What are the side effects of Mesalamine (5-Aminosalicylic acid)?

From the Guidelines

Mesalamine is generally well-tolerated, but patients should be aware of potential side effects, including common issues like headache, nausea, and abdominal pain, as well as more serious reactions such as acute intolerance syndrome and allergic reactions. When considering the management of mild-to-moderate ulcerative colitis, the use of standard-dose mesalamine (2–3g/day) has been shown to be effective in inducing and maintaining remission, with a high quality of evidence 1. The anticipated absolute effects of standard-dose mesalamine compared to placebo include a reduction in the risk of failure to induce remission and failure to maintain remission 1.

Some key points to consider when evaluating the side effects of mesalamine include:

• Common side effects: headache, nausea, abdominal pain, diarrhea, and mild hair loss
• Serious reactions: acute intolerance syndrome, allergic reactions, kidney problems, and liver issues
• Rare but serious side effects: pancreatitis, pericarditis, and blood disorders
• The importance of reporting concerning symptoms to a healthcare provider immediately, especially severe abdominal pain, bloody diarrhea, fever, rash, or changes in urination patterns

In terms of the evidence, a study published in Gastroenterology in 2019 1 provides high-quality evidence for the effectiveness of standard-dose mesalamine in managing mild-to-moderate ulcerative colitis. Another study published in Gut in 2004 1 provides guidelines for the management of inflammatory bowel disease in adults, including the use of mesalamine as a first-line therapy for mild to moderately active disease. However, the more recent and higher-quality study 1 takes precedence in informing clinical decision-making.

From the FDA Drug Label

The following clinically significant adverse reactions are described elsewhere in labeling: Renal impairment, including renal failure [see Warnings and Precautions (5.1)] Mesalamine-induced acute intolerance syndrome [see Warnings and Precautions (5.2)] Hypersensitivity reactions [see Warnings and Precautions (5. 3)] Hepatic failure [see Warnings and Precautions (5.4)] Severe cutaneous adverse reactions [see Warnings and Precautions (5.5)] Upper gastrointestinal tract obstruction [see Warnings and Precautions (5.6)] Photosensitivity [see Warnings and Precautions (5.7)] Nephrolithiasis [see Warnings and Precautions (5.8)]

The most common adverse reactions occurring in at least 1% of mesalamine-or placebo-treated adult patients with mildly to moderately active ulcerative colitis in two eight-week, randomized, double-blind, placebo-controlled trials (Study 1 and Study 2) [see Clinical Studies (14. 1)]are listed in Table 2.

Table 2: Adverse Reactions* in Two Eight-Week, Placebo-Controlled Trials of Induction Therapy (Study 1 and Study 2) in Adults with Mildly to Moderately Active Ulcerative Colitis Adverse Reaction Mesalamine delayed-release tablets 2.4 g once daily (n = 177) Mesalamine delayed-release tablets 4. 8 g once daily (n = 179) Placebo (n = 179) Headache 6% 3% < 1% Flatulence 4% 3% 3% Liver Function Test Abnormal < 1% 2% 1% Alopecia 0 1% 0 Pruritus < 1% 1% 1%

The most common adverse reactions with mesalamine in these maintenance trials are listed in Table 3.

Table 3: Adverse Reactions* in Three Trials of Maintenance of Remission in Adults with Ulcerative Colitis Mesalamine delayed-release tablets 2. 4 g/day † (n = 1082) Adverse Reaction % Headache 3% Liver function test abnormal 2% Abdominal pain 2% Diarrhea 2% Abdominal distension 1% Abdominal pain upper 1% Dyspepsia 1% Back pain 1% Rash 1% Arthralgia 1% Fatigue 1% Hypertension 1%

Ear and Labyrinth Disorders: ear pain Gastrointestinal Disorders: abdominal distention, colitis, diarrhea, flatulence, nausea, pancreatitis, rectal polyp, vomiting General Disorders and Administrative Site Disorders: asthenia, face edema, fatigue, pyrexia Investigations: decreased platelet count Musculoskeletal and Connective Tissue Disorders: arthralgia, back pain Nervous System Disorders: dizziness, somnolence, tremor Respiratory, Thoracic and Mediastinal Disorders: pharyngolaryngeal pain Skin and Subcutaneous Tissue Disorders: acne, prurigo, rash, alopecia, pruritus, urticaria Vascular Disorders: hypertension, hypotension

The following adverse reactions have been identified during post-approval use of mesalamine delayed-release tablets or other mesalamine-containing products. Body as a Whole: lupus-like syndrome, drug fever Cardiac Disorders: pericarditis, pericardial effusion, myocarditis [see Warnings and Precautions (5. 3)] Gastrointestinal: cholecystitis, gastritis, gastroenteritis, gastrointestinal bleeding, perforated peptic ulcer Hepatic: jaundice, cholestatic jaundice, hepatitis, liver necrosis, liver failure, hepatotoxicity, Kawasaki-like syndrome including changes in liver enzymes Hematologic: agranulocytosis, aplastic anemia Immune System Disorders: anaphylactic reaction, angioedema Musculoskeletal and Connective Tissue Disorders: myalgia, lupus-like syndrome Neurological/Psychiatric: peripheral neuropathy, Guillain-Barre syndrome, transverse myelitis, intracranial hypertension Renal Disorders: renal failure, interstitial nephritis, nephrogenic diabetes insipidus, nephrolithiasis [see Warnings and Precautions (5.1,5. 8)] Urine discoloration occurring ex-vivo caused by contact of mesalamine, including inactive metabolite, with surfaces or water treated with hypochlorite-containing bleach Respiratory, Thoracic and Mediastinal Disorders: interstitial lung disease, hypersensitivity pneumonitis (including interstitial pneumonitis, allergic alveolitis, eosinophilic pneumonitis), pleurisy/pleuritis Skin: psoriasis, pyoderma gangrenosum, erythema nodosum, photosensitivity, SJS/TEN, DRESS, and AGEP [see Warnings and Precautions (5.5)] Urogenital: reversible oligospermia

Common side effects of mesalamine include:

• Headache
• Flatulence
• Liver function test abnormal
• Alopecia
• Pruritus
• Abdominal pain
• Diarrhea
• Abdominal distension
• Back pain
• Rash
• Arthralgia
• Fatigue
• Hypertension

Less common side effects include:

• Pancreatitis
• Nephrolithiasis
• Myocarditis
• Peripheral neuropathy
• Guillain-Barre syndrome
• Transverse myelitis
• Intracranial hypertension
• Renal failure
• Interstitial nephritis
• Nephrogenic diabetes insipidus
• Agranulocytosis
• Aplastic anemia
• Anaphylactic reaction
• Angioedema
• Lupus-like syndrome
• Myalgia
• Psoriasis
• Pyoderma gangrenosum
• Erythema nodosum
• Photosensitivity
• SJS/TEN
• DRESS
• AGEP
• Reversible oligospermia

2

From the Research

Mesalamine Side Effects

• Mesalamine has been known to produce occasional diarrhea, with the true incidence of this effect not always recognized 3.
• Sulfasalazine has more frequent side effects than olsalazine, balsalazide, and mesalamine formulations 4.
• Mesalamine can cause severe and persistent diarrhea, which can be made worse by increasing doses of the drug, and can intensify colitis in some cases 3.
• Mesalamine has few serious adverse effects and is generally well tolerated by patients, but can occasionally cause serious side effects leading to various medical problems 5, 6.
• Serious side effects of mesalamine can include cardiomyopathy and pneumonitis, which can be life-threatening if not detected and treated early 6.

Common Side Effects

• Diarrhea is a common side effect of mesalamine treatment, especially at higher doses 3, 5.
• Mesalamine can also cause other gastrointestinal side effects, such as abdominal pain and nausea, although these are less common 4, 7.

Rare but Serious Side Effects

• Cardiomyopathy, a condition where the heart muscle becomes weakened, has been reported as a rare but serious side effect of mesalamine 6.
• Pneumonitis, a condition where the lungs become inflamed, has also been reported as a rare but serious side effect of mesalamine 6.