Name (Reference Only)
with Codeine (generic)
with Codeine (generic)
with Codeine (generic)
with Codeine (generic)
Sustained Release 15mg
with Codeine (generic)
Sustained Release 30mg
Sustained Release 60mg
Sustained Release 100mg
Sustained Release 200mg
* (generic) next to the brand name means that
it is available in generic form.
Opioid Treatment for
The benefits of opioid maintenance therapy
are substantial. The overwhelming majority of patients appear not only to obtain
significant pain relief, but to take advantage of their freedom from disabling
pain to become more physically active, more socially productive, and to live a
generally more fulfilling life. Unfortunately, this treatment also entails a
number of risks. The medications have a variety of dangerous side effects:
sedation, respiratory depression, and death from overdose. These side effects
pose a risk not only to the patient, but to others who may be injured if a
patient is impaired by the medication or behaves irresponsibly. In addition,
such side effects as constipation, nausea, itching, and urinary retention may
make opioid medications difficult to tolerate.
Finally, the risk of illegitimate use or diversion by patients is a
medical, as well as a regulatory, concern. We provide this brochure in the hope
of making this treatment as safe as possible. But providing information is not
enough. More than in most clinical circumstances, the failure of patients to act
intelligently, responsibly, and honestly can lead to disaster. For all of these
reasons, patients who undertake opioid maintenance therapy should behave in a
way that is beyond reproach or suspicion in all matters relating to their use of
medications. Patients who are unwilling or unable to do so jeopardize not only
their own health and safety, but the health and safety of other patients with
Approach to Pain Treatment with Opioid
Treatment is guided by two factual premises:
1) each patient is unique in his perception of pain and in his response to
medications; and 2) there is no limit to tolerance, and therefore, no arbitrary
limit to the dose that may be required to achieve pain relief. Accordingly, a
patient's response is the ultimate guide to treatment.
To learn from patient response, medication trials must be conducted in a
systematic and disciplined way. We try to help patients to become sophisticated
and disciplined observers and reporters of their physical symptoms and of their
responses to medications. These reports allow us to adjust medication and dose
to achieve optimal pain control with minimal side effects at the least expense.
This brochure provides an overview of opioid maintenance therapy. We begin with
the medications and a description of some of their clinically important
We proceed with a description of the three stages of opioid maintenance
therapy: initiation, titration, and maintenance. We conclude with a
discussion of the management of common opioid side effects and the management of
the withdrawal syndrome.
The Opioid Medications
The mainstay of pain management of
intractable pain is provided by opioid medications. These medications are also
referred to as narcotics. Although they are marketed under a number of brand
names, the list is relatively short. The ones used most frequently in our
practice include the following:
Generic listed first
MSIR, MS Contin, Oramorph Methadone
Roxicodone, Percolone, OxyContin
Other opioids are commonly prescribed for the
management of pain. However, our belief is that these medications should be used
less frequently and in restricted dose, or should be avoided altogether. Demerol
(Meperidine), for example, is unsuitable for chronic administration, as it can
lead to the accumulation of a toxic metabolite which predisposes to seizures.
Medicines containing Acetaminophen (Percocet, Lorcet, Vicodin, Tylenol #3 or #4)
are toxic to the liver in high doses, and my lead to kidney damage, if taken
These medications all work to relieve pain in
the same way--by attaching to opioid receptors on nerve cells, which causes a
decrease in the transmission of pain impulses to the brain. These medications
differ in strength, in duration of action, and in their side effects. And, as
noted above, individuals differ in their reactions to the same medication. One
important characteristic of opioid medications is that they are capable of
inducing tolerance. Tolerance refers to a decrease in the effect of a drug in
response to repeat exposure. As applied to opioids, this means that after a few
days to a few weeks of exposure to a particular dose of medication, that dose
becomes less effective in relieving pain. It also becomes less likely to cause
nausea, fatigue, euphoria, or respiratory depression.
The flip side of this is that it takes more medication to achieve the same level
of pain relief.
Fortunately, tolerance to most side effects
develops before tolerance to the pain relieving properties of these medications.
Most patients become tolerant to the depressing effect of these medications on
respiratory drive early in the course of treatment. Early tolerance to
respiratory depression makes these medications safer than is commonly believed
and provides for a considerable range of safe dosing. Tolerance to one
medication may lead to partial tolerance to one of the others. This is often
referred to as cross-tolerance.
The clinical implications of tolerance and
1. Once a medication has been found that provides pain relief, it is likely to
continue to provide pain relief if the dose is increased to compensate for
2. Side effects noted during the initial period of exposure to a medication are
likely to disappear with continued use.
Individuals vary in the extent to which they become tolerant to these
medications. Some maintain adequate pain relief at modest doses for very long
periods of time. Others require doses to be raised frequently to maintain
It is our experience, however, that most
patients reach a plateau within the first few months of treatment, after which
only small adjustments in dose are necessary. Even at high doses, these
medications do not appear to cause organ damage. Their side effects are reversed
after the medication is discontinued.
A variety of non-opioid medications are used
in chronic pain treatment. Some are used to treat related symptoms, like muscle
spasm. Others are used to enhance the effectiveness of the opioids or to
counteract their side effects.
Below is a list of the symptoms most commonly
associated with chronic pain or with opioid medications.
Loss of Menstrual Period
Muscle Spasm or Jerking
Nausea and Vomiting
Weight Gain or Loss
This list is not exhaustive, but its very
length should give an idea of the complexity of managing chronic pain patients.
Each of the medications used to treat opioid side effects may cause new side
effects or interact with other medications. In the "Treatment of Common
Side Effects"section, we review in detail most of these side effects and
the medications used to treat them. It should be clear that managing pain with
opioids can become a complex matter and that a cautious and systematic approach
is needed to find the optimal therapeutic regimen.
Finding the Right Dose
To find the medication or combination of
medications which provides the best pain relief with the fewest side effects at
the lowest cost requires a careful process of medication trials and dosage
adjustments--aided by precise record- keeping of the time and dose of
medication, the degree of pain relief, and the occurrence of side effects. To
prepare for this process please review the Medication Log Instructions and the
sample Medication Log.
The general strategy is to begin treatment
with short-acting opioids (Morphine, Roxicodone, or Dilaudid) trying one
medication at a time. Begin with a low test dose to make sure that the
medication has no serious or intolerable side effects. If it does have a bad
effect, put the medicine aside and try the next one.
If the initial dose is well tolerated, but fails to produce significant pain
relief, try a dose 50-100% higher 3-4 hours later.
If the second dose is well tolerated but ineffective, 3-4 hours later try a
third 50 % higher than the second dose.
With each dose, reevaluate the degree of pain relief and the presence of side
effects and keep a record of your response.
Once a pain relief response has been achieved
at a particular dose, repeat that dose as you notice the level of pain begin to
rise. This usually occurs within 4 to 6 hours. Again, record the time you take
the medication, the degree and duration of pain relief, and any side effects.
Adjust the dose up or down, depending on the degree of pain relief and the
presence of side effects. If a medication causes noticeable sedation,
discontinue the medication or decrease the dose. If your companion observes that
you are very sedated and not easy to arouse, this is an emergency requiring
medical supervision. As a general matter, if a given dose has been well-
tolerated for a period of days, but becomes progressively less effective, it is
safe to increase the dose by 50%. If a medicine provides less than satisfactory
pain relief or unpleasant side effects, put it aside and repeat the process with
a different medication.
After your tolerance to short acting
medications has been demonstrated, it may be possible to achieve equivalent pain
relief with fewer doses of medication by substituting an equivalent long- acting
opioid medication (methadone, MS Contin, OxyContin, Kadian, or Duragesic). These
long- acting medications may be supplemented with rescue doses of short-acting
medicines to control break- through pain.
If methadone is used, wait three days before making each upward dose adjustment.
This is because methadone's slow excretion may lead to increasing serum levels
over two or three days on constant dosing. The rising serum level may sneak up
on patient, leading to increasing sedation and respiratory depression.
Many patients have had prior experience with
opioid medications for pain relief. For patients who know which medication has
worked well in the past, we begin with that medication at the dose to which you
have become accustomed. However, if the prior medication contained Acetaminophen
(Percocet, Vicodin, Lorcet, or Tylenol #3 or #4), we reduce the dose to allow no
more than 4 grams per day of Acetaminophen. If the reduced dose is ineffective,
supplement the prior medication with an opioid that does not contain
Acetaminophen. Again, begin with 1 tablet, assess the response, and make
adjustments as described above. This process is not so complicated in practice
as it may seem in this description.
During the first weeks of treatment, you will become familiar with the
medications and the record-keeping system. If you have any questions or
problems, we are always available to help you.
The Management of Opioid Maintenance
After an effective dose of medication is
determined, patients generally obtain reliable pain control by repeating the
customary dose in a routine pattern, varying the timing or dose only to
accommodate changes in activity level or exacerbations of pain. Although the
choice of medicine and dose are relatively routine during this phase,
circumstances arise which require adjustments in the regimen or more aggressive
First, new side effects may emerge or become clinically more significant with
prolonged opioid administration and their treatment may require dosage
adjustment or the addition of adjunctive medications. Second, the underlying
condition causing pain may worsen, requiring new evaluation and therapeutic
intervention. And third, a patient may experience new medical or psychological
symptoms the evaluation and treatment of which is complicated by the medications
to treat pain.
To ensure patient safety, continued routine
patient reporting and monitoring is required during this phase. Patients are
asked to report not only on their medical conditions and medication
requirements, but on any changes in their activity, employment, or social
situation. By systematic monitoring, we hope to increase our understanding of
the clinical, social, and economic consequences of opioid maintenance therapy.
To facilitate reporting and monitoring, we have designed Interval Report Forms
that patients and physicians are asked to fill out and submit on a monthly
Possible Side Effects of Opioids
Opioid medications are associated with a
number of side effects.
This section will review the most common problems that patients encounter and
how to respond to them.
Patients with chronic pain often have constipation as a side effect of their
medications. Constipation may produce nausea, vomiting, and abdominal cramping
pain. The strategy for managing constipation from chronic opioid maintenance is
to follow a regimen on a routine basis to counteract the constipating effect of
the opioid medication. For many patients, a diet high in certain fruits or
cereals is sufficient. Many patients find that laxatives are necessary, however.
The following laxatives have been found to be effective: Senekot, PeriColace (Docusate
Plus Casanthrol), Milk of Magnesia, Maalox (or generic equivalent), and Dulcolax
tablets or suppositories. The laxatives should be taken in whatever dose is
necessary to provide regular BMs. Do not wait for a crisis. For patients who do
not respond to conventional measures of diet and over-the- counter laxatives,
Mestinon 60 mg, ½ -1 tab 3-4 times daily may be effective. This medicine,
normally used to treat Myasthenia Gravis, has a direct effect on the muscles of
the bowel to counteract the constipating effect of the opioids. It also relieves
the dry mouth often associated with opioid therapy.
If your bowels have not moved for a number of days, you may try a higher dose
than usual of your customary laxative. If constipation is associated with severe
nausea or vomiting, use an enema (tap water, soap suds, or commercial Fleet's
enema) to relieve the obstruction from below. If these measures are ineffective,
seek medical attention.
Men may lose interest in sex or suffer from decreased potency with chronic
opioid use. In most cases, this is due to suppression of
testosterone production and can be reversed by administering supplemental
testosterone as an oral tablet or as an injection.
Just as chronic pain may lead to depression and a sense of hopelessness, pain
relief may bring a renewed sense of vitality and enjoyment of life. If
pain relief and increased activity do not by themselves relieve depression,
antidepressant medications may be useful. The selection of the right
medication is a trial and error process made more complicated by interactions
between pain medications and the antidepressant medicines. Occasionally,
depression may be caused or worsened by tranquilizing medications like Valium or
Klonopin. Discontinuing such medication is the first step in evaluating
and treating depression.
Edema (fluid retention)
Many patients on opioids develop swelling in their feet and lower legs. This may
be a response to increased fluid intake to relieve a chronically dry mouth, or
it may be due to fluid retention or vascular dilatation caused by opioids. In
either case, the treatment is a low salt diet and the restriction of fluid
intake. The patient should also lie down in bed with legs raised on pillows
until the edema disappears. If these measures are ineffective, a diuretic, such
as Demadex , Maxzide, Aldactone, or Lasix, may be added. Headache
Opioids may trigger vascular headaches, characterized by a sense of heaviness or
throbbing in the back of the skull or in the forehead and temples. Often these
headaches will respond to Acetaminophen (Tylenol), Aspirin, or Ibuprofen (Advil
or Motrin). In susceptible patients, opioids can trigger Migraines. Ritalin may
prevent or abort these headaches.
Paradoxically, insomnia is often a side effect of opioid medication. If it is
found that one of the opioids causes sedation (usually Methadone or Morphine),
this medication may be reserved for use at bed time. If a patient awakens in
pain, a long acting form of Morphine may be used at bedtime (MS Contin).
Increasing the level of physical activity and exercise helps to promote sleep,
as does keeping to a consistent schedule. Some patients have benefited from
Melatonin, the hormone the body produces to induce sleep, which is available
without a prescription.
If these strategies are not successful, insomnia may be treated with medication
which do not have a significant risk of respiratory depression. The
anti-depressant medications, such as Desyrel (Trazadone) 50-100 mg or
Pamelor(Nortriptyline) 25-50 mg at bed time are safe for this purpose. In many
patients the use of stimulants, such as Ritalin or caffeine, early in the day
may improve sleep at night by promoting daytime physical activity and, perhaps,
as a rebound effect from the stimulant. Occasionally, such sedating medicines as
Valium or Serax (Oxazepam) may be necessary, although these medications pose a
higher risk of respiratory depression and are often associated with worse pain
control and psychological depression.
Itching and Skin Rash
Itching without a rash is a pharmacological side effect of opioid medication
rather than a true allergic reaction. It will respond to treatment with Vistaril
25 mg or Benadryl 25 mg every 4-6 hours. As tolerance to the medication
develops, the itching will usually become less or cease altogether. Itching
associated with a rash is an allergic symptom. When this occurs, the offending
medication should be discontinued and an alternative substituted.
Nausea and Vomiting
Nausea and vomiting are among the most frequent early side effects of opioid
treatment. Nausea and vomiting can arise from a direct effect of opioids on the
brain, or from constipation. If the nausea is mild it may be controlled by
decreasing the dose or frequency of opioid medication and by taking Vistaril 25
mg 1 tab every 4-6 hours as needed. An alternative medication is: Phenergan 25
mg 1 tab every 4-6 hours. Nausea usually disappears as patients become tolerant
to the medication that causes it, but some patients are unable ever to tolerate
certain of the opioid medications. During the initial medication trial, if a
medication causes significant nausea, that medication should be stopped and an
alternative tried instead.
Although all of the opioids can cause nausea and vomiting, Hydromorphone (Dilaudid)
and Levorphanol (LevoDromoran) seem to do so less frequently. Severe nausea and
vomiting to the point that a patient is unable to keep any liquids down is a
serious medical situation that requires evaluation by a physician. Some patients
may require IV fluids to maintain hydration. These symptoms may indicate serious
conditions other than opioid toxicity, such as bowel obstruction, stomach
ulcers, Acetaminophen toxicity, or gastroenteritis.
Although sedation is a common side effect during the initiation of opioid
treatment, particularly with Methadone and Morphine, this symptom often becomes
less troubling as tolerance to the medication develops. However even for opioid-tolerant
patients, the addition of Muscle Relaxants, such as Soma, (Carisoprodol) and
Tranquilizers, such as Valium, Klonopin, Ativan (Lorazepam) may have an
exaggerated sedative effect. Patients on opioids should also abstain from
alcohol. Excess sedation may be manifest by slurred speech, poor balance and
coordination, and excessive sleepiness. These symptoms may indicate significant
danger, as in some cases, excess sedation may proceed to respiratory depression
and death. Such medication may also impair memory and judgment and the ability
to recognize the above symptoms in one's self.
Anyone with a history of sleep apnea (pauses
in respiration for 15-20 seconds during sleep) should not take these
medications. Spouses, room-mates, or close friends should be advised to seek
medical assistance if they observe any of the above signs of excess sedation.
These medications should be used sparingly, in the minimum dose and frequency to
Anyone who has been taking opioid medication routinely is likely to suffer
withdrawal symptoms if the medication is abruptly discontinued. Occasionally,
the withdrawal syndrome occurs as a side effect of taking Talwin (Pentazocine) a
pain medication that has opioid antagonist activity. The intensity and duration
of the syndrome varies from person to person, depending on the dose of
medication they routinely take. The acute symptoms may last from a few days to
more than a week.
The most common symptoms of withdrawal are: increased pain, generalized aching,
cold sweats, restlessness, tremors, involuntary movements, dizziness, nausea,
vomiting, diarrhea, sneezing and yawning. The syndrome can be stopped by
resuming opioid medications. If you anticipate discontinuation of opioids, the
withdrawal syndrome can be made more tolerable by gradually tapering the dose. A
reduction of 10-20 % of the initial dose every 3-6 days will reduce the severity
of the withdrawal syndrome. The addition of Clonidine 0.1-0.3 mg 1-2 tabs every
6-8 hours will further mitigate symptoms. Clonidine is also available as a
transdermal administration in the Catapress TTS patch. Restlessness and tremors
respond to tranquilizers, such as Valium 5-10 mg every 6 hours.
To avoid running out of medications and
suffering unplanned withdrawal symptoms, take precautions to avoid loss, keep
track of your rate of utilization of medication, order refills in a timely
manner, and maintain a reserve supply for emergencies. The development of severe
nausea and vomiting may make it impossible for a patient to take his or her
customary medications. As noted above, inability to take food or fluids that
doesn't resolve in a few hours requires medical attention to maintain hydration
and to administer opioids by means of injection. For patients who suffer
frequently recurrent nausea and vomiting, the Duragesic Patch may provide an
alternative route of opioid administration. MS Contin, OxyContin, and Methadone
may be administered rectally, if oral administration is not tolerated.
This article was written by Dr.
PAIN RELIEF PUMP #1449
Television News Service/Medical Breakthroughs
©Ivanhoe Broadcast News, Inc. July 1999
When fighting a painful, terminal condition, prolonging life is just one
battle. The other is maintaining a decent quality of life. According to
a Wake Forest University pain specialist, about 20 to 30 percent of
terminal patients don't get adequate pain relief. Others can't tolerate
their side effects. Now there's a new method of pain relief for these
With painful cancer inside his bones, Bill Webster can't get around like
he used to. That doesn't stop him from going places. "A lot of times I
imagine I'm on a trip, going to Tennessee or somewhere," says Bill.
Bill's got something inside that helps him control the pain that not
many other Americans have -- a morphine pump beneath his skin. He says,
"I don't know it's there until I use it. It's just part of my body."
Richard Rauck, M.D., a pain specialist at Wake Forest University's
Baptist Medical Center in Winston-Salem, N.C., headed a clinical trial
at the university to test the new device. He expects FDA approval by
"I can give somebody like Bill about one one-hundredth of the amount of
morphine he would take by mouth or even through an intravenous line.
It's a much more powerful way to deliver the morphine," say Dr. Rauck.
Bill pushes buttons through his skin. One dose of morphine travels from
the implanted pouch straight into his spinal cord. The pouch holds 50
doses and is refilled by syringe once a month.
Dr. Rauck says, "Before now, patients either stayed in very bad pain, or
they were almost anesthetized or asleep all the time." That's not the
life Bill wants. He's ready to roll.
The pump has a built-in safety mechanism that keeps the patient from
being able to overdose on the medication. It only allows a dose to be
given every 60 to 90 minutes. The manufacturer of the device expect it
to be available this winter.
If you would like more information, please contact:
Wake Forest University/Baptist Medical Center
Health on Call
Medical Center Blvd.
Winston-Salem, NC 27157
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