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mesalamine (Asacol HD, Pentasa, Delzicol, Lialda, Apriso)

 

Classes: 5-Aminosalicylic Acid Derivatives

Dosing and uses of Asacol HD, Pentasa (mesalamine)

 

Adult dosage forms and strengths

capsule, extended-release

  • 250mg (Pentasa)
  • 375mg (Apriso)
  • 500mg (Pentasa)

tablet, delayed-release

  • 400mg (Asacol)
  • 800mg (Asacol HD)
  • 1.2g (Lialda)

capsule, delayed-release

  • 400mg (Delzicol)

 

Ulcerative Colitis

Remission induction of active, mild to moderate disease

  • Asacol HD: 1.6 g PO three times daily
  • Delzicol: 800 mg PO three times daily 1 hr ac or 2 hr pc
  • Lialda: 2.4-4.8 g PO qDay with meal up to 8 weeks
  • Pentasa: 1 g PO four times daily for 8 weeks

Remission maintenance

  • Apriso: 1.5 g PO qDay in am
  • Delzicol: 1.6 g/day PO in divided doses 1 hr ac or 2 hr pc
  • Asacol: 1.6 g/day PO in divided doses 1 hr ac or 2 hr pc
  • Lialda: 2.4 g PO qDay with food
  • Pentasa: 1 g/day PO four times daily for up to 8 weeks

 

Crohn Disease (Off-label)

Remission induction of active, mild-to-moderate disease

Asacol HD: 1.6 g three times daily

Lialda: 2.4-4.8 g PO qDay with meal for up to 8 weeks

Pentasa: 1 g PO four times daily for 8 weeks

 

Pediatric dosage forms and strengths

tablet, delayed-release

  • 400mg (Asacol)

capsule, delayed-release

  • 400mg (Delzicol)

 

Ulcerative Colitis

Asacol or Delzicol: Indicated for mildly to moderately active ulcerative colitis in children aged ≥5 yr

<5 years

  • Safety and efficacy not established

≥5 years

  • Duration of treatment: 6 weeks
  • 17 to <33 kg: 36-71 mg/kg/day PO divided twice daily; not to exceed 1.2 g/day
  • 33 to <54 kg: 37-61 mg/kg/day PO divided twice daily; not to exceed 2 g/day
  • 54 to 90 kg: 27-44 mg/kg/day PO divided twice daily; not to exceed 2.4 g/day

 

Asacol HD, Pentasa (mesalamine) adverse (side) effects

1-10%

Abdominal pain (4-8%)

GI discomfort (4-8%)

Headache (7%)

Flatulence (1-6%)

Nausea (1-6%)

Fatigue (3%)

Asthenia (3%)

Malaise (3%)

Weakness (3%)

Fever (3%)

Exacerbation of colitis (3%)

Dizziness (2-3%)

Rash (1-3%)

Pruritus (1-3%)

Acne (1-3%)

 

Frequency not defined

Pericarditis (rare)

Pharyngitis

Sensitivity reaction

Cholestatic hepatitis

Creatinine clearance decreased

Flulike syndrome

Discolored urine

 

Postmarketing Reports

Body as a whole: Lupus-like syndrome, drug fever

Cardiac disorders: Pericarditis, pericardial effusion, myocarditis

Gastrointestinal: Pancreatitis, cholecystitis, gastritis, gastroenteritis, gastrointestinal bleeding, perforated peptic ulcer

Hepatic: Jaundice, cholestatic jaundice, hepatitis, liver necrosis, liver failure, Kawasaki-like syndrome including changes in liver enzymes

Hematologic: Agranulocytosis, aplastic anemia

Immune system disorders: Anaphylactic reaction, Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), angioedema

Musculoskeletal and connective tissue disorders: Myalgia

Neurological/psychiatric: Peripheral neuropathy, Guillain-Barre syndrome, transverse myelitis

Renal disorders: Interstitial nephritis

Respiratory, thoracic and mediastinal disorders: Hypersensitivity pneumonitis (including interstitial pneumonitis, allergic alveolitis, eosinophilic pneumonitis)

Skin: Psoriasis, pyoderma gangrenosum, erythema nodosum

Urogenital: Reversible oligospermia

 

Warnings

Contraindications

Hypersensitivity to mesalamine or salicylates

Breastfeeding

Rectal suspension: Patients with history of sulfite hypersensitivity

Children with chickenpox or flulike symptoms

 

Cautions

Sulfasalazine hypersensitivity, renal insufficiency, coagulation abnormalities, pyloric stenosis

Use caution in active PUD, severe renal failure

Do not use with lactulose or drugs that lower intestinal pH

Although pericarditis rarely occurs, investigate any chest pain or dyspnea

Oligospermia has been reported in males

Hepatic failure may occur, particularly with preexisting liver impairment

May lead to falsely elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection, because of the similarity in the chromatograms of normetanephrine and mesalamine’s main metabolite, N-acetyl aminosalicylic acid; an alternative, selective assay for normetanephrine should be considered

Worsening of colitis/IBD may occur following initiation of therapy

Evaluate renal function prior to initiation of Asacol Hd

Evaluate the risks and benefits in patients with known renal impairment or taking nephrotoxic drugs; monitor renal function

Acute intolerance syndrome may occur; symptoms may be difficult to distinguish from an ulcerative colitis exacerbation; monitor for worsening symptoms; discontinue if acute intolerance syndrome suspected

Hypersensitivity reactions, including myocarditis and pericarditis reported; evaluate patients immediately and discontinue if hypersensitivity reaction suspected

Evaluate the risks and benefits in patients with known liver impairment

 

Pregnancy and lactation

Pregnancy category: B/C dependent on dosage form

Lactation: Not known whether drug or metabolites are distributed into breast milk; use caution

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Asacol HD, Pentasa (mesalamine)

Mechanism of action

Anti-inflammatory agent; mesalamine (5-aminosalicylic acid) is the active component of sulfasalazine, but specific MOA is unknown; probably inhibits prostaglandin and leukotriene synthesis and release in colon

 

Absorption

Bioavailability: Immediate-release is extensively and rapidly absorbed; extended-release 20-30% absorbed

Onset: Improvement usually evident in 1 week-3 months

Peak serum time: 4 hr (Apriso); 3 hr (Pentasa); 4-16 hr (Delzicol); 4-7 hr (rectal); 9-12 hr (Lialda); 8 hr (Mezavant); 4-12 hr (Asacol); 10-16 hr (Asacol HD)

 

Distribution

Protein bound: 43% (5-ASA); 78% (N-acetyl-5-ASA)

Vd: 0.2 L/kg

 

Metabolism

Rapidly acetylated in colon wall and liver, independent of pt acetylator status, into N-acetyl-5-aminosalicylic acid

Metabolites: N-acetyl-5-aminosalicylic acid (inactive)

 

Elimination

Half-life: 0.5-10 hr (5-ASA); 2-15 hr (N-acetyl-5-ASA )

Excretion: Feces 72%; urine: 19-30%

 

Administration

Instructions

Apriso, Asacol HD: May take with or without food

Delzicol: Take 1 hr before or 2 hr after meals

Lialda: Take with food

Do not substitute one Asacol HD 800 tablet for two mesalamine delayed-release 400 mg oral products

Swallow whole; do not chew, break, or crush

Patients unable to swallow tablet or capsule whole

  • Pentasa
    • Capsules may, alternatively, be opened and the entire contents sprinkled onto applesauce or yogurt
    • The entire contents should be consumed immediately; the capsules and capsule contents must not be crushed or chewed
  • Delzicol
    • For patients who are unable to swallow the capsules whole, carefully open the capsule(s) and swallow the contents (four 100 mg tablets)
    • Open the number of capsules required to make up a complete dose
    • There are 4 tablets per capsule; ensure all tablets per capsule are swallowed and no tablets are retained in the mouth
    • Swallow the tablets whole; do not cut, break, crush or chew the tablets
    • Intact, partially intact, and/or tablet shells have been reported in the stool; instruct patients to contact their physician if this occurs repeatedly