Interactions : אינטראקציות

        8     DRUG INTERACTIONS
Tables 3 and 4 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with DEXILANT and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.


Table 3. Clinically Relevant Interactions Affecting Drugs Co-Administered with DEXILANT and Interactions with Diagnostics

Antiretrovirals

The effect of PPIs on antiretroviral drugs is variable. The clinical importance Clinical         and the mechanisms behind these interactions are not always known.
Impact:
• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with dexlansoprazole may reduce antiviral effect and promote the development of drug resistance.
•   Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with dexlansoprazole may increase toxicity of the antiretroviral drugs.
•   There are other antiretroviral drugs which do not result in clinically relevant interactions with dexlansoprazole.
Rilpivirine-containing products: Concomitant use with DEXILANT is
Intervention:   contraindicated [see Contraindications (5)]. See prescribing information.
Atazanavir: See prescribing information for atazanavir for dosing information.
Nelfinavir: Avoid concomitant use with DEXILANT. See prescribing information for nelfinavir.
Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities.
Other antiretrovirals: See prescribing information.

Warfarin

Increased INR and prothrombin time in patients receiving PPIs and
Clinical         warfarin concomitantly. Increases in INR and prothrombin time may lead Impact:          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.

Methotrexate
Concomitant use of PPIs with methotrexate (primarily at high dose) may Clinical          elevate and prolong serum concentrations of methotrexate and/or its Impact:           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 (6.10)].
A temporary withdrawal of DEXILANT may be considered in some
Intervention:    patients receiving high-dose methotrexate.


Digoxin
Clinical          Potential for increased exposure of digoxin.
Impact:
Monitor digoxin concentrations. Dose adjustment of digoxin may be needed Intervention:    to maintain therapeutic drug concentrations. See prescribing information for digoxin.
Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenoloate mofetil, ketoconazole/itraconazole)
Clinical          Dexlansoprazole can reduce the absorption of other drugs due to its effect on Impact:           reducing intragastric acidity.
Mycophenolate mofetil (MMF): Co-administration of PPIs in healthy
Intervention:    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. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving DEXILANT and MMF. Use
DEXILANT with caution in transplant patients receiving MMF.
See the prescribing information for other drugs dependent on gastric pH for absorption.

Tacrolimus
Clinical        Potentially increased exposure of tacrolimus, especially in transplant patients Impact:         who are intermediate or poor metabolizers of CYP2C19.

Monitor tacrolimus whole blood trough concentrations. Dose adjustment Intervention: of tacrolimus may be needed to maintain therapeutic drug concentrations. See prescribing information for tacrolimus.

Interactions with Investigations of Neuroendocrine Tumors
CgA levels increase secondary to PPI-induced decreases in gastric acidity. The Clinical        increased CgA level may cause false positive results in diagnostic Impact: investigations for neuroendocrine tumors [see Warnings and Precautions (6.9), Clinical Pharmacology (12.2)].
Temporarily stop DEXILANT treatment at least 14 days before assessing CgA Intervention: 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.

Interaction with Secretin Stimulation Test
Clinical       Hyper-response in gastrin secretion in response to secretin stimulation test, Impact:        falsely suggesting gastrinoma.
Temporarily stop DEXILANT treatment at least 30 days before assessing to Intervention: allow gastrin levels to return to baseline [see Clinical Pharmacology (12.2)].


False Positive Urine Tests for THC
Clinical       There have been reports of false positive urine screening tests for Impact:        tetrahydrocannabinol (THC) in patients receiving PPIs.
Intervention: An alternative confirmatory method should be considered to verify positive results.


Table 4. Clinically Relevant Interactions Affecting DEXILANT When Co-administered with Other Drugs and Substances
CYP2C19 or CYP3A4 Inducers
Clinical       Decreased exposure of dexlansoprazole when used concomitantly with Impact:        strong inducers [see Clinical Pharmacology (12.3)].
St. John’s Wort, rifampin: Avoid concomitant use with
Intervention: DEXILANT. Ritonavir-containing products: See prescribing information.

CYP2C19 or CYP3A4 Inhibitors

Increased exposure of dexlansoprazole is expected when used concomitantly Clinical       with strong inhibitors [see Clinical Pharmacology (12.3)].
Impact:
Intervention: Voriconazole: See prescribing information.