Pantoprazole

Concomitant use not recommended. Pantoprazole substantially decreases atazanavir plasma concentrations, resulting in loss of therapeutic effect and development of drug resistance.

Proton pump inhibitors: e.g., Esomeprazole Lansoprazole Omeprazole Pantoprazole Rabeprazole ↓Rilpivirine Coadministration is contraindicated with JULUCA due to decreased rilpivirine concentrations [see Contraindications ( 4 )] .

Proton Pump Inhibitors: e.g., dexlansoprazole esomeprazole lansoprazole omeprazole pantoprazole rabeprazole ↓ RPV Coadministration is contraindicated due to potential for loss of virologic response and development of resistance.

Proton Pump Inhibitors: e.g., dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole ↓ RPV Coadministration is contraindicated due to potential for loss of virologic response and development of resistance.

Proton Pump Inhibitors: e.g., dexlansoprazole esomeprazole lansoprazole omeprazole pantoprazole rabeprazole ↓ RPV Coadministration is contraindicated due to potential for loss of virologic response and development of resistance.

Concomitant use not recommended. Pantoprazole substantially decreases nelfinavir plasma concentrations, resulting in loss of therapeutic effect and development of drug resistance.

Proton Pump Inhibitors: e.g., esomeprazole lansoprazole omeprazole pantoprazole rabeprazole ↓ rilpivirine Coadministration is contraindicated with rilpivirine tablets [see Contraindications (4) ] In addition to the drugs included in Table 6, the interaction between rilpivirine tablets and the following drugs was evaluated in clinical studies and no dose adjustment is needed for either drug [see Clinical Pharmacology ( 12.3 )] : acetaminophen, atorvastatin, chlorzoxazone, cabotegravir, ethinylestradiol, norethindrone, raltegravir, sildenafil, simeprevir and tenofovir disoproxil fumarate.

Proton Pump Inhibitors: e.g., esomeprazole lansoprazole omeprazole pantoprazole rabeprazole ↓ rilpivirine Coadministration is contraindicated with EDURANT or EDURANT PED [see Contraindications (4) ] .

Concomitant use of pantoprazole with methotrexate, particularly at high dose, may elevate and prolong serum concentrations of methotrexate and its metabolite hydroxymethotrexate, leading to toxicities.

Increased exposure of saquinavir when used concomitantly with pantoprazole may increase toxicity of the antiretroviral drug.

Concomitant use of pantoprazole and warfarin may increase INR and prothrombin time, leading to abnormal bleeding and potentially death.

Pantoprazole may decrease ampicillin esters absorption due to increased gastric pH.

CYP2C19 inhibitor with less effect on clopidogrel antiplatelet activity compared to omeprazole or esomeprazole.

CYP2C19 inhibitor with less effect on clopidogrel antiplatelet activity compared to omeprazole or esomeprazole.

Pantoprazole sodium can reduce absorption of dasatinib due to its effect on reducing intragastric acidity.

Pantoprazole sodium can reduce absorption of erlotinib due to its effect on reducing intragastric acidity.

Pantoprazole sodium can reduce absorption of iron salts due to its effect on reducing intragastric acidity.

Pantoprazole sodium can reduce absorption of ketoconazole due to its effect on reducing intragastric acidity.

Examples Lansoprazole, pantoprazole Drugs that Interfere with Enterohepatic Recirculation Clinical Impact Concomitant use with drugs that directly interfere with enterohepatic recirculation, or indirectly interfere with enterohepatic recirculation by altering the gastrointestinal flora, can decrease MPA systemic exposure [see Clinical Pharmacology ( 12.3 )] , which may reduce mycophenolate mofetil efficacy Prevention or Management Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are co-administered with mycophenolate mofetil.

Proton pump inhibitor that decreases mycophenolic acid systemic exposure and may reduce Mycophenolate Mofetil efficacy. Monitor for alterations in efficacy.

Pantoprazole sodium can reduce absorption of nilotinib due to its effect on reducing intragastric acidity.

ketoconazole, ampicillin esters, atazanavir, iron salts, erlotinib and mycophenolate mofetil) ( 7.4 ) • May produce false-positive urine screen for THC ( 7.5 ) • Methotrexate: Pantoprazole sodium may increase serum level of methotrexate ( 7.6 ) 7.1 Interference with Antiretroviral Therapy Concomitant use of atazanavir or nelfinavir with proton pump inhibitors is not recommended. Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, ampicillin esters, atazanavir, iron salts, erlotinib, and mycophenolate mofetil (MMF) can decrease.

7.9 Proton Pump Inhibitors There is no clinically meaningful increase in AUC and C max with concomitant administration of carvedilol phosphate extended-release capsules with pantoprazole.

Impact of Dabigatran on Other Drugs In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.

No clinically significant changes in concentration were observed for doravirine when co-administered with the following agents: dolutegravir, TDF, lamivudine, elbasvir and grazoprevir, ledipasvir and sofosbuvir, ritonavir, ketoconazole, aluminum hydroxide/magnesium hydroxide/simethicone containing antacid, pantoprazole, and methadone [see Clinical Pharmacology (12.3) ].

No clinically significant changes in concentration were observed for doravirine when co-administered with the following agents: TDF, lamivudine, elbasvir and grazoprevir, ledipasvir and sofosbuvir, ritonavir, ketoconazole, aluminum hydroxide/magnesium hydroxide/simethicone containing antacid, pantoprazole, or methadone [see Clinical Pharmacology (12.3) ] .

Proton pump inhibitors: Esomeprazole a , lansoprazole, omeprazole, pantoprazole, rabeprazole Fosamprenavir calcium: ↔ Amprenavir ↑ Esomeprazole Proton pump inhibitors can be administered at the same time as a dose of fosamprenavir calcium with no change in plasma amprenavir concentrations.

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.

pantoprazole ↓ pantoprazole Clinical monitoring and dose adjustment may be needed.

7.11 Pantoprazole Administration of pantoprazole at a dose of 40 mg twice daily for 4 days to healthy volunteers did not alter the pharmacokinetics of a single dose of mycophenolic acid delayed-release tablets [see Clinical Pharmacology ( 12.3 )] .

Pantoprazole: In healthy volunteers the exposure to neither drug was changed significantly in the presence of the other drug.

( 7 ) Table 3 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with pantoprazole sodium and instructions for preventing or managing them. Table 3: Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole Sodium and Interaction with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with pantoprazole sodium may reduce antiviral effect and promote the development of drug resistance.

7 DRUG INTERACTIONS Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with pantoprazole sodium and instructions for preventing or managing them. Table 4: Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole Sodium and Interactions with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. 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.

7 DRUG INTERACTIONS Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with pantoprazole and instructions for preventing or managing them. Table 4: Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole and Interactions with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. 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.

7 DRUG INTERACTIONS Table 2 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with pantoprazole sodium injection and instructions for preventing or managing them. Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole Sodium in 0.9% Sodium Chloride Injection and Interaction with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. • 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.