Olsalazine

Olsalazine is a 5-Aminosalicylic acid derivative belonging to anti-inflammatory agent.

Olsalazine is an anti-inflammatory agent used in the treatment of inflammatory bowel disease and ulcerative colitis.

Olsalazine approximately 2.4% is absorbed from the GI tract; 98-99% reaches the colon. The time to peak plasma concentration approximately 1 hours. Olsalazine enters breast milk (5-ASA). The plasma protein binding is about >99% (olsalazine-S), 74% (5-ASA), 81% (N-acetyl-5-ASA). Olsalazine absorbed drug (approximately 2% of the dose) is partially metabolised in the liver via sulfate conjugation to olsalazine-O-sulfate (olsalazine-S), while majority of the dose (98-99%) passes intact colon and cleaved by the intestinal flora to form 2 molecules of Olsalazine (5-ASA), and metabolised further in the liver and colonic epithelium via N-acetylation to form N-acetyl-5-aminosalicylic acid (Ac-5-ASA). Olsalazine-S is excreted via urine (20-30%, mainly as Ac-5-ASA and 1-2% as unchanged drug). The Elimination half-life: 7 days (olsalazine-S).

Olsalazine shows common side effects like Agitation, bloody diarrhea, blood in the urine, coma, confusion, dark-colored urine, decreased urine output, depression, dizziness, fever, general feeling of tiredness or weakness, headache, hostility, increased sensitivity of the skin to sunlight, irritability, itching, skin rash, lethargy, light-colored stools, muscle twitching, nausea, pain in the groin or genitals, rapid weight gain, redness or other discoloration of the skin, seizures, severe sunburn, sharp back pain just below ribs, stomach pain, swelling of the face, ankles, or hands, unusual tiredness or weakness, vomiting, yellow eyes or skin.

Olsalazine is available in the form of Oral capsule.

Olsalazine is available in India, US, Canada, Italy, Russia, Singapore, Malaysia, China, Japan, and Australia.

Olsalazine belongs to the anti-inflammatory agent acts as a 5-Aminosalicylic acid.

The specific mechanism of action of Olsalazine is unknown; however, it is thought that it modulates local chemical mediators of the inflammatory response, especially leukotrienes, and is also postulated to be a free radical scavenger or an inhibitor of tumor necrosis factor (TNF); action appears topical rather than systemic.

The onset and duration of action of Olsalazine is not clinically established.

The Tmax of Olsalazine is approximately 1 hours.

Olsalazine is available in the form of Oral capsule.

Olsalazine tablet is taken orally, usually in divided doses.

Olsalazine is an anti-inflammatory agent used in the treatment of inflammatory bowel disease and ulcerative colitis.

Olsalazine is a 5-Aminosalicylic acid derivative belonging to anti-inflammatory agent.

Olsalazine is a Olsalazine [5-aminosalicylic acid (5-ASA)] derivative. The exact mechanism of action is still unknown but is thought to diminish inflammation by blocking cyclooxygenase and lipoxygenase pathways thus inhibiting the production of prostaglandin and leukotrienes in the colon; action appears to be topical rather than systemic.

Olsalazine is approved for use in the following clinical indications

• Ulcerative colitis

Olsalazine is an anti-inflammatory agent used in the treatment of inflammatory bowel disease and ulcerative colitis.

• Ulcerative colitis

Remission maintenance: Oral: 1 g/day in 2 divided doses.

Remission induction (off-label use): Oral: 2 to 3 g/day in 2 to 4 divided doses.

Olsalazine is available in various strengths as 250mg.

Olsalazine is available in the form of Oral Capsule.

Olsalazine is contraindicated in patients with

• In patients with known or suspected hypersensitivity to salicylates, aminosalicylates or their metabolites, or to any of the excipients in Olsalazine.

• Dermatologic reactions

Severe cutaneous adverse reactions, including acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported. If a reaction occurs, discontinue immediately and consider further evaluation.

• Diarrhea

Commonly occurs and may be dose related; must be distinguished from underlying symptoms of ulcerative colitis.

• Hypersensitivity reactions

Olsalazine-induced hypersensitivity reactions have been reported and may include internal organ involvement, such as hepatitis, myocarditis, pericarditis, nephritis, hematologic abnormalities, and/or pneumonitis. Monitor for signs and symptoms of hypersensitivity; discontinue treatment if hypersensitivity occurs.

• Intolerance syndrome

May cause an acute intolerance syndrome (cramping, acute abdominal pain, bloody diarrhea; sometimes fever, headache, rash); may be hard to discern from an exacerbation; monitor for worsening of symptoms and discontinue immediately if syndrome occurs or is suspected.

• Photosensitivity

Use with caution in patients with preexisting skin conditions (including atopic dermatitis and atopic eczema); severe photosensitivity reactions have been reported. Use skin protection (protective clothing and broad-spectrum sunscreen) and avoid prolonged exposure to sunlight and ultraviolet light.

• Renal effects

Renal impairment (including minimal change disease, acute and chronic interstitial nephritis, and renal failure) has been reported. A renal function evaluation is recommended prior to initiation of therapy and periodically during treatment. Evaluate risk versus benefit in patients with renal impairment, with a history of renal disease, or concurrently taking nephrotoxic medications. Ensure patients are adequately hydrated during therapy.

Small amounts of the active metabolite of olsalazine (5-ASA) may pass into breast milk. Harmful infant effects (diarrhea) have been reported when 5-ASA was used during breastfeeding. Unless the benefit of the treatment outweighs the risks, olsalazine should not be taken by breast-feeding women, or patients should be advised to discontinue breastfeeding if using olsalazine. Oral administration of olsalazine to lactating rats in doses 5 to 20 times the human dose produced growth retardation in their pups.

Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

• Common

Diarrhea, Pruritus, skin rash, Abdominal cramps, abdominal pain, bloating, nausea, stomatitis, vomiting, Depression, dizziness, vertigo, Arthralgia, Upper respiratory tract infection.

• Rare

Chest pain, hypertension, myocarditis, orthostatic hypotension, palpitations, pericarditis, peripheral edema, second degree atrioventricular block, tachycardia, Alopecia, erythema nodosum, erythema of skin, skin photosensitivity, Dehydration, heavy menstrual bleeding, hot flash, Blood in stool, epigastric discomfort, flatulence, pancreatitis, rectal irritation (discomfort), xerostomia, Dysuria, hematuria, impotence, nephrotic syndrome, proteinuria, urinary frequency, Anemia, eosinophilia, hemolytic anemia, leukopenia, lymphocytopenia, neutropenia, rectal hemorrhage, reticulocytotic, thrombocytopenia, Cholestatic hepatitis, granulomatous hepatitis, hepatitis, increased serum alanine aminotransferase, increased serum aspartate aminotransferase, Chills, emotional lability, insomnia, irritability, paresthesia, rigors, Muscle cramps, tremor, Blurred vision, watery eyes, xerophthalmia, Tinnitus, Interstitial nephritis, Bronchospasm, dyspnea, interstitial pulmonary disease, Fever.

• Nephrotoxic Agents, Including Non-Steroidal Anti-Inflammatory Drugs

The concurrent use of Olsalazine with known nephrotoxic agents, including non-steroidal anti-inflammatory drugs (NSAIDs), may increase the risk of nephrotoxicity. Monitor patients taking nephrotoxic drugs for changes in renal function and Olsalazine-related adverse reactions.

• Azathioprine Or 6-Mercaptopurine

The concurrent use of Olsalazine with azathioprine or 6-mercaptopurine and/or any other drugs known to cause myelotoxicity (e.g., thioguanine) may increase the risk for blood disorders, bone marrow failure, and associated complications. If concomitant use of Olsalazine and azathioprine or 6-mercaptopurine cannot be avoided, monitor blood tests, including complete blood cell counts and platelet counts.

• Low Molecular Weight Heparins or Heparinoids

The co-administration of salicylates and low molecular weight heparins or heparinoids may result in an increased risk of bleeding (i.e., hematomas) following neuraxial anesthesia. Salicylates should be discontinued prior to the initiation of a low molecular weight heparin or heparinoid. If this is not possible, it is recommended to monitor patients closely for bleeding.

• Warfarin

Increased prothrombin time in patients taking concomitant warfarin has been reported. Monitor INR and prothrombin time and adjust the dosage of warfarin, as needed with concomitant use of Olsalazine, to maintain the target INR range.

• Varicella Vaccine

It is recommended not to give salicylates for six weeks after the varicella vaccine to avoid a possible increased risk of developing Reye's syndrome.

The common side effects of Olsalazine include the following

Common side effects

● Agitation, bloody diarrhea, blood in the urine, coma, confusion, dark-colored urine, decreased urine output, depression, dizziness, fever, general feeling of tiredness or weakness, headache, hostility, increased sensitivity of the skin to sunlight, irritability, itching, skin rash, lethargy, light-colored stools, muscle twitching, nausea, pain in the groin or genitals, rapid weight gain, redness or other discoloration of the skin, seizures, severe sunburn, sharp back pain just below ribs, stomach pain, swelling of the face, ankles, or hands, unusual tiredness or weakness, vomiting, yellow eyes or skin.

Rare side effects

● Back pain, fast heartbeat, swelling of the stomach.

• Pregnancy

Pregnancy Category C

Olsalazine has been shown to produce fetal developmental toxicity as indicated by reduced fetal weights, retarded ossifications, and immaturity of the fetal visceral organs when given during organogenesis to pregnant rats in doses 5 to 20 times the human dose (100 to 400 mg/kg). There are no adequate and well-controlled studies in pregnant women. Olsalazine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Nursing Mothers

Small amounts of the active metabolite of olsalazine (5-ASA) may pass into breast milk. Harmful infant effects (diarrhea) have been reported when 5-ASA was used during breastfeeding. Unless the benefit of the treatment outweighs the risks, olsalazine should not be taken by breast-feeding women, or patients should be advised to discontinue breastfeeding if using olsalazine. Oral administration of olsalazine to lactating rats in doses 5 to 20 times the human dose produced growth retardation in their pups.

• Pediatric Use

As per FDA, the safety and effectiveness in a pediatric population have not been established.

• Geriatric Use

Clinical studies of Olsalazine did not include enough subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, elderly patients should be treated with caution due to the greater frequency of decreased hepatic, renal, or cardiac function, co-existence of other disease, as well as concomitant drug therapy.

No overdosage has been reported in humans. The knowledge of overdosage is limited. Possible overdose symptoms include nausea, vomiting and diarrhea. It is recommended to check hematology, acid-base, electrolyte, liver, and kidney status, and to provide supportive treatment. There is no specific antidote to Olsalazine. Maximum single oral doses of 5g/kg in mice and rats and 2 g/kg in dogs were not lethal. Symptoms of acute toxicity were decreased motor activity and diarrhea in all species tested. In addition, vomiting was reported in dogs.

Pharmacodynamic

Olsalazine is an anti-inflammatory drug used in the treatment of Inflammatory Bowel Disease and Ulcerative Colitis. Olsalazine reduces the bowel inflammation, diarrhea (stool frequency), rectal bleeding, and abdominal pain. Olsalazine is thought to work like balsalazide, delivering Olsalazine or 5-aminosalicylic acid past the small intestine to the large intestine to act on the site of disease.

Pharmacokinetics

• Absorption

Olsalazine approximately 2.4% is absorbed from the GI tract; 98-99% reaches the colon.

The time to peak plasma concentration approximately 1 hours.

• Distribution

Olsalazine enters breast milk (5-ASA). The plasma protein binding is about >99% (olsalazine-S), 74% (5-ASA), 81% (N-acetyl-5-ASA).

• Metabolism

Olsalazine absorbed drug (approximately 2% of the dose) is partially metabolised in the liver via sulfate conjugation to olsalazine-O-sulfate (olsalazine-S), while majority of the dose (98-99%) passes intact colon and cleaved by the intestinal flora to form 2 molecules of Olsalazine (5-ASA), and metabolised further in the liver and colonic epithelium via N-acetylation to form N-acetyl-5-aminosalicylic acid (Ac-5-ASA).

• Excretion

Olsalazine-S is mainly via urine (20-30%, mainly as Ac-5-ASA and 1-2% as unchanged drug). The Elimination half-life: 7 days (olsalazine-S).

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