Indications : התוויות

2 THERAPEUTIC INDICATIONS
Dexilant 30 mg is indicated in adults and in adolescents aged 12 to 17 years for the following:
• Maintenance of healed erosive reflux oesophagitis and maintenance of relief of heartburn
• Short-term treatment of heartburn and acid regurgitation associated with
symptomatic non-erosive gastro-oesophageal reflux disease (GORD).

Dexilant 60 mg is indicated in adults and in adolescents aged 12 to 17 years for the following:
• Treatment of erosive reflux oesophagitis

3    DOSAGE AND ADMINISTRATION
3.1 Recommended Dosage in Adults and adolescents aged 12 to 17 years
DEXILANT is available as capsules in 30 mg and 60 mg strengths for adult and
adolescents aged 12 to 17 years use. Directions for use in each indication are
summarized in Table 1.

Table 1. Recommended DEXILANT Capsules dosage regimen by
indication in Adults and adolescents aged 12 to 17 years
Dosage of DEXILANT
Indication                                         Duration
Capsules
Treatment of
One 60 mg capsule once
erosive reflux                                    Up to 8 weeks
daily
oesophagitis
Maintenance of
healed erosive
reflux                                   Controlled studies did not
oesophagitis    One 30 mg capsule once     extend beyond 6 months in
and                 daily                adults and 16 weeks in
maintenance of                               patients 12 to 17 years of
relief of                                            age
heartburn
Symptomatic     One 30 mg capsule once
non-erosive            daily                       4 weeks
        gastro-
oesophageal
reflux disease
(GORD)



3.2 Dosage Adjustment in Patients with Hepatic Impairment
For the treatment of erosive reflux oesophagitis
For patients with moderate hepatic impairment (Child-Pugh Class B), the
recommended dosage is 30 mg DEXILANT once daily for up to eight weeks.
DEXILANT is not recommended in patients with severe hepatic impairment (Child-
Pugh Class C) [see Use in Specific Populations (9.5)].

3.3 Important Administration Information
• Take without regard to food.
•  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.
• Swallow whole; do not chew.
• For patients who have trouble swallowing capsules, DEXILANT capsules can
be opened and administered with applesauce as follows:
1. Place one tablespoonful of applesauce into a clean container.
2. Open capsule.
3. Sprinkle intact granules on applesauce.
4. Swallow applesauce and granules immediately. Do not chew granules. Do
not save the applesauce and granules for later use.
•    Alternatively, the capsule can be administered with water via oral syringe or nasogastric (NG) tube.
Administration with Water in an Oral Syringe
1. Open the capsule and empty the granules into a clean container with 20 mL
of water.
2. Withdraw the entire mixture into a syringe.
3. Gently swirl the syringe in order to keep granules from settling.
4. Administer the mixture immediately into the mouth. Do not save the water
and granule mixture for later use.
5. Refill the syringe with 10 mL of water, swirl gently, and administer.
6. Refill the syringe again with 10 mL of water, swirl gently, and administer.
Administration with Water via a NG Tube (≥16 French)
1. Open the capsule and empty the granules into a clean container with 20 mL
of water.
2. Withdraw the entire mixture into a catheter-tip syringe.
       3. Swirl the catheter-tip syringe gently in order to keep the granules from settling, and immediately inject the mixture through the NG tube into the
stomach. Do not save the water and granule mixture for later use.
4. Refill the catheter-tip syringe with 10 mL of water, swirl gently, and flush
the tube.
5. Refill the catheter-tip syringe again with 10 mL of water, swirl gently, and
administer.

4   DOSAGE FORMS AND STRENGTHS
DEXILANT modified-release capsules
• 30 mg strength is an opaque, blue and gray capsule imprinted with TAP and “30”.
• 60 mg strength is an opaque, blue capsule imprinted with TAP and “60”. 
5   CONTRAINDICATIONS
•   DEXILANT is contraindicated in patients with known hypersensitivity to any component of the formulation [see Description (11)]. Hypersensitivity reactions,
may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute
tubulointerstitial nephritis and urticaria [see Warning and Precautions (6.2),
Adverse Reactions (7)]
•   PPIs, including DEXILANT, are contraindicated with rilpivirine-containing products [see Drug Interactions (8)].

6   WARNINGS AND PRECAUTIONS
6.1 Presence of Gastric Malignancy
In adults, symptomatic response to therapy with DEXILANT 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. 6.2 Acute Tubulointerstitial Nephritis
Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms
of decreased renal function (e.g., malaise, nausea, anorexia). In reported case
series, some patients were diagnosed on biopsy and in the absence of extra-renal
manifestations (e.g., fever, rash or arthralgia).
Discontinue DEXILANT and evaluate patients with suspected acute TIN [see
Contraindications (5)].
6.3 Clostridium difficile - Associated Diarrhea
Published observational studies suggest that PPI therapy like DEXILANT may be
associated with an increased risk of Clostridium difficile associated diarrhea,
especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (7.2)].
Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.
6.4 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 conditions being treated. Patients at risk for osteoporosis-related fractures should be managed
according to established treatment guidelines [see Dosage and Administration (3),
Adverse Reactions (7.2)].


6.5 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 (7.2)].
Discontinue DEXILANT at the first signs or symptoms of severe cutaneous adverse
reactions or other signs of hypersensitivity and consider further evaluation.

6.6 Cutaneous and Systemic Lupus Erythematosus
Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have
been reported in patients taking PPIs. 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 DEXILANT,
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.

6.7 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 DEXILANT.
6.8 Hypomagnesemia and Mineral Metabolism
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.
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 (7.2)].
Consider monitoring magnesium and calcium levels prior to initiation of
DEXILANT 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.
6.9 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 dexlansoprazole 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 [see Drug Interactions (8),
Clinical Pharmacology (12.2)].
6.10 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 [see Drug
Interactions (8)].
6.11 Fundic Gland Polyps
PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed
fundic gland polyps were asymptomatic and fundic gland polyps were identified
incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated.

7   ADVERSE REACTIONS
The following serious adverse reactions are described below and elsewhere in
labeling:
• Acute Tubulointerstitial Nephritis [see Warnings and Precautions (6.2)]
• Clostridium difficile - Associated Diarrhea [see Warnings and Precautions
(6.3)]
• Bone Fracture [see Warnings and Precautions (6.4)]
• Severe Cutaneous Adverse Reactions [see Warnings and Precautions
(6.5)]
•Cutaneous and Systemic Lupus Erythematosus [see Warnings and
Precautions (6.6)]
         •Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (6.7)]
• Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions
(6.8)]
• Fundic Gland Polyps [see Warnings and Precautions (6.11)]
7.1 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 practice.

Adults

The safety of DEXILANT was evaluated in 4548 adult patients in controlled and
single-arm clinical trials, including 863 patients treated for at least six months and 203 patients treated for one year. Patients ranged in age from 18 to 90 years (median age 48 years), with 54% female, 85% Caucasian, 8% Black, 4% Asian, and 3% Other
races. Six randomized controlled clinical trials were conducted for the treatment of erosive reflux oesophagitis, maintenance of healed erosive reflux oesophagitis, and symptomatic GORD, which included 896 patients on placebo, 455 patients on
DEXILANT 30 mg, 2218 patients on DEXILANT 60 mg, and 1363 patients on
lansoprazole 30 mg once daily.

Common Adverse Reactions
The most common adverse reactions (≥2%) that occurred at a higher incidence for
DEXILANT than placebo in the controlled studies are presented in Table 2.
Table 2. Common Adverse Reactions in Controlled Studies in Adults
Placebo     DEXILAN        DEXILAN         DEXILAN        Lansoprazol
T              T              T                e
Adverse
(N=896       30 mg          60 mg           Total           30 mg
Reaction
)        (N=455)        (N=2218)       (N=2621)        (N=1363)
%            %              %              %                %
Diarrhea         2.9          5.1             4.7            4.8              3.2
Abdominal        3.5          3.5             4.0            4.0              2.6
Pain
Nausea           2.6          3.3             2.8            2.9              1.8
Upper            0.8          2.9             1.7            1.9              0.8
Respirator
y Tract
Infection
Vomiting         0.8          2.2             1.4            1.6              1.1
Flatulence       0.6          2.6             1.4            1.6              1.2
Adverse Reactions Resulting in Discontinuation
In controlled clinical studies, the most common adverse reaction leading to
discontinuation from DEXILANT was diarrhea (0.7%).
Less Common Adverse Reactions
Other adverse reactions that were reported in controlled studies at an incidence of less than 2% are listed below by body system:
Blood and Lymphatic System Disorders: anemia, lymphadenopathy
Cardiac Disorders: angina, arrhythmia, bradycardia, chest pain, edema, myocardial
infarction, palpitation, tachycardia
Ear and Labyrinth Disorders: ear pain, tinnitus, vertigo
Endocrine Disorders: goiter
Eye Disorders: eye irritation, eye swelling
Gastrointestinal Disorders: abdominal discomfort, abdominal tenderness, abnormal
feces, anal discomfort, Barrett’s esophagus, bezoar, bowel sounds abnormal, breath odor, colitis microscopic, colonic polyp, constipation, dry mouth, duodenitis,
dyspepsia, dysphagia, enteritis, eructation, oesophagitis, gastric polyp, gastritis, gastroenteritis, gastrointestinal disorders, gastrointestinal hypermotility disorders, GORD, GI ulcers and perforation, hematemesis, hematochezia, hemorrhoids,
impaired gastric emptying, irritable bowel syndrome, mucus stools, oral mucosal
blistering, painful defecation, proctitis, paresthesia oral, rectal hemorrhage, retching General Disorders and Administration Site Conditions: adverse drug reaction,
asthenia, chest pain, chills, feeling abnormal, inflammation, mucosal inflammation, nodule, pain, pyrexia
Hepatobiliary Disorders: biliary colic, cholelithiasis, hepatomegaly
Immune System Disorders: hypersensitivity
Infections and Infestations: candida infections, influenza, nasopharyngitis, oral
herpes, pharyngitis, sinusitis, viral infection, vulvo-vaginal infection
Injury, Poisoning and Procedural Complications: falls, fractures, joint sprains,
overdose, procedural pain, sunburn
Laboratory Investigations: ALP increased, ALT increased, AST increased, bilirubin
decreased/increased, blood creatinine increased, blood gastrin increased, blood
glucose increased, blood potassium increased, liver function test abnormal, platelet count decreased, total protein increased, weight increase
Metabolism and Nutrition Disorders: appetite changes, hypercalcemia, hypokalemia
Musculoskeletal and Connective Tissue Disorders: arthralgia, arthritis, muscle
cramps, musculoskeletal pain, myalgia
Nervous System Disorders: altered taste, convulsion, dizziness, headaches, migraine, memory impairment, paresthesia, psychomotor hyperactivity, tremor, trigeminal
neuralgia
Psychiatric Disorders: abnormal dreams, anxiety, depression, insomnia, libido
changes
Renal and Urinary Disorders: dysuria, micturition urgency
Reproductive System and Breast Disorders: dysmenorrhea, dyspareunia, menorrhagia,
menstrual disorder
Respiratory, Thoracic and Mediastinal Disorders: aspiration, asthma, bronchitis,
cough, dyspnea, hiccups, hyperventilation, respiratory tract congestion, sore throat Skin and Subcutaneous Tissue Disorders: acne, dermatitis, erythema, pruritus, rash, skin lesion, urticaria
Vascular Disorders: deep vein thrombosis, hot flush, hypertension
Additional adverse reactions that were reported in a long-term single-arm trial and were considered related to DEXILANT by the treating physician included:
anaphylaxis, auditory hallucination, B-cell lymphoma, bursitis, central obesity,
cholecystitis acute, dehydration, diabetes mellitus, dysphonia, epistaxis, folliculitis, gout, herpes zoster, hyperlipidemia, hypothyroidism, increased neutrophils, MCHC
decrease, neutropenia, rectal tenesmus, restless legs syndrome, somnolence, tonsillitis. 

Pediatrics
The safety of DEXILANT was evaluated in controlled and single-arm clinical trials
including 166 pediatric patients, 12 to 17 years of age for the treatment of
symptomatic non-erosive GORD, treatment of erosive reflux oesophagitis,
maintenance of healed erosive reflux oesophagitis and maintenance of relief of
heartburn [see Clinical Studies (14.4)].
The adverse reaction profile was similar to that of adults. The most common adverse reactions that occurred in ≥ 5% of patients were headache, abdominal pain, diarrhea, nasopharyngitis and oropharyngeal pain.
Other Adverse Reactions
See the full prescribing information for lansoprazole for other adverse reactions not observed with DEXILANT.
7.2 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of
DEXILANT. Because these reactions are reported voluntarily from a population of
uncertain size, it is not always possible to reliably estimate their frequency or
establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders: autoimmune hemolytic anemia, idiopathic
thrombocytopenic purpura
Ear and Labyrinth Disorders: deafness
Eye Disorders: blurred vision
Gastrointestinal Disorders: oral edema, pancreatitis, fundic gland polyps
General Disorders and Administration Site Conditions: facial edema
Hepatobiliary Disorders: drug-induced hepatitis
Immune System Disorders: anaphylactic shock (requiring emergency intervention),
exfoliative dermatitis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some fatal), DRESS, AGEP.
Infections and Infestations: Clostridium difficile associated diarrhea
Metabolism and Nutrition Disorders: hypomagnesemia, hypocalcemia, hypokalemia,
hyponatremia
Musculoskeletal System Disorders: bone fracture
Nervous System Disorders: cerebrovascular accident, transient ischemic attack
Renal and Urinary Disorders: acute renal failure
Respiratory, Thoracic and Mediastinal Disorders: pharyngeal edema, throat tightness         Skin and Subcutaneous Tissue Disorders: generalized rash, leukocytoclastic vasculitis 
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form
https://sideeffects.health.gov.il

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



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

Antiretrovirals

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

Warfarin

Increased INR and prothrombin time in patients receiving PPIs and
Clinical         warfarin concomitantly. Increases in INR and prothrombin time may lead Impact:          to abnormal bleeding and even death.
    Intervention:    Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for
warfarin.

Methotrexate

Concomitant use of PPIs with methotrexate (primarily at high dose) may
Clinical          elevate and prolong serum concentrations of methotrexate and/or its Impact:           metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have
been conducted [see Warnings and Precautions (6.10)].
A temporary withdrawal of DEXILANT may be considered in some
Intervention:    patients receiving high-dose methotrexate.


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

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

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

Interactions with Investigations of Neuroendocrine Tumors
                  CgA levels increase secondary to PPI-induced decreases in gastric acidity. The Clinical       increased CgA level may cause false positive results in diagnostic
Impact:        investigations for neuroendocrine tumors [see Warnings and Precautions (6.9), Clinical Pharmacology (12.2)].
Temporarily stop DEXILANT treatment at least 14 days before assessing CgA
Intervention: levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory
should be used for testing, as reference ranges between tests may vary.

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

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



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

CYP2C19 or CYP3A4 Inhibitors

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

9      USE IN SPECIFIC POPULATIONS
9.1 Pregnancy
Risk Summary
There are no studies with dexlansoprazole use in pregnant women to inform a drug- associated risk.
Dexlansoprazole is the R-enantiomer of lansoprazole, and published observational
studies of lansoprazole use during pregnancy did not demonstrate an association of adverse pregnancy-related outcomes with lansoprazole (see Data).
In animal reproduction studies, oral administration of lansoprazole to rats during organogenesis through lactation at 1.8 times the maximum recommended human
dexlansoprazole dose produced reductions in the offspring in femur weight, femur
length, crown-rump length and growth plate thickness (males only) on postnatal Day 21 (see Data). These effects were associated with reduction in body weight gain.
Advise pregnant women of the potential risk to the fetus.


The estimated background risk of major birth defects and miscarriage for the
indicated population is unknown. All pregnancies have a background risk of birth
defect, loss, or other adverse outcomes. 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.

Data
Human Data
Dexlansoprazole is the R-enantiomer of lansoprazole. Available data from published observational studies failed to demonstrate an association of adverse pregnancy-
related outcomes and lansoprazole use. Methodological limitations of these
observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. In a prospective study by the European Network of Teratology
Information Services, outcomes from a group of 62 pregnant women administered
median daily doses of 30 mg of lansoprazole were compared to a control group of 868 pregnant women who did not take any PPIs. There was no difference in the rate of
major malformations between women exposed to PPIs and the control group,
corresponding to a Relative Risk (RR)=1.04, [95% Confidence Interval (CI) 0.25-