PROTONIX® Drug Interactions

(pantoprazole sodium)

7 DRUG INTERACTIONS

Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with PROTONIX and instructions for preventing or managing them.

Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.

Table 4: Clinically Relevant Interactions Affecting Drugs Co-Administered with PROTONIX and Interactions with Diagnostics

Antiretrovirals

Clinical Impact:

The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with pantoprazole may reduce antiviral effect and promote the development of drug resistance.
Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with pantoprazole may increase toxicity of the antiretroviral drugs.
There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole.

Intervention:

Rilpivirine-containing products: Concomitant use with PROTONIX is contraindicated [see Contraindications (4)]. See prescribing information.

Atazanavir: See prescribing information for atazanavir for dosing information.

Nelfinavir: Avoid concomitant use with PROTONIX. See prescribing information for nelfinavir.

Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities.

Other antiretrovirals: See prescribing information.

Warfarin

Clinical Impact:

Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.

Intervention:

Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin.

Clopidogrel

Clinical Impact:

Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition [see Clinical Pharmacology (12.3)].

Intervention:

No dose adjustment of clopidogrel is necessary when administered with an approved dose of PROTONIX.

Methotrexate

Clinical Impact:

Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [see Warnings and Precautions (5.13)].

Intervention:

A temporary withdrawal of PROTONIX may be considered in some patients receiving high-dose methotrexate.

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole)

Clinical Impact:

Pantoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity.

Intervention:

Mycophenolate mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH [see Clinical Pharmacology (12.3)]. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PROTONIX and MMF. Use PROTONIX with caution in transplant patients receiving MMF.
See the prescribing information for other drugs dependent on gastric pH for absorption.

Interactions with Investigations of Neuroendocrine Tumors

Clinical Impact:

CgA levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors [see Warnings and Precautions (5.11), Clinical Pharmacology (12.2)].

Intervention:

Temporarily stop PROTONIX treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.

False Positive Urine Tests for THC

Clinical Impact:

There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs [see Warnings and Precautions (5.12)].

Intervention:

An alternative confirmatory method should be considered to verify positive results.

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Health Professional Information

Drug Interactions

7 DRUG INTERACTIONS

Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with PROTONIX and instructions for preventing or managing them.

Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.

Table 4: Clinically Relevant Interactions Affecting Drugs Co-Administered with PROTONIX and Interactions with Diagnostics

Antiretrovirals

Clinical Impact:

The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with pantoprazole may reduce antiviral effect and promote the development of drug resistance.
Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with pantoprazole may increase toxicity of the antiretroviral drugs.
There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole.

Intervention:

Rilpivirine-containing products: Concomitant use with PROTONIX is contraindicated [see Contraindications (4)]. See prescribing information.

Atazanavir: See prescribing information for atazanavir for dosing information.

Nelfinavir: Avoid concomitant use with PROTONIX. See prescribing information for nelfinavir.

Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities.

Other antiretrovirals: See prescribing information.

Warfarin

Clinical Impact:

Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.

Intervention:

Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin.

Clopidogrel

Clinical Impact:

Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition [see Clinical Pharmacology (12.3)].

Intervention:

No dose adjustment of clopidogrel is necessary when administered with an approved dose of PROTONIX.

Methotrexate

Clinical Impact:

Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [see Warnings and Precautions (5.13)].

Intervention:

A temporary withdrawal of PROTONIX may be considered in some patients receiving high-dose methotrexate.

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole)

Clinical Impact:

Pantoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity.

Intervention:

Mycophenolate mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH [see Clinical Pharmacology (12.3)]. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PROTONIX and MMF. Use PROTONIX with caution in transplant patients receiving MMF.
See the prescribing information for other drugs dependent on gastric pH for absorption.

Interactions with Investigations of Neuroendocrine Tumors

Clinical Impact:

CgA levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors [see Warnings and Precautions (5.11), Clinical Pharmacology (12.2)].

Intervention:

Temporarily stop PROTONIX treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.

False Positive Urine Tests for THC

Clinical Impact:

There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs [see Warnings and Precautions (5.12)].

Intervention:

An alternative confirmatory method should be considered to verify positive results.

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