Amoxicil-Clarithromy-Lansopraz (lansoprazole/amoxicillin trihydrate/clarithromycin)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Amoxicillin is an aminopenicillin antibiotic that is structurally related to ampicillin.
Clarithromycin is a semisynthetic macrolide antibiotic with a broader spectrum than that of erythromycins.
Lansoprazole, commonly referred to as an acid- or proton-pump inhibitor, is a gastric antisecretory agent.
Lansoprazole is a substituted benzimidazole gastric antisecretory agent. Lansoprazole is structurally and pharmacologically related to dexlansoprazole, esomeprazole, omeprazole, pantoprazole, and rabeprazole; lansoprazole differs structurally from omeprazole by the presence of a trifluoroethoxy group in position 4 of the pyridine ring and the absence of methyl and methoxy groups on the pyridine and benzimidazole rings, respectively. The drugs are chemically and pharmacologically unrelated to H2-receptor antagonists, antimuscarinics, or prostaglandin analogs.
Lansoprazole is a racemic mixture of R- and S-isomers. Both isomers inhibit hydrogen/potassium adenosine triphosphatase (H+K+-exchanging ATPase), but plasma clearance of the R-isomer (dexlansoprazole) is slower than that of the S-isomer; following oral administration of racemic lansoprazole, plasma concentrations of the R-isomer are markedly higher than those of the S-isomer.
Lansoprazole binds to H+K+-exchanging ATPase in gastric parietal cells; inactivation of this enzyme system (also known as the proton, hydrogen, or acid pump) blocks the final step in the secretion of hydrochloric acid by these cells. Therefore, gastric antisecretory agents such as lansoprazole are commonly referred to as acid- or proton-pump inhibitors. Lansoprazole, a weak base, does not directly inhibit this enzyme system, but instead, it concentrates under the acid conditions of the parietal cell secretory canaliculi, where the drug undergoes rearrangement to active sulfenamide metabolites; these active metabolites then react with the sulfhydryl groups of H+K+-exchanging ATPase inactivating the proton pump.
Because the sulfenamide metabolites form an irreversible covalent bond to H+K+-exchanging ATPase, acid secretion is inhibited until additional enzyme is synthesized, resulting in a prolonged duration of action.
Lansoprazole inhibits basal and stimulated gastric acid secretion; in addition, because the drug inhibits the final step in the secretory pathway, it inhibits such secretion regardless of the stimulus. The degree of inhibition of gastric acid secretion is related to the dose and duration of therapy, but lansoprazole is a more potent inhibitor of such secretion than are H2-receptor antagonists. Following oral administration of 15 or 30 mg of lansoprazole, inhibition of gastric acid secretion is apparent within 2-3 or 1-2 hours, respectively.
After multiple daily doses, increased gastric pH is apparent within 1 hour of administration of 30 mg of lansoprazole and within 1-2 hours after administration of 15 mg of the drug.
Although lansoprazole has a short terminal plasma half-life, the drug has a long duration of action (secondary to the prolonged presence of active lansoprazole metabolites within the parietal cell where they bind to H+K+-exchanging ATPase). Following continuous oral administration of 15 or 30 mg of lansoprazole, the percent of time during a 24-hour period that the gastric pH exceeds 4 is 49 or 66%, respectively. Inhibition of basal gastric secretion is 71% after an initial oral dose of 30 mg and 80% or greater after 7 days of oral administration of 30 mg of lansoprazole daily.
Stimulated gastric secretion initially is reduced 81% after an oral dose of 30 mg of lansoprazole and gastric secretion is reduced 88% after 7 days of oral administration of 30 mg of lansoprazole daily. Oral administration of lansoprazole 60 mg produced almost complete inhibition of gastric acid secretion in some patients. Following discontinuance of lansoprazole therapy, gastric acid secretion returns to baseline over a 2- to 4-day period, without rebound gastric acidity.
The degree of inhibition of gastric acid secretion is similar following oral or IV administration (a parenteral formulation no longer is commercially available in the US) of lansoprazole 30 mg daily for 7 days in healthy individuals. Following oral or IV administration of the drug, the percent of time during a 24-hour period that the gastric pH exceeds 4 is about 67 or 71%, respectively, after an initial dose of 30 mg and about 78 or 80%, respectively, after 5 days of administration of lansoprazole 30 mg daily in healthy individuals.
Lansoprazole increases plasma gastrin concentrations; this increase occurs in response to a negative feedback mechanism resulting from decreased gastric acid secretion. Although a single oral dose of 30 mg of lansoprazole did not affect serum gastrin levels in healthy adults, patients with gastric ulcer receiving 30-60 mg of lansoprazole once daily for 2 months developed a 50-100% increase from baseline in median fasting serum gastrin concentration; however, median serum gastrin levels remained within the normal range. Serum gastrin concentrations reach a plateau within 2 months of lansoprazole therapy and return to pretreatment values within 1-12 weeks after discontinuing therapy with the drug.
Although marked hypergastrinemia with subsequent enterochromaffin-like (ECL) cell proliferation and carcinoid lesions have been observed in animal studies, no evidence of similar ECL cell effects were observed in patients receiving the drug for periods of at least one year. Longer-term study and experience are needed to rule out the possibility of an increased risk of gastric tumors in patients receiving prolonged lansoprazole therapy.
Lansoprazole also decreases pepsin secretion and activity and increases serum pepsinogen; however, these effects are not as pronounced as the drug's inhibition of gastric acid secretion. Suppression of pepsin activity appears to be secondary to increased gastric pH, as conversion of the inactive precursor pepsinogen to pepsin requires an acidic gastric milieu. Pepsin output is inhibited in healthy adults receiving 30 mg of lansoprazole daily for 7 days in the morning or evening by 42-58 or 67-88%, respectively.
When the dose is increased to 60 mg daily, no additional inhibition of pepsin secretion is observed. Pepsin activity also is inhibited by lansoprazole 30 mg daily administered in the morning or evening by 23 or 35%, respectively. Lansoprazole also substantially prolongs gastric emptying of digestible solids, but does not appear to affect lower esophageal sphincter pressure.
Lansoprazole can suppress Helicobacter pylori (formerly Campylobacter pylori or C. pyloridis) in patients with gastric or duodenal ulcers infected with the organism. Combined therapy with lansoprazole and one or more appropriate anti-infectives (e.g., amoxicillin, clarithromycin) can effectively eradicate H. pylori gastric infection.
Lansoprazole is extensively metabolized in the liver. Cytochrome P-450 (CYP) isoenzymes 2C19 and 3A4 are involved in the metabolism of the drug. Following single-dose oral administration of lansoprazole, approximately one-third of the administered dose is eliminated in urine and two-thirds in feces; unchanged drug is not recovered in urine.
Therapy with proton-pump inhibitors, particularly in high dosages and/or for prolonged periods of time, may be associated with an increased risk of osteoporosis-related fractures of the hip, wrist, or spine. The mechanism by which these drugs may increase risk of such fractures has not been elucidated but may involve decreased insoluble calcium absorption secondary to increased gastric pH.
Amoxicillin shares the uses of other aminopenicillins and is used principally for the treatment of infections caused by susceptible gram-negative bacteria (e.g., Haemophilus influenzae, Escherichia coli, Proteus mirabilis, Salmonella). Amoxicillin also is used for the treatment of infections caused by susceptible gram-positive bacteria (e.g., Streptococcus pneumoniae, enterococci, nonpenicillinase-producing staphylococci, Listeria); however, like other aminopenicillins, amoxicillin generally should not be used for the treatment of streptococcal or staphylococcal infections when a natural penicillin would be effective.
Generic name: lansoprazole/amoxicillin trihydrate/clarithromycin
Pronunciation: (lan-SOE-pra-zole/a-MOX-i-SIL-in/kla-RITH-roe-MYE-sin)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Amoxicil-Clarithromy-Lansopraz
Indications
The following indications are listed for Amoxicil-Clarithromy-Lansopraz:
- Duodenal Ulcer Due To H. Pylori
- Helicobacter Pylori Gastritis
Also known as: Campylobacter Gastritis, Du Due To H. Pylori, Duodenal Ulcer Due To Campylobacter Pylori, Duodenal Ulcer Due To Helicobacter Pylori, H. Pylori Gastritis.
Dosing
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.
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.
Lansoprazole is administered orally. Lansoprazole also has been administered by IV infusion; however, a parenteral dosage form no longer is commercially available in the US.
If a dose of lansoprazole is missed, the dose should be taken as soon as possible. However, if the next scheduled dose is due, the missed dose should be omitted, and the next dose taken at the regularly scheduled time. A double dose should not be administered to make up for a missed dose.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Known severe hypersensitivity to lansoprazole or any ingredient in the formulation.
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 reactions
Adverse effects occurring in 1% or more of patients receiving oral lansoprazole and more frequently than with placebo include abdominal pain, diarrhea, nausea, and constipation.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of oral lansoprazole in pediatric patients 1-17 years of age have been established for short-term treatment of symptomatic gastroesophageal reflux disease (GERD) and erosive esophagitis. In an open-label study in children 1-11 years of age, symptomatic improvement occurred following 8-12 weeks of lansoprazole therapy in 76% of children with symptomatic GERD; in a limited subset of children with endoscopically documented erosive esophagitis, rates of symptomatic improvement and healing were 81 and 100%, respectively. Lansoprazole was initiated at a dosage of 15 mg daily in children weighing 30 kg or less and a dosage of 30 mg daily in those weighing more than 30 kg; dosage could be increased up to 30 mg twice daily in children who continued to experience symptoms 2 or more weeks after initiating therapy with the drug. In an open-label study in adolescents 12-17 years of age with GERD, symptomatic improvement occurred following 8 weeks of therapy with lansoprazole 15 mg daily in 71% of those with nonerosive disease; in a smaller group of adolescents with erosive esophagitis, rates of symptomatic improvement and healing were 78 and 96%, respectively, following 8-12 weeks of therapy with lansoprazole 30 mg daily. The most commonly reported adverse effects in pediatric patients receiving lansoprazole include headache, abdominal pain, constipation, nausea, and dizziness.
Efficacy of oral lansoprazole has not been established in infants younger than 1 year of age. In a controlled study in infants 1 month to younger than 1 year of age with symptomatic GERD, lansoprazole was no more effective than placebo in reducing feeding-associated episodes of crying, fussing, or irritability; in both the placebo and lansoprazole groups, the response rate was 54%.
Safety and efficacy of lansoprazole for self-medication of frequent heartburn have not been established in children younger than 18 years of age.
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.
Category B.
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.
Lansoprazole or its metabolites are distributed into milk in rats; it is not known whether lansoprazole is distributed into human milk. The manufacturer states that a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
The frequency of adverse effects in geriatric patients appears to be similar to that in younger patients. Clearance of lansoprazole may be decreased in geriatric patients, but accumulation of the drug does not occur with once-daily dosing and dosage adjustment is not necessary.
ICD codes
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Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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