Cipquin Tablet

Ciprofloxacin hydrochloride.

Each film-coated tablet contains: Ciprofloxacin Hydrochloride equivalent to Ciprofloxacin 250 mg or 500 mg.

Pharmacology: Pharmacodynamics: Mode or Mechanisms of Action: Ciprofloxacin is a DNA gyrase inhibitor used as an antibacterial agent. It is bactericidal and acts intra-cellularly by inhibiting the A subunit of DNA gyrase (topoisomerase II) which is an essential bacterial enzyme that is a critical catalyst in the duplication, transcription, and repair of bacterial DNA. The process is necessary for compacting the bacterial chromosome within the cell. Other investigators have suggested that the quinolones induce the formation of drug-gyrase-DNA complex through which DNA polymerase cannot proceed. At effective concentrations of ciprofloxacin, selective inhibition of topoisomerase II leads to death of exposed bacteria without producing dysfunction or toxicity of mammalian cells.
Spectrum of activity: Ciprofloxacin has a broader spectrum of activity and is more potent in vitro than the non-fluorinated quinolone, nalidixic acid. Activity may be reduced in acid media. Ciprofloxacin is one of the most active of the fluoroquinolones. Among Gram-negative aerobic bacteria, ciprofloxacin is active in vitro against Enterobacteriaceae including Escherichia coli and Citrobacter, Enterobacter, Klebsiella, Proteus, Providencia, Salmonella, Serratia, Shigella and Yersinia spp. It is also active against Pseudomonas aeruginosa, but less so against other Pseudomonas spp. Haemophilus ducreyi, H. influenzae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae, and N. meningitidis are all very sensitive, including beta-lactamase-producing strains of H. influenzae, M. catarrhalis, and N. gonorrhoeae. Other Gram-negative aerobic bacteria reported to be sensitive to ciprofloxacin have included Acinetobacter spp., Campylobacter spp., Gardnerella vaginalis, Helicobacter pylori, Legionella spp., Pasteurella multocida, and Vibrio spp. Variable activity has been reported against Brucella melitensis. Among Gram-positive aerobic bacteria, ciprofloxacin is active against staphylococci including penicillinase-producing and -non-producing strains and against some methicillin-resistant strains. Streptococci, in particular Streptococcus pneumoniae, and enterococci are less susceptible. Other Gram-positive bacteria sensitive to ciprofloxacin in vitro are Corynebacterium spp., and Listeria monocytogenes. Most anaerobic bacteria, including Bacteroides fragilis and Clostridium difficile, are resistant to ciprofloxacin. Ciprofloxacin has some activity against mycobacteria, mycoplasmas, rickettsias, and the protozoan Plasmodium falciparum. Chlamydia trachomatis is not very susceptible and Nocardia asteroides and Ureaplasma urealyticum are usually considered to be resistant. The spirochaete Treponema pallidum and fungi are also resistant.
Activity with other antimicrobial agents: There have been some reports of enhanced activity in vitro when ciprofloxacin has been used with other antimicrobial agents such as azlocillin against Staphylococcus aureus and Pseudomonas aeruginosa, imipenem against Ps. Aeruginosa, and cefotaxime or clindamycin against anaerobic bacteria.
Pharmacokinetics: Ciprofloxacin is rapidly and well absorbed from the gastro-intestinal tract. Oral availability is approximately 70% and a peak plasma concentration of about 2.5 g per ml is achieved 1 to 2 hours after a dose of 500 mg by mouth. The plasma half-life is about 3.5 to 4.5 hours. Plasma protein binding ranges from 20 to 40%.
Ciprofloxacin is widely distributed in the body and tissue penetration is generally good. The volume of distribution is high (approx. 2.8 l/kg). It appears in the cerebrospinal fluid, but concentrations are only about 10% of those in plasma when the meninges are not inflamed. Ciprofloxacin crosses the placenta and is excreted in breast milk. High concentrations are achieved in bile. Ciprofloxacin is eliminated principally by urinary excretion. At least 4 active metabolites have been identified. Oxociprofloxacin appears to be the major urinary metabolite and sulphociprofloxacin the primary faecal metabolite. Urinary excretion is by active tubular secretion as well as glomerular filtration and is reduced by probenecid. Excretion is virtually complete within 24 hours; about 40 to 50% of an oral dose is excreted unchanged in the urine and about 15% as metabolites. Only small amounts of ciprofloxacin are removed by haemodialysis or peritoneal dialysis.

Uncomplicated and complicated infections caused by ciprofloxacin-sensitive pathogens.
Infections of the respiratory tract: In the treatments of outpatients with pneumonia due to Pneumococcus, ciprofloxacin should not be used as a first choice of drug. Ciprofloxacin can be regarded as an advisable treatment for pneumonias caused by Klebsiella, Enterobacter, Proteus, Pseudomonas, Haemophilus, Branhamella, Legionella and Staphylococcus.
Infections of the middle ear (otitis media), of the paranasal sinuses (sinusitis), especially if these are caused by Gram-negative organisms including Pseudomonas or by Staphylococcus.
Infections of the eyes.
Infections of the kidneys and/or the efferent urinary tract.
Infections of the genital organs, including adnexitis, gonorrhoea, prostatitis.
Infections of the abdominal cavity (e.g., infections of the gastrointestinal tract or of the biliary tract, peritonitis).
Infections of the skin and soft tissue.
Infections of the bones and joints.
Septicaemia.
Infections, or imminent risk of infection (prophylaxis) in immunocompromised patients (e.g., those on immunosuppressants, or have neutropenia).
Selective intestinal decontamination in immunosuppressed patients.

(See table.)

Click on icon to see table/diagram/image

Administration: The tablets should be taken whole with a little fluid.
They do not need to be taken at mealtimes. Absorption of the drug is accelerated if taken on an empty stomach.
Elderly patients should receive as low a dose as possible, taking into account the severity of the illness and the creatinine clearance.
Renal and Hepatic Impairment: 1.0. Impaired Renal Function: 1.1. Where creatinine clearance is between 31 and 60 ml/min/1.73 m² or where the serum creatinine concentration is between 1.4 and 1.9 mg/100 ml, the maximum daily dose should be 1000 mg/day for oral administration.
1.2. Where creatinine clearance is ≤ 30mL/min/1.73 m² or where the serum creatinine concentration is ≥ 2 mg/100 ml, the maximum daily dose should be 500 mg/day for oral administration.
2.0. Impaired Renal Function + Haemodialysis: Dose as in 1.2; on dialysis days after dialysis.
3.0. Impaired Renal Function + CAPD: Administration of ciprofloxacin film coated tablets as 1 x 500 mg film coated tablet or 2 x 250 mg film coated tablets.
4.0 Impaired Liver Function: No dose adjustment is required.
5.0 Impaired Renal and Liver Function: Dose adjustment as in 1.1 and 1.2.

Symptoms and treatment for overdose and antidote(s): Acute overdosage: In the event of acute, excessive oral overdosage, reversible renal toxicity has been reported in some cases. Therefore, apart from routine emergency measures, it is recommended to monitor renal function.
Treatment: Since there is no specific antidote for ciprofloxacin overdose, treatment should be symptomatic and supportive and may consist of the following: To decrease absorption: Induction of emesis or use of gastric lavage to evacuate the stomach to eliminate unabsorbed drug; Administration of Mg- or Ca-containing antacids.
Specific treatment: Maintenance of adequate hydration.
Only a small amount of ciprofloxacin (<10%) is removed from the body after hemodialysis or peritoneal dialysis.

Ciprofloxacin should not be given in patients with known hypersensitivity to Ciprofloxacin or other quinolone antibiotics. Ciprofloxacin should not be prescribed to children, growing adolescents and pregnant or nursing women, since ciprofloxacin and related fluoroquinolones have been shown to cause degenerative changes in weight-bearing joints of young animals.

The ability to drive or operate machinery may be impaired by ciprofloxacin, especially when alcohol is also taken.

Hypersensitivity: Cipquin should not be used where there is hypersensitivity to ciprofloxacin or to other chemotherapeutic agents of the quinolone group. In some instances, hypersensitivity and allergic reactions occurred after the first administration; the doctor should be informed immediately. Anaphylactic/anaphylactoid reactions in very rare instances and can progress to a life threatening shock. In these cases, Ciprofloxacin should be discontinued and medical treatment (e.g. treatment for shock) is required. Ciprofloxacin should be used with caution in the elderly, in patients with epilepsy or a history of CNS disorders, including cerebral arteriosclerosis (fluoroquinolones may cause CNS stimulation or toxicity).
Musculo-skeletal system: Achilles and other tendon ruptures that required surgical repair or resulted in prolonged disability have been reported predominantly in the elderly on prior treatment with glucocorticoids. Ciprofloxacin should be discontinued, physical exercises be avoided, and a physician be consulted, if the patient experiences pain, inflammation, or rupture of a tendon.
Care is necessary in patients with impaired hepatic or renal function (patients with both hepatic and renal function impairment may require a reduction in the dosage of ciprofloxacin), glucose-6-phosphate dehydrogenase deficiency, or myasthenia gravis. An adequate fluid intake should be maintained during treatment with ciprofloxacin and excessive alkalinity of the urine avoided because of the risk of crystalluria. Exposure to strong sunlight or sunlamps should also be avoided (discontinue if photosensitivity occurs).

Effects on the Gastrointestinal Tract: Nausea, diarrhoea, vomiting, digestive disorders, abdominal pain, flatulence, anorexia. The doctor should be advised of any severe or persistent diarrhoea occurring during or after treatment, since these symptoms could conceal a serious intestinal disorder (pseudomembranous colitis) requiring urgent treatment. In such cases, Cipquin should be discontinued and replaced by another appropriate drug. Preparations which inhibit peristalsis are contraindicated.
Effects on the Nervous Systems: Dizziness, headache, insomnia, agitation, trembling. Very Rarely: Peripheral paralgesia, sweating, unsteady gait, convulsions, anxiety states, nightmares, confusion, depressions, hallucinations. In some instances, these reactions occurred after the first administration of Cipquin already. In these cases, Cipquin has to be discontinued and the doctor should be informed immediately.
Hypersensitivity reactions.
Skin reactions, e.g. rashes. Very Rarely: Pruritus, drug fever. Anaphylactic/anaphylactoid reactions (e.g., facial, vascular and laryngeal oedema; dyspnoea progressing to life-threatening shock. In these cases, Cipquin has to be discontinued and medical treatment (e.g., treatment for shock) is required. Punctate skin haemorrhages (petechiae), blister formation with accompanying haemorrhages (haemorrhagic bullae) and small nodules (papules) with crust formation showing vascular involvement (vasculitis), Stevens-Johnson syndrome, interstitial nephritis, hepatitis; very rarely, major liver disorders, including hepatic necrosis.
Effects on the Cardiovascular System: Very rarely: Tachycardia, hot flushes, migraine, fainting.
Effects on Blood and Blood Constituents: Eosinophilia, leucocytopenia, leucocytosis, anaemia; very rarely, thrombocytopenia, thrombocytosis, altered prothrombin levels.
Special senses/sensory organs: Impaired taste and smell, visual disturbances (e.g. double vision, colour vision), tinnitus & transitory impairment of hearing, especially at high frequencies.
Others: Very rarely: Joint pains, general feeling of weakness, muscular pains, tendovaginitis, mild photosensitivity, transient impairment in kidney function, including transient kidney failure.
Effect on Laboratory Values/Urine Deposits: There may be a transient rise in the transaminase and alkaline phosphatase levels, or cholestatic jaundice may occur; transient increase in serum urea, creatinine and bilirubin levels, hyperglycaemia; in individual cases: Crystalluria and haematuria.

Analgesics: Concurrent administration of fenbufen with quinolone antibiotics may increase the incidence of quinolone CNS adverse effects. Convulsions may occur due to an interaction between the quinolones and NSAIDs.
Iron, Sucralfate or Antacids and highly buffered drugs (e.g. anti-retrovirals) containing Magnesium, Aluminium or Calcium: The absorption of ciprofloxacin is reduced by antacids containing aluminium or magnesium and also by calcium, iron and zinc salts. Consequently, Cipquin should be taken either 1-2 hours before, or at least 4 hours after these preparations. This does not apply to antacids, which do not contain aluminium or magnesium hydroxide (e.g., H₂-receptor blockers). Sucralfate releases aluminium ions in the stomach and thereby reduces the absorption of ciprofloxacin.
Antineoplastics and lmmunosuppressants: Absorption of oral ciprofloxacin appears to be reduced after cytotoxic chemotherapy.
Cyclosporin: A transient rise in the concentration of serum creatinine was observed when Cipquin and cyclosporin were administered simultaneously. Therefore, it is necessary to control the serum creatinine concentrations in these patients frequently (twice a week).
Xanthines: Concurrent administration of ciprofloxacin and theophylline can cause undesirable increase in the serum theophylline concentration. This can lead to theophylline-induced side effects; in very rare cases these side effects can be life threatening or fatal. If concurrent use of the two products is unavoidable, the serum theophylline concentration should be checked and the theophylline dose appropriately reduced.
Warfarin: Concurrent use of warfarin with ciprofloxacin has been reported to increase the anticoagulant effect of warfarin, increasing the chance of bleeding.
Glibenclamide: In particular cases, concurrent administration of ciprofloxacin and glibenclamide can intensify the action of glibenclamide (hypoglycaemia).
Probenecid: interferes with renal secretion of ciprofloxacin. Co-administration of probenecid and ciprofloxacin increases the ciprofloxacin serum concentrations.
Metoclopramide: accelerates the absorption of ciprofloxacin resulting in a shorter time to reach maximum plasma concentrations. No effect was seen on the bioavailability of ciprofloxacin.

Auxiliary labelling: May cause dizziness or lightheadedness.
Continue medicine for full time of treatment.
Avoid too much sun or use of sunlamp.
Do not take antacids or iron preparations within 4 hours of this medicine.

Store below 30°C.
Shelf-Life: 3 years.

Quinolones

J01MA02 - ciprofloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.

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