Short-Term Treatment of Active Duodenal Ulcer
Prevacid is indicated for short-term treatment (for 4 weeks) for healing and symptom relief of active duodenal ulcer [see Clinical Studies (14)].
H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence
Triple Therapy: Prevacid/amoxicillin/clarithromycin
Prevacid in combination with amoxicillin plus clarithromycin as triple therapy is indicated 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 [see Clinical Studies (14)].
Please refer to the full prescribing information for amoxicillin and clarithromycin.
Dual Therapy: Prevacid/amoxicillin
Prevacid in combination with amoxicillin as dual therapy is indicated 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 package insert, MICROBIOLOGY section). Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see Clinical Studies (14)].
Please refer to the full prescribing information for amoxicillin.
Maintenance of Healed Duodenal Ulcers
Prevacid is indicated to maintain healing of duodenal ulcers. Controlled studies do not extend beyond 12 months [see Clinical Studies (14)].
Short-Term Treatment of Active Benign Gastric Ulcer
Prevacid is indicated for short-term treatment (up to 8 weeks) for healing and symptom relief of active benign gastric ulcer [see Clinical Studies (14)].
Healing of NSAID-Associated Gastric Ulcer
Prevacid is indicated for the treatment of NSAID-associated gastric ulcer in patients who continue NSAID use. Controlled studies did not extend beyond 8 weeks [see Clinical Studies (14)].
Risk Reduction of NSAID-Associated Gastric Ulcer
Prevacid is indicated 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 [see Clinical Studies (14)].
Gastroesophageal Reflux Disease (GERD)
Short-Term Treatment of Symptomatic GERD
Prevacid is indicated for the treatment of heartburn and other symptoms associated with GERD [see Clinical Studies (14)].
Short-Term Treatment of Erosive Esophagitis
Prevacid is indicated for short-term treatment (up to 8 weeks) for healing and symptom relief of all grades of erosive esophagitis. For patients who do not heal with Prevacid for 8 weeks (5 to 10%), it may be helpful to give an additional 8 weeks of treatment. If there is a recurrence of erosive esophagitis an additional 8-week course of Prevacid may be considered [see Clinical Studies (14)].
Maintenance of Healing of Erosive Esophagitis (EE)
Prevacid is indicated to maintain healing of erosive esophagitis. Controlled studies did not extend beyond 12 months [see Clinical Studies (14)].
Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome (ZES)
Prevacid is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome [see Clinical Studies (14)].
Prevacid Dosage and Administration
Prevacid is available as a capsule and an orally disintegrating tablet, and is available in 15 mg and 30 mg strengths. Directions for use specific to the route and available methods of administration for each of these dosage forms is presented below. Prevacid should be taken before eating. Prevacid products SHOULD NOT BE CRUSHED OR CHEWED. In the clinical trials, antacids were used concomitantly with Prevacid.
Recommended Dose
| Indication |
Recommended Dose |
Frequency |
|---|
|
| Duodenal Ulcers |
|
|
| Short-Term Treatment |
15 mg |
Once daily for 4 weeks |
| Maintenance of Healed |
15 mg |
Once daily |
| H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence |
|
|
| Triple Therapy: |
|
|
| Prevacid |
30 mg |
Twice daily (q12h) for 10 or 14 days |
| Amoxicillin |
1 gram |
Twice daily (q12h) for 10 or 14 days |
| Clarithromycin |
500 mg |
Twice daily (q12h) for 10 or 14 days |
| Dual Therapy: |
|
|
| Prevacid |
30 mg |
Three times daily (q8h) for 14 days |
| Amoxicillin |
1 gram |
Three times daily (q8h) 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 |
| 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§ |
(12 to 17 years of age)
Short-Term Treatment of Symptomatic GERD |
| Nonerosive GERD |
15 mg |
Once daily for up to 8 weeks |
| 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 |
Patients should be instructed that if a dose is missed, it should be taken as soon as possible. However, if the next scheduled dose is due, the patient should not take the missed dose, and should be instructed to take the next dose on time. Patients should be instructed not to take 2 doses at one time to make up for a missed dose.
Special Populations
Renal impairment patients and geriatric patients do not require dosage adjustment. However, consider dose adjustment in patients with severe liver impairment [see Use in Specific Populations (8.5, 8.6 and 8.7)].
Important Administration Information
Administration Options
Prevacid Delayed-Release Capsules – Oral Administration
- Prevacid Delayed-Release Capsules should be swallowed whole.
- Alternatively, for patients who have difficulty swallowing capsules, Prevacid Delayed-Release Capsules can be opened and administered as follows:
- Open capsule.
- Sprinkle intact granules on one tablespoon of either applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears.
- Swallow immediately.
- Prevacid Delayed-Release Capsules may also be emptied into a small volume of either apple juice, orange juice or tomato juice and administered as follows:
- Open capsule.
- Sprinkle intact granules into a small volume of either apple juice, orange juice or tomato juice (60 mL – approximately 2 ounces).
- Mix briefly.
- Swallow immediately.
- To ensure complete delivery of the dose, the glass should be rinsed with two or more volumes of juice and the contents swallowed immediately.
Prevacid Delayed-Release Capsules – Nasogastric Tube (≥16 French) Administration
- For patients who have a nasogastric tube in place, Prevacid Delayed-Release Capsules can be administered as follows:
- Open capsule.
- Mix intact granules into 40 mL of apple juice. DO NOT USE OTHER LIQUIDS.
- Inject through the nasogastric tube into the stomach.
- Flush with additional apple juice to clear the tube.
USE IN OTHER FOODS AND LIQUIDS HAS NOT BEEN STUDIED CLINICALLY AND IS THEREFORE NOT RECOMMENDED.
Prevacid SoluTab Delayed-Release Orally Disintegrating Tablets
- Prevacid SoluTab should not be broken or cut.
- Prevacid SoluTab should not be chewed.
- Place the tablet on the tongue and allow it to disintegrate, with or without water, until the particles can be swallowed.
- The tablet typically disintegrates in less than 1 minute.
- Alternatively, for children or other patients who have difficulty swallowing tablets, Prevacid SoluTab can be delivered in two different ways.
-
- Prevacid SoluTab – Oral Syringe
-
- For administration via oral syringe, Prevacid SoluTab can be administered as follows:
- 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.
- Refill the syringe with approximately 2 mL (5 mL for the 30 mg tablet) of water, shake gently, and administer any remaining contents.
-
- Prevacid SoluTab – Nasogastric Tube (≥8 French) Administration
-
- For administration via a nasogastric tube, Prevacid SoluTab can be administered as follows:
- Place a 15 mg tablet in a syringe and draw up 4 mL of water, or place a 30 mg tablet in a syringe and draw up 10 mL of water.
- Shake gently to allow for a quick dispersal.
- After the tablet has dispersed, inject through the nasogastric tube into the stomach within 15 minutes.
- Refill the syringe with approximately 5 mL of water, shake gently, and flush the nasogastric tube.
Dosage Forms and Strengths
- 15 mg capsules are opaque, hard gelatin, colored pink and green with the TAP logo and "Prevacid 15" imprinted on the capsule.
- 30 mg capsules are opaque, hard gelatin, colored pink and black with the TAP logo and "Prevacid 30" imprinted on the capsule.
- 15 mg tablets are white to yellowish white, uncoated, colored orange to dark brown speckles with "15" debossed on one side of the tablet.
- 30 mg tablets are white to yellowish white, uncoated, colored orange to dark brown speckles with "30" debossed on one side of the tablet.
Contraindications
Prevacid is contraindicated in patients with known severe hypersensitivity to any component of the formulation of Prevacid. For information on contraindications for amoxicillin or clarithromycin, refer to their full prescribing information, CONTRAINDICATIONS sections.
Warnings and Precautions
Gastric Malignancy
Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric malignancy.
Bone Fracture
Several published observational studies suggest that proton pump inhibitor (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 [see Dosage and Administration (2) and Adverse Reactions (6.2)].
For information on warnings and precautions for amoxicillin or clarithromycin, refer to their full prescribing information, WARNINGS and PRECAUTIONS sections.
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), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2)].
Adverse Reactions
Clinical
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.
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.
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 Event |
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 mg 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 has been marketed. The majority of these cases are foreign-sourced and a relationship to Prevacid 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; Digestive System – hepatotoxicity, pancreatitis, vomiting; Hemic and Lymphatic System – agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura; 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); 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 on adverse reactions with amoxicillin or clarithromycin, refer to their full prescribing information, ADVERSE REACTIONS sections.
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 on laboratory value changes with amoxicillin or clarithromycin, refer to their full prescribing information, ADVERSE REACTIONS sections.
Drug Interactions
Drugs with pH-Dependent Absorption Kinetics
Prevacid causes long-lasting inhibition of gastric acid secretion. Prevacid and other PPIs are likely to substantially decrease the systemic concentrations of the HIV protease inhibitor atazanavir, which is dependent upon the presence of gastric acid for absorption, and may result in a loss of therapeutic effect of atazanavir and the development of HIV resistance. Therefore, Prevacid and other PPIs should not be co-administered with atazanavir [see Clinical Pharmacology (12.3)].
Prevacid and other PPIs may interfere with the absorption of other drugs where gastric pH is an important determinant of oral bioavailability (e.g., ampicillin esters, digoxin, iron salts, ketoconazole) [see Clinical Pharmacology (12.3)].
Warfarin
In a study of healthy subjects, co-administration of single or multiple 60 mg doses of Prevacid and warfarin did not affect the pharmacokinetics of warfarin nor prothrombin time [see Clinical Pharmacology (12.3)]. However, there have been reports of 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. Patients treated with PPIs and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time [see Clinical Pharmacology (12.3)].
Tacrolimus
Concomitant administration of lansoprazole and tacrolimus may increase whole blood levels of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19.
Theophylline
A minor increase (10%) in the clearance of theophylline was observed following the administration of Prevacid concomitantly with theophylline. Although the magnitude of the effect on theophylline clearance is small, individual patients may require additional titration of their theophylline dosage when Prevacid is started or stopped to ensure clinically effective blood levels [see Clinical Pharmacology (12.3)].
Clopidogrel
Concomitant administration of lansoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition [see Clinical Pharmacology (12.3)]. No dose adjustment of clopidogrel is necessary when administered with an approved dose of Prevacid.
For information on drug interactions for amoxicillin or clarithromycin, refer to their full prescribing information, DRUG INTERACTIONS sections.
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 Nonclinical Toxicology (13.2)].
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 have been established in pediatric patients 1 to 17 years of age for short-term treatment of symptomatic GERD and erosive esophagitis, however, Prevacid was not effective in patients with symptomatic GERD 1 month to less than 1 year of age in a multicenter, double-blind, placebo controlled study.
Neonate to less than 1 year of age
The pharmacokinetics of lansoprazole were studied in pediatric patients with GERD aged less than 28 days and 1 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 mg/kg/day 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 4 week multicenter, 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 7 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 4 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 (1 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. multicenter study, 66 pediatric patients (1 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 8 to 12 weeks. The Prevacid dose was increased (up to 30 mg twice daily) in 24 of 66 pediatric patients after 2 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 8 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 8 weeks and 100% of patients were healed at 12 weeks by endoscopy (Table 2).
Table 2: 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) |
In a study of 66 pediatric patients in the age group 1 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 Delayed-Release Capsules has been assessed in 66 pediatric patients aged 1 to 11 years of age. Of the 66 patients with GERD 85% (56/66) took Prevacid for 8 weeks and 15% (10/66) took it for 12 weeks.
The most frequently reported (2 or more patients) treatment-related adverse reactions in patients 1 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. multicenter study, 87 adolescent patients (12 to 17 years of age) with symptomatic GERD were treated with Prevacid for 8 to 12 weeks. Baseline upper endoscopies classified these patients into two groups: 64 (74%) nonerosive GERD and 23 (26%) erosive esophagitis (EE). The nonerosive GERD patients received Prevacid 15 mg daily for 8 weeks and the EE patients received Prevacid 30 mg daily for 8 to 12 weeks. At baseline, 89% of these patients had mild to moderate overall GERD symptoms (assessed by investigator interviews). During 8 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 8 weeks of Prevacid treatment. One patient remained unhealed after 12 weeks of treatment (Table 3).
Table 3: 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) |
| Nonerosive 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)‡ |
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 Delayed-Release Capsules has been assessed in these 87 adolescent patients. Of the 87 adolescent patients with GERD, 6% (5/87) took Prevacid for less than 6 weeks, 93% (81/87) for 6 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 package insert as occurring in less than 1% of adult patients, was reported in this study by 3 adolescent patients with nonerosive GERD, who had dizziness concurrently with other reactions (such as migraine, dyspnea, and vomiting).
Geriatric Use
No dosage adjustment of Prevacid is necessary in geriatric patients. The incidence rates of Prevacid-associated adverse reactions and laboratory test abnormalities are similar to those seen in younger patients [see Clinical Pharmacology (12.3)].
Renal Impairment
No dosage adjustment of Prevacid is necessary in patients with renal impairment. The pharmacokinetics of lansoprazole in patients with various degrees of renal impairment were not substantially different compared to those in subjects with normal renal function [see Clinical Pharmacology (12.3)].
Hepatic Impairment
In patients with various degrees of chronic hepatic impairment, an increase in the mean AUC of up to 500% was observed at steady state compared to healthy subjects. Consider dose reduction in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].
Gender
Over 4,000 women were treated with Prevacid. Ulcer healing rates in females were similar to those in males. The incidence rates of adverse reactions in females were similar to those seen in males [see Clinical Pharmacology (12.3)].
Race
The pooled mean pharmacokinetic parameters of Prevacid from twelve U.S. Phase 1 studies (N=513) were compared to the mean pharmacokinetic parameters from two Asian studies (N=20). The mean AUCs of Prevacid in Asian subjects were approximately twice those seen in pooled U.S. data; however, the inter-individual variability was high. The Cmax values were comparable.
Overdosage
Prevacid is not removed from the circulation by hemodialysis. In one reported overdose, a patient consumed 600 mg of Prevacid with no adverse reaction. Oral Prevacid 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.
Prevacid Description
The active ingredient in Prevacid Delayed-Release Capsules and Prevacid SoluTab Delayed-Release Orally Disintegrating Tablets is lansoprazole, a substituted benzimidazole, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl] methyl] sulfinyl] benzimidazole, a compound that inhibits gastric acid secretion. Its empirical formula is C16H14F3N3O2S with a molecular weight of 369.37. Prevacid has the following structure:
Lansoprazole is a white to brownish-white odorless crystalline powder which melts with decomposition at approximately 166°C. Lansoprazole is freely soluble in dimethylformamide; soluble in methanol; sparingly soluble in ethanol; slightly soluble in ethyl acetate, dichloromethane and acetonitrile; very slightly soluble in ether; and practically insoluble in hexane and water.
Lansoprazole is stable when exposed to light for up to two months. The rate of degradation of the compound in aqueous solution increases with decreasing pH. The degradation half-life of the drug substance in aqueous solution at 25°C is approximately 0.5 hour at pH 5.0 and approximately 18 hours at pH 7.0.
Prevacid is supplied in delayed-release capsules and in delayed-release orally disintegrating tablets for oral administration.
The delayed-release capsules are available in two dosage strengths: 15 mg and 30 mg of lansoprazole per capsule. Each delayed-release capsule contains enteric-coated granules consisting of 15 mg or 30 mg of lansoprazole (active ingredient) and the following inactive ingredients: sugar sphere, sucrose, methacrylic acid copolymer, low substituted hydroxypropyl cellulose, starch, magnesium carbonate, talc, polyethylene glycol, titanium dioxide, polysorbate 80, hydroxypropyl cellulose, colloidal silicon dioxide, D&C Red No. 28, FD&C Blue No. 1, FD&C Green No. 3, and FD&C Red No. 40.
Prevacid SoluTab Delayed-Release Orally Disintegrating Tablets are available in two dosage strengths: 15 mg and 30 mg of lansoprazole per tablet. Each delayed-release orally disintegrating tablet contains enteric-coated microgranules consisting of 15 mg or 30 mg of lansoprazole (active ingredient) a
