INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
MAXAQUIN® Tablets

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

MAXAQUIN^® Tablets

COMPOSITION:
Each tablet contains lomefloxacin hydrochloride equivalent to 400 mg lomefloxacin base.

PHARMACOLOGICAL CLASSIFICATION:
A 20.1.1 Broad and medium spectrum anti-biotics.

PHARMACOLOGICAL ACTION:
MAXAQUIN, a difluoroquinolone, is a synthetic broad spectrum antimicrobial agent.
Pharmacokinetics:
Lomefloxacin is rapidly and well absorbed from the gastrointestinal tract after oral administration, and is 95 - 98% bioavailable. There is no first-pass metabolism. Between doses of 100 mg and 400 mg, plasma concentration and AUC increase proportionately with increasing dose. Maximum plasma concentrations (Cmax) of approximately 2 to 4 micrograms/mL are attained 1 to 1,5 hours (tmax) after a single 400 mg oral dose. Tmaxis independent of dose and dosing frequency.
The elimination half-life (t½) in normal healthy volunteers is approximately 8 hours. Steady-state concentrations with once-a-day dosing are achieved by the end of the second day of dosing. There is no accumulation with once-a-day dosing in patients with normal renal function.
In healthy volunteers between the ages of 61 and 76 years, the mean t½ and mean Cmax following a single 400 mg dose were similar to those seen in younger volunteers.
Following oral administration, lomefloxacin is widely distributed throughout the body. About 10% is bound to plasma proteins.
Lomefloxacin is minimally metabolised, although five inactive metabolites, accounting for approximately 10% of the dose, have been identified in human urine.
Approximately 65% of an orally administered dose is excreted as unchanged drug in the urine of patients with normal renal function. Following a single 400 mg dose or multiple daily doses of 400 mg, urine concentrations are in excess of 400 mcg/mL by 4 hours post dose and remain above 35 mcg/mL for at least 24 hours after dosing. Urinary excretion is virtually complete within 72 hours after cessation of dosing. The renal clearance exceeds the normal glomerular filtration rate averaging approximately 150 mL/min in subjects with normal renal function, indicating tubular secretion. Approximately 10% of an oral dose is recovered as unchanged drug in the faeces.
The elimination of lomefloxacin is prolonged in patients with renal insufficiency, with increased AUC ant t½ (see Dosage and Directions for Use of dosing recommendations).
No significant change in any pharmacokinetic parameter was observed in patients with hepatic cirrhosis.
Pharmacodynamics:
The bactericidal action of lomefloxacin results from inhibition of the activity of the bacterial enzyme DNA gyrase, needed for the transcription and replication of bacterial DNA. The minimum bactericidal concentration (MBC) generally does not exceed the minimum inhibitory concentration (MIC) by more than a factor of two.
There is cross-resistance between lomefloxacin and other quinolone-class antimicrobial agents.
The minimal dose of UVA light needed to cause erythema is inversely proportional to plasma lomefloxacin concentration. Increasing the interval between lomefloxacin dosing and exposure to UVA light increases the amount of light energy for photoreaction.

INDICATIONS
Treatment:
MAXAQUIN is indicated for the treatment of mild to moderate infections caused by susceptible strains in the conditions listed below:

•	Uncomplicated urinary tract infections (cystitis) caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus saprophyticus.
•	Complicated, including recurrent, urinary tract infections caused by Citrobacter diversus, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa. In the treatment of infections caused by Pseudomonas aeruginosa, an aminoglycoside must be administered concomitantly.
•	Acute exacerbation of chronic bronchitis caused by Branhamella catarrhalis [beta lactamase (+) and (-)]. Haemophilus influenzae [beta lactamase (+) and (-)].

Note:
MAXAQUIN is not indicated for the empiric treatment of acute bacterial exacerbation of chronic bronchitis when it is probable that S. pneumoniae is a causative pathogen. S. pneumoniae exhibits in vitro resistance to lomefloxacin. Safety and efficacy of lomefloxacin in the treatment of patients with acute bacterial exacerbation of chronic bronchitis caused by S. pneumoniae have not been demonstrated. If lomefloxacin is to be prescribed for Gram-stain guided empiric therapy of acute bacterial exacerbation of chronic bronchitis, it should be used only if sputum gram stain demonstrates an adequate quality of specimen (>25 polymorphonucleocytes / low power field) and there is both a predominance of gram negative organisms and not a predominance of gram positive organisms.
Prevention:
MAXAQUIN is indicated preoperatively to reduce the incidence of postoperative urinary tract infections in patients undergoing transurethral surgical procedures.

CONTRA-INDICATIONS:
MAXAQUIN is contra-indicated in patients with a history of hypersensitivity to lomefloxacin or to other quinolones. MAXAQUIN is also contra-indicated in pregnancy and lactation as teratogenicity has been shown in experimental animals..
Should not be used in children and growing adolescents.
Severe renal impairment - creatinine clearance <30 mL/min/1,73 m².

DOSAGE AND DIRECTIONS FOR USE:
MAXAQUIN is recommended at the doses and for the durations of treatment listed in the following table, and may be taken with or without food:

Disorder	Dose/Regimen	Duration of treatment
Uncomplicated urinary tract infection	400 mg once daily	3 days
Complicated urinary tract infection	400 mg once daily	10-14 days
Acute exacerbation of chronic bronchitis	400 mg once daily	7-10 days
Prophylaxis of urinary tract infection following transurethral surgery	400 mg	single dose 2-6 hours prior to surgery

The risk of reaction to solar UV light may be reduced by taking lomefloxacin in the evening.
Elderly:
No dosage adjustment is required in elderly patients if creatinine clearance is >30 mL/min/1,73 m²).

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
SIDE EFFECTS:
The most common side-effects seen are headache, nausea, phototoxicity, dizziness, diarrhoea and abdominal pain.
Less frequently occurring side-effects are:
Body as a whole: anaphylaxis
Cardiovascular disorders: cardiopulmonary arrest
Gastro-intestinal system disorders: painful oral mucosa, pseudomembranous colitis
Liver and biliary system disorders: hepatitis
Metabolic and nutritional disorders: hypoglycaemia
Musculoskeletal disorders: tendinitis, tendon rupture
Nervous system disorders: ataxia , convulsions.
Platelet, bleeding and clotting disorders: cerebral thrombosis
Psychiatric disorders: hallucinations, phobia
Red blood cell disorders: haemolytic anaemia
Respiratory system disorders: laryngeal oedema, pulmonary oedema
Skin and appendage disorders: exfoliative dermatitis, hyperpigmentation, Stevens-Johnson syndrome, toxic epidermal necrolysis
Urinary system disorders: interstitial nephritis, polyuria, renal failure, urinary retention
Vascular disorders: vasculitis
Vision disorders: diplopia, photophobia
Other disorders: dysgeusia
IN addition, the following adverse reactions occur with lomefloxacin: anaphylactoid reactions, CNS stimulation, drowsiness, elevation of SGOT (AST), elevation of SGPT (ALT), leucopenia, myalgia.
PRECAUTIONS:
General:
Lomefloxacin has been shown to cause phototoxicity. Patients should be advised to avoid exposure to direct or indirect ultraviolet light (eg. sunlight, sunlamps and solaria), including exposure through glass, while taking lomefloxacin and for a few days after therapy. Phototoxicity has occurred even with use of a sun protective agent. Lomefloxacin therapy should be discontinued if phototoxicity occurs.
As a class quinolones may cause central nervous system (CNS) stimulation. Therefore MAXAQUIN should be used with caution in patients with known or suspected CNS disorders such as epilepsy or other conditions which predispose to seizures.
MAXAQUIN may cause tendon rupture. If tendinitis occurs, discontinue lomefloxacin.
Drug interactions:
In comparative clinical studies MAXAQUIN has not been shown to have any interaction with theophylline.
Sucralfate, antacids containing magnesium or aluminium and metal cations from other sources such as mineral supplements, form chelation complexes with lomefloxacin and interfere with its bioavailability. Administration of these agents should precede MAXAQUIN dosing by 4 hours or follow lomefloxacin dosing by at least 2 hours.
Toxicology:
Lomefloxacin and related agents have been shown to cause arthropathy in immature animals.
Effects on ability to drive and use machines:
Because of the potential for CNS effects patients should be cautioned regarding driving and use of machinery during lomefloxacin treatment.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Information on overdosage in humans is limited. In the event of acute overdosage, the stomach should be emptied by inducing vomiting or by gastric lavage, and the patient care fully observed and given supportive treatment. Adequate hydration should be maintained. Haemodialysis or peritoneal dialysis is of no benefit. Treatment is supportive and symptomatic.

IDENTIFICATION:
MAXAQUIN is available in 400 mg white to off-white, oval, biconvex, film coated tablets, scored on one side and debossed Maxaquin 400 on the other.

PRESENTATION:
Blister pack (3 or 5 tablets).

STORAGE INSTRUCTIONS:
Keep out of reach of children.
Protect from light.
Store between 15°C and 30°C.

REGISTRATION NUMBER:
Z/20.1.1/74

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Pharmacare Limited
7 Fairclough Road
Korsten
Port Elizabeth
6020

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
5 March 1999.

        D390

Updated on this site: October 2001
SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2000