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HIGHLIGHTS OF PRESCRIBING INFORMATION
Use caution when treating patients who are hypersensitive to These highlights do not include all the information needed to use LIALDA
safely and effectively. See full prescribing information for LIALDA.
Mesalamine-induced cardiac hypersensitivity reactions (myocarditis LIALDA® (mesalamine) delayed-release tablets, for oral use
and pericarditis) have been reported. (5.3) Initial U.S. Approval: 1987
Hepatic failure has been reported in patients with preexisting liverdisease. Use caution when treating patients with liver disease. (5.4) ---------------------------RECENT MAJOR CHANGES---------------------------
Upper GI tract obstruction may delay onset of action. (5.5) Warnings and Precautions, Interference with Laboratory Tests (5.6), 08/2013 Use of mesalamine may lead to spuriously elevated test results when ---------------------------INDICATIONS AND USAGE----------------------------
measuring urinary normetanephrine by liquid chromatography with LIALDA is a locally acting 5-aminosalicylic acid (5-ASA) indicated for the induction of remission in adults with active, mild to moderate ulcerative ------------------------------ADVERSE REACTIONS------------------------------
colitis and for the maintenance of remission of ulcerative colitis. (1) The most common adverse reactions (incidence ≥ 2 %) are ulcerative ------------------------DOSAGE AND ADMINISTRATION------------------------
colitis, headache, flatulence, liver function test abnormality, and For induction of remission of active, mild to moderate ulcerative colitis, two to four 1.2 g tablets taken once daily with food. (1, 2) To report SUSPECTED ADVERSE REACTIONS, contact Shire US Inc. at
For maintenance of remission of ulcerative colitis, two 1.2 g tablets taken 1-800-828-2088 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
-------------------------------DRUG INTERACTIONS-----------------------------
----------------------DOSAGE FORMS AND STRENGTHS----------------------
Nephrotoxic agents including NSAIDs: renal reactions have been Azathioprine or 6-mercaptopurine: blood disorders have been reported. (7.2) ------------------------------CONTRAINDICATIONS------------------------------
Patients with known hypersensitivity to salicylates or aminosalicylates or ------------------------USE IN SPECIFIC POPULATIONS------------------------
to any of the ingredients of LIALDA tablets. (4) Renal impairment: Use LIALDA with caution in patients with a historyof renal disease. (5.1, 7.1, 8.5, 13.2) ------------------------WARNINGS AND PRECAUTIONS------------------------
Nursing Women: Caution should be exercised when administered to a Renal impairment may occur. Assess renal function at the beginning of treatment and periodically during treatment. (5.1) Geriatric Patients: Monitor blood cell counts in geriatric patients. (8.5) Mesalamine-induced acute intolerance syndrome has been reported.
Observe patients closely for worsening of these symptoms while on See 17 for PATIENT COUNSELING INFORMATION
Revised: September 2013
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
8 USE IN SPECIFIC POPULATIONS
16 HOW SUPPLIED/STORAGE AND HANDLING
2 DOSAGE AND ADMINISTRATION
17 PATIENT COUNSELING INFORMATION
3 DOSAGE FORMS AND STRENGTHS
*Sections or subsections omitted from the full 4 CONTRAINDICATIONS
prescribing information are not listed.
5 WARNINGS AND PRECAUTIONS
10 OVERDOSAGE
11 DESCRIPTION
Mesalamine-Induced Acute IntoleranceSyndrome 12 CLINICAL PHARMACOLOGY
13 NONCLINICAL TOXICOLOGY
6 ADVERSE REACTIONS
7 DRUG INTERACTIONS
14 CLINICAL STUDIES
Maintenance of Remission in Patientswith Ulcerative Colitis FULL PRESCRIBING INFORMATION
INDICATIONS AND USAGE
In two 8-week placebo-controlled clinical trials involving 535 ulcerative colitis LIALDA is indicated for the induction of remission in patients with active, mild to patients, 356 received 2.4 g/day or 4.8 g/day LIALDA tablets and 179 received moderate ulcerative colitis and for the maintenance of remission of ulcerative colitis.
placebo. The most frequent adverse reaction leading to discontinuation from LIALDAtherapy was exacerbation of ulcerative colitis (0.8%). Pancreatitis occurred in less DOSAGE AND ADMINISTRATION
than 1% of patients during clinical trials and resulted in discontinuation of therapy The recommended dosage for the induction of remission in adult patients with active, with LIALDA in patients experiencing this event.
mild to moderate ulcerative colitis is two to four 1.2 g tablets taken once daily with a Adverse reactions occurring in LIALDA or placebo groups at a frequency of at least meal for a total daily dose of 2.4 g or 4.8 g. The recommended dosage for the 1% in two 8-week, double blind, placebo-controlled trials are listed in Table 1. The maintenance of remission is two 1.2 g tablets taken once daily with a meal for a total most common adverse reactions with LIALDA 2.4 g/day and 4.8 g/day were headache (5.6% and 3.4%, respectively) and flatulence (4% and 2.8%, respectively).
DOSAGE FORMS AND STRENGTHS
Table 1: Adverse Reactions in Two Eight-Week Placebo-Controlled Trials Experienced
The red-brown ellipsoidal delayed-release tablet containing 1.2 g mesalamine is by at Least 1% of the LIALDA Group and at a Rate Greater than Placeboa
debossed on one side and imprinted with S476.
CONTRAINDICATIONS
2.4 g/day
4.8 g/day
LIALDA is contraindicated in patients with known hypersensitivity to salicylates or Adverse Reaction
aminosalicylates or to any of the ingredients of LIALDA [see Warnings and Precautions (5.3), Description (11), Adverse Reactions (6.2)].
WARNINGS AND PRECAUTIONS
5.1 Renal Impairment
Renal impairment, including minimal change nephropathy, acute and chronic interstitialnephritis, and, rarely, renal failure, has been reported in patients given products such as LIALDA that contain mesalamine or are converted to mesalamine.
It is recommended that patients have an evaluation of renal function prior to initiation a: Adverse reactions for which the placebo rate equalled or exceeded the rate for of LIALDA therapy and periodically while on therapy. Exercise caution when using at least one of the LIALDA treatment groups were abdominal pain, dizziness, LIALDA in patients with known renal dysfunction or a history of renal disease.
In animal studies, the kidney was the principal organ for toxicity. [See Drug Interactions(7.1) and Nonclinical Toxicology (13.2)] The following adverse reactions, presented by body system, were reportedinfrequently (less than 1%) by LIALDA-treated ulcerative colitis patients in the two 5.2 Mesalamine-Induced Acute Intolerance Syndrome
Mesalamine has been associated with an acute intolerance syndrome that may be difficult to distinguish from an exacerbation of ulcerative colitis. Although the exactfrequency of occurrence has not been determined, it has occurred in 3% of patients in Vascular Disorders: hypertension, hypotension controlled clinical trials of mesalamine or sulfasalazine. Symptoms include cramping, Skin and Subcutaneous Tissue Disorders: acne, prurigo, rash, urticaria acute abdominal pain and bloody diarrhea, and sometimes fever, headache, and rash.
Gastrointestinal Disorders: abdominal distention, colitis, diarrhea, pancreatitis, rectal Observe patients closely for worsening of these symptoms while on treatment. If acute intolerance syndrome is suspected, promptly discontinue treatment with LIALDA.
Investigations: decreased platelet count 5.3 Hypersensitivity Reactions
Musculoskeletal and Connective Tissue Disorders: arthralgia, back pain Some patients who have experienced a hypersensitivity reaction to sulfasalazine may Nervous System Disorders: somnolence, tremor have a similar reaction to LIALDA tablets or to other compounds that contain or are Respiratory, Thoracic and Mediastinal Disorders: pharyngolaryngeal pain General Disorders and Administrative Site Disorders: asthenia, face edema, fatigue, Mesalamine-induced cardiac hypersensitivity reactions (myocarditis and pericarditis) have been reported with LIALDA and other mesalamine medications. Caution should Ear and Labyrinth Disorders: ear pain be taken in prescribing this medicine to patients with conditions predisposing themto the development of myocarditis or pericarditis.
Maintenance of Remission of Ulcerative ColitisThe dose evaluated in three studies of LIALDA given for the maintenance of 5.4 Hepatic Impairment
remission in patients with ulcerative colitis was 1.2 g twice daily or 2.4 g/once daily.
There have been reports of hepatic failure in patients with pre-existing liver disease One of these studies was a 6-month double-blind comparator study while two were who have been administered mesalamine. Caution should be exercised when administering LIALDA to patients with liver disease.
The most common adverse reactions with LIALDA in the maintenance arms oflong-term trials were colitis ulcerative (5.8%), headache (2.9%), liver function test 5.5 Upper GI Tract Obstruction
abnormal (2.3%), and abdominal pain (2.2%). Of the 1082 subjects in the all Pyloric stenosis or other organic or functional obstruction in the upper gastrointestinal maintenance studies pooled, 1.9% had severe adverse reactions. The most common tract may cause prolonged gastric retention of LIALDA which would delay mesalamine severe adverse reactions were gastrointestinal disorders; these were mainly symptoms associated with ulcerative colitis.
5.6 Interference With Laboratory Tests
Table 2: Adverse Reactions in Three Maintenance Trials Experienced by at Least
Use of mesalamine may lead to spuriously elevated test results when measuring 1% of the LIALDA Group (maintenance phases of trials)
urinary normetanephrine by liquid chromatography with electrochemical detectionbecause of the similarity in the chromatograms of normetanephrine and All LIALDA
mesalamine’s main metabolite, N-acetylaminosalicylic acid (N-Ac-5-ASA). An (n=1082)
alternative, selective assay for normetanephrine should be considered.
Adverse Reaction
ADVERSE REACTIONS
The most serious adverse reactions seen in Lialda clinical trials or with other products that contain or are metabolized to mesalamine are: • Renal impairment, including renal failure [See Warnings and Precautions (5.1)] • Mesalamine-induced acute intolerance syndrome [See Warnings and Precautions • Hypersensitivity reactions [See Warnings and Precautions (5.3)] • Hepatic impairment, including hepatic failure [See Warnings and Precautions (5.4)] 6.1 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.
LIALDA has been evaluated in 1368 ulcerative colitis patients in controlled and The following adverse reactions, presented by body system, were reported reported clinical experience has not identified differences in responses between the infrequently (less than 1%) by LIALDA-treated ulcerative colitis patients in the three elderly and younger patients. Systemic exposures are increased in elderly subjects.
long-term maintenance trials (maintenance phases of these trials): [see Clinical Pharmacology (12.3)]. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflectingthe greater frequency of decreased hepatic, renal, or cardiac function, and of Skin and Subcutaneous Tissue Disorders: acne, alopecia, pruritus, urticaria concurrent disease or other drug therapy in elderly patients.
Gastrointestinal Disorders: colitis, flatulence, nausea, pancreatitis, rectal polyp, vomitingNervous System Disorders: dizziness OVERDOSAGE
Respiratory, Thoracic and Mediastinal Disorders: pharyngolaryngeal pain LIALDA is an aminosalicylate, and symptoms of salicylate toxicity may include tinnitus,vertigo, headache, confusion, drowsiness, sweating, seizures, hyperventilation, General Disorders and Administrative Site Disorders: asthenia, pyrexia dyspnea, vomiting, and diarrhea. Severe intoxication may lead to disruption of Ear and Labyrinth Disorders: ear pain electrolyte balance and blood-pH, hyperthermia, dehydration, and end organ damage.
6.2 Postmarketing Experience
There is no specific known antidote for mesalamine overdose; however, conventional In addition to the adverse reactions reported above in clinical trials involving LIALDA, therapy for salicylate toxicity may be beneficial in the event of acute overdosage.
the adverse reactions listed below have been identified during post-approval use of Fluid and electrolyte imbalance should be corrected by the administration of LIALDA and other mesalamine-containing products. Because these reactions are appropriate intravenous therapy. Adequate renal function should be maintained.
reported voluntarily from a population of uncertain size, it is not always possible to DESCRIPTION
reliably estimate their frequency or establish a causal relationship to drug exposure.
Each LIALDA delayed-release tablet for oral administration contains 1.2 g Body as a Whole: lupus-like syndrome, drug fever 5-aminosalicylic acid (5-ASA; mesalamine), an anti-inflammatory agent. Mesalamine Cardiac Disorders: pericarditis, pericardial effusion, myocarditis also has the chemical name 5-amino-2-hydroxybenzoic acid and its structural Gastrointestinal: pancreatitis, cholecystitis, gastritis, gastroenteritis, gastrointestinal bleeding, perforated peptic ulcerHepatic: jaundice, cholestatic jaundice, hepatitis, liver necrosis, liver failure,Kawasaki-like syndrome including changes in liver enzymesHematologic: agranulocytosis, aplastic anemiaImmune System Disorders: anaphylactic reaction, Stevens-Johnson syndrome(SJS), drug reaction with eosinophilia and systemic symptoms (DRESS) Musculoskeletal and Connective Tissue Disorders: myalgia Neurological/Psychiatric: peripheral neuropathy, Guillain-Barre syndrome, transverse The tablet is coated with a pH dependent polymer film, which breaks down at or above pH 6.8, normally in the terminal ileum where mesalamine then begins to be Renal Disorders: interstitial nephritis released from the tablet core. The tablet core contains mesalamine with hydrophilic Respiratory, Thoracic and Mediastinal Disorders: hypersensitivity pneumonitis and lipophilic excipients and provides for extended release of mesalamine.
(including interstitial pneumonitis, allergic alveolitis, eosinophilic pneumonitis) The inactive ingredients of LIALDA are sodium carboxymethylcellulose, carnauba Skin: psoriasis, pyoderma gangrenosum, erythema nodosum wax, stearic acid, silica (colloidal hydrated), sodium starch glycolate (type A), talc, Urogenital: reversible oligospermia magnesium stearate, methacrylic acid copolymer types A and B, triethylcitrate,titanium dioxide, red ferric oxide and polyethylene glycol 6000.
DRUG INTERACTIONS
CLINICAL PHARMACOLOGY
No investigations of interaction between LIALDA and other drugs except for certainantibiotics have been performed [see Pharmacokinetics (12.3)]. However, the 12.1 Mechanism Of Action
following drug-drug interactions have been reported for products containing The mechanism of action of mesalamine is not fully understood, but appears to have a topical anti-inflammatory effect on the colonic epithelial cells. Mucosal productionof arachidonic acid metabolites, both through the cyclooxygenase and lipoxygenase 7.1 Nephrotoxic Agents, Including Non-Steroidal Anti-Inflammatory Drugs
pathways, is increased in patients with chronic inflammatory bowel disease, and it The concurrent use of mesalamine with known nephrotoxic agents, including non- is possible that mesalamine diminishes inflammation by blocking cyclooxygenase steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of renal reactions.
and inhibiting prostaglandin production in the colon.
7.2 Azathioprine or 6-mercaptopurine
Mesalamine has the potential to inhibit the activation of nuclear factor kappa B (NFκB) and consequently the production of key pro-inflammatory cytokines. It has been The concurrent use of mesalamine with azathioprine or 6-mercaptopurine may proposed that reduced expression of PPARγ nuclear receptors (γ-form of peroxisome increase the risk for blood disorders.
proliferator-activated receptors) may be implicated in ulcerative colitis. There is USE IN SPECIFIC POPULATIONS
evidence that mesalamine produces pharmacodynamic effects through directactivation of PPARγ receptors in the colonic/rectal epithelium.
8.1 Pregnancy
Pregnancy Category B. Reproduction studies with mesalamine have been performed
12.2 Pharmacodynamics
in rats at doses up to 1000 mg/kg/day (1.8 times the maximum recommended The pharmacodynamic actions of mesalamine occur in the colonic/rectal mucosae human dose based on a body surface area comparison) and rabbits at doses up to local to the delivery of drug from LIALDA into the lumen. There is information 800 mg/kg/day (2.9 times the maximum recommended human dose based on a body suggesting that severity of colonic inflammation in ulcerative colitis patients treated surface area comparison) and have revealed no evidence of impaired fertility or harm with mesalamine is inversely correlated with mucosal concentrations of mesalamine.
to the fetus due to mesalamine. There are, however, no adequate and well-controlled Plasma concentrations representing systemically absorbed mesalamine are not studies in pregnant women. Because animal reproduction studies are not always believed to contribute extensively to efficacy.
predictive of human response, this drug should be used during pregnancy only ifclearly needed.
12.3 Pharmacokinetics
Mesalamine is known to cross the placental barrier.
AbsorptionThe total absorption of mesalamine from LIALDA 2.4 g or 4.8 g given once daily for 8.3 Nursing Mothers
14 days to healthy volunteers was found to be approximately 21-22% of the Low concentrations of mesalamine and higher concentrations of its N-acetyl metabolite have been detected in human breast milk. The clinical significance of this Gamma-scintigraphy studies have shown that a single dose of LIALDA 1.2 g (one tablet) has not been determined and there is limited experience of nursing women using passed intact through the upper gastrointestinal tract of fasted healthy volunteers.
mesalamine. Caution should be exercised if LIALDA is administered to a nursing woman.
Scintigraphic images showed a trail of radio-labeled tracer in the colon, suggesting thatmesalamine had distributed through this region of the gastrointestinal tract.
8.4 Pediatric Use
In a single dose study, LIALDA 1.2 g, 2.4 g and 4.8 g were administered in the fasted Safety and effectiveness of LIALDA in pediatric patients have not been established.
state to healthy subjects. Plasma concentrations of mesalamine were detectable after 8.5 Geriatric Use
2 hours and reached a maximum by 9-12 hours on average for the doses studied.
Reports from uncontrolled clinical studies and postmarketing reporting systems The pharmacokinetic parameters are highly variable among subjects (Table 3).
suggested a higher incidence of blood dyscrasias, i.e., neutropenia and pancytopenia Mesalamine systemic exposure in terms of area under the plasma concentration-time in patients who were 65 years or older who were taking mesalamine-containing curve (AUC) was slightly more than dose proportional between 1.2 g and 4.8 g products such as LIALDA. Caution should be taken to closely monitor blood cell LIALDA. Maximum plasma concentrations (Cmax) of mesalamine increased approximately dose proportionately between 1.2 g and 2.4 g and sub-proportionatelybetween 2.4 g and 4.8 g LIALDA, with the dose normalized value at 4.8 g representing, Clinical trials of LIALDA did not include sufficient numbers of patients aged 65 and on average, 74% of that at 2.4 g based on geometric means.
over to determine whether they respond differently from younger patients. Other Table 3: Mean (SD) PK Parameters for Mesalamine Following Single Dose
ciprofloxacin XR (single 500 mg dose), metronidazole (750 mg twice daily for 3.5 Administration of LIALDA Under Fasting Conditions
days), and sulfamethoxazole/trimethoprim (800 mg/160 mg twice daily for 3.5 days).
Coadministration of Lialda did not result in clinically significant changes in the Parameter1 of
LIALDA 1.2 g
LIALDA 2.4 g
LIALDA 4.8 g
pharmacokinetics of any of the four antibiotics. The change in Cmax and AUC of Mesalamine
amoxicillin, ciprofloxacin and metronidazole when they were co-administered withLialda were all ≤ 3%. There was an increase of 12% in Cmax and an increase of 15% in AUC of sulfamethoxazole when sulfamethoxazole/trimethoprim wascoadministered with Lialda [see Drug Interactions (7)].
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 104-week dietary carcinogenicity study in CD-1 mice, mesalamine at doses upto 2500 mg/kg/day was not tumorigenic. This dose is 2.2 times the maximum recommended human dose (based on a body surface area comparison) of LIALDA.
Furthermore, in a 104-week dietary carcinogenicity study in Wistar rats, mesalamineup to a dose of 800 mg/kg/day was not tumorigenic. This dose is 1.4 times the 1 Arithmetic mean of parameter values are presented except for Tmax and Tlag.
recommended human dose (based on a body surface area comparison) of LIALDA.
* Median (min, max); +N=43, •N=27, §N=33, #N=36, **N=46 Administration of a single dose of LIALDA 4.8 g with a high fat meal resulted in No evidence of mutagenicity was observed in an in vitro Ames test or an in vivo further delay in absorption, and plasma concentrations of mesalamine were detectable 4 hours following dosing. However, a high fat meal increased systemic exposure of mesalamine (mean Cmax: ↑ 91%; mean AUC: ↑ 16%) compared to No effects on fertility or reproductive performance were observed in male or female results in the fasted state. LIALDA was administered with food in the controlled rats at oral doses of mesalamine up to 400 mg/kg/day (0.7 times the maximum clinical trials that supported its approval.
recommended human dose based on a body surface area comparison).
In a single and multiple dose pharmacokinetic study of LIALDA, 2.4 g or 4.8 g wasadministered once daily with standard meals to 28 healthy volunteers per dose group.
13.2 Animal Toxicology and/or Pharmacology
Plasma concentrations of mesalamine were detectable after 4 hours and were In animal studies with mesalamine, a 13-week oral toxicity study in mice and maximal by 8 hours after the single dose. Steady state was achieved generally by 13-week and 52-week oral toxicity studies in rats and cynomolgus monkeys have 2 days after dosing. Mean AUC at steady state was only modestly greater (1.1- to shown the kidney to be the major target organ of mesalamine toxicity. Oral daily 1.4-fold) than predictable from single dose pharmacokinetics.
doses of 2400 mg/kg in mice and 1150 mg/kg in rats produced renal lesions In a single dose pharmacokinetic study of LIALDA, 4.8 g was administered in the fasted including granular and hyaline casts, tubular degeneration, tubular dilation, renal state to 71 healthy male and female volunteers (28 young (18-35yrs); 28 elderly infarct, papillary necrosis, tubular necrosis, and interstitial nephritis. In cynomolgus (65-75yrs); 15 elderly (>75yrs)). Increased age resulted in increased systemic monkeys, oral daily doses of 250 mg/kg or higher produced nephrosis, papillary max), to mesalamine and its metabolite N-acetyl-5- aminosalicylic acid. Increased age resulted in a slower apparent elimination of CLINICAL STUDIES
mesalamine, though there was high between-subject variability. Systemic exposures inindividual subjects were inversely correlated with renal function as assessed by 14.1 Active, Mild to Moderate Ulcerative Colitis
Two similarly designed, randomized, double blind, placebo-controlled trials wereconducted in 517 adult patients with active, mild to moderate ulcerative colitis. The Table 4: Mean (SD) PK Parameters for Mesalamine Following Single Dose
study population was primarily Caucasian (80%), had a mean age of 42 years (6% Administration of LIALDA 4.8 g under Fasting Conditions to Young and Elderly
age 65 years or older), and was approximately 50% male. Both studies used LIALDA Subjects
doses of 2.4 g/day and 4.8 g/day administered once daily for 8 weeks except for the2.4 g/day group in Study 1, which was given in two divided doses (1.2 g twice daily).
Parameter of
Young Subjects
Elderly Subjects
Elderly Subjects
The primary efficacy end-point in both trials was to compare the percentage of (18-35 yrs)
(65-75 yrs)
(>75 yrs)
patients in remission after 8 weeks of treatment for the LIALDA treatment groups versus placebo. Remission was defined as an Ulcerative Colitis Disease Activity Index(UC-DAI) of ≤ 1, with scores of zero for rectal bleeding and for stool frequency, and a sigmoidoscopy score reduction of 1 point or more from baseline.
In both studies, the LIALDA doses of 2.4 g/day and 4.8 g/day demonstrated superiority over placebo in the primary efficacy endpoint (Table 5). Both LIALDA doses also provided consistent benefit in secondary efficacy parameters, including clinical improvement, treatment failure, clinical remission, and sigmoidoscopic improvement. LIALDA 2.4 g/day and 4.8 g/day had similar efficacy profiles.
Table 5: Patients in Remission at Week 8
Arithmetic mean (SD) data are presented, N = Number of subjects a Median (min - max), bN=15, cN=16, dN=13 LIALDA 2.4 g/day
LIALDA 4.8 g/day
Mesalamine is approximately 43% bound to plasma proteins at the concentration of2.5 µg/mL.
14.2 Maintenance of Remission in Patients with Ulcerative Colitis
A multicenter, randomized, double-blind, active comparator study was conducted in The only major metabolite of mesalamine (5-aminosalicylic acid) is N-acetyl-5- a total of 826 adult patients in remission from ulcerative colitis. The study aminosalicylic acid. Its formation is brought about by N-acetyltransferase (NAT) population had a mean age of 45 years (8% age 65 years or older), were 52% male, activity in the liver and intestinal mucosa cells, principally by NAT-1.
Maintenance of remission was assessed using a modified Ulcerative Colitis Disease Elimination of mesalamine is mainly via the renal route following metabolism to Activity Index (UC-DAI). For this trial, maintenance of remission was based on N-acetyl-5-aminosalicylic acid (acetylation). However, there is also limited excretion maintaining endoscopic remission defined as a modified UC-DAI endoscopy subscore of of the parent drug in urine. Of the approximately 21-22% of the dose absorbed, less ≤1. An endoscopy subscore of 0 represented normal mucosal appearance with intact than 8% of the dose was excreted unchanged in the urine after 24 hours, compared vascular pattern and no friability or granulation. For this trial the endoscopy score with greater than 13% for N-acetyl-5-aminosalicylic acid. The apparent terminal definition of 1 (mild disease) was modified such that it could include erythema, decreased half-lives for mesalamine and its major metabolite after administration of LIALDA vascular pattern, and minimal granularity; however, it could not include friability.
2.4 g and 4.8 g were, on average, 7-9 hours and 8-12 hours, respectively.
Subjects were randomized in a 1:1 ratio to receive either LIALDA 2.4 g/day administered once daily or mesalamine delayed release 1.6 g/day administered as 0.8 g twice daily.
The potential effect of Lialda (4.8 g given once daily) on the pharmacokinetics of four The proportion of patients who maintained remission at Month 6 in this study using commonly used antibiotics were evaluated in healthy subjects. The four antibiotics LIALDA 2.4 g once daily (83.7%) was similar to that seen using the comparator studied and their dosing regimens were as follows: amoxicillin (single 500 mg dose), (mesalamine delayed release) 1.6 g/day (81.5%).
HOW SUPPLIED/STORAGE AND HANDLING
LIALDA is available as red-brown ellipsoidal film coated delayed-release tabletscontaining 1.2 g mesalamine, and debossed on one side imprinted with S476.
NDC 54092-476-12 HDPE Bottle with a child-resistant closure of 120 delayed-releasetablets.
Store at room temperature 15°C to 25°C (59°F to 77°F); excursions permitted to30°C (86°F).
See USP Controlled Room Temperature.
PATIENT COUNSELING INFORMATION
• Instruct patients not to take LIALDA if they have hypersensitivity to salicylates (e.g., • Inform patients to let their physicians know all medications they are taking and if ■ are allergic to sulfasalazine, salicylates or mesalamine;■ are taking non-steroidal anti-inflammatory drugs (NSAIDs) or other ■ are taking azathioprine, or 6-mercaptopurine;■ experience cramping, abdominal pain, bloody diarrhea, fever, headache or ■ have a history of myocarditis or pericarditis;■ have kidney or liver disease;■ have a history of stomach blockage;■ are pregnant, intend to become pregnant or are breast-feeding.
Patients should be instructed to swallow LIALDA delayed-release tablets whole,taking care not to break the outer coating.
Manufactured for Shire US Inc., 725 Chesterbrook Blvd., Wayne, PA 19087, USA byCosmo S.p.A., Milan, Italy. By license of Nogra Pharma Limited, Dublin, Ireland.
U.S. Patent No. 6,773,720.
2013 Shire US Inc.
Rev. 09/2013LIA-05874

Source: http://pi.shirecontent.com/PI/PDFs/Lialda_USA_ENG.pdf

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