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Loracarbef

Class: Carbacephems
Chemical Name: [6R-[6α,7β(R*)]]-7-[(Aminophe nylacetyl)amino]-3-chloro-8-oxo-1-azabicyclo[4.2.0]oct-2-ene-2-carbo xylic acid monohydrate
CAS Number: 121961-22-6
Brands: Lorabid

Introduction

Antibacterial; carbacephem β-lactam antibiotic.1 2 3

Uses for Loracarbef

Respiratory Tract Infections

Treatment of mild to moderate acute maxillary sinusitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae (non-β-lactamase-producing strains only), or Moraxella catarrhalis (including β-lactamase-producing strains).1 Associated with lower bacteriologic eradication and clinical cure rates than some other anti-infectives (e.g., amoxicillin and clavulanate) in patient populations with high numbers of β-lactamase-producing bacteria.1 The possibility of reduced overall efficacy should be weighed carefully against local susceptibility patterns for common pathogens encountered in these infections.1

Treatment of secondary bacterial infections of acute bronchitis caused by susceptible S. pneumoniae, H. influenzae (including β-lactamase-producing strains), or M. catarrhalis (including β-lactamase-producing strains).1 2

Slideshow: The Shocking Truth About Antibiotic Resistance

Treatment of acute bacterial exacerbations of chronic bronchitis caused by susceptible S. pneumoniae, H. influenzae (including β-lactamase-producing strains), or M. catarrhalis (including β-lactamase-producing strains).1 2

Treatment of mild to moderate pneumonia caused by susceptible S. pneumoniae or H. influenzae (non-β-lactamase-producing strains only)1 when oral therapy is considered appropriate.1 Because of possible lack of efficacy, ATS states that loracarbef should not be used for empiric treatment of community-acquired pneumonia (CAP) if multidrug-resistant S. pneumoniae are suspected.33

Acute Otitis Media

Treatment of acute otitis media (AOM) caused by S. pneumoniae, S. pyogenes (group A β-hemolytic streptococci), H. influenzae (including β-lactamase-producing strains), or M. catarrhalis (including β-lactamase-producing strains).1

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci).1 Generally effective in eradicating S. pyogenes from the nasopharynx, but efficacy in the prevention of subsequent rheumatic fever has not been established.1

CDC, AAP, IDSA, AHA, and others recommend oral penicillin V or IM penicillin G benzathine as treatments of choice;9 20 22 oral cephalosporins and oral macrolides considered alternatives.9 20 21 22 23 24 25 26 Amoxicillin sometimes used instead of penicillin V, especially for young children.22

Skin and Skin Structure Infections

Treatment of mild to moderate uncomplicated skin and skin structure infections caused by susceptible S. aureus (including penicillinase-producing strains) or S. pyogenes;1 abscesses usually require surgical drainage.1

Urinary Tract Infections (UTIs)

Treatment of uncomplicated UTIs (cystitis) caused by susceptible Escherichia coli or S. saprophyticus.1 When selecting loracarbef for UTIs, carefully weigh the lower bacterial eradication rate and lower potential for toxicity against increased eradication rates and increased potential for toxicity associated with other anti-infectives (e.g., fluoroquinolones).1

Treatment of uncomplicated pyelonephritis caused by susceptible E. coli.1

Loracarbef Dosage and Administration

Administration

Oral Administration

Administer orally at least 1 hour before or 2 hours after a meal.1

Reconstitution

Reconstitute oral suspension at the time of dispensing by adding the amount of water specified on the container in 2 portions; shake well after each addition.1

Reconstituted suspension contains 100 or 200 mg of loracarbef/5 mL.1

Dosage

Available as loracarbef monohydrate; dosage expressed in terms of anhydrous loracarbef.1

Pediatric Patients

Respiratory Tract Infections
Acute Sinusitis
Oral

Children 6 months to 12 years of age: 15 mg/kg every 12 hours for 10 days.1

Children ≥13 years of age: 400 mg every 12 hours for 10 days.1

Secondary Bacterial Infections of Acute Bronchitis
Oral

Children ≥13 years of age: 200–400 mg every 12 hours for 7 days.1

Acute Bacterial Exacerbations of Chronic Bronchitis
Oral

Children ≥13 years of age: 400 mg every 12 hours for 7 days.1

Pneumonia
Oral

Children ≥13 years of age: 400 mg every 12 hours for 14 days.1

Acute Otitis Media
Oral

Children 6 months to 12 years of age: 15 mg/kg (as the oral suspension) every 12 hours for 10 days.1 Do not use capsules for treatment of AOM.1

Pharyngitis and Tonsillitis
Oral

Children 6 months to 12 years of age: 7.5 mg/kg every 12 hours for ≥10 days.1

Skin and Skin Structure Infections
Oral

Children 6 months to 12 years of age: 7.5 mg/kg every 12 hours for 7 days.1

Children ≥13 years of age: 200 mg every 12 hours for 7 days.1

Urinary Tract Infections
Uncomplicated Cystitis
Oral

Children ≥13 years of age: 200 mg once every 24 hours for 7 days.1

Uncomplicated Pyelonephritis
Oral

Children ≥13 years of age: 400 mg every 12 hours for 14 days.1

Adults

Respiratory Tract Infections
Acute Sinusitis
Oral

400 mg every 12 hours for 10 days.1

Secondary Bacterial Infections of Acute Bronchitis
Oral

200–400 mg every 12 hours for 7 days.1

Acute Bacterial Exacerbations of Chronic Bronchitis
Oral

400 mg every 12 hours for 7 days.1

Pneumonia
Oral

400 mg every 12 hours for 14 days.1

Skin and Skin Structure Infections
Oral

200 mg every 12 hours for 7 days.1

Urinary Tract Infections
Uncomplicated Cystitis
Oral

200 mg once every 24 hours for 7 days.1

Uncomplicated Pyelonephritis
Oral

400 mg every 12 hours for 14 days.1

Special Populations

Renal Impairment

Dosage adjustment recommended in patients with Clcr <50 mL/minute.1

Patients with Clcr 10–49 mL/minute should receive 50% of the usual dose every 12 hours or the usual dose once every 24 hours.1 Patients with Clcr <10 mL/minute should receive the usual dose once every 3–5 days.1

Patients undergoing hemodialysis should receive a supplementary dose after the procedure.1

Geriatric Patients

No dosage adjustments except those related to renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Cautions for Loracarbef

Contraindications

  • Hypersensitivity to loracarbef or any cephalosporin.1

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible organism.1 Careful observation of the patient is essential.1 Institute appropriate therapy if superinfection occurs.1

Treatment with anti-infectives may permit overgrowth of clostridia.1 27 28 29 30 31 Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.1 27 28 29 30 31

Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone.1 27 28 29 30 31 Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.1 27 28 29 30 31

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions such as anaphylaxis, serum sickness-like reactions, Stevens-Johnson syndrome, and toxic epidermal necrolysis reported with loracarbef and other β-lactams.1

If an allergic reaction occurs, discontinue loracarbef and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).1

Cross-Hypersensitivity

Partial cross-allergenicity among β-lactam antibiotics, including penicillins, cephalosporins, and cephamycins.1

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to loracarbef, cephalosporins, penicillins, or other drugs.1 Cautious use recommended in individuals hypersensitive to penicillins;1 contraindicated in those hypersensitive to cephalosporins.1

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of loracarbef and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

History of GI Disease

Use with caution in patients with a history of GI disease, particularly colitis.1 (See Superinfection/Clostridium difficile-associated Colitis under Cautions.)

Specific Populations

Pregnancy

Category B.1

Lactation

Not known whether distributed into milk.1 Use with caution.1

Pediatric Use

Safety and efficacy not established in children <6 months of age.1

Pediatric patients have higher incidence of GI effects (diarrhea, vomiting, anorexia), rhinitis, somnolence, and rash compared with adults.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function.1 Assess renal function periodically since geriatric patients are more likely to have renal impairment.1

No dosage adjustments except those related to renal function.1 (See Renal Impairment under Dosage and Administration.)

Renal Impairment

Use with caution in patients with known or suspected renal impairment.1 Closely monitor and perform appropriate laboratory studies prior to and during therapy.1

Dosage adjustments recommended in patients with Clcr <50 mL/minute and in those undergoing hemodialysis or peritoneal dialysis.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea, nausea, vomiting, abdominal pain, anorexia); headache; rash.1

Interactions for Loracarbef

Specific Drugs

Drug

Interaction

Comments

Diuretics

Possible adverse effects on renal function1

Use with caution1

Probenecid

Decreased renal tubular secretion of loracarbef; increased loracarbef concentrations and AUC and prolonged half-life1

Loracarbef Pharmacokinetics

Absorption

Bioavailability

90% of a dose absorbed from GI tract.1

In fasting adults, peak plasma concentrations attained within 1.2 hours after capsules and within 0.8 hours after oral suspension. In children, peak plasma concentrations attained within 1 hour after oral suspension.1

Capsules and oral suspension are not bioequivalent; concentrations are higher and attained more quickly with oral suspension.1

Food

Food decreases rate and extent of absorption of capsules; effect of food on oral suspension not studied to date.1

Distribution

Extent

Distributed into middle ear fluid and blister fluid.1

Plasma Protein Binding

Approximately 25%.1

Elimination

Metabolism

Does not appear to be metabolized.1

Elimination Route

Substantially eliminated in urine.1

Half-life

1 hour in adults with normal renal function.1

Special Populations

Half-life and AUC in geriatric adults with normal renal function similar to younger adults.1

Half-life prolonged in patients with renal impairment.1 Approximately 5.6 hours in adults with moderate renal impairment (Clcr 10–50 mL/minute per 1.73 m2) and approximately 32 hours in those with severe renal impairment (Clcr <10 mL/minute per 1.73 m2).1

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).1 Protect from heat.1

For Suspension

25°C (may be exposed to 15–30°C).1 After reconstitution, 15–30°C in tight container; discard after 14 days.1

Actions and Spectrum

  • Carbacephem structurally and pharmacologically related to cephalosporins;1 2 3 the carba analog of cefaclor.3

  • Usually bactericidal.1

  • Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.1

  • Spectrum of activity includes many gram-positive aerobic bacteria, some gram-negative aerobic bacteria, and a few anaerobic bacteria.1

  • Gram-positive aerobes: active in vitro and in clinical infections against Staphylococcus aureus (including penicillinase-producing strains), S. saprophyticus, Streptococcus pneumoniae, and S. pyogenes (group A β-hemolytic streptococci).1 Also active in vitro against S. epidermidis, S. agalactiae (group B streptococci), S. bovis, groups C, F, and G streptococci, and viridans streptococci.1 Oxacillin-resistant (methicillin-resistant) staphylococci are resistant.1

  • Gram-negative aerobes: active in vitro and in clinical infections against Escherichia coli, Haemophilus influenzae (including β-lactamase-producing strains), and Moraxella catarrhalis (including β-lactamase-producing strains).1 Also active in vitro against Citrobacter diversus, H. parainfluenzae, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pasteurella multocida, Proteus mirabilis, Salmonella, Shigella, and Yersinia enterocolitica.1 Inactive against most Acinetobacter, Enterobacter, Morganella, P. vulgaris, Providencia, Pseudomonas, and Serratia.1

  • Anaerobes: although clinical importance unclear, active in vitro against Clostridium perfringens, Fusobacterium necrophorum, Peptococcus niger, Peptostreptococcus intermedius, and Propionibacterium acnes.1

Advice to Patients

  • Advise patients that antibacterials (including loracarbef) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).

  • Importance of completing full course of therapy, even if feeling better after a few days.

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with loracarbef or other antibacterials in the future.

  • Importance of taking loracarbef at least 1 hour before or at least 2 hours after eating.1

  • Importance of discontinuing therapy and informing clinician if an allergic reaction occurs.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Loracarbef

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

200 mg (of anhydrous loracarbef)

Lorabid Pulvules

Monarch

400 mg (of anhydrous loracarbef)

Lorabid Pulvules

Monarch

For suspension

100 mg (of anhydrous loracarbef) per 5 mL

Lorabid (with parabens)

Monarch

200 mg (of anhydrous loracarbef) per 5 mL

Lorabid (with parabens)

Monarch

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

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