Roxatidine Acetate Hydrochloride
Adverse Effects and Precautions as for Cimetidine which are given below :
PRECAUTIONS:
GENERAL: Rare instances of cardiac arrhythmias and hypotension have been
reported following the rapid administration of Tagamed (cimetidine
hydrochloride) Injection by intravenous bolus.
Symptomatic response to Tagamed therapy does not preclude the presence of a
gastric malignancy. There have been rare reports of transient healing of gastric
ulcers despite subsequently documented malignancy.
Reversible confusional states (see Adverse Reactions) have been observed on
occasion, predominantly, but not exclusively, in severely ill patients.
Advancing age (50 or more years) and preexisting liver and/or renal disease
appear to be contributing factors. In some patients these confusional states
have been mild and have not required discontinuation of Tagamed therapy. In
cases where discontinuation was judged necessary, the condition usually cleared
within 3 to 4 days of drug withdrawal.
Administration In renal impairment. Preliminary re-
sults in 6 patients with chronic renal failure and creatinine
clearance less than 20 mL per minute indicated that adminis-
tration of the recommended dose of roxatidine acetate hydro-
chloride. 75 mg every other day, was inadequate to maintain
gastric pH above 4 for more than 6 hours. Subsequent study
in 8 patients showed that a dose of 75 mg daily was well tol-
erated and effective.
ADVERSE REACTIONS:
Adverse effects reported in patients taking Tagamed are described below by body
system. Incidence figures of 1 in 100 and greater are generally derived from
controlled clinical studies.
GASTROINTESTINAL: Diarrhea (usually mild) has been reported in approximately 1
in 100 patients.
CNS: Headaches, ranging from mild to severe, have been reported in 3.5% of 924
patients taking 1600mg/day, 2.1% of 2,225 patients taking 800 mg/day and 2.3% of
1,897 patients taking placebo. Dizziness and somnolence (usually mild) have been
reported in approximately 1 in 100 patients on either 1600 mg/day or 800 mg/day.
Reversible confusional states, e.g., mental confusion, agitation, psychosis,
depression, anxiety, hallucinations, disorientation, have been reported
predominantly, but not exclusively, in severely ill patients. They have usually
developed within 2 to 3 days of initiation of Tagamed therapy and have cleared
within 3 to 4 days of discontinuation of the drug.
ENDOCRINE: Gynecomastia has been reported in patients treated for 1 month or
longer. In patients being treated for pathological hypersecretory states, this
occurred in about 4% of cases while in all others the incidence was 0.3% to 1%
in various studies. No evidence of induced endocrine dysfunction was found, and
the condition remained unchanged or returned toward normal with continuing
Tagamed (cimetidine) treatment.
Reversible impotence has been reported in patients with pathological
hypersecretory disorders, e.g., Zollinger-Ellison Syndrome, receiving Tagamed,
particularly in high doses, for at least 12 months (range 12 to 79 months, mean
38 months). However, in large-scale surveillance studies at regular dosage, the
incidence has not exceeded that commonly reported in the general population.
HEMATOLOGIC: Decreased white blood cell counts in Tagamed-treated patients
(approximately 1 per 100,000 patients), including agranulocytosis (approximately
3 per million patients), have been reported, including a few reports of
recurrence on rechallenge. Most of these reports were in patients who had
serious concomitant illnesses and received drugs and/or treatment known to
produce neutropenia. Thrombocytopenia (approximately 3 per million patients)
and, very rarely, cases of pancytopenia or aplastic anemia have also been
reported. As with some other H2-receptor antagonists, there have been extremely
rare reports of immune hemolytic anemia.
HEPATOBILIARY: Dose-related increases in serum transaminase have been reported.
In most cases they did not progress with continued therapy and returned to
normal at the end of therapy. There have been rare reports of cholestatic or
mixed cholestatic-hepatocellular effects. These were usually reversible. Because
of the predominance of cholestatic features, severe parenchymal injury is
considered highly unlikely. However, as in the occasional liver injury with
other H2-receptor antagonists, in exceedingly rare circumstances fatal outcomes
have been reported.
There has been reported a single case of biopsy- proven periportal hepatic
fibrosis in a patient receiving Tagamed.
Rare cases of pancreatitis, which cleared on withdrawal of the drug, have been
reported.
HYPERSENSITIVITY: Rare cases of fever and allergic reactions including
anaphylaxis and hypersensitivity vasculitis, which cleared on withdrawal of the
drug, have been reported.
RENAL: Small, possibly dose-related increases in plasma creatinine, presumably
due to competition for renal tubular secretion, are not uncommon and do not
signify deteriorating renal function. Rare cases of interstitial nephritis and
urinary retention, which cleared on withdrawal of the drug, have been reported.
CARDIOVASCULAR: Rare cases of bradycardia, tachycardia and A-V heart block have
been reported with H2-receptor antagonists.
MUSCULOSKELETAL: There have been rare reports of reversible arthralgia and
myalgia; exacerbation of joint symptoms in patients with preexisting arthritis
has also been reported. Such symptoms have usually been alleviated by a
reduction in Tagamed (cimetidine) dosage. Rare cases of polymyositis have been
reported, but no causal relationship has been established.
INTEGUMENTAL: Mild rash and, very rarely, cases of severe generalized skin
reactions including Stevens-Johnson syndrome, epidermal necrolysis, erythema
multiforme, exfoliative dermatitis and generalized exfoliative erythroderma have
been reported with H2-receptor antagonists. Reversible alopecia has been
reported very rarely.
IMMUNE FUNCTION: There have been extremely rare reports of strongyloidiasis
hyperinfection in immunocompromised patients.
Interactions
Like cimetidine, roxatidine does not
appear to affect cytochrome P450. and therefore is
considered to have little effect on the metabolism of
other drugs.
Pharmacokinetics
Roxatidine acetate hydrochloride is rapidly and al-
most completely absorbed from the gastro-intestinal
tract with peak concentrations in plasma occurring
about I to 3 hours after administration by mouth. It
is rapidly hydrolysed to the active desacetyl metab-
olite, roxatidine, by esterases in the liver, small in-
testine, and serum.
Over 90% of a dose is excreted in the urine as roxa-
tidine and other metabolites. The elimination half-
life of roxatidine is about 6 hours and is prolonged
in renal impairment.
Small amounts of roxatidine have been reported to
be distributed into breast milk.
Uses and Administration
Roxatidine acetate hydrochloride is a histamine H-2
receptor antagonist with actions and uses similar to
those of cimetidine. It is given by mouth.
In the management of peptic ulcer disease the dose
is 150 mg at bedtime or 75 mg twice daily. Where
appropriate a maintenance dose of 75 mg at bedtime
may be given to prevent the recurrence of duodenal
ulcers. In gastro-oesophageal reflux disease the rec-
ommended dose is 75 mg twice daily.
The dosage should be reduced in patients with renal
impairment. Suggested doses for patients on acute
therapy are: creatinine clearance of 20 to 50 mL per
minute. 75 mg at bedtime: creatinine clearance of
less than 20 mL per minute. 75 mg every 2 days (but
see above).