INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo CIPLOXX 250 (TABLETS)
CIPLOXX 500 (TABLETS)
CIPLOXX 750 (TABLETS)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

CIPLOXX 250 (TABLETS)
CIPLOXX 500 (TABLETS)
CIPLOXX 750 (TABLETS)

COMPOSITION:
CIPLOXX 250
tablet contains ciprofloxacin hydrochloride equivalent to 250 mg of
ciprofloxacin.
CIPLOXX 500 tablet contains ciprofloxacin hydrochloride equivalent to 500 mg of ciprofloxacin.
CIPLOXX 750 tablet contains ciprofloxacin hydrochloride equivalent to 750 mg of ciprofloxacin.

PHARMACOLOGICAL CLASSIFICATION:
A 20.1.1 Broad and medium spectrum antibiotics.

PHARMACOLOGICAL ACTION:
Ciprofloxacin is a synthetic, fluorinated 4-quinolone antimicrobial agent.
It has broad antimicrobial activity and is effective, after oral administration, for the treatment of a wide variety of infectious diseases. The bactericidal action of ciprofloxacin results from interference with the enzyme DNA gyrase, needed for the synthesis of bacterial DNA. It has in vitro bactericidal activity against the following gram-negative and gram-positive organisms (in vitro sensitivity does not necessarily imply in vivo efficacy):
Aerobic Gram-positive micro-organisms:
  Corynebacterium species
  Staphylococcus aureus
  Staphylococcus epidermidis
  Staphylococcus hominis
  Staphylococcus haemolyticus
  Staphylococcus saprophyticus
  Streptococcus species (incl. S. pneumoniae)
  Streptococcus pyogenes
  Viridans streptococci
Aerobic Gram-negative micro-organisms:
  Acinetobacter species (incl. A. lwoffi)
  Aeromonas species (incl. A. hydrophila)
  Brucella species
  Campylobacter jejuni
  Citrobacter species (incl. C. diversus, C. freundii)
  Edwardsiella species (incl. E. tarda)
  Enterobacter species (incl. E. aerogenes, E. cloacae)
  Escherichia coli
  Haemophilus influenzae
  Haemophilus parainfluenzae
  Hafnia species
  Klebsiella species (incl. K. oxytoca, K. pneumoniae)
  Moraxella catarrhalis
  Morganella morganii
  Neisseria gonorrhoeae
  Pasteurella species (incl. P. multocida)
  Proteus mirabilis
  Proteus vulgaris
  Providencia rettgeri
  Providencia stuartii
  Pseudomonas aeruginosa
  Salmonella species (incl. S. enteritidis, S. typhi)
  Serratia marcescens
  Shigella species (incl. S. boydii, S. dysenteriae, S. flexneri, S. sonnei)
  Vibrio species (incl. V. cholerae, V. parahaemolyticus, V. vulnificus)
  Yersinia species (incl. Y. enterocolitica)
Anaerobic micro-organisms:
  Listeria species
  Plesiomonas species
  Streptococcus faecalis
The following organisms display varying degrees of in vitro sensitivity to ciprofloxacin: Alcaligenes, Enterococcus faecalis, Flavobacterium, Gardnerella, Legionella, Mycobacterium fortuitum, Mycobacterium tuberculosis, Mycoplasma hominis, Streptococcus agalactiae and Chlamydia.
The following organisms are usually resistant: Enterococcus faecium, Nocardia asteroides and Ureaplasma urealyticum.
With a few exceptions (see above) anaerobic organisms are moderately sensitive (e.g. Peptococcus, Peptostreptococcus) to resistant (e.g. Bacteroides, Treponema pallidum).
Pharmacokinetics:
Peak plasma concentrations, which are dose-related, are attained 0.5 to 2 hours after oral dosing. Oral bio-availability is approximately 75% with insignificant first pass metabolism. Plasma protein binding is low. Ciprofloxacin is distributed widely throughout the body with extensive tissue penetration, including bone, cartilage, fat, lung, muscle, prostate and skin. It is also present in the aqueous humor of the eye, cerebrospinal fluid, nasal and bronchial secretions, sputum, saliva, peritoneal fluid, bile secretions, prostatic secretions, lymph and skin blister fluid. Once steady state has been reached, no accumulation occurs.
Ciprofloxacin is eliminated principally by urinary excretion (mainly during the first 12 hours) and is virtually complete within 24 hours. The rest undergoes biliary excretion and transluminal intestinal secretion.
About 40 to 50% of an oral dose is excreted unchanged in the urine and about 15% as metabolites.
The metabolites have antimicrobial activity, but are less active than unchanged ciprofloxacin. The elimination half-life is 3-5 hours.

INDICATIONS:
Urinary tract infections, lower respiratory tract infections, gastro-intestinal infections, bone, joint, skin and soft tissue infections (caused by ciprofloxacin sensitive bacteria).
Gonorrhoea (ciprofloxacin is not effective against Treponema pallidum)
An aminoglycoside must be administered with ciprofloxacin in the treatment of infections caused by Pseudomonas aeruginosa.

CONTRA-INDICATIONS:
Safety in pregnancy and lactation has not been established.
CIPLOXX is contra-indicated in children under 18 years and growing adolescents (except where the benefits of treatment outweigh the risks). Experimental studies have shown species variable reversible lesions of the cartilage of weight-bearing joints in immature members of certain animal species.
CIPLOXX is also contra-indicated in patients with hypersensitivity to ciprofloxacin or any other quinolones.

WARNINGS:
CIPLOXX
should be used with caution in patients with epilepsy or a history of CNS disorders. Crystalluria has been observed in association with ciprofloxacin use. Patients on ciprofloxacin should therefore be well hydrated and must avoid excessive alkalinity of the urine.

DOSAGE AND DIRECTIONS FOR USE:
CIPLOXX
tablets should be swallowed with a full glass (240 mL) of water and may betaken with or without meals.
The usual oral dose is 250 to 750 mg (base) every 12 hours for three to fourteen days. Generally, treatment should be continued for at least 3 days after the signs and symptoms of the infection have disappeared. Severe and/or complicated infections may require prolonged therapy.
A MINIMUM OF TEN DAYS TREATMENT IS RECOMMENDED FOR ANY INFECTIONS CAUSED BY STREPTOCOCCI, DUE TO THE RISK OF LATE COMPLICATIONS.
Usual adult prescribing limit: Up to 1.5 g (base) daily.
Dosage guidelines for different infections:
Lower respiratory tract:
Mild/moderate - 250-500 mg 12 hourly, 7 to 14 days
Severe/complicated - 750 mg 12 hourly, 7 to 14 days.
Cystic fibrosis: For acute exacerbations of cystic fibrosis, associated with Pseudomonas aeruginosa infection, ciprofloxacin may be given to adolescents and children aged 5 years or more in a dose of 20 mg per kg by mouth daily, up to a maximum of 750 mg twice daily.
Infectious diarrhoea: 500 mg 12 hourly, 5 to 7 days.
Typhoid fever: 500 mg 12 hourly, 10 days.
Intra-abdominal:
Complicated - 500 mg 12 hourly, 7 to 14 days (in conjunction with metronidazole).
Urinary tract:
Acute uncomplicated cystitis - 250 mg 12 hourly, 3 days.
Mild/moderate - 250 mg 12 hourly, 7 to 14 days.
Severe/complicated - 500 mg 12 hourly, 7 to 14 days.
Chronic bacterial prostatitis: 500 mg 12 hourly, 28 days.
Urethral and endocervical gonorrhoea: 250 mg as a single dose.
Skin and soft tissue: Mild/moderate - 500 mg 12 hourly, 7 to 14 days.
Severe/complicated - 750 mg 12 hourly, 7 to 14 days.
Bone and joint: Mild/moderate - 500 mg 12 hourly, 4 to 6 weeks or longer.
Severe/complicated - 750 mg 12 hourly, 4 to 6 weeks or longer.
Elderly patients should receive a dose as low as possible, depending on the severity of the illness and on the creatinine clearance.
Impaired renal or hepatic function:
No dosage adjustment is necessary in patients with hepatic impairment.
The following table provides dosage guidelines for use in patients with renal impairment; however, monitoring of drug serum levels provides the most reliable basis for dosage adjustment:
Creatinine Clearance (mL/min)(mL/sec) Dose (base) 
>50/0.83 See Usual adult dose 
30-50/0.50-0.83 250-500 mg every 12 hours 
5-29/0.08-0.48 250-500 mg every 18 hours 
Haemodialysis or Peritoneal dialysis patients 250-500 mg every 24 hours after dialysis 

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side effects:
The most common adverse events are nausea, diarrhoea, vomiting, abdominal pain/discomfort, headache, restlessness, dizziness and rash. The following additional events have occurred in patients on ciprofloxacin:
Cardiovascular: Palpitations, tachycardia, syncope, migraine and vasculitis.
Central Nervous System: Agitation, trembling, tiredness and, infrequently, light headedness, insomnia, hallucinations, delirium, seizures (predominantly in patients who were also receiving theophylline or a non-steroidal anti-inflammatory drug), confusion, dysphasia, myoclonus, nystagmus, toxic psychosis, nightmares, ataxia, lethargy, drowsiness, weakness, malaise, paresthesia, depression, sweating, increase in intracranial pressure, headache, nervousness, peripheral paralgesia, unsteady gait and anxiety states.
Gastro-intestinal: Dyspepsia, flatulence, anorexia, constipation, jaundice, pancreatitis, aphthous ulcers and dysphagia. Consider pseudomembranous colitis if severe and persistent diarrhoea occurs during or after treatment. In these events CIPLOXX must be discontinued and appropriate treatment started immediately.
Hemopoietic: Leucopenia, granulocytopenia, eosinophilia, thrombocytopenia, anaemia and, in very rare cases, agranulocytosis, hemolytic anaemia, methemoglobinemia, prolongation of prothrombin time, leucocytosis and thrombocytosis.
Musculoskeletal: Arthralgia, joint swelling and, in rare cases, myalgia, tendinitis (including achillotendinitis), tendon rupture, exacerbation of gout and general feeling of weakness. Renal/Urogenital: Vaginitis, vaginal pruritus, candidiasis and transient renal impairment, including transient renal failure.
Skin/Hypersensitivity reactions: Rashes, including photosensitivity reactions, pruritus, urticaria, flushing and, in less frequent cases, drug fever, petechiae, haemorrhagic bullae, erythema nodosum, erythema multiforme, Stevens-Johnson syndrome, Lyell syndrome and vasculitis.
Anaphylactic or anaphylactoid reactions, which can present with angioedema, oedema of the face, neck, lips, conjunctivae, larynx or hands, dyspnoea and shock, have been reported rarely. Interstitial nephritis, hepatitis and hepatic necrosis.
Special senses: Blurred vision, disturbed vision (including colour perception, photophobia, diplopia), tinnitus, hearing loss, impaired or bad taste and anosmia.
Laboratory changes: There can be temporary elevations of the following: ALT, AST, alkaline phosphatase, LDH, serum bilirubin, serum creatinine, urea, serum glucose, GGT, serum amylase, uric acid. Crystalluria and haematuria have been reported.
Precautions:
Alkalinity of the urine should be avoided in patients receiving ciprofloxacin, as this may predispose to crystalluria.
Excessive sunlight should be avoided to avoid the possibility of phototoxicity, manifested as an exaggerated sunburn reaction.
Ciprofloxacin should be used with caution in patients with known or suspected CNS disorders that may predispose to seizures or lower the seizure threshold (e.g. cerebral arteriosclerosis, epilepsy), or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold (e.g. certain drugs, renal impairment).
Long-term or repeated administration of ciprofloxacin can lead to superinfections with resistant bacteria or yeast-like fungi.
Even when the medicine is taken as prescribed, it can affect the speed of reaction to such an extent that the ability to drive and to operate machinery is impaired. Particularly in combination with alcohol.

INTERACTIONS:
Theophylline
: Concomitant administration may lead to an increased risk of theophylline-related adverse reactions (e.g. tachyarrhythmias, cardiac arrest, seizures and respiratory failure) due to elevated serum concentrations of theophylline and prolongation of its half-life. If this cannot be avoided, serum levels of theophylline should be monitored and the dosage adjusted appropriately.
Non-steroidal anti-inflammatory drugs: There have been reports of potentiation of the CNS stimulant effects and lowering of the seizure threshold when fenbufen was co-administered with quinolones.
Minerals: Concurrent administration with antacids containing magnesium, aluminium, calcium or sucralfate, or divalent or trivalent cations such as iron may substantially interfere with the absorption of ciprofloxacin. CIPLOXX should therefore be administered 1-2 hours before, or at least 4 hours after these preparations.
Glibenclamide: The action of this sulfonylurea can be intensified, resulting in hypoglycaemia. Warfarin: The effects of warfarin and its derivatives may be enhanced. When administered concomitantly, coagulation tests should be closely monitored.
Probenecid: Ciprofloxacin serum concentrations will be elevated due to reduced renal secretion.
Cyclosporine: Transient elevations in serum creatinine have been observed in patients on concomitant ciprofloxacin and cyclosporine.
Metoclopramide: Has been shown to accelerate the absorption of ciprofloxacin, reducing the time to reach maximum plasma concentrations. No effect was seen on the overall bioavailability of ciprofloxacin.
Others: Ciprofloxacin has been shown to increase the half-life of caffeine, and to alter serum levels of phenytoin (increase or decrease).

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Reversible renal toxicity has been reported in the case of oral overdosage.
Renal function should be monitored and Mg- or Ca- containing antacids administered which reduce the absorption of ciprofloxacin. Treatment should be symptomatic and supportive.

IDENTIFICATION:
CIPLOXX 250
: White, film-coated, circular, biconvex tablet, plain on one face and with a deep score 'CP250' engraved on the other face. Coating intact.
CIPLOXX 500: White, film-coated, capsule-shaped, biconvex tablet, plain on one face and with a deep score 'CP500' engraved on the other face. Coating intact.
CIPLOXX 750: White, film-coated, capsule-shaped, biconvex tablet, plain on both sides. Coating intact.

PRESENTATION:
CIPLOXX 250
: Colourless, transparent PVC, aluminium blister packs of 6 and 10 tablets.
CIPLOXX 500: Colourless, transparent PVC, aluminium blister packs of 10 tablets.
CIPLOXX 750: Colourless, transparent PVC, aluminium blister packs of 10 tablets.

STORAGE INSTRUCTIONS:
Store below 25°C. Keep blister strips in outer carton until required for use.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
CIPLOXX 250
: 36/20.1.1/0376
CIPLOXX 500: 36/20.1.1/0377
CIPLOXX 750: 36/20.1.1/0378

NAME AND BUSINESS ADDRESS OF APPLICANT:
CIPLA LIFE SCIENCES (PTY) LTD.
Rosen Heights, Pasita Street, Rosen Park, Bellville 7530 RSA

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
May 2003

© CIPLA LIFE SCIENCES 2002

270 GB JPA-1

Cipla Life Sciences logo

New addition to this site: December 2004
Source: Community Pharmacy

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