hepatocellular, cholestatic, or mixed hepatitis, with or without jaundice. In such circumstances, ranitidine should be immediately discontinued. These events are usually reversible, but in rare circumstances death has occurred. Rare cases of hepatic failure have also been reported.
Musculoskeletal
Rare reports of arthralgias and myalgias.
Hematologic
Blood count changes (leukopenia, granulocytopenia, and thrombocytopenia) have occurred in a few patients. These were usually reversible. Rare cases of agranulocytosis, pancytopenia, sometimes with marrow hypoplasia, and aplastic anemia and exceedingly rare cases of acquired immune hemolytic anemia have been reported.
Endocrine
Controlled studies in animals and humans have shown no stimulation of any pituitary hormone by ZANTAC and no antiandrogenic activity, and cimetidine-induced gynecomastia and impotence in hypersecretory patients have resolved when ZANTAC has been substituted. However, occasional cases of impotence and loss of libido have been reported in male patients receiving ZANTAC, but the incidence did not differ from that in the general population. Rare cases of breast symptoms and conditions, including galactorrhea and gynecomastia, have been reported in both males and females.
Integumentary
Rash, including rare cases of erythema multiforme. Rare cases of alopecia and vasculitis.
Respiratory
A large epidemiological study suggested an increased risk of developing pneumonia in current users of histamine-2–receptor antagonists (H2RAs) compared to patients who had stopped H2RA treatment, with an observed adjusted relative risk of 1.63 (95% CI, 1.07–2.48). However, a causal relationship between use of H2RAs and pneumonia has not been established.
Other
Rare cases of hypersensitivity reactions (e.g., bronchospasm, fever, rash, eosinophilia), anaphylaxis, angioneurotic edema, acute interstitial nephritis, and small increases in serum creatinine.
OVERDOSAGE
There has been virtually no experience with overdosage with ZANTAC Injection and limited experience with oral doses of ranitidine. Reported acute ingestions of up to 18 g orally have been associated with transient adverse effects similar to those encountered in normal clinical experience (see ADVERSE REACTIONS). In addition, abnormalities of gait and hypotension have been reported.
When overdosage occurs, clinical monitoring and supportive therapy should be employed.
Studies in dogs receiving dosages of ZANTAC in excess of 225 mg/kg/day have shown muscular tremors, vomiting, and rapid respiration. Single oral doses of 1,000 mg/kg in mice and rats were not lethal. Intravenous LD50 values in mice and rats were 77 and 83 mg/kg, respectively.
DOSAGE AND ADMINISTRATION
Parenteral Administration
In some hospitalized patients with pathological hypersecretory conditions or intractable duodenal ulcers, or in patients who are unable to take oral medication, ZANTAC may be administered parenterally according to the following recommendations:
Intramuscular Injection
50 mg (2 mL) every 6 to 8 hours. (No dilution necessary.)
Intermittent Intravenous Injection
a. Intermittent Bolus
50 mg (2 mL) every 6 to 8 hours. Dilute ZANTAC Injection, 50 mg, in 0.9% sodium chloride injection or other compatible IV solution (see Stability) to a concentration no greater than 2.5 mg/mL (20 mL). Inject at a rate no greater than 4 m
