Side Effects of Pentasa (mesalamine)

Pentasa (mesalamine) is an anti-inflammatory agent used to treat ulcerative colitis and mild to moderate Crohn's disease. 

The exact mechanism of Pentasa is not known but is believed to be by reducing inflammation in the colon. 

Ulcerative colitis and other inflammatory diseases cause excessive production of chemicals, for example, prostaglandins, that produce inflammation in the colon. Prostaglandins are produced by the enzymes, cyclooxygenase and lipoxygenase. These enzymes are over-active in individuals with ulcerative colitis. 

Pentasa may work by blocking the activity of cyclooxygenase and lipoxygenase, thereby, reducing the production of prostaglandins. Reduced production of prostaglandins decreases inflammation in the colon and the symptoms associated with ulcerative colitis. 

Available forms of mesalamine differ in their route of administration and how often they are administered.

Common side effects of Pentasa include

• headache,
• gas (flatulence),
• hair loss, and
• itching.

Less common side effects include

• increased heart rate,
• acne,
• back pain,
• fatigue,
• tremor, and
• ear pain.  

Serious side effects of Pentasa include

• pancreatitis,
• blood disorders,
• kidney dysfunction, and
• an acute intolerance syndrome that resembles a flare of inflammatory bowel disease (Crohn's disease or ulcerative colitis) with cramping, abdominal pain, and bloody diarrhea.

Fever, headache, itching, and rash also may occur. Symptoms usually subside once Pentasa is discontinued.

Drug interactions of Pentasa include drugs that affect kidney function, for example, nonsteroidal anti-inflammatory drugs (NSAIDs) or ibuprofen, because it may increase the likelihood of reduced function of the kidneys. 

Concurrent use of Pentasa and 6-mercaptopurine or azathioprine may increase the likelihood of disorders of the blood cells, particularly reduced numbers of cells. 

Pentasa may increase the blood-thinning effect of warfarin. 

There are no adequate human studies of Pentasa during pregnancy. Pentasa is known to cross the placenta into the fetus, but animal studies revealed no evidence of harm to the fetus. Pentasa should only be used during pregnancy if it is felt that the benefit of its use justifies the unknown risks. 

Pentasa is excreted in breast milk. Pentasa should only be used by breastfeeding mothers if it is felt that the benefit of its use justifies the potential but unknown risk to the infant.

The most common side effects of mesalamine are:

• headache,
• flatulence,
• hair loss, and
• itching.

Infrequent side effects include:

• increased heart rate,
• acne,
• pancreatitis,
• back pain,
• fatigue,
• tremor,
• ear pain, and
• blood disorders.

Kidney dysfunction has been associated with mesalamine. Kidney function should be evaluated prior to and periodically during mesalamine therapy.

Mesalamine may cause an acute intolerance syndrome that resembles a flare of inflammatory bowel disease (Crohn's disease or ulcerative colitis) with cramping, abdominal pain, and bloody diarrhea. Fever, headache, itching, and rash also may occur. Symptoms usually subside once mesalamine is discontinued.

Mesalamine enemas contain sulfites and should be avoided in persons who are sensitive to sulfites.

Since mesalamine is related to aspirin in structure, individuals who are allergic to aspirin should not take mesalamine.

In combined domestic and foreign clinical trials, more than 2100 patients with ulcerative colitis or Crohn's disease received Pentasa therapy. Generally, Pentasa therapy was well tolerated. The most common events (ie, greater than or equal to 1%) were

• diarrhea (3.4%),
• headache (2.0%),
• nausea (1.8%),
• abdominal pain (1.7%),
• dyspepsia (1.6%),
• vomiting (1.5%), and
• rash (1.0%).

In two domestic placebo-controlled trials involving over 600 ulcerative colitis patients, adverse events were fewer in Pentasa (mesalamine)-treated patients than in the placebo group (Pentasa 14% vs placebo 18%) and were not dose-related.

Events occurring in more than 1% are shown in the table below. Of these, only nausea and vomiting were more frequent in the Pentasa group. Withdrawal from therapy due to adverse events was more common on placebo than Pentasa (7% vs 4%).

Table 1: Adverse Events Occurring in More than 1% of Either Placebo or Pentasa Patients in Domestic Placebo-controlled Ulcerative Colitis Trials. (Pentasa Comparison to Placebo)

Clinical laboratory measurements showed no significant abnormal trends for any test, including measurement of hematological, liver, and kidney function.

The following adverse events, presented by body system, were reported infrequently (ie, less than 1%) during domestic ulcerative colitis and Crohn's disease trials. In many cases, the relationship to Pentasa has not been established.

Gastrointestinal: abdominal distention, anorexia, constipation, duodenal ulcer, dysphagia, eructation, esophageal ulcer, fecal incontinence, GGTP increase, GI bleeding, increased alkaline phosphatase, LDH increase, mouth ulcer, oral moniliasis, pancreatitis, rectal bleeding, SGOT increase, SGPT increase, stool abnormalities (color or texture change), thirst

Dermatological: acne, alopecia, dry skin, eczema, erythema nodosum, nail disorder, photosensitivity, pruritus, sweating, urticaria

Nervous System: depression, dizziness, insomnia, somnolence, paresthesia

Cardiovascular: palpitations, pericarditis, vasodilation

Other: albuminuria, amenorrhea, amylase increase, arthralgia, asthenia, breast pain, conjunctivitis, ecchymosis, edema, fever, hematuria, hypomenorrhea, Kawasaki-like syndrome, leg cramps, lichen planus, lipase increase, malaise, menorrhagia, metrorrhagia, myalgia, pulmonary infiltrates, thrombocythemia, thrombocytopenia, urinary frequency

One week after completion of an 8-week ulcerative colitis study, a 72-year-old male, with no previous history of pulmonary problems, developed dyspnea. The patient was subsequently diagnosed with interstitial pulmonary fibrosis without eosinophilia by one physician and bronchiolitis obliterans with organizing pneumonitis by a second physician. A causal relationship between this event and mesalamine therapy has not been established.

Published case reports and/or spontaneous postmarketing surveillance have described infrequent instances of pericarditis, fatal myocarditis, chest pain and T-wave abnormalities, hypersensitivity pneumonitis, pancreatitis, nephrotic syndrome, interstitial nephritis, hepatitis, aplastic anemia, pancytopenia, leukopenia, agranulocytosis, or anemia while receiving mesalamine therapy. Anemia can be a part of the clinical presentation of inflammatory bowel disease. Allergic reactions, which could involve eosinophilia, can be seen in connection with Pentasa therapy.

Postmarketing Reports

The following events have been identified during post-approval use of the Pentasa brand of mesalamine in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of seriousness, frequency of reporting, or potential causal connection to mesalamine:

Gastrointestinal

Reports of hepatotoxicity, including elevated liver enzymes (SGOT/AST, SGPT/ALT, GGT, LDH, alkaline phosphatase, bilirubin), hepatitis, jaundice, cholestatic jaundice, cirrhosis, and possible hepatocellular damage including liver necrosis and liver failure. Some of these cases were fatal. One case of Kawasaki-like syndrome which included hepatic function changes was also reported.

Other

Postmarketing reports of anaphylactic reaction, Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), pneumonitis, granulocytopenia, systemic lupus erythematosus, lupus-like syndrome, acute renal failure, interstitial lung disease, Hypersensitivity pneumonitis (including interstitial pneumonitis, allergic alveolitis, eosinophilic pneumonitis), chronic renal failure, nephrogenic diabetes insipidus, intracranial hypertension, angioedema and oligospermia (reversible) have been received in patients taking Pentasa.

There are no data on interactions between Pentasa and other drugs.