Amoxicillin / Lansoprazole / Clarithromycin

Pronunciation: a-MOX-i-SIL-in/lan-SOE-pra-zole/kla-RITH-roe-MYE-sin
Class: Helicobacter Pylori Agent

Trade Names

Prevpac
- Capsules and tablets, oral lansoprazole 30 mg delayed-release capsules, amoxicillin 500 mg capsules, clarithromycin 500 mg tablets

Hp-PAC (Canada)

Pharmacology

Amoxicillin

Inhibits bacterial cell wall mucopeptide synthesis.

Clarithromycin

Inhibits microbial protein synthesis.

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Lansoprazole

Suppresses gastric acid secretion by blocking acid (proton) pump within gastric parietal cells.

Indications and Usage

Eradication of H. pylori to reduce risk of duodenal ulcer recurrence.

Contraindications

Coadministration with astemizole, cisapride, dihydroergotamine, ergotamine, pimozide, or terfenadine; known hypersensitivity to any component of formulation, any macrolide antibiotic, or any penicillin.

Dosage and Administration

Adults

PO Lansoprazole 30 mg/amoxicillin 1 g/clarithromycin 500 mg given together twice daily (morning and evening) for 10 to 14 days.

Renal function impairment
Adults

PO This combination therapy is not recommended in patients with CrCl less than 30 mL/min.

Hepatic function impairment
Adults

PO Consider dosage reduction of lansoprazole in patients with severe hepatic disease.

General Advice

  • Administer all 4 pills twice daily (morning and evening) before meals.
  • Instruct patients to not open capsules or chew or crush tablets; each pill should be swallowed whole.

Storage/Stability

Store between 68° and 77°F. Protect from light and moisture.

Drug Interactions

No drug interaction studies have been conducted specifically for amoxicillin/clarithromycin/lansoprazole. The following drug interactions are for the individual drug components. Therefore, the decision to adjust dosage should depend on the cumulative or net effect of the drug components.

Amoxicillin Live vaccines

Amoxicillin may decrease the effectiveness of live vaccines. Coadministration is not recommended.

Methotrexate

Serum methotrexate concentrations may be elevated, increasing the risk of toxicity. Close clinical and methotrexate concentration monitoring is advised when amoxicillin is coadministered.

Oral contraceptives

The efficacy of oral contraceptives may be reduced. Although infrequently reported, contraceptive failure is possible; the use of an additional form of contraception during amoxicillin therapy is advisable.

Probenecid

Probenecid decreases renal tubular secretion of amoxicillin, which may result in increased and prolonged blood levels of amoxicillin.

Tetracyclines (eg, doxycycline)

The pharmacologic and therapeutic actions of amoxicillin could be reduced. Avoid this combination if possible.

Clarithromycin Cabergoline

Cabergoline plasma concentrations may be elevated, increasing the risk of toxicity. If coadministration cannot be avoided, carefully monitor the clinical response of the patient, especially patients with Parkinson disease who have shown levodopa-induced psychosis or dyskinesia.

Cimetidine

The antimicrobial effects of clarithromycin may be decreased. Closely monitor the response to clarithromycin and adjust the clarithromycin dose as needed.

Clopidogrel

The antiplatelet effect of clopidogrel may be inhibited by clarithromycin. Closely monitor platelet function and adjust the clopidogrel dose as needed. Azithromycin may be a safer alternative. (See Lansoprazole-Clopidogrel.)

Colchicine

Risk of colchicine toxicity may be increased, especially in elderly patients. Deaths have been reported. If coadministration cannot be avoided, the colchicine dose should be reduced.

Digoxin

Elevated serum digoxin levels may occur, increasing the risk of toxicity. Monitor digoxin concentrations and adjust dose as needed.

Diltiazem, fluconazole, grapefruit juice

Clarithromycin plasma levels may be elevated, increasing the risk of adverse effects. If coadministration cannot be avoided, use with caution and closely monitor the patient.

Drugs primarily metabolized by CYP3A4 (eg, alfuzosin, benzodiazepines [eg, alprazolam, midazolam, triazolam], brentuximab, bromocriptine, buspirone, carbamazepine, cilostazol, cinacalcet, conivaptan, cyclosporine, dihydroergotamine, disopyramide, docetaxel, dronedarone, efavirenz, erlotinib, eszopiclone, etravirine, everolimus, felodipine, HMG-CoA reductase inhibitors [eg, lovastatin, simvastatin], iloperidone, imatinib, ixabepilone, lurasidone, methylprednisolone, nifedipine, opioid analgesics [eg, alfentanil, fentanyl, oxycodone], phosphodiesterase type 5 inhibitors [eg, sildenafil, tadalafil, vardenafil], romidepsin, salmeterol, silodosin, sirolimus, tacrolimus, tamsulosin, temsirolimus, ticagrelor, tolvaptan, toremifene, trazodone, tyrosine kinase inhibitors [eg, lapatinib, nilotinib, pazopanib], verapamil)

Plasma concentrations of these agents may be elevated, increasing the pharmacologic effects and risk of adverse reactions or toxicity. If concurrent use is not contraindicated in the respective product information, use with caution and monitor patients for adverse reactions. Dose reduction or alternative antibacterial treatment should be considered. (See Lansoprazole-Erlotinib, Lansoprazole-Tacrolimus, and Lansoprazole-Tyrosine Kinase Receptor Inhibitors.)

Drugs that prolong the QT interval (eg, antiarrhythmic agents [eg, amiodarone, bretylium, disopyramide, dofetilide, procainamide, quinidine, sotalol], arsenic trioxide, chloroquine, chlorpromazine, cisapride, dolasetron, droperidol, gatifloxacin, halofantrine, haloperidol, lapatinib, levomethadyl, maprotiline, mefloquine, mesoridazine, methadone, moxifloxacin, paliperidone, pazopanib, pentamidine, pimozide, probucol, quinupristin/dalfopristin, sparfloxacin, tacrolimus, tetrabenazine, thioridazine, tricyclic antidepressants [eg, desipramine], vandetanib, ziprasidone)

Consider prolongation of the QT interval with possible development of cardiac arrhythmias, including torsades de pointes, when clarithromycin is administered with these agents. Caution is advised when 2 agents that are suspected to prolong the QT interval are used concomitantly. If concurrent use is not contraindicated in the respective product information, monitor patients for QT prolongation, especially when adding clarithromycin to a stable regimen of another QT prolonging agent or vice versa.

Eletriptan

Eletriptan plasma concentrations may be elevated, increasing the pharmacologic and toxic effects. Eletriptan should not be taken within 72 h of potent CYP3A4 inhibitors (eg, clarithromycin).

Eplerenone

Plasma concentrations of eplerenone may be elevated, increasing the risk of hyperkalemia and associated serious arrhythmias. Eplerenone is contraindicated in patients receiving clarithromycin.

Ergot derivatives (dihydroergotamine, ergotamine)

Coadministration with clarithromycin is contraindicated. Coadministration of clarithromycin with dihydroergotamine or ergotamine may increase the risk of acute ergotism.

HIV protease inhibitors (eg, atazanavir)

Clarithromycin doses greater than 1,000 mg daily should not be administered with protease inhibitors. Alternative antibacterial therapy should be considered for treatment of infections other than Mycobacterium avium complex. (See Lansoprazole-Protease Inhibitors.)

Maraviroc

Maraviroc concentration/toxicity may be increased. Maraviroc dosage adjustment is recommended during coadministration. Concurrent use is contraindicated in patients with severe renal impairment (CrCl of 30 mL/min).

Muscarinic receptor antagonists (eg, darifenacin, fesoterodine, solifenacin, tolterodine)

Muscarinic receptor antagonist serum concentrations may be elevated, increasing the pharmacologic effect and risk of adverse reactions. When administered with clarithromycin, the dose of darifenacin should not exceed 7.5 mg daily, the dose of fesoterodine should not exceed 4 mg daily, the dose of tolterodine should not exceed 2 mg daily, and the dose of solifenacin should not exceed 5 mg daily.

Nevirapine

Clarithromycin plasma concentrations may be reduced, while 14-OH-clarithromycin concentrations may be increased. Consider alternative antibacterial treatment.

Quetiapine

Quetiapine plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Closely monitor patients when clarithromycin is started or stopped. The quetiapine dose may need to be adjusted.

Ranolazine

Increased ranolazine plasma concentrations with cardiotoxicity may occur. Coadministration is contraindicated.

Repaglinide

Coadministration may increase repaglinide plasma levels, increasing the pharmacologic and adverse effects. Monitor blood glucose levels carefully and adjust the repaglinide dose as needed.

Rifamycins (eg, rifabutin)

Antimicrobial effects of clarithromycin may be decreased, while the adverse effects of rifamycins may be increased. Azithromycin may be a safer alternative.

Saxagliptin

Saxagliptin concentration/toxicity may be increased. Limit the dose of saxagliptin to 2.5 mg daily in patients receiving clarithromycin.

Sulfonylureas (eg, glipizide, glyburide)

Hypoglycemic action of sulfonylureas may be increased. Monitor blood glucose and observe patients for signs of hypoglycemia when starting clarithromycin.

Theophylline

May increase theophylline plasma concentration; monitor theophylline levels.

Vilazodone

Vilazodone concentration/toxicity may be increased. The vilazodone dose should be reduced to 20 mg in patients receiving clarithromycin.

Warfarin

The anticoagulant effect may be increased, increasing the risk of hemorrhage. Monitor anticoagulant parameters and adjust the warfarin dose as needed. (See Lansoprazole-Warfarin.)

Zidovudine

Serum levels may be increased or decreased by clarithromycin. Separate the administration times by at least 2 h.

Lansoprazole Azole antifungals (eg, itraconazole, ketoconazole)

The bioavailability of certain azole antifungals may be decreased because of a possible reduction in tablet dissolution in the presence of a high gastric pH. Lansoprazole concentrations may be increased. Avoid coadministration if possible.

Calcium salts

The inhibition of gastric acid secretion may interfere with the GI absorption of calcium salts. Closely monitor the clinical response to calcium. Larger dosages of calcium may be needed.

Clopidogrel

The antiplatelet activity of clopidogrel may be decreased by lansoprazole. Use with caution. (See Clarithromycin-Clopidogrel.)

Erlotinib

Plasma concentration and pharmacologic effects of erlotinib may be decreased. Avoid coadministration. (See Clarithromycin-Drugs Primarily Metabolized by CYP3A4.)

Fluvoxamine

Lansoprazole plasma concentrations may be elevated, increasing the risk of adverse reactions. Monitor for an increase in adverse reactions.

Mycophenolate

Plasma concentrations and pharmacologic effects of mycophenolate may be decreased. An interaction is not expected with enteric-coated mycophenolate sodium.

Protease inhibitors (eg, atazanavir, indinavir, saquinavir)

Significant reduction in protease inhibitor exposure may occur with coadministration. Lansoprazole substantially decreases the systemic concentrations of atazanavir, which is dependent on the presence of gastric acid for absorption, and may result in the loss of therapeutic effect of atazanavir and the development of HIV resistance. In contrast, plasma concentrations of saquinavir may be increased. Coadministration of lansoprazole and protease inhibitors is not recommended. If saquinavir is coadministered, monitor the patient for saquinavir-related adverse reactions. (See Clarithromycin-HIV Protease Inhibitors.)

Rilpivirine

Plasma concentrations and pharmacologic effects of rilpivirine may be reduced, possibly resulting in loss of virologic response or resistance. Coadministration is contraindicated.

Salicylates (eg, aspirin)

Enteric-coated salicylates may dissolve more rapidly, increasing gastric adverse reactions. Avoid concurrent use in patients at risk of serious gastric disorders caused by salicylate release.

Sucralfate

Coadministration delays absorption and bioavailability of lansoprazole. Administer lansoprazole at least 30 min before sucralfate.

Tacrolimus

Tacrolimus plasma concentrations may be increased. Closely monitor tacrolimus trough concentrations when lansoprazole is started or stopped. Clinical monitoring for signs and symptoms of toxicity is also advised. (See Clarithromycin-Drugs Primarily Metabolized by CYP3A4.)

Tyrosine kinase receptor inhibitors (eg, dasatinib, lapatinib, nilotinib)

Plasma concentrations and pharmacologic effects of these agents may be decreased by lansoprazole. Concomitant use of lansoprazole with dasatinib is not recommended. Coadministration of lansoprazole with nilotinib should be undertaken with caution. (See Clarithromycin-Drugs Primarily Metabolized by CYP3A4.)

Voriconazole

Plasma concentrations and pharmacologic effects of lansoprazole may be elevated, increasing the risk of adverse reactions. Close clinical monitoring is indicated.

Warfarin

There have been reports of increased INR and prothrombin time with coadministration. Monitor anticoagulant activity and adjust the warfarin dose as needed. (See Clarithromycin-Warfarin.)

Laboratory Test Interactions

Amoxicillin

May cause false-positive urine glucose test results with Benedict solution, Fehling solution, or Clinitest tablets (enzyme-based tests, such as Clinistix, are recommended); in pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol may occur.

Adverse Reactions

CNS

Headache (6%); confusion, dizziness (less than 3%).

Dermatologic

Skin reactions (less than 3%).

GI

Diarrhea (7%); taste perversion (5%); abdominal pain, dark stools, dry mouth/thirst, glossitis, nausea, oral moniliasis, rectal itching, stomatitis, tongue discoloration, tongue disorder, vomiting (less than 3%).

Genitourinary

Vaginitis, vaginal moniliasis (less than 3%).

Musculoskeletal

Myalgia (less than 3%).

Respiratory

Respiratory disorders (less than 3%).

Precautions

Monitor

Periodically assess renal, hepatic, and hematopoietic function during prolonged therapy.


Pregnancy

Category C .

Lactation

Amoxicillin

Excreted.

Clarithromycin/Lansoprazole

Undetermined.

Children

Safety and efficacy not established.

Elderly

Because these patients may suffer from asymptomatic renal or hepatic impairment, administer with caution.

Hypersensitivity

Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions may occur; because cross-allergenicity with cephalosporins may occur in patients with a history of penicillin hypersensitivity, use with caution in patients allergic to either class of antibiotic.

Renal Function

Do not use in patients with a CrCl less than 30 mL/min.

Superinfection

Prolonged use may result in bacterial and fungal overgrowth.

Clostridium difficile –associated diarrhea

C. difficile –associated diarrhea has been reported with use of nearly all antibacterial agents, including clarithromycin and/or amoxicillin, and may range in severity from mild diarrhea to fatal colitis.

Gastric malignancy

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

Myasthenia gravis

Clarithromycin may exacerbate symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome.

Overdosage

Symptoms

Amoxicillin

Interstitial nephritis leading to oliguric renal failure; crystalluria leading to renal failure.

Clarithromycin

GI symptoms (eg, abdominal pain, diarrhea, nausea, vomiting).

Patient Information

  • Inform patient that each dose consists of 4 pills and should be taken twice daily before meals.
  • Advise patient not to open capsules or crush or chew tablet; pills should be swallowed whole.
  • Advise patient that the entire course of therapy (10 or 14 days) must be completed to ensure maximal benefit and to complete the full course of therapy even if symptoms have resolved.
  • Clarithromycin may interact with some drugs; therefore, advise patients to report to their health care provider the use of any other medications.
  • Inform patients that diarrhea is a common problem caused by antibiotics that usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken the last dose of the antibiotic.
  • Inform patient that headache, abnormal taste, and GI symptoms are the most common adverse reactions. Inform health care provider if any symptoms occur and are intolerable.
  • Advise patients to discontinue therapy and contact their health care provider immediately if skin rash, hives, itching, or shortness of breath occurs.

Copyright © 2009 Wolters Kluwer Health.

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