How mesalazine works
Like acetylsalicylic acid, mesalazine inhibits various enzymes that produce pro-inflammatory tissue hormones (prostaglandins, leukotrienes, thromboxanes, etc.). In this way, acute inflammatory reactions (“relapses”), as they occur in chronic inflammatory bowel diseases (such as Crohn’s disease, ulcerative colitis), can often be attenuated or completely suppressed.
In addition, mesalazine can neutralize reactive oxygen species (ROS). These aggressive oxygen compounds, also known as “free radicals,” are often present in increased amounts during inflammatory processes and damage the tissue. The fact that mesalazine reduces the risk of late complications such as colorectal cancer in patients with inflammatory bowel disease may be due to this ability to neutralize ROS.
Mesalazine is also known as 5-aminosalicylic acid (5-ASA). When one molecule of 5-ASA is bound to a second, the active ingredient is called olsalazine. The combination of 5-ASA and sulfapyridine is called sulfasalazine.
Olsalazine and sulfasalazine are first bacterially cleaved (“prodrugs”) in the large intestine (colon). In this way, the drugs act where the inflammation is strongest.
Absorption, degradation and excretion
After ingestion or local application (as suppositories or rectal foam), about 20 to 30 percent of the active ingredient is absorbed in the intestine and inactivated in the intestinal mucosa or liver. The ineffective degradation product is then largely excreted in the urine via the kidneys.
When is mesalazine used?
Mesalazine is approved for the treatment of:
- Crohn’s disease
- ulcerative colitis
- rectal inflammation (proctitis)
- Proctosigmoitis (when the inflammation extends to the last part of the colon, the sigmoid colon)
- Complications of hemorrhoids
Outside the scope of approval (“off-label use”), the active ingredient is also used to treat other, less common chronic inflammatory bowel diseases.
In acute relapses, treatment is given for a short time until improvement. For relapse prevention, the active ingredient can also be taken over a longer period of time.
How mesalazine is used
The anti-inflammatory active ingredient is used in different dosage forms depending on the type of disease. If, as is often the case with ulcerative colitis, the rectum and rectal area are more affected by the inflammation, mesalazine can be used well in the form of suppositories, rectal foam and clysms (solution for an enema).
Depending on the disease and its stage, different doses are taken. Two to four grams of mesalazine distributed over several individual doses taken throughout the day are common. If necessary, different dosage forms are also used in combination.
In severe cases, a strong glucocorticoid (“cortisone”) is often prescribed in addition for acute episodes.
What are the side effects of mesalazine?
In general, treatment with mesalazine has quite few side effects. The most common side effects are headache, high blood pressure, abdominal pain, indigestion, altered liver enzymes, skin rash, itching, muscle and joint pain, fever, and weakness.
When used as sulfasalazine, other side effects may occur due to the sulfapyridine content, such as a decrease in sperm count (reversible) or, rarely, agranulocytosis (decrease in granulocytes, a subgroup of white blood cells).
What should be considered when using mesalazine?
Contraindications
Mesalazine must not be used in:
- hypersensitivity to salicylates
- severe liver or kidney dysfunction
Interactions
The immune-suppressing effects of immunosuppressants such as azathioprine and mercaptopurine may be increased when these drugs are combined with mesalazine.
In addition, the kidney-damaging effects of non-steroidal anti-inflammatory drugs (NSAIDs such as ibuprofen, diclofenac, acetylsalicylic acid) and immunosuppressants (such as azathioprine and methotrexate = MTX) may be increased if mesalazine is also taken simultaneously or promptly.
Concomitant use with agents that increase gastric pH (such as proton pump inhibitors, H2 blockers, antacids) may decrease the release of mesalazine from tablets or granules (per oral dosage forms).
Age Limitation
The drug may be used in children six years of age and older patients without renal impairment.
Pregnancy and lactation
Mesalazine is a drug that has also been well tested in pregnancy. The active ingredient is therefore one of the drugs of choice in the treatment of chronic inflammatory bowel diseases.
During lactation, only traces of mesalazine pass into breast milk, even in very high oral doses. For this reason, mesalazine is also one of the drugs of choice for chronic inflammatory bowel diseases during the breastfeeding period.
How to obtain medicines containing mesalazine
How long has mesalazine been known?
As early as the 1950s, active ingredients such as sulfasalazine were used against chronic inflammatory bowel diseases, releasing mesalazine locally in the intestine. After it was proven that the main effect was due to mesalazine, this was also used individually in a suitable dosage form.
As a result, the side effect profile of the active ingredient was also significantly improved. Today, there are numerous preparations with the active ingredient mesalazine on the German market.
