CONTRAINDICATIONS
Omeprazole
Omeprazole delayed-release capsules are contraindicated in patients with known hypersensitivity to
any component of the formulation.
Clarithromycin
Clarithromycin is contraindicated in patients with a known hypersensitivity to any macrolide
antibiotic.
Concomitant administration of clarithromycin with cisapride, pimozide, or terfenadine is
contraindicated. There have been post-marketing reports of drug interactions when clarithromycin
and/or erythromycin are co-administered with cisapride, pimozide, or terfenadine resulting in cardiac
arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de
pointes) most likely due to inhibition of hepatic metabolism of these drugs by erythromycin and
clarithromycin. Fatalities have been reported. (Please refer to clarithromycin before prescribing.)
WARNINGS
CLARITHROMYCIN: CLARITHROMYCIN SHOULD NOT BE USED IN PREGNANT
WOMEN EXCEPT IN CLINICAL CIRCUMSTANCES WHERE NO ALTERNATIVE
THERAPY IS APPROPRIATE. IF PREGNANCY OCCURS WHILE TAKING
CLARITHROMYCIN, THE PATIENT SHOULD BE APPRISED OF THE POTENTIAL
HAZARD TO THE FETUS. (See Clarithromycin, WARNINGS)
PRECAUTIONS
General: Symptomatic response to therapy with omeprazole does not preclude the presence of
gastric malignancy.
Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated
long-term with omeprazole.
Information for the Patient: Omeprazole delayed-release capsules should be taken before eating.
Patients should be cautioned that the omeprazole delayed-release capsule should not be opened,
chewed or crushed, and should be swallowed whole.
Carcinogenesis, Mutagenesis, and Impairment of Fertility: In two 24-month carcinogenicity
studies in rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44.0 and 140.8 mg/kg/day (approximately
4 to 352 times the human dose, based on a patient weight of 50 kg and a human dose of 20 mg)
produced gastric ECL cell carcinoids in a dose-related manner in both male and female rats; the
incidence of this effect was markedly higher in female rats, which had higher blood levels of
omeprazole. Gastric carcinoids seldom occur in the untreated rat. In addition, ECL cell hyperplasia
was present in all treated groups of both sexes. In one of these studies, female rats were treated
with 13.8 mg omeprazole/kg/day (approximately 35 times the human dose) for one year, then
followed for an additional year without the drug. No carcinoids were seen in these rats. An
increased incidence of treatment-related ECL cell hyperplasia was observed at the end of one year
(94% treated vs 10% controls). By the second year the difference between treated and control rats
was much smaller (46% vs 26%) but still showed more hyperplasia in the treated group. An unusual
primary malignant tumor in the stomach was seen in one rat (2%). No similar tumor was seen in
male or female rats treated for two years. For this strain of rat no similar tumor has been noted
historically, but a finding involving only one tumor is difficult to interpret. A 78-week mouse
carcinogenicity study of omeprazole did not show increased tumor occurrence, but the study was
not conclusive.
Omeprazole was not mutagenic in an in vitro Ames Salmonella typhimurium assay, an in vitro
mouse lymphoma cell assay and an in vivo rat liver DNA damage assay. A mouse micronucleus
test at 625 and 6250 times the human dose gave a borderline result, as did an in vivo bone marrow
chromosome aberration test. A second mouse micronucleus study at 2000 times the human dose,
but with different (suboptimal) sampling times, was negative.
In a rat fertility and general reproductive performance test, omeprazole in a dose range of 13.8 to
138.0 mg/kg/day (approximately 35 to 345 times the human dose) was not toxic or deleterious to the
reproductive performance of parental animals.
Pregnancy Category C: Teratology studies conducted in pregnant rats at doses up to 138
mg/kg/day (approximately 345 times the human dose) and in pregnant rabbits at doses up to 69
mg/kg/day (approximately 172 times the human dose) did not disclose any evidence for a
teratogenic potential of omeprazole.
In rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (approximately 17 to 172 times the
human dose) produced dose-related increases in embryo-lethality, fetal resorptions and pregnancy
disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were
observed in offspring resulting from parents treated with omeprazole 13.8 to 138.0 mg/kg/day
(approximately 35 to 345 times the human dose). There are no adequate or well-controlled studies
in pregnant women. Sporadic reports have been received of congenital abnormalities occurring in
infants born to women who have received omeprazole during pregnancy. Omeprazole should be
used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Clarithromycin: See WARNINGS and clarithromycin before using in pregnant women.
Nursing Mothers: It is not known whether omeprazole is excreted in human milk. In rats,
omeprazole administration during late gestation and lactation at doses of 13.8 to 138 mg/kg/day (35
to 345 times the human dose) resulted in decreased weight gain in pups. Because many drugs are
excreted in human milk, because of the potential for serious adverse reactions in nursing infants
from omeprazole, and because of the potential for tumorigenicity shown for omeprazole in rat
carcinogenicity studies, 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 children have not been established.