DIPENTUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIPENTUM (DIPENTUM).
Olsalazine is a prodrug that is activated in the colon by bacterial azoreductases to release two molecules of 5-aminosalicylic acid (mesalamine), which locally inhibits cyclooxygenase and lipoxygenase pathways, reducing prostaglandin and leukotriene production, and exerts anti-inflammatory effects in the colonic mucosa.
| Metabolism | Olsalazine is a prodrug; it is cleaved by colonic bacterial azoreductases into 5-aminosalicylic acid (mesalamine). The released mesalamine is primarily acetylated by N-acetyltransferase 1 (NAT1) in the colonic epithelium and liver to N-acetyl-5-aminosalicylic acid, which is excreted in urine and feces. |
| Excretion | Primarily renal (80%), with fecal/biliary excretion up to 20% as olsalazine and metabolites (mainly 5-ASA). |
| Half-life | Terminal elimination half-life of olsalazine is approximately 0.9 hours. The active metabolite, 5-ASA, has a half-life in the colon of 2-5 hours due to local retention; systemic half-life is short (0.6-1.4 hours). |
| Protein binding | Olsalazine: ~99% bound to plasma proteins (primarily albumin). 5-ASA: 40-50% bound. |
| Volume of Distribution | Olsalazine Vd: ~0.15 L/kg; 5-ASA Vd: ~0.2 L/kg, reflecting limited systemic distribution due to high protein binding and rapid clearance. |
| Bioavailability | Olsalazine oral bioavailability: ~2% as unchanged drug due to extensive colonic cleavage; systemic 5-ASA from olsalazine is 15-25%. |
| Onset of Action | Colonic 5-ASA release begins within 2-6 hours after oral administration; clinical response in ulcerative colitis typically seen within 3-21 days. |
| Duration of Action | Duration of colonic anti-inflammatory effect persists for 12-24 hours due to local release; typical dosing every 12 hours. |
500 mg orally twice daily, administered as two 250 mg capsules.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated in patients with impaired renal function (GFR < 60 mL/min/1.73 m2). No dose adjustment data available for lesser impairment; use is not recommended. |
| Liver impairment | Contraindicated in patients with hepatic impairment. No dose adjustment studied; use not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no specific dosing recommended. |
| Geriatric use | No specific dose adjustments provided, but caution due to potential renal impairment; consider renal function before use. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIPENTUM (DIPENTUM).
| Breastfeeding | Olsalazine and its active metabolite 5-ASA are excreted in human breast milk in low concentrations. The milk-to-plasma ratio for 5-ASA is approximately 0.4. Although risks to the nursing infant are considered low, caution is advised. Monitor infant for diarrhea. |
| Teratogenic Risk | Dipentum (olsalazine) is a prodrug of 5-aminosalicylic acid (5-ASA). Animal studies have not shown teratogenicity, but there are no adequate and well-controlled studies in pregnant women. 5-ASA crosses the placenta. The risk of congenital malformations is not clearly increased; however, use during the third trimester may be associated with neonatal renal impairment and oligohydramnios. Avoid use near term if possible. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to olsalazine, mesalamine, salicylates, or any component of the formulation; severe renal impairment (GFR <30 mL/min/1.73 m²).
| Precautions | May cause diarrhea, sometimes severe; associated with nephrotoxicity (interstitial nephritis, nephrotic syndrome); caution in patients with renal impairment; may cause hepatic injury; monitor renal function and blood counts; use with caution in patients with pyloric stenosis or other GI obstructive disorders due to possible sustained release of the drug. |
| Food/Dietary | No specific food interactions. Avoid alcohol as it may worsen gastrointestinal side effects. |
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| Fetal Monitoring | Monitor maternal renal function, complete blood count, and hepatic function periodically. During pregnancy, fetal ultrasound should be considered to assess amniotic fluid volume and renal structures due to potential for oligohydramnios. Neonatal monitoring for renal function if used near term. |
| Fertility Effects | No specific studies on fertility effects in humans. Animal studies have not shown impaired fertility at therapeutic doses. There is no evidence that olsalazine adversely affects human fertility. |
| Clinical Pearls |
| Dipentum (olsalazine) is a prodrug of 5-aminosalicylic acid (5-ASA) used for maintenance of remission in ulcerative colitis. It is activated by bacterial azo-reduction in the colon. Monitor renal function periodically; avoid in severe renal impairment. May cause diarrhea in some patients due to increased fluid secretion. |
| Patient Advice | Take with food to reduce gastrointestinal upset. · Swallow capsules whole; do not crush or chew. · Report any worsening diarrhea or abdominal pain to your doctor. · Drink plenty of fluids to prevent dehydration, especially if diarrhea occurs. · Notify your doctor if you have kidney disease or are pregnant/breastfeeding. |