SIDE EFFECTS
Worldwide, controlled clinical trials of nizatidine
included over 6000 patients given nizatidine in studies
of varying durations. Placebo-controlled trials in the United
States and Canada included over 2600 patients given nizatidine
and over 1700 given placebo. Among the adverse events in
these placebo-controlled trials, anemia (0.2% vs 0%) and
urticaria (0.5% vs 0.1%) were significantly more common
in the nizatidine group.
Incidence in Placebo-Controlled Clinical Trials in the United
States and Canada: TABLE 5 lists adverse events that occurred
at a frequency of 1% or more among nizatidine-treated patients
who participated in placebo-controlled trials. The cited
figures provide some basis for estimating the relative contribution
of drug and nondrug factors to the side effect incidence
rate in the population studied.
| TABLE 5
Incidence Of Treatment-Emergent Adverse Events In
Placebo-Controlled Clinical Studies In The United
States And Canada |
| |
Percentage
of Patients Reporting Event |
| Body System/Adverse Event* |
Nizatidine (N=2694) |
Placebo (N=1729) |
| Body
As A Whole |
|
|
16.6 |
15.6 |
|
|
7.5 |
12.5 |
|
|
4.2 |
3.8 |
|
|
3.1 |
2.9 |
|
|
2.4 |
2.6 |
|
|
2.3 |
2.1 |
|
|
1.7 |
1.1 |
|
|
1.6 |
2.3 |
|
|
1.4 |
1.5 |
|
|
1.2 |
0.9 |
| Digestive |
|
|
7.2 |
6.9 |
|
|
5.4 |
7.4 |
|
|
4.9 |
5.4 |
|
|
3.6 |
5.6 |
|
|
3.6 |
4.4 |
|
|
2.5 |
3.8 |
|
|
1.4 |
1.3 |
|
|
1.2 |
1.9 |
|
|
1.2 |
1.6 |
|
|
1.1 |
1.2 |
|
|
1.0 |
0.8 |
| Musculoskeletal |
|
|
1.7 |
1.5 |
| Nervous |
|
|
4.6 |
3.8 |
|
|
2.7 |
3.4 |
|
|
1.9 |
1.9 |
|
|
1.9 |
1.6 |
|
|
1.6 |
1.4 |
|
|
1.1 |
0.8 |
| Respiratory |
|
|
9.8 |
9.6 |
|
|
3.3 |
3.1 |
|
|
2.4 |
2.1 |
|
|
2.0 |
2.0 |
| Skin And Appendages |
|
|
1.9 |
2.1 |
|
|
1.7 |
1.3 |
| Special Senses |
|
|
1.0 |
0.9 |
| * Events
reported by at least 1% of nizatidine-treated patients
are included. |
A variety of less common events were also reported; it
was not possible to determine whether these were caused
by nizatidine.
Hepatic: Hepatocellular injury, evidenced by
elevated liver enzyme tests (SGOT [AST], SGPT [ALT], or
alkaline phosphatase), occurred in some patients and was
possibly or probably related to nizatidine. In some cases
there was marked elevation of SGOT, SGPT enzymes (greater
than 500 IU/L) and, in a single instance, SGPT was greater
than 2000 IU/L. The overall rate of occurrences of elevated
liver enzymes and elevations to 3 times the upper limit
of normal, however, did not significantly differ from
the rate of liver enzyme abnormalities in placebo-treated
patients. All abnormalities were reversible after discontinuation
of nizatidine. Since market introduction, hepatitis and
jaundice have been reported. Rare cases of cholestatic
or mixed hepatocellular and cholestatic injury with jaundice
have been reported with reversal of the abnormalities
after discontinuation of nizatidine.
Cardiovascular: In clinical pharmacology
studies, short episodes of asymptomatic ventricular tachycardia
occurred in 2 individuals administered nizatidine and
in 3 untreated subjects.
CNS: Rare cases of reversible mental
confusion have been reported.
Endocrine: Clinical pharmacology studies
and controlled clinical trials showed no evidence of antiandrogenic
activity due to nizatidine. Impotence and decreased libido
were reported with similar frequency by patients who received
nizatidine and by those given placebo. Rare reports of
gynecomastia occurred.
Hematologic: Anemia was reported significantly
more frequently in nizatidine than in placebo-treated
patients. Fatal thrombocytopenia was reported in a patient
who was treated with nizatidine and another H2-receptor
antagonist. On previous occasions, this patient had experienced
thrombocytopenia while taking other drugs. Rare cases
of thrombocytopenic purpura have been reported.
Integumental: Sweating and urticaria
were reported significantly more frequently in nizatidine-
than in placebo-treated patients. Rash and exfoliative
dermatitis were also reported. Vasculitis has been reported
rarely.
Hypersensitivity: As with other H2-receptor
antagonists, rare cases of anaphylaxis following administration
of nizatidine have been reported. Rare episodes of hypersensitivity
reactions (e.g., bronchospasm, laryngeal edema, rash,
and eosinophilia) have been reported.
Body as a Whole: Serum sickness-like
reactions have occurred rarely in conjunction with nizatidine
use.
Genitourinary: Reports of impotence
have occurred.
Other: Hyperuricemia unassociated with
gout or nephrolithiasis was reported. Eosinophilia, fever,
and nausea related to nizatidine administration have been
reported.
DRUG INTERACTIONS
No interactions have been observed between nizatidine
and theophylline, chlordiazepoxide, lorazepam, lidocaine,
phenytoin, and warfarin. Nizatidine does not inhibit the
cytochrome P-450-linked drug-metabolizing enzyme system;
therefore, drug interactions mediated by inhibition of
hepatic metabolism are not expected to occur. In patients
given very high doses (3900 mg) of aspirin daily, increases
in serum salicylate levels were seen when nizatidine,
150 mg b.i.d., was administered concurrently.
| 
