Drugs and Chemicals of
Concern > NALBUPHINE HYDROCHLORIDE
NALBUPHINE HYDROCHLORIDE
(Trade Name: Nubain®)
August 2007 DEA/OD/ODE
Introduction:
In the search for narcotic analgesics with less abuse potential, a
number of synthetic opiates were developed. These substances are
referred to as mixed agonist-antagonists analgesics. Nalbuphine (Nubain(®))
belongs to this group of substances. It was approved for marketing in
the United States in 1979 and remains as the only narcotic analgesic of
this type (that is marketed in the U.S.) not controlled under the
Controlled Substances Act (CSA).
Licit Uses:
Nalbuphine is approved for use in the U.S. as the hydrochloride salt
in an injectable formulation containing 10 or 20 mg/ml. It is available
by brand name, Nubain®, and generic formulations. Nalbuphine is
indicated for the treatment of moderate to severe acute pain.
Chemistry/Pharmacology:
Nalbuphine hydrochloride (Nubain®) is classified as a synthetic
opioid agonist-antagonist. Chemically, it is related to the opioid
antagonist, naloxone and the potent opioid agonist oxymorphone. The
chemical name for nalbuphine is
17-(cyclobutylmethyl)-4,5(-epoxymorphinan-3,6(, 14-triol hydrochloride.
It is soluble in water and ethanol and available only as an injectable
solution. Nalbuphine is a potent analgesic. Its analgesic potency is
essentially equivalent to morphine. It binds to mu, kappa, and delta
opioid receptors. Nalbuphine is metabolized by the liver and excreted by
the kidneys. The onset of action of nalbuphine occurs within 2 to 3
minutes after intravenous administration, and in less than 15 minutes
following subcutaneous or intramuscular injection. The plasma half-life
is 5 hours and the duration of analgesic activity has been reported to
range from 3 to 6 hours. Nalbuphine, like other potent opioids, is
associated with respiratory depression. Unlike morphine and other potent
mu agonists, nalbuphine produces less respiratory depression as the dose
is increased due to its agonist-antagonist "ceiling" effect.
Nalbuphine produces considerable sedation and may impair mental and
physical abilities in the performance of such tasks as driving
automobile or operating machinery. Nalbuphine may cause psychological or
physical dependence. Abrupt discontinuation after prolonged use can
cause signs and symptoms of opioid withdrawal.
Illicit Uses:
As an injectable formulation, nalbuphine is primarily utilized in
hospitals and rarely prescribed by physicians compared to other opioid
analgesics. In addition, as a drug of abuse it is less attractive as a
substitute by heroin addicts or highly tolerant opioid abusers due to
its potent antagonist effects. Nalbuphine is ten times more potent than
pentazocine as an antagonist and will precipitate withdrawal in an
opiate-tolerant individual. A limited number of anecdotal reports
suggest that nalbuphine is abused by health care professionals and by
body builders (anabolic steroid users). Nalbuphine is rarely encountered
by law enforcement personnel or submitted to forensic laboratories for
analysis. This may, in part, be due to its non-control status. According
to the National Forensic Laboratory Information System (NFLIS), state
and local forensic laboratories analyzed 10, 6, 11, and 16 exhibits of
nalbuphine in 2003, 2004, 2005 and 2006, respectively. According to the
System to Retrieve Information from Drug Evidence (STRIDE), DEA forensic
laboratories analyzed a total of 6 nalbuphine drug exhibits in 2005 and
2006.
Control Status:
When the CSA was enacted in 1971 nalbuphine was placed in schedule
II. Endo Laboratories, Inc. subsequently petitioned the DEA to exclude
nalbuphine from all schedules of the CSA in 1973. After receiving a
medical and scientific review and a scheduling recommendation from the
Department of Health, Education and Welfare, forerunner to the
Department of Health and Human Services, nalbuphine was removed from all
schedules of the CSA in 1976. Today, it remains a non-controlled
substance under the CSA.
Comments and additional information are welcomed by the
Drug and Chemical Evaluation Section, FAX 202-353-1263 or
telephone 202-307-7183.
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