According to the attached image, no therapeutic window is there with regard to diclofenac potassium, because the maximum tolerated dose ( 150 mg/day PO ) is the same as the minimum effective dose ( 50 mg PO 3 to 4 times daily. ) for pain management?
Or there is something I miss, and the minimum effective dose isn't 150 mg (50 three times per day)?
And I have another Q, if there is hepatic impairment, it is said to initiate therapy at the lowest dose, so isn't 50 mg (3 times per day) the lowest dose possible with regard to pain management?
Hi Mostafa,
The use of diclofenac to treat pain is slightly complicated by the adverse effects on the GI tract, such as ulceration, as well as potential hepatotoxicity. In the U.S.A. as detailed by Novartis, the maximum recommended dosage is 200 mg/day while the minimum recommended dosage is 100 mg/day. The dose of 150 mg/day (through either 50 mg TID or 75 mg BID) therefore represents a middle approach.
But Dr.Ron, isn't the therapeutic window should be based on the indication (Pain management)? because I see the therapeutic window which you have mentioned isn't representative of the indication but representative of all the indications. I mean I have searched across different resources and databases, and I haven't seen 100 mg/day as the recommended dose to treat pain but 150 mg divided into 3 doses. And with regard to the maximum tolerated dose, the same thing when it comes to pain management. Is this correct? Or should I base the minimum and maximum dose based on all indications for this Pharmaceutical?
Hi Mostfa,
I feel the dose for this medication needs to be tailored to the individual. The maximum may be 200 mg, but in a person who suffers from GI malaise at 150 mg, that upper dose may not be applicable. I prefer to think in terms of tolerance and therapeutic benefit rather than strict adherence to what is generally prescribed for a given condition. You can find examples of 100 mg being sufficient for pain, though these come through anecdotal evidence from patients commenting on message boards. If a lower dose works, then that is the therapy is sufficient even if it deviates from the norm.
I think Diclofenac potassium is not at all a drug of choice for oral intake to give relief from pain. It is generally used at local application as a pain reliever due to probable toxicity in oral use.
Paracetamol is the drug of choice for oral use to relief pain, as far my knowledge goes. As the Pain center and Thermo-regulatory center are staying very near in Hypothalamus, interaction in effects are seen in almost all the drugs used in related purposes.
I agree with Tony's sentiment about acetaminophen. One of Mostafa's last point in his original post was about hepatic impairment. Given the nature of acetaminophen to induce hepatotoxicty (granted this occurs at high doses) and it's low analgesic properties relative to other agents, I wouldn't be so keen on its use as I can easily envision a patient taking mass quantities of acetaminophen only to suffer from hepatocellular damage instead of achieving pain relief.
The FDA approved dosage for diclofenac is 100-200/day in divided doses, depending on the indication. Naturally, the drug doesn't offer a wide dose range and hence there is limited flexibility in dosage administration. The adverse events of diclofenac, particularly GI intolerance and hepatotoxicity are also well documented. If used judiciously, the drug can be a sigificant therapeutic tool!
Both diclofenac and paracetamol are NSAIDs and peripherally acting analgesics. Only the antipyretic action of paracetamol may be construed to be central in nature. Needless to say, diclofenac is a potent analgesic which is superior to paracetamol. Unlike paracetamol, diclofenac has anti-inflammatory property which makes it beneficial in some painful inflammatory conditions.
Point of correction to A D Paul's comment regarding acetaminophen, which is technically not a NSAID (it doesn't possess anti-inflammatory activity similar to NSAIDs and works via different mechanisms to alleviate pain).
Article Graham GG, Scott KF: Mechanism of action of paracetamol
I agree with Dr Ron Scialis that technically, paracetamol cannot be regarded as an NSAID. I had already indicated that paracetamol lacks anti-inflammatory activity and this differentiates it from diclofenac. Although hepatotoxicty has been reported with both the drugs, paracetamol may be a better drug compared to diclofenac particularly in terms of GI tolerability. Both drugs have their own roles in therapy.
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