Dipentum (olsalazine sodium)
Inflammatory Bowel Agents Oral Capsule
Last reviewed · Source: First Databank (FDB) drug data
Overview
Olsalazine, a 5-aminosalicylic acid derivative, is a GI anti-inflammatory agent.
Olsalazine, a 5-aminosalicylic acid derivative, is a GI anti-inflammatory agent. Olsalazine generally is considered a prodrug of mesalamine (5-aminosalicylic acid) and has little or no anti-inflammatory activity until enzymatically cleaved in the colon to form mesalamine. Thus, the spectrum of pharmacologic activity of olsalazine generally is similar to that of mesalamine.
Mesalamine exhibits anti-inflammatory activity in the GI tract. Although the exact mechanism of action of mesalamine has not been fully elucidated, the drug appears to exert its anti-inflammatory effects locally, in the GI tract, rather than systemically. Limited data indicate that mesalamine may reduce inflammation in the colon by inhibiting cyclooxygenase, an enzyme that catalyzes formation of prostaglandin precursors (endoperoxides) from arachidonic acid.
Mesalamine also inhibits leukotriene synthesis, possibly by inhibiting lipoxygenase, an enzyme that catalyzes the formation of leukotrienes and hydroxyeicosatetraenoic acids (HETEs) from arachidonic acid and its metabolites. Although the role of arachidonic acid metabolites in the pathogenesis of inflammatory bowel disease remains to be determined, mucosal production of these metabolites, both through the cyclooxygenase and the lipoxygenase pathways, appears to be increased in patients with inflammatory bowel disease.
Following oral administration, about 2.4% of an oral dose of olsalazine is absorbed as unchanged drug, which partially undergoes sulfate conjugation. The remainder of an oral dose passes intact into the colon where the azo-linkage of each molecule of olsalazine is cleaved by intestinal flora to form 2 molecules of mesalamine. Mesalamine undergoes rapid N-acetylation, probably in the liver and the colonic epithelium, to form N-acetyl-5-aminosalicylic acid, which is principally excreted in feces; about 20% of mesalamine is excreted in urine, mostly as N-acetyl-5-aminosalicylic acid.
Less than 1% of a dose is excreted in urine as olsalazine. For further information on chemistry, pharmacology, and pharmacokinetics of mesalamine, see Mesalamine 56:36.
Each g of olsalazine sodium provides approximately 5.78 mEq (133 mg) of sodium.
USES: Olsalazine is used to treat a certain type of bowel disease called ulcerative colitis. It does not cure ulcerative colitis, but it may decrease symptoms such as stomach pain, diarrhea, and rectal bleeding caused by irritation/swelling of the colon/rectum. After an attack is treated, olsalazine is used to increase the amount of time between attacks.
Olsalazine is an aminosalicylate anti-inflammatory drug. It is believed to work by blocking the production of certain natural substances (such as prostaglandins) that may cause pain and swelling.
Generic name: olsalazine sodium
Pronunciation: (ohl-SAL-uh-zeen)
Drug class: Inflammatory Bowel Agents
Therapeutic class: Gastrointestinal Therapy Agents
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Dipentum
Indications
The following indications are listed for Dipentum:
- Ulcerative Colitis Remission
Also known as: Colitis Ulcerativa In Remission, Ulcerative Colitis In Remission.
Dosing
No dosing information is available for this tab.
No dosing information is available for this tab.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Dipentum 250 Mg Capsule | Maintenance | Take 2 capsules (500 mg) by oral route 2 times per day. |
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
Moderate Interaction: Assess the risk to the patient and take action as needed.
Aminosalicylate Derivatives/Azathioprine; Mercaptopurine
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: The exact mechanism is not known. Aminosalicylic acid and its derivatives (balsalazide, mesalamine, olsalazine, sulfasalazine) may inhibit azathioprine or mercaptopurine inactivation via the thiopurine methyltransferase (TPMT) pathway. Aminosalicylates, azathioprine and mercaptopurine are all associated risk for neutropenia, thrombocytopenia, and anemia and so these risks could be additive.
CLINICAL EFFECTS: Concurrent use of azathioprine or mercaptopurine with aminosalicylates may increase the risk for anemia, neutropenia, or thrombocytopenia.
PREDISPOSING FACTORS: Patients with reduced or absent thiopurine S-methyltransferase (TPMT) or nucleotide diphosphatase (NUDT15) activity are at higher risk of accumulating thiopurine metabolites and severe myelosuppression. Approximately 0.3 % of patients of European, Latino, or African descent have mutations of the TPMT gene resulting in little to no TPMT activity (homozygous deficiency), and approximately 10 % have intermediate TPMT activity (heterozygous deficiency). NUDT15 deficiency is not seen in patients of African descent and is seen in less than 1 % of patients of European descent. Approximately 1 % of patients of East Asian descent, 0.5 % of patients of central/south Asian descent, and 2 % of patients of Latino descent have homozygous NUDT15 deficiency. About 17 % of patients of East Asian descent, 13 % of patients of central/south Asian descent, and 8 % of patients of Latino descent have heterozygous NUDT15 deficiency. Added risk for myelosuppression would be expected in patients who also receive allopurinol or other agents which block xanthine oxidase (XO), the other major inactivation pathway for azathioprine and mercaptopurine.
PATIENT MANAGEMENT: Use the lowest possible dose of each drug and monitor closely for myelosuppression.
DISCUSSION: Manufacturer prescribing information states that concurrent use of aminosalicylates with azathioprine or mercaptopurine has been reported to cause bone marrow suppression. In a prospective study, 22 inflammatory bowel disease (IBD) patients on concurrent 5-aminosalicylate with (2 g daily and later increased to 4 g daily) with azathioprine had increased levels of 6-thioguanine (6-TGN) metabolites. One patient had signs of myelosuppression.(3) A prospective study in 183 IBD patients on concurrent 5-aminosalicylic acid and thiopurines found no significant interaction between thiopurines and 5-aminosalicylic acid.(4) A retrospective study in 199 IBD patients reported an increased rate of adverse events in the dual 5-aminosalicylates and azathioprine dual therapy group compared (48%) to the monotherapy azathioprine group (30%)(chi = 6.4, p = 0.05). Discontinuation of azathioprine because of adverse events was higher in the dual therapy group (52% vs. 24%).(5) In a prospective study, 16 Crohn's disease patients on a stable dose of azathioprine with sulfasalazine or mesalamine discontinued the aminosalicylate after 3 months, which resulted in an average decrease 0f 10% in 6-TGN levels. Myelosuppression may be related to increased levels of 6-TGN.(6) In a 8 week non-randomized parallel group drug interaction study, 34 patients with Crohn's disease receiving azathioprine or 6-mercaptopurine with mesalamine (4 g/day), or sulfasalazine (4 g/day), or balsalazide (6.75 g/day) had a high frequency of leukopenia (20-55%) and significant increases in whole blood 6-TGN levels.(7) A 16 year-old Crohn's disease patient on concurrent 6-mercaptopurine (75 mg) and olsalazine (1000 mg) developed leukopenia (WBC count 1.7 x 10*9/L, ANC 1.309 x 10*9/L, hemoglobulin 113 gm/L, platelet count 550 x 10*9/L) and required a dose reduction for 6-mercaptopurine. Another episode occurred later on after increasing her dose of olsalazine and 6-mercaptopurine which resulted in discontinuation of olsalazine.(8) An in vitro study showed that sulfasalazine and other aminosalicylate derivatives were able to inhibit recombinant human TPMT.(9) In a prospective study, 17 IBD patients on stable mercaptopurine and mesalamine therapy had a 23% reduction in 6-TGN levels after discontinuing mercaptopurine.(10)
Contraindications
Known hypersensitivity to salicylates. Known hypersensitivity to olsalazine or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
- Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
- Chronic kidney disease stage 5 (failure) GFr<15 ml/min
- Diarrhea
- Disease of liver
- Kidney disease with reduction in glomerular filtration rate (GFr)
Adverse reactions
Adverse effects occurring in 1% or more of patients receiving olsalazine include diarrhea, abdominal pain or cramps, nausea, dyspepsia, heartburn, bloating, anorexia, vomiting, stomatitis, rectal bleeding, headache, fatigue, drowsiness, lethargy, depression, insomnia, vertigo, dizziness or lightheadedness, rash, pruritus, arthralgia or joint pain, and upper respiratory infection.
Rare or Very Rare
- Abnormal hepatic function tests
- Acute generalized exanthematous pustulosis
- Acute pancreatitis
- Anemia
- Angioedema
- Aplastic anemia
- Blurred vision
- Bronchospastic pulmonary disease
- Chest pain
- Chills
- DRESS syndrome
- Drug-induced hepatitis
- Dry eye
- Dyspnea
- Erythema nodosum
- Exacerbation of ulcerative colitis
- Hematuria
- Hemolytic anemia
- Hyperbilirubinemia
- Hypersensitivity drug reaction
- Hypertension
- Increased alanine transaminase
- Increased aspartate transaminase
- Interstitial lung disease
- Interstitial nephritis
- Intracranial hypertension
- Kidney stone
- Leukopenia
- Myocarditis
- Pancytopenia
- Paresthesia
- Pericarditis
- Peripheral edema
- Renal failure
- Stevens-johnson syndrome
- Thrombocytopenic disorder
- Tinnitus
- Toxic epidermal necrolysis
- Vasculitis
More Frequent
- Diarrhea
- Gastrointestinal irritation
Less Frequent
- Abdominal distension
- Arthralgia
- Depression
- Dizziness
- Drowsy
- Dyspepsia
- Headache disorder
- Heartburn
- Insomnia
- Nausea
- Pruritus of skin
- Skin rash
- Stomatitis
- Upper abdominal pain
- Upper respiratory infection
- Vertigo
- Vomiting
Rare or Very Rare
- Alopecia
- Anorexia
- Cramps
- Dysuria
- Erectile dysfunction
- Erythema
- Fever
- Flatulence
- Increased urinary frequency
- Irritability
- Menorrhagia
- Mood changes
- Myalgia
- Orthostatic hypotension
- Palpitations
- Peripheral neuropathy
- Skin photosensitivity
- Tachycardia
- Tremor
- Xerostomia
Precautions
No enhanced messaging available.
Safety and efficacy not established in pediatric patients.
Category C. (See Users Guide.)
In rats, administration of olsalazine sodium in dosages of 5-20 times the usual human dosage during lactation resulted in growth retardation in pups; however, it is not known whether the drug is distributed in human milk. Olsalazine should be administered with caution to nursing women.
Experience in those 65 years of age and older insufficient to determine whether they respond differently from younger adults.
ICD codes
| Code | Type | Description |
|---|---|---|
| Ulcerative colitis remission | ||
| K51.00 | ICD10CM | Ulcerative (chronic) pancolitis without complications |
| K51.20 | ICD10CM | Ulcerative (chronic) proctitis without complications |
| K51.30 | ICD10CM | Ulcerative (chronic) rectosigmoiditis without complications |
| K51.40 | ICD10CM | Inflammatory polyps of colon without complications |
| K51.50 | ICD10CM | Left sided colitis without complications |
| K51.80 | ICD10CM | Other ulcerative colitis without complications |
| K51.90 | ICD10CM | Ulcerative colitis, unspecified, without complications |
ICD code information from First Databank (FDB).
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.