About William J. Walker, Pharm.D. Expertise Homeopathic, alternative, herbal, natural, adverse drug reactions, side effects, risks, outcomes, research, medication, rational therapeutics, infectious diseases, cardiology, pain management, nutrition, psychopharmacology, oncology, pediatrics, sleep disorders, tropical diseases, HIV, drug interactions, substance abuse, illicit drugs of abuse, geriatrics
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Expert: William J. Walker, Pharm.D. Date: 7/22/2005 Subject: converting from Lortab to Methadone
Question How do you figure the doseage of methadone for pain converting from Lortab 7.5 mg. t.i.d.- 3 times a day?
Would a starting dose of 40mg.of methadone 4 times a day be too much? What would be the adverse reactions to methdone and xanax, methadone and soma, methadone and ambien? What would be the adverse reactions to taking all of those drugs together? These drugs are being given to treat fibromyalgia. If a person had emphysema and pnuemonia would it be safe to take methadone 40mg. 4 times a day starting dose along with the other drugs? Any information will be greatly appreciated.
Terry
Answer Technically speaking there is a 2:1 ratio. In other words a dose of 7.5 mg of hydrocodone is equivalent to about 15 mg of methadone. This is based on the standard of morphine mg dosage equivalents. But what is complicated about this is the differences in the fate and distribution of the compounds metabolically and pharmacokinetically. Hydrocodone is unique in that it has a biphasic opiate effect. The first effect is short lived and results from the active hydrocodone itself. Many falsely believe that because of this short duration of action hydrocodone should be dosed more frequently. And sometimes the mathematical computations for dosing equivalents fail to account for all of the phases of activity. The primary metabolite happens to be hydromorphone which gives rise to the second wave of opiate effect. This occurs somewhere between 2-4 hours after the dose, or about the time that the initial wave has ended. Hydromorphone is a potent opiate agent by itself. This second wave of CNS activity is partly responsible for the extreme popularity of hydrocodone as a pain reliever. Over time there has been an accumulation effect as well, which further complicates proper dosing. Methadone, on the other hand, has a longer duration of action and suggests a less frequent dosing interval. But the opiate effect does not correlate well with the pharmacokinetic profile. It becomes necessary to dose the drug more frequently than the half life suggests. This often leads to poorly designed regimens that started out using a simple mathematical relationship. Furthermore methadone seems to take several days to build up an opiate analgesic effect. So that the first few days of a transition will naturally require doses higher than suggested in order to maintain analgesia. This is more often than not the reason that such conversions have failed initially or resulted in a progressively increasing requirement. But after the first week of therapy the accumulation reaches a point where the dose should again be tapered back. And this is another potential point at where clinicians can fail to properly make adjustments. Subjectively patients who are used to the biphasic activity of hydrocodone misperceive the missing second peak of methadone as a less effective agent or dose. They prefer the second spike effect and can, for the wrong reasons, escalate the methadone dose to eventual detriment.
Aside from all of the science and mathematics of opiate equivalents we must always remember that all opiates should be dosed to effect. In other words we should provide the lowest dosage possible that renders effective pain relief and the fewest side effects. Not being afraid to increase the dose as needed over time. With no ceiling dose. Or to put it another way the phrase "too much" is never an absolute.
In your cited example there are some glaring problems. First is that hydrocodone dosed three times a day is not enough to remain pain free. It is a lousy drug for this chronic condition. It is already going to create craving and or breakthrough pain for the latter portion of the dosing interval. This only complicates the transition even more. Jumping right away to methadone 40 mg four times a day is probably excessive. Logic says it should start at 15 mg three times day. But therapeutically it would be best as 12 mg four times a day because of the short analgesic action. Perhaps even as much as 10 mg every four hours initially. Then later tailored back to 15 mg every 8 hours. But once the dosage reaches 40 mg four times a day without significant adverse events then it is safe to assume that this dosage is indeed appropriate. No matter what the dosages were in previous weeks.
I think you already know the answer to the rest of your questions. The adverse reactions to combining any or all of the above listed medications is implicitly obvious. They are all psychoactive compounds with profound sedative properties. All can actually potentiate each other and the effects are additive. Sedation to the point of frank coma is possible. Especially when some of these are agents with a long or lingering duration of action. They also depress the respiratory center and can result in respiratory arrest. That is the inherent danger really. Not to mention the huge potential for serious dependencies. There are many persons who would downright succumb and die after ingesting these agents together. Others can tolerate these together and more without as much as even a missed step. It all depends on tolerance.
Treating fibromyalgia is seldom simple. There are many cases where perhaps this regimen is required. Especially if there are other medical problems as well. Suppression of the respiratory drive center intuitively suggests enormous risk in patients with respiratory disease. And in fact this is true most of the time. But opiates have also been shown to assist in oxygen starvation by reducing the stridor. In end stage lung disease it actually turns into a benefit.
If you are concerned about this regimen and whether or not it is appropriate it is always a good idea to have the patient worked up by another internist. Sometimes this helps to get another opinion. Someone who can see something that has been too easy to overlook out of familiarity. I have found this to happen most often with controlled substances that have included a fair amount of back and forth dialogue. Once a physician has resolved to meet the ever present needs of a patient, month after month listening to the requests for more, it becomes too easy to lose sight of the goal.
