- Methadone at Work
- Smack is Back- Big Time!
- From the Editor
- Events to Note
- Reader Survey Responses
- Methadone World Watch
- Enlightened Belgium
- Where to Get Info
Methadone at Work
In clinical practice spanning over 35 years, methadone taken daily and in appropriate doses has proven to be a safe, well-tolerated medication that is free of general and organ-specific toxicity. However, as with any medication, there are certain cautions associated with its use.
Contraindications
Methadone may interact with other substances resulting in symptoms that are associated with unexpected and/or undesirable blood levels of methadone. So it is usually advisable to consider which additional pharmaceuticals the patient may be taking – whether obtained via prescription, over-the-counter (OTC), or illicitly.
TABLE 1 (below) lists some drugs which are contraindicated for use in patients on methadone, since they may precipitate withdrawal. It should be noted that rifampin, which is listed on another table, might also induce withdrawal symptoms if administered in dosages sufficient to deplete methadone plasma levels.
| Generic Name | Action/Use | Brands/Examples |
| ·naltrexone | ·opioid antagonist used for treatment of alcoholism and/or blockade of opioid effects | ReVia |
| ·buprenorphine, butor phanol, dezocine, nabuphine, pentazocine, | ·pain relievers with opioid-antagonist activity | ·Buprenex®, Stado®, Dalganr®, Nubain®, Talwin® |
| ·tramadol | ·synthetic analgesic (not considered opiod antagonist, but does decrease levels of opiates) | ·Ultram® |
| ·nalmefene, naloxone | ·reversal of opioid effects | ·Revex, Narcan® |
Drug Interactions
TABLES 2-4 (below) list drugs which MAY interact with methadone. While many of those agents are still prescribed for patients receiving methadone, such patients should be monitored more closely.
| Generic Name | Action/Use | Brands/Examples |
| ·butabarbital sodium, mephobarbital, phenobarbital, pentobarbital, secobarbital | ·barbiturate sedatives and/or hypnotics | ·Bitosol Sodium®, Mebaral®, Nembutal®, Phenobarbital, Seconal® |
| ·carbamazepine | ·anticonvulsant for epilepsy and trigeminal neuralgia | ·Atretol®, Tegretol® |
| ·ethanol | ·chronic use | ·wine, beer, whiskey, etc. |
| ·phenytoin | ·control of seizures | ·Dilantin® |
| rifampin | ·treatment of pulmonary tuberculosis | ·Rifadin®, Rifamate®, Rifater®, Rimactane® |
| ·urinary acidifiers, ascorbic acid | ·keeps calcium soluble, controls urine-induced skin irritations, vitamin C | ·K-Phose®, Vitamin C (large doses) |
| Generic Name | Action/Use | |
| ·amitriptyline | ·treatment of depression and anxiety | ·Elavil®, Endep®, Etrafon®, Limbitrol®, Triavil® |
| ·cimetidine | ·H2 receptor antagonist for the treatment of gastric and duodenal ulcers, and gastric reflux disease | ·Tagamet® |
| ·diazepam | ·control of anxiety and stress | ·Dizac, Vairelease®, Valium |
| ·ethanol | ·acute use | ·wine, beer, whiskey, etc. |
| ·fluvoxamine maleate | ·serotonin reuptake inhibitor for treatment of depression and compulsive disorders | ·Luvox |
| ·ketoconazole | ·anti-fungal agent | ·Nizoral® Tablets |
| ·urinary alkalinizers | ·treatment of kidney stones, gout therapy | ·Bicitra®, Polycitra® |
| Generic Name | Action/Use | Brands/Examples |
| ·desipramine | tricyclic antidepressive | Norpramin® |
| ·zidovudine | initial treatment of HIV | Retrovir®, AZT combinations |
PLEASE NOTE: These tables are not presented as being all-inclusive of drugs which are contraindicated or may interact with methadone in some fashion. New pharmacologic therapies are being constantly introduced – especially for the treatment of psychiatric and neurologic disorders, and patients with HIV/AIDS – and only further clinical experience will determine their compatibilities with methadone. Even clinical experience with current drugs may not be complete, and there are often variations in individual reactions to any pharmaceutical combinations.
Methadone maintenance patients, as might be expected with any population of drug or alcohol addicted persons, are often dual diagnosed with “substance-induced mood disorders” (APA DSM-IV) and the TABLES list many agents used for treating such conditions – particularly anxiety and depression. Hence, such patients may encounter drug interactions that will alter their methadone blood levels. Besides those interactions noted in the TABLES, Scott Andersen, RPh – Clinical Pharmacist with the Addiction Medicine Program of Hennepin Faculty Associates (HFA), Hennepin County Medical Center, Minneapolis, MN – observes that all benzodiazepines, sedatives, and antidepressants may generally augment the effects of methadone to induce drowsiness.
Andersen also notes that some of the newer medications used to treat HIV infections, such as protease inhibitors, may also impact the metabolism of methadone, but specific effects have not been studied. Further, Hepatitis B and C, which are more common in certain addict populations, may alter the pharmacokinetics of methadone metabolism by the liver resulting in unexpected blood levels – either higher or lower.
Finally, J. Thomas Payte, MD, Director of Drug Dependence Associates, San Antonio, TX, comments that cimetidine (Tagamet) which might increase methadone’s effects has been used clinically to offset the metabolism stimulating effects of drugs such as carbamazepine (Tegretol, Atretol) to achieve therapeutic blood levels.
OTC Drugs, Juice, Vitamins
John St. Peter, PharmD, BCPS – Pharmacist in Charge for HFA, and Assistant Professor, College of Pharmacy at the University of Minnesota – has previously expressed concern in Addiction Treatment Forum (Vol. IV, #2) about the potential interactions of methadone with OTC medications, tobacco, and caffeine. He noted, for example, that acetaminophen (e.g., Excedrin®, Tylenol®) has inherent toxicities which can affect hepatic drug metabolism and impact methadone blood levels.
St. Peter and his clinical team have also observed that there are drug metabolism differences between ethnic groups, such as Asians, Caucasians, and African-Americans. Age also plays a role affecting changes in drug metabolism. Other sources have noted that some persons are naturally “aberrant metabolizers” and “burn away” methadone up to four times faster than others. The specific roles of these differences regarding methadone metabolism, however, are still under investigation by the HFA team.
There has been some mention, often anecdotally, of grapefruit juice intensifying methadone’s effects when the two are regularly taken together. According to Andersen and Payte, grapefruit juice appears to inhibit certain enzymes (CYP-450 activity) that metabolize methadone in the liver, thus slowing its breakdown. Hence, higher blood plasma levels of methadone than expected might possibly result. Some sources have attributed naturally high concentrations of flavonoids in grapefruit juice as producing this effect.
Contrary to current myth, there is no accepted evidence that orange juice produces similar potentiating effects. However, Payte mentions that large doses of vitamin C (the amount might vary by individual) could create a more acidic urine leading to decreased methadone blood levels. This is because the acidic condition inhibits reabsorption of methadone by the kidneys, so more of the drug is lost in the urine. The plasma half-life of methadone could be reduced to as little as 16-20 hours in an acid urine. Conversely, in an alkaline urine (pH 7.8) a half-life of 42.1 +/- 8.8 hours has been reported.
False Positives
Finally, Andersen suggests two substances which might lead to urine test results that are falsely positive for alleged illicit opiates. Poppyseeds, while non-narcotic, are found in a variety of foods and have been known to cause such erroneous results. It is not known how many seeds must be eaten to produce the effect, but most of the offending substance would be eliminated after 48-72 hours, as is the case with opiates in general.
Dextromethorphan, a non-narcotic antitussive, is structurally similar to many narcotics, and could produce false positives. It can be found in many of OTC non-narcotic cough suppressants, such as: Robitussin-DM®, Vicks Formula 44®, and Delsym®.
In conclusion, it may be appreciated that methadone works best when administered in optimal therapeutic doses. However, like any potent agent, its pharmacology is complex and many factors may influence its blood serum concentration and ultimate effectiveness. Caution is called for when assessing the origins of reported adverse reactions and in prescribing other drugs as a component of therapy for concurrent mental and/or physical disorders.
REFERENCES…
– Kalvik, A., Isaac, P., & Janecek, E. (October 1996). Help for heroin dependence. Pharmacy Practice, Vol. 12, No 10, 43-54.
– Karlix, J. (Fall 1990). Pharmacists Corner [Untitled discussion re. fruit juice and medication levels in blood serum]. Prescription Plus. Ronkonkoma, NY: Lifecare Pharmaceuticals Services, p. 15.
– Parrino, M.W. (Chair & Editor), (1992). State Methadone Maintenance Treatment Guidelines. Rockville, MD: U.S. Department of Health and Human Services, Center for Substance Abuse Treatment.
– Nillson, M.I. et al. (1982). Effect of urinary pH on the disposition of methadone in man. European J Clin Pharm 22: 337-342.
– Rettig, R.A., & Yarmolinsky, A. (Eds.). (1995). Federal Regulation of Methadone Treatment (Institute of Medicine Report), Washington, D.C.: National Academy Press.
– Update on mood disorders-Part I. (Undated reprint MTL-RP). The Harvard Mental Health Letter, 3. [Primary reference in the article is made to Harvard Mental Health Letter (August/September, 1991)].
– Physicians’ Desk Reference (50th ed.). (1996). Montvale, NJ: Medical Economics Co.
– Woods, J. (Undated). How Methadone Works. [On-line]. Available: http://www.users.interport.net/~clueless/how.html
We wish to thank Tom Payte, John St. Peter, and Scott Andersen for their reviews of and contributions to this article.
Smack is Back- Big Time!
Heroin: Pure, Plentiful, Low-priced
A generation ago, the heroin (colloquially known as “smack”) available in the U.S. was barely five percent pure and used by a relatively small percentage of young people because it had to be injected with a needle. Now, it appears smack is back with a vengeance and it’s addicting large groups of new users.
Merely five years ago, the Office of National Drug Control Policy issued a report (April 1992, No. 5, pp. 1-6) claiming “a massive increase in heroin use and addiction is not likely.” One reason for this was, “…the apparent absence of new initiates (i.e., heroin users with little or no prior drug-using experience).” However, based upon recent news reports and other sources (see the A.T. Forum Web site for News Updates), the ONDCP report appears to have been premature, to say the least.
Just this past February, Attorney General Janet Reno admitted heroin is more plentiful, purer, and less expensive than it was just a few years ago. “If we do not counteract the heroin threat now,” she said, “we risk repeating the terrible consequences of the 1980s’ cocaine and crack epidemic.” Authorities estimate that heroin addiction has increased 20 percent and worldwide production has grown sharply, even as other illegal substance abuse is declining.
Reports of problems have sprung-up countrywide. In California, heroin sold in the San Joaquin Valley is cheap, potent, and plentiful – business is booming in area emergency rooms as two or three overdose cases appear each day. In Colorado, Boulder County officials may establish a methadone clinic for the first time in 16 years to deal with increasing heroin addiction. On the East Coast, heroin is reported to be 40 to 70 percent pure and around $10 for a small packet. The number of heroin-related hospital emergencies has more than doubled in New York City and surrounding areas.
Many drug abusers mistakenly believe inhaling heroin, rather than injecting it, reduces the risks of addiction or overdose. In some areas, “shabanging” – picking up cooked heroin with a syringe and squirting it up the nose – has increased in popularity. Street heroin carries prophetic names: “DOA,” “Body Bag,” “Instant Death,” and “Silence of the Lamb.” Rather than scaring off young initiates, the implied danger seems to actually increase the drug’s allure.
Will MMT Be In Greater Demand?
To better understand what the increased heroin threat might mean for the methadone treatment community, A.T. Forum spoke with Robert Lambert, MA. He is Program Director for the Connecticut Counseling Centers, Inc. (CCC) Norwalk, CT facility. This private, not for profit organization also has a clinic in Waterbury, CT.
“(Heroin) users tend to be younger – people are starting at 15 to 16 years old – and we’re getting more first time users coming into treatment,” he says. “They report that they became addicted faster, which they attribute to the purity of heroin.”
“We were actually starting to see the resurgence in heroin use back in the late-80s, yet the anti-drug messages and prevention programs then were focusing on cocaine. Since we always seem to focus on only one class of drug at a time, we’re always going to have a generation that misses the message on some substance. We may be into another cycle, with heroin as the drug of choice in the 90s and then back to an interest in stimulant use among young people. This is already starting on the West Coast.”
“These days, there’s very little pure addiction to any one substance – maybe among youngsters 12 to 14 who get caught smoking marijuana. But, by late adolescence into adult years we see multiple drug use in just about every case.”
Regarding the need for methadone treatment, Lambert sees a strong increase: “We traditionally had 90 methadone maintenance clients here (Norwalk) and in just the past six months we’ve grown to 110; by next week we’ll likely be at 120.The biggest increase has been at our Waterbury, CT clinic, going from 150 last year to nearly 400 now.” (CCC also offers drug-free substance abuse counseling; a 180 day ambulatory opiate detox program using methadone; a naltrexone program; HIV and TB testing, counseling, case management; pregnant addict care; and psychiatric services.)
However, Lambert believes there may be difficulties in meeting the demand due to changes in funding. “Right now, managed care handles the behavioral health care funds for AFDC clients and that may spread to all of Medicaid and then eventually to all of general assistance in this state. While many of the managed care companies are good about long term methadone maintenance, others are not. Some clients are being pressured to get off of methadone prematurely, we believe, and that may become more prevalent.”
“Most of our clients have insurance, or are on Medicaid or general assistance. Self-paying patients make up less than half and we’re partially funded by DMHAS (Department of Mental Health and Addiction Services) through a grant, which subsidizes our expenses for the self-paying clients. We also have some grants from private foundations and local charitable organizations, including the United Way.”
Is there a question about how MMT programs will increase treatment slots? “Well, there’s just not a great deal of additional funding available,” Lambert says. “There are good, existing programs that could greatly expand their capacity given the funding and it’s something that will have to happen to meet demand. The fall-out from new heroin users is usually three to five years down the line – so, what we’re seeing today is only the beginning, the tip of a growing iceberg. In the next five years or so there will be a major increase in people seeking long-term treatment for chronic heroin addiction.”
Straight Talk… from the Editor
Methadone Just Medicine
Rarely, if ever, has a pharmaceutical product taken on a life of its own as has methadone. Yet, the simple truth – which may seem so obvious to many readers as to need no comment – is that methadone is just a medicine used, among other things, to treat a chronic, relapsing illness – opiate addiction.
We agree with Robert G. Newman, MD, President & CEO of Beth Israel Medical Center, New York City, who commented to us (via e-mail): “The real issue is that in any field of medicine there are generally many different medications and at least as many other therapeutic interventions not using medication at all. In no other area (besides methadone therapy) does anyone suggest that it be a question of EITHER this OR that. Especially when dealing with a potentially fatal disease like narcotic addiction, as many different approaches should be available as offer promise. It all gets back to the fundamental problem: methadone is NOT viewed or accepted as a plain old ordinary medication for a chronic illness.”
In this issue of A.T. Forum we take a closer look at methadone as a medicine from the standpoints of contraindications and possible interactions with other drugs. While our review is not portrayed as being totally inclusive of all possible reactions, thanks to our expert contributors to the article, clinic staff and patients should find new information of interest.
Growing Needs for MMT?
Also in this issue, we look at the resurgence of heroin addiction, especially among younger persons, around the U.S., and growth trends in methadone maintenance treatment (MMT) worldwide. As usual, we invite reader feedback to learn of your views and experiences. Your responses to the following survey questions will be reported in our next issue:
1. Over the past year, has heroin addiction in the area served by your clinic been…
*increasing * about the same
* decreasing?
2. Compared to past years, are heroin users coming into MMT today
* younger * about the same age
* older?
3. Is funding adequate to meet needs for new treatment slots?
* Yes * No * Don’t know
* Additional slots not needed
Please provide your responses and comments on the postage-free feedback card in this issue, OR write or fax us, OR visit our Web site to respond quickly and electronically.
Addiction Treatment Forum
1750 East Golf Rd., Suite 320
Schaumburg, IL 60173
FAX: 847-413-0526
Internet: http://www.atforum.com
Stewart B. Leavitt, Ph.D., Editor
stew202@aol.com
Events to Note
For additional postings & information, see: www.atforum.com
May 1997
Black Alcoholism & Addictions Institute – May 24-28, 1997;
Atlanta Hilton & Towers
Contact Dr. Francis Brisbane: 516/444-2193
11th Pacific Institute on Addiction Studies – May 26-29, 1997;
University of BC, Vancouver
Contact Dave Thompson: 604/874-3466
ADPA Women’s Issues Conference – May 29-31, 1997;
West Coast location
Contact Ann Uhler: 503/590-4240
June 1997
Advanced School of Alcohol & Drug Studies – June 1-6, 1997;
New Brunswick, NJ; Sponsored by Rutgers University
Contact Gail Milgram: 908/445-4317
1997 Annual Meeting NASADAD – June 7-11, 1997;
Portland Marriott at Sables Oaks, Portland, ME
Contact Jo Lynn Reda: 202/783-6868
(To post your event announcement in A.T. Forum and/or our Web site, fax the information to: 847/413-0526 or submit it via e-mail from: http://www.atforum.com)