Rosoxacin
Adverse Effects and Precautions are as for Nalidixic Acid whose details are given below :
PRECAUTIONS
General
Blood counts and renal and liver function tests should be performed periodically if treatment is continued for more than two weeks. DIX should be used with caution in patients with liver disease, epilepsy, or severe cerebral arteriosclerosis. (See WARNINGS .) While caution should be used in patients with severe renal failure, therapeutic concentrations of DIX in the urine, without increased toxicity due to drug accumulation in the blood, have been observed in patients on full dosage with creatinine clearances as low as 2 mL/minute to 8 mL/minute.
Moderate to severe phototoxicity reactions have been observed in patients who are exposed to direct sunlight while receiving DIX or other members of this drug class. Excessive sunlight should be avoided. Therapy should be discontinued if phototoxicity occurs.
If bacterial resistance to DIX emerges during treatment, it usually does so within 48 hours, permitting rapid change to another antimicrobial. Therefore, if the clinical response is unsatisfactory or if relapse occurs, cultures and sensitivity tests should be repeated. Underdosage with DIX during initial treatment (with less than 4 g per day for adults) may predispose to emergence of bacterial resistance. (See DOSAGE AND ADMINISTRATION .)
Information for Patients
Patients should be advised DIX may be taken with or without meals. Patients should be advised to drink fluids liberally and not take antacids.
Patients should be advised that quinolones may be associated with hypersensitivity reactions, even following a single dose, and to discontinue the drug at the first sign of a skin rash or other allergic reactions.
Quinolones may cause dizziness and lightheadedness, therefore, patients should know how they react to DIX before they operate an automobile or machinery or engage in activities requiring mental alertness or coordination.
Patients should be advised that quinolones may increase the effects of theophylline and caffeine. There is a possibility of caffeine accumulation when products containing caffeine are consumed while taking quinolones. Patients should be advised to avoid excessive sunlight or artificial ultraviolet light while receiving nalidixic acid and to discontinue therapy if phototoxicity occurs.
Patients should be advised that convulsions have been reported in patients taking quinolones, including Nalidixic acid, and to notify their physician before taking this drug if there is a history of this condition. Patients should be advised that mineral supplements, vitamins with iron or minerals, calcium-, aluminum-, magnesium-based antacids, sucralfate or Didanosine, chewable/buffered tablets of the pediatric powder for oral solution should not be taken within the two-hour period before or within the two-hour period after taking nalidixic aid (see Drug Interactions ).
Drug Interactions
Elevated plasma levels of theophylline have been reported with concomitant quinolone use. There have been reports of theophylline-related side effects in patients on concomitant therapy with quinolones and theophylline. Therefore, monitoring of theophylline plasma levels should be considered and dosage of theophylline adjusted, as required.
Quinolones have been shown to interfere with the metabolism of caffeine. This may lead to reduced clearance of caffeine and the prolongation of its plasma half-life.
Quinolones, including nalidixic acid, may enhance the effects of the oral anticoagulant warfarin or its derivatives. When these products are administered concomitantly, prothrombin time or other suitable coagulation test should be closely monitored.
Nitrofurantoin interferes with the therapeutic action of nalidixic acid.
Antacids containing magnesium, aluminum, or calcium; sucralfate or divalent or trivalent cations such as iron; multivitamins containing zinc; and Didanosine, chewable/buffered tablets or the pediatric powder for oral solution may substantially interfere with the absorption of quinolones, resulting in systemic levels considerably lower than desired. These agents should not be taken within the two hour period before or within the two-hour period after nalidixic acid administration.
Elevated serum levels of cyclosporine have been reported with the concomitant use of some quinolones and cyclosporine. Therefore, cyclosporine serum levels should be monitored and appropriate cyclosporine dosage adjustments made when these drugs are used concomitantly.
Carcinogenesis, Mutagenesis, Impairment of Fertility
In lifetime studies in the rat given nalidixic acid in the diet, there was an increased incidence of preputial gland neoplasms in the treated males and clitoral gland neoplasms in the treated females. Studies in mice in which nalidixic acid was administered in the feed for two years, or was given in the feed for 76 weeks followed by no treatment for 9 weeks, gave equivocal evidence of carcinogenic activity.
Nalidixic acid was tested in the Ames bacterial mutagenicity test (maximum dose 33 mcg/plate) and the mouse lymphoma assay (L5178Y/TK; maximum dose 100 mcg/mL) with and without metabolic activation, and results were negative.
Pregnancy: Teratogenic Effects.
Pregnancy Category C.
DIX has been shown to be teratogenic and embryocidal in rats when given in oral doses six times the human dose. DIX also prolonged the duration of pregnancy especially at four times the clinical dose. There are no adequate and well-controlled studies in pregnant women. Since nalidixic acid, like other drugs in this class, causes arthropathy in immature animals, DIX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. (See WARNINGS and ANIMAL PHARMACOLOGY .)
Nursing Mothers
It is not known whether DIX is excreted in human milk. Because other drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from DIX, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness in infants below the age of three months have not been established.
Usage in Patients Under 18 Years of Age
Toxicological studies have shown that nalidixic acid and related drugs can produce erosions of the cartilage in weight-bearing joints and other signs of arthropathy in immature animals of most species tested. No such joint lesions have been reported in humans to date. Nevertheless, until the significance of this finding is clarified, this drug should only be used in patients under 18 years of age when the potential benefit justifies the potential risk. (See WARNINGS and ANIMAL PHARMACOLOGY .)
Geriatric Use
Clinical studies of DIX® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Caution should therefore be observed in using nalidixic acid in elderly patients. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See PRECAUTIONS , General .)
ADVERSE REACTIONS
Reactions reported after oral administration of DIX include the following.
CNS effects: drowsiness, weakness, headache, and dizziness and vertigo. Reversible subjective visual disturbances without objective findings have occurred infrequently (generally with each dose during the first few days of treatment). These reactions include overbrightness of lights, change in color perception, difficulty in focusing, decrease in visual acuity, and double vision. They usually disappeared promptly when dosage was reduced or therapy was discontinued. Toxic psychosis or brief convulsions have been reported rarely, usually following excessive doses. In general, the convulsions have occurred in patients with predisposing factors such as epilepsy or cerebral arteriosclerosis. In infants and children receiving therapeutic doses of DIX, increased intracranial pressure with bulging anterior fontanel, papilledema, and headache has occasionally been observed. A few cases of 6th cranial nerve palsy have been reported. Although the mechanisms of these reactions are unknown, the signs and symptoms usually disappeared rapidly with no sequelae when treatment was discontinued.
Gastrointestinal: abdominal pain, nausea, vomiting, and diarrhea.
Allergic: rash, pruritus, urticaria, angioedema, eosinophilia, arthralgia with joint stiffness and swelling, and anaphylactoid reaction. Erythema Multiforme and Stevens-Johnson syndrome have been reported with nalidixic acid and other drugs in this class. Rash was the most frequently reported adverse reaction. Photosensitivity reactions consisting of erythema and bullae on exposed skin surfaces usually resolve completely in 2 weeks to 2 months after DIX is discontinued; however, bullae may continue to appear with successive exposures to sunlight or with mild skin trauma for up to 3 months after discontinuation of drug. (See PRECAUTIONS .)
Other: rarely, cholestasis, paresthesia, metabolic acidosis, thrombocytopenia, leukopenia, or hemolytic anemia, sometimes associated with glucose 6-phosphate dehydrogenase deficiency.
Dizziness, drowsiness. and visual disturbances may occur rel-
atively frequently and patients should be advised not to drive
or operate machinery if affected.
Uses and Administration
Rosoxacin is a 4-quinolone antibacterial with actions simi-
lar to those of nalidixic acid. It is active against Neisseria
gonorrhoeae and is given by mouth in the treatment of
gonorrhoea as a single dose of 300 mg, preferably on
an empty stomach.