Morphine (Systemic)

Hypersensitivity (eg, anaphylaxis) to morphine or any component of the formulation; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days; GI obstruction, including paralytic ileus (known or suspected).

Documentation of allergenic cross-reactivity for opioids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Additional contraindications:

Epidural/intrathecal: Infection at infusion site; concomitant anticoagulant therapy; uncontrolled bleeding diathesis; presence of any other concomitant therapy or medical condition that would render administration hazardous; upper airway obstruction.

Rectal: Severe CNS depression; cardiac arrhythmias, heart failure due to chronic lung disease; increased intracranial or cerebrospinal pressure, head injuries, brain tumor; acute alcoholism, delirium tremens; seizure disorder; use after biliary tract surgery, suspected surgical abdomen, surgical anastomosis

According to the manufacturer's labeling, no specific dosage adjustments are provided (all formulations). In general, the manufacturers recommend starting cautiously with lower doses; titrating slowly while carefully monitoring for side effects. However, the choice of an alternate opioid may be prudent in patients with baseline renal impairment or rapidly changing renal function especially since other analgesics may be safer and reduced initial morphine dosing may result in suboptimal analgesia. Although clearance of morphine is similar to patients with normal renal function, glucuronide metabolites (M3G [inactive as an analgesic; may contribute to CNS stimulation] and M6G [active analgesic]) accumulate in renal impairment resulting in increased sensitivity; patients may experience severe and prolonged respiratory depression which may even be delayed (Lugo 2002; Niscola 2010).

There are no dosage adjustment provided in the manufacturer's labeling. Pharmacokinetics unchanged in mild liver disease; substantial extrahepatic metabolism may occur. In cirrhosis, increases in half-life and AUC suggest dosage adjustment required.

A 0.4 mg/mL oral solution may be made using the 2 mg/mL oral morphine solution. Measure 10 mL (20 mg) of the 2 mg/mL oral morphine solution and transfer to a plastic amber bottle. Measure 40 mL of sterile water for irrigation and add to bottle containing the morphine. Shake to mix. Store at room temperature. Stable for 60 days.

Oral: Do not crush, chew, or dissolve extended release (ER) formulations; swallow whole. Cutting, breaking, crushing, chewing, or dissolving ER formulations may result in uncontrolled delivery of morphine, leading to overdose and death.

Avinza, Kadian: Capsules may be opened and sprinkled on applesauce and eaten immediately without chewing; do not crush, dissolve, or chew the beads, as it can result in a rapid release of a potentially fatal dose of morphine. Ensure all pellets have been swallowed by rinsing mouth. Contents of Kadian capsules may be opened and sprinkled over 10 mL water and flushed through prewetted 16F gastrostomy tube; do not administer Kadian through gastric/nasogastric tubes.

Arymo ER: Swallow tablets whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth; do not pre-soak, lick, or wet tablets prior to placing in the mouth.

IV: Administer single-use prefilled syringes/cartridges via slow IV push over 4 to 5 minutes (rapid administration may result in chest wall rigidity). Concentrated vials are available for preparation of continuous IV infusion or PCA; refer to indication-specific infusion rates in dosing for detailed recommendations.

Epidural, intrathecal: Use only preservative-free solutions indicated for intrathecal or epidural use; refer to indication-specific infusion rates in dosing for detailed recommendations.

Morphine may cause GI upset; take with food if GI upset occurs. Be consistent when taking morphine with or without meals.

Some quinolones may produce a false-positive urine screening result for opioids using commercially-available immunoassay kits. This has been demonstrated most consistently for levofloxacin and ofloxacin, but other quinolones have shown cross-reactivity in certain assay kits. Confirmation of positive opioid screens by more specific methods should be considered.

Because of the risk of severe adverse effects when the epidural or intrathecal route of administration is employed, patients must be observed in a fully equipped and staffed environment for at least 24 hours after the initial dose. Single-dose Duramorph neuraxial administration may result in acute or delayed respiratory depression for up to 24 hours. Monitor patients receiving Infumorph, as appropriate, for the first several days after catheter implantation.

Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products that contain alcohol while taking morphine extended-release (ER) capsules. The coingestion of alcohol with morphine ER may result in increased plasma levels and a potentially fatal overdose of morphine.

Morphine exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing morphine and monitor all patients regularly for the development of these behaviors and conditions.

Serious, life-threatening, or fatal respiratory depression may occur with use of morphine. Monitor for respiratory depression, especially during initiation of morphine or following a dose increase. Swallow morphine ER formulations whole. ER capsule contents may be sprinkled on applesauce and swallowed immediately without chewing. Crushing, chewing, or dissolving the tablets or contents within the capsule can cause rapid release and absorption of a potentially fatal dose of morphine. Because of delay in maximum CNS effect with IV administration (30 minutes), rapid IV administration may result in overdosing. Observe patients in a fully equipped and staffed environment for at least 24 hours after each test dose of Infumorph and, as indicated, for the first several days after surgery.

Prolonged use of morphine during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Accidental ingestion of even one dose of morphine, especially by children, can result in a fatal overdose of morphine.

Ensure accuracy when prescribing, dispensing, and administering morphine oral solution. Dosing errors due to confusion between mg and mL, and other morphine solutions of different concentrations, can result in accidental overdose and death

Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of morphine and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.