Mesalamine Delayed-Release Tablets - Dosage, Uses, and Side Effects

Overview

Mesalamine delayed-release tablets are used to treat ulcerative colitis (a condition characterized by sores and swelling in the lining of the large intestine). It belongs to a class of drugs known as aminosalicylates. It was approved by the United States Food and Drug Administration (USFDA) on January 16, 2007. It is a drug used in the induction and maintenance therapy of ulcerative colitis and is generally safe, effective, and well-tolerated by patients. It causes mucosal healing and reduces the risk of colorectal cancer in the long term. Introducing new drug formulations has led to further research on their secondary outcomes.

How Do Mesalamine Delayed-Release Tablets Work?

Ulcerative colitis is a form of inflammatory bowel disease (IBD) (inflammation of the gastrointestinal tract) that affects the entire colon (large intestine) and the rectum. Mesalamine delayed-release tablet is an anti-inflammatory agent that reduces swelling, treats, and prevents flare-ups of mild to moderate ulcerative colitis and other symptoms such as stomach pain, diarrhea, and rectal bleeding. It is a prescription medicine and must be taken precisely and regularly as the doctor instructs. However, renal function must be evaluated before initiating the treatment.

Indications of Mesalamine Delayed-Release Tablets

Mesalamine delayed-release tablets are indicated for the following conditions:

• Mild to moderately active ulcerative colitis in patients over the age of five years.

• Maintenance of remission of symptoms of ulcerative colitis in adults.

Contraindications of Mesalamine Delayed-Release Tablets

Mesalamine delayed-release tablets are contraindicated in the following conditions:

• Patients with known or suspected hypersensitivity (allergic reactions) to Mesalamine capsules, its components, salicylates, or aminosalicylates.

• Pregnant and lactating women.

• Children below five years of age and elderly individuals over 65 years of age.

• Patients with impaired renal function.

Available Doses and Dose Forms

Mesalamine is available as 400 mg (milligrams), delayed-release tablets (which slowly release the medication), capsules, and extended-release (long-acting) capsules. It must be taken orally three times daily, with or without food. These tablets or capsules must be taken whole and not split, broken, crushed, or chewed. The dosage depends on the location and extent of the disease, and the therapy may be single or in combination.

The recommended dose of Mesalamine is 800 mg (two 400 mg capsules) to be taken thrice a day for six weeks. For children, the recommended dose depends on the weight (maximum 2.4 grams per day) to be taken twice a day for six weeks. For maintenance therapy, the recommended dose is 1.6 g (four 400 mg capsules) daily in two to four doses.

Warnings and Precautions

• Hypersensitivity reactions (severe allergic reactions) can occur in some patients taking Sulfasalazine, Mesalamine, or other compounds that contain or are converted to Mesalamine. Therefore, if any signs or symptoms are observed or suspected, patients must be immediately evaluated, appropriate treatment must be considered, and the drug must be discontinued.

• Mesalamine delayed-release tablet has the potential to cause renal impairment in some individuals. Therefore, renal function must be evaluated before and periodically during treatment with Mesalamine. The risks and benefits must be assessed before recommending the treatment to patients with a history of renal disorders.

• Mesalamine-induced acute intolerance syndrome (sensitivity to Mesalamine) can occur during the treatment, which may be challenging to differentiate from an exaggeration of ulcerative colitis. It can result in abdominal pain, cramps, fever, headache, rash, and bloody diarrhea. However, the exact frequency has yet to be determined, but it has occurred in about three percent of subjects during the clinical trials. Therefore, patients must be closely monitored, and the drug must be discontinued if the symptoms worsen.

• Studies have reported cases of hepatic failure in some patients with a history of liver disease. Therefore, the risks and benefits must be considered before recommending Mesalamine delayed-release tablets to such patients.

Adverse Effects of Mesalamine Delayed-Release Tablets

Some of the adverse effects of Mesalamine delayed-release tablets include:

• Nausea and vomiting.

• Constipation.

• Decreased appetite.

• Back pain.

• Muscle or joint pain.

• Burping.

• Runny nose or sneezing.

• Sore throat.

• Dizziness.

• Hair loss.

• Congestion.

Some of the severe side effects include:

• Itching.

• Skin rash.

• Fever.

• Mouth sores.

• Swelling of the face, eyes, lips, mouth, and tongue.

• Shortness of breath.

• Chest pain.

• Yellowish discoloration of the eyes and skin.

• Abdominal pain.

• Difficulty urination.

• Black stools.

For Patients

What Is Ulcerative Colitis?

Ulcerative colitis (UC) is a type of inflammatory bowel disease (inflammation of the gastrointestinal tract) that causes swelling of the large intestine and rectum. It is a chronic (long-term) condition, and the symptoms can range from mild to severe. The exact cause of this condition has yet to be entirely understood. However, it is known to be an autoimmune disorder (abnormal reactions of the immune system) that causes inflammation and ulcers in the inner lining of the large intestine. This disorder affects men and women equally and can occur at any age, but it mainly develops between 15 and 30.

Symptoms of ulcerative colitis include:

• Abdominal pain.

• Diarrhea.

• Blood or pus in the stools.

• Fatigue.

• Fever.

• Anemia.

• Rectal pain.

• The urgency to defecate.

• Inability to defecate despite urgency.

• Weight loss.

• Loss of appetite.

Ulcerative colitis is mainly managed by medications to reduce pain and inflammation and maintain remission (improvement of symptoms), and surgery is recommended in severe cases or to treat complications.

What Are Mesalamine Delayed-Release Tablets?

Mesalamine delayed-release tablet is a prescription medication used to treat mild to moderate ulcerative colitis in adults and children over the age of five years. It is also used to prevent flare-ups and maintain the improvement of symptoms in patients with ulcerative colitis. It belongs to a group of medications called aminosalicylates and works by preventing the production of certain chemicals that cause inflammation. Thus, it helps reduce swelling in the colon and also symptoms such as stomach pain, cramps, diarrhea, rectal bleeding, fatigue, etc.

How Effective Is Mesalamine Delayed-Release Tablet?

Mesalamine delayed-release tablet is a safe and effective treatment and is well-tolerated among most patients with mildly to moderately active ulcerative colitis. The dose of 4.8 g/day (grams per day) may enhance the success rate compared to a 2.4 g/day dose of Mesalamine. However, there is no evidence of a greater clinical response compared to other similar drugs. The effectiveness of Mesalamine delayed-release tablet is demonstrated by response rates ranging between 40 to 70 percent in patients with active disease and 15 to 20 percent in cases of remission.

How Should Mesalamine Delayed-Release Tablets Be Taken?

Mesalamine delayed-release tablets must be taken orally, with or without food, three times a day for six weeks. In children, the dose is determined depending on the individual's weight. It must be taken exactly as prescribed by the doctor to get better results. The tablets must be swallowed as a whole and must not be split, chewed, or crushed. Plenty of fluids must be consumed while taking Mesalamine delayed-release tablets. This medication must be continued even if the patient feels better and must not be discontinued without the doctor’s consent.

What Are the Side Effects of Mesalamine Delayed-Release Tablets?

Some of the side effects of Mesalamine delayed-release tablets include:

• Stomach pain.

• Bloody diarrhea.

• Rectal bleeding.

• Bloody or dark urine.

• Difficulty breathing.

• Chest tightness.

• Bloody stools.

• Fever.

• Chills.

• Dizziness.

• Bloating sensation.

• Loss of appetite.

• Nausea and vomiting.

• Discomfort.

• Blurred vision.

• Headache.

• Muscle and joint pain.

• Runny nose.

• Skin rash.

• Itching.

• Sore throat.

• Cough.

What Must the Patient Inform the Doctor Before Taking Mesalamine Delayed-Release Tablets?

• Before starting treatment, patients must inform the doctor if they are allergic to Mesalamine, its components, drugs such as Olsalazine and balsalazide, or other medications.

• Before starting treatment, patients must tell the doctor if they have or ever had eczema (skin disease), pericarditis (swelling of the tissues around the heart), myocarditis (swelling of the heart muscles), kidney diseases, gastrointestinal obstruction, or any other medical conditions.

• Before starting treatment with Mesalamine delayed-release tablets, patients must inform the doctor if they take any vitamins or nutritional supplements, herbal products, over-the-counter drugs, or other medications.

• Female patients must tell the doctor if they are pregnant, breastfeeding, or suspect pregnancy before taking Mesalamine delayed-release tablets.

What Are the Precautionary Measures to Be Followed While Taking Mesalamine Delayed-Release Tablets?

• Mesalamine can cause severe allergic reactions or may worsen the symptoms in some patients. Therefore, the doctor must be informed immediately in such cases.

• Two 400 mg capsules cannot be substituted for one 800 mg Mesalamine-delayed release tablet.

• Mesalamine delayed-release tablets can affect liver function; hence, if any symptoms of impaired liver function are observed, the doctor must be informed.

• Mesalamine-delayed release tablets can decrease kidney function; hence, patients must get all the recommended blood tests before starting the treatment.

• Mesalamine may make the skin sensitive to sunlight. Hence, unnecessary exposure to the sun must be avoided, or protective clothing, sunscreen, and sunglasses must be used outdoors.

• Mesalamine must not be taken by people who have received the Varicella virus vaccine in the past six weeks, as it increases the risk of Reye’s syndrome (fat accumulation in the liver, brain, and other parts).

Dietary Considerations

No dietary restrictions are necessary during the treatment with Mesalamine delayed-release tablets unless instructed by the prescribing doctor.

Missed Dose

The missed dose of the Mesalamine delayed-release tablet must be taken as soon as remembered. However, the missed dose can be skipped if it is time for the next dose, and the regular dose schedule must be followed. A double dose must not be taken to compensate for the missed dose.

Overdose

The doctor must be consulted immediately in case of an overdose or if any severe adverse reactions are observed during the treatment with Mesalamine delayed-release tablets.

Storage

Mesalamine delayed-release tablets must be stored in their original packaging at 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit), away from excess heat and moisture, and out of the reach of children.

For Doctors

Pharmacological Aspects of Mesalamine Delayed-Release Tablets

Mechanism of Action

The exact mechanism of action of Mesalamine delayed-release tablets is not understood, but it is known to be topical rather than systemic. In patients with chronic ulcerative colitis, the mucosal production of arachidonic acid metabolites is increased through the cyclooxygenase pathway and the lipooxygenase pathway. Mesalamine delayed-release tablets decrease inflammation by blocking the cyclooxygenase pathway and inhibiting prostaglandin production in the large intestine.

Pharmacodynamics

Mesalamine is a 5-aminosalicylic acid (5-ASA) and a nonsteroidal anti-inflammatory drug (NSAID) used to treat ulcerative colitis. It reduces the inflammatory process by its ability to prevent prostaglandin synthesis, interferes with leukotriene synthesis and consequent leukocyte migration, and is a potent scavenger of free radicals. It is also effective in inducing and maintaining remission of the symptoms of ulcerative colitis.

Pharmacokinetics

• Absorption: After an oral administration of Mesalamine delayed-release tablets, about 28 percent of the drug is absorbed, and the time taken to reach peak concentration (Tmax) is approximately 10 hours, which exhibits the delayed-release characteristics of the drug formulation. The systemic exposure to Mesalamine was increased after a high-fat meal, and the median Tmax was delayed by about four hours compared to a fasting state. However, it is not considered clinically relevant at a total daily dose of 2.4 g per day.

• Distribution: Approximately 37 to 49 percent of 5-ASA and 77 to 79 percent of N-acetyl-5-ASA are bound to plasma proteins, and the apparent volume of distribution is about 4.8 L (liters).

• Metabolism: Mesalamine gets rapidly metabolized by N-acetylation in the mucosal wall of the gut and in the liver to form N-acetyl-5-aminosalicylic acid.

• Excretion: Mesalamine is excreted mainly by the kidneys as N-acetyl-5-aminosalicylic acid, and the unabsorbed drug is excreted in the feces. The median terminal half-life is approximately 25 hours but can be variable.

Drug Interactions

Some of the drugs that interact with Mesalamine delayed-release tablets include:

• Lansoprazole

• Omeprazole.

• Pantoprazole.

• Rabeprazole.

• Diclofenac.

• Aspirin.

• Aceclofenac.

• Ibuprofen.

• Ketorolac.

• Naproxen.

• Meloxicam.

• Piroxicam.

• Sulfasalazine.

• Cefadroxil.

• Cyanocobalamin.

• Verapamil.

• Warfarin.

Clinical Studies

Two randomized, multicenter, placebo-controlled, double-blind clinical trials were conducted in patients with mild to moderate ulcerative colitis to demonstrate the efficacy of Mesalamine delayed-release tablets. Study 1 was conducted for six weeks in 158 patients. Patients received Mesalamine delayed-release tablets at doses of 1.6 g/day and 2.4 g/day compared to placebo. At doses of 2.4 g per day, 21 out of 43 subjects demonstrated an improvement in the sigmoidoscopic appearance of the bowel compared to 12 out of 44 patients taking a placebo. In addition, many patients also showed improvements in stool frequency and rectal bleeding. However, a 1.6 g per day dose is not recommended as it needs to exhibit consistent evidence to determine the drug's effectiveness.

Study 2 was almost similar to Study 1, but was conducted on 87 patients for six weeks. The subjects received 1.6 g/day and 4.8 g/day doses of Mesalamine delayed-release tablets and were compared to a placebo dose four times a day. A 4.8 g/day dose of Mesalamine delayed-release tablets showed significant sigmoidoscopic improvement in about 28 out of 38 patients, compared to 10 out of 38 patients who received a placebo. In addition, many patients also showed improvement in overall symptoms. However, a 4.8 g/day dose is not recommended as it does not exhibit greater efficacy than the 2.4 g/day dose.

Adequate and well-controlled clinical studies also demonstrated the safety and effectiveness of Mesalamine delayed-release tablets in children between 5 and 17 years of age with mild to moderate ulcerative colitis. Treatment success was also reported in patients using Mesalamine delayed-release tablets to maintain remission of symptoms of ulcerative colitis.

Nonclinical Toxicology

• Carcinogenicity: Mesalamine did not exhibit any carcinogenic effects at doses up to 480 mg/kg/day (milligrams per kilogram per day) in rats and 2000 mg/kg/day in mice.

• Mutagenicity: Mesalamine was found to be harmful in the Ames assay, chromosomal aberration, and other mutagenicity tests.

• Impairment of Fertility: Mesalamine did not significantly affect male and female rats' fertility or reproductive performance at oral doses up to 480 mg/kg/day.

Specific Considerations

• Pregnancy: Adequate and well-controlled studies of Mesalamine have not been conducted in pregnant women; hence, it must be avoided during pregnancy as it may cause fetal harm.

• Lactation: Mesalamine can be present in breast milk. Hence, the potential risk of adverse effects on the breastfed infant must be considered along with the necessity of the drug for the lactating woman.

• Pediatric Use: The safety and effectiveness of Mesalamine have not been established in children below five years of age.

• Geriatric Use: A sufficient number of patients over 65 years of age were not included in the studies of Mesalamine to determine the differences in drug response compared to young adults.

• Hepatic and Renal Impairment: Decreased hepatic, renal, and cardiac function were observed in some elderly patients taking Mesalamine. The risk of toxic reactions is also known to be higher in patients with renal disorders. Therefore, complete blood cell counts and renal function tests must be conducted before recommending Mesalamine to such patients.