (OME), see Uses: Otitis Media in the Aminopenicillins General Statement 8:12..08.
Pharyngitis and Tonsillitis
Loracarbef is used in adults and children 6 months of age or older for the treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A b-hemolytic streptococci). Although loracarbef usually is effective in eradicating S. pyogenes from the nasopharynx, efficacy of the drug for prophylaxis of subsequent rheumatic fever has not been established. Results of randomized studies in adults, adolescents, and children 6 months of age or older with streptococcal pharyngitis or tonsillitis indicate that a 10-day regimen of oral loracarbef is as effective as a 10-day regimen of oral penicillin V.
The bacteriologic eradication rate reported following a 10-day regimen of loracarbef in adults or pediatric patients has been 86.-89.%. Because penicillin has a narrow spectrum of activity, is inexpensive, and generally is effective, the CDC, AAP, American Academy of Family Physicians (AAFP), Infectious Diseases Society of America (IDSA), American Heart Association (AHA), American College of Physicians-American Society of Internal Medicine (ACP-ASIM), and others consider natural penicillins (i.e., 10 days of oral penicillin V or a single IM dose of penicillin G benzathine) the treatment of choice for streptococcal pharyngitis and tonsillitis and prevention of initial attacks (primary prevention) of rheumatic fever, although oral amoxicillin often is used instead of penicillin V in small children because of a more acceptable taste. Other anti-infectives (e.g., oral cephalosporins, oral macrolides) generally are considered alternatives.
Skin and Skin Structure Infections
Loracarbef has been used for the treatment of mild to moderate uncomplicated skin and skin structure infections caused by susceptible S. aureus, including penicillinase-producing strains, or S. pyogenes; abscesses usually require surgical drainage.
Urinary Tract Infections
Loracarbef also has been used for the treatment of mild to moderate uncomplicated pyelonephritis caused by susceptible Escherichia coli. While loracarbef also has been used effectively for the treatment of uncomplicated urinary tract infections (cystitis) caused by susceptible E. coli or Staphylococcus saprophyticus, the possibility of lower bacterial eradication rates compared with certain other anti-infectives (e.g., fluoroquinolones) should be weighed carefully when selecting appropriate therapy.
Administration
Loracarbef is administered orally. Because food decreases both the rate of GI absorption and peak plasma concentrations achieved, loracarbef should be administered at least 1 hour before or 2 hours after a meal.
Dosage
Dosage of loracarbef, which is commercially available for oral use as the monohydrate, is expressed in terms of anhydrous loracarbef.
Adult Dosage
Geriatric patients generally can receive usual dosages of loracarbef unless creatinine clearance is less than 50 mL/minute. (See Dosage and Administration: Dosage in Renal Impairment.)
Respiratory Tract Infections
The usual dosage of loracarbef for the treatment of secondary bacterial infections of acute bronchitis in adults and adolescents 13 years of age or older is 200-400 mg every 12 hours for 7 days. For the treatment of acute maxillary sinusitis, acute bacterial exacerbations of chronic bronchitis, or pneumonia in adults and adolescents 13 years of age or older, the usual dosage of loracarbef is 400 mg every 12 hours.
The drug should be continued for 7 days in those with acute bacterial exacerbations of chronic bronchitis, for 10 days in those with sinusitis, or for 14 days in those with pneumonia.
Pharyngitis and Tonsillitis
The usual dosage of loracarbef for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A b-hemolytic streptococci) in adults and adolescents 13 years of age or older is 200 mg every 12 hours for 10 days or longer. (See Uses: Pharyngitis and Tonsillitis.)
Skin and Skin Structure Infections
For the treatment of mild to moderate uncomplicated skin and skin structure infections in adults and adolescents 13 years of age or older, the usual dosage of loracarbef is 200 mg every 12 hours for 7 days.
Urinary Tract Infections
For the treatment of mild to moderate urinary tract infections in adults and adolescents 13 years of age or older, the usual dosage of loracarbef is 200 mg once daily for 7 days for uncomplicated cystitis or 400 mg every 12 hours for 14 days for uncomplicated pyelonephritis.
Pediatric Dosage
Children 13 years of age or older may receive the usual adult dosage of loracarbef.
Acute Maxillary Sinusitis
The usual dosage of loracarbef for the treatment of acute maxillary sinusitis in children 6 months to 12 years of age is 15 mg/kg every 12 hours for 10 days.
Acute Otitis Media
The usual dosage of loracarbef oral suspension for the treatment of acute otitis media in children 6 months to 12 years of age is 15 mg/kg every 12 hours for 10 days. The manufacturer states that loracarbef capsules should not be used for the treatment of acute otitis media. (See Uses: Otitis Media.)
Pharyngitis and Tonsillitis
The usual dosage of loracarbef for the treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A b-hemolytic streptococci) in children 6 months to 12 years of age is 7.5 mg/kg every 12 hours for 10 days or longer. (See Uses: Pharyngitis and Tonsillitis.)
Skin and Skin Structure Infections
The usual dosage of loracarbef for the treatment of uncomplicated skin and skin structure infections (e.g., impetigo) in children 6 months to 12 years of age is 7.5 mg/kg every 12 hours for 7 days.
Dosage in Renal Impairment
Dosage of loracarbef should be modified according to the degree of renal impairment for patients with creatinine clearances less than 50 mL/minute.
The manufacturer recommends that such patients with creatinine clearances of at least 10 mL/minute receive half the usual dose every 12 hours or the usual dose every 24 hours.
For patients with more severe renal impairment, the usual dose can be administered every 3-5 days; in addition, a supplementary dose should be administered after hemodialysis.
Cautions
Adverse effects reported with loracarbef are similar to those reported with other orally administered b-lactam antibiotics, and the drug generally is well tolerated.
Most adverse effects reported in clinical trials of loracarbef were mild and transient, with only 1.5% of patients discontinuing the drug because of adverse effects. Adverse GI, nervous system, and dermatologic effects are the most frequent adverse effects of loracarbef, and adverse GI and dermatologic effects are the most frequent adverse effects requiring discontinuance of the drug.
The frequency of some adverse effects differs substantially between adults and children. (See Cautions: Pediatric Precautions.)
Although the safety profile of loracarbef generally is similar to that of oral amoxicillin, amoxicillin and clavulanate potassium, and cefaclor, the frequency of diarrhea with loracarbef has been less than that observed with these other anti-infectives. Certain other adverse effects also have been reported less frequently with loracarbef (e.g., diaper rash versus that reported with amoxicillin and clavulanate potassium).
GI Effects
Adverse GI effects are the most common adverse effects of loracarbef. The most common adverse effect of loracarbef is diarrhea, which was reported in 4.1% of patients (3.6% of adults and 5.8% of children) receiving the drug in clinical trials. Nausea was reported in 1.9% of patients (2.5% of adults and none in children) and vomiting in 1.4% of patients (0.5% of adults and 3.3% of children) receiving the drug in clinical trials.
Anorexia was reported in less than 1% of patients (0.3% of adults and 2.3% of children) and abdominal pain in 1.4% of patients receiving loracarbef in clinical trials. Oral candidiasis has been reported in children receiving the drug.
The frequency of adverse GI effects, particularly diarrhea, increases with increasing daily doses of loracarbef. Diarrhea and vomiting in adults and diarrhea in children appear to be dose related. Although specific adverse GI effects occur infrequently, they are among the most frequent adverse effects requiring discontinuance of the drug.
Effects on Fecal Flora
Clostridium difficile-associated diarrhea and colitis (also known as antibiotic-associated pseudomembranous colitis) caused by toxin-producing clostridia has been reported with nearly all antibacterial agents. C. difficile-associated diarrhea and colitis may range in severity from mild to life-threatening.
Mild cases of colitis may respond to discontinuance of the drug alone, but management of moderate to severe cases should include appropriate bacteriologic studies and treatment with fluid, electrolyte, and protein supplementation as indicated. If colitis is moderate to severe or is not relieved by discontinuance of the drug, appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) should be administered.
Loracarbef therapy generally has only a minimal effect on normal bowel flora, possibly because the drug is well absorbed from the GI tract. Either no change or a slight increase in total bacterial counts of normal aerobic fecal flora and no change or a slight decrease in total bacterial counts of normal anaerobic fecal flora occur during loracarbef therapy.
Nervous System Effects
The most frequent adverse nervous system effect of loracarbef is headache, which was reported in 2.9% of patients (3.2% of adults and 0.9% of children) receiving the drug in clinical trials. In adults, headache appears to be dose related.
Somnolence was reported in less than 1% of patients receiving loracarbef in clinical trials. Nervousness, insomnia, dizziness, and asthenia have been reported in less than 1% of patients receiving the drug.
Although seizures have not been reported in patients receiving loracarbef, several b-lactam antibiotics have been implicated in precipitating seizures, particularly in patients with renal impairment in whom the dosage was not reduced. If seizures associated with loracarbef therapy occur, the drug should be discontinued and appropriate anticonvulsant therapy instituted if clinically indicated.
Dermatologic and Sensitivity Reactions
Rash is the most common sensitivity reaction to loracarbef and has been reported in 1.2% of patients receiving the drug in clinical trials.
Although rash occurs infrequently, it is among the most frequent adverse effects requiring discontinuance of loracarbef therapy. In young children, loracarbef-associated rash often occurs as diaper rash.
Cutaneous candidiasis has been reported in children receiving loracarbef.
Urticaria, pruritus, and erythema multiforme have been reported in less than 1% of patients receiving loracarbef, and anaphylaxis, Stevens-Johnson syndrome, and serum sickness-like reaction have been reported rarely with the drug. If a sensitivity reaction occurs during loracarbef therapy, the drug should be discontinued. (See Cautions: Precautions and Contraindications.) If a severe hypersensitivity reaction occurs during loracarbef therapy, the drug should be discontinued and the patient given appropriate treatment (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen) as indicated.
Respiratory Effects
Rhinitis was reported in 1.6% of adults and 6.3% of children receiving loracarbef in clinical trials. Increased cough was reported in 3.7% of adults receiving loracarbef for streptococcal pharyngitis/tonsillitis.
Hematologic Effects
Transient thrombocytopenia, leukopenia, and eosinophilia have been reported in less than 1% of patients receiving loracarbef. Prolonged prothrombin time with clinical bleeding has been reported rarely in patients receiving loracarbef and anticoagulants. Although not reported in patients receiving loracarbef, adverse hematologic effects reported in patients receiving b-lactam antibiotics include neutropenia, agranulocytosis, pancytopenia, aplastic anemia, hemolytic anemia, and positive direct antiglobulin (Coombs’) test result.
Cardiovascular Effects
Vasodilation has been reported in less than 1% of patients receiving loracarbef.
Hepatic Effects
Transient increases in serum AST (SGOT), ALT (SGPT), and alkaline phosphatase concentrations have occurred in less than 1% of patients receiving loracarbef. Hepatic dysfunction including cholestasis (with or without jaundice) has been reported rarely in patients receiving loracarbef.
Renal Effects
Transient increases in BUN and serum creatinine concentrations have occurred in less than 1% of patients receiving loracarbef. Biopsy-confirmed acute interstitial nephritis has been reported in at least one 18-month-old infant who received the usual loracarbef dosage for the treatment of acute otitis media. The infant developed vomiting, facial rash, lethargy, eosinophiluria, and renal failure within 5 days of initiation of loracarbef therapy. Renal dysfunction and toxic nephropathy have been reported in patients receiving other b-lactam antibiotics.
Other Adverse Effects
Vaginitis has been reported in 1.3%1 and vaginal candidiasis in 1.1% of patients receiving loracarbef.
Precautions and Contraindications
Prior to initiation of therapy with loracarbef, careful inquiry should be made concerning previous hypersensitivity reactions to loracarbef, b-lactam antibiotics including penicillins and cephalosporins, or other drugs. There is clinical and laboratory evidence of partial cross-allergenicity among b-lactam antibiotics including penicillins, cephalosporins, and cephamycins.
Loracarbef is contraindicated in patients with known allergy to the drug or to cephalosporins and should be used with caution in patients hypersensitive to penicillins. As with other anti-infective agents, prolonged use of loracarbef may result in overgrowth of nonsusceptible organisms.
Careful observation of the patient during loracarbef therapy is essential. If superinfection occurs, appropriate therapy should be initiated.
Because Clostridium difficile-associated diarrhea and colitis has been reported with the use of b-lactam antibiotics, it should be considered in the differential diagnosis of patients who develop diarrhea during loracarbef therapy.
Loracarbef should be used with caution in patients with a history of GI disease, especially colitis. In patients with known or suspected renal impairment, careful observation and appropriate laboratory studies should be performed prior to and during loracarbef therapy.
Because plasma concentrations of loracarbef may be higher and prolonged in these patients, doses and/or frequency of administration should be decreased. (See Dosage and Administration: Dosage in Renal Impairment.) Loracarbef, like other cephalosporins, should be used with caution in patients receiving concomitant therapy with potent diuretics that may adversely affect renal function.
Pediatric Precautions
The manufacturer states that safety and efficacy of loracarbef in infants younger than 6 months of age have not been established.
The manufacturer recommends that only the oral suspension of loracarbef be used for the treatment of otitis media since this formulation is absorbed from the GI tract more rapidly than oral capsules, resulting in higher peak plasma concentrations of the drug, and efficacy studies for this infection were conducted with the suspension.
Diarrhea, vomiting, anorexia, somnolence, rash, and rhinitis occurred substantially more frequently in children than in adults receiving loracarbef in clinical trials.
Biopsy-confirmed acute interstitial nephritis has been reported in at least one infant who received the usual loracarbef dosage for the treatment of acute otitis media. (See Cautions: Renal Effects.)
Geriatric Precautions
Loracarbef generally is well tolerated in geriatric patients; at the usual recommended dosages in clinical trials, efficacy and safety of the drug were comparable in geriatric patients and in younger adults.
There were 3541 adult patients in controlled clinical studies of loracarbef and about 20% were 65 years of age or older. There were no substantial differences in area under the plasma loracarbef concentration-time curve (AUC) or plasma clearance of the drug in healthy geriatric individuals with normal renal function compared with healthy adults 20-40 years of age following a single oral 400-mg dose of loracarbef.
Because geriatric patients frequently have decreased renal function, renal function should be evaluated in these patients and dosage should be carefully selected.
If evidence of renal impairment exists or develops, appropriate adjustments in dosage should be made. (See Dosage and Administration: Dosage in Renal Impairment.) Dosage of loracarbef does not need to be modified in geriatric patients with creatinine clearances of 50 mL/minute or higher.
Mutagenicity and Carcinogenicity
Standard genotoxicity tests, including bacterial mutation tests and in vitro and in vivo mammalian systems, using loracarbef have not shown evidence of mutagenicity. Long-term studies have not been performed to date to evaluate the carcinogenic potential of the drug.
Pregnancy, Fertitlity and Lactation
Reproduction studies in mice, rats, and rabbits using loracarbef at doses up to 33 times the maximum human exposure in mg/kg (4, 10, and 4 times the exposure, respectively, based on mg/m2) have not revealed evidence of harm to the fetus.
There are no adequate and controlled studies to date using loracarbef in pregnant women or during labor and delivery, and the drug should be used during pregnancy or labor and delivery only when clearly needed.
Reproduction studies in mice, rats, and rabbits using loracarbef at doses up to 33 times the maximum human exposure in mg/kg (4, 10, and 4 times the exposure, respectively, based on mg/m2) have not revealed evidence of impaired fertility. In rats, reproductive performance also was not affected by loracarbef at doses up to 33 times the maximum human exposure in mg/kg (10 times the exposure based on mg/m2). Since it is not known whether loracarbef is distributed into milk, the drug should be used with caution in nursing women.
Preparations
Loracarbef Oral Capsules 200 mg (of anhydrous Lorabid® Pulvules®, loracarbef) Monarch 400 mg (of anhydrous Lorabid® Pulvules®, loracarbef) Monarch For suspension 100 mg (of anhydrous Lorabid®, (with parabens) loracarbef) per 5 mL Monarch 200 mg (of anhydrous Lorabid®, (with parabens) loracarbef) per 5 mL Monarch
Sinusitis and Lorabid
Question from Gabriel
I was diagnosed with sinusitis three weeks ago. I was put on Cefaclor for ten days. I just got sick again and the doctor said I still have sinusitis. I am now on pseudoeph/guaifen and LORABID. 1. Is it normal that I’ve been sick this long? 2. I am allergic to penicillin. Should I be taking this?
Dear Gabriel:
Sinusitis can be a very persistent infection, and therefore you may require multiple antibiotics. I usually will treat patients with a three week course of an antibiotic. It is usually good to add a decongestant and a mucolytic agent. With regards to your penicillin allergy, there is about a 10% cross reactivity with LORABID. It sounds like you are being treated correctly. Remember to finish all you medications, even if you feel normal before they are finished.