Nubain Injection :: Endo Labs

DESCRIPTION

NUBAIN (nalbuphine hydrochloride) is a synthetic narcotic agonist-antagonist analgesic of the phenanthrene series. It is chemically related to both the widely used narcotic antagonist, naloxone, and the potent narcotic analgesic, oxymorphone.

data/images/12/62003501.jpg

NUBAIN 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.

CLINICAL PHARMACOLOGY

NUBAIN is a potent analgesic. Its analgesic potency is essentially equivalent to that of morphine on a milligram basis. Receptor studies show that NUBAIN binds to mu, kappa, and delta receptors, but not to sigma receptors. NUBAIN is primarily a kappa agonist/partial mu antagonist analgesic.

The onset of action of NUBAIN 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 narcotic antagonist activity of NUBAIN is one-fourth as potent as nalorphine and 10 times that of pentazocine.

NUBAIN may produce the same degree of respiratory depression as equianalgesic doses of morphine. However, NUBAIN exhibits a ceiling effect such that increases in dose greater than 30 mg do not produce further respiratory depression.

NUBAIN by itself has potent narcotic antagonist activity at doses equal to or lower than its analgesic dose. When administered following or concurrent with mu agonist opioid analgesics (e.g., morphine, oxymorphone, fentanyl), NUBAIN may partially reverse or block narcotic-induced respiratory depression from the mu agonist analgesic. NUBAIN may precipitate withdrawal in patients dependent on opioid narcotic drugs. NUBAIN should be used with caution in patients who have been receiving mu opioid analgesics on a regular basis.

INDICATIONS AND USAGE

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.

CONTRAINDICATIONS

NUBAIN should not be administered to patients who are hypersensitive to nalbuphine hydrochloride, or to any of the other ingredients in NUBAIN.

WARNINGS

NUBAIN should be administered as a supplement to general anesthesia only by persons specifically trained in the use of intravenous anesthetics and management of the respiratory effects of potent opioids.

Naloxone, resuscitative and intubation equipment and oxygen should be readily available.

Drug Abuse   Caution should be observed in prescribing NUBAIN for emotionally unstable patients, or for individuals with a history of narcotic abuse. Such patients should be closely supervised when long-term therapy is contemplated (see DRUG ABUSE AND DEPENDENCE ).

Use in Ambulatory Patients   NUBAIN may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery. Therefore, NUBAIN should be administered with caution to ambulatory patients who should be warned to avoid such hazards.

Use in Emergency Procedures   Maintain patient under observation until recovered from NUBAIN effects that would affect driving or other potentially dangerous tasks.

Use in Pregnancy (other than labor)   Safe use of NUBAIN in pregnancy has not been established. Although animal reproductive studies have not revealed teratogenic or embryotoxic effects, nalbuphine should be administered to pregnant women only if clearly needed.

Use During Labor and Delivery   The placental transfer of nalbuphine is high, rapid, and variable with a maternal to fetal ratio ranging from 1:0.37 to 1:1.6. Fetal and neonatal adverse effects that have been reported following the administration of nalbuphine to the mother during labor include fetal bradycardia, respiratory depression at birth, apnea, cyanosis and hypotonia. Maternal administration of naloxone during labor has normalized these effects in some cases. Severe and prolonged fetal bradycardia has been reported. Permanent neurological damage attributed to fetal bradycardia has occurred. A sinusoidal fetal heart rate pattern associated with the use of nalbuphine has also been reported. NUBAIN should be used with caution in women during labor and delivery, and newborns should be monitored for respiratory depression, apnea, bradycardia, and arrhythmias if NUBAIN has been used.

Head Injury and Increased Intracranial Pressure   The possible respiratory depressant effects and the potential of potent analgesics to elevate cerebrospinal fluid pressure (resulting from vasodilation following CO 2 retention) may be markedly exaggerated in the presence of head injury, intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, potent analgesics can produce effects which may obscure the clinical course of patients with head injuries. Therefore, NUBAIN should be used in these circumstances only when essential, and then should be administered with extreme caution.

Interaction With Other Central Nervous System Depressants   Although NUBAIN possesses narcotic antagonist activity, there is evidence that in nondependent patients it will not antagonize a narcotic analgesic administered just before, concurrently, or just after an injection of NUBAIN. Therefore, patients receiving a narcotic analgesic, general anesthetics, phenothiazines, or other tranquilizers, sedatives, hypnotics, or other CNS depressants (including alcohol) concomitantly with NUBAIN may exhibit an additive effect. When such combined therapy is contemplated, the dose of one or both agents should be reduced.

PRECAUTIONS

General

Impaired Respiration At the usual adult dose of 10 mg/70 kg, NUBAIN causes some respiratory depression approximately equal to that produced by equal doses of morphine. However, in contrast to morphine, respiratory depression is not appreciably increased with higher doses of NUBAIN. Respiratory depression induced by NUBAIN can be reversed by NARCAN® (naloxone hydrochloride) when indicated. NUBAIN should be administered with caution at low doses to patients with impaired respiration (e.g., from other medication, uremia, bronchial asthma, severe infection, cyanosis, or respiratory obstructions).

Impaired Renal or Hepatic Function Because NUBAIN is metabolized in the liver and excreted by the kidneys, NUBAIN should be used with caution in patients with renal or liver dysfunction and administered in reduced amounts.

Myocardial Infarction As with all potent analgesics, NUBAIN should be used with caution in patients with myocardial infarction who have nausea or vomiting.

Biliary Tract Surgery As with all narcotic analgesics, NUBAIN should be used with caution in patients about to undergo surgery of the biliary tract since it may cause spasm of the sphincter of Oddi.

Cardiovascular System During evaluation of NUBAIN in anesthesia, a higher incidence of bradycardia has been reported in patients who did not receive atropine pre-operatively.

Information for Patients

Patients should be advised of the following information:

Laboratory Tests

NUBAIN may interfere with enzymatic methods for the detection of opioids depending on the specificity/sensitivity of the test. Please consult the test manufacturer for specific details.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of carcinogenicity was found in a 24-month carcinogenicity study in rats and an 18-month carcinogenicity study in mice at oral doses as high as the equivalent of approximately three times the maximum recommended therapeutic dose.

No evidence of a mutagenic/genotoxic potential to NUBAIN was found in the Ames, Chinese Hamster Ovary HGPRT, and Sister Chromatid Exchange, mouse micronucleus, and rat bone marrow cytogenicity assays. Nalbuphine induced an increased frequency of mutation in mouse lymphoma cells.

Usage in Pregnancy

Teratogenic Effects

Pregnancy Category B--Reproduction studies have been performed in rabbits and in rats at dosages as high as approximately 14 and 31 times respectively the maximum recommended daily dose and revealed no evidence of impaired fertility or harm to the fetus due to NUBAIN. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed (see WARNINGS ).

Non-teratogenic Effects

Neonatal body weight and survival was reduced when NUBAIN was subcutaneously administered to female rats prior to mating and throughout gestation and lactation or to pregnant rats during the last third of gestation and throughout lactation at doses approximately 8 to 17 times the maximum recommended therapeutic dose. The clinical significance of this effect is unknown.

Use During Labor and Delivery

See WARNINGS .

Nursing Mothers

Limited data suggest that NUBAIN (nalbuphine hydrochloride) is excreted in maternal milk but only in a small amount (less than 1% of the administered dose) and with a clinically insignificant effect. Caution should be exercised when NUBAIN is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

ADVERSE REACTIONS

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. Other allergic-type reactions reported include stridor, bronchospasm, wheezing, edema, rash, pruritus, nausea, vomiting, diaphoresis, weakness, and shakiness.

Post-marketing   Other reports include pulmonary edema, agitation and injection site reactions such as pain, swelling, redness, burning, and hot sensations.

DRUG ABUSE AND DEPENDENCE

NUBAIN has been shown to have a low abuse potential. When compared with drugs which are not mixed agonist-antagonists, it has been reported that nalbuphine's potential for abuse would be less than that of codeine and propo-xyphene. Drug abuse has been reported infrequently. Psychological and physical dependence and tolerance may follow the abuse or misuse of nalbuphine (see WARNINGS ).

Care should be taken to avoid increases in dosage or frequency of administration which in susceptible individuals might result in physical dependence.

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

OVERDOSAGE

The immediate intravenous administration of NARCAN® (naloxone hydrochloride) is a specific antidote. Oxygen, intravenous fluids, vasopressors and other supportive measures should be used as indicated.

The administration of single doses of 72 mg of NUBAIN subcutaneously to eight normal subjects has been reported to have resulted primarily in symptoms of sleepiness and mild dysphoria.

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 narcotic antagonist NARCAN® (naloxone hydrochloride).

NUBAIN is physically incompatible with nafcillin and keterolac.

Patients Dependent on Narcotics   Patients who have been taking narcotics chronically may experience withdrawal symptoms upon the administration of NUBAIN. If unduly troublesome, narcotic 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 narcotic 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.

HOW SUPPLIED

NUBAIN® (nalbuphine hydrochloride) injection for intramuscular, subcutaneous, or intravenous use is a sterile solution available in:

NDC 63481-508-05 (sulfite-free) 10 mg/mL, 10 mL multiple dose vials (box of 1)

NDC 63481-432-10 (sulfite/paraben-free) 10 mg/mL, 1 mL ampuls (box of 10)

NDC 63481-509-05 (sulfite-free) 20 mg/mL, 10 mL multiple dose vials (box of 1)

NDC 63481-433-10 (sulfite/paraben-free) 20 mg/mL, 1 mL ampuls (box of 10)

Store at controlled room temperature 15°-30°C (59°-86°F). Protect from excessive light. Store in carton until contents have been used.

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

NUBAIN® is a Registered Trademark of Endo Pharmaceuticals Inc.

NARCAN® is a Registered Trademark of Endo Pharmaceuticals Inc.

             Copyright © Endo Pharmaceuticals Inc. 1999

                                                    6494-01/Rev. April, 1999



Search product (brand or generic name): or browse alphabetical:
ABCDEFGHIJKLMNOPQRSTUVWXYZ