What Is Salsalate?
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Salsalate - Uses, Mechanism of Action, Precautions, and Side Effects

Published on Dec 19, 2022 and last reviewed on Sep 08, 2023   -  16 min read


Salsalate reduces pain and swelling from rheumatoid arthritis. Learn more about it in detail in the article given below.


Salsalate is an orally available nonsteroidal anti-inflammatory drug (NSAID) in a group of drugs called salicylates. It provides symptomatic relief for rheumatoid arthritis, an inflammatory disorder affecting many joints, including the hands and feet. In addition, the drug reduces pain and stiffness associated with osteoarthritis (a degenerative disease affecting middle age due to wear and tear). Salsalate reduces the levels of prostaglandins produced by the body and is responsible for pain, fever, and inflammation. Salsalate is a prescription drug and may be used alone or with other medications.

How Does Salsalate Work?

Salsalate is converted in the body to salicylic acid. It works by reducing the prostaglandins (involved in dealing with injury and illness), which are responsible for pain, fever, and inflammation. Salsalate blocks the enzyme that makes prostaglandins, resulting in lower concentrations of prostaglandins.

Uses of Salsalate:

  • Salsalate relieves pain, swelling, tenderness, and stiffness caused by rheumatoid arthritis and osteoarthritis.

  • It is also used for minor to moderate pain.


  • When given in higher doses, Salsalate causes transient serum aminotransferase elevation.

  • Salsalate causes serious complications, like stomach bleeding and kidney problems, when taken for long periods.

  • The drug is not FDA-approved (Food and Drug Administration) and is not proven safe for children.

  • Salsalate is not recommended for use during pregnancy.


1. Route of Administration - Oral

2. Dosage Strengths-

  • Available tablets or capsules of 500 milligrams and 750 milligrams.

3. Dosage Forms -

  • Five hundred milligrams aqua or white capsule.

  • Five hundred milligrams aqua, film-coated, round, bisected tablet.

  • Seven hundred fifty milligrams aqua, film-coated, capsule-shaped, bisected tablet

4. Typical Dosage -

  • The typical dose for Rheumatoid arthritis is 3000 milligrams per day. The dose is divided into two or three doses.

  • It is prescribed as two doses of two 750 milligrams tablets, two doses of three 500 milligrams tablets, or three doses of 500 milligrams tablets.

  • The lowest effective dose is used for the shortest possible duration.

  • The elderly require a lower dosage to achieve therapeutic blood concentrations and to avoid side effects.

Special Considerations:

  • Pregnancy- Salsalate is used only if the possible benefits outweigh the risk to the mother and the unborn baby. The use should be avoided during the third trimester of pregnancy.

  • Lactation - Salicylic acid appears in human breast milk. The excretion of Salsalate into the milk increases disproportionately as the maternal dosage is increased.

  • Pediatric Population - Salicylates cause a severe illness called Reye’s syndrome in children recovering from flu, chickenpox, or other viral infections.

  • Geriatric Patients - Systemic clearance of salicylate is reduced by ade. Therefore, it can increase the risk of toxicity in older adults.

  • Renal Impairment - Salsalate is not recommended in patients with renal dysfunction. Closely monitor the renal function if the therapy is necessary.

  • Hepatic Impairment - Salsalate must be avoided, as it can cause severe liver damage. Patients with abnormal liver tests should be evaluated for hepatic reaction, and the drug may be discontinued.

  • Alcohol - Avoid drinking alcohol while taking Salsalate because it can raise the risk of stomach or intestinal ulcers and bleeding. The symptoms may include black, bloody, or tarry stools, coughing up blood, or vomit that looks like coffee grounds.

Warnings and Contraindications


  • Hypersensitivity - Salsalate is contraindicated in patients with a prior reaction to the drug or any of its components. The drug should not be used if one has had an allergic reaction to Aspirin, Salsalate, or other arthritis medicines such as Ibuprofen, Naproxen, or Celebrex. Therapy with Salsalate is contraindicated in these cases.

  • Cardiovascular Risk - NSAIDs increase the risk of cardiovascular thrombotic events, such as myocardial infarction or stroke, which can be fatal. Salsalate is contraindicated for perioperative pain, such as during coronary artery bypass graft (CABG) surgery.

  • Asthma - Salsalate tablets are contraindicated in patients with asthma as they can exacerbate the condition. The patient should stop taking the medication if they experience hives, difficulty breathing, or severe allergic reactions.

  • Alcohol - Avoid drinking alcohol while taking Salsalate because it can raise the risk of stomach or intestinal ulcers and bleeding. The symptoms may include black, bloody, tarry stools, coughing up blood, or vomit that looks like coffee grounds.

  • Smoking - Avoid smoking while taking Salsalate, as it can increase the risk of stomach bleeding.

Warnings and Precautions:

  • Gastrointestinal Toxicity - Taking Salsalate can cause dose-related gastrointestinal bleeding and mucosal damage. Therefore, therapy with salicylates should be administered cautiously in patients with a history of stomach bleed or peptic ulcer disease. Alcoholic and elderly patients may be more susceptible to gastrointestinal toxicity as they have less tolerance to ulceration and bleeding.

  • Renal Dysfunction - Salicylate and its metabolites are eliminated by the kidneys. Therefore, therapy with Salsalate should be administered cautiously in patients with severe renal impairment. In addition, clinical monitoring of renal function is recommended during prolonged therapy, as it may be associated with renal toxicities, including serum creatinine elevation, renal papillary necrosis (a disorder in which renal papilla of kidneys die), and acute tubular necrosis leading to renal failure.

  • Reye’s Syndrome - Salsalate in children with varicella infections or influenza is associated with a risk of causing Reye’s syndrome, a rare and potentially life-threatening reaction. When given to children with flu or chickenpox, the medication may have symptoms like brain swelling, liver damage, confusion, and seizures.

  • Heart Attack and Stroke - Long-term therapy can raise the risk of heart attack or stroke, especially in patients with a history of heart disease. Take Salsalate for the shortest amount of time. The drug can worsen the symptoms of heart failure, including the fluid build-up, which can lead to heart attacks.

  • Anemia - Chronic therapy of Salsalate can increase the risk of bleeding, leading to anemia (low red blood cells). Prolonged therapy should be administered cautiously in patients with or predisposed to anemia. In addition, it should be periodically monitored for signs of fatigue, weakness, or shortness of breath after taking the medication.

  • Coagulation - Salsalate interferes with vitamin K and induces a dose-dependent alteration in hepatic synthesis of coagulation factors VII, IX, and X. It may cause a slight increase in the prothrombin time (PT). High medication dosages should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including coagulation defects, vitamin K deficiency, or thrombocytopenia.

  • Dialysis - Salsalate and its metabolites are readily removed by hemodialysis by peritoneal dialysis. Doses can be scheduled for administration after the dialysis, or supplemental doses may be given after dialysis.

  • G-6-PD Deficiency - Salsalate may cause or aggravate hemolysis in patients with pyruvate kinase or glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. The effect has yet to be established.

  • Hepatotoxicity - High doses of Salsalate have occasionally been associated with acute, reversible hepatotoxicity, manifestations such as elevations of serum transaminases, alkaline phosphatase, or bilirubin. It is recommended to perform periodic monitoring of liver function.

For Patients

What Is Rheumatoid Arthritis?

Rheumatoid arthritis is a chronic, inflammatory, and autoimmune condition in which the immune system mistakenly sends antibodies to the lining of the joints, where it attacks the tissue surrounding the joint. It causes soreness and inflammation of the synovium (thin layer of cells) covering the joints, damaging nearby bones, cartilage, tendons, and ligaments. Some possible risk factors that increase the risk of developing rheumatoid arthritis include

  • Genes - Gene HLA-DR4 (a human leukocyte antigen genetic anomaly found in white blood cells) is associated with rheumatoid arthritis. People with this gene are more likely to develop rheumatoid arthritis than those without, and symptoms may worsen.

  • Hormones - The disease is more common in women than men because of the effects of the hormone estrogen (a hormone that develops and regulates the female reproductive tract).

  • Smoking - Some evidence suggests that people who smoke are more likely to have rheumatoid arthritis.

Symptoms of Rheumatoid Arthritis:

The main symptoms of rheumatoid arthritis include

  • Rheumatoid arthritis usually affects joints symmetrically on both sides of the body simultaneously and to the same extent. As a result, joint pain can occur in any joint, although the small joints in the hands and feet are often the first to be affected. The pain is throbbing and aching and worse in the morning.

  • The lining of the joints becomes inflamed, which can cause the joints to swell and tender to the touch. Firm swelling and rheumatoid nodules may develop under the skin around the affected joints.

  • The affected joints feel stiff, and one cannot bend the area thoroughly. It is worse in the morning or after a period of inactivity.

  • Other general symptoms include tiredness, sweating, weight loss, a high temperature, or a poor appetite.

Why Is Salsalate Prescribed For Rheumatoid Arthritis?

Salsalate helps reduce joint swelling and stiffness and improves the mobility of joints in people with rheumatoid arthritis. In addition, the drug causes fewer side effects than other alternatives, such as corticosteroids, used to treat rheumatoid arthritis. Salsalate is also less likely to induce asthma in known AS-sensitive patients (acetylsalicylic acid) with asthma.

Facts One Should Know About Salsalate:

  • The usual dosage of Salsalate is 3000 milligrams daily, given in divided doses. To avoid potentially toxic concentrations, Salsalate patients should not take other salicylates, such as Ibuprofen, Aspirin, or Naproxen.

  • Salsalate is taken with food or milk to prevent stomach upset, nausea, and hyperacidity. However, taking the medication with food may take a little longer to start working.

  • Taking Salsalate may take three to four days to show its full effects.

  • People allergic to Aspirin are at a higher risk of being allergic to Salsalate.

  • Salsalate can cause some severe health issues. Brief the doctor about other medical conditions and over-the-counter- drugs that one may be taking.

How Should One Take Salsalate?

  • Salsalate is available in tablet form that can be taken by mouth.

  • Take the Salsalate tablets two to three times a day.

  • Salsalate is taken with food to prevent stomach upset.

  • The drug must be taken at the same time each day.

  • When taking Salsalate, as when needed, The medication must be started as the first sign of pain occurs.

  • It is advised to avoid taking doses other than the prescribed dose of Salsalate.

  • It may take four to five days to feel the full benefits of the drug.

  • Medical tests need to be done when taking the medication for the long term.

Information Be Given to the Doctor Before Taking Salsalate:

  • Allergies- Inform the doctor if Salsalate or any other NSAIDs have caused symptoms like rash, tongue, face, or throat swelling, and other signs of allergic reaction.

  • Medical History- Inform the doctor of any concurrent illnesses one may be suffering from, especially brain-related damages such as head injury, cancer, seizures, prolonged breathing problems such as asthma, sleep apnea, obstructive pulmonary disease, kidney disease, liver disease, mental disorders such as confusion, depression, suicidal thoughts, or history of substance abuse.

  • Drug History- Give the doctor a complete list of the prescription and non-prescription medications one may be taking, including any herbal supplements, nutritional supplements, and vitamins. Ensure to inform the doctor if one is already taking other medicines containing salicylates, such as Aspirin, magnesium salicylate, choline salicylate, or Diflunisal.

  • Pregnancy- Inform the doctor if one is pregnant or planning a pregnancy. Taking Salsalate during the last 20 weeks of pregnancy causes heart problems in the baby or may complicate the pregnancy.

  • Lactation - Salsalate passes into the breast milk. Large amounts of the medicine may be avoided.

  • Geriatrics - Salsalate can cause serious adverse renal effects in older adults.

  • Children - Do not give salicylates such as Salsalate to children with fever or other symptoms of a virus infection, especially flu or chickenpox. It can increase the risk of Reye’s syndrome.

  • Surgery - NSAIDs such as Salsalate must be stopped before surgical intervention, such as dental surgery.

Safety of Salsalate:

  • People who take nonsteroidal anti-inflammatory medications, such as Salsalate, have an increased risk of heart attack or stroke compared to those not taking these medications.

  • Salsalate has a lower bleeding risk when compared with Aspirin.

  • Avoid driving or hazardous activity until one knows how the drug affects the body. The medication may impair the reactions.

Effectiveness of Salsalate:

  • Salsalate takes three to four days to relieve symptoms of rheumatoid arthritis.

  • The drug relieves pain, swelling, tenderness, and stiffness, which are symptoms of rheumatoid arthritis.

Side Effects Expected With Salsalate:

The common side effects that occur with the use of Salsalate are as follows:

  • Ringing in the ears.

  • Hearing loss.

  • Nausea.

  • Spinning sensation (vertigo).

  • Rash.

  • Unusual tiredness.

  • Stomach pain.

  • Diarrhea.

  • Low blood pressure.

  • Hives.

Serious side effects may include

  • Swelling in the hands or feet.

  • Rapid weight gain.

  • Severe Headache.

  • Blurred vision.

  • Unusual bleeding or bruising.

  • Fever.

  • Severe headache.

  • Blood clots.

  • Cold hands and feet.

  • Yellowing of the skin and eyes.

Can One Stop Taking Salsalate Suddenly Without the Doctor's Approval?

  • Never stop taking medicines without talking to the doctor. The doctor will decrease the dose gradually.

  • Do not take the drug more than advised by the doctor.

Dietary Restrictions to Consider When Taking Salsalate:

  • Avoid high-salicylate fruits and vegetables such as apples, apricots, berries, cherries, dates, currants, grapes, raisins, and gooseberries.

  • Avoid high-salicylate beverages such as beer, bubbly drinks, regular coffee, tea, and wine.

  • Avoid too sugary and fatty foods.

Storage of Salsalate Tablets:

  • Keep them in their original packing.

  • Store at room temperature between 15 to 30 degrees.

  • Direct contact with heat, air, and light may damage the medicines. Therefore, keep the medicines away from direct light and heat.

  • Keep all medicines out of reach of children and pets. Always lock the safety caps of the medication to protect small children from poisoning themselves.

Disposal of Salsalate Medicines:

  • Do not keep outdated medicines or medicines that are no longer needed.

  • Likewise, unneeded tablets should not be disposed of by flushing or throwing them out with regular garbage.

  • Dispose of the medicine through the local medicine take-back program, which can be accessed or learned more about through the local pharmacist.

  • Some people may not have access to a drug take-back program. Ask the local pharmacist about any other drug disposal options available.


  • In case of an overdose, call the poison control helpline.

  • Call the emergency services if the person has collapsed or has trouble breathing.

  • Overdose symptoms include nausea, vomiting, dizziness, confusion, Extreme thirst, fainting, headache, flushing, or loss of consciousness.

  • Supportive treatment is initiated following the patient's clinical signs and symptoms.

For Doctors


  • Salsalate is indicated to relieve pain, swelling, tenderness, and stiffness caused by rheumatoid arthritis (arthritis caused by swelling of the lining of the joints).

  • The drug is also prescribed to relieve pain and swelling caused by osteoarthritis.

What Is the Pharmacology of Salsalate?


Salsalate is a nonsteroidal and anti-inflammatory drug used for oral administration. It is a dimer of salicylic acid with a structural formula of 2-hydroxy-benzoic acid, 2-carboxyphenyl ester.


1. Active Ingredients

  • Salicylic acid.

2. Inactive Ingredients

  • Colloidal silicon dioxide.

  • Hypromellose.

  • Microcrystalline cellulose.

  • Sodium starch glycolate. Stearic acid. Titanium dioxide. Triacetin.

Clinical Pharmacology:

Mechanism of Action:

Salsalate is a nonsteroidal anti-inflammatory drug that inhibits the synthesis and release of prostaglandins. The inhibition of prostaglandin synthesis is done through the inactivation of cyclooxygenase-1 and COX-2. These are responsible for catalyzing the formation of prostaglandins in the arachidonic acid pathway. Salicylates are weak prostaglandin inhibitors.


Salsalate is insoluble in gastric acid fluids but is readily soluble and hydrolyzed to two molecules in the small intestine. Salsalate is hydrolyzed to salicylic acid as a prodrug, inhibiting cyclooxygenase enzyme expression.


  • The mean Cmax- 114 ng/ml and 14,000 ng/ml.

  • Median Tmax- Approximately 24 to 72 hours.

[Cmax- Maximum concentration achieved by a drug in the blood, cerebrospinal fluid, or target organ after administration of a dose]

[Tmax- Time taken for a drug to reach maximum concentration after administration of a dose]

Pharmacokinetic Changes - The presence of food slows the absorption of all salicylates, including Salsalate.

A. Distribution

  • Steady-State Plasma Levels - 90 % to 95 %.

  • Time to Approach Steady-State Levels - 16 hours.

  • Mean Volume of Distribution - 19.2 liters and 17.4 liters.

B. Metabolism

  • Metabolic Processes- Salsalate is readily soluble in the small intestine, partially hydrolyzed to two salicylic acid molecules. However, a significant portion of the parent compound is absorbed unchanged and undergoes rapid esterase hydrolysis in the body.

C. Elimination: Half-life - One hour.

Special Considerations

  • Pregnancy - Salsalate should be used during pregnancy only if the benefits justify the potential risk to the fetus.

  • Renal Impairment - Salsalate should be avoided in patients with renal impairment, as NSAIDs have been associated with acute kidney injury and disease progression in chronic kidney disease patients.

  • Hepatic Impairment - NSAIDs, such as Salsalate, should be avoided in patients with advanced chronic liver disease or cirrhosis. These drugs increase the risk of liver injury.

  • Alcohol - Alcohol consumption should be avoided while taking Salsalate. Alcohol increases the risk of stomach bleeding.

  • Age - The safety and effectiveness of the drug in children have not been established and should be avoided.

Drug Interactions:

  • Dichlorphenamine - The use of Dichlorphenamine increases levels of Salsalate. Coadministration of Chlorphenamine with Salsalate is contraindicated, causing adverse effects such as anorexia, tachypnea (fast, shallow breathing), lethargy, and coma.

  • Lithium - Salsalate increases levels of lithium by decreasing renal clearance. The drug should be administered cautiously and regularly monitored.

  • Benazepril - Coadministration of Benazepril and Salsalate may result in a significant reduction in renal function. Salsalate may diminish the blood pressure-lowering effect of ACE (acetylcholine) inhibitors, such as Enalapril, Captopril, or Benazepril, by reducing the synthesis of vasodilating renal prostaglandins.

  • Methotrexate - Salsalate increased levels of Methotrexate by a decrease in renal clearance. The risk of drug interaction is greater during high-dose Methotrexate therapy and should be administered cautiously.

  • Diuretics - Taking diuretics such as Furosemide or Aldactone with Salsalate may cause the diuretic not to work well.The patient may experience a decrease in the beneficial effects of the diuretic (water pill).

  • Live Vaccine of Measles, Mumps, or Rubella - Avoid using Salsalate for at least six weeks after the measles, mumps, rubella, or varicella vaccine. The use of Salsalate may increase the risk of Reye’s syndrome.

  • Warfarin - Coadministration of Salsalate and oral blood thinners, such as Warfarin, Dabigatran, or Edoxaban, should be avoided as both drugs thin the blood. Excessive blood thinning may lead to bleeding.

What Have Clinical Trials Shown About Salsalate?

Trial 1:

Objective - To study the efficacy of Salsalate and Piroxicam in relieving arthritic symptoms based on the endoscopic evaluation.

  • A double-blind study to compare the clinical efficacy and gastric tolerability of Salsalate and Piroxicam in treating rheumatoid arthritis was performed.

  • A total of 23 patients were treated with 1.5 grams of Salsalate taken twice daily and 20 with milligrams of Piroxicam for four weeks.

  • Patients with normal baseline gastroscopy were admitted to the trial.

End Point - At the end of the planned treatment period, a statistically significant improvement of all clinical variables was observed in both treatment groups.

Final End Point - Five of 20 Piroxicam-treated patients and only 11 % of Salsalate patients showed gastric lesions at the final endoscopy. However, no significant relationship was found between specific symptoms and endoscopic lesions in either of the treatment groups.

Result - Salsalate and Piroxicam have equal efficacy in relieving arthritic symptoms. Salsalate, however, caused fewer gastric lesions.

Trial 2:

Objective - To investigate Salsalate's efficacy in treating patients with rheumatoid arthritis.

  • More than three hundred and one patients meeting the ACR criteria (scale to measure the change in rheumatoid arthritis symptoms) participated.

  • Patients received drugs, Salsalate or Diclofenac, for eight weeks in a double-blind, double-dummy protocol.

  • Initial doses of Salsalate 3.0 grams per day and Diclofenac 75 milligrams per day were titrated for the first five weeks.

Primary Outcome - A multivariate analysis was done at eight weeks of tenderness in the joint, pain, visual analog scale score, and given physician’s global assessment.

  • Both treatments produced significant improvement.

  • Significant differences between the two drugs; however, no statistically significant or clinically essential treatment differences were recorded.

  • There was a difference in erythrocyte sedimentation rate in Salsalate.

Result - Salsalate is as productive as Diclofenac. It can be considered an alternative to other NSAIDs in the first-line treatment of patients with rheumatoid arthritis.

Patient Counseling Information

Administration Instructions-

  • Use the lowest dose of Salsalate.

  • It may take up to four days before the patient receives the full benefits of taking Salsalate.

  • The patient may need to stop taking Salsalate for a short time if they need surgery, dental work, or a medical procedure.

  • A frequent test may be required when taking Salsalate for the long term.

  • Avoid taking larger or smaller amounts of Salsalate without talking to the doctor. Also, do not take the medication for a longer time than recommended.

  • Avoid drinking alcohol while taking Salsalate, as it can raise the risk of stomach or intestinal ulcers and bleeding.

  • People over 65 should take the lowest dose of Salsalate for the shortest time necessary to treat the pain.

Complications or Side Effects:

  • High Blood Pressure - Salsalate can raise blood pressure, especially if the person has a history of high blood pressure. Check the blood pressure regularly.

  • Severe Allergic Reactions - Patients who have had a serious allergic reaction to Aspirin or other NSAIDs have a higher chance of developing allergic reactions to Salsalate. Inform the health care provider if one experiences symptoms, such as hives, difficulty breathing, or swelling of the face, lips, or throat.

  • Children - A rare and potentially life-threatening reaction, Reye's syndrome, may develop in children with viral infections, such as flu or chickenpox, while taking Salsalate. It causes symptoms that include brain and liver damage, confusion, and seizure.

  • Low Kidney Function - Salsalate can lower kidney function or cause permanent kidney damage. The patient may experience irregular heartbeat, shortness of breath, or less urination while taking these medications.

  • Stomach Bleeding - Taking Salsalate increases the risk of ulcers and gastrointestinal bleeding. The patient may experience sharp pain in the stomach, bright red blood in the vomit, or dark, black, or tarry stools.

Article Resources

Last reviewed at:
08 Sep 2023  -  16 min read




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