Drug General Information (ID: DDIFUL9BCJ)
Drug Name			Sulindac		Drug Info		Dimethyl sulfoxide		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antiinflammatory Agents				Genitourinary Tract Agents
Structure

Mechanism of Sulindac-Dimethyl sulfoxide Interaction (Severity Level: Moderate)
Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Drug Name		Sulindac				Dimethyl sulfoxide
Mechanism 1		Methionine sulfoxide reductase inhibitor				Methionine sulfoxide reductase substrate
Key Mechanism Factor 1
		Factor Name		Peptide methionine sulfoxide reductase				Structure Sequence
		Protein Family		MsrA Met sulfoxide reductase family
		Protein Function		Has an important function as a repair enzyme for proteins that have been inactivated by oxidation. Catalyzes the reversible oxidation-reduction of methionine sulfoxide in proteins to methionine.     Click to Show/Hide
Mechanism Description		Decreased metabolism of Dimethyl sulfoxide caused by Sulindac mediated inhibition of non-CYP450 enzyme
Increased risk of peripheral neuropathy Click to Show/Hide Mechanism Graph
Drug Name		Sulindac				Dimethyl sulfoxide
Mechanism 2		Peripheral neuropathy				Peripheral neuropathy
Key Mechanism Factor 2
		Factor Name		Peripheral neuropathy
		Factor Description		Peripheral neuropathy is a disorder of the peripheral nerves that can cause sensory and motor symptoms, and even paralysis in severe cases. Signs and symptoms of peripheral neuropathy may include: gradual numbness, tingling or prickling in the feet or hands that can spread up the legs and arms; sharp, stinging, pricking or burning sensations; extreme sensitivity to touch; pain during activities that should not cause pain; lack of coordination and falls; muscle weakness; and paralysis if the motor nerves are affected.
Mechanism Description		Increased risk of peripheral neuropathy by the combination of Sulindac and Dimethyl sulfoxide

Recommended Action
Management		It may be advisable to avoid this drug combination.

References
1	Cerner Multum, Inc. "Australian Product Information.".
2	Product Information. Clinoril (sulindac). Merck & Co, Inc, West Point, PA.
3	Reinstein L, Mahon R, Russso GL "Peripheral neuropathy after concomitant dimethyl sulfoxide use and sulindac therapy." Arch Phys Med Rehabil 63 (1982): 581-4. [PMID: 6291491]
4	Swanson BN, Boppana Vk, Vlasses PH, Rotmensch HH, Ferguson RK "Dimethyl sulfoxide inhibits bioactivation of sulindac." J Lab Clin Med 102 (1983): 95-101. [PMID: 6854139]
5	Swanson BN, Ferguson RK, Raskin NH, Wolf BA "Peripheral neuropathy after concomitant administration of dimethyl sulfoxide and sulindac." Arthritis Rheum 26 (1983): 791-3. [PMID: 6305373]