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Adomal

Adomal - General Information

A salicylate derivative and anti-inflammatory analgesic with actions and side effects similar to those of aspirin.

 

Pharmacology of Adomal

Adomal is a nonsteroidal drug with analgesic, anti-inflammatory and antipyretic properties. It is a peripherally-acting non-narcotic analgesic drug. Habituation, tolerance and addiction have not been reported. Adomal is a difluorophenyl derivative of salicylic acid. Chemically, diflunisal differs from aspirin (acetylsalicylic acid) in two respects. The first of these two is the presence of a difluorophenyl substituent at carbon 1. The second difference is the removal of the 0-acetyl group from the carbon 4 position. Adomal is not metabolized to salicylic acid, and the fluorine atoms are not displaced from the difluorophenyl ring structure.

 

Adomal for patients

Diflunisal, like other drugs of its class, is not free of side effects. The side effects of these drugs can cause discomfort and, rarely, there are more serious side effects such as gastrointestinal bleeding, which may result in hospitalization and even fatal outcomes.

NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) are often essential agents in the management of arthritis and have a major role in the treatment of pain, but they also may be commonly employed for conditions which are less serious.

Physicians may wish to discuss with their patients the potential risks and likely benefits of NSAID treatment, particularly when the drugs are used for less serious conditions where treatment without NSAIDs may represent an acceptable alternative to both the patient and physician.

 

Adomal Interactions

Oral Anticoagulants: In some normal volunteers, the concomitant administration of diflunisal and warfarin, acenocoumarol, or phenprocoumon resulted in prolongation of prothrombin time. This may occur because diflunisal competitively displaces coumarins from protein binding sites. Accordingly, when diflunisal is administered with oral anticoagulants, the prothrombin time should be closely monitored during and for several days after concomitant drug administration. Adjustment of dosage of oral anticoagulants may be required.

Tolbutamide: In diabetic patients receiving diflunisal and tolbutamide, no significant effects were seen on tolbutamide plasma levels or fasting blood glucose.

Hydrochlorothiazide: In normal volunteers, concomitant administration of diflunisal and hydrochlorothiazide resulted in significantly increased plasma levels of hydrochlorothiazide. Diflunisal decreased the hyperuricemic effect of hydrochlorothiazide.

Furosemide: In normal volunteers, the concomitant administration of diflunisal and furosemide had no effect on the diuretic activity of furosemide. Diflunisal decreased the hyperuricemic effect of furosemide.

Antacids: Concomitant administration of antacids may reduce plasma levels of diflunisal. This effect is small with occasional doses of antacids, but may be clinically significant when antacids are used on a continuous schedule.

Acetaminophen: In normal volunteers, concomitant administration of diflunisal and acetaminophen resulted in an approximate 50% increase in plasma levels of acetaminophen. Acetaminophen had no effect on plasma levels of diflunisal. Since acetaminophen in high doses has been associated with hepatotoxicity, concomitant administration of diflunisal and acetaminophen should be used cautiously, with careful monitoring of patients.

Concomitant administration of diflunisal and acetaminophen in dogs, but not in rats, at approximately 2 times the recommended maximum human therapeutic dose of each (40 to 52 mg/kg/day of diflunisal/acetaminophen) resulted in greater gastrointestinal toxicity than when either drug was administered alone. The clinical significance of these findings has not been established.

Methotrexate: Caution should be used if diflunisal is administered concomitantly with methotrexate. Nonsteroidal anti-inflammatory drugs have been reported to decrease the tubular secretion of methotrexate and to potentiate its toxicity.

Cyclosporine: Administration of nonsteroial anti-inflammatory drugs concomitantly with cyclosporine has been associated with an increase in cyclosporine-induced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs should be used with caution in patients taking cyclosporine, and renal function should be carefully monitored.

Nonsteroidal Anti-Inflammatory Drugs

The administration of diflunisal to normal volunteers receiving indomethacin decreased the renal clearance and significantly increased the plasma levels of indomethacin. In some patients the combined use of indomethacin and diflunisal has been associated with fatal gastrointestinal hemorrhage. Therefore, indomethacin and diflunisal should not be used concomitantly.

The concomitant use of diflunisal tablets and other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy. The following information was obtained from studies in normal volunteers.

Aspirin: In normal volunteers, a small decrease in diflunisal levels was observed when multiple doses of diflunisal and aspirin were administered concomitantly.

Sulindac: The concomitant administration of diflunisal and sulindac in normal volunteers resulted in lowering of the plasma levels of the active sulindac sulfide metabolite by approximately one-third.

Naproxen: The concomitant administration of diflunisal and naproxen in normal volunteers had no effect on the plasma levels of naproxen, but significantly decreased the urinary excretion of naproxen and its glucuronide metabolite. Naproxen had no effect on plasma levels of diflunisal.

 

Drug laboratory Test Interactions

Serum Salicylate Assays: Caution should be used in interpreting the results of serum salicylate assays when diflunisal is present. Salicylate levels have been found to be falsely elevated with some assay methods.

 

Adomal Contraindications

Patients who are hypersensitive to this product. Patients in whom acute asthmatic attacks, urticaria, or rhinitis are precipitated by aspirin or other nonsteroidal anti-inflammatory drugs.

 

Additional information about Adomal

Adomal Indication: For acute or long-term use for symptomatic treatment of mild to moderate pain, osteoarthritis, and rheumatoid arthritis.
Mechanism Of Action: The precise mechanism of the analgesic and anti-inflammatory actions of diflunisal is not known. Adomal is a prostaglandin synthetase inhibitor. In animals, prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain. Since prostaglandins are known to be among the mediators of pain and inflammation, the mode of action of diflunisal may be due to a decrease of prostaglandins in peripheral tissues.
Drug Interactions: Alendronate Increased risk of gastric toxicity
Anisindione The NSAID increases the anticoagulant effect
Dicumarol The NSAID increases the anticoagulant effect
Warfarin The NSAID increases the anticoagulant effect
Indomethacin Increases the effect and toxicity of indomethacin
Probenecid Probenecid increases toxicity of diflunisal
Acenocoumarol The NSAID increases the anticoagulant effect
Food Interactions: Take with food to reduce irritation.
Avoid alcohol.
Generic Name: Diflunisal
Synonyms: Not Available
Drug Category: Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors
Drug Type: Small Molecule; Approved
Other Brand Names containing Diflunisal: Adomal; Difludol; Dolisal; Dolobid; Dolobil; Dolobis; Flovacil; Fluniget; Fluodonil; Flustar;
Absorption: Rapidly and completely absorbed following oral administration, with a bioavailability of 80-90%.
Toxicity (Overdose): Oral LD50 in rat, mouse, and rabbit is 392 mg/kg, 439 mg/kg, and 603 mg/kg, respectively. Symptoms of overdose include coma, tachycardia, stupor, and vomiting. The lowest dose without the presence of other medicines which caused death was 15 grams.
Protein Binding: More than 99% of diflunisal in plasma is bound to proteins.
Biotransformation: Hepatic, primarily via glucuronide conjugation (90% of administered dose).
Half Life: 8 to 12 hours.
Dosage Forms of Adomal: Tablet Oral
Chemical IUPAC Name: 5-(2,4-difluorophenyl)-2-hydroxybenzoic acid
Chemical Formula: C13H8F2O3
Diflunisal on Wikipedia: http://en.wikipedia.org/wiki/Diflunisal
Organisms Affected: Humans and other mammals