Mesalamine

Introduction Overview

Generic Name

mesalamine

Brand Name

Delzicol

Dosage Form

oral delayed-release capsule

Drug Class

5-aminosalicylates

Pharmacokinetics

Absorption: Delzicol is formulated as a delayed-release capsule designed to dissolve at a pH of 7 or higher, targeting the terminal ileum and colon where ulcerative colitis-related inflammation predominates. This pH-dependent release mechanism ensures minimal absorption in the stomach and proximal small intestine, allowing localized delivery of mesalamine directly to affected intestinal mucosa. Clinical pharmacokinetic studies indicate that systemic absorption of mesalamine after oral administration of Delzicol is limited, minimizing systemic exposure and reducing systemic adverse effects. The delayed-release mechanism leads to a lag time before measurable plasma concentrations are reached, consistent with colonic targeting. Factors such as gastrointestinal pH variations, motility, and concurrent medications could influence absorption characteristics.

Distribution: Once absorbed, mesalamine undergoes distribution primarily in plasma and extracellular fluid compartments. Due to its local action and low systemic absorption, significant plasma protein binding and tissue distribution are limited. Mesalamine exhibits moderate plasma protein binding; however, distribution to non-gastrointestinal tissues is minimal. Typical plasma concentrations post-Delzicol administration are relatively low, reflecting its therapeutic design as a topical colonic anti-inflammatory agent. There is limited penetration into protected compartments such as cerebrospinal fluid or central nervous system, consistent with its safety profile.

Metabolism: Mesalamine undergoes extensive metabolism primarily in the intestinal mucosa and liver through acetylation to form N-acetyl-5-aminosalicylic acid (N-acetylmesalamine). This metabolite exhibits significantly less pharmacologic activity. The acetylation process is enzyme-mediated via N-acetyltransferase enzymes and represents the principal metabolic pathway. There is some enterohepatic recirculation of mesalamine and its metabolites, which may prolong local gastrointestinal exposure. Genetic polymorphisms in acetylation enzymes could potentially influence metabolism and therapeutic response, though clinical significance remains to be fully elucidated.

Elimination: Elimination of mesalamine and its metabolites occurs primarily through renal excretion. The majority of the drug is excreted as N-acetylmesalamine in the urine. The elimination half-life of mesalamine after delayed-release capsule administration is approximately 20 to 50 hours, reflecting slow systemic absorption and metabolism. Renal function plays a crucial role in clearance; hence, patients with impaired renal function may require monitoring. Minimal fecal excretion occurs, corresponding to drug released locally in the colon that is not absorbed. No significant biliary excretion has been documented. Clinical monitoring for renal parameters is recommended during therapy due to potential nephrotoxicity in rare cases.

Dosage Forms

Available Dosage Forms: Delzicol is available exclusively as oral delayed-release capsules containing 400 mg mesalamine. Each capsule contains four inner tablets, intended to be swallowed whole or, if swallowing is difficult, the capsules may be opened and the tablets taken whole without crushing or chewing to preserve delayed-release properties.

Dosages for Adults and Adolescents: For the treatment of mildly to moderately active ulcerative colitis, adults are generally prescribed 800 mg (two 400 mg capsules) three times daily for 6 weeks. For maintenance of remission, the adult dose is typically 1.6 grams daily (four 400 mg capsules) administered in two to four divided doses. Pediatric patients aged 5 years and older receive weight-based dosing with adjustments made according to body weight, with twice-daily dosing recommended for 6 weeks; doses range from approximately 36 to 71 mg/kg/day up to a maximum of 2.4 grams per day depending on weight category.

Specific Patient Populations: Pediatric dosing requires careful weight-based adjustment with guidance to avoid exceeding maximum daily dose thresholds. There is limited data on dosing adjustment in patients with hepatic or renal impairment; however, caution and regular monitoring, especially for renal function, are advised. Dose modifications have not been formally established for elderly patients, but renal function decline with age necessitates monitoring. Pregnancy and breastfeeding patients require risk-benefit assessment as safety data are limited, and use is recommended only if clearly needed.

Delzicol 400 mg delayed-release capsule formulation is not interchangeable with other mesalamine-containing products such as mesalamine delayed-release 800 mg tablets; dosing equivalency has not been established. Patients should be advised against substituting brands or formulations without consulting healthcare professionals.

Mechanism Of Action

Mesalamine, the active ingredient in Delzicol, acts primarily as a topical anti-inflammatory agent in the gastrointestinal tract, particularly targeting the colon and terminal ileum where ulcerative colitis inflammatory lesions are localized. Its mechanism involves inhibition of the cyclooxygenase (COX) enzyme pathways, specifically COX-1 and COX-2, which are crucial in the conversion of arachidonic acid to pro-inflammatory prostaglandins. By blocking COX enzymes, mesalamine reduces prostaglandin synthesis, thereby diminishing the inflammatory response, vascular permeability, and edema within the intestinal mucosa.

Additionally, mesalamine exerts several other biochemical effects contributing to its therapeutic action. It scavenges free radicals and reactive oxygen species, limiting oxidative damage implicated in ulcerative colitis pathogenesis. Mesalamine also modulates the activity of nuclear factor kappa B (NF-kB), a transcription factor pivotal in controlling genes linked to inflammation, cytokine production, and immune responses. This modulation leads to downregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins.

On the cellular level, mesalamine promotes mucosal healing by enhancing epithelial barrier function and inhibiting leukocyte chemotaxis, thus reducing the influx of inflammatory cells into the gut mucosa. It may also induce apoptosis in activated T lymphocytes involved in the autoimmune inflammatory process. The local delivery mechanism of Delzicol ensures that mesalamine exerts these effects directly at the site of inflammation, optimizing efficacy and minimizing systemic adverse effects.

Comparatively, other 5-aminosalicylates such as sulfasalazine deliver mesalamine but are associated with higher rates of systemic side effects due to sulfapyridine moiety metabolism. Delzicol’s formulation as a delayed-release capsule provides a targeted release without sulfapyridine, potentially improving tolerability. Clinical studies have demonstrated Delzicol’s effectiveness in induction and maintenance therapy of ulcerative colitis by virtue of these mechanisms, highlighting its place as a mainstay in mild to moderate disease management.

Pharmacological Actions

Topical anti-inflammatory effect in the colon and terminal ileum by inhibiting cyclooxygenase enzymes.
Inhibition of prostaglandin synthesis leading to reduction of inflammatory mediators.
Antioxidant activity via scavenging of free radicals and reactive oxygen species.
Modulation of nuclear factor kappa B (NF-kB) signaling pathway to downregulate pro-inflammatory cytokines.
Reduction of leukocyte chemotaxis and infiltration into the intestinal mucosa.
Promotion of mucosal healing through enhanced epithelial barrier function.
Induction of apoptosis in activated immune cells involved in the inflammatory response.
Selective delayed-release targeting to terminal ileum and colon due to pH-dependent dissolution.
Minimal systemic absorption reducing systemic immunosuppressive effects.
Non-immunosuppressive anti-inflammatory action distinct from corticosteroids or biologics.

Therapeutic Or Clinical Uses

Treatment of mildly to moderately active ulcerative colitis in patients aged 5 years and older.
Maintenance of remission in adult patients with ulcerative colitis.
Reduction of colonic inflammation to alleviate symptoms such as diarrhea, rectal bleeding, and abdominal pain.
Management of autoimmune-mediated inflammation localized mainly to the colon and rectum.
Alternative first-line therapy for ulcerative colitis with a better safety profile than sulfasalazine in some patients.
Use as a steroid-sparing agent to reduce dependence on corticosteroids in IBD management.
Off-label uses may include treatment of proctitis, proctosigmoiditis depending on formulation and clinical judgment.
Adjunctive therapy in combination with other agents in moderate ulcerative colitis under specialist supervision.
Suitable therapeutic option for pediatric patients with ulcerative colitis due to targeted release and tolerability.
Utility in patients unable to tolerate oral sulfasalazine due to allergic or adverse reactions.

Side Or Adverse Effects

Kidney problems including potential nephrotoxicity; monitoring of renal function is recommended.
Acute intolerance syndrome characterized by cramping, abdominal pain, bloody diarrhea, fever, headache, and chest pain.
Allergic reactions including myocarditis, pericarditis, blood dyscrasias, and multi-organ hypersensitivity reactions.
Liver injury or liver failure particularly in patients with pre-existing hepatic conditions.
Severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, rash, and blistering.
Sun sensitivity leading to increased risk of phototoxic reactions, especially in patients with atopic dermatitis or eczema.
Kidney stones, with symptoms including severe flank pain and hematuria; adequate hydration advised.
Common gastrointestinal side effects including belching, stomachache, constipation, diarrhea, and upset stomach.
Neurological symptoms such as dizziness and headache reported.
Upper respiratory symptoms including runny nose, nasal congestion or inflammation.
Fatigue, flu-like symptoms, and generalized malaise in some patients.
Rash or skin eruptions that may require discontinuation if severe.
Rare but serious hypersensitivity reactions necessitating immediate medical attention.
Possible elevation of pancreatic enzymes such as lipase in pediatric population.
Potential worsening of ulcerative colitis symptoms early in treatment due to intolerance.

Precautions

Inform the healthcare provider of any history of kidney problems before initiating treatment.
Avoid use in patients with known allergy to salicylates or aminosalicylates, including aspirin sensitivity.
Use caution in patients with history of sulfasalazine allergy due to cross-reactivity risk.
Patients with pre-existing liver disease should be monitored closely for hepatotoxicity.
Discontinue if acute intolerance syndrome or severe allergic reactions develop.
Advise patients not to crush, break, or chew capsules or inner tablets to preserve delayed-release properties.
Encourage adequate hydration to reduce risk of kidney stones.
Advise limited sun exposure and use of sunscreen, especially in patients with photosensitive skin conditions.
Use caution in patients with potential or established gastrointestinal obstruction.
Monitor renal function periodically during long-term treatment.
Discuss pregnancy and breastfeeding status as safety data are limited; use only if benefits outweigh risks.
Assess for potential drug interactions, especially with NSAIDs, azathioprine, and 6-mercaptopurine.
Instruct patients to report any signs of allergic reactions, unusual fatigue, or yellowing of skin and eyes.
Advise against substitution or switching brands/formulations without healthcare professional guidance.
Consider dose adjustments or discontinuation in cases of significant adverse reactions.

Warnings

Risk of nephrotoxicity: kidney function should be evaluated before and during therapy.
Potential for acute intolerance syndrome, presenting with severe gastrointestinal and systemic symptoms.
Warning for serious allergic-type reactions including myocarditis and pericarditis.
Risk of liver failure in patients with history of liver impairment or prior mesalamine use.
Severe cutaneous adverse reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
Sun sensitivity leading to phototoxic reactions especially in patients with underlying skin diseases.
Possible kidney stone formation necessitating adequate fluid intake.
Not interchangeable on a mg-to-mg basis with other mesalamine formulations; improper substitution may lead to suboptimal therapy.
Use during pregnancy only if clearly needed due to limited safety data.
Passes into breast milk; caution advised when used during breastfeeding.
Close monitoring recommended when used concomitantly with nephrotoxic or myelosuppressive agents.
Not to be used in patients with known hypersensitivity to mesalamine or related compounds.
May exacerbate pre-existing allergies or sensitivities to aspirin and other salicylates.
Avoid abrupt discontinuation that may lead to flare-ups of ulcerative colitis symptoms.
In pediatric patients, monitor closely for adverse effects, including headache, rash, and gastrointestinal disturbances.

Contraindication

Known hypersensitivity to mesalamine, salicylates, including aspirin, or any component of Delzicol.
History of allergic or anaphylactic reactions to aminosalicylates or sulfasalazine.
Patients with intestinal obstruction or stricture where delayed-release capsules cannot pass or dissolve appropriately.
Severe renal impairment due to increased risk of accumulation and toxicity.
Patients with severe hepatic impairment unless under rigorous medical supervision.
Known cases of mesalamine-induced acute intolerance syndrome.
Use contraindicated in patients with previously documented mesalamine-induced myocarditis or pericarditis.
Patients with active severe ulcerative colitis flare who require immediate systemic corticosteroid or biologic therapy as sole treatment.
Infants and children under 5 years of age due to insufficient safety and efficacy data.
Patients with severe skin reactions attributable to mesalamine use should not be re-challenged.
Known hypersensitivity to dye/colorants used in the capsule shell.
Contraindicated in patients concurrently on incompatible medications with high risk of interactions unless carefully managed.
Use contraindicated in patients with active infections where immunomodulation could worsen condition.
Patients who cannot swallow capsules or tablets and refuse to adhere to proper administration of inner tablets.
Contraindicated in patients with known hypersensitivity to any inactive ingredients such as lactose monohydrate or other excipients in the formulation.

Drug Interactions

Concomitant use with nonsteroidal anti-inflammatory drugs (NSAIDs) increases risk of kidney damage.
Co-administration with azathioprine or 6-mercaptopurine may enhance hematological toxicity such as leukopenia.
Potential additive nephrotoxic effects when used with other nephrotoxic medications (e.g., cyclosporine, tacrolimus).
Interaction with sulfasalazine and other salicylates may increase risk of hypersensitivity reactions.
Use with warfarin or other anticoagulants requires monitoring due to potential alteration of coagulation parameters.
Drugs altering gastric pH or gastrointestinal motility may affect the delayed-release properties of Delzicol.
Possible interaction with iron-containing supplements which may affect drug absorption or exacerbate side effects.
Caution advised when used with other drugs metabolized via acetylation pathways due to competition.
No significant interactions have been documented with commonly used antibiotics, but clinical monitoring is prudent.
Combination with corticosteroids used in ulcerative colitis may complicate assessment of side effects.
Live vaccines should be used cautiously during mesalamine therapy due to altered immune response.
Patients on immunomodulatory therapies should be monitored for additive immunosuppression.
Concomitant use with cholestyramine or other resins may reduce absorption of mesalamine.
Drug interactions with herbal supplements, especially those affecting coagulation or kidney function, are theoretically possible.
Regular monitoring and dose adjustments may be needed during polypharmacy to optimize safety and efficacy.

Preparations Of The Drug

Delzicol 400 mg oral delayed-release capsules containing four inner tablets.
Each capsule designed for pH-dependent delayed release targeting terminal ileum and colon.
Inactive ingredients include silicon dioxide, dibutyl sebacate, ferric oxide red and yellow, lactose monohydrate, magnesium stearate, methacrylic acid and methyl methacrylate copolymer (Eudragit S), polyethylene glycol, povidone, sodium starch glycolate type A potato, talc, and hypromelloses.
Available in prescription-only formulations distributed by Allergan USA, Inc.
Packaged in blister packs or bottles with specific storage instructions to maintain stability.
Capsules intended to be swallowed whole; however, for patients unable to swallow capsules, the outer shell can be opened with tablets swallowed whole without crushing or chewing.
Not available as extended-release tablets; alternative mesalamine formulations exist under different brand names (e.g., Lialda, Pentasa) with varying release modalities.
Manufactured to maintain stability within pH and temperature ranges specified (storage at 20° to 25° C with excursions permitted).
Contains colorants such as ferric oxide used to identify dosage strength.
Formulated without sulfasalazine moiety, differentiating it from sulfasalazine-based delivery systems.
Suitable for use in adults and pediatric patients aged 5 years and older with weight-based dosing adjustments.
Packaging includes child-resistant features to prevent accidental ingestion.
Available in unit dose packaging or bulk supply depending on prescription requirements.
Intended exclusively for oral administration with no intravenous or rectal formulations under the Delzicol brand.
Delzicol has a FDA-approved generic version, enhancing accessibility and affordability.