DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Prilosec (Omeprazole) - Warnings and Precautions



Concomitant Gastric Malignancy

Symptomatic response to therapy with omeprazole does not preclude the presence of gastric malignancy.

Atrophic Gastritis

Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with omeprazole.

Combiniation Use of PRILOSEC with Amoxicillin

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy with amoxicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. If an allergic reaction occurs, amoxicillin should be discontinued and appropriate therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids and airway management, including intubation, should also be administered as indicated.

Pseudomembranous colitis has been reported with nearly all antibacterial agents 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 a 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 discontinuation of the drug 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 Clostridium difficile colitis.

Combination Use of PRILOSEC with 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 Warnings in prescribing information for clarithromycin.)

Co-administration of omeprazole and clarithromycin has resulted in increases in plasma levels of omeprazole, clarithromycin, and 14-hydroxy-clarithromycin. [ See Clinical Pharmacology (12) ]

Concomitant administration of clarithromycin with cisapride or pimozide, is contraindicated.



Pregnancy Category C

Reproductive studies in rats and rabbits with omeprazole and multiple cohort studies in pregnant women with omeprazole use during the first trimester do not show an increased risk of congenital anomalies or adverse pregnancy outcomes. There are no adequate and well controlled studies on the use of omeprazole in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. The vast majority of reported experience with omeprazole during human pregnancy is first trimester exposure and the duration of use is rarely specified, e.g., intermittent vs. chronic. An expert review of published data on experiences with omeprazole use during pregnancy by TERIS – the Teratogen Information System – concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as fair). Three epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women exposed to H2–receptor antagonists or other controls. A population-based prospective cohort epidemiological study from the Swedish Medical Birth Registry, covering approximately 99% of pregnancies, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. In utero exposure to omeprazole was not associated with increased risk of any malformation (odds ratio 0.82, 95% CI 0.50–1.34), low birth weight or low Apgar score. The number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed infants than the expected number in the normal population. The author concluded that both effects may be random.

A retrospective cohort study reported on 689 pregnant women exposed to either H2–blockers or omeprazole in the first trimester (134 exposed to omeprazole). The overall malformation rate was 4.4% (95% CI 3.6–5.3) and the malformation rate for first trimester exposure to omeprazole was 3.6% (95% CI 1.5–8.1). The relative risk of malformations associated with first trimester exposure to omeprazole compared with non-exposed women was 0.9 (95% CI 0.3–2.2). The study could effectively rule out a relative risk greater than 2.5 for all malformations. Rates of preterm delivery or growth retardation did not differ between the groups.

A controlled prospective observational study followed 113 women exposed to omeprazole during pregnancy (89% first trimester exposures). The reported rates of major congenital malformations was 4% for the omeprazole group, 2% for controls exposed to non-teratogens, and 2.8% in disease-paired controls (background incidence of major malformations 1–5%). Rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight did not differ between the groups. The sample size in this study has 80% power to detect a 5–fold increase in the rate of major malformation.

Several studies have reported no apparent adverse short-term effects on the infant when single dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia.

Reproductive studies conducted with omeprazole on rats at oral doses up to 56 times the human dose and in rabbits at doses up to 56 times the human dose did not show any evidence of teratogenicity. In pregnant rabbits, omeprazole at doses about 5.5 to 56 times the human dose produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy loss. In rats treated with omeprazole at doses about 5.6 to 56 times the human dose, dose-related embryo/fetal toxicity and postnatal developmental toxicity occurred in offspring. [ See Animal Toxicology and/or Pharmacology (13.2) ].

Nursing Mothers

Omeprazole concentrations have been measured in breast milk of a woman following oral administration of 20 mg. The peak concentration of omeprazole in breast milk was less than 7% of the peak serum concentration. This concentration would correspond to 0.004 mg of omeprazole in 200 mL of milk. Because omeprazole is 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

Use of PRILOSEC in pediatric and adolescent patients 1 to 16 years of age for the treatment of GERD is supported by a) extrapolation of results, already included in the currently approved labeling, from adequate and well-controlled studies that supported the approval of PRILOSEC for adults, and b) safety and pharmacokinetic studies performed in pediatric and adolescent patients. [ See Clinical Pharmacology, Pharmacokinetics, Pediatric for pharmacokinetic information (12.3) and Dosage and Administration (2). Adverse Reactions (6.1) and Clinical Studies, (14.6) ]. The safety and effectiveness of PRILOSEC for the treatment of GERD in patients < 1 year of age have not been established. The safety and effectiveness of PRILOSEC for other pediatric uses have not been established.

Geriatric Use

Omeprazole was administered to over 2000 elderly individuals (≥ 65 years of age) in clinical trials in the U.S. and Europe. There were no differences in safety and effectiveness between the elderly and younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

Pharmacokinetic studies have shown the elimination rate was somewhat decreased in the elderly and bioavailability was increased. The plasma clearance of omeprazole was 250 mL/min (about half that of young volunteers) and its plasma half-life averaged one hour, about twice that of young healthy volunteers. However, no dosage adjustment is necessary in the elderly. [ See Clinical Pharmacology (12.3) ]

Hepatic Impairment

Consider dose reduction, particularly for maintenance of healing of erosive esophagitis. [ See Clinical Pharmacology (12.3) ]

Renal Impairment

No dosage reduction is necessary. [ See Clinical Pharmacology (12.3) ]

Asian Population

Consider dose reduction, particularly for maintenance of healing of erosive esophagitis. [ See Clinical Pharmacology (12.3) ]

Page last updated: 2008-03-27

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017