morphine/naltrexone

General

**REMS Drug**
High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

**Off Market Drug**
This medication is no longer available in the United States. Information provided here is for reference purposes only.

Pronunciation
MOR-feen/nal-TREX-one

Trade Name(s)

• Embeda

Controlled Substance Schedule
II

Pregnancy Category
Category C

Ther. class.
opioid analgesics

Pharm. class.
opioid agonists

Indications

Management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is required for an extended time; not for PRN use.

Action

Morphine—Binds to opiate receptors in the CNS. Alters the perception of and response to painful stimuli while producing generalized CNS depression. Naltrexone—Competitively blocks the effects of opioids, including CNS and respiratory depression, without producing any agonist (opioid-like) effects.

Therapeutic Effect(s):
Decreased severity of pain; addition of naltrexone is designed to prevent abuse or misuse by altering the formulation. Naltrexone has no effect unless the capsule is crushed or chewed..

Pharmacokinetics

Absorption: Morphine—Variably absorbed following oral administration (20–40%); absorption is delayed due to characteristics of formulation. Naltrexone—minimally absorbed from sequestered formulation.

Distribution: Morphine—distributes to skeletal muscle, kidneys, liver, intestinal tract, lungs, spleen, and brain; only small quantities pass the blood brain barrier; also crosses placenta. Naltrexone—enters breast milk (only after crushing or chewing).

Metabolism and Excretion: Morphine—Mostly metabolized by the liver, metabolites are renally excreted, 10% excreted unchanged in urine, minimal biliary excretion/enterohepatic recycling. Naltrexone—Extensive hepatic metabolism; major metabolite (6–ß-naltrexol) has opioid antagonist activity, metabolites are excreted in urine.

Half-life: Morphine in Embeda formulation—29 hr; naltrexone (following crushing or chewing)—4 hr; 6–ß-naltrexol—5–10 days.

TIME/ACTION PROFILE (analgesia)

ROUTE	ONSET	PEAK	DURATION
PO	delayed	7.5 hr†	12 hr

† blood level

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;

• Paralytic ileus;

• Any situation in which opioids are contraindicated.;

• Respiratory depression;

• Acute/severe asthma or hypercarbia;

• Lactation: Avoid use while breastfeeding.

Use Cautiously in:

• Hepatic/renal impairment or debility; initial dosage ↓ recommended;

• Patients who are not already opioid-tolerant, especially those who are receiving concurrent treatment with muscle relaxants, sedatives, or other CNS active medications (use lower initial doses).;

• History of substance abuse;

• Biliary tract disease, including pancreatitis;

• History of seizure disorders;

• Addison's disease, myxedema, hypothyroidism, prostatic hypertrophy or urethral stricture;

• Geri: Consider ↑ sensitivity, age-related ↓ in hepatic, pulmonary, renal and cardiovascular function, concurrent disease states and drug therapy; initial dosage ↓ recommended;

• OB: Use during pregnancy if need for strong opioids justifies potential risk to fetus; chronic maternal use of opioids during pregnancy may result in neonatal withdrawal syndrome (NWS);

• Pedi: Safety and effectiveness not established.

Exercise Extreme Caution in:
Patients susceptible to effects of CO₂ retention, including altered consciousness and head injury.

Adverse Reactions/Side Effects

CNS: drowsiness, anxiety, depression, dizziness, dizziness, fatigue, insomnia, irritability, , restlessness, syncope.

Resp: APNEA, RESPIRATORY ARREST, RESPIRATORY DEPRESSION.

CV: CARDIAC ARREST, CIRCULATORY DEPRESSION, SHOCK, hypotension.

GI: constipation, nausea, abdominal pain, ↑ amylase, ↓ appetite, diarrhea, dry mouth, flatulence, vomiting.

GU: urinary retention (↑ in elderly males).

Derm: hot flush, hyperhidrosis, pruritus.

MS: arthralgia, muscle spasm.

Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS , chills.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug

• ↑ risk CNS and respiratory depression with muscle relaxants , antihistamines , sedative/hypnotics and alcohol .

• Mixed agonist/antagonist opioids including pentazocine , nalbuphine and butorphanol may ↓ analgesia and/or may precipitate withdrawal.

• MAO inhibitors should not be used within 14 days preceding or following morphine/naltrexone due to ↑ risk of potentially serious adverse reactions.

• Phenothiazines and general anesthetics may ↑ risk of hypotension.

• May ↓efficacy of diuretics.

• ↑ risk of urinary retention and/or severe constipation with anticholinergics . PGP inhibitors including quinidine ↑ absorption/blood levels and risk of toxicity; use with caution.

Route/Dosage

• PO (Adults): Initial dose should be based on previous 24 hour dose of oral morphine equivalent, divided into two doses given every 12 hr, starting somewhat lower and providing adequate breakthrough and titration to optimal dosing..

Availability

• Capsules containing pellets of extended-release morphine surrounding an inner core of naltrexone : Morphine 30 mg/naltrexone 2 mg per capsule, morphine 50 mg/naltrexone 2 mg per capsule , morphine 60 mg/naltrexone 2.4 mg per capsule, morphine 80 mg/naltrexone 3.2 mg per capsule , morpine 100 mg/naltrexone 4 mg per capsule

Assessment

• Assess type, location, and intensity of pain prior to and every 12 hrs.

• Patients taking sustained-release morphine may require additional short-acting opioid doses for breakthrough pain. Doses should be equivalent to 10–20% of 24 hr total and given every 2 hr as needed.

• An equianalgesic chart (see Equianalgesic Dosing Guidelines) should be used when changing routes or when changing from one opioid to another.

• High Alert: Assess level of consciousness, BP, pulse, and respirations before and periodically during administration. If respiratory rate is <10/min, assess level of sedation. Physical stimulation may be sufficient to prevent significant hypoventilation. Subsequent doses may need to be decreased by 25–50%. Initial drowsiness will diminish with continued use.Geri: Assess geriatric patients frequently; older adults are more sensitive to the effects of opioid analgesics and may experience side effects and respiratory complications more frequently.

• Prolonged use may lead to physical and psychological dependence and tolerance. This should not prevent patient from receiving adequate analgesia. Most patients who receive morphine for pain do not develop psychological dependence. Progressively higher doses may be required to relieve pain with long-term therapy.

• Assess bowel function routinely. Institute prevention of constipation with increased intake of fluids and bulk and with laxatives to minimize constipating effects. Administer stimulant laxatives routinely if opioid use exceeds 2–3 days, unless contraindicated.

Lab Test Considerations

• May ↑ plasma amylase and lipase levels.

Toxicity and Overdose

• If an opioid antagonist is required to reverse respiratory depression or coma, naloxone (Narcan) is the antidote. Dilute the 0.4-mg ampule of naloxone in 10 ml of 0.9% NaCl and administer 0.5 ml (0.02 mg) by direct IV push every 2 min. For children and adults weighing <40 kg, dilute 0.1 mg of naloxone in 10 ml of 0.9% NaCl for a concentration of 10 mcg/ml and administer 0.5 mcg/kg every 2 min. Titrate dose to avoid withdrawal, seizures, and severe pain.

Potential Nursing Diagnoses

• Chronic pain (Indications)

• Disturbed sensory perception (visual, auditory) (Side Effects)

• Risk for injury (Side Effects)

Implementation

• High Alert: Do not confuse morphine with hydromorphone or meperidine—errors have resulted in death. Consider patient's previous analgesic use and current requirements, but clarify doses that greatly exceed normal range. Have second practitioner independently check original order, dose calculations and infusion pump settings.

• Explain therapeutic value of medication prior to administration to enhance the analgesic effect.

» Coadministration with nonopioid analgesics may have additive analgesic effects and may permit lower doses.

» Morphine should be discontinued gradually to prevent withdrawal symptoms after long-term use.

• PO: Doses may be administered with food or milk to minimize GI irritation.

» Swallow capsules whole; do not crush, break, dissolve or chew (could result in rapid release and absorption of a potentially toxic dose).

» Capsules may be opened and the pellets sprinkled onto applesauce immediately prior to administration.

Patient/Family Teaching

• Instruct patient how and when to ask for and take pain medication.

• May cause drowsiness or dizziness. Caution patient to call for assistance when ambulating or smoking and to avoid driving or other activities requiring alertness until response to medication is known.

• Advise patient to change positions slowly to minimize orthostatic hypotension.

• Caution patient to avoid concurrent use of alcohol or other CNS depressants with this medication.

• Encourage patients who are immobilized or on prolonged bedrest to turn, cough, and breathe deeply every 2 hr to prevent atelectasis.

• Home Care Issues: Emphasize the importance of aggressive prevention of constipation with the use of morphine.

Evaluation/Desired Outcomes

Decrease in severity of pain without a significant alteration in level of consciousness or respiratory status.