NUBAIN Solution for injection Ref.[27884] Active ingredients: Nalbuphine

Dosing Considerations

NUBAIN (nalbuphine hydrochloride) injection should be used with caution within 12 hours pre-operatively and within the first 12-24 hours post-operatively (see WARNINGS AND PRECAUTIONS, Peri-operative Considerations).

Rapid intravenous injection of opioid analgesics increases the possibility of hypotension and respiratory depression.

For acute pain, it is recommended that NUBAIN be used for a maximum of 7 days at the lowest dose that provides adequate pain relief.

All doses of opioids carry an inherent risk of fatal or non-fatal adverse events. This risk is increased with higher doses. If NUBAIN is used for more than 7 days for the management of chronic non-cancer, non-palliative pain, it is recommended that 90 mg (90 morphine milligram equivalent) of NUBAIN not be exceeded. Each patient should be assessed for their risk prior to prescribing NUBAIN as the likelihood of experiencing serious adverse events can depend upon the type of opioid, duration of treatment, level of pain as well as the patient’s own level of tolerance. In addition, the level of pain should be assessed routinely to confirm the most appropriate dose and the need for further use of NUBAIN (see DOSAGE AND ADMINISTRATION, Adjustment or reduction of Dosage).

Analgesia

The usual recommended adult dose of NUBAIN (nalbuphine hydrochloride) is 10 mg for a 70 kg individual, administered subcutaneously, intramuscularly or intravenously. This dose may be repeated every 3 to 6 hours as required. In non-tolerant individuals, the recommended dosage range is 10 mg to 20 mg, with a maximum single dose of 20 mg and a maximum total daily dose of 160 mg. 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 WARNING).

Recommended Dose and Dosage Adjustment

Opioid Rotation: Conversion ratios for opioids are subject to variations in kinetics governed by genetics and other factors. When switching from one opioid to another, consider reducing the calculated dose by 25-50% to minimize the risk of overdose. Subsequently, up-titrate the dose, as required, to reach the appropriate maintenance dose.

Opioid Analgesics – Approximate Analgesic Equivalences¹:

Footnotes:

¹ References: Expert Advisory Committee on the Management of Severe Chronic Pain in Cancer Patients, Health and Welfare Canada. Cancer pain: A monograph on the management of cancer pain. Ministry of Supplies and Services Canada, 1987. Cat. No. H42-2/5-1984E. Foley KM. The treatment of cancer pain. N Engl J Med 1985;313(2):84-95. Aronoff GM, Evans WO. Pharmacological management of chronic pain: A review. In: Aronoff GM, editor. Evaluation and treatment of chronic pain. 2nd ed. Baltimore (MD): Williams and Wilkins; 1992. p. 359-68. Cherny NI, Portenoy RK. Practical issues in the management of cancer pain. In: Wall PD, Melzack R, editors. Textbook of pain. 3rd ed. New York: Churchill Livingstone; 1994. p. 1437-67.
² Most of the data were derived from single-dose, acute pain studies and should be considered an approximation for selection of doses when treating chronic pain. As analgesic conversion factors are approximate and patient response may vary, dosing should be individualized according to relief of pain and side effects. Because of incomplete cross-tolerance, dose reductions of 25% to 50% of the equianalgesic dose may be appropriate in some patients when converting from one opioid to another, particularly at high doses.† Upward titration may be required to reach appropriate maintenance doses. † Levy MH. Pharmacologic treatment of cancer pain. N Engl J Med 1996;335:1124-1132.
³ For acute pain, the oral or rectal dose of morphine is six times the injectable dose. However, for chronic dosing, clinical experience indicates that this ratio is 2-3:1 (i.e., 20-30 mg of oral or rectal morphine is equivalent to 10 mg of parenteral morphine).
⁴ Based on single entity oral oxycodone in acute pain.
⁵ Extremely variable equianalgesic dose. Patients should undergo individualized titration starting at an equivalent to 1/10 of the morphine dose.
⁶ Not recommended for the management of chronic pain.
⁷ Mixed agonist-antagonists can precipitate withdrawal in patients on pure opioid agonists.

Patients with Hepatic Impairment: Patients with liver dysfunction may show an exaggerated response to customary doses. In these individuals, NUBAIN should be used with caution and administered in reduced amounts.

Patients with Renal Impairment: Patients with renal dysfunction may show an exaggerated response to customary doses. In these individuals, NUBAIN should be used with caution and administered in reduced amounts.

Geriatrics: Respiratory depression has occurred in the elderly following administration of large initial doses of opioids to patients who were not opioid-tolerant or when opioids were co-administered with other agents that can depress respiration. NUBAIN should be initiated at a low dose and slowly titrated to effect (see WARNINGS AND PRECAUTIONS and ACTION AND CLINICAL PHARMACOLOGY).

Use with Non-Opioid Medications: If a non-opioid analgesic is being provided, it may be continued. If the non-opioid is discontinued, consideration should be given to increasing the opioid dose to compensate for the non-opioid analgesic. NUBAIN can be safely used concomitantly with usual doses of other non-opioid analgesics.

Dose Titration: Dose titration is the key to success with opioid analgesic therapy. Proper optimization of doses scaled to the relief of the individual’s pain should aim at administration of the lowest dose which will achieve the overall treatment goal of satisfactory pain relief with acceptable side effects.

Dosage adjustments should be based on the patient’s clinical response.

Adjustment or Reduction of Dosage: Physical dependence with or without psychological dependence tends to occur with chronic administration of opioids, including NUBAIN. Withdrawal (abstinence) symptoms may occur following abrupt discontinuation of therapy. These symptoms may include body aches, diarrhea, gooseflesh, loss of appetite, nausea, nervousness or restlessness, runny nose, sneezing, tremors or shivering, stomach cramps, tachycardia, trouble with sleeping, unusual increase in sweating, palpitations, unexplained fever, weakness and yawning.

Following successful relief of moderate to severe pain, periodic attempts to reduce the opioid dose should be made. Smaller doses or complete discontinuation may become feasible due to a change in the patient’s condition or mental state. Patients on prolonged therapy should be withdrawn gradually from the drug if it is no longer required for pain control. In patients who are appropriately treated with opioid analgesics and who undergo gradual withdrawal for the drug, these symptoms are usually mild (see WARNINGS AND PRECAUTIONS). Tapering should be individualised and carried out under medical supervision.

Patients should be informed that reducing and/or discontinuing opioids decreases their tolerance to these drugs. If treatment needs to be re-initiated, the patient must start at the lowest dose and titrate up to avoid overdose.

Balanced Anesthesia

Balanced anesthesia with NUBAIN requires larger doses than for the multiple doses recommended above for analgesia. Induction schedules with NUBAIN range from 0.3 mg/kg to 5 mg/kg intravenously over a 10 to 15 minute period.

After induction with NUBAIN is completed, maintenance doses of 0.25 mg/kg to 0.5 mg/kg can be used as required in single doses. Significant respiratory depression at the end of anesthesia rarely occurs with proper use of NUBAIN. Naloxone remains the specific antidote for any respiratory depression.

As a component to regional anesthesia, NUBAIN can be used in doses of 0.2 mg/kg to 0.5 mg/kg of body weight. NUBAIN produces sedation and additional analgesia to such regional techniques as alveolar nerve block and can be an adjunct to spinal anesthesia, regional nerve blocks, block of extremities, etc.

Incompatibility With Other Therapeutic Agents

NUBAIN is physically incompatible with nafcillin and ketorolac. Solutions of these drugs should not be mixed.

Disposal

NUBAIN should be kept in a safe place, out of the sight and reach of children before, during and after use. NUBAIN should never be disposed of in trash. Disposal via a pharmacy take back program is recommended. Unused or expired NUBAIN should be properly disposed of as soon as it is no longer needed to prevent accidental exposure to others.

Missed Dose

If a dose has been missed, the next dose should be administered at the next scheduled time and in the normal amount.

For management of a suspected drug overdose, contact your regional Poison Control Centre for the most current information.

Symptoms

These are expected to be similar to those of other drugs of this class. The administration of single I.M. doses of 72 mg of NUBAIN to eight normal subjects has been reported to have resulted primarily in symptoms of sleepiness and mild dysphoria.

Treatment

Naloxone hydrochloride administered intravenously is a specific antidote for NUBAIN. Since the duration of action of NUBAIN may exceed that of naloxone, the patient should be kept under continued surveillance and repeated doses of naloxone should be administered as necessary. Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated.

Store at controlled room temperature (15°c to 30°c). Protect from excessive light. Store in carton until contents have been used.