The most frequent adverse reaction in 1066 patients
treated with nalbuphine hydrochloride injection was sedation 381 (36%). Less
frequent reactions were: sweaty/clammy 99 (9%), nausea/vomiting 68 (6%),
dizziness/vertigo 58 (5%), dry mouth 44 (4%), and headache 27 (3%).
Other adverse reactions which occurred (reported
incidence of 1% or less) were:
CNS Effects : Nervousness, depression,
restlessness, crying, euphoria, floating, hostility, unusual dreams, confusion,
faintness, hallucinations, dysphoria, feeling of heaviness, numbness, tingling,
unreality. The incidence of psychotomimetic effects, such as unreality,
depersonalization, delusions, dysphoria and hallucinations has been shown to be
less than that which occurs with pentazocine.
Cardiovascular: Hypertension, hypotension,
Gastrointestinal: Cramps, dyspepsia, bitter taste.
Respiratory: Depression, dyspnea, asthma.
Dermatologic: Itching, burning, urticaria.
Miscellaneous : Speech difficulty, urinary
urgency, blurred vision, flushing and warmth.
Allergic Reactions : Anaphylactic/anaphylactoid
and other serious hypersensitivity reactions have been reported following the
use of nalbuphine and may require immediate, supportive medical treatment. These
reactions may include shock, respiratory distress, respiratory arrest,
bradycardia, cardiac arrest, hypotension, or laryngeal edema. Some of these allergic
reactions may be life-threatening. Other allergic-type reactions reported
include stridor, bronchospasm, wheezing, edema, rash, pruritus, nausea,
vomiting, diaphoresis, weakness, and shakiness.
Events Observed During Post-marketing Surveillance Of Nalbuphine
Due to the nature and limitations of spontaneous
reporting, causality has not been established for the following adverse events
received for nalbuphine hydrochloride injection: abdominal pain, pyrexia, depressed
level or loss of consciousness, somnolence, tremor, anxiety, pulmonary edema,
agitation, seizures, and injection site reactions such as pain, swelling,
redness, burning, and hot sensations. Death has been reported from severe
allergic reactions to nalbuphine hydrochloride treatment. Fetal death has been
reported where mothers received nalbuphine hydrochloride during labor and
- serotonin syndrome
- adrenal insufficiency
Chronic use of opioids may influence the
hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may
manifest as symptoms of hypogonadism, such as impotence, erectile dysfunction,
or amenorrhea. The causal role of opioids in the syndrome of hypogonadism is
unknown because the various medical, physical, lifestyle, and psychological
stressors that may influence gonadal hormone levels have not been adequately
controlled for in studies conducted to date. Patients presenting with symptoms
of androgen deficiency should undergo laboratory evaluation.
Drug Abuse And Dependence
Nalbuphine hydrochloride is a substance with a high
potential for abuse similar to other opioids. Nalbuphine hydrochloride can be
abused and is subject to misuse, addiction, and criminal diversion [see WARNINGS].
All patients treated with opioids require careful
monitoring for signs of abuse and addiction, since use of opioid analgesic
products carries the risk of addiction even under appropriate medical use.
Prescription drug abuse is the intentional non-therapeutic
use of a prescription drug, even once, for its rewarding psychological or
Drug addiction is a cluster of behavioral, cognitive, and
physiological phenomena that develop after repeated substance use and includes:
a strong desire to take the drug, difficulties in controlling its use, persisting
in its use despite harmful consequences, a higher priority given to drug use
than to other activities and obligations, increased tolerance, and sometimes a
“Drug-seeking” behavior is very common in
persons with substance use disorders. Drug-seeking tactics include emergency
calls or visits near the end of office hours, refusal to undergo appropriate examination,
testing, or referral, repeated “loss” of prescriptions, tampering
with prescriptions and reluctance to provide prior medical records or contact
information for other treating health care provider(s). “Doctor
shopping” (visiting multiple prescribers) to obtain additional
prescriptions is common among drug abusers and people suffering from untreated
addiction. Preoccupation with achieving adequate pain relief can be appropriate
behavior in a patient with poor pain control.
Abuse and addiction are separate and distinct from
physical dependence and tolerance. Health care providers should be aware that
addiction may not be accompanied by concurrent tolerance and symptoms of
physical dependence in all addicts. In addition, abuse of opioids can occur in
the absence of true addiction.
Nalbuphine hydrochloride, like other opioids, can be
diverted for non-medical use into illicit channels of distribution. Careful
record-keeping of prescribing information, including quantity, frequency, and renewal
requests, as required by state and federal law, is strongly advised.
Proper assessment of the patient, proper prescribing
practices, periodic re-evaluation of therapy, and proper dispensing and storage
are appropriate measures that help to limit abuse of opioid drugs.
Both tolerance and physical dependence opioid therapy can
develop during chronic opioid therapy. Tolerance is the need for increasing
doses of opioids to maintain a defined effect such as analgesia (in the absence
of disease progression or other external factors). Tolerance may occur to both
the desired and undesired effects of drugs, and may develop at different rates
for different effects.
Physical dependence results in withdrawal symptoms after
abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal
also may be precipitated through the administration of drugs with opioid
antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist
analgesics (pentazocine, butorphanol, nalbuphine), or partial agonists
(buprenorphine). Physical dependence may not occur to a clinically significant
degree until after several days to weeks of continued opioid usage. Nalbuphine
hydrochloride should not be abruptly discontinued [see DOSAGE AND ADMINISTRATION].
If nalbuphine hydrochloride is abruptly discontinued in a physically-dependent patient,
a withdrawal syndrome may occur. Some or all of the following can characterize
this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration,
chills, myalgia, and mydriasis. Other signs and symptoms also may develop,
including: irritability, anxiety, backache, joint pain, weakness, abdominal
cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood
pressure, respiratory rate, or heart rate.
Infants born to mothers physically dependent on opioids
will also be physically dependent and may exhibit respiratory difficulties and
withdrawal signs [see PRECAUTIONS; Pregnancy].