Does intramuscular (IM) Voltaren (diclofenac) reduce fever and increase the risk of bleeding?

Does IM Voltaren (Diclofenac) Reduce Fever and Cause Bleeding?

Yes, intramuscular diclofenac effectively reduces fever through its anti-inflammatory mechanism, but it significantly increases bleeding risk through multiple pathways including platelet inhibition and gastrointestinal mucosal damage. 1

Antipyretic (Fever-Reducing) Effects

Diclofenac does reduce fever, but this effect may mask important diagnostic signs of infection or complications. 1

• The pharmacological activity of diclofenac in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions 1
• As a non-steroidal anti-inflammatory drug, diclofenac inhibits prostaglandin synthesis, which is the primary mechanism for its antipyretic effect 2
• When administered intramuscularly, diclofenac has a fast onset and long duration of action for its analgesic and anti-inflammatory effects 2

Bleeding Risk Profile

Platelet Function Impairment

Diclofenac inhibits platelet aggregation and prolongs bleeding time, though this effect is less pronounced and shorter-lasting than aspirin. 1

• NSAIDs including diclofenac inhibit platelet aggregation and have been shown to prolong bleeding time in some patients 1
• Unlike aspirin, the effect on platelet function is quantitatively less, of shorter duration, and reversible 1
• Like many other NSAIDs, diclofenac increases platelet aggregation time 3
• Patients receiving diclofenac who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored 1

Gastrointestinal Bleeding Risk

Diclofenac carries a dose-dependent risk of serious gastrointestinal bleeding, ulceration, and perforation, which can be fatal. 4

• 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 4
• These events can occur at any time during use and without warning symptoms 4
• The GI bleeding risk is dose-dependent: OR = 2.2 (95% CI 0.8 to 5.8) for diclofenac 75 mg, 3.2 (1.9 to 5.5) for 75-150 mg, and 12.2 (5.6 to 26.7) for >150 mg daily 4
• The increased likelihood of peptic ulceration is due to interference with prostaglandin-mediated cytoprotection of the gastrointestinal mucosa 4
• Upper gastrointestinal hemorrhage has been documented even with cutaneous application of diclofenac gel, with some cases requiring blood transfusions 5

Hematological Effects

Diclofenac can cause anemia through multiple mechanisms including occult or gross GI blood loss. 1

• Anemia is sometimes seen in patients receiving NSAIDs, including diclofenac, which may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis 1
• Patients on long-term treatment with diclofenac should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia 1
• Rare but serious hematological complications include severe thrombocytopenia and neutropenia 6

High-Risk Populations Requiring Extreme Caution

Patients on anticoagulants face compounded bleeding risk when combined with diclofenac. 4

• The added bleeding risk when platelet function inhibitors like aspirin and clopidogrel are taken during anticoagulant therapy is compounded for NSAIDs by the increased likelihood of peptic ulceration 4
• These mechanisms are independent from any pharmacokinetic drug-drug interactions (none was demonstrated between dabigatran etexilate and diclofenac) 4
• Drugs that can lead to gastrointestinal bleeding include NSAIDs like diclofenac, platelet inhibitors, and anticoagulants, with combination therapy increasing risk compared to monotherapy 7

Elderly patients are at greater risk for serious gastrointestinal bleeding events. 4

Clinical Monitoring Algorithm

When prescribing IM diclofenac, assess the following:

1. Bleeding risk factors: 1

   • Current anticoagulant or antiplatelet therapy
   • History of peptic ulcer disease or GI bleeding
   • Coagulation disorders
   • Advanced age

2. Warning signs requiring immediate evaluation: 1

   • Epigastric pain, dyspepsia, melena, or hematemesis
   • Signs or symptoms of anemia
   • Unusual bruising or prolonged bleeding

3. Baseline and monitoring labs: 1

   • Hemoglobin/hematocrit for patients on long-term therapy
   • Complete blood count if symptoms of thrombocytopenia or neutropenia develop

Critical Pitfalls to Avoid

• Do not assume topical or IM routes are safer: Even cutaneous application of diclofenac has caused massive upper GI hemorrhage requiring transfusions 5
• Do not rely on symptoms to detect bleeding: Serious GI tract ulcerations and bleeding can occur without warning symptoms 1
• Do not combine with other NSAIDs or aspirin: Aspirin markedly reduces the bioavailability of diclofenac and increases bleeding risk 3
• Do not use as a fever reducer when infection is suspected: The antipyretic effect may mask diagnostic signs of complications 1