chapter
Proton pump inhibitors
Pages 5

No dose adjustment is recommended. Interaction is considered useful for Helicobacter pylori eradication

PROTON PUMP INHIBITORS

ANTICANCER AND IMMUNOMODULATING DRUGS

OMEPRAZOLE IMATINIB ≠ plasma concentrations, with risk of toxic effects of these drugs

Imatinib is a potent inhibitor of CYP2C9 isoenzymes, which metabolize these drugs

Watch for the early toxic effects of these drugs. If necessary, consider using alternative drugs while the patient is being given imatinib

PROTON PUMP INHIBITORS

METHOTREXATE Likely ≠ plasma concentrations of methotrexate and ≠ risk of toxic effects, e.g. blood dyscrasias, liver cirrhosis, pulmonary toxicity, renal toxicity

Attributed to omeprazole ↓ renal elimination of methotrexate

Monitor clinically and biochemically for blood dyscrasias, liver toxicity, renal toxicity and pulmonary toxicity

OMEPRAZOLE CICLOSPORIN Conflicting information. Possible altered efficacy of ciclosporin

Unclear Monitor closely. Studies have reported combination use with no significant changes in ciclosporin levels

Altered metabolism from CYP2C19 to CYP3A4 in patients with low CYP2C19 levels

Monitor levels more closely

PROTON PUMP INHIBITORS

ANTICOAGULANTS – ORAL

Possibly ≠ anticoagulant effect when esomeprazole, lansoprazole or omeprazole is added to warfarin

Uncertain at present. Omeprazole and lansoprazole are known to induce CYP1A2, which plays a role in the activation of coumarins

Monitor INR more closely. ↓ dose may be required. If values are 10%, 20% or 30% over range, omit the dose for 1, 2 or 3 days respectively, and consider ↓ maintenance dose by 10%. Regular dosing of a proton pump inhibitor is preferable if it affects INR significantly. Not reported with pantoprazole or rabeprazole

PROTON PUMP INHIBITORS

ANTIDEPRESSANTS

OMEPRAZOLE/ ESOMEPRAZOLE

MAOIs – MOCLOBEMIDE

Possible ≠ efficacy and adverse effects of moclobemide

Inhibition of CYP2C19 Monitor more closely. Effect is seen only in extensive CYP2C19 metabolizers. ↓ dose may be required

OMEPRAZOLE SSRIs – FLUVOXAMINE ↓ fluvoxamine levels with loss of therapeutic efficacy

Inhibition of CYP1A2-mediated metabolism

Monitor for lack of therapeutic effect. When omeprazole is withdrawn, monitor for fluvoxamine toxicity

PROTON PUMP INHIBITORS

ANTIDIABETIC DRUGS – SULPHONYLUREAS

Possible ≠ efficacy and adverse effects of sulphonylurea, e.g. hypoglycaemia

Possible ≠ absorption Monitor capillary blood glucose more closely; ↓ dose may be required

PROTON PUMP INHIBITORS

ANTIEPILEPTICS

PROTON PUMP INHIBITORS

CARBAMAZEPINE Possible altered efficacy of carbamazepine

Unclear; possibly via ↓ clearance Use with caution. Monitor carbamazepine levels when starting or stopping therapy, and use the proton pump inhibitor regularly, not PRN. Not reported with pantoprazole or rabeprazole

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DRUGS ACTING ON THE GASTROINTESTINAL TRACT PROTON PUMP INHIBITORS

Unclear; possible altered metabolism via CYP2C19

↓ dose may be required. Use the proton pump inhibitor regularly, not PRN. Monitor phenytoin levels when starting or stopping treatment. Patients have received omeprazole for 3-5 weeks without altered phenytoin levels. Not reported with pantoprazole or rabeprazole

PROTON PUMP INHIBITORS

ANTIFUNGALS

PROTON PUMP INHIBITORS

ITRACONAZOLE, KETOCONAZOLE

Possible ↓ efficacy of antifungal ↓ absorption Monitor for ↓ efficacy; ≠ dose may be required. Separate doses by at least 2 hours and give ketoconazole with a carbonated drink

OMEPRAZOLE VORICONAZOLE Possible ≠ efficacy and adverse effects of both drugs

1. Inhibition of voriconazole metabolism via CYP2C19 and CYP3A4 2. Inhibition of metabolism of omeprazole

1. No dose adjustment of voriconazole recommended 2. Half omeprazole dose

PROTON PUMP INHIBITORS

ANTIPLATELET AGENTS

PROTON PUMP INHIBITORS

DIPYRIDAMOLE Possible ↓ bioavailability of dipyridamole

Dipyridamole tablets require an acidic environment for adequate dissolution; ≠ pH of the stomach impairs dissolution and may therefore ↓ absorption of the drug

≠ dose of dipyridamole or consider using an alternative antiplatelet drug

suffer reinfarction with concomitant proton pump inhibitor treatment

Proton pump inhibitors inhibit CYP2C19, which converts clopidogrel to the active metabolite

Pantoprazole is not known as yet to cause this effect. Consider using acid suppression therapy with H2 blockers when clopidogrel is used as secondary prevention of coronary heart disease

OMEPRAZOLE ANTIPSYCHOTICS – CLOZAPINE

Possible ↓ efficacy of clozapine ≠ metabolism via CYP1A2 Clinical significance unclear; monitor more closely

PROTON PUMP INHIBITORS

ANTIVIRALS – PROTEASE INHIBITORS

PROTON PUMP INHIBITORS

ATAZANAVIR, NELFINAVIR

↓ plasma levels of atazanavir and nelfinavir with esomeprazole, and ≠ risk of therapeutic failure of the antiviral agent

Uncertain; possibly due to enzyme induction

Avoid co-administration

PROTON PUMP INHIBITORS

SAQUINAVIR Significantly ≠ plasma concentrations of saquinavir during concomitant treatment with esomeprazole. ≠ risk of toxic effects of saquinavir

Uncertain FDA in April 2009 recommended that patients should be monitored for toxic effects of saquinavir and that ↓ dose of saquinavir may be required

OMEPRAZOLE INDINAVIR Possibly ↓ plasma concentrations and ↓ efficacy of indinavir

Uncertain ≠ dose of indinavir from 800 mg three times a day to 1 g three times a day, or preferably add ritonavir 200 mg once daily

OMEPRAZOLE/ ESOMEPRAZOLE

ANXIOLYTICS AND HYPNOTICS – BZDs

≠ efficacy and adverse effects, e.g. prolonged sedation

Inhibition of metabolism via CYP450 (some show competitive inhibition via CYP2C19)

Monitor for ≠ side-effects; ↓ dose as necessary. May take longer for patients to recover from interventions or surgical procedures, particularly when BZDs have been used. Consider an alternative proton pump inhibitor, e.g. lansoprazole or pantoprazole

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DRUGS ACTING ON THE GASTROINTESTINAL TRACT PROTON PUMP INHIBITORS

Omeprazole inhibits CYP2D6-and CYP2C19-mediated metabolism of propanolol

Monitor BP at least weekly until stable

OMEPRAZOLE CALCIUM CHANNEL BLOCKERS – NIFEDIPINE

Possible ≠ efficacy and adverse effects

Small ≠ bioavailability possible via ≠ intragastric pH

Unlikely to be clinically significant

PROTON PUMP INHIBITORS

CARDIAC GLYCOSIDES – DIGOXIN

Plasma concentrations of digoxin are possibly ≠ by proton pump inhibitors

Small ≠ bioavailability, possibly via ≠ intragastric pH or altered intestinal P-gp transport

Not thought to be clinically significant unless a poor CYP2C19 metabolizer. No specific recommendations. Different proton pump inhibitors may interact differently – monitor if changing therapy or doses

PROTON PUMP INHIBITORS

CNS STIMULANTS – MODAFINIL

May cause moderate ≠ plasma concentrations of these substrates

Modafinil is a reversible inhibitor of CYP2C19 when used in therapeutic doses

Be aware

OMEPRAZOLE DRUG DEPENDENCE THERAPIES – DISULFIRAM

Possible ≠ adverse effects of disulfiram

Accumulation of metabolites Monitor closely for ≠ side-effects, although patients have received the combination without reported problems

PROTON PUMP INHIBITORS

LIPID-LOWERING DRUGS – ATORVASTATIN

Possible ≠ efficacy and adverse effects of atorvastatin

Inhibition of P-gp; ↓ first pass clearance

Monitor closely

LANSOPRAZOLE MUSCLE RELAXANTS – VECURONIUM

Possible ≠ efficacy and adverse effects of vecuronium

Unclear Altered duration of action. May need ≠ recovery time

LANSOPRAZOLE OESTROGENS – ORAL CONTRACEPTIVES

Possible altered efficacy of contraceptive

Unclear Clinical significance is uncertain. It would seem to be wise to advise patients to use an alternative form of contraception during and for 1 month after stopping co-administration with lansoprazole