Approved Drug Label (PDF)
5
Warnings and Precautions
Newly added subsection:
5.5 Severe Cutaneous Adverse Reactions
Severe cutaneous adverse reactions,
including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN),
drug reaction with eosinophilia and systemic symptoms (DRESS), and acute
generalized exanthematous pustulosis (AGEP) have been reported in association
with the use of PPIs [see Adverse
Reactions (6.2)]. Discontinue PRILOSEC at the first signs or symptoms of
severe cutaneous adverse reactions or other signs of hypersensitivity and
consider further evaluation.
Additions and/or revisions underlined:
5.9 Hypomagnesemia and Mineral
Metabolism
… Serious adverse events include tetany,
arrhythmias, and seizures.
Hypomagnesemia may lead to hypocalcemia
and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk
patients. In
most patients, treatment of hypomagnesemia required magnesium replacement and
discontinuation of the PPI.
For patients expected to be on prolonged
treatment or who take PPIs with medications such as digoxin or drugs that may
cause hypomagnesemia (e.g., diuretics), health care professionals may consider
monitoring magnesium levels prior to initiation of PPI treatment and
periodically [see Adverse Reactions
(6.2)].
Consider monitoring magnesium and calcium
levels prior to initiation of PRILOSEC and periodically while on treatment in
patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism).
Supplement with magnesium and/or calcium, as necessary. If hypocalcemia is
refractory to treatment, consider discontinuing the PPI.
6
Adverse Reactions
Additions and/or revisions underlined:
Severe Cutaneous
Adverse Reactions [see Warnings and Precautions (5.5)]
Hypomagnesemia and
Mineral Metabolism [see Warnings and Precautions (5.9)]
Fundic Gland
Polyps [see Warnings and Precautions (5.13)]
6.3 Postmarketing Experience
Additions and/or revisions underlined:
Metabolism
and Nutritional disorders: Hypomagnesemia, hypocalcemia, hypokalemia [Warnings and Precautions 5.9], hyponatremia,
hypoglycemia, weight gain
Skin:
Severe
generalized skin reactions including toxic SJS/TEN (some fatal), DRESS,
AGEP, cutaneous lupus erythematosus and erythema multiforme;
photosensitivity; urticaria; rash; skin inflammation; pruritus; petechiae;
purpura; alopecia; dry skin; hyperhidrosis
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions
and/or revisions underlined:
Before taking PRILOSEC, tell your doctor about all
of your medical conditions, including if you:
What are the
possible side effects of PRILOSEC?
PRILOSEC can
cause serious side effects, including:
Newly
added information:
Skin rash which may have blistering, peeling or
bleeding on any part of your skin (including your lips, eyes, mouth, nose,
genitals, hands or feet).
You may also have fever, chills, body aches,
shortness of breath, or enlarged lymph nodes.
Stop taking
PRILOSEC and call your doctor right away. These symptoms may be the first sign
of a severe skin reaction.
PATIENT COUNSELING INFORMATION
Newly added information:
Severe Cutaneous Adverse Reactions
Advise the patient or caregiver to
discontinue PRILOSEC and report to their healthcare provider at the first
appearance of a severe cutaneous adverse reaction or other sign of
hypersensitivity [see Warnings and
Precautions (5.5)].
Additions and/or revisions underlined:
Hypomagnesemia and Mineral Metabolism
Advise the patient or caregiver to report
any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia,
and/or hypokalemia, to the patient’s healthcare provider, if they have been
receiving PRILOSEC for at least 3 months [see
Warnings and Precautions (5.9)].
Approved Drug Label (PDF)
4
Contraindications
Proton
pump inhibitors (PPIs), including PRILOSEC, are contraindicated in patients
receiving rilpivirine-containing products.
5
Warnings and Precautions
5.1 Presence of Gastric Malignancy
In adults, symptomatic response to therapy with
PRILOSEC does not preclude the presence of gastric malignancy. Consider
additional follow-up and diagnostic testing in adult patients who have a
suboptimal response or an early symptomatic relapse after completing treatment
with a PPI. In older patients, also consider an endoscopy. (Additions and/or revisions underlined)
5.11 Interaction with Methotrexate (revised subheading)
5.3 Clostridium difficile-Associated Diarrhea
Clostridium
difficile-associated diarrhea (CDAD) has been reported with use of nearly
all antibacterial agents. For more information specific to antibacterial agents
(clarithromycin and amoxicillin) indicated for use in combination with
PRILOSEC, refer to Warnings and Precautions
sections of the corresponding prescribing information.
5.5 Cutaneous and Systemic Lupus Erythematosus (added section)
Cutaneous lupus erythematosus (CLE) and systemic lupus
erythematosus (SLE) have been reported in patients taking PPIs, including PRILOSEC.
These events have occurred as both new onset and an exacerbation of existing
autoimmune disease. The majority of PPI-induced lupus erythematosus cases were
CLE.
The most common form of CLE reported in patients treated with PPIs
was subacute CLE (SCLE) and occurred within weeks to years after continuous
drug therapy in patients ranging from infants to the elderly. Generally,
histological findings were observed without organ involvement.
Systemic lupus erythematosus (SLE) is less commonly reported than
CLE in patients receiving PPIs. PPI associated SLE is usually milder than
non-drug induced SLE. Onset of SLE typically occurred within days to years
after initiating treatment primarily in patients ranging from young adults to
the elderly. The majority of patients presented with rash; however, arthralgia
and cytopenia were also reported.
Avoid administration of PPIs for longer than medically indicated.
If signs or symptoms consistent with CLE or SLE are noted in patients receiving
PRILOSEC, discontinue the drug and refer the patient to the appropriate
specialist for evaluation. Most patients improve with discontinuation of the
PPI alone in 4 to 12 weeks. Serological testing (e.g. ANA) may be positive and
elevated serological test results may take longer to resolve than clinical
manifestations.
5.9 Interaction with St. John’s Wort or Rifampin (revised subheading)
6
Adverse Reactions
The
following serious adverse reactions are described below and elsewhere in labeling:
- Acute
Interstitial Nephritis
- Clostridium
difficile-Associated Diarrhea
- Bone
Fracture
- Cutaneous
and Systemic Lupus Erythematosus
- Cyanocobalamin
(Vitamin B-12) Deficiency
- Hypomagnesemia
6.1 Clinical Trials Experience with PRILOSEC Monotherapy
,,,The safety data described below reflects exposure to PRILOSEC
delayed-release capsules in 3096 patients from worldwide clinical trials (465
patients from US studies and 2,631 patients from international studies).
Indications clinically studied in US trials included duodenal ulcer, resistant
ulcer, and Zollinger-Ellison syndrome. The international clinical trials were
double blind and open-label in design. The most common adverse reactions
reported (i.e., with an incidence rate greater than or equal to 2%) from
PRILOSEC-treated patients enrolled in these studies included headache (7%),
abdominal pain (5%), nausea (4%), diarrhea (4%), vomiting
(3%), and flatulence (3%).
Additional adverse reactions that were reported with an incidence
?1% included acid regurgitation (2%), upper respiratory infection (2%),
constipation (2%), dizziness (2%), rash (2%), asthenia (1%),
back pain (1%), and cough (1%)…
… The
clinical trial safety profile in pediatric patients who received PRILOSEC
delayed-release capsules was similar to that in adult patients. Unique to the
pediatric population, however, adverse reactions of the respiratory system were
frequently reported in the 1 month to
less than 1 year age group, the 1 to less than 2 year age group, and the 2
to 16 year age group (42%, 75%, and 19%, respectively). In addition, otitis
media was frequently reported in the 1 month to less than 1 year age group
(22%), fever was frequently reported in the 1 to less than 2 year age group
(33% ), and accidental injuries were frequently reported in the 2 to 16 year
age group (4%).
6.3 Postmarketing Experience
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.
Skin: Severe generalized
skin reactions including toxic epidermal necrolysis (some fatal), Stevens-Johnson
syndrome, cutaneous lupus erythematosus and erythema multiforme …
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 (Added; please refer to label)
Table 4:
Clinically Relevant Interactions Affecting PRILOSEC When Co-Administered with
Other Drugs (Added; please refer to label)
8
Use in Specific Populations
8.1 Pregnancy
(PLLR
Conversion)
Risk Summary (additions underlined)
There are no adequate and well-controlled studies with PRILOSEC in pregnant women. Available epidemiologic data fail
to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use. Reproduction studies in rats and rabbits resulted
in
dose-dependent embryo-lethality at
omeprazole doses that were approximately 3.4 to 34 times an
oral
human dose of 40 mg (based
on a
body surface area for
a 60 kg person).
Teratogenicity was not observed in animal reproduction
studies with administration
of oral esomeprazole (an enantiomer of omeprazole) magnesium in rats and rabbits during organogenesis with doses about 68 times and 42 times,
respectively, an oral human
dose
of 40 mg esomeprazole or 40 mg omeprazole (based on body surface area for a 60
kg
person). However,
changes in bone morphology were observed in
offspring of rats dosed through most of pregnancy and
lactation
at doses equal to
or greater than approximately 34
times an oral human dose
of 40 mg esomeprazole or 40
mg omeprazole.
The estimated background risks of major birth
defects and miscarriage for the indicated
population are unknown.
In the
U.S. general population, the estimated background
risk of major birth
defects and miscarriage in clinically recognized pregnancies is 2% to 4% and
15% to 20%, respectively.
Animal Data
Omeprazole
Reproductive studies conducted with omeprazole in
rats at oral doses up
to
138 mg/kg/day (about 34 times an oral human dose
of 40 mg on a body surface area basis) and in rabbits at doses up to
69.1 mg/kg/day (about 34
times an
oral human
dose of 40 mg on
a body surface area basis) during organogenesis did not disclose any evidence for a teratogenic potential of omeprazole.
In rabbits, omeprazole in a dose range of 6.9 to
69.1 mg/kg/day (about 3.4 to 34 times an oral human
dose of 40 mg on a body surface area basis) administered during organogenesis produced
dose-related increases in embryo-
lethality, fetal resorptions, and
pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal
developmental toxicity were observed in
offspring resulting from parents treated with omeprazole at 13.8 to
138.0 mg/kg/day (about 3.4 to
34 times an
oral human doses
of 40 mg on a body surface area basis),
administered prior to mating through the lactation
period.
Esomeprazole
The data described
below was generated from studies using esomeprazole,
an enantiomer of omeprazole. The animal to
human dose multiples are based on
the assumption
of
equal systemic exposure to esomeprazole in
humans following oral
administration of either 40 mg esomeprazole or 40
mg omeprazole.
No
effects on embryo-fetal development were observed
in reproduction
studies with esomeprazole magnesium in
rats at oral doses up to 280
mg/kg/day (about 68 times an oral human
dose of 40 mg on
a body surface area basis) or in rabbits at oral doses up to 86 mg/kg/day (about 42
times an
oral human dose
of 40 mg esomeprazole or 40
mg
omeprazole
on a body surface area basis) administered during organogenesis.
A pre- and
postnatal developmental toxicity study in
rats with additional endpoints to
evaluate bone development was
performed
with esomeprazole magnesium at oral doses of 14 to
280 mg/kg/day (about 3.4
to
68 times an oral human
dose of 40 mg esomeprazole or 40
mg
omeprazole
on a
body surface area basis).
Neonatal/early postnatal (birth to weaning)
survival was decreased at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human
dose of 40 mg esomeprazole or 40
mg
omeprazole
on a body surface area basis). Body weight and
body weight gain
were reduced and neurobehavioral or general developmental delays in the immediate post-weaning timeframe were evident at doses equal to
or greater than
69 mg/kg/day (about 17 times an oral human dose
of 40 mg esomeprazole or 40
mg
omeprazole
on a
body surface area basis). In
addition, decreased
femur length,
width and thickness of cortical bone,
decreased thickness of the
tibial growth plate and minimal to
mild
bone marrow hypocellularity were noted at doses equal to
or
greater than
14 mg/kg/day (about 3.4 times an oral human dose
of 40 mg esomeprazole or 40 mg
omeprazole on a body surface area
basis). Physeal dysplasia in the femur was observed in offspring of rats treated
with oral doses of esomeprazole
magnesium at doses equal to
or greater than
138 mg/kg/day (about 34 times an
oral
human dose of 40 mg esomeprazole or
40 mg omeprazole
on a
body surface area basis).
Effects on maternal bone were observed in
pregnant and lactating rats in the pre- and
postnatal toxicity study when
esomeprazole magnesium was administered at oral doses of 14 to 280 mg/kg/day (about 3.4 to
68 times an oral human
dose of 40 mg esomeprazole or 40 mg omeprazole
on a
body surface area basis). When rats were dosed from gestational
day 7 through weaning on postnatal day 21, a statistically significant decrease in maternal femur weight of up to
14%
(as compared to placebo treatment) was observed at doses equal to
or
greater than
138 mg/kg/day (about 34 times an oral
human dose of 40 mg esomeprazole or 40
mg
omeprazole on a body surface area basis).
8.2 Lactation
(PLLR Conversion)
Risk Summary
Limited data suggest omeprazole may be present in
human milk. There is no information
on the effects of omeprazole on the breastfed infant or on milk
production. The developmental and health benefits of breastfeeding should
be considered along with the mother's clinical need for PRILOSEC and
any potential adverse effects on the breastfed infant from PRILOSEC or from the
underlying maternal condition.
8.4 Pediatric Use
The safety and effectiveness of PRILOSEC have
been established in pediatric patients 1 to 16 years for the treatment of
symptomatic GERD, treatment of EE due to acid-mediated GERD, and
maintenance of healing of EE due to
acid- mediated GERD. Use of PRILOSEC in this age group is supported by
adequate and well-controlled studies in adults and uncontrolled
safety, efficacy and pharmacokinetic studies performed in pediatric and
adolescent patients.
The safety and effectiveness of PRILOSEC
have been established in pediatric patients 1 month to less than 1 year of age
for the treatment of EE due to acid-mediated GERD and is supported by adequate
and well-controlled studies in adults and safety, pharmacokinetic, and
pharmacodynamic studies performed in pediatric patients.
In the pediatric population, adverse
reactions of the respiratory system were frequently reported in the entire (1
month to 16 year) age group. Otitis
media was frequently reported in the 1 month to less than 1 year age group,
fever was frequently reported in the 1 to less than 2 year age group, and
accidental injuries were frequently reported in the 2 to 16 year age group.
The
safety and effectiveness of PRILOSEC have not been established in:
- patients less than 1 year of
age for:
- Treatment
of symptomatic GERD
- Maintenance
of healing of EE due to acid-mediated GERD
- pediatric patients for:
- Treatment
of active duodenal ulcer
- H.
pylori eradication
to reduce the risk of duodenal ulcer recurrence
- Treatment
of active benign gastric ulcer
- Pathological
hypersecretory conditions
- patients less than 1 month
of age for any indication.
Juvenile
Animal Data
Esomeprazole, an enantiomer of
omeprazole,
was shown to decrease body weight, body weight gain, femur weight, femur
length, and overall growth at oral doses about 34 to 68 times a daily human
dose of 40 mg esomeprazole or 40 mg omeprazole based on body surface
area in a juvenile rat toxicity study.
The animal to human dose multiples are based on the assumption of equal
systemic exposure to esomeprazole in humans following oral administration of
either 40 mg esomeprazole or 40 mg omeprazole.
A 28-day toxicity study with a 14-day
recovery phase was conducted in juvenile rats with esomeprazole magnesium at
doses of 70 to 280 mg/kg/day (about 17 to 68 times a daily oral human dose of
40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). An
increase in the number of deaths at the high dose of 280 mg/kg/day was observed
when juvenile rats were administered esomeprazole magnesium from postnatal day
7 through postnatal day 35. In addition,
doses equal to or greater than 140 mg/kg/day (about 34 times a daily oral human
dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis),
produced treatment-related decreases in body weight (approximately 14%) and
body weight gain, decreases in femur weight and femur length, and affected
overall growth. Comparable findings described above have also been observed in
this study with another esomeprazole salt, esomeprazole strontium, at equimolar
doses of esomeprazole.
8.6 Hepatic Impairment
In patients with hepatic impairment (Child-Pugh Class A, B,
or C) exposure to
omeprazole
substantially increased
compared to healthy subjects.
Dosage reduction
of PRILOSEC to
10 mg once daily is recommended
for
patients with hepatic impairment
for maintenance of healing of EE.
8.7 Asian Population
In studies of healthy subjects, Asians had
approximately a four-fold higher exposure than Caucasians. Dosage reduction PRILOSEC
to 10 mg once daily is recommended for Asian patients for maintenance of healing of EE.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
What
is the most important information I should know about PRILOSEC?
PRILOSEC
may help your acid-related symptoms, but you could still have serious stomach
problems. Talk with your doctor.
PRILOSEC
can cause serious side effects, including:
- A type of kidney problem (acute interstitial
nephritis). Some people who take proton
pump inhibitor (PPI) medicines, including PRILOSEC, may develop a kidney
problem called acute interstitial nephritis that can happen at any time
during treatment with PRILOSEC. Call your doctor if you have a decrease in
the amount that you urinate or if you have blood in your urine.
- Certain
types of lupus erythematosus. Lupus erythematosus is an autoimmune
disorder (the body’s immune cells attack other cells or organs in the
body). Some people who take PPI medicines, including PRILOSEC, may develop
certain types of lupus erythematosus or have worsening of the lupus they
already have. Call your doctor right away if you have new or worsening
joint pain or a rash on your cheeks or arms that gets worse in the sun.
What
is PRILOSEC?
PRILOSEC
is a prescription medicine called a proton pump inhibitor (PPI). PRILOSEC
reduces the amount of acid in your stomach.
PRILOSEC
is used in adults:
for
up to 8 weeks for the healing of duodenal ulcers. The duodenal area is the area
where food passes when it leaves the stomach.
with
certain antibiotics for 10 to 14 days to treat an infection caused by
bacteria called H. pylori. If
needed, your doctor may decide to prescribe another 14 to 18 days of PRILOSEC
by itself after the antibiotics. Sometimes H. pylori bacteria can cause duodenal ulcers…
for
up to 8 weeks to treat
gastroesophageal reflux disease (GERD) with acid-related damage to the
lining of the esophagus [called erosive esophagitis (or EE) due to
acid-mediated GERD].
For children 1 month to less than 12
months (1 year) of age, PRILOSEC is used:
for up to 6 weeks to treat gastroesophageal reflux
disease (GERD) with acid-related damage to the lining of the esophagus [called
erosive esophagitis (or EE) due to acid-mediated GERD]. It is not
known if PRILOSEC is safe and effective for other uses in children 1
month to less than 12 months (1 year) of age, or in children less than 1 month
of age.
Who should not take PRILOSEC? Do
not take PRILOSEC if you:
are taking a medicine that contains rilpivirine
(EDURANT, COMPLERA) used to treat HIV-1 (Human Immunodeficiency Virus).
What should I tell my doctor before taking PRILOSEC?
Before taking PRILOSEC, tell your doctor about all of your medical conditions, including if you:
Tell your doctor about all
of
the medicines you take
including prescription and over-the-counter medicines, vitamins
and herbal supplements. PRILOSEC may affect how other medicines work, and other medicines may affect how
PRILOSEC works. Especially tell
your
doctor if you take an antibiotic that contains clarithromycin or amoxicillin, or if you take clopidogrel (Plavix), methotrexate (Otrxup, Rasuvo, Trexall), St. John’s Wort (Hypericum perforatum), or rifampin (Rimactane, Rifater, Rifamate).
How
should I take PRILOSEC?
PRILOSEC is usually taken 1 time each day. Your doctor will tell you the time of day to
take PRILOSEC, based on your medical condition.
Antacids may be taken with PRILOSEC.
PRILOSEC
Delayed-Release Capsules
• Swallow PRILOSEC Capsules whole. Do
not chew or crush PRILOSEC Capsules.
• If you have trouble swallowing
a whole capsule, you can open the capsule
and take the contents in applesauce. See the “Instructions for Use”
at the end of this Medication Guide for instructions on how to take PRILOSEC
Capsules with applesauce.
PRILOSEC
For Delayed-Release Oral Suspension
PRILOSEC Suspension is mixed with water and can be
taken by mouth, or given through a nasogastric tube (NG tube) or gastric tube.
See the “Instructions for Use” at the end of this
Medication Guide for instructions on how to take PRILOSEC Suspension, and how
to mix and give PRILOSEC Suspension through a nasogastric tube or gastric tube.
If you miss a
dose of PRILOSEC, take it as soon as you remember. If it is almost time for
your next dose, do not take the missed dose. Take the next dose at your
regular time. Do not take 2 doses at the same time to make up for
the missed dose.
If you take too
much PRILOSEC, call your doctor or your poison control center at
1-800-222-1222 right away or go to the nearest emergency room.
What
are the possible side effects of PRILOSEC? PRILOSEC can cause serious side
effects, including:
See
“What is the most important information I should know about PRILOSEC?”
Low magnesium levels in your body. This problem can be serious. Low magnesium can happen in some people who
take
a PPI medicine for at
least 3 months.
Your doctor may stop PRILOSEC if these symptoms happen. Tell
your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects with PRILOSEC. For more information, ask your doctor or pharmacist. Call
your doctor for medical advice about side effects.
PATIENT COUNSELING INFORMATION
“Advise the patient to read the
FDA-approved patient labeling (Medication Guide and Instructions for
Use).
Adverse Reactions
Advise
patients to report to their healthcare provider if they experience any signs or
symptoms consistent with:
• Hypersensitivity reactions
• Acute Interstitial Nephritis
• Clostridium
difficile-Associated Diarrhea.
• Bone Fracture
• Cutaneous and Systemic Lupus
Erythematosus
• Cyanocobalamin (Vitamin B-12)
Deficiency
• Hypomagnesemia
Drug Interactions
Advise patients to report to their
healthcare provider if they start treatment with clopidogrel, St. John’s Wort
or rifampin; or, if they take high-dose methotrexate.
Administration
• Take
PRILOSEC before meals.
• Antacids
may be used concomitantly with PRILOSEC.
• Missed
doses: If a dose is missed, administer as soon as possible. However, if the
next scheduled dose is due, do not take
the missed dose, and take the next dose on time. Do not take two doses at one
time to make up for a missed dose.
PRILOSEC Delayed-Release Capsules
• Swallow
PRILOSEC delayed-release capsules whole; do not chew.
• For
patients unable to swallow an intact capsule, PRILOSEC delayed-release capsules
can be opened and administered in applesauce, as described in the Medication
Guide.
PRILOSEC For Delayed-Release Oral Suspension
• PRILOSEC
for delayed-release oral suspension is intended to be prepared in water and
administered orally or via a nasogastric (NG) or gastric tube, as
described in the Medication Guide.
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