Diclofenac

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Contents

[edit] BRAND NAMES

[edit] COMBINATION FORMULATIONS

Diclofenac/Misoprostol:

  • Artrotec (Italy)
  • Misofenac (Italy)

[edit] STRUCTURE

Diclofenac.jpg

[edit] MECHANISM OF ACTION

Diclofenac is a nonsteroidal antiinflammatory drug (NSAID) with analgesic, antipyretic and antirheumatic properties.

Diclofenac inhibits the enzyme, cyclooxygenase (COX), an early component of the arachidonic acid cascade, resulting in the reduced formation of prostaglandins and thromboxanes. Prostaglandins act as messenger molecules in the process of inflammation.

In rheumatic diseases, the anti-inflammatory and analgesic properties of Diclofenac elicit a clinical response characterised by relief from signs and symptoms such as pain at rest, pain on movement, morning stiffness, and swelling of the joints, as well as by an improvement in function

[edit] INDICATIONS

  • Rheumatoid arthritis and osteoarthritis.
  • Relief of acute or chronic pain states in which there is an inflammatory component.
  • Symptomatic treatment of primary dysmenorrhoea (painful periods)
  • Pain due to gallstones or kidney stones (IM injection)
  • Severe migraine attacks (IM injection)
  • Diclofenac GEL (1%-2%): is indicated for the relief of the pain of osteoarthritis of joints amenable to topical treatment, such as the knees and those of the hands.
  • Diclofenac Gel 3% (Solaraze) is indicated for the topical treatment of actinic keratosis (AK). Sun avoidance is indicated during therapy.

[edit] DOSAGE

Adults:

  • Intramuscular injection: The dose is generally one 75 mg ampoule daily, given by deep intragluteal injection into the upper outer quadrant. In severe cases (e.g. colic), the daily dose can exceptionally be increased to two injections of 75 mg, separated by an interval of a few hours (one into each buttock).
    Alternatively, one ampoule of 75 mg can be combined with other pharmaceutical forms of diclofenac sodium (e.g. tablets, suppositories) up to a total maximum daily dose of 150 mg.
    Diclofenac sodium solution for injection should not be given for more than 2 days; if necessary, treatment can be continued with diclofenac sodium tablets or suppositories
  • Tablets and Suppositories: Initial dosage is 75 to 150 mg daily in 2 or 3 fractional doses. For long-term therapy, 75 to 100 mg daily is usually sufficient.
  • Diclofenac gel 3% (Solaraze): is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently.
    The amount needed depends upon the size of the lesion site. Assure that enough gel is applied to adequately cover each lesion. The recommended duration of therapy is from 60 days to 90 days. Complete healing of the lesion(s) or optimal therapeutic effect may not be evident for up to 30 days following cessation of therapy. Lesions that do not respond to therapy should be carefully re-evaluated and management reconsidered.

[edit] CONTRAINDICATIONS

  • Tablets, solution for injection and Suppositories:
    • Gastric or duodenal ulcer, gastro-intestinal bleeding or perforation.
    • Known hypersensitivity to diclofenac
    • Diclofenac should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients
    • Last trimester of pregnancy
    • Severe hepatic, renal or cardiac failure

[edit] WARNINGS AND PRECAUTIONS

  • Cardiovascular Risk: NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
  • Gastrointestinal Risk: NSAIDs cause an increased risk of serious gastrointestinal adverse events including inflammation, bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events. To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration
  • Hypertension: NSAIDs can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of cardiovascular events. Patients taking thiazides (Hydrochlorothiazide) or loop diuretics (Bumetanide, Etacrynic acid, Furosemide, Torasemide) may have impaired response to these therapies when taking NSAIDs. NSAIDs, including diclofenac, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
  • Heart failure: Fluid retention and edema have been observed in some patients taking NSAIDs, including diclofenac, therefore caution is advised in patients with fluid retention or heart failure.

[edit] INTERACTIONS

  • Aspirin, Ibuprofen, other systemic NSAIDs or Corticosteroids: Concomitant administration of diclofenac and other systemic NSAIDs or corticosteroids may increase the frequency of gastrointestinal undesirable effects.
  • Warfarin: Caution is recommended since concomitant administration could increase the risk of bleeding.
  • Digoxin: If used concomitantly, diclofenac may raise plasma concentrations of digoxin. Monitoring of the serum digoxin level is recommended.
  • Lithium carbonate: If used concomitantly, diclofenac may raise plasma concentrations of lithium. Monitoring of the serum lithium level is recommended.
  • Diuretics, ACE inhibitors or Beta blockers : concomitant use of diclofenac with diuretics or antihypertensive agents (e.g. beta blockers, angiotensin converting enzyme (ACE) inhibitors) may cause a decrease in their antihypertensive effect. Therefore, the combination should be administered with caution and patients, especially the elderly, should have their blood pressure periodically monitored.
  • Selective serotonin reuptake inhibitors (SSRIs): Concomitant administration of systemic NSAIDs, including diclofenac, and SSRIs may increase the risk of gastrointestinal bleeding
  • Oral antidiabetic agents: Diclofenac can be given together with oral antidiabetic agents without influencing their clinical effect. However, there are isolated reports of both hypoglycemic and hyperglycemic effects in the presence of diclofenac which necessitated changes in the dosage of the antidiabetic agents. For this reason, monitoring of the blood glucose level is recommended as a precautionary measure during concomitant therapy
  • Methotrexate: Caution is recommended when NSAIDs, including diclofenac, are administered less than 24 hours before or after treatment with methotrexate, since blood concentrations of methotrexate may rise and the toxicity of this substance be increased.
  • Cyclosporin: Diclofenac, like other NSAIDs, may increase the nephrotoxicity of cyclosporin due to the effect on renal prostaglandins. Therefore, it should be given at doses lower than those that would be used in patients not receiving cyclosporin
  • Concomitant treatment with potassium-sparing drugs (Diuretics:Amiloride, Eplerenone, Potassium canrenoate, Spironolactone,Triamterene; Cyclosporin; Tacrolimus or Trimethoprim) may be associated with increased serum potassium levels, which should therefore be monitored frequently.
  • Quinolones: There have been isolated reports of convulsions which may have been due to concomitant use of quinolones and NSAIDs.
  • Sulfinpyrazone (a medicine used to treat gout):Caution is recommended when using Sulfinpyrazone (a potent CYP2C9 inhibitor) concomitantly with diclofenac, which could result in a significant increase in peak plasma concentrations and exposure to diclofenac due to inhibition of diclofenac metabolism.
  • Voriconazole: Caution is recommended when using voriconazole (a potent CYP2C9 inhibitor) concomitantly with diclofenac, which could result in a significant increase in peak plasma concentrations and exposure to diclofenac due to inhibition of diclofenac metabolism.
  • Phenytoin (a medicine used to treat seizures): When using phenytoin concomitantly with diclofenac, monitoring of phenytoin plasma concentrations is recommended due to an expected increase in exposure to phenytoin

[edit] PREGNANCY AND LACTATION

  • Nursing Mothers: Because of the potential for serious adverse reactions in nursing infants from diclofenac sodium, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

[edit] SIDE EFFECTS

Common adverse reactions are: Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal), vomiting, dizziness, elevated liver enzymes, headaches, increased bleeding time, pruritus and rashes.

Most common adverse reactions with Diclofenac GEL are application site reactions, including dermatitis.

[edit] RELATED LINKS

NSAIDs: MOAs and Clinical Considerations...

[edit] BIBLIOGRAPHY

[edit] REFERENCES

Non-steroidal anti-inflammatory drugs (NSAIDs)
Non-selective (COX-1 and COX-2 inhibitors) Aceclofenac   Acetylsalicylic acid   Benzydamine   Diclofenac   Flurbiprofen   Ibuprofen   Indometacin   Ketoprofen   Ketorolac   Ketorolac   Lornoxicam   Mefenamic acid   Morniflumate   Nabumetone   Naproxen   Niflumic acid   Piroxicam   Tenoxicam
Relatively COX-2 selective Meloxicam   Nimesulide
COX-2 selective inhibitors (Coxibs) Celecoxib   Etoricoxib   Parecoxib
Ophthalmic NSAIDs Bromfenac (ophthalmic)   Diclofenac (ophthalmic)   Flurbiprofen (ophthalmic)   Ketorolac (ophthalmic)   Nepafenac (ophthalmic)
Veterinary use Carprofen   Deracoxib   Firocoxib   Mavacoxib   Robenacoxib
Antimigraine preparations
5 HT1 agonists (Triptans) Almotriptan (Almogran, Axert)   Eletriptan (Relpax)   Frovatriptan (Frova, Migard, Menatriptan)   Rizatriptan (Maxalt)   Sumatriptan (Imigran)   Zolmitriptan (Zomig)
Ergot alkaloids Dihydroergotamine   Ergotamine
NSAIDs/ Analgesics Indometacin   Acetylsalicylic acid (Aspirin)   Diclofenac (Voltaren)   Ibuprofen (Advil, Brufen, Dolgit, Nurofen)   Ketorolac (Toradol)   Naproxen (Naprosyn, Aleve)   Nimesulide   Paracetamol (Efferalgan, Panadol...)
Prophylaxis Cinnarizine (Stugeron, Stugeron forte)   Flunarizine (Sibelium)   Nifedipine (Adalat)   Pizotifen   Propranolol (Inderal)   Topiramate (Topamax)