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]
- Mesalamine-induced acute intolerance syndrome [See Warnings and Precautions]
- Hypersensitivity reactions [See Warnings and Precautions]
- Hepatic impairment, including hepatic failure [See Warnings and Precautions]
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 open-label trials.
Induction of Remission
In two 8-week placebo-controlled clinical trials involving 535 ulcerative colitis patients, 356 received 2.4 g/day or 4.8 g/day LIALDA tablets and 179 received placebo. The most frequent adverse reaction leading to discontinuation from LIALDA therapy was exacerbation of ulcerative colitis (0.8%). Pancreatitis occurred in less than 1% of patients during clinical trials and resulted in discontinuation of therapy with LIALDA in patients experiencing this event.
Adverse reactions occurring in LIALDA or placebo groups at a frequency of at least 1% in two 8-week, double blind, placebo-controlled trials are listed in Table 1. The 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).
Table 1: Adverse Reactions in Two Eight-Week Placebo-Controlled Trials Experienced by at Least 1% of the LIALDA Group and at a Rate Greater than Placeboa
Adverse Reaction
|
LIALDA 2.4 g/day (n = 177)
|
LIALDA 4.8 g/day (n = 179)
|
Placebo
(n = 179)
|
Headache |
10 (5.6%) |
6 (3.4%) |
1 (0.6%) |
Flatulence |
7 (4%) |
5 (2.8%) |
5 (2.8%) |
Liver Function Test Abnormal |
1 (0.6%) |
4 (2.2%) |
2 (1.1%) |
Alopecia |
0 |
2 (1.1%) |
0 |
Pruritus |
1 (0.6%) |
2 (1.1%) |
2 (1.1%) |
a: Adverse reactions for which the placebo rate equalled or exceeded the rate for at least one of the LIALDA treatment groups were abdominal pain, dizziness, dyspepsia, and nausea. |
The following adverse reactions, presented by body system, were reported infrequently (less than 1%) by LIALDA-treated ulcerative colitis patients in the two controlled trials.
Cardiac Disorder: tachycardia
Vascular Disorders: hypertension, hypotension
Skin and Subcutaneous Tissue Disorders: acne, prurigo, rash, urticaria
Gastrointestinal Disorders: abdominal distention, colitis, diarrhea, pancreatitis, rectal polyp, vomiting
Investigations: decreased platelet count
Musculoskeletal and Connective Tissue Disorders: arthralgia, back pain
Nervous System Disorders: somnolence, tremor
Respiratory, Thoracic and Mediastinal Disorders: pharyngolaryngeal pain
General Disorders and Administrative Site Disorders: asthenia, face edema, fatigue, pyrexia
Ear and Labyrinth Disorders: ear pain
Maintenance of Remission of Ulcerative Colitis
The dose evaluated in three studies of LIALDA given for the maintenance of remission in patients with ulcerative colitis was 1.2 g twice daily or 2.4 g/once daily. One of these studies was a 6-month double-blind comparator study while two were 12- to 14-month open-label studies.
The most common adverse reactions with LIALDA in the maintenance arms of long-term trials were colitis ulcerative (5.8%), headache (2.9%), liver function test abnormal (2.3%), and abdominal pain (2.2%). Of the 1082 subjects in the all maintenance studies pooled, 1.9% had severe adverse reactions. The most common severe adverse reactions were gastrointestinal disorders; these were mainly symptoms associated with ulcerative colitis.
Table 2: Adverse Reactions in Three Maintenance Trials Experienced by at Least 1% of the LIALDA Group (maintenance phases of trials)
|
All LIALDA (n=1082)
|
Adverse Reaction |
n |
% |
Colitis ulcerative |
63 |
(5.8%) |
Headache |
31 |
(2.9%) |
Liver function test abnormal |
25 |
(2.3%) |
Abdominal pain |
24 |
(2.2%) |
Diarrhea |
18 |
(1.7%) |
Abdominal distension |
14 |
(1.3%) |
Abdominal pain upper |
13 |
(1.2%) |
Dyspepsia |
13 |
(1.2%) |
Back pain |
13 |
(1.2%) |
Rash |
13 |
(1.2%) |
Arthralgia |
12 |
(1.1%) |
Fatigue |
11 |
(1.0%) |
Hypertension |
10 |
(1.0%) |
The following adverse reactions, presented by body system, were reported infrequently (less than 1%) by LIALDA-treated ulcerative colitis patients in the three long-term maintenance trials (maintenance phases of these trials):
Cardiac Disorder: tachycardia
Skin and Subcutaneous Tissue Disorders: acne, alopecia, pruritis, urticaria
Gastrointestinal Disorders: colitis, flatulence, nausea, pancreatitis, rectal polyp, vomiting
Nervous System Disorders: dizziness
Respiratory, Thoracic and Mediastinal Disorders: pharyngolaryngeal pain
General Disorders and Administrative Site Disorders: asthenia, pyrexia
Ear and Labyrinth Disorders: ear pain
Postmarketing Experience
In addition to the adverse reactions reported above in clinical trials involving LIALDA, the adverse reactions listed below have been identified during post-approval use of LIALDA and other mesalamine-containing products. 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.
Body as a Whole: lupus-like syndrome, drug fever
Cardiac Disorders: pericarditis, pericardial effusion, myocarditis
Gastrointestinal: pancreatitis, cholecystitis, gastritis, gastroenteritis, gastrointestinal bleeding, perforated peptic ulcer
Hepatic: jaundice, cholestatic jaundice, hepatitis, liver necrosis, liver failure, Kawasaki-like syndrome including changes in liver enzymes
Hematologic: agranulocytosis, aplastic anemia
Immune System Disorders: anaphylactic reaction, angioedema, 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 myelitis
Renal Disorders: interstitial nephritis
Respiratory, Thoracic and Mediastinal Disorders: hypersensitivity pneumonitis (including interstitial pneumonitis, allergic alveolitis, eosinophilic pneumonitis)
Skin: psoriasis, pyoderma gangrenosum, erythema nodosum
Urogenital: reversible oligospermia
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