Ciprogen 250 mg, 500 mg, 750 mg FC tablets.

CIPROGEN tablets are indicated for treatment of the following infections that are caused by bacteria sensitive to ciprofloxacin:

• Lower Respiratory Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae and Haemophilus parainfluenzae.
• Urinary Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus mirabilis, Providencia rettgeri, Morganella morganii, Citrobacter diversus, Citrobacter freundii, Pseudomonas aeruginosa, Staphylococcus epidermidis and Streptococcus faecalis.
• Skin and Soft Tissue Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, Providencia stuartii, Morganella morganii, Citrobacter freundii, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes.
• Gastrointestinal Infections: Infective diarrhoea caused by Escherichia coli, Campylobacter jejuni, Shigella flexneri and Shigella sonnei.
• Bone Infections: Osteomyelitis due to susceptible Gram-negative organisms.
• Gonorrhoea. Ciprofloxacin is ineffective against Treponema pallidum. In the treatment of infections caused by Pseudomonas aeruginosa, an aminoglycoside must be administered concomitantly.

CIPROGEN tablets should be swallowed whole with plenty of liquid and may be taken before or after meals. The dose ranges from 250 - 750 mg twice daily and the duration of treatment depends upon the severity of the infection, clinical response and bacteriological findings. Severe and complicated infections may require prolonged therapy. The usual treatment period for acute infections is 5 u2013 10 days. Streptococcal infections should be treated for at least 10 days because of the possibility of late complications.

Lower respiratory tract infections: Mild to moderate: 250 to 500 mg twice daily; severe or complicated: 750 mg twice daily. In cystic fibrosis patients, the dosage is 7,5 to 15 mg/kg body mass/day in two divided doses.

Urinary tract infections: Acute uncomplicated cystitis and mild to moderate infections: 250 mg twice daily; severe or complicated infections: 500 mg twice daily.

Skin infections: Mild to moderate infections: 500 mg twice daily; severe or complicated infections: 750 mg twice daily.

Infectious diarrhoea: 500 mg twice daily.

Bone infections: Mild to moderate infections: 500 mg twice daily; severe or complicated infections: 750 mg twice daily. Treatment may be required for 6 weeks or longer.

Gonorrhoea: A single dose of 250 mg.

Special populations

Elderly: Elderly people should receive doses as low as possible depending on the creatinine clearance and severity of the infection.

Dose adjustment for patients with kidney and/or liver insufficiency: In patients with reduced renal function, the half-life of ciprofloxacin is prolonged, and the dosage needs to be adjusted. For patients with changing renal function or patients with renal impairment and hepatic insufficiency, monitoring of drug serum levels provides the most reliable basis for dose adjustment.

Method of administration

Oral use. CIPROGEN tablets should be swallowed whole with plenty of liquid and may be taken before or after meals.

Safety during pregnancy and lactation has not been established. CIPROGEN is contra-indicated in patients who have shown hypersensitivity to ciprofloxacin or other quinolones.

Concomitant use of fluoroquinolones with ACE inhibitors/Renin-Angiotensin blockers is contraindicated in patients with moderate to severe renal impairment.

CIPROGEN is contra-indicated in children under 18 years and in growing adolescents, except where the benefit of treatment exceeds the risks. Experimental evidence indicates that species variable reversible lesions of the cartilage of weight-bearing joints have been seen in immature members of certain animal species.

CIPROGEN should be used with caution in patients with a history of convulsive disorders. CIPROGEN may cause crystalluria and patients receiving CIPROGEN should be well hydrated and excessive alkalinity of the urine should be avoided.

Disturbances in blood glucose, including both hyperglycaemia and hypoglycaemia have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycaemic medicine or with insulin. Cases of hypoglycaemic coma have been reported. In diabetic patients, careful monitoring of blood glucose is recommended.

Concomitant use of fluoroquinolones and ACE inhibitors/renin-angiotensin receptor blockers may precipitate acute kidney injury in patients, especially those with moderate to severe renal impairment and elderly patients. (see section 4.3). Renal function should be assessed before initiating treatment, and monitored during treatment, with fluoroquinolones of ACE inhibitors/renin-angiotensin receptor blockers.

Severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis (TEN) Stevens Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), which could be life-threatening or fatal, have been reported with CIPROGEN (see section 4.8). At the time of prescription, patients should be advised of the signs and symptoms of severe skin reactions and be closely monitored. If signs and symptoms suggestive of these reactions appear, CIPROGEN should be discontinued immediately, and an alternative treatment should be considered. If the patient has developed a serious reaction such as SJS, TEN or DRESS with the use of CIPROGEN, treatment with CIPROGEN must not be restarted in this patient at any time.

Concomitant use of fluoroquinolones and ACE inhibitors/renin-angiotensin receptor blockers may precipitate acute kidney injury (see section 4.3).

In a study of volunteers treated with rifampin, moxifloxacin, or both drugs, rifampin reduced the moxifloxacin AUC 0-24 by 27 % via induction of sulfate conjugation (Weiner et al., 2007). In another study, rifapentine reduced moxifloxacin AUC 0-24 by 17 % (Dooley et al., 2008). These studies suggest that the most important cause of pharmacokinetic variability for moxifloxacin is concomitantly administered drugs for tuberculosis.

Concurrent administration of CIPROGEN with theophylline may lead to elevated plasma concentrations of theophylline and prolongation of its elimination half-life. This may result in increased risk of theophylline-related adverse reactions. If concomitant use cannot be avoided, the plasma levels of theophylline should be monitored, and dosage adjustments made as appropriate.

CIPROGEN tablets should be administered 1 - 2 hours before, or at least 4 hours after taking iron preparations, antacids containing magnesium, aluminium, calcium, or sucralfate, as interference with absorption may occur. H2-receptor blockers have no effect on the absorption of ciprofloxacin after oral administration.

Administration of fenbufen (a nonsteroidal anti-inflammatory agent) with quinolones may increase the risk of central nervous system stimulation and convulsive seizures.

Transient increases in serum creatinine concentrations may occur in patients receiving cyclosporin concomitantly and monitoring of the serum creatinine is advised.

The action of warfarin may be intensified if administered together with CIPROGEN. The action of glibenclamide (hypoglycaemia) may be intensified if administered together with CIPROGEN. Co-administration of probenecid and CIPROGEN increases serum concentrations of ciprofloxacin as probenecid interferes with the renal excretion of ciprofloxacin. Metoclopramide accelerates the absorption of ciprofloxacin, resulting in a shorter time to reach Cmax. No effect was seen on the bioavailability of ciprofloxacin.

Safety and/or efficacy has not been established.

Even when taken as prescribed, CIPROGEN can affect the speed of reaction to such an extent that the ability to drive or to operate machinery is impaired. This applies particularly in combination with alcohol.

The following side-effects have been reported:

Blood and lymphatic system disorders: Eosinophilia, leukocytopenia, granulocytopenia, anaemia, thrombocytopenia. Less frequent: leucocytosis, thrombocytosis, haemolytic anaemia, altered prothrombin values.

Metabolism and nutritional disorders: Less frequent: Hypoglycaemia, particularly in diabetic patients. Frequency unknown: Hyperglycaemia, hypoglycaemic coma.

Nervous system disorders: Dizziness, headache, tiredness, nervousness, agitation, trembling, insomnia, peripheral paralgesia, sweating, unsteady gait, convulsions, increase in intracranial pressure, anxiety states, nightmares, confusion, depression, hallucinations, in individual cases psychotic reactions (even progressing to self-endangering behaviour). These reactions may already occur after the first administration of CIPROGEN. CIPROGEN should be discontinued, and a medical doctor consulted immediately.

Eye, Ear and labyrinth disorders: Impaired taste and smell, visual disturbances (e.g., diplopia, colour vision), tinnitus, transitory impairment of hearing (high frequencies).

Cardiac disorders: Tachycardia, hot flushes, migraine, fainting.

Gastrointestinal disorders: Nausea, diarrhoea, vomiting, dyspepsia, abdominal pain, flatulence, anorexia. If severe or persistent diarrhoea occurs during or after treatment, a doctor must be consulted. This side-effect can hide a serious intestinal disease (pseudomembranous colitis) which may require immediate treatment. Treatment with CIPROGEN should be discontinued immediately and appropriate therapy initiated. Medicines that inhibit peristalsis should not be given.

Hypersensitivity reactions: Rashes, pruritus, drug fever, petechiae, haemorrhagic bullae, vasculitis. Erythema nodosum, erythema exsudativum multiforme, Stevens-Johnson syndrome, Lyell syndrome, interstitial nephritis, hepatitis, hepatic necrosis. Anaphylactic/anaphylactoid reactions (facial, vascular and laryngeal oedema, dyspnoea progressing to life-threatening shock), in some instances after the first administration. In these cases, CIPROGEN has to be discontinued and medical treatment (e.g., treatment for shock) is required.

Skin and subcutaneous tissue disorder: Frequency: Not known u2013 DRESS.

Other side-effects: Joint pain, joint swelling. Less frequently: general feeling of weakness, muscular pains, tendosynovitis, photosensitivity, transient impairment in kidney function including transient kidney failure. Achillotendinitis: Cases of partial or complete rupture of the Achilles tendon have been reported especially in the elderly on prior systemic treatment with glucocorticoids. At any signs of achillotendinitis (e.g., painful swelling) the administration of CIPROGEN should be discontinued and a physician consulted. Long-term or repeated administration of CIPROGEN can lead to superinfections with resistant bacteria or yeast-like fungi.

Care is necessary in patients with impaired hepatic or renal function, glucose u20136-phosphate dehydrogenase deficiency or myasthenia gravis. Exposure to strong sunlight or sunlamps should also be avoided.

Influence on laboratory parameters/urinary sediment: There can be a temporary increase in transaminases, alkaline phosphatase or cholestatic jaundice, especially in patients with previous liver damage; temporary increase in urea, creatinine or bilirubin in the serum; in individual cases: hyperglycaemia, crystalluria or haematuria.

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Acute, excessive overdosage may lead to reversible renal toxicity. Monitoring of renal function is recommended together with routine emergency measures and administration of magnesium and calcium containing antacids to reduce the absorption of ciprofloxacin. Less than 10 % of ciprofloxacin in the serum is removed with haemodialysis or peritoneal dialysis. Treatment is symptomatic and supportive.