A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Neggram Warnings, Precautions, Pregnancy, Nursing, Abuse - Nalidixic Acid
Neggram Warnings, Precautions, Pregnancy, Nursing, Abuse - Nalidixic Acid
WARNINGS
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.
Nalidixic acid and other members of the quinolone drug class have been shown
to cause arthropathy in juvenile animals. (See PRECAUTIONS
and ANIMAL PHARMACOLOGY
.)
Pseudomembranous colitis has been reported with nearly all antibacterial agents,
including quinolones, and may range in severity from mild to life-threatening.
Therefore, it is important to consider this diagnosis in patients who present
with diarrhea subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and
may permit overgrowth of clostridia. Studies indicate that a toxin produced
by Clostridium difficile is one primary cause of "antibiotic-associated
colitis".
After the diagnosis of pseudomembranous colitis has been established, therapeutic
measures should be initiated. Mild cases of pseudomembranous colitis usually
respond to drug discontinuation alone. In moderate to severe cases, consideration
should be given to management with fluids and electrolytes, protein supplementation,
and treatment with an antibacterial drug clinically effective against C.
difficile colitis.
PRECAUTIONS
General
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
.) While caution should be used in patients with severe renal
failure, therapeutic concentrations of NegGram 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 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.)
Information for Patients
Patients should be advised NegGram 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 NegGram 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 Videx®, (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 Videx®,
(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.
Drug Laboratory Test Interactions
When Benedict's or Fehling's solution or Clinitest® Reagent Tablets are used
to test the urine of patients taking NegGram, a false-positive reaction for
glucose may be obtained, due to the liberation of glucuronic acid from the metabolites
excreted. However, a colorimetric test for glucose based on an enzyme reaction
(e.g., with Clinistix® Reagent Strips or Tes-Tape®) does not give a false-positive
reaction to the liberated glucuronic acid.
Incorrect values may be obtained for urinary 17-keto and ketogenic steroids
in patients receiving NegGram, because of an interaction between the drug and
the m -dinitrobenzene used in the usual assay method. In such cases,
the Porter-Silber test for 17-hydroxycorticoids may be used.
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.
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 .)
Nursing Mothers
It is not known whether NegGram 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 NegGram, 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 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 .)
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