Lorabid

Loracarbef is a synthetic oral antibiotic in the cephalosporin family of antibiotics. The cephalosporin family includes cephalexin (Keflex), cefaclor (Ceclor), cefuroxime (Zinacef), cefpodoxime (Vantin), cefprozil (Cefzil), and many injectable antibiotics. Like other cephalosporins, loracarbef stops bacteria from multiplying by preventing bacteria from forming the walls that surround them. The walls are necessary to protect bacteria from their environment and to keep the contents of the bacterial cell together. Bacteria cannot survive without a cell wall. Loracarbef is effective against a wide variety of bacteria such as Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, E. coli, and many others. Loracarbef was approved in December 1991.

The nature of adverse reactions to loracarbef are similar to those observed with orally administered b-lactam antimicrobials. The majority of adverse reactions observed in clinical trials were of a mild and transient nature; 1.5% of patients discontinued therapy because of drug-related adverse reactions. No one reaction requiring discontinuation accounted for >0.03% of the total patient population; however, of those reactions resulting in discontinuation, gastrointestinal events (diarrhea and abdominal pain) and skin rashes predominated.

All Patients

The following adverse events, irrespective of relationship to drug, have been reported following the use of loracarbef in clinical trials. Incidence rates (combined for all dosing regimens and dosage forms) were less than 1% for the total patient population, except as otherwise noted:

Gastrointestinal: The most commonly observed adverse reactions were related to the gastrointestinal system. The incidence of gastrointestinal adverse reactions increased in patients treated with higher doses. Individual event rates included diarrhea, 4.1%; nausea, 1.9%; vomiting 1.4%; abdominal pain, 1.4%; and anorexia.

Hypersensitivity: Hypersensitivity reactions including, skin rashes (1.2%), urticaria, pruritus, and erythema multiforme.

Central Nervous System: Headache (2.9%), somnolence, nervousness, insomnia, and dizziness.

Hemic and Lymphatic Systems: Transient thrombocytopenia, leukopenia, and eosinophilia.

Hepatic: Transient elevations in AST (SGOT), ALT (SGPT), and alkaline phosphatase.

Renal: Transient elevations in BUN and creatinine.

Cardiovascular System: Vasodilatation.

Genitourinary: Vaginitis (1.3%), vaginal moniliasis (1.1%).

As with other b-lactam antibiotics, the following potentially severe adverse experiences have been reported rarely with loracarbef in worldwide post-marketing surveillance: anaphylaxis, hepatic dysfunction including cholestasis, prolongation of the prothrombin time with clinical bleeding in patients taking anticoagulants, and Stevens-Johnson syndrome.

Pediatric Patients

The incidences of several adverse events, irrespective of relationship to drug, following treatment with loracarbef were significantly different in the pediatric population and the adult population as follows (TABLE 12):

b-Lactam Antimicrobial Class Labeling

The following adverse reactions and altered laboratory test results have been reported in patients treated with b-lactam antibiotics:

Adverse Reactions: Allergic reactions, aplastic anemia, hemolytic anemia, hemorrhage, agranulocytosis, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy. As with other b-lactam antibiotics, serum sickness-like reactions have been reported rarely with loracarbef.

Several b-lactam antibiotics have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy should occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Altered Laboratory Tests: Increased prothrombin time, positive direct Coombs' test, elevated LDH, pancytopenia, and neutropenia.

BEFORE THERAPY WITH LORACARBEF IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO LORACARBEF, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG b-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 LORACARBEF OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE THE USE OF 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 and may range 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 broad-spectrum antibiotics alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of "antibiotic-associated colitis."

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

Signs and Symptoms: The toxic symptoms following an overdose of b-lactams may include nausea, vomiting, epigastric distress, and diarrhea.

Loracarbef is eliminated primarily by the kidneys. Forced diuresis, peritoneal dialysis, hemodialysis, or hemoperfusion have not been established as beneficial for an overdose of loracarbef. Hemodialysis has been shown to be effective in hastening the elimination of loracarbef from plasma in patients with chronic renal failure.

Lorabid is part of the drug class:

• Second generation cephalosporins

If your symptoms do not improve within a few days, or if they become worse, check with your doctor.

In some patients, loracarbef may cause diarrhea.

• Severe diarrhea may be a sign of a serious side effect. Do not take any diarrhea medicine without first checking with your doctor . Diarrhea medicines may make your diarrhea worse or last longer.
• For mild diarrhea, diarrhea medicine containing kaolin or attapulgite (e.g., Kaopectate tablets, Diasorb) may be taken. However, other kinds of diarrhea medicine should not be taken. They may make your diarrhea worse or last longer.
• If you have any questions about this or if mild diarrhea continues or gets worse, check with your health care professional.

Lorabid is indicated in the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below. (As recommended dosages, durations of therapy, and applicable patient populations vary among these infections, please see DOSAGE AND ADMINISTRATION for specific recommendations.)

Lower Respiratory Tract

Secondary Bacterial Infection of Acute Bronchitis caused by S. pneumoniae, H. influenzae (includingβ-lactamase-producing strains), or M. catarrhalis (including β-lactamase-producing strains).

Acute Bacterial Exacerbations of Chronic Bronchitis caused by S. pneumoniae, H. influenzae (includingβ-lactamase-producing strains), or M. catarrhalis (including β-lactamase-producing strains).

Pneumonia caused by S. pneumoniae or H. influenzae (non-β-lactamase-producing strains only). Data are insufficient at this time to establish efficacy in patients with pneumonia caused by β-lactamase-producing strains of H. influenzae.

Upper Respiratory Tract

Otitis Media † caused by S. pneumonia, H. influenzae (including β-lactamase-producing strains), M. catarrhalis (including β-lactamase-producing strains), or S. pyogenes.

Acute Maxillary Sinusitis† caused by S. pneumoniae, H. influenzae (non-β-lactamase-producing strains only), or M. catarrhalis (includingβ-lactamase-producing strains). Data are insufficient at this time to establish efficacy in patients with acute maxillary sinusitis caused by β-lactamase-producing strains of H. influenzae.

† NOTE: In a patient population with significant numbers of β-lactamase-producing organisms, loracarbef's clinical cure and bacteriological eradication rates were somewhat less than those observed with a product containing a β-lactamase inhibtor. Lorabid's decreased potential for toxicity compared to products containing β-lactamase inhibitors along with the susceptibility patterns of the common microbes in a given geographic area should be taken into account when considering the use of an antimicrobial (see CLINICAL STUDIES section). For information on use in pediatric patients, seePRECAUTIONSPediatric Use.

Pharyngitis and Tonsillitis caused by S. pyogenes. (The usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever, is penicillin administered by the intramuscular route. Lorabid is generally effective in the eradication of S. pyogenes from the nasopharynx; however, data establishing the efficacy of Lorabid in the subsequent prevention of rheumatic fever are not available at present.)

Skin and Skin Structure

Uncomplicated Skin and Skin Structure Infections caused by S. aureus (including penicillinase-producing strains) or S. pyogenes. Abscesses should be surgically drained as clinically indicated.

Urinary Tract

Uncomplicated Urinary Tract Infections (cystitis) caused by E.coli or S. saprophyticus*.

NOTE: In considering the use of Lorabid in the treatment of cystitis, Lorabid's lower bacterial eradication rates and lower potential for toxicity should be weighed against the increased eradication rates and increased potential for toxicity demonstrated by some other classes of approved agents (see CLINICAL STUDIES section).

Uncomplicated Pyelonephritis caused by E. coli.

*Although treatment of infections due to this organism in this organ system demonstrated a clinically acceptable overall outcome, efficacy was studied in fewer than 10 infections.

Culture and susceptibility testing should be performed when appropriate to determine the causative organism and its susceptibility to loracarbef. Therapy may be started while awaiting the results of these studies. Once these results become available, antimicrobial therapy should be adjusted accordingly.

CONTRAINDICATION

Lorabid is contraindicated in patients with known allergy to loracarbef or cephalosporin-class antibiotics.

The nature of adverse reactions to loracarbef are similar to those observed with orally administered β-lactam antimicrobials. The majority of adverse reactions observed in clinical trials were of a mild and transient nature; 1.5% of patients discontinued therapy because of drug-related adverse reactions. No one reaction requiring discontinuation accounted for >0.03% of the total patient population; however, of those reactions resulting in discontinuation, gastrointestinal events (diarrhea and abdominal pain) and skin rashes predominated.

All Patients

The following adverse events, irrespective of relationship to drug, have been reported following the use of Lorabid in clinical trials. Incidence rates (combined for all dosing regimens and dosage forms) were less than 1% for the total patient population, except as otherwise noted:

Gastrointestinal: The most commonly observed adverse reactions were related to the gastrointestinal system. The incidence of gastrointestinal adverse reactions increased in patients treated with higher doses. Individual event rates included diarrhea, 4.1%; nausea, 1.9%; vomiting, 1.4%; abdominal pain, 1.4%; and anorexia.

Hypersensitivity:Hypersensitivity reactions including, skin rashes (1.2%), urticaria, pruritus, and erythema multiforme.

Central Nervous System: Headache (2.9%), somnolence, nervousness, insomnia, and dizziness.

Hemic and Lymphatic Systems: Transient thrombocytopenia, leukopenia, and eosinophilia.

Hepatic: Transient elevations in AST (SGOT), ALT (SGPT), and alkaline phosphatase.

Renal:Transient elevations in BUN and creatinine.

Cardiovascular System: Vasodilatation.

Genitourinary: Vaginitis (1.3%), vaginal moniliasis (1.1%).

As with other β-lactam antibiotics, the following potentially severe adverse experiences have been reported rarely with loracarbef in worldwide post-marketing surveillance: anaphylaxis, hepatic dysfunction including cholestasis (with or without jaundice), prolongation of the prothrombin time with clinical bleeding in patients taking anticoagulants, and Stevens-Johnson syndrome.

Pediatric Patients

The incidences of several adverse events, irrespective of relationship to drug, following treatment with Lorabid were significantly different in the pediatric population and the adult population as follows:

β-Lactam Antimicrobial Class Labeling:

The following adverse reactions and altered laboratory test results have been reported in patients treated with β-lactam antibiotics:

Adverse ReactionsAllergic reactions, aplastic anemia, hemolytic anemia, hemorrhage, agranulocytosis, toxic epidermal necrolysis, renal dysfunction, and toxic nephropathy. As with other β-lactam antibiotics, serum sickness-like reactions have been reported rarely with loracarbef.

Several β-lactam antibiotics have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy should occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Altered Laboratory TestsIncreased prothrombin time, positive direct Coombs' test, elevated LDH, pancytopenia, and neutropenia.

Pulvules:

Keep tightly closed. Store at 25°C (77°F); excursion permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Protect from heat.

For Oral Suspension (strawberry bubble gum flavor):

Prior to mixing, store at 25°C (77°F); excursion permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature].

Applies to loracarbef: oral capsule, oral powder for suspension

Along with its needed effects, loracarbef (the active ingredient contained in Lorabid) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur while taking loracarbef:

• Itching
• skin rash

Some side effects of loracarbef may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea
• loss of appetite
• nausea and vomiting
• stomach pain

• Dizziness
• drowsiness
• headache
• itching or discharge from the vagina
• nervousness
• trouble in sleeping