Tag Archive: naloxone


Four Cases Involving Extraction of Fentanyl From
Transdermal Patches

Amy M. Tharp, MD, Ruth E. Winecker, PhD, and David C. Winston, MD, PhD

Abstract: The transdermal fentanyl system delivers a specific dose
at a constant rate. Even after the prescribed application time has
elapsed, enough fentanyl remains within a patch to provide a
potentially lethal dose. Death due to the intravenous injection of
fentanyl extracted from transdermal patches has not been previously
reported. We present 4 cases in which the source of fentanyl was
transdermal patches and was injected. In all of these cases, the
victim was a white male who died at home. Case 1 was a 35-year-old
with no known history of drug use, who was found by his wife on
the floor of his workshop. Police recovered a fentanyl patch, needle,
and syringe at the scene. Case 2 was a 38-year-old with a known
history of drug use whose family claimed that he was in a treatment
program that used fentanyl patches for unknown reasons. His
brother found him dead in bed, and law enforcement officers found
a hypodermic needle beside the body; a ligature around his left hand,
and apparent needle marks between his first and second digits were
also noted. Case 3 was a 42-year-old with a recent attempted suicide
via overdose who was found dead at his home. An empty box of
fentanyl patches, Valium, Ritalin, and 2 syringes were found at the
scene. Case 4 was a 39-year-old found by his mother, who admitted
to removing a needle with attached syringe from the decedent’s arm.
Medications at the scene included hydrocodone, alprazolam, zolpidem,
and fentanyl patches. All reported deaths were attributed to
fentanyl intoxication, with blood concentrations ranging from 5 to
27 g/L.

From the Department of Pathology, Wake Forest University School of
Medicine, Winston-Salem, North Carolina (A.M.T.); Office of the Chief
Medical Examiner, Chapel Hill, North Carolina (R.E.W.); Forensic
Science Center, Tucson, Arizona (D.C.W.); and Department of Pathology,
University of Arizona College of Medicine (D.C.W.).

entanyl overdose is classically associated with intravenous
use of -methyl-fentanyl (“China White”),1 a powder
form that is chemically different from therapeutic fentanyl.
However, fentanyl overdose has also been reported in
cases of excessive transdermal application2 and ingestion3,4
or inhalation5 of transdermal patches. Fentanyl is a narcotic
analgesic, which primarily binds to opioid -receptors, producing
not only the analgesia for which it is primarily used
but also sedation, euphoria, and at high doses, respiratory
depression and death.6 Transdermal fentanyl therapy (Duragesic;
Janssen Pharmaceutica, Beerse, Belgium) has been used
successfully to treat postoperative pain, as well as pain
associated with malignancies, but as with all opioid agents,
the potential for abuse exists. The transdermal fentanyl system
is designed to deliver a specific dose at a constant rate
based on the initial concentration present in the patch. This
delivery system effectively limits the peak versus trough
concentration, which is a common problem associated with
other routes of administration. Following 3 days of continuous
therapeutic use, enough fentanyl remains within a patch
to provide a potentially lethal dose.7 We present 4 cases
occurring in North Carolina between January 1997 and July
2001 in which the fatal dose of fentanyl was extracted from
transdermal patches and injected intravenously.

MATERIALS AND METHODS

Case Selection

The case files of the Office of the Chief Medical
Examiner (Chapel Hill, NC) were searched from 1991 to
2001 for deaths related to fentanyl. An initial search identified
53 cases,8 of which only 4 involved intravenous abuse of
a transdermal fentanyl patch. Case histories are listed below.

Toxicologic Analysis

All toxicologic analyses were performed at the Office
of the Chief Medical Examiner (Chapel Hill, NC). All cases
were screened for volatiles, common drugs of abuse (eg,
cocaine and morphine), and other basic drugs. Other tests (eg,
fentanyl) were performed as needed.

Fentanyl Screen

The specimens were screened by enzyme linked immunoassay,
with a 1 g/L cutoff concentration (Orasure Technologies,
Bethlehem, PA) utilizing a Biochem Personal Laboratory
Autoanalyzer (Allentown, PA). The assays were performed in
accordance with the manufacturers instructions and as validated
for use in the Office of the Chief Medical Examiner Toxicology
Laboratory.9

Fentanyl Confirmation and Quantification

Quantification and confirmation analyses were performed
by first isolating fentanyl by basic extraction6 of a 1to
5-mL (g) specimen. Underivatized specimens were analyzed
on an Agilent Technologies (Wilmington, DE) gas
chromatograph/mass spectrometer (GC/MS). The GC/MS
system was composed of an Agilent 6890 gas chromatograph,
a 5973 mass selective detector (MSD) and a 7683 liquid
auto-sampler. The GC/MS was fitted with a HP-1MS capillary
column (30 m .
0.25 mm inside diameter .
0.25-m
film thickness). A 13.19-minute run time occurred after 1-L
splitless injection into a 275°C injection port equipped with
0.4-mm gooseneck liner with base-deactivated fused silica
wool. Oven temperature programming began at 125°C, holding
for 1.00 minute, then ramping at 3 intervals: 35°C/minute
to 195°C, 7°C/minute to 230°C and 32°C/minute to a final
temperature of 300°C, holding for 3 minutes. Helium was
used as the carrier gas at a linear velocity 61 cm/s; flows
included a septum purge of 15.0 mL/minute at 2.0 minutes
and a constant column flow of 2.6 mL/minute. The MSD was
operated in selective ion mode, with a transfer line temperature
of 280°C.

CASE PRESENTATIONS

Case 1

A 35-year-old Caucasian man with no known history of
drug use was working in his workshop at home one evening.
His wife reported that at approximately 12:30 AM, she asked
him to come into the house, but that he stated that he would
probably continue building porch swings through the night.
His father, who stated that he “appeared OK,” last saw him
alive at 2:30 AM. At approximately 5:00 AM, the decedent’s
wife found him lying on the floor of his workshop. Paramedics
were unable to resuscitate him. Police investigating the
scene found a fentanyl patch, a needle, and syringe in the
workshop. External examination of the body revealed no
evidence of trauma, except for a 3/4-inch recent contusion
with some yellow discoloration at its margins in the left
antecubital fossa and a faint petechial-like contusion along a
vein on the right forearm. Pulmonary congestion and edema,
with a combined lung weight of 920 g, were the only other
significant autopsy findings. Toxicological analysis of aortic
blood was remarkable for a fentanyl concentration of 5 g/L,

as well as a concentration of 0.8 mg/L of propoxyphene
(generally considered to be a nontoxic concentration), and
therapeutic concentrations of amitriptyline (0.08 mg/L) and
its metabolite nortriptyline (0.33 mg/L). No other organic
bases were detected, and testing for norpropoxyphene was
not performed. The cause of death was attributed to “fentanyl
poisoning,” with the manner of death listed as accident.

Case 2

A 38-year-old Caucasian man with a history of drug use
was living with his relatives. His family claimed that he had
begun a treatment of his drug use in a program that used
“morphine patches” for unknown therapeutic purposes. He
was last seen alive at 10:00 PM, at which time he complained
of nausea. His brother found him dead in bed the following
morning at 8:15 AM. Resuscitative efforts were attempted but
were unsuccessful. Law officers found a hypodermic needle
in the bed beside the body and a ligature on his left hand, with
apparent needle marks between the thumb and forefinger. On
external examination at the time of autopsy, scars were noted
in the right antecubital fossa as well as over each wrist,
including a relatively recent puncture site over the dorsum of
the left hand, between the thumb and second digit. Internal
examination revealed pulmonary congestion and edema, with
a combined lung weight of 1500 g, and cardiomegaly (450 g).
A focus of granulomatous inflammation was present within
the left lung with caseous necrosis, which was found to be
due to Coccidioides immitis on silver stains. Focal chronic
hepatitis and moderate coronary atherosclerosis were also
identified. Toxicologic studies of aortic blood were positive
fora27 g/L concentration of fentanyl, with no other
substances identified. The cause of death was listed as “fentanyl
poisoning” with the manner of death as accident.

Case 3

A 42-year-old Caucasian man was found dead in his
home, lying prone in the hallway, with his eyeglasses broken
and hanging from his face. He had last been known to be
alive on the previous day at 10:30 PM, when he had answered
a phone call. At the scene, a bottle of diazepam with 11 pills
missing from the prescribed number, a methylphenidate tablet,
and 2 syringes (1 empty and 1 filled with a clear liquid),
as well as an empty box of fentanyl patches were recovered.
He had a history of ethanol and multisubstance abuse and was
seen in his local emergency room the week prior to his death
for treatment of an attempted suicide by Percocet and Restoril
overdose, as well as self-inflicted abrasions and lacerations,
and ethanol intoxication. Following a work-up, gastric decontamination,
and observation, he was sent to a psychiatric
hospital for involuntary commitment. It was not determined
how he came to be at his home on the day of his death.
External examination was unremarkable, with the exception
of abundant healed apparently self-inflicted incised wounds

© 2004 Lippincott Williams & Wilkins

on the wrists, abdomen, and forearms. No fentanyl patches
were found on the body. Pulmonary congestion and edema,
with a combined lung weight of 1920 g, cardiomegaly (450
g), with mild coronary atherosclerosis, and mild hepatic
steatosis were found at autopsy. Aortic blood was sent for
toxicologic analyses and was positive for 17 g/L of fentanyl,
0.49 mg/L of paroxetine, low concentrations of cocaine

(0.061 mg/L) and its metabolite, benzoylecgonine (0.36 mg/
L), and diazepam (0.15 mg/L). Fentanyl overdose was listed
as the cause of death and the manner of death was classified
as suicide.
Case 4

A 39-year-old Caucasian man complained of a fever,
sore throat, and malaise. He was seen in his local urgent care
facility and given hydrocodone cough syrup. Two weeks
later, he was found unresponsive in the bathroom of his home
by his mother, who admitted removing a needle with attached
syringe from his arm. Also found at the scene were 2 empty
bottles of hydrocodone, a one-third full bottle of hydrocodone
syrup, empty bottles of alprazolam and zolpidem, 2 additional
syringes, and 2 empty wrappers from fentanyl patches. He
was taken to the local emergency room, where he was
pronounced dead. Further investigation revealed a history of
drug use, asthma, depression, and psychosis. At the time of
autopsy, old needle puncture sites were found within bilateral
antecubital fossae, with a relatively recent needle puncture in
the left antecubital fossa. Microscopic examination of these
sites revealed dermal foreign body giant cells with polarizable
material. Internal findings included cardiomegaly (510
g) with left ventricular hypertrophy and hepatosplenomegaly.
Numerous foreign body giant cells with polarizable material
were present within the lungs, surrounding the pulmonary
blood vessels. Toxicologic analysis of femoral blood was
positive for 13 g/L of fentanyl, 0.083 mg/L of hydrocodone,
and 0.076 mg/L of oxycodone. Testing of the syringe found
at the scene was positive for fentanyl. The cause of death was
determined to be fentanyl toxicity, with hydrocodone and
oxycodone listed as significant contributing factors. The manner
of death was determined to be accident.

DISCUSSION

Fentanyl, developed by Janssen Pharmaceutica, was
originally introduced in the United States in 1968 for use as
an intravenous analgesic-anesthetic drug. The abuse of fentanyl
has classically been by health care professionals who
had access to the controlled drug. In the 1980s, a street
version began to appear, resulting in many deaths. “China
White,” or -methyl-fentanyl, was found to be up to 1000
times more potent than heroin1 and with demographics similar
to those of heroin abuse.10 In particular, Caucasian men
with an average age of 32 years old and a prior history of
intravenous drug use were most likely to abuse China White

usually in combination with other drugs (alcohol, cocaine,
other opiates). The FDA approved Duragesic (Janssen Pharmaceutica,
Beerse, Belgium), the first transdermal fentanyl
system, in 1990 for use in the control of chronic and postsurgical
pain.

Since their introduction in 1990, transdermal fentanyl
patches have been abused in a number of ways. Edinboro et
al2 reported a case of an 83-year-old female with terminal
cancer who was found to have fatal levels of fentanyl in her
blood (25 g/L) after applying 3 patches to her chest. Arvanitis
and Satonik3 described a case of a 38-year-old man who
was found unresponsive on 3 separate occasions after chewing
transdermal fentanyl patches. He was treated successfully
with naloxone the first 2 times, but the final time, he was
found dead with a fentanyl patch in his oropharynx. Complete
postmortem evaluation and toxicologic analyses were not
complete at the time of publication. Another case of intentional
oral ingestion of fentanyl patches was reported by
Purucker and Swann,4 who described a 24-year-old woman
who reported to her local emergency room complaining of
pain due to miscarriage, as well as chronic pain and muscle
spasms. She received an intramuscular injection of meperidine
and a fentanyl patch was applied for continued pain
relief. She was found shortly thereafter in the lavatory,
unresponsive and apneic. She was successfully resuscitated,
and an empty Duragesic (Janssen Pharmaceutica) patch was
found in her wallet, with bite marks found on the polyester
backing and none of the fentanyl gel remaining in the patch.
Neither a urine drug screen nor serum fentanyl level was
obtained. Marquardt and Tharratt5 reported a case of a 36year-
old man who became apneic, hypotensive, and tachycardic
following heating of a fentanyl patch with subsequent
inhalation of the evolving vapors, which was witnessed by his
girlfriend. Naloxone was administered and he was able to be
resuscitated; urine or serum drug screens were not performed
at that time. This man subsequently died as a result of further
inhalation abuse of fentanyl patches, and (according to Marquardt
and Tharratt5) he was found at autopsy to have the
following fentanyl concentrations: femoral blood, 2.66 ng/
mL; urine, 41 ng/mL; and liver, 122 ng/mL.

Transdermal fentanyl therapy consists of a patch composed
of 4 layers with an outer protective liner. The 4 layers
include a polyester film backing; the drug reservoir, which
contains a mixture of fentanyl, alcohol, and hydroxyethyl
cellulose; a membrane that controls the rate of fentanyl
delivery; and a silicone adhesive, which also contains fentanyl.
The rate-limiting step in absorption is through the lipophilic,
keratinous stratum corneum by passive diffusion.11
Extraction of the contents of the drug reservoir followed by
intravenous injection of the fentanyl effectively bypasses this
rate-limiting step and provides a bolus dose. This unique
method of abuse, therefore, increases a person’s risk of fatal
overdose by rapidly administering larger than the usual in

© 2004 Lippincott Williams & Wilkins

The American Journal of Forensic Medicine and Pathology • Volume 25, Number 2, June 2004 Fatal Intravenous Fentanyl Abuse

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source is again : http://drogriporter.hu/en/ddt

Treatment for OIC


Treatment options for OIC

Although opioids are very effective for treating and managing pain, their use frequently results in opioid-induced constipation (OIC). Treatment options for OIC may be as simple as changing diet or as complicated as requiring several medicines and laxatives.


How can changing lifestyle factors treat OIC?

Changing lifestyle factors is usually the first recommendation that physicians make for the prevention or treatment of constipation. This includes:

  • Increasing dietary fiber
  • Increasing fluid intake
  • Increasing exercise or physical activity
  • Increasing time and privacy for toileting

Changes in lifestyle, however, may not be possible for many patients. In addition, these changes may be ineffective in treating OIC. If there is a concurrent underlying disease or medicine that is causing constipation, the disease may need to be treated separately or another treatment regimen may have to be considered.


What drugs or medicines treat OIC?

medication

OIC treatment usually requires additional medicines to be prescribed along with the opioid painkillers that are causing the constipation. Withholding the opioid treatment is ill-advised because it results in a decrease in the patient’s quality of life. Often, laxatives and/or cathartics are prescribed at the same time as the opioid painkillers so that treatment for the constipation beings immediately. A cathartic accelerates defecation, while a laxative eases defecation, usually by softening the stool; some medicines are considered to be both laxatives and cathartics.

For the treatment of OIC, doctors may prescribe:

  • Osmotic laxatives – increase the amount of water in the gut, increasing bulk and softening stools.
  • Emollient or lubricant cathartics – soften and lubricate stools.
  • Bulk cathartics – increase bulk and soften stools.
  • Stimulant cathartics – directly counteract the effect of the opioid medications by increasing intestinal motility, helping the gut to push the stools along.
  • Prostaglandins or prokinetic drugs – change the way the intestines absorb water and electrolytes, and they increase the weight and frequency of stools while reducing transit time.
  • Other medicines block the effects of opioids on the bowel to reverse opioid-induced constipation.

Although the treatments listed above are usually successful in treating OIC, sometimes a physician will recommend rectal intervention. As discussed, prophylaxis with laxatives are/or cathartics is considered usual – as some clinicians assume [constipation] to be virtually universal in patients who are prescribed opioid analgesics1.

Rectal interventions are indicated if the appropriate oral measures have been ineffective2. Rectal intervention means the following treatments:

  • Suppositories
  • Enemas (micro and larger volume)
  • Rectal irrigation (sometimes known as colonic irrigation)
  • Manual evacuation

The first choice rectal intervention for uncomplicated constipation is glycerine suppositories2. If these are ineffective, then a stimulant enema might be administered. Oral and rectal stimulant laxatives should be avoided if there is possible or proven bowel obstruction. Gentle rectal measures can sometimes be effective in emptying the rectum and lower colon. Oral softening agents are useful if the obstruction is incomplete. It should be remembered that constipation can cause bowel obstruction.

If none of the rectal laxatives above prove adequate to remove impacted faeces, rectal irrigation with normal saline can be performed3. Manual evacuation should be used as a last resort when all other methods of bowel management have been shown to be ineffective.


Combination therapy

Constipation is a known side effect of opioid analgesics and should be addressed before opioid therapy begins. As opioid-induced constipation can be severe and adversely impact quality of life and compliance with therapy, prophylaxis with laxatives is considered to be the best approach. A British Pain Society survey conducted in March 2009 showed that nearly half of GPs (44%) surveyed believe that the negative impact of such side effects is the key factor in patient non-compliance with prescribed opioid treatments.

Concurrent management on initiation of opioids frequently includes recommending certain lifestyle or dietary adjustments (as listed above) and initiating a scheduled regimen of laxatives. Laxative and cathartic therapy may be needed throughout opioid therapy and beyond. Effective management requires a composite of strategies, including behavioral and lifestyle changes (diet, activity, and fluid intake, as appropriate).

However medications used to manage opioid-induced constipation, such as laxatives, do not address the underlying opioid receptor-mediated cause of constipation and are often ineffective4.


Newer targeted treatments for opioid induced constipation

Methylnaltrexone (available as Relistor(R)) helps restore bowel function in patients who have advanced illness and receive opioids for pain relief. Methylnaltrexone is delivered via subcutaneous injection and specifically targets opioid-induced constipation. When given alongside opioid therapy, it is designed to displace the opioid from binding to peripheral receptors in the gut, decreasing the opioid’s constipating effects and inducing laxation.

Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist that decreases the constipating effects of opioid pain medications in the gastrointestinal tract without diminishing their ability to relieve pain.

Methylnaltrexone blocks peripheral opioid receptors in the gut and unlike other opioid antagonists has restricted ability to cross the blood-brain barrier. As a result, it antagonizes only the peripherally located opioid receptors in the GI tract, so it’s action reverses opioid-induced constipation without precipitating withdrawal symptoms or affecting or reversing the central analgesic effects of opioids5.

Another new medication for severe pain (long-term pain that can be experienced as a result of conditions such as back pain, arthritis and osteoarthritis)6, are tablets combining prolonged release oxycodone, an opioid which treats pain, and prolonged release naloxone, a compound which counteracts the potential negative effects of the opioid on the GI function (available as TarginactTM). This novel combination has been proven to provide equivalent pain relief to oxycodone alone, whilst significantly improving bowel function7. Naloxone is an opioid receptor antagonist that, when taken orally, has negligible systemic bioavailability8 providing a full inhibitory effect on local opioid receptors in the gut – counteracting opioid-induced constipation – without impacting on the centrally acting analgesic efficacy of oxycodone.

diagram of opioids with mu-opioid receptors

* Image borrowed from Wyeth library


1. Hanks G, Cherny N, Fallon M. Symptom Management. The management of pain: Opioid Analgesic Therapy. In Oxford textbook of Palliative Medicine, 3rd Ed. Oxford University Press, 2003.
2. Cancer – a cpomprehensive clinical guide, By David L. Morris, John Henry Kearsley, Christopher John Hacon Williams
3. Oxford textbook of palliative medicine, By Derek Doyle, Geoffrey Hanks, Nathan I. Cherny, Kenneth Calman
4. Reimer K, Hopp M, Zenz M, Maier C, Holzer P, Mikus G, Bosse B, Smith K, Buschmann-Kramm C, Leyendecker P: Meeting the Challenges of Opioid-Induced Constipation in Chronic Pain Management – A Novel Approach.
Pharmacology 2009;83:10-17 (DOI: 10.1159/000165778)
5. Ho et al. 2003; Kurz and Sessler 2003; Schmidt 2001; Foss 2001
6. Severe pain, which can be adequately managed only with opioid analgesics
7. Vondrackova D, Leyendecker P, Meissner W. et al. Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain.J Pain. 2008; 9(12): 1144-1154.
Meissner W, Leyendecker P, Müller-Lissner S, et al. A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation. Eur J Pain. 2008; doi:10.1016/j.ejpain.2008.06.012.
Simpson K, Leyendecker P, Hopp M, et al. Fixed-ratio combination oxycodone/naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-to-severe non-cancer pain. Curr Med Res Opin. 2008; 24(12): 3503-3512.
8. Nadstawek J, Leyendecker P, Hopp M, et al. Patient assessment of a novel therapeutic approach for the treatment of severe, chronic pain. Int J Clin Pract. 2008; 62: 1159-116.

source: http://www.medicalnewstoday.com/info/oic/treatment-for-opioid-induced-constipation.php

 

Oral Naloxone Reverses Opioid-Associated Constipation

Meissner W, Schmidt U, Hartmann M, et al
Pain. 2000; 84(1):105-9

Opioid-related constipation is one of the most frequent side effects of chronic pain treatment. Enteral administration of naloxone blocks opioid action at the intestinal receptor level but has low systemic bioavailability due to marked hepatic first-pass metabolism. The aim of this study was to examine the effects of oral naloxone on opioid-associated constipation in an intraindividually controlled manner. Twenty-two chronic pain patients with oral opioid treatment and constipation were enrolled in this study. Constipation was defined as lack of laxation and/or necessity of laxative therapy in at least 3 out of 6 days. Laxation and laxative use were monitored for the first 6 days without intervention (‚control period‘). Then, oral naloxone was started and titrated individually between 3×3 to 3×12 mg/day depending on laxation and withdrawal symptoms. After the 4-day titration period, patients were observed for further 6 days (’naloxone period‘). The Wilcoxon signed rank test was used to compare number of days with laxation and laxative therapy in the two study periods. Of the 22 patients studied, five patients did not reach the ’naloxone period‘ due to death, operation, systemic opioid withdrawal symptoms, or therapy-resistant vomiting. In the 6 day ’naloxone‘ compared to the ‚control period‘, the mean number of days with laxation increased from 2.1 to 3.5 (P<0.01) and the number of days with laxative medication decreased from 6 to 3.8 (P<0.01). The mean naloxone dose in the ’naloxone period‘ was 17.5 mg/day. The mean pain intensity did not differ between these two periods. Moderate side effects of short duration were observed in four patients following naloxone single dose administrations between 6 and 20 mg, resulting in yawning, sweating, and shivering. Most of the patients reported mild or moderate abdominal propulsions and/or abdominal cramps shortly after naloxone administration. All side effects terminated after 0.5-6 h. This controlled study demonstrates that orally administered naloxone improves symptoms of opioid associated constipation and reduces laxative use. To prevent systemic withdrawal signs, therapy should be started with low doses and patients carefully monitored during titration.

 

source is: http://www.medscape.com/viewarticle/435954


Zitat:
Abstract

BACKGROUND: In Finland, buprenorphine (Subutex) is the most abused opioid. In order to curb this problem, many treatment centres transferred („forced transfer“) their buprenorphine patients to the buprenorphine plus naloxone (Suboxone) combination product in late 2003.

METHODS: Data from a retrospective study involving five different treatment centers, examining the effects of switching patients to Suboxone, were gathered from 64 opioid-dependent patients who had undergone the medication transfer.

RESULTS: Most patients (90.6%) switched to Suboxone at the same dose of buprenorphine that they had been receiving as Subutex (average 22 mg). The majority of these patients (71.9%) were maintained at the same dose of Suboxone throughout the 4-week study period. During the first 4 weeks, 50% of the patients reported adverse events and at the four month time point, 26.6% reported adverse events. However, due to adverse events one patient only discontinued treatment with Suboxone during the 4-week study period, and five during the four month follow-up period. Of the 26 patients in the follow-up period, Suboxone was misused intravenously once each by 4 patients and twice by 1 patient. These 5 patients all reported that injecting Suboxone was like injecting „nothing“ with any euphoria, or that it was a bad experience.

CONCLUSION: We conclude that when patients are transferred from high doses (> 22 mg) of buprenorphine to the combination product, dose adjustments may be necessary especially in the later phase of the treatment. We recommend that a transfer from Subutex to Suboxone should be carefully discussed and planned in advance with the patients and after the transfer adverse events should be regularly monitored. With regard of buprenorphine IV abuse, the combination product seems to have a less abuse potential than buprenorphine alone.


Source:
http://www.ncbi.nlm.nih.gov/pubmed/18559110

Versus

Zitat:
Abstract

Abuse and misuse of pharmacological therapies represent major challenges in the healthcare system, particularly in patients receiving long-acting opioid drugs for the treatment of heroin or opioid addiction. The partial mu-opioid receptor agonist buprenorphine is used to treat opioid dependence, but diversion and misuse may occur.

The sublingual combination formulation of buprenorphine and the opioid receptor antagonist naloxone (buprenorphine/naxolone) is associated with a reduced abuse potential, and has been shown to have promising efficacy for the treatment of opioid dependence. This observational study assessed the safety and efficacy of sublingual buprenorphine/naloxone combination therapy in patients with opioid dependence after therapeutic switch from buprenorphine monotherapy. A total of 94 patients being treated with buprenorphine monotherapy (average dose 8 mg/day; mean duration of therapy 840 days) were switched to buprenorphine/naloxone combination therapy. Patients were asked to rate their level of satisfaction with buprenorphine/naloxone combination treatment with respect to the management of withdrawal symptoms, and urinary toxicology tests were carried out before and 14 days after switching to combination therapy. Within 3 months, 75/94 patients (80%) previously treated with buprenorphine monotherapy had switched to sublingual buprenorphine/naloxone combination treatment (average dose buprenorphine 8 mg).

Among patients receiving combination treatment for >3 months, 83% were receiving medication either weekly or fortnightly, based on the results of toxicological testing. A reduction in positive urinary toxicology tests was observed in patients within two weeks after being switched to combination treatment (before switch: 28, 9 and 2 positive tests for heroin, cocaine and heroin + cocaine, respectively vs 11, 3 and 1 after switch) and a total of 64 patients of the 75 who switched to combination therapy (85%) were satisfied with the management of withdrawal symptoms during buprenorphine/naloxone treatment.

Few adverse events were reported and no patients dropped out of treatment. This study shows that switching from buprenorphine monotherapy to sublingual buprenorphine/naloxone combination therapy is effective and well tolerated, and associated with good control of withdrawal symptoms in the majority of patients. In addition, combination therapy reduced illicit drug use (based on negative urinary toxicology texts) and allowed the time between clinic visits to be increased.

Source: http://www.ncbi.nlm.nih.gov/pubmed/20450243

WASHINGTON — The FDA has approved a new sublingual film formulation of the opioid dependence treatment combination buprenorphrine/naloxone (Suboxone).

The new formulation will be released in the same 2 mg buprenorphrine/0.5 mg naloxone and 8 mg buprenorphrine/2 mg naloxone doses as the drug’s sublingual tablet form.

„During clinical tests, Suboxone sublingual film was shown to be faster dissolving than Suboxone sublingual tablets,“ Shaun Thaxter, president of manufacturer Reckitt Benckiser Pharmaceuticals, said in a prepared statement.

Drug approval included a risk evaluation and mitigation strategy program, which requires the company to monitor patients to determine whether potential treatment benefits outweigh potential risks, especially with accidental overdose, misuse, and abuse of the film, the brief said.

The drug can be abused in ways similar to other opioids. Healthcare professionals should monitor patients for proper use, the company said in the statement.

Buprenorphrine reduces patient opioid cravings and withdrawal symptoms, and also blocks the effects of other opioids. Naloxone triggers withdrawal symptoms in patients who crush and inject the drug, but has limited bioavailability when taken sublingually, and should cause no adverse events.

Chronic use of the drug may result in physical dependence and a sudden or rapid decrease in dose may result in withdrawal symptoms, though the symptoms are milder and more delayed than those occurring with full opioid agonists, the brief said.

Patients taking the film, particularly if injected or through other improper means and with central nervous system depressants, may experience life-threatening respiratory depression or death. Healthcare professionals should consider a reduced dose of the central nervous system depressant, the combination, or both when prescribing buprenophrine/naloxone, the statement said.

Pediatric patients taking the drug may have severe, potentially fatal respiratory depression.

Those taking the film should have liver function monitored before and during drug treatment.

Patients who take the drug prior to use or abuse of other full agonists, such as heroin or oxycodone, may experience withdrawal symptoms due to interactions with the drug’s naloxone.

Healthcare professionals should only prescribe pregnant or nursing patients the drug combination if potential gain outweighs potential risk, due to possible neonatal withdrawal symptoms associated with the drug, according to the manufacturer.

The drug is contraindicated in patients hypersensitive to buprenophrine or naloxone.

Adverse events associated with the film include numb mouth, sore tongue, mouth redness, headache, nausea, vomiting, sweating, constipation, insomnia, pain, swelling of limbs, attention disturbance, palpitations, blurred vision, cytolytic hepatitis, jaundice, and anaphylactic shock.

For more than 20 years, local heroin addicts have relied on a collection of needle exchanges for clean works. But in recent months, crack users too have quietly found an outlet in the city.

In a nondescript alley in the University District, users can pick up clean crack pipes, pipe filters and ascorbic acid for injecting crack. Heroin users can also pick up a drug that reverses a heroin overdose — an apparent first for a city needle exchange.

„We take a different philosophy approach than most government institutions or public health departments. They have a budget, and have to pick and choose who they’re going to help,“ said Shilo Murphy, executive director of the non-profit People’s Harm Reduction Alliance, which runs the U-District needle exchange.

„We say this is our community, this is our neighborhood, and we should decide what we have at the table.“

The exchange, which celebrated 20 years in the neighborhood this week, has come a long way from its roots — when a man named Bob walked the Ave. and dispensed sterile needles from his backpack.
These days, the largely volunteer-driven exchange, which serves 400 to 600 people a month, is better known for branching ahead of its peers in the harm reduction world.

Public health officials know of no other local program that gives out crack kits or Naloxone, the heroin-overdose reversal drug. But they see the potential benefits.

Just as sterile syringes reduce the spread of HIV and other diseases, new and unbroken glass pipes are believed to prevent lip cuts and the spread of hepatitis strains. Rubber tips and new filters ward off mouth burns. Ascorbic acid helps prevent users from using lemon juice to dissolve cocaine rocks into an injectable liquid — a common practice that can lead to fungal infections.

„Our program is primarily an HIV prevention program,“ said Michael Hanrahan, manager of education and prevention services of the HIV/STD program with Public Health — Seattle & King County. The agency, which runs four exchange programs, has watched the demand for clean needles surge from 1.8 million in 2006 to nearly 3.4 million last year.
Hanrahan said research has documented HIV transmission from dirty needles, but he wasn’t aware of rigorous studies showing disease spread via crack sores.

„But it’s certainly theoretically plausible,“ he said.
Last year, the Legislature passed a law allowing lay people to legally administer Naloxone, which counters the effects of an opioid overdose. Hanrahan said Public Health is interested in giving the drug to users, but because it is a prescription drug, the agency first needs to work on protocols with the state Board of Pharmacy.

At the People’s Harm Reduction Alliance – partially comprised of former users who run a table at Northeast 43rd Street and University Avenue Northeast – there is less need to follow protocols and studies.
The program began giving out crack kits a few months ago, after staffers felt the need to support crack users, who still make up a major local drug trend, according to a recent University of Washington study.
And the exchange began giving out Naloxone soon after the new law took effect in June.

Murphy estimated his program gives out two million needles a year and 10 pipes a day. This month, it handed out 25 vials of Naloxone.
„We don’t have clients, we just have community members. I make it clear to everyone that everyone is family here,“ Murphy said.
„We believe all drug users should have the right to not get diseases and have the ability to prevent diseases.“

Friday, August 6, 2010
By VANESSA HO
SEATTLEPI.COM STAFF

source: http://www.seattlepi.com/local/42462…ml?source=mypi

In a haunted world of heroin and hurt and heartless hustles, located between a dusty brickyard and rusty railroad tracks along the border of Chicago and blue-collar Cicero, Steve Kamenicky is the go-to guy.

Longtime addicts and novice users seek out Mr. Kamenicky, known as Pony Tail Steve, sometimes in the middle of the day, other times deep into the night. They go to him, usually in a panic, desperate for an injection for a fallen buddy or lover of what some call a miracle drug. They hurry over the paving bricks that Mr. Kamenicky neatly laid to lead the way to his tent, pitched among the tall weeds and trees in one of a string of small encampments of the homeless on the edge of the brickyard.

Mr. Kamenicky, 52, is not a dealer. His own heroin addiction is much too strong. He shoots every $10 bag of heroin he can.

But his fellow addicts consider Mr. Kamenicky a savior.

“I’ve saved more people than the paramedics,” he boasted the other evening as he sat in a Cicero parking lot, his long, salt-and-pepper ponytail snaking down his back.

The drug he administers to fellow heroin users is called Naloxone or Narcan, its brand name. Mr. Kamenicky estimated that in the last few years he had brought back from the deadly depths of heroin overdose at least 35 addicts — in abandoned buildings, crack houses and around kitchen tables.

Naloxone, which is injected, reverses the effects of an opiate overdose. A drug that was a few years ago given by doctors and paramedics, Naloxone is now directly dispensed to drug users like Mr. Kamenicky, who are trained by the Chicago Recovery Alliance and receive Naloxone through a doctor-supervised program. The effort is part of an up-from-the bottom movement in the struggle to rescue those addicted to heroin and other opiates.

“It saves lives,” said Dr. Virgilio Arenas, who leads the addiction division at Northwestern Memorial Hospital. “Naloxone is an effective antidote. It works within minutes once administered.”

Mr. Kamenicky receives Naloxone free, as do drug users across the city, from the alliance, a nonprofit needle-exchange and H.I.V.-prevention program. The alliance also dispenses fresh syringes, condoms and other paraphernalia to users in the hope that they will stay alive long enough to make “any positive change,” the group’s mantra.

Dr. Arenas said there were similar “harm-reduction” projects in Milwaukee, New York and other cities where needles and Naloxone were distributed.

Not everyone endorses the effort. “Some people in the addiction field feel it might foster more drug use,” Dr. Arenas said, adding, “but I don’t think people will use more because they have the antidote. I favor the harm-reduction approach.”

Anecdotal evidence suggests that the Naloxone campaign is saving lives in the Chicago metropolitan area, which led the nation in heroin-related hospital emergency-room visits from 2004 to 2008, according to a recent study. The Illinois Consortium on Drug Policy at Roosevelt University found that there were 23,931 such cases during that period, 50 percent more than were reported in New York City, which ranked second.

Dan Bigg, director and co-founder of the Chicago Recovery Alliance, said the group had collected about 2,000 reports of overdose reversals since 2001 when it began widely dispensing Naloxone to addicts — and even to family members, including one Lake Forest mother, who keeps a vial in her home in case her heroin-addicted daughter has another overdose.

“She wants a living daughter,” Mr. Bigg said, “despite whatever potential challenges she might bring in terms of struggling with drugs or education or marriage or anything else.”

Mr. Bigg said he had used Naloxone to reverse five overdoses. Greg Scott, a sociology professor at DePaul University and the recovery alliance’s research director, said he had reversed 24 overdoses, including a case two years ago when he used Naloxone on Mr. Kamenicky.

For years, Professor Scott has been documenting life in the “Brickyard,” Mr. Kamenicky’s encampment. In the last three years, he said, he has interviewed up to 300 suburban residents who come to the Brickyard to use the heroin they buy in surrounding neighborhoods before slipping back into mainstream society.

Mr. Scott said he had interviewed suburban housewives, hard-driving commodities traders and “weekend warriors,” who shoot up and get a thrill from hanging out at the Brickyard. He said the traders were the least responsive to his offers of Naloxone.

They don’t want to admit they might have a problem,” he said.

Mr. Scott, 42, has also been on the other end of the needle. He said he was addicted to opiates until a few years ago, overdosing on three occasions. Each time, he said, the overdose was reversed by Naloxone.

“It really is a kind of miracle drug,” he said.

Not everyone is as lucky as Mr. Kamenicky or Mr. Scott. In 2008, the most recent year for which statistics are available, there were 390 opiate-related overdose deaths in Cook County, up from 280 in 2007, said Dr. Nancy Jones, the Cook County medical examiner.

Dr. Jones said it was impossible to say how many might have been saved by Naloxone and not “end up on my table.”

The Chicago Recovery Alliance dispenses Naloxone from a fleet of silver panel trucks, which are parked in designated spots around the city every day. One truck recently sat baking in the sun at 61st Street and Calumet Avenue. Cheryl Hull, an alliance employee, has dispensed syringes, advice and compassion from the trucks for nearly 17 years.

Ms. Hull said she gave addicts a bottle of Naloxone and a DVD instructing them on its use. For those without DVD players or places to watch, Ms. Hull pops a disc into the truck’s portable player. Many people do not take the time to watch the instructions, she said, adding that young suburbanites were the most reluctant to linger and learn because they were afraid of the police and city crime.

On Wednesday night, Mr. Kamenicky sat on a plastic bucket, waiting for the alliance truck at a Cicero parking lot. He said it felt good to save a life, to give someone a second chance.

“I’ve only lost one person,” he said.

The victim, he said, was his boss at a suburban print shop. The man started snorting a $10 bag of heroin and then lost consciousness. Mr. Kamenicky ran to find his miracle drug.

“But somebody took it,” he said. “I tried to get some other people to help me, but they were too busy getting high. They couldn’t be bothered.

“By the time I found some Narcan, it was too late. I gave him a shot, but he was already dead.”