Omeprazole

Combination Therapy with Clarithromycin and Amoxicillin Clinical Impact: Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated. Amoxicillin also has drug interactions. See Drug Interactions in prescribing information for amoxicillin.

Omeprazole reduces plasma levels of atazanavir substantially (AUC decreased by 94%), which may result in loss of therapeutic effect and development of drug resistance. Concomitant use is not recommended.

Combination Therapy with Clarithromycin and Amoxicillin Clinical Impact: Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated. Intervention: See Contraindications, Warnings and Precautions in prescribing information for clarithromycin.

Avoid concomitant use. Omeprazole significantly reduces the antiplatelet activity of clopidogrel bisulfate when given concomitantly or 12 hours apart.

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.

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. Fosamprenavir calcium/ritonavir: ↔ Amprenavir ↔ Esomeprazole Sedative/hypnotics: Midazolam, triazolam ↑Midazolam ↑Triazolam Coadministration is contraindicated due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression [see Contraindications (4)].

Omeprazole reduces plasma levels of nelfinavir significantly (AUC decreased by 92%), which may result in loss of therapeutic effect and development of drug resistance. Concomitant use is not recommended.

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) ] .

CYP2C19 inhibitor increases systemic exposure of cilostazol active metabolites. Requires cilostazol dose reduction to 50 mg twice daily.

Omeprazole or Esomeprazole Avoid concomitant use of clopidogrel with omeprazole or esomeprazole. In clinical studies, omeprazole was shown to reduce significantly the antiplatelet activity of clopidogrel when given concomitantly or 12 hours apart. A similar reduction in antiplatelet activity was observed with esomeprazole when given concomitantly with clopidogrel.

Proton pump inhibitor: omeprazole ↓ omeprazole ↔ darunavir When omeprazole is co-administered with darunavir/ritonavir, monitor patients for decreased efficacy of omeprazole. Consider increasing the omeprazole dose in patients whose symptoms are not well controlled; avoid use of more than 40 mg per day of omeprazole.

Proton pump inhibitor: omeprazole ↓ omeprazole ↔ darunavir When omeprazole is co-administered with darunavir/ritonavir, monitor patients for decreased efficacy of omeprazole. Consider increasing the omeprazole dose in patients whose symptoms are not well controlled; avoid use of more than 40 mg per day of omeprazole.

Inhibits hepatic enzymes (CYP3A and 2C19), leading to increased and prolonged sedation.

Concomitant use with omeprazole may elevate and prolong serum concentrations of methotrexate and/or metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities.

Increased exposure of saquinavir when used concomitantly with omeprazole may increase toxicity.

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., erythromycin, fluconazole), calcium channel blockers (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions (5.6, 5.11, 5.12)].

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions ( 5.7 , 5.10 , 5.11 )] .

Omeprazole Clinical Effect Clarithromycin concentrations in the gastric tissue and mucus were increased by concomitant administration of omeprazole [see Clinical Pharmacology (12.3) ] . Prevention or Management Avoid concomitant use of VOQUEZNA TRIPLE PAK with omeprazole.

Increased INR and prothrombin time in patients receiving omeprazole and warfarin concomitantly, which may lead to abnormal bleeding and death.

CYP1A2 and CYP3A4 inducer that decreases warfarin effect and INR; requires close monitoring.

Monitor for toxicity and consider dose reduction of saquinavir ( 7.1 ) • May interfere with drugs for which gastric pH affects bioavailability (e.g., ketoconazole, iron salts, erlotinib, ampicillin esters, and digoxin). Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, ampicillin esters, iron salts and erlotinib can decrease, while the absorption of drugs such as digoxin can increase during treatment with omeprazole.

Omeprazole may interfere with ampicillin esters absorption as gastric pH affects its bioavailability.

CYP1A2 inducer may decrease anagrelide exposure; dose titration may be needed to maintain efficacy.

CYP1A2 inducer may decrease anagrelide exposure; dose titration may be necessary.

Effects of Armodafinil Tablets on CYP2C19 Substrates: Elimination of drugs that are substrates for CYP2C19 (e.g., phenytoin, diazepam, propranolol, omeprazole, and clomipramine) may be prolonged by armodafinil tablets via inhibition of metabolic enzymes, with resultant higher systemic exposure. ( 7 ) • CYP2C19 substrates, such as omeprazole, phenytoin, and diazepam: exposure of these medications may be increased. In a clinical study, concomitant administration of armodafinil tablets 400 mg resulted in a 40% increase in exposure to omeprazole after a single oral dose (40 mg), as a result of moderate inhibition of CYP2C19 activity [see Drug Interactions (7) ].

CYP3A4 inhibitor that increases carbamazepine plasma levels. Close monitoring of carbamazepine levels and dosage adjustment may be required.

CYP2C19 inhibitor that could result in increased carisoprodol exposure and decreased meprobamate exposure; full pharmacological impact unknown.

CYP2C19 substrate; concomitant use with omeprazole may alter citalopram exposure.

Potent CYP2C19 inhibitor that might decrease clearance of citalopram.

Dosage adjustment of clobazam oral suspension may be necessary when co-administered with strong CYP2C19 inhibitors (e.g., fluconazole, fluvoxamine, ticlopidine) or moderate CYP2C19 inhibitors (e.g., omeprazole) [see Clinical Pharmacology ( 12.3 )].

Omeprazole can prolong elimination of cyclosporine. Monitor and determine need for dose adjustments.

Increases digoxin concentrations; magnitude unclear. Requires monitoring and dose adjustment.

Omeprazole can prolong elimination of disulfiram. Monitor and determine need for dose adjustments.

COCs Increasing the Plasma Concentrations of CYP450 Enzymes : In clinical studies, administration of a hormonal contraceptive containing EE did not lead to any increase or only to a weak increase in plasma concentrations of CYP3A4 substrates (e.g., midazolam) while plasma concentrations of CYP2C19 substrates (e.g., omeprazole and voriconazole) and CYP1A2 substrates (e.g., theophylline and tizanidine) can have a weak or moderate increase. The potential effect of DRSP on CYP2C19 activity was investigated in a clinical pharmacokinetic study using omeprazole as a marker substrate. In the study with 24 postmenopausal women [including 12 women with homozygous (wild type) CYP2C19 genotype and 12 women with heterozygous CYP2C19 genotype] the daily oral administration of 3 mg DRSP for 14 days did not affect the oral clearance of omeprazole (40 mg, single oral dose) and the CYP2C19 product 5-hydroxy omeprazole.

COCs Increasing the Plasma Concentrations of CYP450 Enzymes : In clinical studies, administration of a hormonal contraceptive containing EE did not lead to any increase or only to a weak increase in plasma concentrations of CYP3A4 substrates (e.g., midazolam) while plasma concentrations of CYP2C19 substrates (e.g., omeprazole and voriconazole) and CYP1A2 substrates (e.g., theophylline and tizanidine) can have a weak or moderate increase.

COCs Increasing the Plasma Concentrations of CYP450 Enzymes: In clinical studies, administration of a hormonal contraceptive containing EE did not lead to any increase or only to a weak increase in plasma concentrations of CYP3A4 substrates (e.g., midazolam) while plasma concentrations of CYP2C19 substrates (e.g., omeprazole and voriconazole) and CYP1A2 substrates (e.g., theophylline and tizanidine) can have a weak or moderate increase.

Elagolix increases omeprazole plasma concentrations. No dose adjustment needed for 40 mg once daily; consider dosage reduction for higher doses.

ORIAHNN may increase omeprazole plasma concentrations. No dose adjustment needed for 40 mg once daily; consider dosage reduction for higher doses.

Monitor for toxicity and consider dose reduction of saquinavir ( 7.1 ) • May interfere with drugs for which gastric pH affects bioavailability (e.g., ketoconazole, iron salts, erlotinib, ampicillin esters, and digoxin). Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, ampicillin esters, iron salts and erlotinib can decrease, while the absorption of drugs such as digoxin can increase during treatment with omeprazole.

Proton pump inhibitor that decreases erlotinib exposure by increasing gastric pH. Avoid concomitant use if possible.

Eslicarbazepine acetate can inhibit CYP2C19, causing increased plasma concentrations of omeprazole. Dose adjustment may be needed.

7 DRUG INTERACTIONS • May affect plasma levels of antiretroviral drugs - use with atazanavir and nelfinavir is not recommended; if saquinavir is used with esomeprazole magnesium delayed-release capsules, monitor for toxicity and consider saquinavir dose reduction. Patients treated with esomeprazole magnesium delayed-release capsules and digoxin may need to be monitored for digoxin toxicity. (7.2) • Combined inhibitor of CYP2C19 and 3A4 may raise esomeprazole levels.

7 DRUG INTERACTIONS May affect plasma levels of antiretroviral drugs – use with atazanavir and nelfinavir is not recommended; if saquinavir is used with esomeprazole magnesium, monitor for toxicity and consider saquinavir dose reduction. Patients treated with esomeprazole magnesium and digoxin may need to be monitored for digoxin toxicity. ( 7.2 ) Combined inhibitor of CYP 2C19 and 3A4 may raise esomeprazole levels.( 7.3 ) Clopidogrel: esomeprazole magnesium decreases exposure to the active metabolite of clopidogrel.

Potential interaction due to fluvoxamine inhibition of CYP2C19, which is involved in omeprazole metabolism.

May increase phenytoin serum levels; monitoring of phenytoin levels recommended.

Omeprazole may interfere with iron salts absorption as gastric pH affects its bioavailability.

Monitor for toxicity and consider dose reduction of saquinavir ( 7.1 ) • May interfere with drugs for which gastric pH affects bioavailability (e.g., ketoconazole, iron salts, erlotinib, ampicillin esters, and digoxin). Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, ampicillin esters, iron salts and erlotinib can decrease, while the absorption of drugs such as digoxin can increase during treatment with omeprazole.

Proton Pump Inhibitors: Omeprazole No Dose Adjustment Omeprazole : The mean 24 hour gastric pH value was 5.2 when omeprazole was administered alone and 5.7 when coadministered with clarithromycin as a result of increased omeprazole exposures (see also Omeprazole under "Drugs That Affect Clarithromycin Tablets" in the table below). Saquinavir (in patients with normal renal function) Ritonavir (in patients with normal renal function) No Dose Adjustment Proton Pump Inhibitors: Omeprazole Use With Caution Omeprazole : Clarithromycin concentrations in the gastric tissue and mucus were also increased by concomitant administration of omeprazole.

Elimination may be prolonged by modafinil with resultant higher systemic exposure. Dose adjustment may be necessary when used concomitantly.

Omeprazole may interfere with mycophenolate mofetil bioavailability due to effects on gastric pH.

Omeprazole can prolong elimination of benzodiazepines. Monitor and determine need for dose adjustments.

May cause an increase in olanzapine clearance.

Omeprazole may increase olanzapine clearance.

( 7.1 ) • Drugs metabolized by cytochrome P450 (e.g., diazepam, warfarin, phenytoin, cyclosporine, disulfiram, benzodiazepines): Omeprazole and sodium bicarbonate can prolong their elimination. Monitor to determine the need for possible dose adjustments when taken with omeprazole and sodium bicarbonate. ( 7.2 ) • Voriconazole: May increase plasma levels of omeprazole.

CYP2C19 substrate; concomitant use with omeprazole may alter phenytoin exposure.

May increase phenytoin serum levels; monitoring of phenytoin levels recommended.

Probe substrate for CYP2C19; modest inhibition at first dose but marked induction at steady state with APTIVUS/ritonavir; may require monitoring.

Tocilizumab may decrease omeprazole exposure by up to 28% due to increased CYP2C19 and CYP3A4 metabolism. Therapeutic monitoring recommended.

Tocilizumab may decrease omeprazole exposure by up to 28%; monitor effect and adjust dose as needed.

Voriconazole, a combined inhibitor of CYP2C19 and CYP3A4, may raise omeprazole levels.

No clinically significant drug interactions observed when coadministered with bortezomib.

Concomitant administration of 20 mg omeprazole did not affect the pharmacokinetics of cysteamine when PROCYSBI was administered with orange juice or water.

In vivo study with omeprazole did not show an inhibitory effect on omeprazole pharmacokinetics despite in vitro potential to inhibit CYP2C19.

Darunavir/ritonavir, lopinavir/ritonavir, rilpivirine, tenofovir, boceprevir, prednisone, rifabutin, and omeprazole had no clinically significant effect on the pharmacokinetics of dolutegravir.

albuterol, systemic and inhaled amoxicillin ampicillin, with or without sulbactam atenolol azithromycin caffeine, dietary ingestion cefaclor co-trimoxazole (trimethoprim and sulfamethoxazole) diltiazem dirithromycin enflurane famotidine felodipine finasteride hydrocortisone isoflurane isoniazid isradipine influenza vaccine ketoconazole lomefloxacin mebendazole medroxyprogesterone methylprednisolone metronidazole metoprolol nadolol nifedipine nizatidine norfloxacin ofloxacin omeprazole prednisone, prednisolone ranitidine rifabutin roxithromycin sorbitol (purgative doses do not inhibit theophylline absorption) sucralfate terbutaline, systemic terfenadine tetracycline tocainide The Effect of Other Drugs on Theophylline Serum Concentration Measurements: Most serum theophylline assays in clinical use are immunoassays which are specific for theophylline.

In addition, no dosage adjustment is necessary for substrates of CYP2D6 (e.g., dextromethorphan, fluoxetine, paroxetine, or venlafaxine), CYP2C9 (e.g., warfarin), CYP2C19 (e.g., omeprazole, warfarin, escitalopram), or CYP3A4 (e.g., dextromethorphan) when co-administered with aripiprazole.

In addition, no dosage adjustment is necessary for substrates of CYP2D6 (e.g., dextromethorphan, fluoxetine, paroxetine, or venlafaxine), CYP2C9 (e.g., warfarin), CYP2C19 (e.g., omeprazole, warfarin, escitalopram), or CYP3A4 (e.g., dextromethorphan) when co-administered with ARISTADA.

In addition, no dosage adjustment is necessary for substrates of CYP2D6 (e.g., dextromethorphan, fluoxetine, paroxetine, or venlafaxine), CYP2C9 (e.g., warfarin), CYP2C19 (e.g., omeprazole, warfarin, escitalopram), or CYP3A4 (e.g., dextromethorphan) when co-administered with aripiprazole.

Proton-pump inhibitors (PPI): (e.g., omeprazole) ↓ atazanavir In treatment-naive patients, administer EVOTAZ a minimum of 12 hours after administration of the PPI. The dose of the PPI should not exceed a dose comparable to omeprazole 20 mg daily.

Proton-pump inhibitors: omeprazole ↓ atazanavir Coadministration of atazanavir with or without ritonavir and omeprazole may result in loss of virologic response and development of resistance. In HIV-treatment-naive adult patients: The proton-pump inhibitor (PPI) dose should not exceed a dose comparable to omeprazole 20 mg and must be taken approximately 12 hours prior to the atazanavir 300 mg with ritonavir 100 mg dose.

7.9 Drugs that Affect Gastric pH Drugs that elevate gastric pH (magnesium hydroxide/aluminum hydroxide, omeprazole) had no effect on atomoxetine bioavailability.

7.9 Drugs that Affect Gastric pH Drugs that elevate gastric pH (magnesium hydroxide/aluminum hydroxide, omeprazole) had no effect on atomoxetine bioavailability.

7.2 Drugs Having No Clinically Important Interactions with REXULTI Based on pharmacokinetic studies, no dosage adjustment of REXULTI is required when administered concomitantly with CYP2B6 inhibitors (e.g., ticlopidine) or gastric pH modifiers (e.g., omeprazole).

Proton-pump Inhibitors (PPIs) e.g., omeprazole ↓ atazanavir TYBOST coadministered with atazanavir in adult patients: In treatment-naïve adult patients, administer TYBOST with atazanavir a minimum of 12 hours after administering PPIs. The dose of the PPI should not exceed a dose comparable to omeprazole 20 mg daily.

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact: Omeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity.

7.2 Drugs Having No Clinically Important Interactions with Amphetamine From a pharmacokinetic perspective, no dose adjustment of XELSTRYM is necessary when XELSTRYM is co-administered with guanfacine, venlafaxine, or omeprazole. omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g.

An example of a proton pump inhibitor is omeprazole.

An example of a proton pump inhibitor is omeprazole. An example of a proton pump inhibitor is omeprazole.

An example of a proton pump inhibitor is omeprazole.

If a patient requires dofetilide and anti-ulcer therapy, it is suggested that omeprazole, ranitidine, or antacids (aluminum and magnesium hydroxides) be used as alternatives to cimetidine, as these agents have no effect on the pharmacokinetic profile of dofetilide. Other Drugs: In healthy volunteers, amlodipine, phenytoin, glyburide, ranitidine, omeprazole, hormone replacement therapy (a combination of conjugated estrogens and medroxyprogesterone), antacid (aluminum and magnesium hydroxides), and theophylline did not affect the pharmacokinetics of dofetilide.

b 7.4 Drugs without Clinically Significant Interactions with Dolutegravir Based on drug interaction trial results, the following drugs can be coadministered with dolutegravir without a dose adjustment: atazanavir/ritonavir, darunavir/ritonavir, elbasvir/grazoprevir, methadone, midazolam, omeprazole, oral contraceptives containing norgestimate and ethinyl estradiol, prednisone, rifabutin, rilpivirine, sofosbuvir/velpatasvir, and tenofovir [see Clinical Pharmacology ( 12.3 )] .

7.2 Influence of SLYND on other Medicinal Products Based on in vitro studies and in vivo interaction studies in female volunteers using omeprazole, simvastatin and midazolam as marker substrate, an interaction of drospirenone with the metabolism of other active substances is unlikely.

( 7.1 ) 7.1 Metabolic Interactions Effect of Drospirenone on Other Drugs The potential effect of DRSP on CYP2C19 activity was investigated in a clinical pharmacokinetic study using omeprazole as a marker substrate. No significant effect of DRSP on the systemic clearance of the CYP3A4 product omeprazole sulfone was found.

7.6 Drugs without Clinically Significant Interactions with GENVOYA Based on drug interaction studies conducted with the components of GENVOYA, no clinically significant drug interactions have been observed or are expected when GENVOYA is combined with the following drugs: famciclovir, famotidine, ledipasvir, methadone, omeprazole, prasugrel (active metabolite), sertraline, sofosbuvir, velpatasvir, and voxilaprevir.

7.6 Drugs without Clinically Significant Interactions with STRIBILD Based on drug interaction studies conducted with the components of STRIBILD, no clinically significant drug interactions have been observed or are expected when STRIBILD is combined with the following drugs: famciclovir, famotidine, methadone, omeprazole, prasugrel (active metabolite), and sertraline.

Omeprazole, of which esomeprazole is an enantiomer, has been reported to interact with some antiretroviral drugs. Increased gastric pH during omeprazole treatment may change the absorption of the antiretroviral drug. Reduced concentrations of atazanavir and nelfinavir For some antiretroviral drugs, such as atazanavir and nelfinavir, decreased serum levels have been reported when given together with omeprazole.

7 DRUG INTERACTIONS Tables 5 and 6 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with esomeprazole and instructions for preventing or managing them. Table 5: Clinically Relevant Interactions Affecting Drugs Co-Administered with Esomeprazole 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 esomeprazole may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ].

Omeprazole, of which esomeprazole is an enantiomer, has been reported to interact with some antiretroviral drugs. Increased gastric pH during omeprazole treatment may change the absorption of the antiretroviral drug. Reduced concentrations of atazanavir and nelfinavir For some antiretroviral drugs, such as atazanavir and nelfinavir, decreased serum levels have been reported when given together with omeprazole.

7.4 Drugs Without Clinically Significant Interactions with Etravirine Tablets In addition to the drugs included in Table 4, the interaction between etravirine tablets and the following drugs were evaluated in clinical studies and no dose adjustment is needed for either drug [see Clinical Pharmacology (12.3) ] : didanosine, enfuvirtide (ENF), ethinylestradiol/norethindrone, omeprazole, paroxetine, raltegravir, ranitidine, and tenofovir disoproxil fumarate. 7.4 Drugs Without Clinically Significant Interactions with Etravirine Tablets In addition to the drugs included in Table 4, the interaction between etravirine tablets and the following drugs were evaluated in clinical studies and no dose adjustment is needed for either drug [see Clinical Pharmacology (12.3) ] : didanosine, enfuvirtide (ENF), ethinylestradiol/norethindrone, omeprazole, paroxetine, raltegravir, ranitidine, and tenofovir disoproxil fumarate.

7.5 Drugs with No Observed Clinically Significant Interactions with MAVYRET No dose adjustment is required when MAVYRET is coadministered with the following medications: abacavir, amlodipine, caffeine, dextromethorphan, dolutegravir, elvitegravir/ cobicistat, emtricitabine, ethinyl estradiol of 20 mcg or less, felodipine, lamivudine, lamotrigine, losartan, midazolam, norethindrone or other progestin-only contraceptives, omeprazole, raltegravir, rilpivirine, sofosbuvir, tacrolimus, tenofovir alafenamide, tenofovir disoproxil fumarate, tolbutamide, and valsartan.

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact: Omeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity.

Proton-pump inhibitors (e.g., omeprazole) Proton-pump inhibitor doses comparable to omeprazole 20 mg or lower can be administered simultaneously with HARVONI under fasted conditions.

Proton Pump Inhibitors omeprazole ↓ omeprazole Clinical monitoring and dose adjustment may be needed.

7.2 Drugs Having No Clinically Important Interactions with Lisdexamfetamine Dimesylate From a pharmacokinetic perspective, no dose adjustment of lisdexamfetamine dimesylate is necessary when lisdexamfetamine dimesylate is co-administered with guanfacine, venlafaxine, or omeprazole. From a pharmacokinetic perspective, no dose adjustment for drugs that are substrates of CYP1A2 (e.g., theophylline, duloxetine, melatonin), CYP2D6 (e.g., atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g., omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g., midazolam, pimozide, simvastatin) is necessary when lisdexamfetamine dimesylate is co-administered [see Clinical Pharmacology (12.3) ] .

7.2 Drugs Having No Clinically Important Interactions with Lisdexamfetamine Dimesylate Capsules From a pharmacokinetic perspective, no dose adjustment of lisdexamfetamine dimesylate capsules is necessary when lisdexamfetamine dimesylate capsules is co-administered with guanfacine, venlafaxine, or omeprazole. From a pharmacokinetic perspective, no dose adjustment for drugs that are substrates of CYP1A2 (e.g., theophylline, duloxetine, melatonin), CYP2D6 (e.g., atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g., omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g., midazolam, pimozide, simvastatin) is necessary when VYVANSE is co-administered [see Clinical Pharmacology (12.3) ] .

7.2 Drugs Having No Clinically Important Interactions with Lisdexamfetamine Dimesylate Capsules From a pharmacokinetic perspective, no dose adjustment of lisdexamfetamine dimesylate capsules is necessary when lisdexamfetamine dimesylate capsules are co-administered with guanfacine, venlafaxine, or omeprazole. From a pharmacokinetic perspective, no dose adjustment for drugs that are substrates of CYP1A2 (e.g., theophylline, duloxetine, melatonin), CYP2D6 (e.g., atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g., omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g., midazolam, pimozide, simvastatin) is necessary when lisdexamfetamine dimesylate capsules are co-administered [see Clinical Pharmacology ( 12.3 )] .

7.4 Drugs with No Observed or Predicted Interactions with Lopinavir And Ritonavir Drug interaction or clinical studies reveal no clinically significant interaction between lopinavir and ritonavir and desipramine (CYP2D6 probe), etravirine, pitavastatin, pravastatin, stavudine, lamivudine, omeprazole, raltegravir, ranitidine, or rilpivirine.

7.13 Proton Pump Inhibitors, H 2 Blockers, Antacids ORKAMBI may reduce the exposure and effectiveness of proton pump inhibitors such as omeprazole, esomeprazole, and lansoprazole, and may alter the exposure of ranitidine.

7 DRUG INTERACTIONS See Table 3 and Table 4 for clinically significant drug interactions and interactions with diagnostics with naproxen and esomeprazole magnesium. Table 3: Clinically Significant Drug Interactions with Naproxen and Esomeprazole Magnesium – Affecting Drugs Co-Administered with Naproxen and Esomeprazole magnesium delayed-release tablets and Interactions with Diagnostics Clinical Impact: Naproxen • Naproxen and anticoagulants such as warfarin have a synergistic effect on bleeding. Esomeprazole Magnesium • Increased INR and prothrombin time in patients treated with PPIs, including esomeprazole, and warfarin concomitantly.

PROTON PUMP INHIBITORS Omeprazole ↓ nelfinavir Omeprazole decreases the plasma concentrations of nelfinavir.

Antisecretory Drugs Omeprazole: In healthy volunteers receiving a single dose of 10 mg nifedipine, AUC and C max of nifedipine after pretreatment with omeprazole 20 mg q.d. Pretreatment with or co-administration of omeprazole did not impact the effect of nifedipine on blood pressure or heart rate. The impact of omeprazole on nifedipine is not likely to be of clinical relevance.

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact: Omeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity.

Agents that induce CYP1A2 or glucuronyl transferase enzymes, such as omeprazole and rifampin, may cause an increase in olanzapine clearance.

7 DRUG INTERACTIONS Table 3 and Table 4 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with omeprazole and instructions for preventing or managing them. Table 3: Clinically Relevant Interactions Affecting Drugs Co-Administered with Omeprazole 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 omeprazole may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology ( 12.3 )].

The drug interaction information described here is based on the prescribing information of individual TALICIA components: omeprazole, amoxicillin, and rifabutin. Omeprazole is a substrate and an inhibitor of CYP2C19, and a substrate of CYP3A4. Co-administration of TALICIA and other drugs that are substrates, inhibitors, or inducers of these enzymes may alter concentrations of rifabutin/omeprazole or other co-administered drugs [See Table 2 below and Clinical Pharmacology (12.3) ].

While no formal drug interaction studies have been performed, the following concomitant drugs were used in at least 10% of patients in either or both Sjogren's efficacy studies: acetylsalicylic acid, artificial tears, calcium, conjugated estrogens, hydroxychloroquine sulfate, ibuprofen, levothyroxine sodium, medroxyprogesterone acetate, methotrexate, multivitamins, naproxen, omeprazole, paracetamol, and prednisone.

While no formal drug interaction studies have been performed, the following concomitant drugs were used in at least 10% of patients in either or both Sjogren's efficacy studies: acetylsalicylic acid, artificial tears, calcium, conjugated estrogens, hydroxychloroquine sulfate, ibuprofen, levothyroxine sodium, medroxyprogesterone acetate, methotrexate, multivitamins, naproxen, omeprazole, paracetamol, and prednisone.

Although in normal subjects no interaction with theophylline or propranolol was found, there have been clinical reports of interaction with other drugs metabolized via the cytochrome P450 system (e.g., cyclosporine, disulfiram, benzodiazepines).

No interaction was observed with omeprazole. No interaction was observed with omeprazole.

Conversely, the pharmacokinetics of quinidine are not significantly affected by caffeine, ciprofloxacin, digoxin, felodipine, omeprazole, or quinine .

Conversely, the pharmacokinetics of quinidine are not significantly affected by caffeine, ciprofloxacin, digoxin, diltiazem, felodipine, omeprazole , or quinine .

This degree of inhibition is similar to that by omeprazole at equivalent concentrations.

Moreover, atazanavir, atazanavir/ritonavir, boceprevir, calcium carbonate antacids, darunavir/ritonavir, efavirenz, etravirine, omeprazole, or tipranavir/ritonavir did not have a clinically meaningful effect on the pharmacokinetics of 400 mg twice daily raltegravir. No dose adjustment is recommended when ISENTRESS HD 1200 mg once daily is coadministered with atazanavir, atazanavir/ritonavir, hormonal contraceptives, methadone, lamivudine, tenofovir disoproxil fumarate, darunavir/ritonavir, boceprevir, efavirenz and omeprazole.

Interaction studies of concomitant administration of ramelteon with fluoxetine (CYP2D6 inhibitor), omeprazole (CYP1A2 inducer/CYP2C19 inhibitor), theophylline (CYP1A2 substrate), dextromethorphan (CYP2D6 substrate), sertraline, venlafaxine, escitalopram, gabapentin, and zolpidem did not produce clinically meaningful changes in either peak or total exposures to ramelteon or the M-II metabolite. Concomitant administration of ramelteon with omeprazole (CYP2C19 substrate), dextromethorphan (CYP2D6 substrate), midazolam (CYP3A4 substrate), theophylline (CYP1A2 substrate), digoxin (p-glycoprotein substrate), warfarin (CYP2C9 [S]/CYP1A2 [R] substrate), venlafaxine, fluvoxamine, donepezil, doxepin, sertraline, escitalopram, and gabapentin did not produce clinically meaningful changes in peak and total exposures to these drugs.

Ritonavir-containing products: see prescribing information for specific drugs.

Proton-pump inhibitors (e.g., omeprazole) Omeprazole 20 mg can be administered with VOSEVI.

7 DRUG INTERACTIONS Table 1 Oral drugs that can be administered concomitantly with Velphoro Calcitriol Ciprofloxacin Digoxin Enalapril Furosemide HMG-CoA reductase inhibitors Hydrochlorothiazide Losartan Metoprolol Nifedipine Omeprazole Quinidine Warfarin Oral drugs that are to be separated from Velphoro Dosing Recommendations Doxycycline Acetylsalicylic acid Cephalexin Take at least 1 hour before Velphoro. Velphoro can be administered concomitantly with oral calcitriol, ciprofloxacin, digoxin, enalapril, furosemide, HMG‑CoA reductase inhibitors, hydrochlorothiazide, losartan, metoprolol, nifedipine, omeprazole, quinidine and warfarin.

7.3 Drugs Without Clinically Significant Interactions With TPOXX Based on a drug interaction study, no clinically significant drug interactions have been observed when TPOXX is co-administered with bupropion, flurbiprofen, or omeprazole [see Clinical Pharmacology ( 12.3 )] .

Drugs that have been documented not to interact with theophylline or drugs that produce no clinically significant interaction with theophylline.* albuterol, systemic and inhaled mebendazole amoxicillin medroxyprogesterone ampicillin, with or without methylprednisolone sulbactam metronidazole atenolol metoprolol azithromycin nadolol caffeine, dietary ingestion nifedipine cefaclor nizatidine co-trimoxazole (trimethoprim and sulfamethoxazole) norfloxacin ofloxacin diltiazem omeprazole dirithromycin prednisone, prednisolone enflurane ranitidine famotidine rifabutin felodipine roxithromycin finasteride Sorbitol (purgative doses do not inhibit hydrocortisone theophylline absorption) isoflurane sucralfate isoniazid terbutaline, systemic isradipine terfenadine influenza vaccine tetracycline ketoconazole tocainide lomefloxacin * Refer to PRECAUTIONS, Drug Interactions for information regarding table.

albuterol, systemic and inhaled mebendazole amoxicillin medroxyprogesterone ampicillin, with or without sulbactam methylprednisolone atenolol metronidazole azithromycin metoprolol caffeine, dietary ingestion nadolol cefaclor nifedipine co-trimoxazole (trimethoprim and sulfamethoxazole) nizatidine diltiazem norfloxacin dirithromycin ofloxacin enflurane omeprazole famotidine prednisone, prednisolone felodipine ranitidine finasteride rifabutin hydrocortisone roxithromycin isoflurane Sorbitol (purgative doses do not inhibit theophylline absorption) isoniazid sucralfate isradipine terbutaline, systemic influenza vaccine terfenadine ketoconazole tetracycline lomefloxacin tocainide

7.4 Other Drugs Metabolized by Cytochrome P450 Isoenzymes In vivo drug-interaction data show that tolterodine immediate release does not result in clinically relevant inhibition of CYP1A2, 2D6, 2C9, 2C19, or 3A4 as evidenced by lack of influence on the marker drugs caffeine, debrisoquine, S-warfarin, and omeprazole [ see CLINICAL PHARMACOLOGY ( 12.3 ) ] .

7.4 Other Drugs Metabolized by Cytochrome P450 Isoenzymes In vivo drug-interaction data show that tolterodine immediate release does not result in clinically relevant inhibition of CYP1A2, 2D6, 2C9, 2C19, or 3A4 as evidenced by lack of influence on the marker drugs caffeine, debrisoquine, S-warfarin, and omeprazole [see Clinical Pharmacology (12.3) ] . In vivo drug-interaction data show that tolterodine immediate release does not result in clinically relevant inhibition of CYP1A2, 2D6, 2C9, 2C19, or 3A4 as evidenced by lack of influence on the marker drugs caffeine, debrisoquine, S-warfarin, and omeprazole.

Proton-pump inhibitors (e.g., omeprazole) Coadministration of omeprazole or other proton-pump inhibitors is not recommended. If it is considered medically necessary to coadminister, EPCLUSA should be administered with food and taken 4 hours before omeprazole 20 mg.