Products

Nalbuphine

Description

Drug Nalbuphine (nalbuphine hydrochloride) is a synthetic opioid agonist-antagonist analgesic of the phenanthrene series. It is chemically related to both the widely used opioid antagonist, naloxone, and the potent opioid analgesic, oxymorphone. Chemically nalbuphine hydrochloride is 17-(cyclobutylmethyl)-4,5a-epoxymorphinan-3,6a,14-triol hydrochloride. Nalbuphine hydrochloride molecular weight is 393.91 and is soluble in H2O (35.5 mg/mL @ 25ºC) and ethanol (0.8%); insoluble in CHCl3 and ether. Nalbuphine hydrochloride has pKa values of 8.71 and 9.96. The molecular formula is C21H27NO4.HCl.

Nalbuphine is a sterile solution suitable for subcutaneous, intramuscular, or intravenous injection. NUBAIN is available in two concentrations, 10 mg and 20 mg of nalbuphine hydrochloride per mL. Both strengths in 10 mL vials contain 0.94% sodium citrate hydrous, 1.26% citric acid anhydrous, and 0.2% of a 9:1 mixture of methylparaben and propylparaben as preservatives; pH is adjusted, if necessary, to 3.5 to 3.7 with hydrochloric acid. The 10 mg/mL strength contains 0.2% sodium chloride.

NUBAIN is also available in ampuls in a sterile, 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, and 1.26% citric acid anhydrous; pH is adjusted, if necessary, to 3.5 to 3.7 with hydrochloric acid. The 10 mg/mL strength contains 0.2% sodium chloride.

NUBAIN is indicated for the relief of moderate to severe pain. NUBAIN can also be used as a supplement to balanced anesthesia, for preoperative and postoperative analgesia, and for obstetrical analgesia during labor and delivery.

Dosage and Administration

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. (See Interaction with Other Central Nervous System Depressants under WARNINGS). In non-tolerant individuals, the recommended single 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 mg/kg intravenously to be administered over a 10 to 15 minute period with maintenance doses of 0.25 to 0.5 mg/kg in single intravenous administrations as required. The use of NUBAIN may be followed by respiratory depression which can be reversed with the opioid antagonist NARCAN® (naloxone hydrochloride).

NUBAIN is physically incompatible with nafcillin and keterolac.

Patients Dependent on Opioids

Patients who have been taking opioids chronically may experience withdrawal symptoms upon the administration of Nalbuphine. If unduly troublesome, opioid withdrawal symptoms can be controlled by the slow intravenous administration of small increments of morphine, until relief occurs. If the previous analgesic was morphine, meperidine, codeine, or other opioid with similar duration of activity, one-fourth of the anticipated dose of NUBAIN can be administered initially and the patient observed for signs of withdrawal, i.e., abdominal cramps, nausea and vomiting, lacrimation, rhinorrhea, anxiety, restlessness, elevation of temperature or piloerection. If untoward symptoms do not occur, progressively larger doses may be tried at appropriate intervals until the desired level of analgesia is obtained with NUBAIN.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

The most frequent adverse reaction in 1066 patients treated in clinical studies with NUBAIN 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, bradycardia, tachycardia.

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 NUBAIN: 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 NUBAIN treatment. Fetal death has been reported where mothers received NUBAIN during labor and delivery.

Drug Abuse And Dependence

There have been reports of abuse and dependence associated with NUBAIN among health care providers, patients and bodybuilders. There have been reported instances of psychological and physical dependence and tolerance in patients abusing NUBAIN. Individuals with a prior history of opioid or other substance abuse or dependence may be at greater risk in responding to reinforcing properties of nalbuphine.

Abrupt discontinuation of NUBAIN following prolonged use has been followed by symptoms of opioid withdrawal, i.e., abdominal cramps, nausea and vomiting, rhinorrhea, lacrimation, restlessness, anxiety, elevated temperature and piloerection.