Overdose
Lansoprazole is not removed
from the circulation by hemodialysis. In one reported overdose, a patient
consumed 600 mg of PREVACID with no adverse reaction. Oral lansoprazole doses
up to 5000 mg/kg in rats [approximately 1300 times the 30 mg human dose based
on body surface area (BSA)] and in mice (about 675.7 times the 30 mg human dose
based on BSA) did not produce deaths or any clinical signs.
In the event of over-exposure,
treatment should be symptomatic and supportive.
If over-exposure occurs, call
your poison control center at 1-800-222-1222 for current information on the
management of poisoning or over-exposure.
Contraindications
- PREVACID and PREVACID SoluTab are contraindicated in
patients with known severe hypersensitivity to any component of the
formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic
shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria.
- Proton Pump Inhibitors (PPIs), including PREVACID and
PREVACID SoluTab, are contraindicated with rilpivirine-containing products.
- For information about contraindications of antibacterial
agents (clarithromycin and amoxicillin) indicated in combination with PREVACID
or PREVACID SoluTab, refer to the Contraindications section of their
prescribing information.
Undesirable effects
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 B12) Deficiency
- Hypomagnesemia
Clinical Trials Experience
Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical trials of a
drug cannot be directly compared to rates in the clinical trials of another
drug and may not reflect the rates observed in clinical practice.
Worldwide, over 10,000 patients have been treated with
PREVACID in Phase 2 or Phase 3 clinical trials involving various dosages and
durations of treatment. In general, PREVACID treatment has been well-tolerated
in both short-term and long-term trials.
The following adverse reactions were reported by the
treating physician to have a possible or probable relationship to drug in 1% or
more of PREVACID-treated patients and occurred at a greater rate in PREVACID-treated
patients than placebo-treated patients in Table 1.
Table 1: Incidence of Possibly or Probably
Treatment-Related Adverse Reactions in Short-Term, Placebo-Controlled PREVACID
Studies
| Body System/ Adverse Reaction |
PREVACID
(N= 2768) % |
Placebo
(N= 1023) % |
| Body as a Whole |
| Abdominal Pain |
2.1 |
1.2 |
| Digestive System |
| Constipation |
1.0 |
0.4 |
| Diarrhea |
3.8 |
2.3 |
| Nausea |
1.3 |
1.2 |
Headache was also seen at
greater than 1% incidence but was more common on placebo. The incidence of
diarrhea was similar between patients who received placebo and patients who
received 15 and 30 mg of PREVACID, but higher in the patients who received 60
mg of PREVACID (2.9, 1.4, 4.2, and 7.4%, respectively).
The most commonly reported
possibly or probably treatment-related adverse event during maintenance therapy
was diarrhea.
In the risk reduction study of
PREVACID for NSAID-associated gastric ulcers, the incidence of diarrhea for
patients treated with PREVACID, misoprostol, and placebo was 5, 22, and 3%,
respectively.
Another study for the same indication, where patients
took either a COX-2 inhibitor or lansoprazole and naproxen, demonstrated that
the safety profile was similar to the prior study. Additional reactions from
this study not previously observed in other clinical trials with PREVACID
included contusion, duodenitis, epigastric discomfort, esophageal disorder,
fatigue, hunger, hiatal hernia, hoarseness, impaired gastric emptying,
metaplasia, and renal impairment.
Additional adverse experiences occurring in less than 1%
of patients or subjects who received PREVACID in domestic trials are shown
below:
Body as a Whole - abdomen enlarged, allergic reaction,
asthenia, back pain, candidiasis, carcinoma, chest pain (not otherwise
specified), chills, edema, fever, flu syndrome, halitosis, infection (not
otherwise specified), malaise, neck pain, neck rigidity, pain, pelvic pain
Cardiovascular System - angina, arrhythmia, bradycardia,
cerebrovascular accident/cerebral infarction, hypertension/hypotension,
migraine, myocardial infarction, palpitations, shock (circulatory failure),
syncope, tachycardia, vasodilation
Digestive System - abnormal stools, anorexia, bezoar,
cardiospasm, cholelithiasis, colitis, dry mouth, dyspepsia, dysphagia,
enteritis, eructation, esophageal stenosis, esophageal ulcer, esophagitis,
fecal discoloration, flatulence, gastric nodules/fundic gland polyps, gastritis,
gastroenteritis, gastrointestinal anomaly, gastrointestinal disorder,
gastrointestinal hemorrhage, glossitis, gum hemorrhage, hematemesis, increased
appetite, increased salivation, melena, mouth ulceration, nausea and vomiting,
nausea and vomiting and diarrhea, gastrointestinal moniliasis, rectal disorder,
rectal hemorrhage, stomatitis, tenesmus, thirst, tongue disorder, ulcerative
colitis, ulcerative stomatitis
Endocrine System - diabetes mellitus, goiter,
hypothyroidism
Hemic and Lymphatic System - anemia, hemolysis,
lymphadenopathy
Metabolism and Nutritional Disorders - avitaminosis,
gout, dehydration, hyperglycemia/hypoglycemia, peripheral edema, weight
gain/loss
Musculoskeletal System - arthralgia, arthritis, bone
disorder, joint disorder, leg cramps, musculoskeletal pain, myalgia,
myasthenia, ptosis, synovitis
Nervous System - abnormal dreams, agitation, amnesia,
anxiety, apathy, confusion, convulsion, dementia, depersonalization,
depression, diplopia, dizziness, emotional lability, hallucinations,
hemiplegia, hostility aggravated, hyperkinesia, hypertonia, hypesthesia,
insomnia, libido decreased/increased, nervousness, neurosis, paresthesia, sleep
disorder, somnolence, thinking abnormality, tremor, vertigo
Respiratory System - asthma, bronchitis, cough increased,
dyspnea, epistaxis, hemoptysis, hiccup, laryngeal neoplasia, lung fibrosis,
pharyngitis, pleural disorder, pneumonia, respiratory disorder, upper
respiratory inflammation/infection, rhinitis, sinusitis, stridor
Skin and Appendages - acne, alopecia, contact dermatitis,
dry skin, fixed eruption, hair disorder, maculopapular rash, nail disorder,
pruritus, rash, skin carcinoma, skin disorder, sweating, urticaria
Special Senses - abnormal vision, amblyopia, blepharitis,
blurred vision, cataract, conjunctivitis, deafness, dry eyes, ear/eye disorder,
eye pain, glaucoma, otitis media, parosmia, photophobia, retinal
degeneration/disorder, taste loss, taste perversion, tinnitus, visual field
defect
Urogenital System - abnormal menses, breast enlargement,
breast pain, breast tenderness, dysmenorrhea, dysuria, gynecomastia, impotence,
kidney calculus, kidney pain, leukorrhea, menorrhagia, menstrual disorder,
penis disorder, polyuria, testis disorder, urethral pain, urinary frequency,
urinary retention, urinary tract infection, urinary urgency, urination
impaired, vaginitis.
Postmarketing Experience
Additional adverse experiences have been reported since
PREVACID and PREVACID SoluTab have been marketed. The majority of these cases
are foreign-sourced and a relationship to PREVACID or PREVACID SoluTab has not
been established. Because these reactions were reported voluntarily from a
population of unknown size, estimates of frequency cannot be made. These events
are listed below by COSTART body system.
Body as a Whole - anaphylactic/anaphylactoid reactions,
systemic lupus erythematosus;
Digestive System - hepatotoxicity, pancreatitis,
vomiting;
Hemic and Lymphatic System - agranulocytosis, aplastic
anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia,
thrombocytopenia, and thrombotic thrombocytopenic purpura;
Infections and Infestations - Clostridium difficile-associated
diarrhea;
Metabolism and Nutritional Disorders - hypomagnesemia;
Musculoskeletal System - bone fracture, myositis;
Skin and Appendages - severe dermatologic reactions
including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal
necrolysis (some fatal), cutaneous lupus erythematosus;
Special Senses - speech disorder;
Urogenital System - interstitial nephritis, urinary
retention.
Combination Therapy With Amoxicillin And Clarithromycin
In clinical trials using combination therapy with
PREVACID plus amoxicillin and clarithromycin, and PREVACID plus amoxicillin, no
adverse reactions peculiar to these drug combinations were observed. Adverse
reactions that have occurred have been limited to those that had been
previously reported with PREVACID, amoxicillin, or clarithromycin.
Triple Therapy: PREVACID/Amoxicillin/Clarithromycin
The most frequently reported adverse reactions for
patients who received triple therapy for 14 days were diarrhea (7%), headache
(6%), and taste perversion (5%). There were no statistically significant
differences in the frequency of reported adverse reactions between the 10 and
14 day triple therapy regimens. No treatment-emergent adverse reactions were
observed at significantly higher rates with triple therapy than with any dual
therapy regimen.
Dual Therapy: PREVACID/Amoxicillin
The most frequently reported adverse reactions for
patients who received PREVACID three times daily plus amoxicillin three times
daily dual therapy were diarrhea (8%) and headache (7%). No treatment-emergent
adverse reactions were observed at significantly higher rates with PREVACID
three times daily plus amoxicillin three times daily dual therapy than with
PREVACID alone.
For information about adverse reactions with
antibacterial agents (amoxicillin and clarithromycin) indicated in combination
with PREVACID or PREVACID SoluTab, refer to the Adverse Reactions section of
their prescribing information.
Laboratory Values
The following changes in laboratory parameters in
patients who received PREVACID were reported as adverse reactions:
Abnormal liver function tests, increased SGOT (AST),
increased SGPT (ALT), increased creatinine, increased alkaline phosphatase,
increased globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal
AG ratio, abnormal RBC, bilirubinemia, blood potassium increased, blood urea
increased, crystal urine present, eosinophilia, hemoglobin decreased,
hyperlipemia, increased/decreased electrolytes, increased/decreased
cholesterol, increased glucocorticoids, increased LDH,
increased/decreased/abnormal platelets, increased gastrin levels and positive
fecal occult blood. Urine abnormalities such as albuminuria, glycosuria, and
hematuria were also reported. Additional isolated laboratory abnormalities were
reported.
In the placebo controlled studies, when SGOT (AST) and
SGPT (ALT) were evaluated, 0.4% (4/978) and 0.4% (11/2677) patients, who
received placebo and PREVACID, respectively, had enzyme elevations greater than
three times the upper limit of normal range at the final treatment visit. None
of these patients who received PREVACID reported jaundice at any time during
the study.
In clinical trials using combination therapy with
PREVACID plus amoxicillin and clarithromycin, and PREVACID plus amoxicillin, no
increased laboratory abnormalities particular to these drug combinations were
observed.
For information about laboratory value changes with
antibacterial agents (amoxicillin and clarithromycin) indicated in combination
with PREVACID or PREVACID SoluTab, refer to the Adverse Reactions section of
their prescribing information.
Therapeutic indications
Treatment Of Active Duodenal
Ulcer
PREVACID and PREVACID SoluTab
are indicated in adults for short-term treatment (for four weeks) for healing
and symptom relief of active duodenal ulcer.
Eradication Of H. Pylori
To Reduce The Risk Of Duodenal Ulcer Recurrence
Triple Therapy: PREVACID Or PREVACID
SoluTab/amoxicillin/clarithromycin
PREVACID or PREVACID SoluTab in
combination with amoxicillin plus clarithromycin as triple therapy is indicated
in adults for the treatment of patients with H. pylori infection and
duodenal ulcer disease (active or one year history of a duodenal ulcer) to
eradicate H. pylori. Eradication of H. pylori has been shown to
reduce the risk of duodenal ulcer recurrence.
Please refer to the full
prescribing information for amoxicillin and clarithromycin.
Dual Therapy: PREVACID Or PREVACID
SoluTab/amoxicillin
PREVACID or PREVACID SoluTab in
combination with amoxicillin as dual therapy is indicated in adults for the
treatment of patients with H. pylori infection and duodenal ulcer
disease (active or one year history of a duodenal ulcer) who are either
allergic or intolerant to clarithromycin or in whom resistance to
clarithromycin is known or suspected (see the clarithromycin prescribing
information, Microbiology section). Eradication of H. pylori has been
shown to reduce the risk of duodenal ulcer recurrence.
Please refer to the full
prescribing information for amoxicillin.
Maintenance Of Healed Duodenal
Ulcers
PREVACID and PREVACID SoluTab
are indicated in adults to maintain healing of duodenal ulcers. Controlled
studies do not extend beyond 12 months.
Treatment Of Active Benign
Gastric Ulcer
PREVACID and PREVACID SoluTab
are indicated in adults for short-term treatment (up to eight weeks) for
healing and symptom relief of active benign gastric ulcer.
Healing Of NSAID-Associated
Gastric Ulcer
PREVACID and PREVACID SoluTab
are indicated in adults for the treatment of NSAID-associated gastric ulcer in
patients who continue NSAID use. Controlled studies did not extend beyond eight
weeks.
Risk Reduction Of NSAID-Associated
Gastric Ulcer
PREVACID and PREVACID SoluTab
are indicated in adults for reducing the risk of NSAID-associated gastric
ulcers in patients with a history of a documented gastric ulcer who require the
use of an NSAID. Controlled studies did not extend beyond 12 weeks.
Treatment Of Symptomatic
Gastroesophageal Reflux Disease (GERD)
PREVACID and PREVACID SoluTab
are indicated in adults and pediatric patients one year of age and older for
the treatment of heartburn and other symptoms associated with GERD for up to
eight weeks.
Treatment Of Erosive
Esophagitis (EE)
PREVACID and PREVACID SoluTab
are indicated for short-term treatment in adults and pediatric patients 12 to
17 years of age (up to eight weeks) and pediatric patients one to 11 years of
age (up to 12 weeks) for healing and symptom relief of all grades of EE.
For adults who do not heal with
PREVACID or PREVACID SoluTab for eight weeks (5 to 10%), it may be helpful to
give an additional eight weeks of treatment. If there is a recurrence of
erosive esophagitis an additional eight week course of PREVACID or PREVACID
SoluTab may be considered.
Maintenance Of Healing Of EE
PREVACID and PREVACID SoluTab
are indicated in adults to maintain healing of EE. Controlled studies did not
extend beyond 12 months.
Pathological Hypersecretory
Conditions Including Zollinger-Ellison Syndrome (ZES)
PREVACID and PREVACID SoluTab
are indicated in adults for the long-term treatment of pathological
hypersecretory conditions, including Zollinger-Ellison syndrome.
Pharmacodynamic properties
Antisecretory Activity
After oral administration, lansoprazole was shown to
significantly decrease the basal acid output and significantly increase the
mean gastric pH and percent of time the gastric pH was greater than three and
greater than four. Lansoprazole also significantly reduced meal-stimulated
gastric acid output and secretion volume, as well as pentagastrin-stimulated
acid output. In patients with hypersecretion of acid, lansoprazole
significantly reduced basal and pentagastrin-stimulated gastric acid secretion.
Lansoprazole inhibited the normal increases in secretion volume, acidity and
acid output induced by insulin.
The intragastric pH results of a five day,
pharmacodynamic, crossover study of 15 and 30 mg of once daily lansoprazole are
presented in Table 6:
Table 6: Mean Antisecretory Effects After Single and
Multiple DailyPREVACID Dosing
| Parameter |
Baseline Value |
PREVACID |
| 15 mg |
30 mg |
| Day 1 |
Day 5 |
Day 1 |
Day 5 |
| Mean 24 Hour pH |
2.1 |
2.7* |
4.0* |
3.6† |
4.9† |
| Mean Nighttime pH |
1.9 |
2.4 |
3.0* |
2.6 |
3.8† |
| % Time Gastric pH>3 |
18 |
33* |
59* |
51† |
72† |
| % Time Gastric pH>4 |
12 |
22* |
49* |
41† |
66† |
NOTE: An intragastric pH of greater than four reflects a
reduction in gastric acid by 99%.
*(p<0.05) vs baseline only.
†(p<0.05) vs baseline and lansoprazole 15 mg. |
After the initial dose in this
study, increased gastric pH was seen within one to two hours with 30 mg of
lansoprazole and two to three hours with 15 mg of lansoprazole. After multiple
daily dosing, increased gastric pH was seen within the first hour post-dosing
with 30 mg of lansoprazole and within one to two hours post-dosing with 15 mg
of lansoprazole.
Acid suppression may enhance
the effect of antimicrobials in eradicating Helicobacter pylori (H.
pylori). The percentage of time gastric pH was elevated above five and six
was evaluated in a crossover study of PREVACID given daily, twice daily and
three times daily (Table 7).
Table 7: Mean Antisecretory Effects After Five Days of
Twice Daily and Three Times Daily Dosing
| Parameter |
PREVACID |
| 30 mg daily |
15 mg twice daily |
30 mg twice daily |
30 mg three times daily |
| % Time Gastric pH>5 |
43 |
47 |
59* |
77† |
| % Time Gastric pH>6 |
20 |
23 |
28 |
45† |
*(p<0.05) vs PREVACID 30 mg
daily
†(p<0.05) vs PREVACID 30 mg daily, 15 and 30 mg twice daily. |
The inhibition of gastric acid
secretion as measured by intragastric pH gradually returned to normal over two
to four days after multiple doses. There was no indication of rebound gastric
acidity.
Enterochromaffin-like (ECL) Cell Effects
During lifetime exposure of
rats with up to 150 mg/kg/day of lansoprazole dosed seven days per week, marked
hypergastrinemia was observed followed by ECL cell proliferation and formation
of carcinoid tumors, especially in female rats. Gastric biopsy specimens from
the body of the stomach from approximately 150 patients treated continuously
with lansoprazole for at least one year did not show evidence of ECL cell
effects similar to those seen in rat studies. Longer term data are needed to
rule out the possibility of an increased risk of the development of gastric
tumors in patients receiving long-term therapy with lansoprazole.
Other Gastric Effects In Humans
Lansoprazole did not
significantly affect mucosal blood flow in the fundus of the stomach. Due to
the normal physiologic effect caused by the inhibition of gastric acid
secretion, a decrease of about 17% in blood flow in the antrum, pylorus, and
duodenal bulb was seen. Lansoprazole significantly slowed the gastric emptying
of digestible solids. Lansoprazole increased serum pepsinogen levels and
decreased pepsin activity under basal conditions and in response to meal
stimulation or insulin injection. As with other agents that elevate
intragastric pH, increases in gastric pH were associated with increases in
nitrate-reducing bacteria and elevation of nitrite concentration in gastric
juice in patients with gastric ulcer. No significant increase in nitrosamine
concentrations was observed.
Serum Gastrin Effects
In over 2100 patients, median
fasting serum gastrin levels increased 50 to 100% from baseline but remained
within normal range after treatment with 15 to 60 mg of oral lansoprazole. These
elevations reached a plateau within two months of therapy and returned to
pre-treatment levels within four weeks after discontinuation of therapy.
Increased gastrin causes
enterochromaffin-like cell hyperplasia and increased serum CgA levels. The
increased CgA levels may cause false positive results in diagnostic
investigations for neuroendocrine tumors.
Endocrine Effects
Human studies for up to one
year have not detected any clinically significant effects on the endocrine
system. Hormones studied include testosterone, luteinizing hormone (LH),
follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG),
dehydroepiandrosterone sulfate (DHEA-S), prolactin, cortisol, estradiol,
insulin, aldosterone, parathormone, glucagon, thyroid stimulating hormone
(TSH), triiodothyronine (T3), thyroxine (T4), and somatotropic hormone (STH).
Lansoprazole in oral doses of 15 to 60 mg for up to one year had no clinically
significant effect on sexual function. In addition, lansoprazole in oral doses
of 15 to 60 mg for two to eight weeks had no clinically significant effect on
thyroid function. In 24 month carcinogenicity studies in Sprague-Dawley rats
with daily lansoprazole dosages up to 150 mg/kg, proliferative changes in the
Leydig cells of the testes, including benign neoplasm, were increased compared
to control rats.
Other Effects
No systemic effects of lansoprazole on the central
nervous system, lymphoid, hematopoietic, renal, hepatic, cardiovascular, or
respiratory systems have been found in humans. Among 56 patients who had
extensive baseline eye evaluations, no visual toxicity was observed after
lansoprazole treatment (up to 180 mg/day) for up to 58 months. After lifetime
lansoprazole exposure in rats, focal pancreatic atrophy, diffuse lymphoid
hyperplasia in the thymus, and spontaneous retinal atrophy were seen.
Pharmacokinetic properties
Absorption
PREVACID and PREVACID SoluTab contain an enteric-coated
granule formulation of lansoprazole (because lansoprazole is acid-labile), so
that absorption of lansoprazole begins only after the granules leave the
stomach. The mean peak plasma levels of lansoprazole occur at approximately 1.7
hours. After a single-dose administration of 15 to 60 mg of oral lansoprazole,
the peak plasma concentrations (Cmax) of lansoprazole and the area under the
plasma concentration curves (AUCs) of lansoprazole were approximately
proportional to the administered dose. Lansoprazole does not accumulate and its
pharmacokinetics are unaltered by multiple dosing. The absolute bioavailability
is over 80%. In healthy subjects, the mean (±SD) plasma half-life was 1.5
(±1.0) hours. Both the Cmax and AUC are diminished by about 50 to 70% if
lansoprazole is given 30 minutes after food, compared to the fasting condition.
There is no significant food effect if lansoprazole is given before meals.
Distribution
Lansoprazole is 97% bound to plasma proteins. Plasma
protein binding is constant over the concentration range of 0.05 to 5 mcg/mL.
Elimination Metabolism
Lansoprazole is extensively metabolized in the liver. Two
metabolites have been identified in measurable quantities in plasma (the
hydroxylated sulfinyl and sulfone derivatives of lansoprazole). These
metabolites have very little or no antisecretory activity. Lansoprazole is
thought to be transformed into two active species which inhibit acid secretion
by blocking the proton pump [(H+, K+)-ATPase enzyme system] at the secretory
surface of the gastric parietal cell. The two active species are not present in
the systemic circulation. The plasma elimination half-life of lansoprazole is
less than two hours while the acid inhibitory effect lasts more than 24 hours.
Therefore, the plasma elimination half-life of lansoprazole does not reflect
its duration of suppression of gastric acid secretion.
Excretion
Following single-dose oral administration of PREVACID,
virtually no unchanged lansoprazole was excreted in the urine. In one study,
after a single oral dose of 14C-lansoprazole, approximately
one-third of the administered radiation was excreted in the urine and
two-thirds was recovered in the feces. This implies a significant biliary
excretion of the lansoprazole metabolites.
Date of revision of the text
Oct 2017
Name of the medicinal product
Prevacid
Fertility, pregnancy and lactation
Teratogenic Effects
Pregnancy Category B.
Reproduction studies have been performed in pregnant rats at oral doses up to
40 times the recommended human dose and in pregnant rabbits at oral doses up to
16 times the recommended human dose and have revealed no evidence of impaired
fertility or harm to the fetus due to lansoprazole. There are, however, no
adequate or well-controlled studies in pregnant women. Because animal
reproduction studies are not always predictive of human response, this drug
should be used during pregnancy only if clearly needed.
See full prescribing
information for clarithromycin before using in pregnant women.
Qualitative and quantitative composition
Dosage Forms And Strengths
PREVACID delayed-release capsules:
- 15 mg strength is an opaque, pink and green capsule
imprinted with TAP and “PREVACID 15”.
- 30 mg strength is an opaque, pink and black capsule
imprinted with TAP and “PREVACID 30”.
PREVACID SoluTab delayed-release orally disintegrating
tablets:
- 15 mg strength is a white to yellowish white, uncoated
round tablet containing orange to dark brown speckles with “15” debossed on one
side.
- 30 mg strength is a white to yellowish white, uncoated
round tablet containing orange to dark brown speckles with “30” debossed on one
side.
Storage And Handling
PREVACID delayed-release
capsules, 15 mg, are opaque, pink and green with “TAP” and “PREVACID 15”
imprinted on the capsules. The 30 mg delayed-release capsules are opaque, pink
and black with “TAP” and “PREVACID 30” imprinted on the capsules. They are
available as follows:
| NDC Number |
Size |
| 64764-541-30 |
Unit of use bottles of 30: 15 mg capsules |
| 64764-541-19 |
Bottles of 1000: 15 mg capsules |
| 64764-541-11 |
Unit dose package of 100: 15 mg capsules |
| 64764-046-13 |
Bottles of 100: 30 mg capsules |
| 64764-046-19 |
Bottles of 1000: 30 mg capsules |
| 64764-046-11 |
Unit dose package of 100: 30 mg capsules |
PREVACID SoluTab delayed-release orally disintegrating tablets, 15 mg, are white to yellowish
white, round uncoated tablets containing orange to dark brown speckles, with
“15” debossed on one side of the tablet. The 30 mg are white to yellowish
white, round uncoated tablets containing orange to dark brown speckles, with
“30” debossed on one side of the tablet. The tablets are available as follows:
| NDC Number |
Size |
| 64764-543-11 |
Unit dose packages of 100: 15 mg tablets |
| 64764-544-11 |
Unit dose packages of 100: 30 mg tablets |
Store at 25°C (77°F); excursions
permitted to 15-30°C (59-86°F).
Distributed by: Takeda Pharmaceuticals America, Inc.,
Deerfield, IL 60015. Revised: Oct 2017
Special warnings and precautions for use
WARNINGS
Included as part of the PRECAUTIONS section.
PRECAUTIONS
Presence Of Gastric Malignancy
In adults, symptomatic response to therapy with PREVACID
or PREVACID SoluTab 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.
Acute Interstitial Nephritis
Acute interstitial nephritis has been observed in
patients taking PPIs including PREVACID and PREVACID SoluTab. Acute
interstitial nephritis may occur at any point during PPI therapy and is
generally attributed to an idiopathic hypersensitivity reaction. Discontinue
PREVACID or PREVACID SoluTab if acute interstitial nephritis develops.
Clostridium Difficile-Associated Diarrhea
Published observational studies suggest that PPI therapy
like PREVACID and PREVACID SoluTab may be associated with an increased risk of Clostridium
difficile-associated diarrhea (CDAD), especially in hospitalized patients.
This diagnosis should be considered for diarrhea that does not improve.
Patients should use the lowest dose and shortest duration
of PPI therapy appropriate to the condition being treated.
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 PREVACID
or PREVACID SoluTab, refer to Warnings and Precautions section of their
prescribing information.
Bone Fracture
Several published observational studies suggest that PPI
therapy may be associated with an increased risk for osteoporosis-related
fractures of the hip, wrist or spine. The risk of fracture was increased in
patients who received high-dose, defined as multiple daily doses, and long-term
PPI therapy (a year or longer). Patients should use the lowest dose and
shortest duration of PPI therapy appropriate to the condition being treated.
Patients at risk for osteoporosis-related fractures should be managed according
to established treatment guidelines.
Cutaneous And Systemic Lupus Erythematosus
Cutaneous lupus erythematosus (CLE) and systemic lupus
erythematosus (SLE) have been reported in patients taking PPIs, including
lansoprazole. 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 PREVACID or PREVACID SoluTab, discontinue the drug and refer
the patient to the appropriate specialist for evaluation. Most patients improve
with discontinuation of the PPI alone in four to 12 weeks. Serological testing
(e.g., ANA) may be positive and elevated serological test results may take
longer to resolve than clinical manifestations.
Cyanocobalamin (Vitamin B12) Deficiency
Daily treatment with any acid-suppressing medications
over a long period of time (e.g., longer than three years) may lead to
malabsorption of cyanocobalamin (Vitamin B12) caused by hypo-or achlorhydria.
Rare reports of cyanocobalamin deficiency occurring with acid-suppressing
therapy have been reported in the literature. This diagnosis should be
considered if clinical symptoms consistent with cyanocobalamin deficiency are
observed in patients treated with PREVACID or PREVACID SoluTab.
Hypomagnesemia
Hypomagnesemia, symptomatic and asymptomatic, has been
reported rarely in patients treated with PPIs for at least three months, in
most cases after a year of therapy. Serious adverse events include tetany,
arrhythmias, and seizures. 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), healthcare professionals may consider
monitoring magnesium levels prior to initiation of PPI treatment and
periodically.
Interactions With Investigations For Neuroendocrine
Tumors
Serum chromogranin A (CgA) levels increase secondary to
drug-induced decreases in gastric acidity. The increased CgA level may cause
false positive results in diagnostic investigations for neuroendocrine tumors.
Healthcare providers should temporarily stop lansoprazole 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 Methotrexate
Literature suggests that concomitant use of PPIs with
methotrexate (primarily at high dose) may elevate and prolong serum levels of
methotrexate and/or its metabolite, possibly leading to methotrexate
toxicities. In high-dose methotrexate administration, a temporary withdrawal of
the PPI may be considered in some patients.
Patients With Phenylketonuria
Phenylalanine can be harmful to patients with phenylketonuria
(PKU). PREVACID SoluTab contains phenylalanine, a component of aspartame. Each
15 mg tablet contains 2.5 mg and each 30 mg tablet contains 5.1 mg of
phenylalanine. Before prescribing PREVACID SoluTab to a patient with PKU,
consider the combined daily amount of phenylalanine from all sources, including
PREVACID SoluTab.
Patient Counseling Information
Advise the patient to read the
FDA-approved patient labeling (Medication Guide and Instructions for Use).
Advise patients to:
Acute Interstitial Nephritis
To call their healthcare
provider if they experience signs and/or symptoms associated with acute
interstitial nephritis.
Clostridium difficile-Associated Diarrhea
To immediately call their
healthcare provider if they experience diarrhea that does not improve.
Bone Fracture
To report any fractures,
especially of the hip, wrist or spine, to their healthcare provider.
Cutaneous And Systemic Lupus
Erythematosus
To immediately call their
healthcare provider for any new or worsening of symptoms associated with
cutaneous or systemic lupus erythematosus.
Cyanocobalamin (Vitamin B12)
Deficiency
To report any clinical symptoms
that may be associated with cyanocobalamin deficiency to their healthcare
provider, if they have been receiving PREVACID or PREVACID SoluTab for longer
than three years.
Hypomagnesemia
To report any clinical symptoms
that may be associated with hypomagnesemia to their healthcare provider, if
they have been receiving PREVACID or PREVACID SoluTab for at least three months
.
Drug Interactions
Advise patients to report to
their healthcare provider if they are taking rilpivirine-containing products or high-dose methotrexate.
Administration
- 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.
- PREVACID or PREVACID SoluTab should be taken before
eating.
- Do not crush or chew PREVACID capsule or PREVACID
SoluTab.
- Take PREVACID or PREVACID SoluTab at least 30 minutes
prior to sucralfate.
- Phenylketonurics: Contains Phenylalanine 2.5 mg per 15
mg PREVACID SoluTab Tablet and 5.1 mg per 30 mg PREVACID SoluTab Tablet.
PREVACID Capsules
- Swallow whole; do not chew.
- For patients who have difficulty swallowing capsules:
- PREVACID capsules can be opened and sprinkled on
applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears.
- PREVACID capsules may also be emptied into a small volume
of either apple juice, orange juice or tomato juice
- Alternatively, PREVACID capsules can be administered with
apple juice via nasogastric tube
- See the Instructions for Use for a description of all
preparation and administration instructions
PREVACID SoluTab
- Do not break or cut.
- Place the tablet on the tongue; allow it to disintegrate,
with or without water, until the particles can be swallowed. Do not chew the
particles.
- The tablet typically disintegrates in less than one
minute.
- Alternatively, for children or other patients who have
difficulty swallowing tablets, PREVACID SoluTab can be administered with water
via oral syringe or NG tube, as described in the Instructions for Use.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis,
Impairment Of Fertility
In two 24 month carcinogenicity studies, Sprague-Dawley
rats were treated with oral lansoprazole doses of five to 150 mg/kg/day, about
one to 40 times the exposure on a body surface (mg/m²) basis of a 50 kg person
of average height [1.46 m² body surface area (BSA)] given the recommended human
dose of 30 mg/day. Lansoprazole produced dose-related gastric
enterochromaffin-like (ECL) cell hyperplasia and ECL cell carcinoids in both
male and female rats. It also increased the incidence of intestinal metaplasia
of the gastric epithelium in both sexes. In male rats, lansoprazole produced a
dose-related increase of testicular interstitial cell adenomas. The incidence
of these adenomas in rats receiving doses of 15 to 150 mg/kg/day (four to 40
times the recommended human dose based on BSA) exceeded the low background
incidence (range = 1.4 to 10%) for this strain of rat.
In a 24 month carcinogenicity
study, CD-1 mice were treated with oral lansoprazole doses of 15 to 600
mg/kg/day, two to 80 times the recommended human dose based on BSA.
Lansoprazole produced a dose-related increased incidence of gastric ECL cell
hyperplasia. It also produced an increased incidence of liver tumors
(hepatocellular adenoma plus carcinoma). The tumor incidences in male mice
treated with 300 and 600 mg/kg/day (40 to 80 times the recommended human dose
based on BSA) and female mice treated with 150 to 600 mg/kg/day (20 to 80 times
the recommended human dose based on BSA) exceeded the ranges of background
incidences in historical controls for this strain of mice. Lansoprazole
treatment produced adenoma of rete testis in male mice receiving 75 to 600
mg/kg/day (10 to 80 times the recommended human dose based on BSA).
A 26 week p53 (+/-) transgenic
mouse carcinogenicity study was not positive.
Lansoprazole was positive in
the Ames test and the in vitro human lymphocyte chromosomal aberration assay.
Lansoprazole was not genotoxic in the ex vivo rat hepatocyte unscheduled DNA
synthesis (UDS) test, the in vivo mouse micronucleus test, or the rat bone
marrow cell chromosomal aberration test.
Lansoprazole at oral doses up
to 150 mg/kg/day (40 times the recommended human dose based on BSA) was found
to have no effect on fertility and reproductive performance of male and female
rats.
Use In Specific Populations
Pregnancy
Teratogenic Effects
Pregnancy Category B.
Reproduction studies have been performed in pregnant rats at oral doses up to
40 times the recommended human dose and in pregnant rabbits at oral doses up to
16 times the recommended human dose and have revealed no evidence of impaired
fertility or harm to the fetus due to lansoprazole. There are, however, no
adequate or well-controlled studies in pregnant women. Because animal
reproduction studies are not always predictive of human response, this drug
should be used during pregnancy only if clearly needed.
See full prescribing
information for clarithromycin before using in pregnant women.
Nursing Mothers
Lansoprazole or its metabolites
are excreted in the milk of rats. It is not known whether lansoprazole is
excreted in human milk. Because many drugs are excreted in human milk, because
of the potential for serious adverse reactions in nursing infants from
lansoprazole, and because of the potential for tumorigenicity shown for
lansoprazole in rat carcinogenicity studies, a decision should be made whether
to discontinue nursing or to discontinue lansoprazole, taking into account the
importance of lansoprazole to the mother.
Pediatric Use
The safety and effectiveness of
PREVACID and PREVACID SoluTab have been established in pediatric patients one
to 17 years of age for short-term treatment of symptomatic GERD and erosive
esophagitis, however, lansoprazole was not effective in patients with
symptomatic GERD one month to less than one year of age in a multi-center,
double-blind, placebo controlled study.
Neonate To Less Than One Year Of Age
The pharmacokinetics of
lansoprazole were studied in pediatric patients with GERD aged less than 28
days and one to 11 months. Compared to healthy adults receiving 30 mg, neonates
had higher exposure (mean weight-based normalized AUC values 2.04 and 1.88 fold
higher at doses of 0.5 and 1 mg/kg/day, respectively). Infants aged ≤ 10
weeks had clearance and exposure values that were similar to neonates. Infants
aged greater than 10 weeks who received 1 mg/kg/day had mean AUC values that
were similar to adults who received a 30 mg dose.
Lansoprazole was not found to
be effective in a U.S. and Polish four week multi-center, double-blind,
placebo-controlled, parallel-group study of 162 patients between one month and
less than 12 months of age with symptomatic GERD based on a medical history of
crying/fussing/irritability associated with feedings who had not responded to
conservative GERD management (i.e., non-pharmacologic intervention) for seven
to 14 days.
Patients received lansoprazole
as a suspension daily (0.2 to 0.3 mg/kg/day in infants ≤ 10 weeks of age
or 1.0 to 1.5 mg/kg/day in infants greater than 10 weeks or placebo) for up to
four weeks of double-blind treatment.
The primary efficacy endpoint
was assessed by greater than 50% reduction from baseline in either the percent
of feedings with a crying/fussing/irritability episode or the duration
(minutes) of a crying/fussing/irritability episode within one hour after
feeding.
There was no difference in the
percentage of responders between the lansoprazole pediatric suspension group
and placebo group (54% in both groups).
There were no adverse events
reported in pediatric clinical studies (one month to less than 12 months of
age) that were not previously observed in adults.
Based on the results of the
Phase 3 efficacy study, lansoprazole was not shown to be effective. Therefore,
these results do not support the use of lansoprazole in treating symptomatic
GERD in infants.
One To 11 Years Of Age
In an uncontrolled, open-label,
U.S. multi-center study, 66 pediatric patients (one to 11 years of age) with
GERD were assigned, based on body weight, to receive an initial dose of either
PREVACID 15 mg daily if ≤ 30 kg or PREVACID 30 mg daily if greater than 30
kg administered for eight to 12 weeks. The PREVACID dose was increased (up to
30 mg twice daily) in 24 of 66 pediatric patients after two or more weeks of
treatment if they remained symptomatic. At baseline 85% of patients had mild to
moderate overall GERD symptoms (assessed by investigator interview), 58%
had non-erosive GERD and 42% had erosive esophagitis (assessed by endoscopy).
After eight to 12 weeks of PREVACID treatment, the
intent-to-treat analysis demonstrated an approximate 50% reduction in frequency
and severity of GERD symptoms.
Twenty one of 27 erosive esophagitis patients were healed
at eight weeks and 100% of patients were healed at 12 weeks by endoscopy (Table
4).
Table 4: GERD Symptom Improvement and Erosive
Esophagitis Healing Rates in Pediatric Patients Age 1 to 11
| GERD |
Final Visit* % (n/N) |
| Symptomatic GERD |
| Improvement in Overall GERD Symptoms† |
76% (47/62‡) |
| Erosive Esophagitis |
| Improvement in Overall GERD Symptoms† |
81% (22/27) |
| Healing Rate |
100% (27/27) |
*At Week 8 or Week 12
†Symptoms assessed by patients diary kept by caregiver.
‡No data were available for four pediatric patients. |
In a study of 66 pediatric patients in the age group one
year to 11 years old after treatment with PREVACID given orally in doses of 15
mg daily to 30 mg twice daily, increases in serum gastrin levels were similar
to those observed in adult studies. Median fasting serum gastrin levels
increased 89% from 51 pg/mL at baseline to 97 pg/mL [interquartile range (25th to
75th percentile) of 71 to 130 pg/mL] at the final visit.
The pediatric safety of
PREVACID capsules has been assessed in 66 pediatric patients aged one to 11
years of age. Of the 66 patients with GERD 85% (56/66) took PREVACID for eight
weeks and 15% (10/66) took it for 12 weeks.
The most frequently reported
(two or more patients) treatment-related adverse reactions in patients one to
11 years of age (N=66) were constipation (5%) and headache (3%).
Twelve To 17 Years Of Age
In an uncontrolled, open-label,
U.S. multi-center study, 87 adolescent patients (12 to 17 years of age) with
symptomatic GERD were treated with PREVACID for eight to 12 weeks. Baseline
upper endoscopies classified these patients into two groups: 64 (74%)
non-erosive GERD and 23 (26%) erosive esophagitis (EE). The non-erosive GERD
patients received PREVACID 15 mg daily for eight weeks and the EE patients
received PREVACID 30 mg daily for eight to 12 weeks. At baseline, 89% of these
patients had mild to moderate overall GERD symptoms (assessed by investigator
interviews). During eight weeks of PREVACID treatment, adolescent patients
experienced a 63% reduction in frequency and a 69% reduction in severity of
GERD symptoms based on diary results.
Twenty one of 22 (95.5%)
adolescent erosive esophagitis patients were healed after eight weeks of
PREVACID treatment. One patient remained unhealed after 12 weeks of treatment (Table
5).
Table 5: GERD Symptom Improvement and Erosive
Esophagitis Healing Rates in Pediatric Patients Age 12 to 17
| GERD |
Final Visit % (n/N) |
| Symptomatic GERD (All Patients) |
| Improvement in Overall GERD Symptoms* |
73.2% (60/82)† |
| Non-erosive GERD |
| Improvement in Overall GERD Symptoms* |
71.2% (42/59)† |
| Erosive Esophagitis |
| Improvement in Overall GERD Symptoms* |
78 3% (18/23) |
| Healing Rate‡ |
95.5% (21/22)‡ |
*Symptoms assessed by patient
diary (parents/caregivers as necessary).
†No data available for five patients.
‡Data from one healed patient was excluded from this analysis due to timing of
final endoscopy. |
In these 87 adolescent patients, increases in serum
gastrin levels were similar to those observed in adult studies, median fasting
serum gastrin levels increased 42% from 45 pg/mL at baseline to 64 pg/mL
[interquartile range (25th to 75th percentile) of 44 to 88 pg/mL] at the final
visit. (Normal serum gastrin levels are 25 to 111 pg/mL.)
The safety of PREVACID capsules
has been assessed in these 87 adolescent patients. Of the 87 adolescent
patients with GERD, 6% (5/87) took PREVACID for less than six weeks, 93%
(81/87) for six to 10 weeks, and 1% (1/87) for greater than 10 weeks.
The most frequently reported
(at least 3%) treatment-related adverse reactions in these patients were
headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%).
Treatment-related dizziness, reported in this prescribing information as
occurring in less than 1% of adult patients, was reported in this study by
three adolescent patients with non-erosive GERD, who had dizziness concurrently
with other reactions (such as migraine, dyspnea, and vomiting).
Geriatric Use
Of the total number of patients
(n=21,486) in clinical studies of PREVACID, 16% of patients were aged 65 years
and over, while 4% were 75 years and over. No overall differences in safety or
effectiveness were observed between these patients and younger patients and other
reported clinical experience has not identified significant differences in
responses between geriatric and younger patients, but greater sensitivity of
some older individuals cannot be ruled out.
Hepatic Impairment
In patients with various
degrees of chronic hepatic impairment the exposure to lansoprazole was
increased compared to healthy subjects with normal hepatic function. No dosage adjustment for PREVACID or PREVACID SoluTab is
necessary for patients with mild (Child-Pugh Class A) or moderate (Child-Pugh
Class B) hepatic impairment. The recommended dosage is 15 mg orally daily in
patients with severe hepatic impairment (Child-Pugh Class C).
Dosage (Posology) and method of administration
Recommended Adult Dosage By Indication
| Indication |
Recommended Dose |
Frequency |
| Duodenal Ulcers |
| Short-Term Treatment |
15 mg |
Once daily for 4 weeks |
| Maintenance of Healed |
15 mg |
Once daily |
| Eradication of H. pylori to Reduce the Risk of Duodenal Ulcer Recurrence* |
| Triple Therapy: |
| PREVACID or PREVACID SoluTab |
30 mg |
Twice daily for 10 or 14 days |
| Amoxicillin |
1 gram |
Twice daily for 10 or 14 days |
| Clarithromycin |
500 mg |
Twice daily for 10 or 14 days |
| Dual Therapy: |
| PREVACID or PREVACID SoluTab |
30 mg |
Three times daily for 14 days |
| Amoxicillin |
1 gram |
Three times daily for 14 days |
| Benign Gastric Ulcer |
| Short-Term Treatment |
30 mg |
Once daily for up to 8 weeks |
| NSAID-associated Gastric Ulcer |
| Healing |
30 mg |
Once daily for 8 weeks† |
| Risk Reduction |
15 mg |
Once daily for up to 12 weeks† |
| Gastroesophageal Reflux Disease (GERD) |
| Short-Term Treatment of Symptomatic GERD |
15 mg |
Once daily for up to 8 weeks |
| Short-Term Treatment of Erosive Esophagitis |
30 mg |
Once daily for up to 8 weeks‡ |
| Maintenance of Healing of Erosive Esophagitis |
15 mg |
Once daily¶ |
| Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome |
60 mg |
Once daily§ |
*Please refer to the amoxicillin and clarithromycin full
prescribing information, Contraindications and Warnings and Precautions sections,
and for information regarding dosing in elderly and renally-impaired patients.
†Controlled studies did not extend beyond indicated duration.
‡For patients who do not heal with PREVACID or PREVACID SoluTab for eight weeks
(5 to 10%), it may be helpful to give an additional eight weeks of treatment.
If there is a recurrence of erosive esophagitis, an additional eight week
course of PREVACID or PREVACID SoluTab may be considered.
§Varies with individual patient. Recommended adult starting dose is 60 mg once
daily. Doses should be adjusted to individual patient needs and should continue
for as long as clinically indicated. Dosages up to 90 mg twice daily have been
administered. Daily dose of greater than 120 mg should be administered in
divided doses. Some patients with Zollinger-Ellison syndrome have been treated
continuously with PREVACID for more than four years.
¶Controlled studies did not extend beyond 12 months. |
Recommended Pediatric Dosage By Indication
| Indication |
Recommended Dose |
Frequency |
| Pediatric (1 to 11 years of age) |
| Short-Term Treatment of Symptomatic GERD and Short-Term Treatment of Erosive Esophagitis |
| ≤30 kg |
15 mg |
Once daily for up to 12 weeks* |
| >30 kg |
30 mg |
Once daily for up to 12 weeks* |
| *The PREVACID dose was increased (up to 30 mg twice
daily) in some pediatric patients after two or more weeks of treatment if they
remained symptomatic. For pediatric patients unable to swallow an intact
capsule please see Administration Options. |
| Indication |
Recommended Dose |
Frequency |
| Pediatric (12 to 17 years of age) |
| Short-Term Treatment of Symptomatic GERD |
| Non-erosive GERD |
15 mg |
Once daily for up to 8 weeks |
| Erosive Esophagitis |
30 mg |
Once daily for up to 8 weeks |
Hepatic Impairment
The recommended dosage is 15 mg
orally daily in patients with severe liver impairment (Child-Pugh C).
Important Administration
Information
- Take PREVACID or PREVACID SoluTab before meals.
- Do not crush or chew PREVACID capsule or PREVACID SoluTab.
- Take PREVACID or PREVACID SoluTab at least 30 minutes
prior to sucralfate.
- Antacids may be used concomitantly with PREVACID or
PREVACID SoluTab.
- 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.
PREVACID Capsules
- Swallow whole; do not chew.
- For patients who have difficulty swallowing capsules,
PREVACID capsules can be opened and administered orally or via a nasogastric
tube in the soft foods or liquids specified below.
- Administration of PREVACID in foods or liquids other than
those discussed below have not been studied clinically and therefore are not
recommended.
Administration In Soft Foods (applesauce, ENSURE pudding,
cottage cheese, yogurt or strained pears)
- Open capsule.
- Sprinkle intact granules on one tablespoon of either
applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears.
- Swallow immediately.
Administration In Liquids (apple juice, orange juice or
tomato juice)
- Open capsule.
- Sprinkle intact granules into a small volume of either
apple juice, orange juice or tomato juice (60 mL - approximately two ounces).
- Mix briefly.
- Swallow immediately.
- To ensure complete delivery of the dose, rinse the glass
with two or more volumes of juice and swallow the contents immediately.
Administration With Apple Juice Through a Nasogastric
Tube (≥ 16 French)
- Open capsule.
- Sprinkle intact granules into 40 mL of apple juice.
- Mix briefly.
- Using a catheter tipped syringe, draw up the mixture.
- Inject through the nasogastric tube into the stomach.
- Flush with additional apple juice to clear the tube.
PREVACID SoluTab
- Do not break or cut.
- Place the tablet on the tongue, allow it to disintegrate,
with or without water, until the microgranules can be swallowed. Do not chew
the microgranules.
- The tablet typically disintegrates in less than one
minute.
- Alternatively, for children or other patients who have
difficulty swallowing tablets, PREVACID SoluTab can be administered with water
via oral syringe or NG tube as follows:
Administration With Water In An Oral Syringe
- Place a 15 mg tablet in oral syringe and draw up 4 mL of
water, or place a 30 mg tablet in oral syringe and draw up 10 mL of water.
- Shake gently to allow for a quick dispersal.
- After the tablet has dispersed, administer the contents
within 15 minutes of mixing into the mouth. Do not save the water and
microgranule mixture for later use.
- Refill the syringe with approximately 2 mL (5 mL for the
30 mg tablet) of water, shake gently, and administer any remaining contents.
Administration With Water Via A NG Tube (≥ 8 French)
- Place a 15 mg tablet in a catheter-tip syringe and draw
up 4 mL of water, or place a 30 mg tablet in a catheter-tip syringe and draw up
10 mL of water.
- Shake gently to allow for a quick dispersal.
- After the tablet has dispersed, shake the catheter-tip
syringe gently in order to keep the microgranules from settling, and
immediately inject the mixture through the NG tube into the stomach within 15
minutes of mixing. Do not save the water and microgranule mixture for later
use.
- Refill the catheter-tip syringe with approximately 5 mL
of water, shake gently, and flush the tube.
Interaction with other medicinal products and other forms of interaction
SIDE EFFECTS
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 B12) Deficiency
- Hypomagnesemia
Clinical Trials Experience
Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical trials of a
drug cannot be directly compared to rates in the clinical trials of another
drug and may not reflect the rates observed in clinical practice.
Worldwide, over 10,000 patients have been treated with
PREVACID in Phase 2 or Phase 3 clinical trials involving various dosages and
durations of treatment. In general, PREVACID treatment has been well-tolerated
in both short-term and long-term trials.
The following adverse reactions were reported by the
treating physician to have a possible or probable relationship to drug in 1% or
more of PREVACID-treated patients and occurred at a greater rate in PREVACID-treated
patients than placebo-treated patients in Table 1.
Table 1: Incidence of Possibly or Probably
Treatment-Related Adverse Reactions in Short-Term, Placebo-Controlled PREVACID
Studies
| Body System/ Adverse Reaction |
PREVACID
(N= 2768) % |
Placebo
(N= 1023) % |
| Body as a Whole |
| Abdominal Pain |
2.1 |
1.2 |
| Digestive System |
| Constipation |
1.0 |
0.4 |
| Diarrhea |
3.8 |
2.3 |
| Nausea |
1.3 |
1.2 |
Headache was also seen at
greater than 1% incidence but was more common on placebo. The incidence of
diarrhea was similar between patients who received placebo and patients who
received 15 and 30 mg of PREVACID, but higher in the patients who received 60
mg of PREVACID (2.9, 1.4, 4.2, and 7.4%, respectively).
The most commonly reported
possibly or probably treatment-related adverse event during maintenance therapy
was diarrhea.
In the risk reduction study of
PREVACID for NSAID-associated gastric ulcers, the incidence of diarrhea for
patients treated with PREVACID, misoprostol, and placebo was 5, 22, and 3%,
respectively.
Another study for the same indication, where patients
took either a COX-2 inhibitor or lansoprazole and naproxen, demonstrated that
the safety profile was similar to the prior study. Additional reactions from
this study not previously observed in other clinical trials with PREVACID
included contusion, duodenitis, epigastric discomfort, esophageal disorder,
fatigue, hunger, hiatal hernia, hoarseness, impaired gastric emptying,
metaplasia, and renal impairment.
Additional adverse experiences occurring in less than 1%
of patients or subjects who received PREVACID in domestic trials are shown
below:
Body as a Whole - abdomen enlarged, allergic reaction,
asthenia, back pain, candidiasis, carcinoma, chest pain (not otherwise
specified), chills, edema, fever, flu syndrome, halitosis, infection (not
otherwise specified), malaise, neck pain, neck rigidity, pain, pelvic pain
Cardiovascular System - angina, arrhythmia, bradycardia,
cerebrovascular accident/cerebral infarction, hypertension/hypotension,
migraine, myocardial infarction, palpitations, shock (circulatory failure),
syncope, tachycardia, vasodilation
Digestive System - abnormal stools, anorexia, bezoar,
cardiospasm, cholelithiasis, colitis, dry mouth, dyspepsia, dysphagia,
enteritis, eructation, esophageal stenosis, esophageal ulcer, esophagitis,
fecal discoloration, flatulence, gastric nodules/fundic gland polyps, gastritis,
gastroenteritis, gastrointestinal anomaly, gastrointestinal disorder,
gastrointestinal hemorrhage, glossitis, gum hemorrhage, hematemesis, increased
appetite, increased salivation, melena, mouth ulceration, nausea and vomiting,
nausea and vomiting and diarrhea, gastrointestinal moniliasis, rectal disorder,
rectal hemorrhage, stomatitis, tenesmus, thirst, tongue disorder, ulcerative
colitis, ulcerative stomatitis
Endocrine System - diabetes mellitus, goiter,
hypothyroidism
Hemic and Lymphatic System - anemia, hemolysis,
lymphadenopathy
Metabolism and Nutritional Disorders - avitaminosis,
gout, dehydration, hyperglycemia/hypoglycemia, peripheral edema, weight
gain/loss
Musculoskeletal System - arthralgia, arthritis, bone
disorder, joint disorder, leg cramps, musculoskeletal pain, myalgia,
myasthenia, ptosis, synovitis
Nervous System - abnormal dreams, agitation, amnesia,
anxiety, apathy, confusion, convulsion, dementia, depersonalization,
depression, diplopia, dizziness, emotional lability, hallucinations,
hemiplegia, hostility aggravated, hyperkinesia, hypertonia, hypesthesia,
insomnia, libido decreased/increased, nervousness, neurosis, paresthesia, sleep
disorder, somnolence, thinking abnormality, tremor, vertigo
Respiratory System - asthma, bronchitis, cough increased,
dyspnea, epistaxis, hemoptysis, hiccup, laryngeal neoplasia, lung fibrosis,
pharyngitis, pleural disorder, pneumonia, respiratory disorder, upper
respiratory inflammation/infection, rhinitis, sinusitis, stridor
Skin and Appendages - acne, alopecia, contact dermatitis,
dry skin, fixed eruption, hair disorder, maculopapular rash, nail disorder,
pruritus, rash, skin carcinoma, skin disorder, sweating, urticaria
Special Senses - abnormal vision, amblyopia, blepharitis,
blurred vision, cataract, conjunctivitis, deafness, dry eyes, ear/eye disorder,
eye pain, glaucoma, otitis media, parosmia, photophobia, retinal
degeneration/disorder, taste loss, taste perversion, tinnitus, visual field
defect
Urogenital System - abnormal menses, breast enlargement,
breast pain, breast tenderness, dysmenorrhea, dysuria, gynecomastia, impotence,
kidney calculus, kidney pain, leukorrhea, menorrhagia, menstrual disorder,
penis disorder, polyuria, testis disorder, urethral pain, urinary frequency,
urinary retention, urinary tract infection, urinary urgency, urination
impaired, vaginitis.
Postmarketing Experience
Additional adverse experiences have been reported since
PREVACID and PREVACID SoluTab have been marketed. The majority of these cases
are foreign-sourced and a relationship to PREVACID or PREVACID SoluTab has not
been established. Because these reactions were reported voluntarily from a
population of unknown size, estimates of frequency cannot be made. These events
are listed below by COSTART body system.
Body as a Whole - anaphylactic/anaphylactoid reactions,
systemic lupus erythematosus;
Digestive System - hepatotoxicity, pancreatitis,
vomiting;
Hemic and Lymphatic System - agranulocytosis, aplastic
anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia,
thrombocytopenia, and thrombotic thrombocytopenic purpura;
Infections and Infestations - Clostridium difficile-associated
diarrhea;
Metabolism and Nutritional Disorders - hypomagnesemia;
Musculoskeletal System - bone fracture, myositis;
Skin and Appendages - severe dermatologic reactions
including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal
necrolysis (some fatal), cutaneous lupus erythematosus;
Special Senses - speech disorder;
Urogenital System - interstitial nephritis, urinary
retention.
Combination Therapy With Amoxicillin And Clarithromycin
In clinical trials using combination therapy with
PREVACID plus amoxicillin and clarithromycin, and PREVACID plus amoxicillin, no
adverse reactions peculiar to these drug combinations were observed. Adverse
reactions that have occurred have been limited to those that had been
previously reported with PREVACID, amoxicillin, or clarithromycin.
Triple Therapy: PREVACID/Amoxicillin/Clarithromycin
The most frequently reported adverse reactions for
patients who received triple therapy for 14 days were diarrhea (7%), headache
(6%), and taste perversion (5%). There were no statistically significant
differences in the frequency of reported adverse reactions between the 10 and
14 day triple therapy regimens. No treatment-emergent adverse reactions were
observed at significantly higher rates with triple therapy than with any dual
therapy regimen.
Dual Therapy: PREVACID/Amoxicillin
The most frequently reported adverse reactions for
patients who received PREVACID three times daily plus amoxicillin three times
daily dual therapy were diarrhea (8%) and headache (7%). No treatment-emergent
adverse reactions were observed at significantly higher rates with PREVACID
three times daily plus amoxicillin three times daily dual therapy than with
PREVACID alone.
For information about adverse reactions with
antibacterial agents (amoxicillin and clarithromycin) indicated in combination
with PREVACID or PREVACID SoluTab, refer to the Adverse Reactions section of
their prescribing information.
Laboratory Values
The following changes in laboratory parameters in
patients who received PREVACID were reported as adverse reactions:
Abnormal liver function tests, increased SGOT (AST),
increased SGPT (ALT), increased creatinine, increased alkaline phosphatase,
increased globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal
AG ratio, abnormal RBC, bilirubinemia, blood potassium increased, blood urea
increased, crystal urine present, eosinophilia, hemoglobin decreased,
hyperlipemia, increased/decreased electrolytes, increased/decreased
cholesterol, increased glucocorticoids, increased LDH,
increased/decreased/abnormal platelets, increased gastrin levels and positive
fecal occult blood. Urine abnormalities such as albuminuria, glycosuria, and
hematuria were also reported. Additional isolated laboratory abnormalities were
reported.
In the placebo controlled studies, when SGOT (AST) and
SGPT (ALT) were evaluated, 0.4% (4/978) and 0.4% (11/2677) patients, who
received placebo and PREVACID, respectively, had enzyme elevations greater than
three times the upper limit of normal range at the final treatment visit. None
of these patients who received PREVACID reported jaundice at any time during
the study.
In clinical trials using combination therapy with
PREVACID plus amoxicillin and clarithromycin, and PREVACID plus amoxicillin, no
increased laboratory abnormalities particular to these drug combinations were
observed.
For information about laboratory value changes with
antibacterial agents (amoxicillin and clarithromycin) indicated in combination
with PREVACID or PREVACID SoluTab, refer to the Adverse Reactions section of
their prescribing information.
DRUG INTERACTIONS
Tables 2 and 3 include drugs with clinically important
drug interactions and interaction with diagnostics when administered
concomitantly with PREVACID or PREVACID SoluTab and instructions for preventing
or managing them.
Consult the labeling of concomitantly used drugs to
obtain further information about interactions with PPIs.
Table 2: Clinically Relevant Interactions Affecting
Drugs Co-Administered with PREVACID or PREVACID SoluTab and Interactions 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 lansoprazole may reduce antiviral effect and promote the development of drug resistance.
- Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with lansoprazole may increase toxicity of the antiretroviral drugs.
- There are other antiretroviral drugs which do not result in clinically relevant interactions with lansoprazole.
|
| Intervention: |
Rilpivirine-containing products: Concomitant use with PREVACID or PREVACID SoluTab is contraindicated. See prescribing information.
Atazanavir: See prescribing information for atazanavir for dosing information.
Nelfinavir: Avoid concomitant use with PREVACID or PREVACID SoluTab. See prescribing information for nelfinavir.
Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities.
Other antiretrovirals: See prescribing information. |
| Warfarin |
| Clinical Impact: |
Increased INR and prothrombin time in patients receiving PPIs and warfarin concomitantly. Increases in INR and prothrombin time may lead 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 |
| Clinical Impact: |
Concomitant use of PPIs 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. |
| Intervention: |
A temporary withdrawal of PREVACID or PREVACID SoluTab may be considered in some patients receiving high-dose methotrexate. |
| Digoxin |
| Clinical Impact: |
Potential for increased exposure of digoxin. |
| Intervention: |
Monitor digoxin concentrations. Dose adjustment of digoxin may be needed to maintain therapeutic drug concentrations. See prescribing information for digoxin. |
| Theophylline |
| Clinical Impact: |
Increased clearance of theophylline. |
| Intervention: |
Individual patients may require additional titration of their theophylline dosage when PREVACID or PREVACID SoluTab is started or stopped to ensure clinically effective blood concentrations. |
| Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) |
| Clinical Impact: |
Lansoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity. |
| Intervention: |
Mycophenolate mofetil (MMF): Co-administration of PPIs 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 PREVACID and MMF. Use PREVACID and PREVACID SoluTab with caution in transplant patients receiving MMF.
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 and Warnings and Precautions in prescribing information for clarithromycin.
- See Drug Interactions in prescribing information for amoxicillin.
|
| Tacrolimus |
| Clinical Impact: |
Potentially increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19. |
| Intervention: |
Monitor tacrolimus whole blood trough concentrations. Dose adjustment of tacrolimus may be needed to maintain therapeutic drug concentrations. See prescribing information for tacrolimus. |
| Interactions with Investigations of Neuroendocrine Tumors |
| Clinical Impact: |
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. |
| Intervention: |
Temporarily stop PREVACID or PREVACID SoluTab 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 PREVACID or PREVACID SoluTab treatment at least 28 days before assessing to allow gastrin levels to return to baseline. |
| 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. |
Table 3: Clinically Relevant Interactions Affecting PREVACID or PREVACID SoluTab When Co-Administered with
Other Drugs
| CYP2C19 OR CYP3A4 Inducers |
| Clinical Impact: |
Decreased exposure of lansoprazole when used concomitantly with strong inducers. |
| Intervention: |
St John’s Wort, rifampin: Avoid concomitant use with PREVACID or PREVACID SoluTab.
Ritonavir-containing products: See prescribing information. |
| CYP2C19 or CYP3A4 Inhibitors |
| Clinical Impact: |
Increased exposure of lansoprazole is expected when used concomitantly with strong inhibitors. |
| Intervention: |
Voriconazole: See prescribing information. |
| Sucralfate |
| Clinical Impact: |
Decreased and delayed absorption of lansoprazole. |
| Intervention: |
Take PREVACID or PREVACID SoluTab at least 30 minutes prior to sucralfate. |
