Intravenous Solutions - OTSUFLOX
Ciprofloxacin – 200mg/100ml IV Infusion
INDICATIONS AND USAGE
OTSUFLOX I.V. (Ciprofloxacin) is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions and patient populations listed below when the intravenous administration offers a route of administration advantageous to the patient.
DESCRIPTION
OTSUFLOX I.V. (ciprofloxacin) is a synthetic broad-spectrum antimicrobial agent for intravenous (I.V.) administration. Ciprofloxacin, a fluoroquinolone, is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1 piperazinyl)-3-quinolinecarboxylic acid. Its empirical formula is C17H18FN3O3.
Ciprofloxacin is a faint to light yellow crystalline powder with a molecular weight of 331.4. It is soluble in dilute (0.1N) hydrochloric acid and is practically insoluble in water and ethanol. The pH range for the 0.2% ready-for-use infusion solutions is 3.5 to 4.6.
CLINICAL PHARMACOLOGY
Absorption
Following 60-minute intravenous infusions of 200 mg ciprofloxacin to normal volunteers, the mean maximum serum concentrations achieved were 2.1 and 4.6 µg/mL, respectively; the concentrations at 12 hours were 0.1 and 0.2 µg/mL, respectively. The absolute bioavailability of oral ciprofloxacin is within a range of 70–80% with no substantial loss by first pass metabolism. An infusion of 200 mg ciprofloxacin given every 12 hours produces an AUC equivalent to that produced by a 250-mg oral dose given every 12 hours.
Distribution
After intravenous administration, ciprofloxacin is present in saliva, nasal and bronchial secretions, sputum, skin blister fluid, lymph, peritoneal fluid, bile, and prostatic secretions. It has also been detected in the lung, skin, fat, muscle, cartilage, and bone. Although the drug diffuses into cerebrospinal fluid (CSF), CSF concentrations are generally less than 10% of peak serum concentrations. Levels of the drug in the aqueous and vitreous chambers of the eye are lower than in serum.
Metabolism
After I.V. administration, three metabolites of ciprofloxacin have been identified in human urine which together account for approximately 10% of the intravenous dose. The binding of ciprofloxacin to serum proteins is 20 to 40%. Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. Co-administration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the co-administered drug.
Excretion
The serum elimination half-life is approximately 5–6 hours and the total clearance is around 35 L/hr. After intravenous administration, approximately 50% to 70% of the dose is excreted in the urine as unchanged drug. Following a 200-mg I.V. dose, concentrations in the urine usually exceed 200 µg/mL 0–2 hours after dosing and are generally greater than 15 µg/mL 8–12 hours after dosing. The renal clearance is approximately 22 L/hr. The urinary excretion of ciprofloxacin is virtually complete by 24 hours after dosing. Although bile concentrations of ciprofloxacin are several folds higher than serum concentrations after intravenous dosing, only a small amount of the administered dose (< 1%) is recovered from the bile as unchanged drug. Approximately 15% of an I.V. dose is recovered from the feces within 5 days after dosing.
Drug-drug Interactions
Concomitant administration with tizanidine is contraindicated. The potential for pharmacokinetic drug interactions between ciprofloxacin and theophylline, caffeine, cyclosporins, phenytoin, sulfonylurea glyburide, metronidazole, warfarin, probenecid, and piperacillin sodium has been evaluated.
CONTRAINDICATIONS
Ciprofloxacin is contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components. Concomitant administration with tizanidine is contraindicated.
Pregnant & Lactating Women: The safety and effectiveness of ciprofloxacin in pregnant and lactating women have not been established.
OVERDOSAGE
In the event of acute overdosage, the patient should be carefully observed and given supportive treatment, including monitoring of renal function. Adequate hydration must be maintained. Only a small amount of ciprofloxacin (< 10%) is removed from the body after hemodialysis or peritoneal dialysis.
DOSAGE AND ADMINISTRATION - ADULTS
OTSUFLOX I.V. should be administered to adults by intravenous infusion over a period of 60 minutes at dosages described in the Adult Dosage Guidelines table. Slow infusion of a dilute solution into a larger vein will minimize patient discomfort and reduce the risk of venous irritation.
The determination of dosage for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative microorganism, the integrity of the patient’s host-defense mechanisms, and the status of renal and hepatic function.
WARNING
Fluoroquinolones, including Ciprofloxacin I.V., are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart, or lung transplants.
Fluoroquinolones, including Ciprofloxacin I.V., may exacerbate muscle weakness in persons with myasthenia gravis. Avoid Ciprofloxacin I.V. in patients with a known history of myasthenia gravis.