Disalcid

Salsalate is a non-steroidal anti-inflammatory drug (NSAID) in a group of drugs called salicylates (sa-LIS-il-ates). This medicine works by reducing substances in the body that cause pain, fever, and inflammation.

Salsalate is used to reduce pain, swelling, and joint stiffness caused by arthritis.

Salsalate may also be used for purposes not listed in this medication guide.

You should not use this medication if you are allergic to aspirin or to an NSAID (non-steroidal anti-inflammatory drug).

Before taking salsalate, tell your doctor if you have asthma, heart disease, high blood pressure, stomach or intestinal bleeding, diabetes, anemia, a bleeding disorder, liver or kidney disease, nasal polyps, a genetic enzyme deficiency, or if you are dehydrated.

This medicine may cause life-threatening heart or circulation problems such as heart attack or stroke, especially if you use it long term. Do not use salsalate just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

Get emergency medical help if you have chest pain, weakness, shortness of breath, slurred speech, or problems with vision or balance.

This medicine may also cause serious effects on the stomach or intestines, including bleeding or perforation (forming of a hole). These conditions can be fatal and can occur without warning while you are taking salsalate, especially in older adults.

Call your doctor at once if you have symptoms of stomach bleeding such as black, bloody, or tarry stools, or coughing up blood or vomit that looks like coffee grounds.

This medication should not be given to a child or teenager who has a fever, especially if the child also has flu symptoms or chicken pox. Salicylates can cause a serious and sometimes fatal condition called Reye's syndrome in children.

Salicylates may cause life-threatening heart or circulation problems such as heart attack or stroke, especially if you use it long term. Do not use salsalate just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

Salicylates may also cause serious effects on the stomach or intestines, including bleeding or perforation (forming of a hole). These conditions can be fatal and can occur without warning while you are taking salsalate, especially in older adults.

You should not use this medication if you are allergic to aspirin or to an NSAID (non-steroidal anti-inflammatory drug).

To make sure you can safely take salsalate, tell your doctor if you have any of these other conditions:

• asthma;
• heart disease, high blood pressure, congestive heart failure;
• a history of stroke or heart attack;
• a stomach ulcer or intestinal bleeding;
• a bleeding or blood clotting disorder;
• diabetes;
• swelling or fluid retention;
• anemia (a lack of red blood cells);
• liver disease;
• kidney disease;
• an enzyme deficiency called glucose-6-phosphate dehydrogenase deficiency (G6PD);
• nasal polyps; or
• if you are dehydrated.

FDA pregnancy category C. Salsalate may be harmful to an unborn baby if the mother takes the medication during the last 3 months of pregnancy. Do not take this medication without telling your doctor if you are pregnant or plan to become pregnant during treatment.

Salsalate can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

This medication should not be given to a child or teenager who has a fever, especially if the child also has flu symptoms or chicken pox. Salicylates can cause a serious and sometimes fatal condition called Reye's syndrome in children.

Older adults may be more likely to have side effects from salsalate.

JUNE 1998

3M Pharmaceuticals
Northridge, CA 91324

DISALCID (salsalate) is insoluble in acid gastric fluids (< 0.1 mg/ml at pH 1.0), but readily soluble in the small intestine where it is partially hydrolyzed to two molecules of salicylic acid. A significant portion of the parent compound is absorbed unchanged and undergoes rapid esterase hydrolysis in the body; its half-life is about one hour. About 13% is excreted through the kidneys as a glucuronide conjugate of the parent compound, the remainder as salicylic acid and its metabolites. Thus, the amount of salicylic acid available from DISALCID (salsalate) is about 15% less than from aspirin, when the two drugs are administered on a salicylic acid molar equivalent basis (3.6 g salsalate/5 g aspirin).

Salicylic acid biotransformation is saturated at anti-inflammatory doses of DISALCID (salsalate) . Such capacity limited biotransformation results in an increase in the half-life of salicylic acid from 3.5 to 16 or more hours. Thus, dosing with DISALCID (salsalate) twice a day will satisfactorily maintain blood levels within the desired therapeutic range (10 to 30 mg/100 ml) throughout the 12-hour intervals. Therapeutic blood levels continue for up to 16 hours after the last dose. The parent compound does not show capacity-limited biotransformation, nor does it accumulate in the plasma on multiple dosing. Food slows the absorption of all salicylates including DISALCID (salsalate) .

The mode of anti-inflammatory action of DISALCID (salsalate) and other nonsteroidal anti-inflammatory drugs is not fully defined. Although salicylic acid (the primary metabolite of DISALCID (salsalate) ) is a weak inhibitor of prostaglandin synthesis in vitro, DISALCID (salsalate) appears to selectively inhibit prostaglandin synthesis in vivo, providing anti-inflammatory activity equivalent to aspirin and indomethacin. Unlike aspirin, DISALCID (salsalate) does not inhibit platelet aggregation.

The usefulness of salicylic acid, the active in vivo product of DISALCID (salsalate) , in the treatment of arthritic disorders has been established. In contrast to aspirin, DISALCID (salsalate) causes no greater fecal gastrointestinal blood loss than placebo.

Since salsalate is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Salsalate may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Ask a doctor or pharmacist before using any other over-the-counter medicine. Salicylates and NSAIDs are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains aspirin, ibuprofen, naproxen, ketoprofen, magnesium salicylate, or similar medicines.

If you are also taking low-dose aspirin because your doctor has prescribed it to prevent heart attack or stroke, do not stop taking it or change your dose without your doctor's advice. Aspirin should be used for cardiovascular conditions only under the supervision of a doctor.

Avoid drinking alcohol. It may increase your risk of stomach bleeding.

Avoid smoking, since it can also increase your risk of stomach bleeding.

You should not use this medication if you are allergic to aspirin or to an NSAID (non-steroidal anti-inflammatory drug).

Before taking salsalate, tell your doctor if you have asthma, heart disease, high blood pressure, stomach or intestinal bleeding, diabetes, anemia, a bleeding disorder, liver or kidney disease, nasal polyps, a genetic enzyme deficiency, or if you are dehydrated.

This medicine may cause life-threatening heart or circulation problems such as heart attack or stroke, especially if you use it long term. Do not use salsalate just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

Get emergency medical help if you have chest pain, weakness, shortness of breath, slurred speech, or problems with vision or balance.

This medicine may also cause serious effects on the stomach or intestines, including bleeding or perforation (forming of a hole). These conditions can be fatal and can occur without warning while you are taking salsalate, especially in older adults.

Call your doctor at once if you have symptoms of stomach bleeding such as black, bloody, or tarry stools, or coughing up blood or vomit that looks like coffee grounds.

This medication should not be given to a child or teenager who has a fever, especially if the child also has flu symptoms or chicken pox. Salicylates can cause a serious and sometimes fatal condition called Reye's syndrome in children.

Many drugs can interact with salsalate. Below is just a partial list. Tell your doctor if you are using:

• acetazolamide (Diamox);

• cyclosporine (Gengraf, Neoral, Sandimmune);

• lithium (Eskalith, LithoBid);

• methotrexate (Rheumatrex, Trexall);

• pemetrexed (Alimta);

• tenofovir (Viread);

• an antidepressant such as fluoxetine (Prozac) or sertraline (Zoloft);

• a blood thinner such as warfarin (Coumadin);

• oral diabetes medication;

• a diuretic (water pill);

• gout medication such as probenecid (Benemid);

• heart or blood pressure medication such as atenolol (Tenormin), captopril (Capoten), lisinopril (Prinivil, Zestril), losartan (Cozaar, Hyzaar), metoprolol (Lopressor, Toprol), and others;

• medication used to prevent blood clots, such as cilostazol (Pletal) or clopidogrel (Plavix);

• osteoporosis medication such as alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel), and others;

• sodium bicarbonate, potassium citrate (K-Lyte, Urocit-K), sodium citrate and citric acid (Bicitra, Oracit), or sodium citrate and potassium (Citrolith, Polycitra);

• seizure medication such as phenytoin (Dilantin), phenobarbital (Solfoton), valproic acid (Depakene); or

• steroid medicine (prednisone and others).

This list is not complete and there are many other drugs that can interact with salsalate. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Signs of high potassium levels like a heartbeat that does not feel normal; feeling confused; feeling weak, lightheaded, or dizzy; feeling like passing out; numbness or tingling; or shortness of breath.
• Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Chest pain or pressure or a fast heartbeat.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Ringing in ears.
• Hearing loss.
• Very bad belly pain.
• Feeling very tired or weak.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Upset stomach.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Disalcid, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Disalcid. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Disalcid.

Review Date: October 4, 2017

Cardiovascular Thrombotic Events

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious Gastrointestinal (GI) events (see Gastrointestinal WARNINGS).

Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS).

No information is available from controlled clinical studies regarding the use of Disalcid (Salsalate) TABLETS in patients with advanced renal disease. Therefore, treatment with Disalcid (Salsalate) TABLETS is not recommended in these patients with advanced renal disease. If Disalcid (Salsalate) TABLETS therapy must be initiated, close monitoring of the patient's renal function is advisable.

It is not known whether salsalate as such is excreted in human milk; salicylic acid, the primary metabolite of salsalate, has been shown to appear in human milk in concentrations approximating the maternal blood level. Thus, the infant of a mother on salsalate therapy might ingest in mother’s milk 30 to 80% as much salicylate per kg body weight as the mother is taking. Accordingly, caution should be exercised when salsalate is administered to a nursing woman.

500 mg Tablets: Supplied in bottles of 100 count (NDC 75854-201-10); white, round-shaped tablets, debossed with “Syntho” on one side, and 112 on the other side.

750 mg Tablets: Supplied in bottles of 100 count (NDC 75854-202-10); white, capsule-shaped tablets, debossed with “D-1200” on one side.

Dispense contents with a child-resistant closure (as required) and in a tight container as defined in the USP.

Store at 15° - 30°C (59° - 86°F) [See USP].

Rx only

Applies to salsalate: oral capsule, oral tablet

General

The most frequently reported side effects were usually reversible and included tinnitus, nausea, hearing impairment, rash, and vertigo.[Ref]

Gastrointestinal

Frequency not reported: Nausea, abdominal pain, diarrhea, gastrointestinal bleeding[Ref]

Cardiovascular

Frequency not reported: Hypotension[Ref]

Dermatologic

Frequency not reported: Rash, angioedema, urticaria[Ref]

Hepatic

Frequency not reported: Hepatic function abnormal, hepatitis[Ref]

Renal

Frequency not reported: Nephritis[Ref]

Respiratory

Frequency not reported: Bronchospasm[Ref]

Other

Frequency not reported: Tinnitus, hearing impaired, vertigo, creatinine clearance decreased[Ref]

Immunologic

Frequency not reported: Anaphylactic shock[Ref]

Some side effects of Disalcid may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Summary of Use during Lactation

Salsalate has not been studied during breastfeeding, but salsalate results in salicylic acid in the blood. Salicylic acid and aspirin have been studied during breastfeeding. The excretion of salicylate into breastmilk increases disproportionately as the maternal dosage increases. Long-term, high-dose maternal aspirin ingestion probably caused metabolic acidosis in one breastfed infant. Reye's syndrome is associated with aspirin administration to infants with viral infections, but the risk of Reye's syndrome from salicylate in breastmilk is unknown. An alternate drug is preferred over salsalate.

Drug Levels

Milk levels have not been measured after maternal ingestion of salsalate, but have been measured after other salicylates, such as aspirin and sodium salicylate. All of these products result in salicylic acid in the blood and milk; however, some studies have not measured salicylate metabolites in breastmilk that may be hydrolyzed in the infant's gut and absorbed as salicylate.[1]

Maternal Levels. Milk and blood levels of the salicylate metabolites of aspirin were determined in 8 lactating women following oral administration of 1 g of aspirin. Peak salicylic acid milk levels averaging 2.4 mg/L occurred 3 hours after the dose. Milk contents of salicyluric acid were greater than those of salicylic acid; a mean peak level of 10.2 mg/L was reached after 9 hours, and averaged 4.4 mg/L 24 hours after the dose. Total salicylate and metabolite levels were 5.1 mg/L at 3 hours, 9.9 mg/L at 6 hours, 11.2 mg/L at 9 hours and 10.2 mg/L at 12 hours after the dose. Acid labile conjugates were less than 0.2 mg/L.[2] Using an average salicylate plus salicylurate level over the first 12 hours, a fully breastfed infant would receive an average of 9.4% of the maternal weight-adjusted dosage.

Six nursing mothers who were 2 to 8 months postpartum (average 5 months) were given aspirin doses of 500, 1000 and 1500 mg of aspirin orally on 3 separate occasions. Peak breastmilk salicylate levels were 5.8 mg/L, 15.8 mg/L, and 38.8 mg/L, respectively. Salicylate metabolites were not measured. The time of the peak salicylate levels occurred between 2 and 6 hours after ingestion, with little variation in levels over time. The disproportionate increase in milk levels as the dose increased was attributed to nonlinear metabolism and protein binding.[3]

Two women given aspirin 454 mg orally had peak salicylate milk levels of about 1 mg/L 1 hour after the dose. The authors estimated that about 0.1% of the mothers' total dose would appear in breastmilk in 48 hours.[4] However, salicylate metabolites were not measured in milk.

A woman who was breastfeeding a 4-month-old was taking long-term aspirin therapy in dosages ranging from 2 to 5.9 g daily. During this therapy, milk was obtained 4 hours after a 650 mg dose and just before taking a dose of 975 mg. The trough milk salicylate level was 2 mg/L and a peak level of 10 mg/L occurred 3 hours after the dose. Salicylate levels ranged from 4 to 7 mg/L over the 5 hours after the peak.[5] Using the peak level from this study, a fully breastfed infant would receive about 10% of the maternal weight-adjusted dosage of salicylate. The assay method used should have measured both salicylate and metabolites in milk.

Infant Levels. Four nursing mothers were given oral sodium salicylate in a dose of 20 mg/kg. Their exclusively breastfed infants ranged from 23 to 43 days of age. The infants' urine was collected until salicylate excretion was complete and found to contain 0.18 to 0.36% of the maternal dose, primarily as salicyluric acid.[1]

A 9-week-old infant who was born at 36 weeks gestation was receiving about 50% breastmilk and 50% formula. The infant's mother was taking 2.4 g of aspirin daily and the infant's serum contained 65 mg/L of salicylate.[6]

Effects in Breastfed Infants

A 16-day-old breastfed infant developed metabolic acidosis with a salicylate serum level of 240 mg/L and salicylate metabolites in the urine. The mother was taking 3.9 g/day of aspirin for arthritis, and salicylate in breastmilk probably caused the infant's illness, but the possibility of direct administration to the infant could not be ruled out.[7]

Thrombocytopenia, fever, anorexia and petechiae occurred in a 5-month-old breastfed infant 5 days after her mother started taking aspirin for fever. One week after recovery, the infant was given a single dose of aspirin 125 mg and the platelet count dropped once again. The original symptoms were probably caused by salicylate in breastmilk.[8]

Hemolysis after aspirin and phenacetin taken by the mother of a 23-day-old, G-6-PD-deficient infant was possibly due to aspirin in breastmilk.[9]

In a telephone follow-up study, mothers reported no side effects among 15 infants exposed to aspirin (dose and infant age unspecified) in breastmilk.[10]

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Acetaminophen, Ibuprofen

References

1. Levy G. Salicylate pharmacokinetics in the human neonate. In, Morselli PL, Garattini S, Sereni F, eds. Basic and therapeutic aspects of perinatal pharmacology. 1975;Raven Press :New York:319-30.

2. Putter J, Satravaha P, Stockhausen H. Quantitative analysis of the main metabolites of acetylsalicylic acid. Comparative analysis in the blood and milk of lactating women. Z Geburtshilfe Perinatol. 1974;178:135-8. PMID: 4422623

3. Jamali F, Keshavarz E. Salicylate excretion in breast milk. Int J Pharm. 1981;8:285-90.

4. Findlay JW, DeAngelis RL, Kearney MF et al. Analgesic drugs in breast milk and plasma. Clin Pharmacol Ther. 1981;29:625-33. PMID: 7214793

5. Bailey DN, Welbert RT, Naylor A. A study of salicylate and caffeine excretion in the breast milk of two nursing mothers. J Anal Toxicol. 1982;6:64-8. PMID: 7098450

6. Unsworth J, d'Assis-Fonseca A, Beswick DT. Serum salicylate levels in a breast fed infant. Ann Rheum Dis. 1987;46:638-9. PMID: 3662653

7. Clark JH, Wilson WG. A 16-day-old breast-fed infant with metabolic acidosis caused by salicylate. Clin Pediatr (Phila). 1981;20:53-4. PMID: 7449246

8. Terragna A, Spirito L. [Thrombocytopenic purpura in an infant after administration of acetylsalicylic acid to the wet-nurse] . Minerva Pediatr. 1967;19:613-6.

9. Harley JD, Robin H. "Late" neonatal jaundice in infants with glucose-6-phosphate dehydrogenase-deficient erythrocytes. Australas Ann Med. 1962;11:148-55. PMID: 13960788

10. Ito S, Blajchman A, Stephenson M et al. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol. 1993;168:1393-9. PMID: 8498418