Nalbuphine
Encyclopedia
Nalbuphine is a semi-synthetic opioid
used commercially as an analgesic
under a variety of trade names, including Nubain. It is noteworthy in part for the fact that at low dosages, it is found much more effective by women than by men, and may even increase pain
in men, leading to its discontinuation in the UK in 2003.
(CSA).
When the Controlled Substances Act (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 schedule II of the CSA in 1976. Presently, nalbuphine is not a controlled substance under the CSA. Kentucky has controlled nalbuphine in schedule IV of state law.
series. It is chemically related to both the widely used opioid antagonist, naloxone
, and the potent opioid analgesic, oxymorphone
. It is available in two concentrations, 10 mg and 20 mg of nalbuphine hydrochloride per mL. Both strengths contain 0.94% sodium citrate hydrous, 1.26% citric acid anhydrous, 0.1% sodium metabisulfite, and 0.2% of a 9:1 mixture of methylparaben and propylparaben as preservatives; pH is adjusted, if necessary, with hydrochloric acid. The 10 mg/mL strength contains 0.1% sodium chloride.
Nalbuphine is also available in a sulfite and paraben-free formulation in two concentrations, 10 mg and 20 mg of nalbuphine hydrochloride per mL. One mL of each strength contains 0.94% sodium citrate hydrous, 1.26% citric acid anhydrous; pH is adjusted, if necessary, with hydrochloric acid. The 10 mg/mL strength contains 0.2% sodium chloride.
Nalbuphine is a potent analgesic. Its analgesic potency is essentially equivalent to that of morphine on a milligram basis. Its onset of action occurs within 2 to 3 minutes after intravenous administration, and in less than 15 minutes following subcutaneous or intramuscular injection. The plasma half-life of nalbuphine is 5 hours and in clinical studies the duration of analgesic activity has been reported to range from 3 to 6 hours.
The opioid antagonist activity of Nalbuphine is one-fourth as potent as nalorphine
and 10 times that of pentazocine
.
Although Nalbuphine possesses opioid antagonist activity, there is evidence that in nondependent patients it will not antagonize a opioid analgesic administered just before, concurrently, or just after an injection. Therefore, patients receiving an opioid analgesic, general anesthetics, phenothiazines, or other tranquilizers, sedatives, hypnotics, or other CNS depressants (including alcohol) concomitantly with Nalbuphine may exhibit an additive effect. When such combined therapy is contemplated, the dose of one or both agents should be reduced.
maximum dose is 20 mg, with a maximum total daily dose of 160 mg.
The use of NUBAIN as a supplement to balanced anesthesia requires larger doses than those recommended for analgesia. Induction doses of NUBAIN range from 0.3 mg/kg to 3.0 mg/kg intravenously to be administered over a 10 to 15 minute period with maintenance doses of 0.25 to 0.50 mg/kg in single intravenous administrations as required.
In case of overdose or adverse reaction, the immediate intravenous administration of naloxone
(Narcan) is a specific antidote. Oxygen, intravenous fluids, vasopressors and other supportive measures should be used as indicated.
Other, less frequent reactions are: feeling sweaty/clammy 99 (9%), nausea/vomiting 68 (6%), dizziness/vertigo 58 (5%), dry mouth 44 (4%), and headache 27 (3%). Other adverse reactions which may occur (reported incidence of 1% or less) are:
Other possible, but rare side effects include speech difficulty, urinary urgency, blurred vision, flushing and warmth.
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
used commercially as an analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
under a variety of trade names, including Nubain. It is noteworthy in part for the fact that at low dosages, it is found much more effective by women than by men, and may even increase pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
in men, leading to its discontinuation in the UK in 2003.
History and control status
In the search for opioid analgesics with less abuse potential, a number of semi-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 opiod analgesic of this type (marketed in the U.S.) not controlled under the Controlled Substances ActControlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
(CSA).
When the Controlled Substances Act (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 schedule II of the CSA in 1976. Presently, nalbuphine is not a controlled substance under the CSA. Kentucky has controlled nalbuphine in schedule IV of state law.
Clinical pharmacology
Nalbuphine is a semi-synthetic opioid agonist-antagonist analgesic of the phenanthrenePhenanthrene
Phenanthrene is a polycyclic aromatic hydrocarbon composed of three fused benzene rings. The name phenanthrene is a composite of phenyl and anthracene. In its pure form, it is found in cigarette smoke and is a known irritant, photosensitizing skin to light...
series. It is chemically related to both the widely used opioid antagonist, naloxone
Naloxone
Naloxone is an opioid antagonist drug developed by Sankyo in the 1960s. Naloxone is a drug used to counter the effects of opiate overdose, for example heroin or morphine overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory...
, and the potent opioid analgesic, oxymorphone
Oxymorphone
Oxymorphone or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic first developed in Germany circa 1914, patented in the USA by Endo Pharmaceuticals in 1955 and introduced to the United States market in January 1959 and other countries around the same time...
. It is available in two concentrations, 10 mg and 20 mg of nalbuphine hydrochloride per mL. Both strengths contain 0.94% sodium citrate hydrous, 1.26% citric acid anhydrous, 0.1% sodium metabisulfite, and 0.2% of a 9:1 mixture of methylparaben and propylparaben as preservatives; pH is adjusted, if necessary, with hydrochloric acid. The 10 mg/mL strength contains 0.1% sodium chloride.
Nalbuphine is also available in a sulfite and paraben-free formulation in two concentrations, 10 mg and 20 mg of nalbuphine hydrochloride per mL. One mL of each strength contains 0.94% sodium citrate hydrous, 1.26% citric acid anhydrous; pH is adjusted, if necessary, with hydrochloric acid. The 10 mg/mL strength contains 0.2% sodium chloride.
Nalbuphine is a potent analgesic. Its analgesic potency is essentially equivalent to that of morphine on a milligram basis. Its onset of action occurs within 2 to 3 minutes after intravenous administration, and in less than 15 minutes following subcutaneous or intramuscular injection. The plasma half-life of nalbuphine is 5 hours and in clinical studies the duration of analgesic activity has been reported to range from 3 to 6 hours.
The opioid antagonist activity of Nalbuphine is one-fourth as potent as nalorphine
Nalorphine
Nalorphine trade names Lethidrone and Nalline. Nalorphine acts at two opioid receptors, at the mu receptor it has antagonistic effects and at the kappa receptors it exerts agonistic characteristics. It is used to reverse opioid overdose and in a challenge test to determine opioid dependence....
and 10 times that of pentazocine
Pentazocine
Pentazocine is a synthetically prepared prototypical mixed agonist-antagonist narcotic drug of the benzomorphan class of opioids used to treat moderate to moderately severe pain...
.
Indication
Nalbuphine is indicated for the relief of moderate to severe pain. It can also be used as a supplement to balanced anesthesia, for preoperative and postoperative analgesia, and for obstetrical analgesia during labor and delivery.Although Nalbuphine possesses opioid antagonist activity, there is evidence that in nondependent patients it will not antagonize a opioid analgesic administered just before, concurrently, or just after an injection. Therefore, patients receiving an opioid analgesic, general anesthetics, phenothiazines, or other tranquilizers, sedatives, hypnotics, or other CNS depressants (including alcohol) concomitantly with Nalbuphine may exhibit an additive effect. When such combined therapy is contemplated, the dose of one or both agents should be reduced.
Dosing
The usual recommended adult dose is 10 mg for a 70 kg individual, administered subcutaneously, intramuscularly or intravenously; this dose may be repeated every 3 to 6 hours as necessary. Dosage should be adjusted according to the severity of the pain, physical status of the patient, and other medications which the patient may be receiving. In non-tolerant individuals, the recommended singlemaximum dose is 20 mg, with a maximum total daily dose of 160 mg.
The use of NUBAIN as a supplement to balanced anesthesia requires larger doses than those recommended for analgesia. Induction doses of NUBAIN range from 0.3 mg/kg to 3.0 mg/kg intravenously to be administered over a 10 to 15 minute period with maintenance doses of 0.25 to 0.50 mg/kg in single intravenous administrations as required.
In case of overdose or adverse reaction, the immediate intravenous administration of naloxone
Naloxone
Naloxone is an opioid antagonist drug developed by Sankyo in the 1960s. Naloxone is a drug used to counter the effects of opiate overdose, for example heroin or morphine overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory...
(Narcan) is a specific antidote. Oxygen, intravenous fluids, vasopressors and other supportive measures should be used as indicated.
Side effects
The most frequent side effect in 1066 patients treated with nalbuphine was sedation in 381 (36%).Other, less frequent reactions are: feeling sweaty/clammy 99 (9%), nausea/vomiting 68 (6%), dizziness/vertigo 58 (5%), dry mouth 44 (4%), and headache 27 (3%). Other adverse reactions which may occur (reported incidence of 1% or less) are:
- 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 pentazocinePentazocinePentazocine is a synthetically prepared prototypical mixed agonist-antagonist narcotic drug of the benzomorphan class of opioids used to treat moderate to moderately severe pain...
. - Cardiovascular: Hypertension, hypotension, bradycardia, tachycardia, pulmonary edema.
- Gastrointestinal: Cramps, dyspepsia, bitter taste.
- Respiration: Depression, dyspnea, asthma.
- Dermatological: Itching, burning, urticaria.
- Obstetric: Pseudo-sinusoidal fetal heart rhythm.
Other possible, but rare side effects include speech difficulty, urinary urgency, blurred vision, flushing and warmth.