What is diflunisal used for. How does diflunisal work as an NSAID. What are the potential side effects of diflunisal. How can diflunisal affect liver function. What precautions should be taken when using diflunisal.

Understanding Diflunisal: An Overview of the Medication

Diflunisal, also known by its brand name Dolobid, is a nonsteroidal anti-inflammatory drug (NSAID) that belongs to the salicylate family. It is a difluorophenol derivative of salicylic acid, structurally related to aspirin but with distinct properties and effects. Diflunisal was approved for use in the United States in 1982 and has since been utilized for various therapeutic purposes.

How does diflunisal work? Like other NSAIDs, diflunisal primarily acts by inhibiting cyclooxygenase enzymes (COX-1 and COX-2) in the body. This inhibition leads to a decrease in the synthesis of prostaglandins, which are important mediators in inflammatory and pain pathways. By reducing prostaglandin production, diflunisal helps alleviate inflammation, pain, and fever.

Medical Uses and Indications for Diflunisal

Diflunisal is prescribed for several medical conditions, primarily focusing on pain management and inflammatory disorders. The main indications for diflunisal include:

• Chronic arthritis (osteoarthritis and rheumatoid arthritis)
• Mild to moderate acute pain
• Off-label use in familial amyloidosis

Can diflunisal be used for conditions other than arthritis? Interestingly, research has shown that diflunisal can stabilize transthyretin variants involved in the pathogenesis of amyloidosis. This discovery has led to its off-label use in treating familial amyloidosis, a rare genetic disorder characterized by the abnormal buildup of amyloid proteins in various organs.

Dosage and Administration of Diflunisal

Diflunisal is available as 500 mg tablets and is only obtainable through prescription. The recommended dosage regimen for adults typically follows this pattern:

1. Initial dose: 1000 mg
2. Maintenance dose: 500 to 1500 mg daily, divided into two or three doses

How should the dosage be adjusted? The maintenance dose should be based on the individual patient’s response and tolerance to the medication. It’s crucial for healthcare providers to monitor patients closely and adjust the dosage as needed to achieve optimal therapeutic effects while minimizing potential side effects.

Common Side Effects and Tolerability of Diflunisal

While diflunisal is generally well-tolerated, like all medications, it can cause side effects in some individuals. Common side effects associated with diflunisal use include:

• Gastrointestinal disturbances (nausea, heartburn, intestinal upset)
• Headache
• Somnolence (drowsiness)
• Dizziness
• Peripheral edema (swelling in the extremities)
• Hypersensitivity reactions

Are these side effects severe enough to discontinue treatment? In most cases, these side effects are mild and transient, often resolving on their own or with minor adjustments to the dosage. However, if side effects persist or worsen, patients should consult their healthcare provider for guidance.

Diflunisal and Liver Function: Understanding the Hepatic Impact

One of the critical aspects of diflunisal use is its potential impact on liver function. While severe liver injury is rare, it’s essential to understand the possible hepatic effects of this medication:

• Mild, transient elevations in serum aminotransferase levels
• Rare instances of idiosyncratic drug-induced liver disease
• Potential for clinically apparent liver injury with jaundice (uncommon)

How does diflunisal-induced liver injury present? When liver injury does occur, it often resembles an immunoallergic hepatitis, which is distinct from the liver injury pattern seen with aspirin or other salicylates. The onset of liver-related symptoms typically occurs within 1 to 4 weeks of starting treatment.

Characteristics of Diflunisal-Induced Liver Injury

When liver injury does occur due to diflunisal use, it often presents with specific characteristics:

• Cholestatic or mixed pattern of enzyme elevations
• Immunoallergic manifestations (rash, fever, arthralgias)
• Eosinophilia or atypical lymphocytosis

Is diflunisal-induced liver injury related to aspirin allergy? Interestingly, a history of aspirin allergy has not been reported among cases with allergic reactions to diflunisal, suggesting a distinct mechanism of action for the liver injury caused by diflunisal compared to other salicylates.

Monitoring and Managing Liver Function During Diflunisal Treatment

Given the potential for liver-related side effects, it’s crucial to monitor liver function in patients taking diflunisal. Healthcare providers should consider the following approaches:

• Regular liver function tests, especially during the first few weeks of treatment
• Patient education on signs and symptoms of liver injury
• Prompt discontinuation of diflunisal if liver injury is suspected
• Consideration of alternative treatments for patients with pre-existing liver conditions

How frequently should liver function be monitored? The frequency of liver function monitoring may vary depending on individual patient factors and the duration of treatment. Typically, more frequent monitoring is recommended during the initial weeks of therapy, with less frequent follow-ups if no abnormalities are detected.

Diflunisal vs. Other NSAIDs: Comparative Safety Profile

When considering the use of diflunisal, it’s important to understand how its safety profile compares to other NSAIDs. While all NSAIDs carry some risk of side effects, diflunisal has some unique characteristics:

• Lower risk of gastrointestinal bleeding compared to some other NSAIDs
• Distinct mechanism of liver injury compared to aspirin and other salicylates
• Potential benefits in specific conditions like familial amyloidosis

Does diflunisal have any advantages over other NSAIDs? While diflunisal may offer some benefits in terms of its unique pharmacological properties and potential applications in rare diseases like familial amyloidosis, its overall safety profile is generally comparable to other NSAIDs. The choice of NSAID should be based on individual patient factors, medical history, and the specific condition being treated.

Special Considerations and Precautions for Diflunisal Use

When prescribing or taking diflunisal, several important considerations and precautions should be kept in mind:

• Cardiovascular risk: Like all NSAIDs, diflunisal may increase the risk of cardiovascular events, especially with long-term use or in patients with pre-existing cardiovascular conditions.
• Renal function: NSAIDs can affect kidney function, so caution is advised in patients with renal impairment.
• Gastrointestinal risk: Although diflunisal may have a lower risk of GI bleeding compared to some other NSAIDs, patients with a history of peptic ulcer disease or gastrointestinal bleeding should use it with caution.
• Drug interactions: Diflunisal may interact with other medications, including anticoagulants, antihypertensives, and certain antidepressants.
• Pregnancy and breastfeeding: The safety of diflunisal during pregnancy and lactation has not been firmly established, and its use should be carefully considered in these populations.

Are there any specific patient groups who should avoid diflunisal? Patients with a known hypersensitivity to NSAIDs, those with severe liver disease, and individuals with a history of asthma exacerbated by aspirin or other NSAIDs should generally avoid diflunisal. Additionally, caution is advised in elderly patients, who may be more susceptible to adverse effects.

Monitoring and Follow-up

To ensure safe and effective use of diflunisal, regular monitoring and follow-up are essential. This may include:

• Periodic assessment of pain relief and functional improvement
• Monitoring of blood pressure and renal function
• Evaluation of gastrointestinal symptoms
• Liver function tests, especially in the early stages of treatment
• Assessment of cardiovascular risk factors

How often should patients on long-term diflunisal therapy be evaluated? The frequency of follow-up evaluations may vary depending on individual patient factors, but generally, patients on long-term diflunisal therapy should be assessed at least every 3-6 months, with more frequent monitoring if risk factors or concerns are present.

Future Perspectives and Research Directions for Diflunisal

While diflunisal has been in clinical use for several decades, ongoing research continues to explore its potential applications and refine our understanding of its mechanisms of action. Some areas of current interest include:

• Further investigation of its role in treating familial amyloidosis
• Exploration of potential neuroprotective effects
• Development of novel formulations or delivery methods to enhance efficacy and reduce side effects
• Studies on long-term safety and efficacy in specific patient populations

Could diflunisal have applications beyond its current indications? Emerging research suggests that diflunisal may have potential benefits in neurological conditions and certain rare diseases. However, more extensive clinical trials are needed to confirm these findings and establish new therapeutic applications.

Challenges and Opportunities

As with many long-established medications, diflunisal faces both challenges and opportunities in the evolving landscape of pain management and anti-inflammatory therapy:

• Competition from newer NSAIDs and alternative pain management strategies
• Increasing focus on personalized medicine and tailored treatment approaches
• Growing awareness of the long-term risks associated with NSAID use
• Potential for repurposing in rare diseases and novel therapeutic areas

How might the role of diflunisal evolve in clinical practice? As our understanding of pain mechanisms and inflammatory processes continues to advance, the positioning of diflunisal in treatment algorithms may shift. Its unique properties, particularly in relation to amyloidosis, may lead to increased interest in specific clinical scenarios or patient populations.

In conclusion, diflunisal remains an important tool in the management of chronic arthritis and acute pain. Its distinct pharmacological profile and potential applications in rare diseases make it a valuable option in the NSAID arsenal. However, as with all medications, its use must be carefully considered in the context of individual patient factors, potential risks, and alternative treatment options. Ongoing research and clinical experience will continue to refine our understanding of diflunisal’s place in modern therapeutic practice.

Diflunisal – LiverTox – NCBI Bookshelf

Last Update: January 3, 2018.

OVERVIEW

Introduction

Diflunisal is a salicylic acid derivative that is used in the therapy of chronic arthritis and mild to moderate acute pain. Diflunisal has been linked mild, transient elevations in serum aminotransferase levels during therapy as well as to rare instances of idiosyncratic drug induced liver disease.

Background

Diflunisal (dye floo’ ni sal) is a difluorophenol derivative of salicylic acid that has antiinflammatory, analgesic and antipyretic actions similar to aspirin. Diflunisal is metabolized by the liver, but not to salicylate. Diflunisal is considered a nonsteroidal antiinflammatory agent (NSAID) and is believed to act by inhibition of tissue cyclo-oxygenases (Cox-1 and Cox-2), which leads to a decrease in synthesis of proinflammatory prostaglandins, important mediators in inflammatory and pain pathways. Diflunisal was approved for use in the United States in 1982 and current indications are for chronic arthritis due to osteoarthritis or rheumatoid arthritis and for mild-to-moderate pain. Diflunisal has been shown to stabilize transthyretin variants which are involved in the pathogenesis of amyloidosis, which has led to the off-label use of diflunisal in familial amyloidosis. Diflunisal is available as tablets of 500 mg in generic forms and formerly under the brand name of Dolobid. Diflunisal is available by prescription only. The recommended regimen in adults is an initial dose of 1000 mg, followed by 500 to 1500 mg daily in two to three divided doses based upon response and tolerance. Diflunisal, like most NSAIDs, is generally well tolerated, but side effects can include intestinal upset, nausea, heartburn, headache, somnolence, dizziness, peripheral edema and hypersensitivity reactions.

Hepatotoxicity

Diflunisal therapy is reported to be associated with a low rate of asymptomatic and transient serum aminotransferase elevations, which may resolve even with drug continuation. Marked aminotransferase elevations (>3 fold elevated) occur rarely. Clinically apparent liver injury with jaundice from diflunisal is uncommon; only case reports have been published. The clinical and histologic features of diflunisal hepatotoxicity, however, are distinct and resemble an immunoallergic hepatitis, which is quite different from the liver injury that occurs with aspirin or other salicylates (Case 1). The latency to onset ranges from 1 to 4 weeks and the pattern of enzyme elevations is typically cholestatic, but can also be mixed. Most patients have immunoallergic manifestations such as rash, fever and arthralgias; eosinophilia or atypical lymphocytosis are also common. A history of aspirin allergy has not been reported among cases with allergic reactions to diflunisal. Diflunisal is not a commonly used drug and is not mentioned in large case series on drug induced liver injury or acute liver failure.

Likelihood score: C (probable cause of clinically apparent liver injury).

Mechanism of Liver Injury

The mechanism of diflunisal hepatotoxicity is likely hypersensitivity and is different from that of acetylsalicylic acid (aspirin).

Outcome and Management

Severity ranges from asymptomatic elevations in serum aminotransferase levels, to symptomatic cholestatic hepatitis with or without jaundice. It is not clear if there is cross sensitivity to liver injury between diflunisal and other salicylates.

Drug Class: Salicylates, Nonsteroidal Antiinflammatory Drugs

CASE REPORT

CHEMICAL FORMULA AND STRUCTURE

CITED REFERENCE

1.

Geoffroy P, Carteret E, Salagnac V, Kalis B, Zeitoun P. Therapie. 1987;42:253. [Hepatitis caused by diflunisal (Dolobis). Apropos of a case] French. [PubMed: 3617008]

ANNOTATED BIBLIOGRAPHY

References updated: 03 January 2018

• Zimmerman HJ. Drugs used to treat rheumatic and musculospastic disease. Chapter 19: The NSAIDS. In Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott Williams & Williams, 1999, pp. 517-41.

  (Review of hepatotoxicity of NSAIDs published in 1999).

• Lewis JH, Stine JG. Nonsteroidal anti-inflammatory drugs and leukotriene receptor antagonists. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 369-402.

  (Expert review of liver injury caused by NSAIDs mentions that diflunisal is a difluorophenol derivative of salicylate and can cause cholestatic injury but that there have been few published reports).

• Grosser T, Smyth E, FitzGerald GA. Anti-inflammatory, antipyretic, and analgesic agents; pharmacotherapy of gout. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 959-1004.

  (Textbook of pharmacology and therapeutics).

• Warren JS. Diflunisal-induced cholestatic jaundice. Br Med J. 1978;2:736–7. [PMC free article: PMC1607620] [PubMed: 698699]

  (64 year old man who was previously treated with multiple NSAIDs without relief was placed on diflunisal [while also receiving indomethacin] and developed itching 5 days later [bilirubin 3.4 mg/dL, AST 120 U/L, Alk P 780 U/L] without eosinophilia, rash or fever, and resolving within 2 months of stopping).

• Brogden RN, Heel RC, Pakes GE, Speight TM, Avery GS. Diflunisal: a review of its pharmacological properties and therapeutic use in pain and musculoskeletal strains and sprains and pain in osteoarthritis. Drugs. 1980;19:84–106. [PubMed: 6988202]

  (Review of pharmacology, pharmacokinetics, clinical efficacy and safety of diflunisal; “no consistent alteration in tests of renal or liver function have been reported”).

• Umbenhauer ER. Diflunisal in the treatment of the pain of osteoarthritis. Summary of clinical studies. Pharmacotherapy. 1983;3:55S–60S. [PubMed: 6344040]

  (Review of results of 5 controlled studies of diflunisal vs aspirin or ibuprofen or placebo in 1218 patients; side effects were more frequent with aspirin and ibuprofen than diflunisal but discontinuations for AST elevations occurred in 0.9% of diflunisal- vs 1% of aspirin- and none of ibuprofen-treated patients).

• Geoffroy P, Carteret E, Salagnac V, Kalis B, Zeitoun P. Therapie. 1987;42:253. [Hepatitis caused by diflunisal (Dolobis). Apropos of a case] French. [PubMed: 3617008]

  (65 year old woman developed mild cholestatic jaundice 5 days after a 3 day course of diflunisal [bilirubin 2.6 mg/dL, AST 60 U/L and Alk P 1216 U/L, eosinophilia], resolving in several months: Case #1).

• Cook DJ, Achong MR, Murphy FR. Three cases of diflunisal hypersensitivity. CMAJ. 1988;138:1029–30. [PMC free article: PMC1267889] [PubMed: 2967101]

  (Three patients with onset of fever, rash and eosinophilia [23-31%] or atypical lymphocytosis after 2-4 weeks of diflunisal therapy responding to oral and topical steroids; with bilirubin levels of normal, 0.9 and 4.9 mg/dL, ALT normal, 500 and 810 U/L, Alk P 185, 545 and 349 U/L).

• Zimmerman HJ. Update of hepatotoxicity due to classes of drugs in common clinical use: non-steroid drugs, anti-inflammatory drugs, antibiotics, antihypertensives, and cardiac and psychotropic agents. Semin Liver Dis. 1990;10:322–8. [PubMed: 2281340]

  (Extensive review article on liver injury due to NSAIDs; diflunisal said to cause cholestatic injury rarely).

• Muller AF, Toghill PJ, Smith P. ‘Relapse’ of chronic active hepatitis–not always what it seems. Postgrad Med J. 1996;72:431–2. [PMC free article: PMC2398514] [PubMed: 8935606]

  (Patient with typical autoimmune hepatitis treated with excellent response with steroids and then switched to azathioprine alone for 6 years; developed jaundice 1 month after starting diflunisal [bilirubin 2. 9 mg/dL, ALT 668 U/L, Alk P 262 U/L], resolving upon stopping).

• Björnsson E, Jerlstad P, Bergqvist A, Olsson R. Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden. Scand J Gastroenterol. 2005;40:1095–101. [PubMed: 16165719]

  (Survey of all cases of drug induced liver injury with fatal outcome from Swedish Adverse Drug Reporting system from 1966-2002; among 103 cases, none were attributed to diflunisal).

• Rostom A, Goldkind L, Laine L. Nonsteroidal anti-inflammatory drugs and hepatic toxicity: a systematic review of randomized controlled trials in arthritis patients. Clin Gastroenterol Hepatol. 2005;3:489–98. [PubMed: 15880319]

  (Review of randomized clinical trials of NSAIDS for frequency of adverse events; ALT elevations above 3 fold ULN occurred in 0.43% of ibuprofen, 0.43% naproxen, 0.42% celecoxib, 1.8% rofecoxib, 3.55% diclofenac and 0.29% of placebo recipients; review deals largely with commonly used NSAIDs and does not mention diflunisal).

• Lapeyre-Mestre M, de Castro AM, Bareille MP, et al. Non-steroidal anti-inflammatory drug-related hepatic damage in France and Spain: analysis from national spontaneous reporting systems. Fundam Clin Pharmacol. 2006;20:391–5. [PubMed: 16867024]

  (Analysis of reports of liver injury from NSAIDs from France and Spain from 1982-2001; diflunisal is not listed in tables of adverse event reports from NSAIDs).

• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J., Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135:1924–34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US collected from 2004 to 2008, NSAIDs were implicated as a sole agent in 8 cases [4 diclofenac, 2 celecoxib, 1 meloxicam and 1 oxaprozin] and as one of several agents in 3 cases [1 diclofenac, 1 celecoxib, 1 ibuprofen]; diflunisal is not mentioned).

• Reuben A, Koch DG, Lee WM., Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52:2065–76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, of which 7 were due to NSAIDs, including 4 attributed to bromfenac, 2 to diclofenac and 1 to etodolac, but none to diflunisal).

• Gulmez SE, Larrey D, Pageaux GP, Lignot S, Lassalle R, Jové J, Gatta A, et al. Transplantation for acute liver failure in patients exposed to NSAIDs or paracetamol (acetaminophen): the multinational case-population SALT study. Drug Saf. 2013;36:135–44. [PMC free article: PMC3568201] [PubMed: 23325533]

  (Analysis of cases of idiopathic acute liver failure undergoing liver transplantation in 52 centers in Europe between 2005 and 2007, found 40 had been exposed to an NSAID, but none to diflunisal).

• Lapeyre-Mestre M, Grolleau S, Montastruc JL., Adsociation Française des Centres Régionaux de Pharmacovigilance (CRPV). Adverse drug reactions associated with the use of NSAIDs: a case/noncase analysis of spontaneous reports from the French pharmacovigilance database 2002-2006. Fundam Clin Pharmacol. 2013;27:223–30. [PubMed: 21929527]

  (Analysis of 42,389 spontaneous serious adverse event reports to the French Pharmacovigilance database on 8 NSAIDs between 2002 and 2006; liver adverse events were most frequent with nimesulide [0.15 per million daily doses] compared to diclofenac [0.09], ketoprofen [0.09] piroxicam [0.06], naproxen [0.04], meloxicam [0.03], and tenoxicam [0.03]; diflunisal is not discussed).

• Berk JL, Suhr OB, Obici L, Sekijima Y, Zeldenrust SR, Yamashita T, Heneghan MA, et al. Diflunisal Trial Consortium. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA. 2013;310:2658–67. [PMC free article: PMC4139164] [PubMed: 24368466]

  (Among 130 patients with familial amyloid polyneuropathy treated with diflunisal [250 mg] or placebo twice daily for 2 years, disease progression was less with diflunisal therapy and the overall rates of adverse events were similar with no mention of ALT elevations or hepatotoxicity and no liver related serious adverse events or deaths).

• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, Presentation and Outcomes in Patients with Drug-Induced Liver Injury in the General Population of Iceland. Gastroenterology. 2013;144:1419–25. [PubMed: 23419359]

  (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, 6% of which were attributed to NSAIDS, but none to diflunisal).

• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A, Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America. An analysis of published reports. Ann Hepatol. 2014;13:231–9. [PubMed: 24552865]

  (Systematic review of literature of drug induced liver injury from Latin American countries published between 1996 and 2012 identified 176 cases; while NSAIDs were the most frequent class of drugs implicated (n=62: 32%], no case was attributed to diflunisal).

• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015;148:1340–52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 20 cases [2%] were attributed to NSAIDs, but none to diflunisal).

• Sekijima Y, Tojo K, Morita H, Koyama J, Ikeda S. Safety and efficacy of long-term diflunisal administration in hereditary transthyretin (ATTR) amyloidosis. Amyloid. 2015;22:79–83. [PubMed: 26017328]

  (Among 40 Japanese patients with familial amyloidosis treated with diflunisal [500 mg daily] for up to 10 years, 3 patients stopped therapy because of side effects [thrombocytopenia and renal dysfunction which improved upon stopping]; no mention of ALT elevations or hepatotoxicity).

Dolobid: Uses, Side effects, Reviews, Composition, Expert Advice and Precautions

About Dolobid Products

Diclofenac+Serratiopeptidase is used for pain relief.

Common

Side Effects of Dolobid are Nausea, Vomiting, Diarrhea, Dizziness, Headache, Vertigo, Dyspepsia, Abdominal pain, Flatulence, Decreased appetite, Increased transaminase level in blood, Rash.

Diclofenac + Serratiopeptidase is a combination of two medicines: Diclofenac + Serratiopeptidase1 and Diclofenac + Serratiopeptidase2. Diclofenac + Serratiopeptidase1 is a non-steroidal anti-inflammatory drug (NSAID) which works by blocking the release of certain chemical messengers in the brain that cause pain and inflammation (redness and swelling). Diclofenac + Serratiopeptidase2 is an enzyme which works by breaking down abnormal proteins at the site of inflammation and promotes healing.

Patient Concerns about Dolobid Products

Frequently asked questions about Dolobid Products

Q. What is Dolobid 50mg/15mg Tablet?

Dolobid 50mg/15mg Tablet is a combination of two medicines: Diclofenac and Serratiopeptidase. This medication helps in relieving pain and inflammation. It works by lowering the levels of chemical substances in the body that cause pain and inflammation.

Q. Is it safe to use Dolobid 50mg/15mg Tablet?

Yes, Dolobid 50mg/15mg Tablet is safe for most of the patients. However, in some patients it may cause common unwanted side effects like nausea, vomiting, stomach pain, heartburn and diarrhea. Inform your doctor as soon as possible if you experience any persistent problem due to the medication.

Q. Can I stop taking Dolobid 50mg/15mg Tablet when my pain is relieved?

Dolobid 50mg/15mg Tablet is usually used for short term and can be discontinued when the pain is relieved. However, Dolobid 50mg/15mg Tablet should be continued if your physician has advised you to do so.

Q. Can the use of Dolobid 50mg/15mg Tablet cause nausea and vomiting?

Yes, the use of Dolobid 50mg/15mg Tablet can cause nausea and vomiting. Taking it with milk, food or with antacids can prevent nausea. Avoid taking fatty or fried foods along with this medicine. In case of vomiting, drink plenty of water or other fluids by taking small frequent sips. Talk to your doctor if vomiting persists and you notice signs of dehydration, like dark colored and strong-smelling urine and a low frequency of urination. Do not take any other medicines without speaking to a doctor.

Q. Can the use of Dolobid 50mg/15mg Tablet cause dizziness?

Yes, the use of Dolobid 50mg/15mg Tablet can cause dizziness (feeling faint, weak, unsteady or lightheaded) in some patients. If you feel dizzy or lightheaded, it is better to rest for some time and resume once you feel better.

Q. Are there any specific contraindications associated with the use of Dolobid 50mg/15mg Tablet?

The use of Dolobid 50mg/15mg Tablet is considered to be harmful in patients with known allergy to any of the components or excipients of this medicine or in patients with known allergy to other painkillers (NSAIDs). The use of this medicine should preferably be avoided in patients with a history of stomach ulcers or in patients with active, recurrent stomach ulcer/bleeding. It should also be avoided in patients with a history of heart failure, high blood pressure, and liver or kidney disease.

Q. Can I take Dolobid 50mg/15mg Tablet with Vitamin B-complex?

Dolobid 50mg/15mg Tablet can be taken with Vitamin B-complex preparations. While Dolobid 50mg/15mg Tablet helps to relieve pain, Vitamin B-complex can help to correct the vitamin deficiency that might be causing the symptoms.

Q. Can I take Dolobid 50mg/15mg Tablet for stomach pain?

No, Dolobid 50mg/15mg Tablet preferably should not be taken for stomach pain without consulting a physician. This drug can increase stomach acid secretion which may aggravate an unknown underlying condition.

Q. What is the storage condition for the Dolobid 50mg/15mg Tablet?

Keep this medicine in the container or the pack it came in, tightly closed. Store it according to the instructions mentioned on the pack or label. Dispose of the unused medicine. Make sure it is not consumed by pets, children and other people.

Information last updated by Dr. Varun Gupta, MD Pharmacology on 13th Oct 2022.
The medicine details are for information purpose only. Consult a doctor before taking any medicine.

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Indomethacin Sopharma: instructions, price, analogues | Sopharma

Indomethacin Sopharma (active ingredient – indomethacin) is an NSAID, which is most often used to relieve pain and morning stiffness in rheumatic diseases, including rheumatoid arthritis (RA). It can be used to relieve pain in dysmenorrhea and acute musculoskeletal pain. Indomethacin is also used to relieve pain and swelling after orthopedic surgery and is the first line of treatment for some rare forms of headache, such as chronic paroxysmal hemicrania and episodic paroxysmal hemicrania (Pareja J.A. et al., 2001).

Indomethacin Sopharma is available as 10% ointment, tablets and rectal suppositories. The ointment is used mainly as an additional local drug for the symptomatic treatment of lesions of the musculoskeletal system, both traumatic and inflammatory, accompanied by pain and swelling. Tablets and suppositories are used both in the complex therapy of rheumatological pathology, and to alleviate pain in injuries, dysmenorrhea, radiculoneuritis, after surgical interventions.

Indomethacin is also used to relieve pain in relapses of gouty arthritis and, somewhat less frequently, to relieve acute postoperative pain (Moore R.A. et al. , 2004).

Indomethacin was synthesized in 1963, approved by the FDA as an NSAID for use in the USA in 1965. The anti-inflammatory effect of indomethacin is mainly mediated by the inhibition of COX, a key enzyme catalyzing the synthesis of prostaglandins from arachidonic acid (Hao L. et al., 2018) .

According to the chemical structure, indomethacin is 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid (Helleberg L., 1981).

After oral administration, the drug is absorbed rapidly and completely. As a rule, C _max in blood plasma is reached after 1-2 hours, the simultaneous intake of food increases the time of onset of C _max . When administered rectally, it causes a faster achievement of C _max of the active substance in the blood plasma. However, the absorption of indomethacin with rectal administration is somewhat lower than with oral administration. In blood plasma up to 90% indomethacin binds to albumin.

Indomethacin is found in synovial fluid, breast milk and crosses the placenta in significant amounts. It is metabolized to O-desmethylindomethacin, N-deschlorobenzoylindomethacin and O-desmethyl-N-deschlorobenzoylindomethacin, which lack anti-inflammatory activity and are found in significant amounts in plasma. About 60% of the oral dose is excreted in the urine mainly in the glucuronidated form, while about 40% enters the intestine with bile and then is excreted in the feces, while part of the drug is subject to enterohepatic recirculation (excreted in the bile, reabsorbed in the intestine) (Helleberg L., 1981).

Use of

Indomethacin Sopharma for gout

Gout is a common disease that predominantly affects middle-aged men. The peak incidence occurs at the age of 50–60 years.

The prevalence of gout among women increases in the postmenopausal period, and the risk of gout increases with the use of diuretics and the presence of concomitant chronic renal failure (CRF). This disease is characterized by the occurrence of recurrent episodes of acute arthritis.

Risk factors for gout include obesity, impaired kidney function, alcohol use, use of diuretics, a diet rich in meat, seafood, and foods/drinks high in fructose.

Another important point is that patients with gout have an increased risk of developing cardiovascular disease. In addition, gouty arthritis significantly reduces the quality of life of patients. Acute gouty arthritis is the most common form of inflammatory arthritis. The main role in its development belongs to prostaglandins.

Acute gouty arthritis is characterized by the development of a sharply painful swelling of the joint, the skin over the joint is reddened, its temperature rises locally. Pain and swelling peak within 24 hours of the onset of an attack of recurrent acute gouty arthritis. The joints of the lower extremities are mainly affected, in particular the metatarsophalangeal joint.

The American College of Rheumatology (2012) recommends that NSAIDs, including indomethacin, colchicine, and prednisone, be used alone or as part of complex regimens for the management of acute gouty arthritis.

COX-1 is constitutively expressed in most cells and is responsible for homeostatic functions, including platelet aggregation and regulation of renal blood flow, and is involved in the initial phase of the inflammatory response. COX-2 is induced by pro-inflammatory mediators, and its activation occurs several hours after the start of the inflammatory response cascade. Indomethacin inhibits both of these enzymes and thus both the initial phase of the inflammatory response and subsequent inflammatory responses. The effectiveness of indomethacin in reducing the severity of pain and swelling in acute gouty arthritis has been confirmed in clinical studies (Lin T. M. et al., 2019).

Indomethacin Sopharma : possible use in the treatment of postoperative pain

The search for effective pain relief and relief of inflammatory response in the postoperative period is an important task of modern surgery. One study conducted in the USA found that postoperative pain is the main cause of restless behavior of patients before surgery (57% of the patients surveyed). In a survey of 5150 surgical patients in the UK, it was recorded that 61% of respondents experienced postoperative pain. It is assumed that effective relief of acute postoperative pain can reduce the likelihood of developing chronic pain syndrome (Moore R.A. et al., 2004).

One study (n=52) demonstrated similar efficacy of rectal indomethacin and IM ketorolac for postoperative pain relief in patients after cholecystectomy for cholecystolithiasis (Forse A. et al., 1996).

Potential applications of indomethacin

Indomethacin also has therapeutic potential in various eosinophilic skin diseases, in particular eosinophilic pustular folliculitis, in which the main mechanism of the inflammatory response is the interaction of prostaglandin D2 and the chemoattractant receptor expressed on Th3 cells (CRTh3) (T-helper ah type 2).

Eosinophilic pustular folliculitis (EPF) is an eosinophilic inflammatory skin disease characterized by pruritic follicular papulopustules that tend to form a group of annular configurations on the face and sometimes on the trunk and extremities. Histopathological changes include eosinophil infiltration of hair follicles and adjacent skin. Unusually, EPF also affects the palms and soles despite the absence of hair follicles. The main treatment for EPF are topical and systemic glucocorticoids. At the same time, in some patients, the use of glucocorticoids is ineffective.

Prostaglandin D2 exhibits a wide range of biological effects, including vasodilation, bronchoconstriction, inhibition of platelet aggregation and regulation of the sleep-wake cycle, and is also involved in allergic inflammation by stimulating eosinophilia and the production of Th3-type cytokines. Prostaglandin D2 is responsible for the development of skin inflammation in IgE-mediated skin diseases and contact allergies.

The biological activity of prostaglandin D2 is mediated by its binding to the homologous molecule of the chemoattractant receptor expressed on Th3 cells (CRTh3) and the prostanoid DP2 receptor. Expression of CRTh3 on eosinophils is increased in atopic dermatitis, chronic urticaria, and soft tissue injury (eg, contusion). CRTh3 antagonists reduce the severity of inflammatory changes in the skin in IgE-mediated skin diseases and help reduce the severity of skin infiltration by eosinophils. As a result of one study, indomethacin was found to be effective in the treatment of eosinophilic pustular folliculitis, as well as angiolymphoid hyperplasia with eosinophilia. Treatment with indomethacin resulted in a decrease in the expression of CRTh3 on the eosinophil cell membrane and a decrease in the migration of eosinophils into the skin. In addition, basophils also express CRTh3, and indomethacin reduces their migration to peripheral tissues. At the same time, diclofenac, another COX inhibitor, did not suppress the migration of eosinophils into the skin in studies (Kataoka N. et al., 2013).

Obesity has become an important public health problem in recent decades. Over ⅔ of US adults are overweight or obese. Obesity increases the risk of diseases such as type 2 diabetes, cardiovascular disease, gallbladder disease, osteoarthritis, and even some types of cancer.

Currently FDA-approved drugs to treat obesity either suppress appetite or reduce intestinal absorption of nutrients (orlistat). However, these drugs cause serious cardiovascular and/or psychiatric side effects and weight gain may occur if they are discontinued.

A number of studies in vivo reported the effect of indomethacin on obesity. As a result of the study, it was found that the use of indomethacin prevented the development of obesity caused by a high fat diet in C57BL/6 mice, but did not prevent hyperglycemia and impaired glucose tolerance. These data indicate the need for further research to explore the potential use of indomethacin in the treatment of obesity (Hao L., 2018).

Indomethacin Sopharma : Patient-Friendly Formulation for Every Case

Topical NSAIDs provide pain relief in acute musculoskeletal pain, including conditions such as sprains, bruises, and trauma (Derry S. et al., 2015). The most common cause of acute musculoskeletal pain is an injury to the ligamentous apparatus of the ankle joint and muscle injuries (sprains, bruises). These conditions often tend to resolve on their own within 2–3 weeks. However, in the acute period, they are characterized by a significant severity of pain, which limits physical activity. Topical NSAIDs penetrate the skin and underlying musculoskeletal apparatus, reduce the severity of pain and swelling. At the same time, with topical application, the level of the active substance of NSAIDs in the blood plasma is much lower than when it is taken orally. This minimizes the risk of side effects.

A review of three studies (n=341) confirms the efficacy of topical indomethacin in acute musculoskeletal pain. When compared with placebo, indomethacin showed better efficacy in reducing the severity of pain symptoms (Derry S. et al., 2015).

Indomethacin can be used in the treatment of rheumatoid arthritis in both oral and rectal forms. Studies have shown that 100 mg rectal indomethacin is as effective as the same dose orally in reducing morning stiffness and pain in patients with rheumatoid arthritis (Baber N. et al., 1980).

Safety of indomethacin use

For the treatment of chronic pain, the maximum recommended daily oral dose of indomethacin is 200 mg (instruction of the Ministry of Health of Ukraine). It is believed that the incidence of side effects when taking indomethacin is slightly higher compared to other NSAIDs (Moore R.A. et al., 2004). The most common adverse reactions are gastrointestinal disturbances (including mucosal ulceration, upper gastrointestinal bleeding and diarrhoea), headache, and dizziness. Less common adverse reactions: daytime sleepiness, insomnia, convulsions, mental disorders, hypertension, hyperglycemia, peripheral neuropathy and intestinal stricture. The risk of side effects is significantly lower with short-term use of the drug, for example, in the treatment of postoperative pain (Moore R.A. et al., 2004). In addition, the risk of side effects is reduced when the drug is applied topically (Derry S. et al., 2015).

Indomethacin Sopharma : conclusion

Indomethacin Sopharma is an NSAID characterized by antipyretic, analgesic and anti-inflammatory effects. This drug is available in the form of tablets, suppositories and 10% ointment, which allows you to choose the method of application that is most optimal for a particular clinical situation. Indomethacin has been used in the treatment of mild to moderate pain since the mid-1960s. Its effectiveness in the symptomatic treatment of gouty arthritis, rheumatoid arthritis, acute musculoskeletal pain and various other pain conditions has been proven in clinical studies. Today, clinical studies are being conducted on other potential uses of indomethacin (Nalamachu S., Wortmann R., 2014).

Indomethacin instructions for use, price: Analogues, side effects, composition POSSIBLE SIDE EFFECTS. A SPECIALIST’S CONSULTATION IS REQUIRED.PainkillersSuppositories for inflammationPills for inflammation 110

World Health Organization statistics show that 30 million people worldwide take non-steroidal anti-inflammatory drugs (NSAIDs) every day. These drugs came in second place in the use after antibiotics. Now more than 1000 names of drugs of this group are known.

In this article we talk about Indomethacin, which was synthesized in the mid-60s of the last century. Among the group of NSAIDs, it stands out for its powerful anti-inflammatory action. Pharmacist Kristina Khokhrina answered questions about the composition and forms of release, explained why it helps and why it is rarely prescribed.

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Indomethacin: composition

Indomethacin’s active ingredient is the substance of the same name, which belongs to the derivatives of indoleacetic acid. The chemical structure of indomethacin is related to diclofenac and ketorolac.

Indomethacin inhibits the synthesis of prostaglandins, which control the inflammatory process. And inflammation is accompanied by pain, swelling, fever. Thus, Indomethacin acts as an analgesic, antipyretic and anti-inflammatory agent. In addition, the drug reduces blood clotting.

Indomethacin penetrates 80-90% into inflamed tissues. The substance is well absorbed through the skin, mucous membranes of the stomach and intestines, penetrates into the joints through the synovial membrane.

The drug is used for:

• pain in the joints of rheumatic and non-rheumatic origin
• pain syndrome after injuries and operations
• tendon injury and inflammation
• myalgia and neuralgia
• dysmenorrhea

Indomethacin – symptomatic: relieves pain and inflammation at the time of application. It does not affect the causes of the disease.

Presented in pharmacies in the following dosage forms:

• tablets 25 mg
• topical ointment 10%
• rectal suppositories 50 mg and 100 mg

Pharmacy staff are sometimes asked: “Are there injections and eye drops with indomethacin?”. Indomethacin is not available in injections, but eye drops are manufactured by Bausch Health under the name Indocollir.

Indomethacin ointment: what it is used for

Indomethacin ointment penetrates the skin well. The composition of the product includes dimexide, which improves the penetration of the active substance. With regular use, indomethacin accumulates in muscles, joints and synovial fluid.

What the ointment helps with: relieves pain and swelling, improves range of motion and reduces swelling and stiffness of the joints.

What is it used for? Ointment Indomethacin has proven itself in the treatment of:

• gout, arthritis
• osteochondrosis, sciatica
• myalgia and neuralgia
• sciatica, lumbago
• injuries and inflammations of muscles, tendons and ligaments

The ointment is available from a pharmacy without a prescription. The duration of treatment is no more than 10-14 days without consulting a doctor.

Indomethacin suppositories for prostatitis

Most manufacturers do not indicate in the instructions for use of suppositories with Indomethacin such an indication as prostatitis.

Only suppositories of the two companies “Altpharm” LLC (Russia) and “PHARMAPRIM” LLC (Moldova) are indicated as an adjuvant for inflammation in the small pelvis, including prostatitis.

Suppositories are administered after a bowel movement deep into the rectum. The maximum daily dose is 200 mg. For maintenance therapy, the dose is 50-100 mg at night, with course treatment – 50 mg 2-3 times a day.

Indomethacin for hemorrhoids

Hemorrhoids are contraindications for Indomethacin. The remedy causes an exacerbation of the disease, provokes hemorrhoidal bleeding. When using the drug in suppositories, side reactions occur: irritation and heaviness in the anorectal region.

Indomethacin during pregnancy

Indomethacin suppositories and tablets are contraindicated for pregnant women. The drug can cause oligohydramnios, as well as impaired renal function in infants. Ointment up to 20 weeks is allowed only on the recommendation of doctors.

Indomethacin passes into breast milk. If, according to indications, it cannot be replaced with a suitable analogue, then breastfeeding is stopped for the duration of treatment.

Indomethacin side effects

NSAIDs, including Indomethacin, are associated with serious side effects. Their use for months and years damages the gastric mucosa. This is fraught with the appearance of erosions and ulcers, in severe cases – bleeding and perforation.

If long-term use of Indomethacin is indicated for indications, then it is prescribed “under the guise” of drugs that reduce the production of hydrochloric acid. For example, omeprazole.

Other adverse reactions during treatment with Indomethacin:

• abdominal pain, diarrhea
• nausea, vomiting, heartburn
• swelling, increased pressure
• dizziness and headache
• shortness of breath, bronchospasm
• allergic skin reactions
• bleeding (gingival, uterine, hemorrhoidal, gastrointestinal)

To reduce the risk of side effects, indomethacin is prescribed in the lowest effective doses and in short courses.

Indomethacin analogues

NSAIDs are analogues of Indomethacin. Ointments and gels are available without a prescription. They are used for no more than 2 weeks without consulting a doctor.

Indomethacin has a direct analogue – Metindol retard. It is available in long-acting tablets with a dose of indomethacin 75 mg. The list of indications for use is less than that of Indomethacin tablets. It is used strictly according to the doctor’s prescription for rheumatic diseases of the spine, joints and soft tissues, gouty arthritis, pain after injuries and operations.

The following analogues contain other active ingredients:

• Ibuprofen
• Diclovit, Diclofenac, Voltaren
• Nise, Nimesulide
• Naproxen, Motrin, Nalgezin
• Piroxicam
• Amelotex, Meloxicam
• Aceclofenac
• Ketorol, Ketorolac, Ketanov
• Ketoprofen, Ketonal

If Indomethacin is prescribed by a doctor, then without his consultation it is better not to replace the medicine with analogues with a different composition.

Indomethacin or Diclofenac: which is better

The drugs have related chemical formulas and have the strongest anti-inflammatory effect of the entire group of NSAIDs. The effectiveness of Indomethacin and Diclofenac has been proven on a large amount of clinical material.

Indomethacin gives the best result in the treatment of ankylosing spondylitis and degenerative diseases of the spine, as well as in acute attacks of gout.

But it is considered more toxic: it severely harms the stomach and intestines, and long-term use increases the risk of bleeding and destruction of cartilage in the joints.

It is safer to take Diclofenac. The drug is allowed for children from 6 years old, and Indomethacin – only from 14. Diclofenac has a larger selection of dosage forms: tablets, ointments, gels, suppositories, injections.

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All products Ibuprofen 25 reviews

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Summary

• Indomethacin is a non-hormonal anti-inflammatory drug with proven efficacy. It consists of the active substance of the same name and auxiliary components.
• Indomethacin ointment relieves pain and swelling, improves range of motion and reduces swelling and stiffness of the joints.
• Indomethacin suppositories are used as an aid in prostatitis.
• It is contraindicated in hemorrhoids, as it aggravates the course of the disease.
• Indomethacin suppositories and tablets are contraindicated for use in pregnant women. Ointment up to 20 weeks is allowed only on the recommendation of doctors.
• One of the “strongest” NSAIDs, but with serious side effects. Available in the form of several dosage forms: tablets, ointment, suppositories.
• Indomethacin has 1000 analogues. Only a doctor can correctly choose the optimal remedy, taking into account the effectiveness, safety and history of the patient.

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