Omeclamox-Pak (omeprazole/clarithromycin/amoxicillin trihydrate)

Dosage of amoxicillin, which is available for oral use as the trihydrate, is expressed in terms of anhydrous amoxicillin.

Safety and efficacy of clarithromycin extended-release tablets have been established for the treatment of acute bacterial exacerbations of chronic bronchitis, acute maxillary sinusitis, and community-acquired pneumonia (CAP) in adults; safety and efficacy of the extended-release formulation of the drug have not been established for the treatment of other infections that are treated with clarithromycin conventional tablets or oral suspension.

Dosage of omeprazole magnesium is expressed in terms of omeprazole.

Clarithromycin generally may be used without dosage adjustment in patients with hepatic impairment and normal renal function. However, in patients with creatinine clearances less than 30 mL/minute with or without hepatic impairment, the dosage should be halved or the dosing interval for clarithromycin doubled. An initial clarithromycin dose of 500 mg (conventional tablets or oral suspension) followed by 250 mg twice daily has been suggested for adults with creatinine clearances less than 30 mL/minute when a usual dosage of 500 mg twice daily would have been used in adults with normal renal function; a dosage of 250 mg (conventional tablets or oral suspension) daily has been suggested for such patients when a usual dosage of 250 mg twice daily would have been used in individuals with normal renal function.

In patients with renal impairment, doses and/or frequency of administration of amoxicillin should be modified in response to the degree of renal impairment, severity of the infection, and susceptibility of the causative organisms. The manufacturer states that adults with severe renal impairment and creatinine clearances less than 30 mL/minute should not receive the commercially available film-coated tablets containing 875 mg of amoxicillin. The recommended dosage of amoxicillin for adults with creatinine clearances of 10-30 mL/minute is 250 or 500 mg every 12 hours, depending on the severity of the infection, and the recommended dosage for adults with creatinine clearances less than 10 mL/minute is 250 or 500 mg every 24 hours, depending on the severity of the infection.

Patients undergoing hemodialysis should receive 250 or 500 mg of amoxicillin every 24 hours, depending on the severity of the infection, and should receive an additional dose of the drug during and after each dialysis period.

The manufacturer states that data are insufficient to recommend dosage for pediatric patients with renal impairment.

Omeprazole delayed-release and immediate-release capsules are administered orally; oral suspensions of the drug are administered orally or through a gastric tube. To avoid decomposition of omeprazole in the acidic pH of the stomach, the commercially available delayed-release capsules and delayed-release oral suspension contain enteric-coated granules of the drug. Immediate-release capsules, immediate-release oral suspension, and the kit for oral suspension (Konvomep(R)) all contain sodium bicarbonate to protect the drug from acid degradation.

Omeprazole magnesium is also available in fixed-combination capsules containing amoxicillin and rifabutin (Talicia(R)). A co-packaged product containing delayed-release omeprazole capsules, clarithromycin tablets, and amoxicillin capsules (Omeclamox-Pak(R)) is also commercially available. See the full prescribing information for administration of these combination products.

Antacids may be administered concomitantly with delayed-release preparations of omeprazole.

For patients receiving continuous feedings via a nasogastric or orogastric tube, enteral feeding should be stopped temporarily for 3 hours before and for 1 hour after administration of preparations of omeprazole oral suspension.

Store omeprazole delayed-release capsules in tight containers or the original carton at 20-25degreesC; protect from light and moisture. Store packets of omeprazole powder for delayed-release suspension at 25degreesC (excursions permitted from 15-30degreesC). Store immediate-release capsules in tight, light-resistant containers at 20-25degreesC and protect from moisture. Store packets of omeprazole powder for immediate-release suspension protected from light and moisture at 25degreesC (excursions permitted from 15-30degreesC). Store omeprazole and sodium bicarbonate powder kit for oral suspension (Konvomep(R)) at 2-8degreesC protected from light; do not freeze.

No dosing information is available for this tab.

No dosing information is available for this tab.

In vivo, omeprazole is a substrate and inhibitor of cytochrome P-450 (CYP) isoenzyme 2C19, and a substrate of CYP3A4. Omeprazole is also an inhibitor of CYP2C19 in vitro.

When co-packaged delayed-release omeprazole capsules, clarithromycin tablets, and amoxicillin capsules (Omeclamox-Pak(R)) are prescribed, drug interactions should be considered for each individual component. Refer to the Omeclamox-Pak(R) prescribing information for drug interaction information.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Known hypersensitivity reactions (including anaphylaxis) to omeprazole, esomeprazole, or other substituted benzimidazoles (e.g., lansoprazole, pantoprazole, rabeprazole), or any ingredient in the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria.

*Concomitant use of proton-pump inhibitors (PPIs), including omeprazole, and rilpivirine is contraindicated.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects reported in >=2% of adults receiving omeprazole in clinical trials include headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence.

Adverse effects reported in pediatric patients 2--16 years of age receiving omeprazole were similar to those reported in adults, except for more frequently reported respiratory system events and fever.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Safety and efficacy of omeprazole magnesium delayed-release oral suspension have been established for the treatment of erosive esophagitis due to acid-mediated gastroesophageal reflux disease (GERD) in pediatric patients >=1 month of age. Safety and efficacy of omeprazole magnesium delayed-release oral suspension have also been established for the treatment of symptomatic GERD and maintenance of healing of erosive esophagitis in pediatric patients 1-16 years of age. Safety and efficacy of omeprazole delayed-release capsules have been established for the treatment of symptomatic GERD and maintenance of healing of erosive esophagitis in pediatric patients 2-16 years of age. Use in pediatric patients is supported by adequate and well-controlled studies in adults and uncontrolled safety, efficacy, and pharmacokinetic studies in pediatric and adolescent patients.

Safety and efficacy of omeprazole magnesium delayed-release oral suspension are not established in pediatric patients <1 month of age or for other uses in pediatric patients. Safety and efficacy of omeprazole delayed-release capsules in pediatric patients <1 year of age for the treatment of symptomatic GERD or maintenance of healing of erosive esophagitis have not been established. Safety and efficacy of omeprazole delayed-release capsules have not been established in pediatric patients for the treatment of active duodenal ulcer, H. pylori eradication to reduce the risk of duodenal ulcer recurrence, treatment of active benign gastric ulcer, or pathological hypersecretory conditions. Safety and efficacy of omeprazole immediate-release capsules and oral suspension have not been established in pediatric patients.

Safety and efficacy of omeprazole and sodium bicarbonate powder kit for oral suspension (Konvomep(R)) have not been established in pediatric patients.

Safety and efficacy of co-packaged omeprazole delayed-release capsules, clarithromycin tablets, and amoxicillin capsules (Omeclamox-Pak(R)) have not been established in pediatric patients with H. pylori.

Respiratory adverse reactions and accidental injuries have been reported more frequently in pediatric patients of all ages than in adults. Otitis and fever have been reported more frequently in patients less than one year of age and patients from one month to less one year to less than 2 years of age, respectively, than in other pediatric and adult patients.

Safe use of amoxicillin during pregnancy has not been definitely established. There are no adequate or controlled studies using aminopenicillins in pregnant women, and amoxicillin should be used during pregnancy only when clearly needed. However, amoxicillin has been administered to pregnant women without evidence of adverse effects to the fetus. In addition, amoxicillin is included in the US Centers For Disease Control and Prevention (CDC) recommendations for the treatment of chlamydial infections+ during pregnancy and included in CDC recommendations for the treatment of cutaneous anthrax+ or for postexposure prophylaxis+ following exposure to Bacillus anthracis spores.

Although there are no adequate and controlled studies to date in humans, clarithromycin has been associated with adverse effects on pregnancy outcome and/or embryofetal development in animals at dosages that produced plasma drug concentrations 2-17 times those achieved with the maximum recommended human dosage. While the potential risk to the fetus has not been clearly elucidated to date, the manufacturer states that clarithromycin should be used during pregnancy only when safer drugs cannot be used or are ineffective. If clarithromycin is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus.

Teratogenicity studies in rats with oral or IV clarithromycin dosages up to 160 mg/kg daily administered during the period of major organogenesis and in rabbits at oral dosages up to 125 mg/kg daily (approximately twice the maximum recommended human dosage on a mg/m2 basis) or IV dosages of 30 mg/ kg daily administered during days 6-18 of gestation did not demonstrate evidence of teratogenicity. However, other studies in a different rat strain demonstrated a low incidence of cardiovascular anomalies at a clarithromycin dosage of 150 mg/kg daily (resulting in plasma concentrations 2 times those in humans) administered during gestation days 6-15. Studies in mice revealed a variable incidence of cleft palate with oral dosages of 1000 mg/kg daily (resulting in plasma concentrations 17 times those in humans) during gestation days 6-15; cleft palate also was observed at a dosage of 500 mg/kg daily. In monkeys, an oral dosage of 70 mg/kg daily (approximately equivalent to the maximum recommended human dosage on a mg/m2 basis) produced fetal growth retardation at plasma concentrations twice those attained in humans.

Reproductive studies in rats and rabbits using omeprazole dosages during organogenesis of up to 138 and 69.1 mg/kg daily (about 34 times the human dosage of 40 mg daily based on body surface area (BSA)), respectively, have not revealed evidence of teratogenicity. However, in rabbits given omeprazole dosages of 6.9-69.1 mg/kg daily during organogenesis (about 3.4-34 times the human dosage of 40 mg daily based on BSA), dose-related increases in embryolethality, fetal resorptions, and pregnancy loss occurred. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from administration of omeprazole in dosages of 13.8-138 mg/kg daily (about 3.4-34 times the human dosage of 40 mg daily based on BSA) prior to mating through the lactation period.

Reproductive studies of oral esomeprazole (an enantiomer of omeprazole) in rats and rabbits during organogenesis using dosages approximately 68 and 42 times the usual human dosage of 40 mg daily based on BSA, did not reveal evidence of embryo/fetal toxicity. When administered through most of pregnancy and lactation, effects on bone morphology were observed in rat offspring at dosages approximately 34 times the human dosage of 40 mg daily based on BSA of esomeprazole; however, when confined to administration during the gestational period only, no effects on bone morphology were observed in another study.

There are no adequate and well controlled studies using omeprazole in pregnant women. Available epidemiologic data have not demonstrated an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester exposure to omeprazole. Reproductive studies in rats and rabbits using omeprazole dosages approximately 3.4-34 times the human dosage of 40 mg daily (based on BSA) resulted in dose-dependent increases in embryolethality.

A population-based retrospective cohort epidemiologic study using data from the Swedish Medical Birth Registry reported on outcomes in infants whose mothers used omeprazole during pregnancy; most (about 86%) were exposed to omeprazole during the first trimester, 5% during and beyond the first trimester, and about 14% were exposed only after the first trimester of pregnancy. The number of infants exposed to omeprazole in utero with any malformation, low birth weight, low Apgar score, or hospitalization was similar to the number in this population. 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 this population.

In a population-based retrospective cohort study in Denmark reporting on 1800 live births whose mothers received omeprazole during the first trimester and 837,317 live births whose mothers did not receive a PPI, the overall rate of birth defects was 2.9% in infants whose mothers received omeprazole during the first trimester and 2.6% in infants born to mothers not exposed to any PPI during the first trimester.

In a retrospective cohort study, the incidence of congenital malformations in 689 women who received omeprazole or histamine H2-antagonists in the first trimester of pregnancy was compared with a control group of women who were not exposed to acid-suppressant drugs. The malformation rate associated with histamine H2-antagonists exposure was 5.5%, the malformation rate for nonexposed women was 4.1%, and the malformation rate associated with omeprazole exposure was 3.6%.

A small prospective cohort study followed women exposed to omeprazole (89% during the first trimester) during pregnancy; major congenital malformations occurred in 4% of live births in omeprazole-exposed women, 2.8% of disease-paired controls, and 2% exposed to non-teratogenic agents. Rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight were similar among the groups.

The manufacturers state that several studies reported that adverse short-term effects were not observed in infants when a single oral or IV dose of omeprazole was administered to pregnant women as premedication for cesarean section under general anesthesia.

Available data on sodium bicarbonate administration during pregnancy have not identified a drug-associated risk of major fetal malformations or miscarriage.

Because amoxicillin is distributed into milk and may lead to sensitization of infants, the drug should be used with caution in nursing women. Because of its general safety in infants, CDC states that amoxicillin is an option for anti-infective prophylaxis in breast-feeding women when B. anthracis is known to be penicillin susceptible and there is no contraindication to maternal amoxicillin use.

Clarithromycin should be used with caution in nursing women. The drug is distributed into milk. In 12 women who received oral clarithromycin in a dosage of 250 mg twice daily for 6 days, mean peak concentrations of clarithromycin and 14-hydroxyclarithromycin in milk were 25 and 75%, respectively, of corresponding serum concentrations. Pre-weaned rats, exposed indirectly via consumption of milk from dams treated with 150 mg/kg daily of clarithromycin for 3 weeks, did not demonstrate adverse effects despite evidence indicating higher drug concentrations in milk than in plasma.

Limited data suggest omeprazole is distributed into human milk. The effects of omeprazole on milk production and on the breast-fed infant are unknown. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for the drug and any potential adverse effects on the breast-fed infant from omeprazole or from the underlying maternal condition.

Although the elimination rate of omeprazole is somewhat decreased in geriatric patients and the bioavailability increased, no adjustment of the usual recommended dosage is required in geriatric patients.

In US and European clinical trials, more than 2000 patients treated with omeprazole were >=65 years of age. Although no overall differences in efficacy or safety were observed between geriatric and younger patients, and other clinical experience revealed no evidence of age-related differences, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.