Print This

Pharmacology

5-Aminosalicylic acid (5-ASA) is considered to be the active component of sulfasalazine. Although its mode of action has not been definitely elucidated, 5-ASA is thought to have a topical anti-inflammatory effect which is produced by inhibition of prostaglandin and/or leukotriene synthesis.

The tablets have an acrylic-based resin coating which is specifically designed to release 5-ASA in the terminal ileum and colon. Urinary recovery studies have shown that 35% of the 5-ASA is absorbed. The absorbed 5-ASA is rapidly acetylated and excreted mainly by the kidney.

Detectable plasma levels of 5-ASA were seen 4hours after a single oral dose of tablets (2´250mg). Peak plasma levels of 5-ASA and N-acetyl-5-ASA were 1.2and 1.9µg/mL, respectively, and occurred 6.5 to 7hours post-dosing. Mean steady-state plasma levels of 5-ASA and N-acetyl-5-ASA using a 500mg 3times a day dosage schedule are 0.7 and 1.2µg/mL, respectively.

Except for a delay of 1.5 to 3hours in time to peak of5-ASA and N-acetyl-5-ASA plasma levels, Mesasal pharmacokinetics are essentially the same in fasted and fed subjects.

Indications

5-Aminosalicylic Acid (5-ASA) Is Considered To Be The Active Component Of Sulfasalazine. Although Its Mode Of Action Has Not Been Definitely Elucidated, 5-ASA Is Thought To Have A Topical Anti-inflammatory Effect Which Is Produced By Inhibition Of Prostaglandin And/or Leukotriene Synthesis.

The Tablets Have An Acrylic-based Resin Coating Which Is Specifically Designed To Release 5-ASA In The Terminal Ileum And Colon. Urinary Recovery Studies Have Shown That 35% Of The 5-ASA Is Absorbed. The Absorbed 5-ASA Is Rapidly Acetylated And Excreted Mainly By The Kidney.

Detectable Plasma Levels Of 5-ASA Were Seen 4hours After A Single Oral Dose Of Tablets (2´250mg). Peak Plasma Levels Of 5-ASA And N-acetyl-5-ASA Were 1.2and 1.9µg/mL, Respectively, And Occurred 6.5 To 7hours Post-dosing. Mean Steady-state Plasma Levels Of 5-ASA And N-acetyl-5-ASA Using A 500mg 3times A Day Dosage Schedule Are 0.7 And 1.2µg/mL, Respectively.

Except For A Delay Of 1.5 To 3hours In Time To Peak Of5-ASA And N-acetyl-5-ASA Plasma Levels, Mesasal Pharmacokinetics Are Essentially The Same In Fasted And Fed Subjects.

 

Contraindications
Hypersensitivity to salicylates; in cases of hemorrhagic diathesis; in patients with existing gastric and duodenal ulcers; in patients with urinary tract obstruction; in children under 2years of age.

Safety Information / Warning

In cases of severe liver and kidney disorders, caution should be exercised.

Pregnancy and Lactation: Adequate human data on use during pregnancy are not available. 5-ASA should not be prescribed during the last weeks of pregnancy or during lactation. In the first 3months of pregnancy, treatment is recommended only if potential benefits outweigh the possible risks. Adequate human data on use during lactation and adequate animal reproduction studies are not available.

Children: There is limited experience with respect to the use of this drug in children; potential benefits should be weighed against possible risks.

Precautions
Drug Interactions : Caution should be exercised when 5-ASA and sulfonylureas are prescribed concomitantly, since the blood-sugar reducing effect of sulfonylureas may be enhanced. Interactions with coumarins, probenecid, sulfinpyrazone, spironolactone, furosemide and rifampicin cannot be excluded. 5-ASA may delay the excretion of methotrexate.

In long-term therapy, periodic urinalysis should be conducted. Caution should be exercised when therapy is first initiated in patients known to be allergic to sulfasalazine.

Side Effects / Adverse Effects
In controlled clinical trials in 395patients who received 5-ASA, the following adverse reactions were reported: headache (3.0%), nausea (2.0%), abdominal pain (1.5%) and diarrhea (1.5%). Rash (including pruritus and urticaria) has also been reported. Other adverse effects common to salicylates, such as occasional transitory abnormal liver function tests or hypersensitivity reactions, including pulmonary and cardiac changes, may be expected to occur rarely. There have been a few spontaneous reports of pancreatitis, acute and chronic interstitial nephritis and pericarditis associated with 5-ASA therapy. Neuropathy, hepatitis and alterations in peripheral blood counts such as leukopenia, neutropenia, thrombocytopenia and aplastic anemia have been rarely reported.

Overdose
Symptoms and Treatment: There is no specific antidote. Gastric lavage should be employed, followed by promotion of diuresis by the i.v. infusion of an electrolyte solution.

Recommended Dosage
During the acute inflammatory stage and in long-term maintenance therapy, 5-ASA must be taken reliably and consistently by the patient in order to ensure therapeutic success.

Although symptomatic relief may be seen as early as 3to 21days, therapy should be continued depending on clinical findings.

The following dosage regimens are recommended: Adults: The tablets should be swallowed whole before meals with plenty of fluid.

For the management of acute ulcerative colitis, 1.5to 3g daily in divided doses.

For prevention of relapses of acute ulcerative colitis, 1.5g daily in divided doses.

Supplied / Packaging
Each oval, red-orange enteric coated tablet contains: 5-aminosalicylic acid 500mg. Nonmedicinal ingredients: calcium stearate, glycine, iron oxide (red), iron oxide (yellow), methacrylic acid copolymer, microcrystalline cellulose, polyethylene glycol 6000, povidone, silicon dioxide, sodium carbonate, sodium croscarmellose, talc and titanium dioxide. Mesasal tablets are acrylic coated to prevent release of 5-ASA until the tablets reach the terminal ileum and proximal colon. Polyethylene bottles of 100.