"The U.S. Food and Drug Administration today approved Zerbaxa (ceftolozane/tazobactam), a new antibacterial drug product, to treat adults with complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI).
Central Nervous System (CNS) effects including convulsions, increased intracranial pressure, and toxic psychosis have been reported with nalidixic acid therapy. Convulsive seizures have been reported with other drugs in this class. Quinolones may also cause CNS stimulation which may lead to tremor, restlessness, lightheadedness, confusion, and hallucinations. Therefore, nalidixic acid should be used with caution in patients with known or suspected CNS disorders, such as, cerebral arteriosclerosis or epilepsy, or other factors which predispose seizures. (See ADVERSE REACTIONS) If these reactions occur in patients receiving nalidixic acid, the drug should be discontinued and appropriate measures instituted.
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions, some following the first dose, have been reported in patients receiving quinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Only a few patients had a history of hypersensitivity reactions. Serious anaphylactoid reactions required immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should be administered as indicated.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including NegGram, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving quinolones, including nalidixic acid. Nalidixic acid should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness, and/or weakness, or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength in order to prevent the development of an irreversible condition.
Ruptures of the shoulder, hand, Achilles tendon or other tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones, including nalidixic acid. Post-marketing surveillance reports indicate that this risk may be increased in patients receiving concomitant corticosteroids, especially in the elderly. Nalidixic acid should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon. Patients should rest and refrain from exercise until the diagnosis of tendonitis or tendon rupture has been excluded. Tendon rupture can occur during or after therapy with quinolones, including nalidixic acid.
Blood counts and renal and liver function tests should be performed periodically if treatment is continued for more than two weeks. NegGram should be used with caution in patients with liver disease, epilepsy, or severe cerebral arteriosclerosis. (See WARNINGS) Caution should be used in patients with renal insufficiency. (See DOSAGE AND ADMINISTRATION)
Moderate to severe phototoxicity reactions have been observed in patients who are exposed to direct sunlight while receiving NegGram or other members of this drug class. Excessive sunlight should be avoided. Therapy should be discontinued if phototoxicity occurs.
If bacterial resistance to NegGram 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 NegGram during initial treatment (with less than 4 g per day for adults) may predispose to emergence of bacterial resistance. (See DOSAGE AND ADMINISTRATION)
Cross-resistance between nalidixic acid and other quinolone derivatives such as oxolinic acid and cinoxacin has been observed.
Prescribing NegGram in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
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 Category C
NegGram has been shown to be teratogenic and embryocidal in rats when given in oral doses six times the human dose. NegGram 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, NegGram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. (See WARNINGS and Animal Pharmacology)
Since nalidixic acid is excreted in breast milk, it is contraindicated during lactation.
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. If arthralgia occurs, treatment with nalidixic acid should be stopped. (See WARNINGS and Animal Pharmacology)
Clinical studies of NegGram 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)This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 6/10/2011
Additional NegGram Caplets Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.