* if ulcer present, continue omeprazole delayed-release capsules 20 mg once daily for an additional 18 days.
** if ulcer present, continue omeprazole delayed-release capsules 20 mg once daily for an additional 14 days. *** an additional 4 weeks of treatment may be given if no response; if recurrence additional 4 to 8 week courses may be considered. **** studied for 12 months. Reduce the dosage to 10 mg once daily for patients with hepatic impairment (Child-Pugh Class A, B, or C) and Asian patients ( |
||
|
|
|
Treatment of Active Duodenal Ulcer
|
20 mg once daily for 4 weeks; some patients may require an additional 4 weeks (
|
|
|
||
|
|
|
Omeprazole delayed- release capsules
|
20 mg
|
Each drug twice daily for 10 days (
|
Amoxicillin
|
1000 mg
|
|
Clarithromycin
|
500 mg
|
|
|
|
|
Omeprazole delayed- release capsules
|
40 mg once daily for 14 days**
|
|
Clarithromycin
|
500 mg three times daily for 14 days (
|
|
Active Benign Gastric Ulcer
|
40 mg once daily for 4 to 8 weeks (
|
|
Symptomatic GERD
|
20 mg once daily for up to 4 weeks (
|
|
EE due to Acid-Mediated GERD
|
20 mg once daily for 4 to 8 weeks (
|
|
Maintenance of Healing of EE due to Acid-Mediated GERD
|
20 mg once daily (
See full prescribing information for weight based dosing in pediatric patients 2 years of age and older ( |
|
Pathological Hypersecretory Conditions
|
Starting dose is 60 mg once daily (varies with individual patient, see full prescribing information) as long as clinically indicated (
|
1. Most patients heal within 4 weeks; some patients may require an additional 4 weeks of therapy to achieve healing
2. The efficacy of omeprazole delayed-release capsules used for longer than 8 weeks in patients with EE has not been established. If a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. If there is recurrence of EE or GERD symptoms (e.g., heartburn), additional 4 to 8 week courses of omeprazole delayed-release capsules may be considered. 3. Dosage reduction to 10 mg once daily is recommended for patients with hepatic impairment (Child-Pugh Class A, B or C) and Asian patients when used for the maintenance of healing of EE |
||
|
|
|
Treatment of Active Duodenal
Ulcer |
20 mg once daily
|
4 weeks
1
|
|
Omeprazole delayed-release capsules 20 mg Amoxicillin 1000 mg Clarithromycin 500 mg Take all three drugs twice daily |
10 days
In patients with an ulcer present at the time of initiation of therapy, continue omeprazole delayed-release capsules 20 mg once daily for an additional 18 days for ulcer healing and symptom relief. |
|
Omeprazole delayed-release capsules 40 mg once daily Clarithromycin 500 mg three times daily |
14 days
In patients with an ulcer present at the time of initiation of therapy, an additional 14 days of omeprazole delayed-release capsules 20 mg once daily is recommended for ulcer healing and symptom relief. |
Active Benign Gastric Ulcer
|
40 mg once daily
|
4 to 8 weeks
|
Treatment of Symptomatic GERD
|
20 mg once daily
|
Up to 4 weeks
|
Treatment of EE due to Acid-Mediated GERD
|
20 mg once daily
|
4 to 8 weeks
2
|
Maintenance of Healing of EE due to Acid-Mediated GERD
|
20 mg once daily
3
|
Controlled studies do not extend beyond 12 months.
|
Pathological Hypersecretory Conditions
|
Starting dose is 60 mg once daily;
adjust to patient needs Daily dosages of greater than 80 mg should be administered in divided doses. Dosages up to 120 mg three times daily have been administered. |
As long as clinically indicated.
Some patients with Zollinger- Ellison syndrome have been treated continuously for more than 5 years. |
1. The efficacy of omeprazole delayed-release capsules used for longer than 8 weeks in patients with EE has not been established. If a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. If there is recurrence of EE or GERD symptoms (e.g., heartburn), additional 4 to 8 week courses of omeprazole delayed-release capsules may be considered.
|
|||
|
|
||
|
|
|
|
Treatment of Symptomatic GERD
|
2 to 16 years
|
10 to less than 20 kg: 10 mg
|
Once daily for up to 4 weeks
|
20 kg and greater: 20 mg
|
|||
Treatment of EE due to Acid- Mediated GERD
|
2 to 16 years
|
10 to less than 20 kg: 10 mg
|
Once daily for 4 to 8 weeks
1
|
20 kg and greater: 20 mg
|
|||
Maintenance of Healing of EE due to Acid-Mediated GERD
|
2 to 16 years
|
10 to less than 20 kg: 10 mg
|
Once daily. Controlled studies do not extend beyond 12 months
|
20 kg and greater: 20 mg
|
|
|
|
The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.
|
|
|
|
|
|
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.
|
|
Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to maintain target INR range.
|
|
|
|
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
|
|
A temporary withdrawal of omeprazole may be considered in some patients receiving high-dose methotrexate.
|
|
|
|
|
|
Concomitant use of omeprazole 80 mg results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition
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 |
|
Avoid concomitant use with omeprazole. Consider use of alternative anti-platelet therapy
|
|
|
|
Increased exposure of citalopram leading to an increased risk of QT prolongation
|
|
Limit the dose of citalopram to a maximum of 20 mg per day. See prescribing information for citalopram.
|
|
|
|
Increased exposure of one of the active metabolites of cilostazol (3,4-dihydro-cilostazol)
|
|
Reduce the dose of cilostazol to 50 mg twice daily. See prescribing information for cilostazol.
|
|
|
|
Potential for increased exposure of phenytoin.
|
|
Monitor phenytoin serum concentrations. Dose adjustment may be needed to maintain therapeutic drug concentrations. See prescribing information for phenytoin.
|
|
|
|
Increased exposure of diazepam
|
|
Monitor patients for increased sedation and reduce the dose of diazepam as needed.
|
|
|
|
Potential for increased exposure of digoxin
|
|
Monitor digoxin concentrations. Dose adjustment may be needed to maintain therapeutic drug concentrations. See digoxin prescribing information.
|
|
|
|
Omeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity.
|
|
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 omeprazole and MMF. Use omeprazole with caution in transplant patients receiving MMF
See the prescribing information for other drugs dependent on gastric pH for absorption. |
|
|
|
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
See |
|
|
|
Potential for increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19
|
|
Monitor tacrolimus whole blood concentrations. Dose adjustment may be needed to maintain therapeutic drug concentrations. See prescribing information for tacrolimus.
|
|
|
|
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
|
|
Temporarily stop omeprazole 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.
|
|
|
|
Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma.
|
|
Temporarily stop omeprazole treatment at least 14 days before assessing to allow gastrin levels to return to baseline
|
|
|
|
There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs.
|
|
An alternative confirmatory method should be considered to verify positive results.
|
|
|
|
There have been clinical reports of interactions with other drugs metabolized via the cytochrome P450 system (e.g., cyclosporine, disulfiram).
|
|
Monitor patients to determine if it is necessary to adjust the dosage of these other drugs when taken concomitantly with omeprazole.
|
|
|
|
Decreased exposure of omeprazole when used concomitantly with strong inducers
|
|
|
|
|
|
Increased exposure of omeprazole
|
|
See prescribing information for voriconazole. |
Omeprazole
20 mg |
Omeprazole
40 mg |
|||
---|---|---|---|---|
Parameter | Max | Min | Max | Min |
1. Single Studies
|
||||
% Decrease in Basal Acid Output
|
78
|
58 to 80
|
94
|
80 to 93
|
% Decrease in Peak Acid Output
|
79
1
|
50 to 59
|
88
|
62 to 68
|
% Decrease in 24-hr. Intragastric Acidity
|
|
80 to 97
|
|
92 to 94
|
1. Mean ± SD (mcg/g)
|
||
Tissue
|
Clarithromycin
|
Clarithromycin + Omeprazole
|
Antrum
|
10.48 ± 2.01 (n = 5)
|
19.96 ± 4.71 (n = 5)
|
Fundus
|
20.81 ± 7.64 (n = 5)
|
24.25 ± 6.37 (n = 5)
|
Mucus
|
4.15 ± 7.74 (n = 4)
|
39.29 ± 32.79 (n = 4)
|
1. Data from single and repeated dose studies. Doses of 10, 20 and 40 mg omeprazole as enteric-coated granules.
2. Data from a single and repeated dose study. Doses of 10, 20 and 40 mg omeprazole as enteric-coated granules. 3. Plasma concentration adjusted to an oral dose of 1 mg/kg. |
|||
Single or Repeated
Oral Dosing/Parameter |
Children
1
≤ 20 kg 2 to 5 Years 10 mg |
Children
1
> 20 kg 6 to 16 Years 20 mg |
Adults
2
(Mean 76 kg) 23 to 29 Years (n=12) |
Single Dosing
|
|||
C
max
3(ng/mL)
|
288 (n=10)
|
495 (n=49)
|
668
|
AUC
3(ng h/mL)
|
511 (n=7)
|
1140 (n=32)
|
1220
|
Repeated Dosing
|
|
|
|
C
max
3(ng/mL)
|
539 (n=4)
|
851 (n=32)
|
1458
|
AUC
3(ng h/mL)
|
1179 (n=2)
|
2276 (n=23)
|
3352
|
1. Includes only patients with pretreatment clarithromycin susceptibility test results. 2. Susceptible (S) MIC ≤ 0.25 mcg/mL, Intermediate (I) MIC 0.5 to 1 mcg/mL, Resistant (R) MIC ≥ 2 mcg/mL. |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Clarithromycin Susceptibility Test Results and Clinical/Bacteriological Outcomes
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Clarithromycin Pretreatment Results
|
Clarithromycin Post-treatment Results
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Post-treatment susceptibility results |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S
|
I
|
R
|
No MIC
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dual Therapy – (omeprazole 40 mg once daily/clarithromycin 500 three times daily for 14 days followed by omeprazole 20 mg once daily for another 14 days) (Studies 4, 5)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Susceptible
|
108
|
72
|
1
|
|
26
|
9
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intermediate
|
1
|
|
|
|
1
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Resistant
|
4
|
|
|
|
4
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Triple Therapy – (omeprazole 20 mg twice daily/clarithromycin 500 mg twice daily/amoxicillin 1 g twice daily for 10 days – Studies 1, 2, 3; followed by omeprazole 20 mg once daily for another 18 days – Studies 1, 2)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Susceptible
|
171
|
153
|
7
|
|
3
|
8
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intermediate
|
|
|
|
|
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Resistant
|
14
|
4
|
1
|
|
6
|
3
|
1. (p ≤ 0.01) | ||||||||
Omeprazole 20 mg a.m.
(n = 99) |
Placebo
a.m. (n = 48) |
|||||||
Week 2
|
41
|
13
|
||||||
Week 4
|
75
|
27
|
1. (p < 0.01) | ||||||||
Omeprazole
20 mg a.m. (n = 145) |
Ranitidine
150 mg Twice Daily (n = 148) |
|||||||
Week 2
|
42
|
34
|
||||||
Week 4
|
82
|
63
|
1. (p ≤ 0.01) | |||||||||||||||||
Omeprazole
|
Ranitidine 150 mg Twice Daily
(n = 35) |
||||||||||||||||
20 mg
(n = 34) |
40 mg
(n = 36) |
||||||||||||||||
Week 2
|
83
|
83
|
53
|
||||||||||||||
Week 4
|
97
|
100
|
82
|
||||||||||||||
Week 8
|
100
|
100
|
94
|
1. Patients were included in the analysis if they had confirmed duodenal ulcer disease (active ulcer, studies 1 and 2; history of ulcer within 5 years, study 3) and
2. Patients were included in the analysis if they had documented 3. (p < 0.05) versus clarithromycin plus amoxicillin. |
||||
|
|
|||
|
|
|
|
|
Study 1
|
77
(n = 64) |
69
(n = 80) |
43 [31, 56]
(n = 67) |
37 [27, 48]
(n = 84) |
Study 2
|
78
(n = 65) |
73
(n = 77) |
41 [29, 54]
(n = 68) |
36 [26, 47]
(n = 83) |
Study 3
|
90
(n = 69) |
83
(n = 84) |
33 [24, 44]
(n = 93) |
32 [23, 42]
(n = 99) |
1. Statistically significantly higher than clarithromycin monotherapy (p < 0.05).
2. Statistically significantly higher than omeprazole monotherapy (p < 0.05). |
|||
|
|
|
|
|
|||
Study 4
|
74 [60, 85]
(n = 53) |
0 [0, 7]
(n = 54) |
31 [18, 47]
(n = 42) |
Study 5
|
64 [51, 76]
(n = 61) |
0 [0, 6]
(n = 59) |
39 [24, 55]
(n = 44) |
|
|||
Study 6
|
83 [71, 92]
(n = 60) |
1 [0, 7]
(n = 74) |
N/A
|
Study 7
|
74 [64, 83]
(n = 86) |
1 [0, 6]
(n = 90) |
N/A
|
1.
2. Combined results for omeprazole + clarithromycin, omeprazole, and clarithromycin treatment arms. 3. Combined results for omeprazole + clarithromycin and omeprazole treatment arms. 4. (p ≤ 0.01) versus proportion with duodenal ulcer recurrence who were not |
||
|
|
|
|
|
|
6 months post-treatment
|
|
|
Study 4
|
35
(n = 49) |
60
(n = 88) |
Study 5
|
8
(n = 53) |
60
(n = 106) |
|
||
6 months post-treatment
|
|
|
Study 6
|
5
(n = 43) |
46
(n = 78) |
Study 7
|
6
(n = 53) |
43
(n = 107) |
12 months post-treatment
|
|
|
Study 6
|
5
(n = 39) |
68
(n = 71) |
1. (p < 0.01) omeprazole 40 mg or 20 mg versus placebo.
2. (p < 0.05) omeprazole 40 mg versus 20 mg. |
|||
Omeprazole
20 mg Once Daily (n = 202) |
Omeprazole
40 mg Once Daily (n = 214) |
Placebo
(n = 104) |
|
Week 4
|
47.5
|
55.6
|
30.8
|
Week 8
|
74.8
|
82.7
|
48.1
|
1. (p < 0.01) omeprazole 40 mg versus ranitidine.
2. (p < 0.01) omeprazole 40 mg versus 20 mg. |
|||
Omeprazole
20 mg Once Daily (n = 200) |
Omeprazole
40 mg Once Daily (n = 187) |
Ranitidine
150 mg Twice Daily (n = 199) |
|
Week 4
|
63.5
|
78.1
|
56.3
|
Week 8
|
81.5
|
91.4
|
78.4
|
1. Defined as complete resolution of heartburn.
2. (p < 0.005) versus 10 mg. 3. (p < 0.005) versus placebo. |
|||||||||||
Omeprazole
20 mg a.m. |
Omeprazole
10 mg a.m. |
Placebo
a.m. |
|||||||||
All patients
|
46
(n = 205) |
31
(n = 199) |
13
(n = 105) |
||||||||
Patients with confirmed GERD
|
56
(n = 115) |
36
(n = 109) |
14
(n = 59) |
1. (p < 0.01) omeprazole versus placebo. | |||
20 mg
Omeprazole (n = 83) |
40 mg
Omeprazole (n = 87) |
Placebo
(n = 43) |
|
Week 4
|
39
|
45
|
7
|
Week 8
|
74
|
75
|
14
|
1. (p < 0.01) omeprazole 20 mg once daily versus omeprazole 20 mg 3 consecutive days per week or placebo. | |||
Omeprazole
20 mg Once Daily (n = 138) |
Omeprazole
20 mg 3 Days per Week (n = 137) |
Placebo
(n = 131) |
|
Percent in endoscopic remission at 6 months
|
70
|
34
|
11
|
1. (p = 0.01) omeprazole 20 mg once daily versus omeprazole 10 mg once daily or Ranitidine.
2. (p = 0.03) omeprazole 10 mg once daily versus Ranitidine. |
|||
Omeprazole
20 mg Once Daily (n = 131) |
Omeprazole
10 mg Once Daily (n = 133) |
Ranitidine
150 mg Twice Daily (n = 128) |
|
Percent in endoscopic remission at 12 months
|
77
|
58
|
46
|