New Treatments for Cancer Pain. Part 5.
Darvon itself has a 13-hour half life and what you get from a single dose study of Darvocet is Tylenol’s activity. You have to take Darvocet for a couple of days in order for the propoxyphene component to reach steady state and be a reasonable analgesic. And it is. It’s a reasonably good analgesic for those patients who understand that Darvon’s metabolism is saturable, which most of your patients have figured that out. And if you take twice as much as the doctor orders it works a hell of a lot better. That’s why most of your patients who get prescriptions say Darvocet in 100, one tablet every four to six hours p.r.n. pain, number 50. Come back to the drugstore in five days asking for a refill. Because they figured out that 10 a day works really good for moderate pain. Of course that’s six grams of Tylenol, which means I get another consultation sometime down the line to talk about the likelihood of liver toxicity from 6 grams of Tylenol a day. So this is the activity.
We have an injectable non-steroidal now. It is really potent, the injectable. The oral product isn’t nearly as potent but it is so potent there are a number of caveats. If you give this drug to patients with a history of GI bleeding, they will bleed just as sure and night follows day. This drug has killed a lot of people who had a history of GI bleed, who got the drug. We had one patient die in our institution. They were given a 60 mg – it was a 70-year-old patient with a history of GI bleed – was given a single dose in a surgical center, not associated with us. Came into the emergency room about 14 hours later and frank GI hemorrhage. Took him down to the operating room and he died. If you give this drug to patients with a history of renal dysfunction you will be absolutely amazed at how fast their creatinine rises. There are reported instances in 20-year-olds with moderate renal dysfunction, of the creatinine clearance going to 0 within a three or four day period following a single dose. But it’s a good dose for people who are younger and have healthy kidneys as long as you don’t use it for longer than five days. Because after more than five days therapy the incidence of renal dysfunction or GI bleeding starts rising dramatically. Almost logarithmically. The oral product says you may only use it after the patient has had a parenteral dose. What that means is, the reason for that, is there is a very high incidence of anaphylactic reaction to this dose. It’s a first-dose phenomena with this drug and they want to make sure that if the patient is allergic to the drug that they get that allergic reaction in your office, in your clinic or in the hospital, not in their living room. Now if the patient has had the drug before, no problem.
Remember, the oral is only a 10 mg tablet and the reason it is only a 10 mg tablet is because we know that although even not all that is absorbed, is the side effects are so great they couldn’t market more than a 10 mg tablet. I don’t suggest you use it. Now there are some patients with migraines who respond very well to this, so the question I get asked very often by primary care practitioners is, “You mean, I have to tell this patient they can’t have this drug anymore?” I say, “No, I don’t think so.” Because the problem is with more than 5 days of consecutive use, you tell the patient take it when you have a migraine and then stop and you can’t take it again for 4 or 5 days, then they are going to be safe. Because pharmacologically they are starting over each time. And they should be relatively safe. Although I would make sure you do assessments of renal function and you occasionally make sure they are not having any indications of GI bleed. If you have migraine patients taking this drug all the time, and you’d better write those prescriptions indicating that that’s how they are to do it. If you write take as directed and I’m the pharmacist, I’m not going to fill it because I don’t want my neck on the chopping block either.