Morphine

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Some dosage forms may be contraindicated in patients with severe CNS depression.

May cause constipation which may be problematic in patients with unstable angina and patients post-myocardial infarction. Consider preventive measures (eg, stool softener, increased fiber) to reduce the potential for constipation.

May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), circulatory shock, or drugs that may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock. Some dosage forms may be contraindicated in patients with cardiac arrhythmias or heart failure due to chronic lung disease.

Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).

Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely for respiratory depression, especially during initiation or dose escalation. Swallow morphine ER formulations whole (or may sprinkle the contents of the capsule on applesauce and swallow without chewing); crushing, chewing, or dissolving the ER formulations can cause rapid release and absorption of a potentially fatal dose of morphine. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Disease-related concerns:

May obscure diagnosis or clinical course of patients with acute abdominal conditions.

Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis (Brennan 2013).

Use with caution in patients with biliary tract dysfunction or acute pancreatitis; opioids may cause constriction of sphincter of Oddi.

Avoid use in patients with impaired consciousness or coma, as these patients are susceptible to intracranial effects of CO2 retention.

Use with caution in patients with delirium tremens. Some dosage forms may be contraindicated in patients with delirium tremens.

Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur. Some dosage forms may be contraindicated in patients with increased intracranial or cerebrospinal pressure, head injuries, or brain tumor.

Use with caution in patients with severe hepatic impairment.

Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (Dowell [CDC 2016]).

Use with caution in patients who are morbidly obese.

Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

Use with caution in patients with toxic psychosis.

Use with caution in patients with renal impairment.

Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale and patients having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or preexisting respiratory depression, particularly when initiating therapy and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

Use opioids with caution for chronic pain and titrate dosage cautiously in patients with risk factors for sleep-disordered breathing, including HF and obesity. Avoid opioids in patients with moderate to severe sleep-disordered breathing (Dowell [CDC 2016]).

Use with caution in patients with seizure disorders; may cause or exacerbate preexisting seizures. Some dosage forms may be contraindicated in patients with seizure disorder.

Use with caution in patients with thyroid dysfunction. Concurrent drug therapy issues:

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 dosage and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation. Some dosage forms may be contraindicated in patients with acute alcoholism.

Extended-release capsules: [US Boxed Warning]: Patients should not consume alcoholic beverages or medication containing ethanol while taking ER capsules; ethanol may increase morphine plasma levels, resulting in a potentially fatal overdose.

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

Use with caution in elderly patients; may be more sensitive to adverse effects, including life-threatening respiratory depression. Decrease initial dose. In the setting of chronic pain, monitor closely due to an increased potential for risks, including certain risks such as falls/fracture, cognitive impairment, and constipation. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increasing the risk for respiratory depression or overdose (Dowell [CDC 2016]). Consider the use of alternative nonopioid analgesics in these patients.

Neonatal withdrawal syndrome: [US Boxed Warning]: Prolonged maternal use of opioids during pregnancy can cause neonatal withdrawal syndrome in the newborn, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. If prolonged opioid therapy is required in a pregnant woman, ensure treatment is available and warn patient of risk to the neonate. Signs and symptoms include irritability, hyperactivity, abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn.

Infants Dosage form specific issues:

Neuroaxial administration: [US Boxed Warning]: 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 for the first several days after catheter implantation. Naloxone injection should be immediately available. Thoracic epidural administration has been shown to dramatically increase the risk of early and late respiratory depression. High doses (> 20 mg/day) of neuraxial morphine may produce myoclonic events. Patients with reduced circulating blood volume or impaired myocardial function, or on concomitant sympatholytic drugs should be monitored for orthostatic hypotension, a frequent complication in single-dose neuraxial morphine.

Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

Therapy should only be prescribed by health care professionals familiar with the use of potent opioids for chronic pain. Extended-release products are not interchangeable. When determining a generic equivalent or switching from one extended-release product to another, a thorough understanding of the pharmacokinetic properties is important in determining the proper generic equivalent or proper dose of the other extended-release product (review of the manufacturer's label may be necessary). - Arymo ER: Moistened tablets may become sticky, leading to difficulty in swallowing the tablets; choking, gagging, regurgitation, and tablets getting stuck in the throat may occur. Tablet stickiness and swelling may also predispose patients to intestinal obstruction and exacerbation of diverticulitis. Do not to pre-soak, lick, or otherwise wet tablets prior to placing in the mouth; take one tablet at a time with enough water to ensure complete swallowing. Consider use of an alternative analgesic in patients who have difficulty swallowing and patients at risk for underlying GI disorders resulting in a small GI lumen (eg, esophageal cancer, colon cancer). - Avinza capsules: Dosage form contains fumaric acid; dangerous quantities of fumaric acid may be ingested when >1,600 mg/day is used. Serious renal toxicity may occur above the maximum dose.

Risk of medication errors: [US Boxed Warning]: 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. The 100 mg per 5 mL (20 mg/mL) is for use in opioid-tolerant patients only.

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. Products are designed for administration by specific routes (ie, IV, intrathecal, epidural). Use caution when prescribing, dispensing, or administering to use formulations only by intended route(s). Rapid IV administration may result in chest wall rigidity. Use with caution when injecting IM into chilled areas or in patients with hypotension or shock (impaired perfusion may prevent complete absorption); if repeated injections are administered, an excessive amount may be suddenly absorbed if normal circulation is re-established.

Should only be used in microinfusion devices; not for IV, IM, or SubQ administration or for single-dose administration. Administer intrathecal doses of 10 and 25 mg/mL to the lumbar area. Monitor closely, especially in the first 24 hours. Inflammatory masses (eg, granulomas), some resulting in severe neurologic impairment, have occurred when receiving Infumorph via indwelling intrathecal catheter; monitor carefully for new neurologic signs/symptoms.

Improper or erroneous substitution of Infumorph for regular Duramorph is likely to result in serious overdosage, leading to seizures, respiratory depression, and possibly a fatal outcome.

Some dosage forms may contain sulfites that may cause allergic reactions in sulfite sensitive patients. Other warnings/precautions:

Morphine exposes patients and other users to the risks of addiction, abuse, and misuse, potentially leading to overdose and death. Assess each patient’s risk prior to prescribing; monitor all patients regularly for development of these behaviors or conditions. Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Other factors associated with increased risk include younger age, concomitant depression (major), and psychotropic medication use. Consider offering naloxone prescriptions in patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents/day orally), and concomitant benzodiazepine use (Dowell [CDC 2016]).

Oral: formulations: [US Boxed Warning]: Accidental ingestion of even one dose, especially in children, can result in a fatal overdose of morphine.

Chronic pain (outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder) in outpatient setting in adults: Opioids should not be used as first-line therapy for chronic pain management (pain >3-month duration or beyond time of normal tissue healing) due to limited short-term benefits, undetermined long-term benefits, and association with serious risks (eg, overdose, MI, auto accidents, risk of developing opioid use disorder). Preferred management includes nonpharmacologic therapy and nonopioid therapy (eg, NSAIDS, acetaminophen, certain anticonvulsants and antidepressants). If opioid therapy is initiated, it should be combined with nonpharmacologic and nonopioid therapy, as appropriate. Prior to initiation, known risks of opioid therapy should be discussed and realistic treatment goals for pain/function should be established, including consideration for discontinuation if benefits do not outweigh risks. Therapy should be continued only if clinically meaningful improvement in pain/function outweighs risks. Therapy should be initiated at the lowest effective dosage using immediate-release opioids (instead of extended-release/long-acting opioids). Risk associated with use increases with higher opioid dosages. Risks and benefits should be re-evaluated when increasing dosage to ≥50 morphine milligram equivalents (MME)/day orally; dosages ≥90 MME/day orally should be avoided unless carefully justi

An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the type of pain being treated (acute versus chronic), the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.

Opioids decrease bowel motility; monitor for decreased bowel motility in postop patients receiving opioids. Use with caution in the perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics. Some dosage forms may be contraindicated after biliary tract surgery, suspected surgical abdomen, or surgical anastomosis.

Concurrent use of mixed agonist/antagonist analgesics (eg, pentazocine, nalbuphine, butorphanol) or partial agonist (eg, buprenorphine) analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Taper dose gradually when discontinuing.