Aminosalicylates

• What are aminosalicylates?
• What are aminosalicylates used for?
• Different formulations of 5-ASA
• How do aminosalicylates work?
• Precautions
• Drug interactions

What are aminosalicylates?

5-Aminosalicylate (5-ASA), also known as mesalamine, is a bowel-specific anti-inflammatory class of drugs that are metabolised by the commensal bacteria in the bowel (often refered to as good bacteria). Metabolisation by the bacteria enables them to exert their pharmacological effects at the site of inflammation. This in turn results in less systemic absorption and fewer adverse effects.

What are aminosalicylates used for?

5-ASA is used to treat mild-to-moderate inflammatory bowel disease (IBD), with the ultimate aim of relieving symptoms, inducing and maintaining remission, preventing further complications, and improving quality of life. IBD is a relapsing (worsening) and remitting (resolving) condition characterised by the non-specific or unknown inflammation of the gastrointestinal tract (GIT).

The two forms of IBD, ulcerative colitis and Crohn’s disease, differ in presentation, site, progression and treatment. Treatment choice is therefore based on the location of inflammation in the bowel, such as rectum, sigmoid colon or entire colon; the extent and severity of inflammation; complications of the disease; and response to current or previous therapies. 5-ASAs do not provide a cure for IBD, but have been shown to be effective for inducing and maintaining remission of ulcerative colitis.

Different formulations of 5-ASA

Members of this class include balsalazide (Colazide), mesalazine (Mesasal, Salofalk, Pentasa), olsalazine (Dipentum) and sulfasalazine (Salazopyrin, Pyralin, Salazopyrin EN). In comparison to sulfasalazine, the newer drugs balsalazide, mesalazine and olsalazine do not contain sulphonamide and have less associated adverse effects. However, the newer orally acting 5-ASAs are more expensive and are only available on the Pharmaceutical Benefits Scheme (PBS) as an Authority prescription for patients who are intolerant of sulfasalazine. 5-ASA is available in several oral and rectal (topical) formulations, including tablets, micropellets, suppositories, suspension (foam) and enemas, shown in Table 1. The site of inflammation determines the choice of formulation. For example, rectal formulations are used to deliver the therapeutic agent to the terminal site of the colon.

Table 1: Different formulations of 5-ASA.

Oral formulations	Rectal formulations
Balsalazide: Capsule Mesalazine: Granules (sachets) Mesalazine: Enteric coated tablets Olsalazine: Tablets and capsules Sulfasalazine: Tablets and enteric coated tablets	Mesalazine: Enemas, suppositories and rectal foam Sulfasalazine: Suppositories

How do aminosalicylates work?

The exact mechanism is still unknown. However, their action is thought to be predominately topical at the site of inflammation within the colonic mucosa. For most patients with IBD, 5-ASAs must be taken orally. However, if the pure 5-ASA is taken by mouth, it is completely absorbed into the blood from the upper gut before it reaches the colon. In order to maximize the delivery of the 5-ASA to the site of inflammation, and hence its clinical effectiveness, the active agent needs to reach the colonic mucosa intact. Therefore, 5-ASAs have been chemically modified to facilitate drug delivery to the site of inflammation.

• Balsalazide is a capsule in which the 5-ASA is chemically bound to another inactive molecule. Bacterial enzymes in the colon break the bonds between these molecules and release the medication onto the colonic mucosa. As a result of this delivery method, the 5-ASA escapes absorption in the upper gut absorption and is more effective;
• Mesalazine tablet/granules (Pentasa Oral) are comprised of micro-spheres that enclose the 5-ASA within a specialised membrane. The membrane breaks down in the intestinal environment. Mesalazine can be effective in treating both ulcerative colitis and Crohn’s disease;
• Olsalazine consists of two 5-ASA molecules chemically bound together. Bacterial enzymes in the colon break the bond between these molecules and release the medication onto the colonic mucosa;
• Sulfasalazine is a tablet in which the 5-ASA is chemically bound to another active molecule. Sulphonamide is an anti-infective agent. Bacterial enzymes in the colon break the bond between these molecules and release the medication onto the colonic mucosa. Due to its specific properties, sulfasalazine is also used to treat rheumatoid arthritis.

What are the adverse effects of aminosalicylates?

About 10-15% of patients are unable to take sulfasalazine because of its serious and/or severe adverse effects, which are mostly due to sulphonamide. Many of the adverse effects are dose-related. The most common adverse effects, occurring in 1% or more of patients treated with 5-ASAs:

• Nausea and vomiting;
• Diarrhoea(can occur more frequently with olsalazine);
• Abdominal pain;
• Skin rashes;
• Headache;
• Reversible male infertility (associated with sulfasalazine only).

If you are concerned about any of these side effects, contact your doctor. More severe but less common effects, occurring in less than 1% of patients treated with 5-ASAs:

• Anaemia;
• Blood dyscrasia;
• Hepatitis;
• Pancreatitis (reversible);
• Pneumonitis;
• Stevens-Johnson syndrome;
• Encephalitis.

Precautions

You must inform your doctor if:

• You had an allergic reaction to any previous medications, including aspirin;
• You have a history of kidney or liver problems;
• You are pregnant or planning to get pregnant;
• You are breastfeeding;
• You have any co-existing medical history;
• You are taking any other medications.

Drug interactions

This class of medication can interact with other medicines. It is essential that you inform your doctor if you are taking any other medicines, including those obtained from a pharmacy or health food stores. Some examples of drug interactions are:

• Digoxin (heart medication);
• Azathioprine (immunomodulator used in patients with autoimmune disease);
• Mercaptopurine (anti-cancer agent).

References

1. Therapeutic Guidelines: Gastrointestinal. [online]. Drugs used in inflammatory bowel disease. Version 4, 2006. Available at URL: http://www.tg.com.au (last accessed 21/09/07).
2. Australian Medicine Handbook. Adelaide: AMH Pty Ltd; 2007.
3. Cohen R.D. Evolutionary advances in the delivery of aminosalicylates for the treatment of ulcerative colitis. Aliment Pharmacol Ther. 2006; 24: 465-74
4. 5-ASA formulations for the treatment of ulcerative colitis. G&H. 2006; 2 (7): 1-8
5. MIMS Online. Balsalazide. [cited 2007 September 21].
6. MIMS Online. Mesalazine. [cited 2007 September 21].
7. Mims online- MIMS Online. Olsalazine. [cited 2007 September 21]. Available from: http://mims.hcn.net.au.ezproxy.library.uwa.edu.au
8. MIMS Online. Sulfasalazine. [cited 2007 September 21].

Drugs used in this treatment:

• Dipentum (Olsalazine sodium)
• Pyralin EN (Sulfasalazine)
• Salofalk Tablets (Mesalazine)
• Colazide (Balsalazide sodium)

This treatment is used for the following diseases:

• Crohn’s Disease (Inflammatory Bowel Disease)
• Rheumatoid Arthritis
• Ulcerative Colitis (Inflammatory Bowel Disease)