PRILOSEC (Page 4 of 13)

6.2 Clinical Trials Experience with PRILOSEC in Combination Therapy for H. pylori Eradication

In clinical trials using either dual therapy with PRILOSEC and clarithromycin, or triple therapy with PRILOSEC, clarithromycin, and amoxicillin, no adverse reactions unique to these drug combinations were observed. Adverse reactions observed were limited to those previously reported with omeprazole, clarithromycin, or amoxicillin alone.

Dual Therapy (PRILOSEC/clarithromycin)

Adverse reactions observed in controlled clinical trials using combination therapy with PRILOSEC and clarithromycin (n = 346) that differed from those previously described for PRILOSEC alone were taste perversion (15%), tongue discoloration (2%), rhinitis (2%), pharyngitis (1%) and flu-syndrome (1%). (For more information on clarithromycin, refer to the clarithromycin prescribing information, Adverse Reactions section.)

Triple Therapy (PRILOSEC/clarithromycin/amoxicillin)

The most frequent adverse reactions observed in clinical trials using combination therapy with PRILOSEC, clarithromycin, and amoxicillin (n = 274) were diarrhea (14%), taste perversion (10%), and headache (7%). None of these occurred at a higher frequency than that reported by patients taking antimicrobial agents alone. (For more information on clarithromycin or amoxicillin, refer to the respective prescribing information, Adverse Reactions sections.)

6.3 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of PRILOSEC. Because these reactions are voluntarily reported from a population of uncertain size, it is not always possible to reliably estimate their actual frequency or establish a causal relationship to drug exposure.

Body As a Whole: Hypersensitivity reactions including anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis, urticaria, (see also Skin below); fever; pain; fatigue; malaise; systemic lupus erythematosus

Cardiovascular: Chest pain or angina, tachycardia, bradycardia, palpitations, elevated blood pressure, peripheral edema

Endocrine: Gynecomastia

Gastrointestinal: Pancreatitis (some fatal), anorexia, irritable colon, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, stomatitis, abdominal swelling, dry mouth, microscopic colitis. During treatment with omeprazole, gastric fundic gland polyps have been noted rarely. These polyps are benign and appear to be reversible when treatment is discontinued.

Gastroduodenal carcinoids have been reported in patients with ZE syndrome on long-term treatment with PRILOSEC. This finding is believed to be a manifestation of the underlying condition, which is known to be associated with such tumors.

Hepatic: Liver disease including hepatic failure (some fatal), liver necrosis (some fatal), hepatic encephalopathy hepatocellular disease, cholestatic disease, mixed hepatitis, jaundice, and elevations of liver function tests [ALT, AST, GGT, alkaline phosphatase, and bilirubin]

Infections and Infestations: Clostridium difficile- associated diarrhea

Metabolism and Nutritional disorders: Hypoglycemia, hypomagnesemia, with or without hypocalcemia and/or hypokalemia, hyponatremia, weight gain

Musculoskeletal: Muscle weakness, myalgia, muscle cramps, joint pain, leg pain, bone fracture

Nervous System/Psychiatric: Psychiatric and sleep disturbances including depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, apathy, somnolence, anxiety, and dream abnormalities; tremors, paresthesia; vertigo

Respiratory: Epistaxis, pharyngeal pain

Skin: Severe generalized skin reactions including toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome, cutaneous lupus erythematosus and erythema multiforme; photosensitivity; urticaria; rash; skin inflammation; pruritus; petechiae; purpura; alopecia; dry skin; hyperhidrosis

Special Senses: Tinnitus, taste perversion

Ocular: Optic atrophy, anterior ischemic optic neuropathy, optic neuritis, dry eye syndrome, ocular irritation, blurred vision, double vision

Urogenital: Interstitial nephritis, hematuria, proteinuria, elevated serum creatinine, microscopic pyuria, urinary tract infection, glycosuria, urinary frequency, testicular pain

Hematologic: Agranulocytosis (some fatal), hemolytic anemia, pancytopenia, neutropenia, anemia, thrombocytopenia, leukopenia, leukocytosis

7 DRUG INTERACTIONS

Tables 3 and 4 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with PRILOSEC 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 PRILOSEC and Interaction 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 omeprazole may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3)].
Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with omeprazole may increase toxicity [see Clinical Pharmacology (12.3)].
There are other antiretroviral drugs which do not result in clinically relevant interactions with omeprazole.

Intervention:

Rilpivirine-containing products: Concomitant use with PRILOSEC is contraindicated [see Contraindications (4)].

Atazanavir: Avoid concomitant use with PRILOSEC. See prescribing information for atazanavir for dosing information.

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

Saquinavir: See the prescribing information for saquinavir for monitoring of potential saquinavir-related toxicities.

Other antiretrovirals: See prescribing information for specific antiretroviral drugs.

Warfarin

Clinical Impact:

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

Intervention:

Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to maintain target INR range.

Methotrexate

Clinical Impact:

Concomitant use of omeprazole 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 (5.11)].

Intervention:

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

CYP2C19 Substrates (e.g., clopidogrel, citalopram, cilostazol, phenytoin, diazepam)
Clopidogrel

Clinical Impact:

Concomitant use of omeprazole 80 mg results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition [see Clinical Pharmacology (12.3)].

There are no adequate combination studies of a lower dose of omeprazole or a higher dose of clopidogrel in comparison with the approved dose of clopidogrel.

Intervention:

Avoid concomitant use with PRILOSEC. Consider use of alternative anti-platelet therapy [see Warnings and Precautions (5.6)].

Citalopram

Clinical Impact:

Increased exposure of citalopram leading to an increased risk of QT prolongation [see Clinical Pharmacology (12.3)].

Intervention:

Limit the dose of citalopram to a maximum of 20 mg per day. See prescribing information for citalopram.

Cilostazol

Clinical Impact:

Increased exposure of one of the active metabolites of cilostazol (3,4-dihydro-cilostazol) [see Clinical Pharmacology (12.3)].

Intervention:

Reduce the dose of cilostazol to 50 mg twice daily. See prescribing information for cilostazol.

Phenytoin

Clinical Impact:

Potential for increased exposure of phenytoin.

Intervention:

Monitor phenytoin serum concentrations. Dose adjustment may be needed to maintain therapeutic drug concentrations. See prescribing information for phenytoin.

Diazepam

Clinical Impact:

Increased exposure of diazepam [see Clinical Pharmacology (12.3)].

Intervention:

Monitor patients for increased sedation and reduce the dose of diazepam as needed.

Digoxin

Clinical Impact:

Potential for increased exposure of digoxin [see Clinical Pharmacology (12.3)].

Intervention:

Monitor digoxin concentrations. Dose adjustment may be needed to maintain therapeutic drug concentrations. See digoxin prescribing information.

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.

Intervention:

Mycophenolate mofetil (MMF): Co-administration of omeprazole 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. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PRILOSEC and MMF. Use PRILOSEC with caution in transplant patients receiving MMF [see Clinical Pharmacology (12.3)].

See the prescribing information for other drugs dependent on gastric pH for absorption.

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.

Intervention:

See Contraindications, Warnings and Precautions in prescribing information for clarithromycin.

See Drug Interactions in prescribing information for amoxicillin.

Tacrolimus

Clinical Impact:

Potential for increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19.

Intervention:

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

Interactions with Investigations of Neuroendocrine Tumors

Clinical Impact:

Serum chromogranin A (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 (5.10),Clinical Pharmacology (12.2)].

Intervention:

Temporarily stop PRILOSEC 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.

Interaction with Secretin Stimulation Test

Clinical Impact:

Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma.

Intervention:

Temporarily stop PRILOSEC treatment at least 14 days before assessing to allow gastrin levels to return to baseline [see Clinical Pharmacology (12.2)].

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.

Intervention:

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

Other

Clinical Impact:

There have been clinical reports of interactions with other drugs metabolized via the

cytochrome P450 system (e.g., cyclosporine, disulfiram).

Intervention:

Monitor patients to determine if it is necessary to adjust the dosage of these other drugs

when taken concomitantly with PRILOSEC.

Table 4: Clinically Relevant Interactions Affecting PRILOSEC When Co-Administered with Other Drugs

CYP2C19 or CYP3A4 Inducers

Clinical Impact:

Decreased exposure of omeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3)].

Intervention:

St. John’s Wort, rifampin: Avoid concomitant use with PRILOSEC [see Warnings and Precautions (5.9)].

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

CYP2C19 or CYP3A4 Inhibitors

Clinical Impact:

Increased exposure of omeprazole [see Clinical Pharmacology (12.3)].

Intervention:

Voriconazole: Dose adjustment of PRILOSEC is not normally required. However, in patients with Zollinger-Ellison syndrome, who may require higher doses, dose adjustment may be considered.

See prescribing information for voriconazole.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2019. All Rights Reserved.