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Sulindac (Clinoril) - Complete Drug Information

Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) used primarily to relieve symptoms of inflammation, such as pain and swelling. It's commonly prescribed to treat conditions like rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Sulindac works by inhibiting the production of certain chemicals in the body that cause inflammation, namely prostaglandins. These chemicals are involved in the body's response to injury and inflammation, and by blocking their production, sulindac helps to reduce pain and swelling. It's important to note that like other NSAIDs, sulindac can have side effects, including gastrointestinal issues like ulcers or bleeding, and it may also affect kidney function.

Sulindac is a reversible inhibitor of cyclooxygenase-1 and 2 (COX-1 and 2) enzymes which results in decreased formation of precursors of prostaglandins so it has antipyretic, analgesic, and anti-inflammatory properties.

It is used to treat the following conditions:

Acute gouty arthritis:
- It is used to relieve the symptoms and signs of acute gouty arthritis
Ankylosing spondylitis:
- It is used to relieve the symptoms and signs of ankylosing spondylitis.
Rheumatoid Arthritis and osteoarthritis:
- It is used to relieve the symptoms and signs of Rheumatoid arthritis and Osteoarthritis.
Tendinitis or Bursitis of the shoulder:
- It is used to relieve the symptoms and signs of the painful acute shoulder (supraspinatus tendinitis or acute subacromial bursitis)

Sulindac Dose in Adults

The dose required for Acute gouty Arthritis

When treating acute gouty arthritis with sulindac, the usual dose is 200 milligrams taken twice a day for a week.
The maximum amount you should take in a day is 400 milligrams.
This dosage helps to reduce the pain and swelling caused by gouty arthritis.

The dose required for Ankylosing spondylitis:

For ankylosing spondylitis, the typical dose of sulindac is 150 milligrams taken twice daily.
The maximum daily dose should not exceed 400 milligrams.
This dosage is aimed at managing the symptoms of ankylosing spondylitis, such as pain and stiffness in the spine and joints.

The dose required for Tendinitis/Bursitis of the shoulder:

To treat bursitis or tendinitis of the shoulder, the typical dosage of sulindac is 200 milligrams taken twice a day.
This treatment usually lasts for 7 to 14 days.
The maximum daily dose should not exceed 400 milligrams.
Sulindac helps to reduce pain and inflammation associated with these conditions.

The dose required for rheumatoid arthritis/ arthritis:

For osteoarthritis and rheumatoid arthritis, the usual dose of sulindac is 150 milligrams taken twice daily.
The maximum daily dose should not exceed 400 milligrams.
This dosage helps to alleviate the pain and inflammation associated with these conditions.

Sulindac Dose in Children

Dose required for the treatment of Juvenile idiopathic arthritis (JIA):

For the treatment of juvenile idiopathic arthritis (JIA), the dosage of sulindac for children and adolescents is typically 2 to 6 milligrams per kilogram of body weight per day, divided into two doses. The maximum daily dose should not exceed 400 milligrams.

Pregnancy Risk factor C

Sulindac poses a risk to pregnancy, categorized as Pregnancy Risk Factor C.
When taken during pregnancy, sulindac can cross the placenta, potentially leading to birth defects, although studies have conflicting results on this.
It's been linked to various nonteratogenic effects in the fetus or newborn, including issues like constriction of the ductus arteriosus, pulmonary hypertension, and renal problems.
NSAIDs, like sulindac, might cause early closure of the ductus arteriosus in the fetus, which can lead to serious complications.
Thus, it's generally recommended to avoid NSAID use during pregnancy, especially during the later stages.
However, in some cases, NSAIDs could be considered for treating mild rheumatoid arthritis flares in pregnant women, but their use should be minimized, particularly in early and late pregnancy.
Chronic NSAID use in women of reproductive age might also affect fertility, although this is usually reversible upon stopping the medication.
Additionally, taking NSAIDs near conception might increase the risk of miscarriage.

Sulindac use during breastfeeding:

It's uncertain whether sulindac passes into breast milk.
Typically, NSAIDs can be used by postpartum women who want to breastfeed, but other medications are preferred over sulindac.
Avoid using sulindac if breastfeeding infants have platelet dysfunction, thrombocytopenia, or are premature or jaundiced.
The manufacturer advises a decision to be made regarding either stopping breastfeeding or discontinuing the drug, weighing the importance of treatment for the mother against the potential risks to the breastfeeding infant.

Sulindac Renal Dose:

The manufacturer's labeling doesn't offer specific dosage adjustments, so use sulindac cautiously.
Avoid using it in patients with advanced renal disease, but if therapy is necessary, closely monitor renal function.

Hemodialysis

Sulindac isn't removed through hemodialysis.

KDIGO 2012 Guidelines

If a patient's estimated glomerular filtration rate (eGFR) is between 30 to less than 60 mL/minute/1.73 m², consider temporarily discontinuing sulindac if there's an illness that increases the risk of acute kidney injury.
If a patient's eGFR is less than 30 mL/minute/1.73 m², avoid using sulindac altogether.

The dose of sulindac in Liver Disease:

The manufacturer's labeling doesn't include specific dosage adjustments, but due to extensive hepatic metabolism, dosage reduction may be necessary.
Use sulindac cautiously and monitor closely for any signs of adverse effects, especially in patients with liver issues.

Less Common Side Effects of Sulindac Include:

Cardiovascular:
- Edema
Central Nervous System:
- Dizziness
- Headache
- Nervousness
Dermatologic:
- Skin Rash
- Pruritus
Gastrointestinal:
- Gastrointestinal Pain
- Constipation
- Diarrhea
- Dyspepsia
- Nausea
- Abdominal Cramps
- Anorexia
- Flatulence
- Vomiting
Otic:
- Tinnitus

Contraindication to Sulindac Include:

Hypersensitivity: Avoid sulindac if you have a known hypersensitivity to sulindac or any component of the formulation.
CABG Surgery: Do not use sulindac in the setting of coronary artery bypass graft (CABG) surgery.
History of Asthma or Allergic Reactions: Use sulindac with caution if you have a history of asthma, urticaria (hives), or allergic-type reactions after taking aspirin or other NSAIDs.

Warnings and precautions

Anaphylactoid reactions

Even if you haven't been exposed to it before, anaphylactoid reactions might happen with sulindac.
If you have a condition called the "aspirin triad" which includes bronchial asthma, aspirin intolerance, and rhinitis, you might be at a higher risk.
It's not safe to use sulindac if you've experienced bronchospasm, asthma, rhinitis, or hives (urticaria) from using NSAIDs or aspirin in the past.

Cardiovascular events: [US Boxed Warn]

Nonsteroidal anti-inflammatory drugs (NSAIDs), including sulindac, carry a serious warning about an increased risk of cardiovascular events like heart attacks (MI) and strokes, which could be life-threatening.
This risk might rise early during treatment and could increase with longer use.
Even if you don't have known heart problems or risk factors, the risk is still there, but it's higher if you do have these issues or if you're taking higher doses.
NSAIDs can also lead to new or worsened high blood pressure and may interfere with certain medications for hypertension.
They might cause sodium and fluid retention, especially in people with swelling (edema) or heart failure, so use caution.
Avoid using NSAIDs after a recent heart attack unless the benefits outweigh the risks.
To minimize these risks, doctors recommend using the lowest effective dose for the shortest time possible, considering each patient's needs, and exploring alternative treatments for those at high risk of cardiovascular events.

CNS effects

Sulindac can lead to drowsiness, dizziness, blurred vision, and other neurological effects that might affect your physical or mental abilities.
It's important to warn patients about this, especially if they need to do tasks that require mental alertness, like operating machinery or driving.
If you experience blurred or diminished vision while taking sulindac, stop using it and get an eye exam.
Doctors should periodically check the vision of patients on long-term therapy with sulindac.

GI effects: [US Boxed Warning]

NSAIDs, including sulindac, come with a serious warning about an increased risk of severe gastrointestinal problems like inflammation, ulcers, bleeding, and perforation, which could be fatal.
Elderly patients and those with a history of peptic ulcer disease or gastrointestinal bleeding are at higher risk.
These issues can happen at any time during treatment without warning, so it's crucial to avoid using NSAIDs if you have active gastrointestinal bleeding.
If you've had acute lower gastrointestinal bleeding in the past, especially due to conditions like angioectasia or diverticulosis, it's best to steer clear of non-aspirin NSAIDs.
Caution is advised if you have a history of gastrointestinal ulcers, are taking other medications that increase bleeding risk, have advanced liver disease, clotting problems, smoke, use alcohol, or are elderly or debilitated.
To minimize the risk of gastrointestinal problems, doctors recommend using the lowest effective dose for the shortest time possible, tailored to each patient's needs.
For those at high risk, alternative treatments should be considered.
When taking NSAIDs along with aspirin, the risk of gastrointestinal complications significantly increases, so using gastroprotective therapy like proton pump inhibitors is recommended.

Hematologic effects

Sulindac can affect blood clotting by reducing platelet adhesion and aggregation, which may lengthen bleeding time.
Patients with coagulation disorders or those taking anticoagulants need close monitoring.
Anemia is also a possible side effect, especially in patients on long-term NSAID therapy, so regular monitoring is essential.
Although rare, NSAID use has been linked to severe blood disorders such as agranulocytosis, thrombocytopenia, and aplastic anemia.
If you experience any unusual bleeding or signs of blood disorders, it's important to seek medical attention promptly.

Hepatic effects

Sulindac use can lead to elevated levels of liver enzymes (transaminases), so it's crucial to monitor patients with any abnormal liver function tests closely.
In rare cases, severe and potentially fatal liver reactions, such as fulminant hepatitis, hepatic necrosis, and hepatic failure, have occurred with NSAID use.
If you develop any signs or symptoms of liver disease or experience systemic manifestations, discontinue sulindac immediately and seek medical attention.
Early detection and prompt action are essential in managing these serious hepatic reactions.

Hyperkalemia:

Using NSAIDs like sulindac might raise the risk of hyperkalemia, especially in certain groups like the elderly, diabetics, and those with renal disease.
This risk increases when NSAIDs are taken alongside other medications that can also cause hyperkalemia, such as ACE inhibitors.
It's important to closely monitor potassium levels in these patients.
Keeping a check on potassium levels helps to manage this potential side effect and ensure overall safety during treatment with sulindac.

Pancreatitis

There have been reports of pancreatitis associated with sulindac use.
If you suspect pancreatitis while taking sulindac, it's important to discontinue the medication immediately and seek medical attention.
Prompt action can help in managing this serious condition effectively.

Effects on the renal system:

Using NSAIDs like sulindac can potentially worsen existing kidney function.
This happens because NSAIDs reduce the production of prostaglandins, which can decrease renal blood flow and lead to kidney problems, though usually reversible.
Patients with impaired kidney function, dehydration, heart failure, liver problems, those taking diuretics and ACE inhibitors, and the elderly are at higher risk.
Before starting sulindac therapy, ensure patients are well-hydrated, and monitor kidney function closely during treatment.
Long-term use of NSAIDs may lead to serious kidney conditions like renal papillary necrosis and other kidney injuries.
Regular monitoring and proper hydration are crucial to mitigate these risks.

Reactions to skin:

NSAIDs, including sulindac, can lead to severe skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be potentially fatal.
These skin reactions may occur suddenly without warning.
If you develop a skin rash or any signs of hypersensitivity while taking sulindac, it's crucial to discontinue its use immediately and seek medical attention.
Early intervention is essential in managing these serious skin adverse events effectively.

Aseptic meningitis

There's a possibility that using sulindac may increase the risk of aseptic meningitis, particularly in patients with conditions like systemic lupus erythematosus (SLE) and mixed connective tissue disorders.
If you experience symptoms suggestive of meningitis, such as severe headache, fever, stiff neck, or sensitivity to light, it's important to seek medical attention promptly.

Asthma

Sulindac is not recommended for patients with aspirin-sensitive asthma because it could lead to severe and potentially fatal bronchospasm.
Even for patients with other forms of asthma, caution is advised when using sulindac.

Bariatric surgery

After bariatric surgery, it's important to avoid long-term use of oral nonselective NSAIDs like sulindac because they could lead to the development of ulcerations or perforations at the surgical site.
Instead, short-term use of medications like celecoxib or IV ketorolac is recommended as part of a comprehensive pain management plan for postoperative pain.

Coronary bypass surgery for coronary artery bypass: [US Boxed Warn]

Sulindac should not be used after coronary artery bypass graft (CABG) surgery due to the increased risk of heart attack (MI) and stroke.
Using sulindac following CABG surgery can raise the likelihood of these serious cardiovascular events, so it's essential to avoid its use in this setting.

Hepatic impairment

Sulindac should be used cautiously in patients with hepatic impairment because their plasma concentrations of the drug may increase, potentially requiring a dosage reduction.
It's important to monitor these patients closely for any signs of adverse effects.
Additionally, patients with advanced liver disease are at a higher risk of gastrointestinal bleeding when using NSAIDs.

Renal impairment

Patients with renal impairment should use sulindac with caution.
It's important to avoid sulindac use in patients with advanced renal disease, but if therapy is necessary, close monitoring of renal function is required.
Before initiating therapy, assess the patient's renal function carefully, and continue monitoring it regularly during treatment.

Sulindac: Drug Interaction

Risk Factor C (Monitor therapy)
5-Aminosalicylic Acid Derivatives	Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives.
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)	May enhance the antiplatelet effect of other Agents with Antiplatelet Properties.
Alcohol (Ethyl	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination.
Aliskiren:	Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Management: Monitor renal function periodically in patients receiving aliskiren and any nonsteroidal anti-inflammatory agent. Patients at elevated risk of renal dysfunction include those who are elderly, are volume depleted, or have pre-existing renal dysfunction.
Aminoglycosides	Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
Aminolevulinic Acid (Topical)	Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical).
Angiotensin II Receptor Blockers	May enhance the adverse/toxic effect of Nonsteroidal AntiInflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function.
Angiotensin-Converting Enzyme Inhibitors	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors.
Anticoagulants	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin.
Anticoagulants	Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin.
Beta-Blockers	Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol.
Bisphosphonate Derivatives	Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern.
Cephalothin	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased.
Collagenase (Systemic)	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased.
Corticosteroids (Systemic)	May enhance the adverse/toxic effect of Nonsteroidal AntiInflammatory Agents (Nonselective).
Dasatinib	May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Deferasirox	Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.
Deoxycholic Acid	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.
Desmopressin	Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin.
Digoxin	Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin.
Dimethyl Sulfoxide	May decrease the metabolism of Sulindac. Specifically, the concentrations of the active sulfide metabolite are decreased.
Drospirenone	Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Drospirenone.
Eplerenone	Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone.
Fat Emulsion (Fish Oil Based)	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties.
Felbinac	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Glucosamine	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Haloperidol	Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Haloperidol. Specifically including drowsiness and confusion.
HydrALAZINE	Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE.
Ibritumomab Tiuxetan	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding.
Ibrutinib	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties.
Inotersen	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Limaprost	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Multivitamins/Fluoride (with ADE)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Multivitamins/Minerals (with ADEK, Folate, Iron)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Multivitamins/Minerals (with AE, No Iron)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Naftazone	May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents.
Obinutuzumab	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.
Omega-3 Fatty Acids	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Pentosan Polysulfate Sodium	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents.
Pentoxifylline	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Porfimer	Photosensitizing Agents may enhance the photosensitizing effect of Porfimer.
Potassium-Sparing Diuretics	Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics.
PRALAtrexate	Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum levels and/or toxicity if used concomitantly with an NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation.
Probenecid	May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents.
Prostacyclin Analogues	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Prostaglandins (Ophthalmic)	Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic).
Quinolones	Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones.
Salicylates	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result.
Serotonin/Norepinephrine Reuptake Inhibitors	May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective).
Tacrolimus (Systemic)	Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic).
Thiazide and Thiazide-Like Diuretics	May enhance the nephrotoxic effect of Nonsteroidal AntiInflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics.
Thrombolytic Agents	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.
Tipranavir	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Tolperisone	Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may enhance the therapeutic effect of Nonsteroidal Anti-Inflammatory Agents.
Tricyclic Antidepressants (Tertiary Amine)	May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective).
Vancomycin	Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin.
Verteporfin	Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin.
Vitamin E (Systemic)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Risk Factor D (Consider therapy modification)
Apixaban	Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.
Bemiparin	Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin and nonsteroidal anti-inflammatory agents (NSAIDs) due to the increased risk of bleeding. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding.
Bemiparin	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding.
Bile Acid Sequestrants	May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents.
Cladribine	Inhibitors of Equilibrative Nucleoside (ENT1) and Concentrative Nucleoside (CNT3) Transport Proteins may increase the serum concentration of Cladribine. Management: Avoid concomitant use of ENT1 or CNT3 inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider an ENT1 or CNT3 inhibitor dose reduction and separation in the timing of administration.
CycloSPORINE (Systemic)	Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (eg, hypertension) during concomitant therapy with NSAIDs.
Dabigatran Etexilate	Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.
Diclofenac (Systemic)	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Seek alternatives to the combined use of diclofenac with other nonsteroidal anti-inflammatory agents (NSAIDs). Avoid the use of diclofenac/misoprostol with other NSAIDs.
Edoxaban	Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.
Enoxaparin	Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue nonsteroidal anti-inflammatory agents (NSAIDs) prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding.
Enoxaparin	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding.
Heparin	Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or nonsteroidal anti-inflammatory agents (NSAIDs) if coadministration is required.
Heparin	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required.
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures.
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Management: Concomitant treatment with these agents should generally be avoided. If used concomitantly, increased diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds) must be employed.
Loop Diuretics	Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended.
Methotrexate	Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Alternative anti-inflammatory therapy should be considered whenever possible, especially if the patient is receiving higher, antineoplastic doses of methotrexate.
Rivaroxaban	Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.
Salicylates	Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Exceptions: Choline Magnesium Trisalicylate.
Selective Serotonin Reuptake Inhibitors	May enhance the antiplatelet effect of Nonsteroidal AntiInflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk.
Sincalide	Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction.
Sodium Phosphates	May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with NSAIDs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely.
Tenofovir Products	Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose.
Vitamin K Antagonists (eg, warfarin)	Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists.
Risk Factor X (Avoid combination)
Acemetacin	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Aminolevulinic Acid (Systemic)	Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic).
Dexibuprofen	Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Dexibuprofen.
Dexketoprofen	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Floctafenine	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Ketorolac (Nasal)	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Ketorolac (Systemic)	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Macimorelin	Nonsteroidal Anti-Inflammatory Agents may diminish the diagnostic effect of Macimorelin.
Mifamurtide	Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Mifamurtide.
Morniflumate	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective)	Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective).
Omacetaxine	Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of nonsteroidal antiinflammatory drugs (NSAIDs) with omacetaxine in patients with a platelet count of less than 50,000/uL.
Pelubiprofen	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Phenylbutazone	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Talniflumate	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Tenoxicam	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Urokinase	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase.
Zaltoprofen	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

Monitoring Parameters

CBC and Chemistry Profile: Regular blood tests to check blood cell counts and chemistry levels.
Occult Blood Loss: Monitoring for signs of hidden blood loss, especially in the gastrointestinal tract.
Liver Function Tests: Periodic tests to assess liver function.
Renal Function: Monitoring urine output and measuring serum levels of BUN and creatinine to evaluate kidney function.
Blood Pressure: Regular checks to monitor blood pressure levels.
Signs and Symptoms of GI Bleeding: Watching for any signs or symptoms of gastrointestinal bleeding, such as dark stools or abdominal pain.
Ophthalmic Exam: If any eye-related complaints develop during treatment, an eye examination may be necessary to assess ocular health.

Sulindac Administration:

Take with Food or Milk: To reduce gastrointestinal side effects, it's recommended to take sulindac with food or milk. This can help lessen the chances of experiencing stomach upset or other digestive issues.

Mechanism of action of Sulindac:

Sulindac works by temporarily blocking the cyclooxygenase-1 and 2 (COX-1 and COX-2) enzymes, which are involved in making substances called prostaglandins.
By doing this, it reduces the formation of certain precursors of prostaglandins.
This action gives it its antipyretic (fever-reducing), analgesic (pain-relieving), and anti-inflammatory properties.
Additionally, sulindac might also affect other processes in the body that contribute to inflammation, although these mechanisms aren't fully understood yet.
These include things like altering the activity of certain immune cells, inhibiting the movement and activation of certain types of white blood cells, and reducing levels of certain pro-inflammatory proteins.
Together, these actions help to ease pain and reduce inflammation in the body.

The beginning of action:

Sulindac typically starts to show therapeutic effects within one week of starting treatment.

Distribution

Blood-Brain Barrier: Sulindac can cross the blood-brain barrier, but brain concentrations are usually less than 4% of plasma concentrations.

Protein Binding

Sulindac and its metabolites bind primarily to albumin, with high percentages of binding: Sulindac (93.1%), sulfone metabolite (95.4%), and sulfide metabolite (97.9%).

Metabolism

Hepatic Metabolism: Sulindac is metabolized in the liver. It's a prodrug that's converted to an active sulfide metabolite for therapeutic effects, along with inactive sulfone metabolites.
Enterohepatic Recirculation: Both the parent drug and its inactive metabolites undergo extensive enterohepatic recirculation.

Elimination

Half-Life: Sulindac has a half-life of approximately 7.8 hours, while its sulfide metabolite has a longer half-life of about 16.4 hours.
Time to Peak: Sulindac reaches peak levels in the bloodstream around 3 to 4 hours after administration, while the sulfide and sulfone metabolites peak around 5 to 6 hours later.

Excretion

Urinary Excretion: Around 50% of sulindac and its metabolites are excreted in the urine, primarily as inactive metabolites and less than 1% as the active sulfide metabolite.
Fecal Excretion: Approximately 25% of sulindac and its metabolites are excreted in the feces, primarily as metabolites.
Metabolites: Metabolites mainly appear as glucuronide conjugates in urine and bile.