Pentasa (Asacol, Mesalamine, Mesalazine) is a 5-aminosalicylic acid derivative that is used in the treatment of mild to moderately active inflammatory bowel disease (ulcerative colitis and Crohn's disease). In severe disease, other medications including corticosteroids, cyclosporin, and infliximab may be used. Other novel agents include vedolizumab hcp (Entyvio).

Pentasa (Asacol, Mesalamine) Uses:

• US labeling:

  • Oral:
    • Apriso: To maintain of remission of ulcerative colitis in patients ≥18 years
    • Asacol HD: Treatment of moderately active ulcerative colitis in adults
    • Delzicol: Treatment of mildly to moderately active ulcerative colitis in patients ≥5 years; also to maintain remission of ulcerative colitis in adults
    • Lialda, Pentasa: Treatment and maintenance of remission of mildly to moderately active ulcerative colitis
  • Rectal:
    • Treatment of active mild to moderate distal ulcerative colitis (suspension only), proctosigmoiditis (suspension only), or proctitis (suspension and suppository)

• Canadian labeling:

  • Oral:
    • Asacol, Mezavant: Treatment and maintenance of remission of mildly- to moderately active ulcerative colitis
    • Asacol 800: Treatment of moderately active ulcerative colitis
    • Mesasal: Treatment and maintenance of remission of ulcerative colitis
    • Pentasa: Treatment and maintenance of remission of mildly to moderately active ulcerative colitis; treatment and maintenance of remission of mild to moderate Crohn disease
  • Rectal foam:
    • Mezera: Treatment of mildly active ulcerative colitis of the sigmoid colon and rectum
  • Rectal suppository and suspension:
    • Treatment and maintenance of remission of distal ulcerative colitis (extending to splenic flexure) & as adjunctive therapy in more extensive disease (suspension only).
    • Treatment and maintenance of ulcerative proctitis (suppository only)

• Off Label Use of Mesalamine in Adults:

  • Crohn disease (management after surgical resection)

Pentasa (Asacol, Mesalamine) Dose in Adults:

Note:

• Asacol HD formulated with DBP has been discontinued in the US for more than 1 year.

Pentasa (Asacol, Mesalamine) Dose in the treatment of Crohn disease management after surgical resection (off-label):

• Oral:
  • 1.5 g twice daily or 2.4 to 4 g/day in 3 divided doses.

Pentasa (Asacol, Mesalamine) Dose in the treatment of mild to moderate Crohn disease:

• Oral:
  • Pentasa (Canadian labeling; not in US labeling)
    • Initial: 1 g four times a day

Pentasa (Asacol, Mesalamine) Dose in the treatment of mild to moderate Crohn disease, (maintenance of remission):

• Oral:
  • Pentasa (Canadian labeling; not in US labeling): 1 g three times a day

Pentasa (Asacol, Mesalamine) Dose in the treatment of Distal ulcerative colitis or proctosigmoiditis:

• Mild to moderately active:

  • Retention enema (suspension): Rectal:
    • 4 g at bedtime, retained overnight for around 8 hours.

Note:

• • The duration of rectal therapy ranges from 3 to 6 weeks.
  • Some patients may require rectal and oral therapy concurrently.

• Mildly active:

  • Foam (Mezera [Canadian product]):
    • Rectal: 2 g (2 actuations) once a day at bedtime.
    • If the patient is not able to retain 2 g dose, may administer as 1 g (1 actuation) in 2 divided doses, 1 dose at bedtime & another dose during the night (after evacuation of first dose) or early in the morning.
    • It should be continued for at least 6 weeks until endoscopic and/or histological remission.

Pentasa (Asacol, Mesalamine) Dose in the treatment of Distal ulcerative colitis (maintenance of remission):

• Rectal:
  • Retention enema:
    • Salofalk [Canadian product]:
      • 2 g at bedtime daily or 4 g at bedtime every 2 to 3 days

Pentasa (Asacol, Mesalamine) Dose in the treatment of Ulcerative colitis: Oral:

Note:

• Mesalamine may be dosed once a day instead of multiple times daily in patients with mild to moderate ulcerative colitis; there is no significant difference in efficacy and safety.
• The dosing schedule should be according to patients' preferences in order to maximize adherence.
• The usual course of therapy is 6 to 8 weeks:

• US labeling:

  • Asacol HD: 1.6 g thrice daily for 6 weeks
  • Delzicol: 800 mg thrice daily for 6 weeks
  • Lialda: 2.4 or 4.8 g once a day.
  • Pentasa: 1 g four times a day.

• Canadian labeling:

  • Asacol:
    • 800 mg to 3.2 g in divided doses daily
    • For severe active disease may increase to 4.8 g daily
  • Asacol 800:
    • 1.6 g thrice daily for 6 weeks
  • Mesasal:
    • 1.5 to 3 g daily in 3 divided doses
  • Mezavant:
    • 2.4 to 4.8 g OD
  • Pentasa:
    • 500 mg QID
    • May increase to 1 g QID if needed

Pentasa (Asacol, Mesalamine) Dose in the treatment of Ulcerative colitis (maintenance of remission): Oral:

Note:

• Mesalamine may be given in OD dose instead of multiple times daily in patients with mild to moderate ulcerative colitis; there is no significant difference in efficacy and safety.
• The dosing schedule should be according to patient preference in order to maximize adherence.

• US labeling:

  • Apriso:
    • 1.5 g once a day in the morning
  • Delzicol:
    • 1.6 g in 2 to 4 divided doses
  • Lialda:
    • 2.4 g once a day
  • Pentasa:
    • 1 g four times a day

• Canadian labeling:

  • Asacol:
    • 1.6 g daily in divided doses
  • Mesasal:
    • 1.5 g daily in 3 divided doses
  • Mezavant:
    • 2.4 g once a day
  • Pentasa:
    • 500 mg four times a day
    • May increase to 1 g four times a day if needed

Pentasa (Asacol, Mesalamine) Dose in the treatment of active Ulcerative proctitis:

• Retention enema (suspension):

  • 4 g at bedtime
  • Retained overnight
  • For a duration of approximately 8 hours

• Rectal suppository:

  • 1,000 mg (1 suppository) rectally (retain for at least 1 to 3 hours) at bedtime for a duration of 3 to 6 weeks.

• Salofalk [Canadian product]:

  • One 500 mg suppository in rectum 2 to 3 times daily or one 1,000 mg suppository in rectum once daily at bedtime
  • Retained for at least 1 to 3 hours to achieve maximum benefit.
  • Usual dose:
    • 1 to 1.5 g daily until significant clinical response or remission.
    • Taper off gradually
    • Avoid abrupt discontinuation.

Pentasa (Asacol, Mesalamine) Dose in Childrens:

Note:

• Some oral products are not bioequivalent and should not be interchanged (ie, two Delzicol 400 mg capsules are not interchangeable or substitutable with one mesalamine 800 mg delayed-release tablet).

Pentasa (Asacol, Mesalamine) Dose in the treatment of mild to moderate Crohn disease; maintenance of remission: Limited data available:

• Children and Adolescents:

  • Oral:
    • 50 to 100 mg/kg/day divided every 6 to 12 hours
    • Maximum dose: 1,000 mg/dose

Pentasa (Asacol, Mesalamine) Dose in the treatment of mild to moderately active Ulcerative colitis:

Oral:

• Manufacturer's labeling:

  • Delayed-release capsule: Delzicol: Children ≥5 years and Adolescents:

    • 17 to <33 kg:
      • Oral:
        • 800 mg in the morning and 400 mg in the evening for 6 week
        • Maximum daily dose: 1,200 mg/day
    • 33 to <54 kg:
      • Oral:
        • 1,200 mg in the morning and 800 mg in the evening for 6 weeks
        • Maximum daily dose: 2,000 mg/day
    • 54 to 90 kg:
      • Oral:
        • 1,200 mg in the morning and 1,200 mg in the evening for 6 weeks
        • Maximum daily dose: 2,400 mg/day

• Alternate dosing (including proctitis): Limited data available:

  • The usual course of therapy ranges from 3 to 8 weeks & is dependent on the type of treatment:

  • Children and Adolescents:

    • Oral:
      • • 30 to 60 mg/kg/day divided every 6 to 12 hours
        • Doses as high as 100 mg/kg/day have been used
        • Maximum daily dose: 4,000 mg/day
    • Rectal: Limited data available:

• Older Children and Adolescents:

  • Enema:
    • 4,000 mg once daily at bedtime
  • Suppository:
    • 500 mg once daily at bedtime; some have used twice daily

Mesalamine Pregnancy Risk Category: B

• Mesalamine has been shown to cross the placenta.
• Human studies have not shown an increase in congenital malformations.
• These events can be caused by maternal diseases, such as stillbirths, preterm births, or decreased birth weights.
• Some products may contain dibutylphthalate (DBP), which is an inactive ingredient in their enteric coating (e.g. Asacol and Asacol HD).
• Doses higher than recommended for humans were associated with adverse effects in male rats.
• For current formulations, refer to the product labeling.
• Mesalamine can be used to treat inflammatory bowel diseases during pregnancy. However, products with DBP should not be used.
• Reversible oligospermia in males has been reported.

Mesalamine use during breastfeeding:

• Mesalamine (5-ASA) and the metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) are present in breast milk.
• After receiving oral and rectal doses of 500 mg to 4.8% g/day, human breast milk contained lower levels of mesalamine (undetectable up to 0.5 mg/L) and higher concentrations (0.2 to 9.3mg/L) of the metabolite.
• These concentrations would indicate that the infant's exposure to mesalamine is 0 to 0.75 mg/kg/day and Ac-5-ASA at 0.03 to 1.4mg/kg/day, respectively.
• Breastfeeding infants can experience diarrhea if the mother receives mesalamine rectal within 12 hours.
• Breastfeeding is acceptable for mesalamine treatment.

Pentasa (Asacol, Mesalamine) Dose in Kidney Disease:

• There are no specific dosage adjustments provided in the manufacturer's labeling
• However, dosage adjustment may be necessary since mesalamine is renally eliminated.
• Use cautiously.

Pentasa (Asacol, Mesalamine) Dose in Liver disease:

• There are no dosage adjustments provided in the manufacturer's labeling
• Use cautiously.

• Adverse effects vary depending upon the dosage form
• Frequency is similar in adult and pediatric patients unless otherwise noted.
• Incidence is usually on the lower end with enema and suppository dosage forms.

Common Side Effects of Pentasa (Asacol, Mesalamine):

• Central nervous system:

  • Headache

• Gastrointestinal:

  • Eructation
  • Abdominal pain
  • Constipation

• Respiratory:

  • Nasopharyngitis

Less Common Side Effects of Pentasa (Asacol, Mesalamine):

• Cardiovascular:

  • Hypertension

• Central Nervous System:

  • Dizziness
  • Fatigue
  • Pain
  • Vertigo
  • Nervousness
  • Paresthesia

• Dermatologic:

  • Skin Rash
  • Alopecia
  • Acne Vulgaris

• Endocrine & Metabolic:

  • Increased Serum Triglycerides
  • Weight Loss

• Gastrointestinal:

  • Diarrhea
  • Exacerbation Of Ulcerative Colitis
  • Flatulence
  • Upper Abdominal Pain
  • Dyspepsia
  • Nausea
  • Lower Abdominal Pain
  • Gastroenteritis
  • Hemorrhoids
  • Tenesmus
  • Gastrointestinal Hemorrhage
  • Bloody Diarrhea
  • Pancreatitis
  • Sclerosing Cholangitis
  • Vomiting
  • Rectal Pain
  • Abdominal Distention
  • Anorectal Pain
  • Nausea And Vomiting
  • Colitis

• Genitourinary:

  • Hematuria
  • Urinary Frequency

• Hematologic & Oncologic:

  • Decreased Hematocrit
  • Decreased Hemoglobin
  • Rectal Hemorrhage

• Hepatic:

  • Cholestatic Hepatitis
  • Increased Serum Transaminases
  • Hepatic Insufficiency

• Infection:

  • Influenza
  • Infection
  • Viral Infection

• Neuromuscular & Skeletal:

  • Back Pain
  • Arthralgia
  • Arthropathy
  • Leg Pain

• Ophthalmic:

  • Visual Disturbance

• Otic:

  • Tinnitus

• Renal:

  • Decreased Creatinine Clearance

• Respiratory:

  • Rhinitis
  • Sinusitis
  • Cough
  • Dyspnea

• Miscellaneous:

  • Intolerance Syndrome
  • Fever

Contraindications to Pentasa (Asacol, Mesalamine):

• Hypersensitivity to mesalamines, aminosalicylates and salicylates or any other component of the formulation Canadian labeling: Additional contraindications not in the US labeling

  Warnings and precautions

• Grave renal impairment (GFR 30mL/minute/1.73m2)
• Grave hepatic impairment

Additional contraindications can be found on specific Canadian product labels:

• Cardiac hypersensitivity reactions:

  • There have been reports of myocarditis and pericarditis (mesalamine-induced heart hypersensitivity reactions). 
  • Patients with predisposition to these conditions should be supervised.

• Hypersensitivity reactions

  • Mesalamine-induced hypersensitivity reactions were reported.
  • These may include internal organ involvement such as pericarditis and myocarditis. 
  • Stop taking mesalamine-induced hypersensitivity reaction medication.

• Syndrome of intolerance:

  • It may cause an acute intolerance (cramping and abdominal pain; sometimes fever; sometimes headache, malaise; pruritus.rash, conjunctivitis); discontinue use immediately if it occurs.
  • The drug can be stopped and symptoms will usually disappear.
  • Rechallenge to confirm hypersensitivity should be performed at a lower dose. Only use it if absolutely necessary.

• Photosensitivity

  • Patients with pre-existing skin conditions, such as atopic dermatology or atopic eruptions, should be cautious. There have been severe reactions to the medication.

• Effects on the renal system:

  • There have been reports of renal impairment, including minimal change nephropathy and acute and chronic interstitial Nephritis.
  • Rarely, there has been renal failure.
  • It is recommended that you have a renal function assessment done prior to starting therapy, and every so often during treatment.
  • Patients with renal impairment due to treatment of mesalamine should be treated immediately.

• Hypersensitivity to sulfasalazine:

  • Mesalamine may be a reaction for patients with hypersensitivity to sulfurazine.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious; reports of hepatic failure have been made.

• Renal impairment

  • Patients with kidney impairment, a history renal disease, and those taking nephrotoxic medication should be cautious.
  • Prevalent gastric or duodenal ulcers
  • Uterine tract obstruction
  • Use in children under 2 years old (Asacol 800, Mesasal and Mesasal),
  • Hemorrhagic diathesis, Mesasal
  • Patients who are unable to swallow an intact tablet (Asacol and Asacol 800);
  • Renal parenchymal disease (Pentasa).

Monitoring parameters:

• Renal function (prior to and periodically during therapy)
• CBC (particularly in elderly patients)
• Hepatic function
• Signs and symptoms of worsening acute intolerance syndrome

How to administer Pentasa (Asacol, Mesalamine)?

• Oral:

  • Capsules:

  • You can take it with or without food.
    • Apriso:
      • Avoid using antacids.
      • The release of mesalamine after ingestion is not affected by opening the capsule or placing the contents (delayed release granules), on food pH 6 (data on file, Salix Pharmaceuticals Medical Information).
      • This practice is not safe or effective.
    • Delzicol:
      • Take the capsule whole and mix it with water
      • Do not chew, break, crush, or chop.
      • If the patient is unable to swallow the capsule, you can open it and swallow the contents intact (do NOT cut, chew, break or crush the contents).
    • Pentasa:
      • Consume whole capsule
      • Do not crush, chew, or chew
      • You can open the capsule to allow the patient to swallow it.

• Tablets:

  • Consume whole. Do not chew, break, cut or crush.
    • Asacol [Canadian Product]:
      • You can take it with or without food.
    • Asacol HD (product without dibutylphthalate [DBP]).
      • Take the medication on an empty stomach at least one hour before or two hours after eating.
    • Asacol HD (product formulated using DBP), Asacol800 [Canadian Product]:
      • You can take it with or without food.
    • Lialda:
      • Serve a meal with your devotion.
    • Mesasal [Canadian product]:
      • Before meals, take it.
    • Mezavant [Canadian product]:
      • Serve a meal with your devotion.
    • Pentasa [Canadian product]:
      • Take with you.

• Rectal enema:

  • Make sure to shake the bottle.
  • For balance, ask patient to lie on their left side with the right leg extended and the left leg straight out. Or in a "knee-chest".
  • Place the lubricated tip of the applicator into the rectum, and point slightly towards the navel.
  • Grab the bottle tightly and tilt it so that the nozzle is facing the back. Then, squeeze gently to instill the medication.
  • After administering the medication, take out and dispose of the bottle.
  • You can keep enemas for as long as you like, up to 8 hours.

• Rectal foam (Mezera [Canadian product]):

  • Warm canister at room temperature (20degC-30degC [68degF-86degF]).
  • Attach the applicator to the canister and shake for 20 seconds.
  • Applicator should be inserted as far as possible into the rectum.
  • Once you have administered a dose, press the dome button once more. After the dose is administered, hold the applicator in place for between 10 and 15 seconds.
  • Press the dome once more and let go. Wait for 10 to 15 seconds before removing the applicator.

• Supppository:

  • Remove foil wrapper; avoid excessive handling.
  • Insert into the rectum.
  • Keep the suppository in your hand for at least 1 to 3 hours.
  • You should not remove the suppository.

Mechanism of action of Pentasa (Asacol, Mesalamine):

• The active ingredient of sulfasalazine is mesalamine (5-aminosalicylic acids).
• It is not known what the mechanism of action is.
• It is believed that mesalamine modulates local mediators of the inflammatory reaction, particularly leukotrienes. Additionally, mesalamine is postulated as a free radical scavenger (or an inhibitor of Tumor Necrosis Factor (TNF).
• This action seems more topical than systemic

Absorption:

• Rectal:
  • Variable and dependent upon retention time, underlying GI disease, and colonic pH
• Oral:
  • Tablet: ~20% to 28%
  • Capsule: ~20% to 43%

Protein binding:

• Mesalamine (5-ASA): ~43%
• N-acetyl-5-ASA: ~78%

Metabolism:

• Hepatic and via GI tract to N-acetyl-5-aminosalicylic acid

Half-life elimination:

• 5-ASA and N-acetyl-5-ASA:
  • Variable; ~ 25 hours (range: 2 to 296 hours)

Time to peak, serum:

• Capsule:
  • Apriso: ~4 hours
  • Delzicol: ~10 hours
  • Pentasa: ~3 hours
• Foam:
  • Mezera [Canadian product]: ~1 hour
• Rectal:
  • Pentasa, Salofalk [Canadian products]: 2 to 6 hours
• Tablet:
  • Asacol HD (formulated with dibutyl phthalate [DBP]): 10 to 16 hours
  • Asacol HD (formulated without DBP): ~24 hours (mean)
  • Lialda: 9 to 12 hours

Canadian products:

• Asacol: 7 hour
• Asacol 800: 10 hours
• Mesasal: ~7 hours
• Mezavant: 8 hours (range: 4 to 34 hours)

Excretion:

• Oral, suppository:
  • Urine (primarily as N-acetyl-5-ASA, ≤12% as unchanged drug)
  • feces (unabsorbed mesalamine)
• Enema:
  • Feces (primarily)
  • urine (10% to 30%)

International Brands of Mesalamine:

• Apriso
• Asacol HD
• Canasa
• Delzicol
• Lialda
• Pentasa
• Rowasa
• SfRowasa
• Asacol
• Asacol 800
• Mesasal
• Mezavant
• Mezera
• Salofalk
• TEVA-5 ASA
• 5-ASA 400
• Asacol
• Asacolon
• Asalit
• Asasol
• Canasa
• Claversal
• Colitofalk
• Coloncure
• Huma-Col-Asa
• Ibsol
• Lialda
• Lixacol
• Mecolzine
• Mesacol
• Mesala
• Mesalin
• Mesasal
• Meslamin
• Mezacol
• Mezavant
• Mezavant XL
• Octasa
• Pentasa
• Pentasa Enema
• Pentasa SR
• Pentasa Tab
• Rafassal
• Salazine
• Salofalk
• Salofalk Foam Enema
• Suprimal

Mesalamine Brand Names in Pakistan:

• Asacol
• Masacol (Getz Pharma)
• Pentasa (Ferring Pharma)