I understand that it is an NSAID, but its only 1%. Doesn’t that mean a 100g tube only has 1g of diclofenac (I assume its 1% by weight).
Oral diclofenac is dosed at about 100-200mg a day. So wouldn’t you have to go through a fifth of a tube every day to get the same dosage you’d get orally?
I’m assuming the average topical dosage is <10mg. I could be wrong, but I don’t understand what the warning is for in that situation, since the topical dosage is probably a fraction of the oral dosage.
While I have no personal experience with diclofenac, I do know that most drugs taken orally undergo a first-pass metabolism through the liver and possibly the gut, where hepatic enzymes break down the compound and reduce the percentage of the active ingredient before it reaches general circulation in the blood.
In contrast, topical medications are absorbed into the bloodstream through the skin, avoiding the first-pass effect, so it’s not surprising that they are dosed lower than the oral versions of the same drug.
Note that after entering circulation from the skin, the drug can undergo a “second pass” metabolism when the blood containing the drug returns to the liver later on, something that pharmaceutical scientists need to take into consideration when developing the drug.
I got some to use on a sore thumb joint (from excessive knitting!) and about a week later, I noticed that I had more bruises than usual. I stopped using it, and the bruises healed. It didn’t really work on my thumb, either.
Moreover, diclofenac has been shown to undergo considerable first-pass metabolism, limiting its oral bioavailability (50–60%) [3, 4].
So if you’re taking 200mg over the course of a day, thats still 100mg absorbed. And that seems far far more than what the dosage would be when taken topically, even if you assume 100% bioavailability when using it topically.
According to this, the systemic concentrations of topical are much lower than oral doses.
Systemic bioavailability and pharmacodynamics of topical diclofenac sodium gel 1% were compared with those of oral diclofenac sodium 50-mg tablets. In a randomized, 3-way crossover study, healthy volunteers (n = 40) received three 7-day diclofenac regimens: (A) 16 g gel applied as 4 g to 1 knee 4 times daily (4 g on surface area 400 cm(2)), (B) 48 g gel applied as 4 g per knee 4 times daily to 2 knees plus 2 g gel per hand applied 4 times daily to 2 hands (12 g on 1200 cm(2)), and (C) 150 mg oral diclofenac applied as 50-mg tablets 3 times daily. Thirty-nine participants completed all 3 regimens. Systemic exposure was greater with oral diclofenac (AUC(0-24), 3890 +/- 1710 ng x h/mL) than with topical treatments A (AUC(0-24), 233 +/- 128 ng x h/mL) and B (AUC(0-24), 807 +/- 478 ng x h/mL). Oral diclofenac inhibited platelet aggregation, cyclooxygenase-1 (COX-1), and COX-2. Topical diclofenac did not inhibit platelet aggregation and inhibited COX-1 and COX-2 less than oral diclofenac. Treatment-related adverse events were mild and limited to application site reactions with diclofenac sodium gel 1% (n = 4) and gastrointestinal reactions with oral diclofenac (n = 3). Systemic exposure with diclofenac sodium gel 1% was 5- to 17-fold lower than with oral diclofenac. Systemic effects with topical diclofenac were less pronounced.
Basically the people who took 150mg a day orally had 17x the systemic concentration of diclofenac as people who took 16g topically a day. The oral group had about 5x the systemic concentration of the diclofenac group who took 48g a day, which is a pretty high dosage (thats almost half a full sized tube a day).
Even if you’re using half of a 100g tube every day (which is quite a lot, enough to cover 180 square inches four time a day) your biological concentrations are about equal to what you’d have if you took 30mg orally in a day, which is a low dose.
Although I guess if you applied it all over your body several times a day after maybe doing a long hike, that would be several square feet of gel applied to your body. I guess that would equal the concentration you’d get from taking 150mg+ orally, but again you’d have to pretty much go through 2 tubes a day to use that much.
Easy.The lawyers figured out that someone might actually apply ridiculously large amounts and so they cover the company’s ass with a warning. People have been known to do weird things.
Yep. As I’ve had it explained to me by lawyers, nearly every warning on a product or its packaging is because someone did exactly that and sued for it, or did something very similar.
So there’s probably a court case out there where some nimrod covered themselves from head to toe in Ben-Gay or whatever, and caused themselves health problems and sued, because the label didn’t say NOT to do it. So the Voltaren lawyers are probably trying to head that off at the pass- besides not wanting it put all over large parts of the body, they don’t want dumb-asses smearing Voltaren in their butt cracks because they got some diaper rash. Or putting it on their foreheads for headaches. Or whatever other stupid usage you could think up.
There could also be a regulatory component to it; the label is VERY clear that it’s supposed to be used only for arthritis. But it’s an NSAID; it’s not limited to arthritis pain relief. However that’s likely how it’s been tested and approved for OTC status, so they can’t suggest it for other uses as a result.
Are the sections of the Pack Insert you’re referring to the ones that say things like this?
Lower extremities: Apply the gel (4 g) to the affected area 4 times daily. Do not apply more than 16g daily to any one affected joint of the lower extremities.
I think the issue is related to cutaneous adverse events. This is the EU SPC for Solaraze. This is a 3% diclofenac gel and it is used to burn your skin off - specifically to burn off actinic keratoses, precursors of skin cancer. And it will take your skin off - I have personal experience of it - I ended up looking like an accident in a butchers shop.
So strong diclofenac gel will burn your skin off; it’s a reasonable assumption that if you apply enough of the weak gel, you can achieve the same effect. That’s my guess.
There is a second possibility that occurred to me, but it’s less likely (and I confess I haven’t searched the pack insert to see if there’s anything that suggests this explanation). There’s a worry about patients using OTCs in such a way that they mask a significant underlying problem. You have a sore knee, it’s probably osteoarthritis, you talk to your pharmacist, he gives you Voltaren. If that doesn’t do the trick, you’ll go to your doctor.
The worrying scenario is that it works OK, but then the other knee, both ankles and both hips start hurting. At this point you should be thinking, Maybe this ain’t just arthritis - and you should be seeing a doctor - not trying to work through it with huge amounts of Voltaren. That could be a reason for warning against overuse. (I note that large joints like hip or spine are covered by “not tested”).
Yeah, this. Some of these apparently absurd prohibitions are there for liability reasons. So when someone does buy a case of the stuff and cover themselves like the Goldfinger girl and get sick and die they or their survivors can sue and claim, “Well, the directions never said I shouldn’t cover my whole body.”
It’s amazing the stuff that gets included in product descriptions for liability reasons. To wit: on jars of peanut butter you will see the statement: “Contains peanuts.”
But just because it was called “peanut butter,” and I’m allergic to peanuts, I didn’t think there was any danger to me! (Said in a whiny tone)
