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LORABID200 (Capsules); LORABID100P (Granules for Suspension)
LORABID200 (Capsules)
LORABID100P (Granules for Suspension)
LORABID200P (Granules for Suspension)
ProjectSAEPIOwnerMarland HoldernessStatusCopyright 2006PA8442ITUAP
SCHEDULING STATUS:
Schedule4
PROPRIETARY NAME
(and dosage form):
LORABID200 (Capsules)
LORABID100P (Granules for Suspension)
LORABID200P (Granules for Suspension)
COMPOSITION:
Each LORABID200 capsule contains loracarbefequivalent to 200mg of anhydrous activity.
Each 5mLLORABID100P oral suspension contains loracarbef equivalent to 100mg of anhydrous activity.
Each 5mL LORABID200P oral suspension contains loracarbef equivalent to 200mg of anhydrous activity.
LORABID100P and 200P oral suspensions contain methyl parahydroxybenzoate 0,07% (m/v) and propyl parahydroxybenzoate 0,02% (m/v) as preservatives.
Chemically it is: (6R, 7S)-7-[(R)-2-amino-2-phenylacetamido]-3-chloro-8-oxo-1-azabicyclo [4.2.0]oct-2-ene-2-carboxylic acid, monohydrate. It is a white crystalline compound with a molecular mass of 367,8. The empirical formula is C16O4N3H16ClH2O.
PHARMACOLOGICAL CLASSIFICATION:
A 20.1.1 Broad and Medium Spectrum Antibiotics
PHARMACOLOGICAL ACTION:
Loracarbef is a synthetic beta-lactam antibiotic of the carbacephem class for oral administration.
Loracarbef is approximately 90% absorbed from the gastro-intestinal tract after oral administration whether administered with or without food. Following administration of single doses of 200mg and 400mg capsules to fasting subjects, average peak plasma concentrations of approximately 8and 14micrograms/mL, respectively, are obtained within 1,2hours. The average peak plasma concentration in adults following a 400mg single dose of suspension was 17micrograms/mL and was obtained within 0,8hours after dosing.
Following administration of 7,5 and 15mg/kg doses of oral suspension to children, average peak plasma concentrations of approximately 13 and 19micrograms/mL, respectively, are obtained within 40 to 60minutes.
The pharmacokinetics of loracarbef are linear over a dosage range of 100 to 400mg, with no accumulation of the medicine noted when it is given twice daily. When capsules are taken with food, peak plasma concentrations are 50% to 60% of those achieved when the drug is administered to fasting subjects and occur from 30 to 60minutes later. Total absorption, as measured by urinary recovery and AUC, is unchanged. Concomitant administration of probenecid decreases the rate of urinary excretion and increases the AUC by approximately 80%.
The plasma half-life of loracarbef in healthy subjects is independent of dosage form and averages approximately 1hour; this increases to 11/2hours when probenecid is given concurrently. In subjects with moderate impairment of renal function (creatinine clearance 10 to 50mL/min), the plasma half-life is prolonged to approximately 5,6hours. In subjects with severe renal impairment (creatinine clearance <10mL/min), the half-life is increased to approximately 32hours; during haemodialysis the half-life is approximately 4hours. Plasma half-life and AUC are not significantly altered in healthy elderly subjects with normal renal function. There is no evidence of metabolism of loracarbef in humans. The kidney is the major route of elimination.
Approximately 25% of circulating loracarbef is bound to plasma proteins.
Microbiology:Loracarbef exerts its bactericidal action by binding to essential target proteins of the bacterial cell wall, leading to inhibition of cell-wall synthesis. Loracarbef is stable in the presence of some bacterial beta-lactamases. Loracarbef has been shown to be active against most strains of the following organisms both in vitro and in clinical infections:
GRAM-POSITIVE AEROBES:
Staphylococcus aureus.
Staphylococcus saprophyticus.
Streptococcus pneumoniae.
Streptococcus pyogenes (group A beta-haemolytic streptococci).
NOTE: Loracarbef is inactive against methicillin-resistant staphylococci and enterococci.
Gram-negative aerobes:
Escherichia coli.
Haemophilus influenzae (including beta-lactamase-producing strains).
Moraxella (Branhamella) catarrhalis (including beta-lactamase-producing strains).
Loracarbef has been shown to have activity in vitro against most strains of the following organisms; however, clinical efficacy has not been established and in vitro activity does not imply in vivo efficacy.
Gram-positive aerobes:
Staphylococcus epidermidis.
Streptococcus agalactiae (group B streptococci).
Streptococcus bovis.
Streptococci, groups C, F and G.
Streptococci, viridans group.
Gram-negative aerobes:
Haemophilus parainfluenzae.
Citrobacter diversus.
Klebsiella pneumoniae.
Neisseria gonorrhoeae (including penicillinase-producing strains).
Proteus mirabilis.
Pasteurella multocida.
Salmonella species.
Shigella species.
Yersinia enterocolitica.
Anaerobic organisms:
Fusobacterium necrophorum.
Peptostreptococcus intermedius.
Propionibacterium acnes.
NOTE: Loracarbef is inactive against most strains of Acinetobacter, Enterobacter, Morganella morganii, Proteus vulgaris,
Providencia, Pseudomonas and Serratia. Most anaerobes are resistant to loracarbef.
INDICATIONS:
LORABID is indicated in the treatment of patients with mild to moderate infections caused by susceptible organisms:
Otitis media caused by S. pneumoniae, H. influenzae, M.(B.) catarrhalis or S. pyogenes.
Acute bronchitis and acute exacerbations of chronic bronchitis caused by S. pneumoniae, H. influenzae or M.(B.) catarrhalis.
Pneumonia caused by S. pneumoniae or H. influenzae.
Acute maxillary sinusitis caused by S. pneumoniae, H. influenzae or M.(B.) catarrhalis.
Pharyngitis and tonsillitis caused by S. pyogenes.
Uncomplicated lower urinary tract infections (cystitis) caused by E. coli.
Uncomplicated pyelonephritis caused by E. coli.
Skin and skin structure infections caused by S. aureus or S. pyogenes.
CONTRA-INDICATIONS:
Known allergy to loracarbef or cephalosporin antibiotics.
Safety in pregnancy and lactation has not been established.
Safety and efficacy in infants less than 6months have not been established.
Severe renal failure (creatinine clearance <30mL/min).
WARNINGS:
BEFORE THERAPY WITH LORABID IS INSTITUTED, CAREFUL ENQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS ALLERGIC REACTIONS TO LORACARBEF, OTHER beta-LACTAMS, OR OTHER MEDICINES. IF THIS PRODUCT IS TO BE GIVEN TO beta-LACTAM-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG beta-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED. IF AN ALLERGIC REACTION TO LORABID OCCURS, DISCONTINUE THE MEDICINE. SERIOUS ACUTE ALLERGIC REACTIONS MAY REQUIRE THE USE OF ADRENALINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.
DOSAGE AND DIRECTIONS FOR USE:
LORABID is administered orally on an empty stomach.
Adults: The recommended dosage for the treatment of pharyngitis, tonsillitis and skin infections is 200mg twice a day. For sinusitis, pneumonia and uncomplicated pyelonephritis the recommended dosage is 400mg twice a day. For uncomplicated cystitis, the recommended dosage is 200mg given once daily. The dosage for bronchitis is 200 - 400mg twice daily.
Children: The usual recommended daily dosage for pharyngitis, tonsillitis and skin infections in children is 15mg/kg/day given in divided doses twice a day. For acute otitis media 30mg/kg/day in two divided doses is recommended. The following tables provide guidelines for attainment of these dosages:
PAEDIATRIC DOSAGE CHART
DAILY DOSE 15mg/kg/day
Mass
(kg) |
LORABID100P
Dose given twice daily (mL) |
LORABID200P
Dose given twice daily (mL) |
|
7 |
2,5 |
- |
|
13 |
5,0 |
2,5 |
|
20 |
7,5 |
4,0 |
|
26 |
10,0 |
5,0 |
PAEDIATRIC DOSAGE CHART
DAILY DOSE 30mg/kg/day
Mass
(kg) |
LORABID100P
Dose given twice daily (mL) |
LORABID200P
Dose given twice daily (mL) |
|
7 |
5,0 |
2,5 |
|
13 |
10,0 |
5,0 |
|
20 |
- |
7,5 |
|
26 |
- |
10,0 |
In the treatment of otitis media, sinusitis and infections caused by S. pyogenes (group A beta-haemolytic streptococci), a therapeutic dosage of LORABID should be given for at least 10days. In the treatment of pneumonia and pyelonephritis, LORABID should be administered for 14days.
The increased rate of absorption of the suspension should be taken into consideration if the oral suspension is to be substituted for the capsule and capsules should not be substituted for the oral suspension in the treatment of otitis media.
Reconstitution directions for oral suspension: Invert the bottle and tap to loosen powder. Add 30mL of water divided into two portions to the dry mixture in the bottle. Shake well after each addition.
SIDE EFFECTS AND SPECIAL PRECAUTIONS:
The following adverse reactions have been reported following the use of LORABID:
Gastro-intestinal:The most commonly observed adverse reactions were related to the gastro-intestinal system. The incidence of gastro-intestinal adverse reactions increased in patients treated with higher doses. Events included diarrhoea, nausea, vomiting, abdominal pain and anorexia.
Hypersensitivity:Hypersensitivity reactions including skin rashes, urticaria, pruritus and erythema multiforme.
Central nervous system:Headache, somnolence, nervousness, insomnia and dizziness.
Haemic and lymphatic systems:Transient thrombocytopenia, leucopenia and eosinophilia.
Hepatic:Transient elevations in AST, ALT and alkaline phosphatase.
Renal:Transient elevations in urea or creatinine.
Cardiovascular system:Vasodilatation.
Genito-urinary:Vaginitis, vaginal moniliasis.
The following adverse experiences have been reported less frequently following the use of LORABID: anaphylaxis, hepatic dysfunction including cholestasis, prolongation of the prothrombin time with clinical bleeding in patients taking anticoagulants, serum sickness-like reactions and Stevens-Johnson syndrome.
The following adverse reactions and altered laboratory test results have been reported in patients treated with beta-lactam antibiotics:
Adverse reactions:Allergic reactions, aplastic anaemia, haemolytic anaemia, haemorrhage, agranulocytosis, toxic epidermal necrolysis, fever, renal dysfunction and toxic nephropathy.
Several beta-lactam antibiotics have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with medicine therapy should occur, the medicine should be discontinued.
Anticonvulsant therapy can be given if clinically indicated.
Altered laboratory tests:Positive direct Coombs' test, elevated lactic dehydrogenase, pancytopenia and neutropenia.
PRECAUTIONS:
General:In patients with known or suspected renal impairment, careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy. The total daily dose of LORABID should be reduced in these patients because high and/or prolonged plasma antibiotic concentrations can occur in such individuals administered the usual doses. LORABID, like cephalosporins, should be given with caution to patients receiving concurrent treatment with potent diuretics because these diuretics are suspected of adversely affecting renal function.
The possibility of emergence of resistant organisms that might result in overgrowth should be kept in mind, particularly during prolonged treatment. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Use with caution in patients with a history of colitis.
The occurrence of pseudomembranous colitis cannot be excluded, therefore it is important to consider its diagnosis in patients who develop diarrhoea in association with the use of LORABID. Such colitis may be life-threatening and appropriate measures should be taken, including the discontinuation of LORABID.
Healthy geriatric volunteers (=5years old) with normal renal function who received a single 400mg dose of LORABID had no significant differences in AUC or clearance when compared to healthy adult volunteers 20 to 40 years of age. In clinical studies, when geriatric patients received the usual recommended adult doses, clinical efficacy and safety were comparable to results in nongeriatric adult patients. A significant number of elderly patients have decreased renal function which may necessitate adjustment to the dosage of LORABID. eva luation of renal function is therefore recommended before commencement of treatment.
Interactions:Renal excretion of LORABID is inhibited by probenecid (see 'PHARMACOLOGICAL ACTION').
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Signs and symptoms:The toxic symptoms following an overdose of LORABID may include nausea, vomiting, epigastric distress and diarrhoea. Forced diuresis, peritoneal dialysis, haemodialysis or haemoperfusion have not been established as beneficial for an overdose.
Treatment:In managing overdosage, consider the possibility of multiple drug overdoses, interaction between medicines and unusual drug kinetics.
Treatment is symptomatic and supportive.
IDENTIFICATION:
LORABID200 capsule, PU3170, is a size2 capsule with an opaque blue cap and an opaque grey body, imprinted with Lilly3170.
LORABID100P (100mg/5mL suspension), MS5135, is a white free flowing granulation yielding a pink coloured suspension with a strawberry flavour, when suspended in water.
LORABID200P (200mg/5mL suspension), MS5136, is a white free flowing granulation yielding a pink coloured suspension with a strawberry flavour, when suspended in water.
PRESENTATION:
LORABID200 capsules are supplied in blister packs containing 10.
LORABID100P and 200P suspensions are supplied in bottles containing 50mL when mixed.
STORAGE INSTRUCTIONS:
Capsules:Store below 25ºC in blister packs.
Suspensions:
Before reconstitution:Store below 25ºC in tightly closed containers.
After reconstitution:The suspension is stable for 14days when stored below 25ºC in tightly closed containers.
Keep out of reach of children.
REGISTRATION NUMBERS:
27/20.1.1/0090 for 200mg capsules
27/20.1.1/0092 for 100mg/5mL suspension
27/20.1.1/0093 for 200mg/5mL suspension
NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Eli Lilly (S.A.) (Pty) Limited
1 Petunia Street, Private Bag X119
Bryanston, 2021
DATE OF PUBLICATION OF THIS PACKAGE INSERT:
23 October 2003
Note: An Afrikaans package insert is available on request.
PA8442ITUAP
New addition to this site: September 2006
Source: Pharmaceutical Industry
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