Avoiding Deadly Methadone-Medication Interactions 

Methadone interactions with other prescription and non prescription medications, cigarettes and even grapefruit juice, can increase or decrease methadone clearance, from the body.  Many medications commonly prescribed to methadone patients, including benzodiazepines (Xanax, Klonopin, Valium, Ativan, Serax, Restoril), tricyclic and selective serotonin reuptake inhibitor antidepressants, neuroleptics, antibiotics, antifungals, retrovirals, ribavirin and some cardiac drugs can have adverse reactions with methadone, often increasing or decreasing clearance rate of methadone.  Medications decreasing methadone clearance rate can produce fatal methadone overdoses. Nicotine cigarettes also decrease methadone clearance.

Opiate addicts frequently abuse medications decreasing methadone clearance, to obtain a longer or more intense “high,” or “buzz.”   Drugs increasing methadone level are most likely to cause a methadone overdose death.  Drugs or medications interacting with methadone are listed at   http://pain-topics.org/pdf/Methadone-Drug_Intx_2006.pdf.

Medications decreasing methadone level can cause methadone withdrawal which is seldom fatal, but nausea and seizures can occur during methadone withdrawal.  Many physicians prescribing methadone do not appear to adequately consider methadone interactions, with other medications. Tragically, fatal overdoses due to methadone interactions with medications continue to occur.   

I used to know so little about Methadone. I had read some of the major websites on the internet, which try to portray Methadone as safe and effective. What I didn't know was the extreme danger and lethal side effect of this dangerous medication.  With so little knowledge, my son and I decided for Matthew to enter a Methadone Maintenance Treatment program after relapsing on pain-killers for about a week; he had been drug-free for over six months.  Matt had started getting his life back together, enrolled back in college, started going to church, and had goals and dreams for his life.  He started the Methadone Clinic on the early morning of Monday, August 7th.  Matthew started exhibiting adverse reactions to the Methadone treatment within the first day, some of these were normal, some were far from normal. There were other legal prescriptions Matt was taking prior to MMT that the Dr said would be ok; they should NOT have been mixed with methadone (xanax, anti-depressant), plus other rx (promethazine) and OTC med (Benadryl) that the clinic said would be ok.  Matt experienced multiple adverse reactions (problems swallowing, trouble urinating, severe rash, hallucinations, hyper, could not sleep, + more and more) which increased each day. He called the clinic and was told, these reactions were normal.  On the 2nd day, Matthew became more miserable with his side effects and again called the clinic, and again told everything was normal.  On Wednesday, Day 3, when he complained Matt was told his body would "adjust".   On Thursday, Day 4, Matthew was supposed to have a follow-up appointment with the doctor, but the appointment never took place.  When the nurses went to dose Matt at 45 mg, he begged them to reduce the dose; however, they could not do so without doctor's orders.  On Friday, Day 5, Matt went and picked up his college books for the fall semester and went by the clinic for his 50 mg dose.  I never had much of a chance to ask him if he discussed his symptoms again (by this time he could not swallow his own saliva unless he was drinking something to force it down).  I spoke with my sweet baby son around 10am and he was very lethargic; I thought he was tired from not sleeping.  We laughed and I told him to take a nap and call me back at work when he woke up.   He never called.....    
 When I came home from work that Friday afternoon, I found my son sitting in the floor of our hallway, with his body slumped over.  I thought he had just collapsed, but I was not that fortunate.  When I laid his body down, purple splotches (livor mortis) contrasted against stark white covered his handsome face.  I called 911 and while waiting, started to do CPR, hoping I could breathe some of my life back into him.  Rigor mortis had set in and I could not manipulate his mouth or jaw to try to start CPR.  His skin was cold as ice.  It is estimated that he had been dead about 5-6 hours.   When Matt's toxicology report came back he only had Methadone and his prescribed medications the doctor had approved in his system. The clinic has never accepted any responsibility or been held accountable in any way for my son's death.  
So, PLEASE alert anyone you know who is contemplating Methadone for treatment, for pain or for a high to stay away from this lethal drug.  It is unpredictable with a long half-life (up to as long as 72-96 hours) that most people don't understand.  There is no safe way to dispense or control Methadone and its results are FATAL, with no warning signs before death occurs. There are no do-overs, no going back and choosing a different form of treatment.  My son is gone, forever.  My hope now is that the public becomes educated about this fatal drug
MY SON - MATTHEW
What a waste for my son Matthew's life to end so needlessly at the young age of 20 because of an approved drug so dangerous and because of negligence on the part of the clinic and doctor.  Matthew blessed us when he was born on January 10, 1986 and continued blessing us for 20 years.  We watched him grow from a curly-haired, cute little boy into a handsome young man.  Matthew always had a smile on his face from the time he was little.  His smile and sense of humor were uplifting and contagious.  He had a compassionate heart and would give his last penny or the shirt off his back if someone asked.  He never knew a stranger anywhere he went; he would strike up conversation with anyone and as his personality shined through, he would have anyone talking, laughing or giggling within minutues.  Matthew was also very sensitive and emotional, and wore his emotions on his sleeve.  He was also very vulnerable and opened himself to hurt and pain, because he lived without shields or barriers to his heart.  Matthew was one of the most loving, compassionate people I have ever met; he was sweet and kind, loving and trusting.  Matt was also known by anyone that had ever met him for his loving hugs.  He hugged people when he met them, he hugged them when he left, and he held and hugged many friends through difficult times.  As I was getting ready to leave for work on the day Matt passed away, he cupped his hands around my face and told me I was beautiful, and how much he loved me and then gave me a huge hug (I wasn't going on a trip, just to work for 8 hrs).  How many 20 yr old young men do that with their mothers?  It is the last memory I have of Matthew and I together and it is very, very special.  We did not part with regrets or anger, only mutual professions of love between mother and son.

http://www.matthew-fielder.memory-of.com/  

Xanax, Klonopin, Ativan, Valium, Serax, Librium and other benzodiazepine tranquilizer medications can increase blood methadone levels, since the liver detoxifies benzodiazepine tranquilizers, using the same Cytochrome P450 3A4 pathway, which is involved in initial breakdown of methadone.

Benzodiazepines almost never produce death, due to respiratory depression, but when combined with methadone or other opiates, they impair metabolism or breakdown of opiates and increase risk of death, due to opiate overdose. Sadly methadone deaths are skyrocketing, with increased prescriptions for chronic pain, by physicians who do not fully understand how deadly methadone can be.

This abstract discusses three fatal methadone overdoses, caused when normally safe, nonfatal methadone doses were combined with Alprazolam (Xanax).

J Forensic Sci. 1997 Jan;42(1):155-6 Detection of alprazolam in three cases of methadone/benzodiazepine overdose.Rogers WO, Hall MA, Brissie RM, Robinson CA.
University of Alabama at Birmingham 35294, USA.

Benzodiazepine abuse is common among clients at methadone maintenance clinics. Diazepam and lorazepam are readily detected by immunological screening methods and confirmed by GC/MS. Alprazolam has been relatively difficult to confirm. We recently reported a modification of an existing serum HPLC procedure which allows us to analyze whole blood. We report here three cases of fatal drug overdose caused by co-ingestion of methadone and alprazolam. In all three cases, alprazolam was detected by HPLC and could not be identified by alkaline extraction GC/MS. Postmortem blood concentrations of methadone were at the lower range or below the concentrations previously identified in methadone overdose fatalities, suggesting an increased risk from co-ingestion of methadone and alprazolam.

Xanax levels are more difficult to measure, than Valium or Ativan. Methadone fatalities have increased alarmingly, in the last few years, when methadone prescriptions increased. Although medical literature has reported that benzodiazepine medications can increase methadone serum level, some physicians, methadone clinics and methadone patients apparently are unaware of the increased fatal overdose risk, when benzodiazepines medications are combined with methadone.

Requiring physicians to obtain an additional certification to prescribe methadone,might be necessary, since there are accounts of fatal methadone overdoses, where prescribing physicians did not appear to be aware of the methadone overdose risk.

Since Xanax combined with methadone, appears especially risky, compared to Valium and other longer half life benzodiazepines, it appears advisable to avoid prescribing Xanax, with methadone, if possible.

This abstract also explains that the commonly used urine and blood drug tests do not detect Xanax levels and additional specialized tests are required to accurately measure Xanax levels. Unlike Xanax, Valium (diazepam) levels are detectable by the routinely used drug screen tests. The following journal abstract indicates that alprazolam (Xanax), which is one of the most deadly benzodiazepines when overdosed, seldom causes death by itself, but increases deadliness of methadone, other opiates or cocaine. Benzodiazepines appear to cause more deaths, due to accidents resulting from over- sedation, than from toxicity or respiratory arrest. In this study, Alprazolam deaths caused by trauma were 22 times more common, than deaths caused by Alprazolam toxicity.

Am J Forensic Med Pathol. 2005 Mar;26(1):24-7.
Alprazolam-related deaths in Palm Beach County.
• Wolf BC,
• Lavezzi WA,
• Sullivan LM,
• Middleberg RA,
• Flannagan LM.
Office of the Medical Examiner, Palm Beach County, West Palm Beach, Florida, USA. bwolf@leegov.com

Alprazolam is a commonly prescribed benzodiazepine. The abuse of benzodiazepines is most frequently seen in conjunction with the abuse of other drugs. Only rare fatalities have been attributed to alprazolam alone. We undertook a retrospective review of cases investigated by the Palm Beach County Medical Examiner's Office in which postmortem toxicologic studies indicated the presence of alprazolam, to further study the pattern of alprazolam abuse. Our review consisted of 178 cases, including 87 in which death was attributed to combined drug toxicity, 2 to alprazolam toxicity alone, 44 to trauma, 12 to natural causes, and 33 to another drug or drugs. Cocaine and methadone were the most common cointoxicants in the cases of combined drug toxicity, while heroin was less frequently detected. There was considerable overlap in the postmortem blood alprazolam concentrations among the groups. The overlapping ranges of concentrations of alprazolam detected indicate that it may be difficult to define a lethal alprazolam range, and that it may not be possible to determine the actual role of alprazolam as a causal factor in cases of combined drug toxicity. This study confirms that alprazolam alone is rarely a cause of death, and that alprazolam abuse usually occurs within a polydrug use pattern. The high incidence of cocaine as a cointoxicant has not been previously reported. EMPHASIS ADDED