Tag Archives: Marijuana

My mom’s pain

For the last 7 years or so my mom has been living with chronic pain. She has always done a lot physically and could never sit still. After emptying out my Grandmother’s house, the pain got worse… she has tried every pain pill and received a marijuana medical card… nothing has worked… and many pills did more harm. Several doctor’s told her it was in her head… a few others said she needed back surgery which she had on her L5 S1 which made it even worse.

She has just tried this nerve stimulator and it seems to be working… thank God… she said if it didn’t she couldn’t live with the pain any longer.

She is going back tomorrow to have the temporary one removed then have the permanant one put in….so far….so good…..we all pray this works!

Marijuana Policy Discussion

Douglas Hiatt, Seattle criminal defense attorney and co-author of I-1068, joined several other local experts to discuss marijuana legal reform at Seattle Town Hall. The community discussion aired live on Seattle Channel and featured audience participation. Several I-1068 volunteers spoke up and made their voices heard. Watch:

LPHS….What now?

After reading many of the stories on this site, I have come to realize the one thing everyone has in common is the fact that they are alone in how they feel. I have been recently diagnosed with LPHS, my 16 year old daughter is in testing for conformation of this condition also. I relate to her feelings, and though it may seem a blessing to have someone around who understand, it is really a curse to see my daughter falling to the same fate as I. She is just getting started in life, and has so much ahead of her. Treatment options are also different for a child. Narcotic pain meds may work, but further damage the body, and may become addicting. Also not prescribed to a minor child here. Marijuana is an option, but not at 16. How is she to live with this? What can I do for her? Anyone have suggestions?

I can be reached at [email protected]

NY – Beth Israel Medical Center

Russell Portenoy, MD
Pain Medicine Specialist
Chairman, Department of Pain Medicine and Palliative Care, Beth Israel

Depression and Chronic Pain Is Extremely Common

In some patients, depression follows the pain, and if you can effectively treat the pain, the depression would get better. And in some patients the depression seems to drive the pain, says Dr. Portenoy. He explains that when these two conditions coexist, patients need carefully coordinated treatment.

Dr. Portenoy is among New York Magazine’s “Best Doctors” for 2008, as listed in the June 16, 2008 edition of the magazine. The New York Magazine list is excerpted from Castle Connolly’s annual guidebook, “Top Doctors: New York Metro Area.”


First Avenue at 16th Street
New York NY 10003
Telephone:(212) 844-1505

Questions About Using Opioids for Chronic Pain

Q: Would you say that opioids are a last resort?

A: No. Opioids should be considered for every patient with chronic, moderate to severe pain, but in every case, you would only prescribe the opioid after carefully considering the responses to several questions.

Q: What are those questions?

A: First, what is typical treatment with respect to this pain? Second, is there some other therapy that has as good or better efficacy and safety? Third, is this person at relatively high risk of opioid side effects for whatever reason? And fourth, is this patient likely to be a responsible drug taker, or is there a history of substance use problems?

So in some cases, for example a patient with severe pain who has not done well with several steroid or other drug injections and physical therapy, and who presents to the doctor with back pain so severe that he can’t walk—that patient might be considered a candidate right then for a trial.

Q: What is an example of that review process with a typical patient who has arthritis of the knees and hips.

A: Everybody would agree that the first-line therapies typically would include acetaminophen, physical therapy, or a TENS unit, or maybe—if there’s a single joint that has some swelling—an injection.

The next-line therapy would be an NSAID. But if that person has a history of an ulcer or a history of bad heart disease, the NSAID risk gets to be relatively high. So that patient might be considered for a trial of an opioid at that point.

Q: If I’m that patient and I’m put on a trial, how will I use the drugs?

A: Almost everyone with chronic pain appears to benefit more from regular, fixed, scheduled use as opposed to PRN [when needed] use. There is a general perception, two decades old, that patients do better if they have pain medicine in their blood 24/7. It’s done in a sustained way, so that the blood levels don’t fluctuate much.

Q: In the whole range of treatments for chronic pain, where do opioids fit in?

A: The chronic use of opioid therapy to treat noncancer pain syndromes, such as headache and low-back pain, and arthritis, continues to be controversial. Most pain specialists nowadays would say that opioids might be considered in any patient who has chronic, moderate to severe pain, but generally should only be implemented if there are no other treatment options that have a favorable and safe effect. The shortest way of saying this is that most pain specialists would not consider opioids first-line treatment for chronic noncancer pain except in highly selected patients.

But we have accumulated clinical experience that suggests the following: There is a sub-population of patients with chronic pain, who can be given access to long-term opioid therapy, and they will experience sustained and meaningful control of pain in the absence of intolerable side effects and without the development of tolerance or the need for dose escalation. And they will not develop any aberrant drug-related behaviors consistent with abuse, diversion, or addiction.

Q: What about the use of opioids for breakthrough pain?

A: It looks like about 60% of patients with chronic pain have flairs that can be called breakthrough pain, and in the cancer population, the use of a short-acting opioid co-administered with a long-acting drug is the standard of care.

With noncancer pain, it’s a moving target. People are trying to figure out if it should be the standard of care or not. I think it should not. I think it should be a case-by-case decision.

Q: What are some of the risk factors when opioids are being considered? Do they all relate to addiction?

A: No. Suppose you have a patient with very bad lung disease who might be at risk for the respiratory effects. (Opioids can suppress breathing.) Or you have a patient who has severe gastrointestinal problems—where the constipation induced by the opioid might become very problematic. Or you have an elderly person with arthritis who has a mild dementia: In that case, the bias would be to try an NSAID because the opioid has a higher likelihood of causing cognitive impairment.

Q: Is the ultimate concern, though, addiction?

A: No, it’s broader than that. It’s responsible drug use, a term I use purposely because for clinicians, addiction is an uncommon problem—a very, very serious problem, but it’s an uncommon problem.

Q: So there are irresponsible uses that do not involve addiction?

A: What’s much more common for clinicians than addiction is what has been called aberrant drug-related behavior. Behaviors like doctor shopping or frequent visits to the ED [emergency department], or increasing the dose during pain flare-ups without permission. Or taking an opioid to help you get to sleep at night, or taking it when you’re feeling anxious. Or in some cases using an illicit drug, like smoking marijuana on the weekend, without telling you.

A clinician who is trying to prescribe these drugs safely ought to be monitoring all of those behaviors and trying to work with the patient so that the behavior regarding these drugs is responsible—meaning take the drugs as prescribed.

Q: It’s not as simple as saying that opioids deliver a “high,” is it? What “benefits” do abusers get from the drugs?

A: There are studies that have been done that show that in the usual person—with no history, and no family history of addiction—the typical mood response produced by opioids is dysphoria, not euphoria. But in some cases, they might be driven by co-morbid psychiatric disease—they may have anxiety disorder and realize that these drugs produce some reduction in anxiety. Or they have a depressive disorder—these drugs were used in the 1950s as antidepressants before we had any real antidepressants.

Or the patient may have a co-morbid psychiatric disorder associated with impulsive drug use—they would take any centrally-acting drug, any drug that alters their consciousness, impulsively.

There are also people who have an addiction biology, and it’s profound. I talked to a physician who became addicted to opioids, and he told me that the first time he took an opioid, it was like he had discovered something very magical about life. He said, “I knew this was my substance, this was something that I needed.” With a single dose.

Q: What is the risk of actual addiction?

A: Most scientists who work in this area think that about 10% of the population in developed countries have the biological predisposition, the genetic predisposition, to potentially become addicted. Truly addicted. Which is a huge number, 10%.

Q: If a chronic pain patient passes your various tests and is a good candidate for an opioid, what happens then?

A: At the present time the professional community is telling doctors that they have two obligations whenever they prescribe a controlled prescription drug.
Number 1: To know the pharmacology so that the patient’s outcomes—meaning the pain relief they get, and the side effects they experience—those outcomes are optimal.
Number 2: They need to do risk assessment and management to ensure that the patient takes the drugs in a responsible way, and there is minimal risk of abuse, diversion, and addiction.

Q: What does that mean for the patient’s experience?

A: Every patient should undergo a comprehensive assessment and risk stratification. The doctor takes a history and then makes a decision: Is this person at high risk or at low risk of developing problematic drug-related behaviors?

The most accepted factors that put a person into a high-risk category is a personal history of substance abuse now or in the past, a family history of substance abuse now or in the past, or a history of major psychiatric disorder. And there are many, many other factors: Current smoking, history of physical or sexual abuse.

Q: Give an example of a high-risk patient.

A: A young man who injures his back at work and has pain for six months, sees a doctor, and the history reveals that the patient binge drinks on the weekend, uses marijuana three nights a week, and has a brother who has been through detox. If an opioid is being considered for that patient, then the structure of the therapy should be very defined and very rigid, it might include any or all of the following.
An opioid agreement that is used to educate the patient about responsibilities and consequences of bad behavior
A small number of pills prescribed
The requirement that the patient returns with the pill bottle so that a pill count can be done
The requirement that the patient gets urine drug screens periodically
A requirement that the patient gets a consultation with an addiction-medicine specialist
The requirement that the patient uses only one pharmacy, so that you can track what has been dispensed

Q: What about a low-risk example?

A: A patient 70 years old develops bad knee and hip pain from arthritis, and the history reveals no personal history of substance abuse, including no use of alcohol, no family history, and no known psychiatric disease—that patient has very, very low risk of developing problematic behaviors. For that patient, a structure might be to come back in a month and provide a phone call in the middle.

Q: Sounds complicated. Should chronic pain patients seek out a specialist?

A: Only about 5% of people with chronic pain ever see a specialist. This is a type of therapy that, for 20 years, people like myself had been promoting as needing to be done by primary care doctors.

Q: What advice do you give patients who are looking for possible opioid treatment?

A: I would like patients to think, “Opioids may or may not be appropriate. But I need to see a physician who’s comfortable with prescribing opioids and also knows how to do it in a way that’s safe and effective for me. When I go into that physician, I know that I’m going to have to be honest and let that person do a good assessment. And I’m going to have to provide my records to that person. If that means that I have to have urine drug screens, so be it. If I have to sign an opioid agreement, if it’s reasonable and educational, I’ll sign it. If I have to go and get treated by a psychologist at the same time and I can afford it, I’ll do it.”

There has to be a recognition that this is a controversial therapy that takes a lot of effort on the part of the clinician, and the patient has to not only adhere to the therapy, but also has to communicate and be willing to be monitored.

Q: Given all that, do you believe that opioids are underused in the treatment of chronic pain?

A: Absolutely. I’ve seen this controversy in the U.S. going back and forth for about 25 years. This is a pendulum that swings back and forth depending on how frightened people are of addiction and abuse, and depending on how much the advocacy community gets the word out about undertreatment.

There’s a whole political and social context here that is not based on any known science. And in the 2000s we seem to have the pendulum shifting toward more denial that the therapy can be useful, more reluctance to prescribe, more concern about regulation.

Q: That’s an unfortunate swing for those people who would benefit from these drugs.

A: No question. But I want to acknowledge what my colleagues would say, many of them—that 25 years of research has yet to show the evidence that long-term opioid use is effective for chronic pain.

There have been a large number of good clinical trials, but they’ve all been either short-term or in very selected populations, or didn’t measure all the issues.

But the bottom line is that we have about 9,000 years of clinical experience showing that they can work. And you also have a consensus in the professional community of pain specialists—not just in the U.S., but also in Canada and England and other countries in Europe. You have a consensus that has evolved based on the data that do exist and the observations that exist.

The real issue is, let’s stop arguing about should patients ever get opioids and start arguing about who should get them and how you prescribe in a way to optimize the outcomes.

Q: Of course, even when drugs work, patients don’t always take them.

A: In the past 20 years, there’s been all of these new modified-release formulations, so now there are once-a-day drugs, twice-a-day drugs, patches that last three days, all for the treatment of chronic pain.

So you would think that compliance would be easier because it’s more convenient, and in some respects that’s true. But we just did a little study here, which we haven’t fully analyzed yet or published, and what we discovered in our group was this: In almost 100 patients, about 50% were non-adherent, and the vast majority of that group was undertreating.

It raises questions: Why are they undertreating? Are they afraid? Or do they have side effects? Is it money?

The bottom line is, most patients are not out there acting like [drug addicts], most patients are pushing you to give less, or not taking everything you prescribe. They’re not interested in abuse, they’re interested in getting off this stuff!

In Severe Chronic Pain since March 2001

Hi my name is Brian and the severe chronic pain has been a part of my life for seven years. I worked with a moving company. We were moving a family into a very large house they had built and was now compleated.

One of the movers and Iwere told to move the pool table into the garage. (This was the last piece of furniture on the truck). Were were near the garage and decided to catch our breath. As were setting the pool table down I heard a very loud pop, almost a thud, in my head. I wasn’t sure what had happened and looked to see what made the noise. I noticed no pain or discomfort at that time. I did not see what could have made the noise so I just forgot about it.

Now that were done with the move I got into the truck and noticed that my leg was numb. I thought for a minuet that it was because we worked so hard to get the move done. I did tell the driver and the guy I worked with but realy thought nothing of it. That was untill we were back at main office. I got out of the truck and my leg and foot were not there for me to stand on. I knew that I was introuble.

Since the accident I have had surgery and tried almost every pain medication known. I have tried physical theropy with little or no sucess. Nerve blocks, faucet blocks, steroid shots, ect. and hoemeo pathic, wich is natural ways for pain and other things, every type of electro shock TENS units, nerve stimulators, muscle stimulators, accupuncture, orthropedics and did get some relief from it but like everything else I developed an amunity to the efects.

I am now looking into how marijuana has had a positive affect on back pain. If there is anyone who could point me inthe right direction could you please contact me.

Supreme Court to hear medical marijuana case

The Supreme Court this week agreed to hear an appeal of a ninth U.S. circuit court of appeals ruling that the federal ban on marijuana is unconstitutional when applied to seriously ill people who use the drug under a physician’s recommendation in states where such use is permitted, the Los Angeles Times reports. The appeal was filed by Atty. Gen. John Ashcroft, who maintains that marijuana use is banned under federal law in all instances. The circuit court ruling says the ban does not apply to marijuana use in the nine states that have legislature- or voter-approved medical marijuana laws so long as the drug is not sold, transported across state lines, or used for nonmedical purposes.

The original case stemmed from two California women who received letters from their doctors authorizing them to use medical marijuana, which is permitted in the state, and who filed a lawsuit in 2002 against Ashcroft and former DEA administrator Asa Hutchison asking for an injunction against federal prosecution. A judge initially ruled against the women, but that ruling was overturned by the ninth circuit court. The case is scheduled to be heard by the Supreme Court this fall, and a decision is expected by the end of June 2005.

Currently, California, Alaska, Colorado, Hawaii, Maine, Nevada, Oregon, Vermont, and Washington have laws permitting the use of medical marijuana. Thirty-five other states have enacted legislation recognizing the drug’s medicinal value; the federal government considers marijuana to have no legitimate medical benefits.


ACTIQ is a medication in a unique oral transmucosal delivery system (OTS?). It offers personal pain control by providing pain relief in 15 minutes (though you may not experience full relief for up to 45 minutes after finishing an ACTIQ unit). Actiq is designed to be dissolved slowly in the mouth in a manner to facilitate transmucosal absorption.

Actiq is supplied in six dosage strengths. Each unit is individually wrapped in a child-resistant, protective blister package.

Active Ingredient: Fentanyl citrate C-II

Pregnancy – Category C

Fentanyl has been shown to impair fertility and to have an embryocidal effect with an increase in resorptions in rats when given for a period of 12 to 21 days in doses of 30 mcg/kg IV or 160 mcg/kg subcutaneously.

Actiq Dose
200 mcg, 400 mcg, 600 mcg, 800 mcg, 1200 mcg, 1600 mcg

General considerations: Each
transmucosal unit contains about 2 g of sugar. Frequent consumption of products containing sugar may increase
the risk of dental caries, and dry mouth associated with opioid use may add to
the risk.
Patient counseling:  Diabetic
patients should be advised that each
unit contains about 2 g of sugar. To ensure appropriate oral hygiene, all
patients should be told to consult their dentist.

Manufacturer: Cephalon
Manufacturer’s website: www.cephalon.com
Product website: www.actiq.com


Breakthrough cancer pain in patients with malignancies who are already
receiving and who are tolerant to opioid therapy for their underlying persistent
cancer pain:
200 µg to start; thereafter, closely follow patient
and change dosage level until patient reaches a dose providing adequate
analgesia using a single dosage unit per breakthrough cancer pain episode.
Redosing within a single episode: Until appropriate dose is reached,
patients may need to use an additional unit during a single episode. Start
redosing 15 min after previous unit has been completed (30 min after start
of previous unit. While patient is in titration phase and consuming units
that might be subtherapeutic individually, patient should take to more
than two units for each individual cancer breakthrough pain episode.

Patients considered to be opioid tolerant are taking at least 60
mg/day of morphine, 50 µg/h of transdermal fentanyl, or an equianalgesic
dose of another opioid for at least 1 wk.

Initial prescription: Prescribe an initial titration supply of
six 200-µg units to limit the number of units in the home during
titration; patient should use all units before increasing to a higher dose.

Increasing dose: If more than one unit
is needed per episode during treatment of several consecutive breakthrough
cancer pain episodes, consider an increase in dose. At each new dose during
titration, prescribe six units of the titration dose. Evaluate each
new dose over several episodes of breakthrough cancer pain (generally 1-2
days) to determine whether new dose provides adequate efficacy with acceptable
adverse events. Incidence of side effects is likely to be greater during
initial titration period.

Administration: Immediately before use, open foil package with
scissors. Place unit between cheek and lower gum, occasionally moving drug
matrix from one side to another using handle. Unit should not be chewed;
if chewed or swallowed, lower peak concentration and bioavailability may
occur. Advise patient to consume unit over 15 min; longer or shorter
consumption time may lead to lesser efficacy.

Titration of dosage: Individually titrate to a dose providing
adequate analgesia and minimal side effects. If signs of excessive opioid
effects appear before unit is consumed, remove dosage unit from patient’s
mouth immediately, dispose of unit properly, and decrease subsequent doses.
Patients should record their use of drug over several episodes of breakthrough
cancer pain and review their experience with their physicians.

Maximum daily dose: Once successful dose has been found, limit
consumption to four or less units/day. If consumption increases above this
level, reevaluate dose of long-acting opioid used for persistent cancer

Dosage adjustment: Dosage adjustment of both fentanyl and the
maintenance opioid analgesic may be needed to continue to provide adequate
relief of breakthrough cancer pain (see "Increasing
," above). Consider increasing around-the-clock opioid dose
used for persistent cancer pain in patients who have over four breakthrough
cancer pain episodes daily.

Disposal of units: Advise patients to dispose of completely used
and partially used units. After complete consumption of unit and total
dissolution of matrix, throw handle away in a trash container out of reach
of children. If any drug matrix remains on handle, place handle under hot
running tap water until all of the drug matrix is dissolved, and then dispose
as above. Dispose of handles in the child-resistant container at least
once daily. If patient does not consume the entire unit and remaining drug
cannot be dissolved immediately as above, temporarily store the unit in
the provided child-resistant container until proper disposal is possible.
To dispose of unused units, remove unit from pouch using scissors, hold
unit by handle over the toilet bowl, cut off drug matrix end using wire-cutting
pliers so that it falls into the toilet, and dispose of handle in a place
out of reach of children; then flush toilet twice after 5 units have been
cut and deposited into the toilet. Do not flush entire units, handles,
foil pouches, or carton. If caregivers need more information, instruct
them to call 800/615-0187.

Discontinuation of therapy: A gradual downward titration is recommended
for patients discontinuing opioid therapy; it is not known at what dose
level the opioid may be discontinued without producing signs and symptoms
of abrupt withdrawal.

Patient Monitoring

Patient instructions: Question patients or caregivers of the
presence of children in the home on a full-time or visiting basis. Advise
patients and caregivers that this dosage form contains a medicine in an
amount that could be fatal to a child; partially consumed units pose a
particular risk. Instruct patients and caregivers to keep all units out
of the reach of children, and to discard opened units properly in a secured
container. Supply patients and providers with the Actiq Welcome Kit, which
contains educational materials, safe storage containers, and a patient
safety video; give patients the opportunity to discuss the video. For more
information on these materials, call 800/615-0187. Advise patients to consult
their dentist to ensure appropriate oral hygiene. Inform diabetics that each
unit contains about 2 g of sugar.

General Considerations

Hypersensitivity: Contraindicated in patients hypersensitive
to fentanyl or any component.

Inappropriate uses: Because of risk of life-threatening hypoventilation
at any dose in patients not taking chronic opiates, drug is contraindicated
in managing acute or postoperative pain. Risk of respiratory depression
begins at fentanyl plasma levels of 2 ng/mL in opioid nontolerant individuals;
do not use in opioid nontolerant patients.

Respiratory depression: Clinically significant hypoventilation
may occur; carefully observe patients for symptoms of respiratory depression.
Hypoventilation may occur more readily when opioids are given with other
respiratory depressants. Titrate with caution in patients with chronic
obstructive pulmonary disease or preexisting medical conditions that may
predispose to hypoventilation; normal analgesic doses of opioids may further
decrease respiratory drive to point of respiratory failure.

Ambulatory patients: Caution patients not to engage in potentially
hazardous activities requiring full mental alertness.

Sugar content/dental caries: Each unit contains about 2 g of sugar.
Frequent consumption of products containing sugar may increase risk of dental
caries, and dry mouth associated with opioid use may add to risk.

Renal or hepatic impairment: Use caution because of importance
of the liver and kidney in the metabolism and excretion of drugs and effects
on plasma binding proteins.

Advanced age: Elderly patients are twice as sensitive to effects
of fentanyl as are younger patients. Use caution.

Adverse reactions: Side effects seen are typical of opioids;
adverse events frequently will stop or decrease in intensity with continued
use, as patient is properly titrated. Manage side effects accordingly.

Dependence: Physical dependence usually does not occur until
after several weeks of continued opioid usage; tolerance initially is manifested
by shortened duration of analgesic effect and decreased intensity of analgesia.

Head injuries, increased intracranial pressure: Use extreme caution
in patients who may be particularly susceptible to intracranial effects
of CO2 retention (eg, those with increased intracranial
pressure, impaired consciousness). Opioids may obscure clinical course
of patients with head injury; use only if clinically warranted.

Cardiac disease: Use caution in patients with bradyarrhythmias;
drug may produce bradycardia.

Pregnancy: Use only if expected benefits justify potential fetal
risks (Pregnancy Category C).

Labor and delivery: Not indicated for analgesia during labor
and delivery.

Breast-feeding: Do not use in nursing mothers.

Pediatric use: Appropriate dosing and safety in opioid tolerant
children under 16 yr of age with breakthrough cancer pain not established.

Adverse Reactions
Frequent reactions (incidence of 1% or more) are printed
in italics. Reactions were reported in 254 patients taking any dose
tested. All patients also were taking concomitant opioids, such as sustained-release
morphine or transdermal fentanyl, for persistent cancer pain.

Cardiovascular: Migraine (1% or more); deep
thrombophlebitis, hypertension, and hypotension (< 1%).

Dermatologic: Pruritus, rash, and sweating (2%); alopecia
and exfoliative dermatitis (< 1%).

Digestive: Nausea (23%), vomiting (12%), constipation (4%);
diarrhea, dyspnea, and flatulence (1% or more);
anorexia, eructation,
esophageal stenosis, fecal impaction, gum hemorrhage, mouth ulceration,
and oral moniliasis (< 1%).

Genitourinary: Vaginal hemorrhage, dysuria, hematuria, urinary
incontinence, and urinary tract infection (< 1%).

Neurologic: Dizziness and somnolence (17%), asthenia (9%),
headache (6%), confusion (4%), anxiety (3%), abnormal gait, dry mouth,
nervousness, and vasodilatation (2%), hallucinations, insomnia, abnormal
thinking, vertigo, and hypesthesia (1% or more);
abnormal dreams, urinary
retention, agitation, amnesia, emotional lability, euphoria, incoordination,
decreased libido, neuropathy, paresthesia, and speech disorder (< 1%).

Respiratory: Dyspnea (4%); pharyngitis, increased cough (1%
or more);
hemoptysis, pleural effusion, rhinitis, asthma, hiccup, pneumonia,
respiratory insufficiency, and increased sputum (< 1%).

Miscellaneous: Accidental injury and abnormal vision (2%);
pain, fever, abdominal pain, chills, back pain, chest pain, infection,
peripheral edema, and dehydration (1% or more)
; flu syndrome, abscess,
bone pain, anemia, leukopenia, edema, hypercalcemia, weight loss, myalgia,
pathological fracture, myasthenia, and taste perversion (< 1%).

Drug Interactions

CNS depressants, including alcohol; sedatives, hypnotics, general
anesthetics, phenothiazines, tranquilizers, skeletal muscle relaxants,
sedating antihistamines, other opioids:
Increased CNS depression. Hypoventilation,
hypotension, and profound sedation may occur.

Potent inhibitors of cytochrome P450 3A4 isoform (eg, ketoconazole,
erythromycin, and certain protease inhibitors [eg, ritonavir]):
or prolonged CNS depression. Hypoventilation, hypotension, and profound
sedation may occur. Monitor patients for a change in opioid effects and
adjust dose, if warranted.

MAO inhibitors: Not recommended for use in patients who
have received MAO inhibitors within 14 days, since severe and unpredictable
potentiation by MAO inhibitors reported with use of opioids.