morphine hydrochloride ◆
Morphitec ◆, M.O.S. ◆

morphine sulfate
Astramorph PF, Avinza, Duramorph, Epimorph ◆, Infumorph, Kadian, MS Contin, MSIR, MS/L, MS/S, OMS Concentrate, Oramorph SR, RMS Uniserts, Roxanol, Statex ◆

Available forms
Available by prescription only
morphine hydrochloride ◆
Suppositories: 5 mg, 10 mg, 20 mg, 30 mg
Syrup: 1 mg/ml, 5 mg/ml, 10 mg/ml, 20 mg/ml, 50 mg/ml
Tablets: 10 mg, 20 mg, 40 mg, 60 mg
morphine sulfate
Capsules: 15 mg, 30 mg
Capsules (extended-release): 30 mg, 60 mg, 90 mg, 120 mg
Capsules (sustained-release): 20 mg, 50 mg, 100 mg
Injection (with preservative): 1 mg/ml, 2 mg/ml, 4 mg/ml, 5 mg/ml, 8 mg/ml, 10 mg/ml, 15 mg/ml, 25 mg/ml, 50 mg/ml
Injection (without preservative): 500 mcg/ml, 1 mg/ml, 10 mg/ml, 15 mg/ml, 25 mg/ml, 50 mg/ml
Oral solution: 10 mg/2.5 ml, 10 mg/5 ml, 20 mg/5 ml, 20 mg/ml, 30 mg/1.5 ml, 100 mg/5 ml
Suppositories: 5 mg, 10 mg, 20 mg, 30 mg
Tablets: 15 mg, 30 mg
Tablets (extended-release): 15 mg, 30 mg, 60 mg, 100 mg, 200 mg
Tablets (soluble): 10 mg, 15 mg, 30 mg

Indications and dosages
 Severe pain.
Adults: 10 mg q 4 hours S.C. or I.M., or 10 to 30 mg P.O., or 10 to 20 mg P.R. q 4 hours, p.r.n., or around the clock. May be injected slow I.V. (over 4 to 5 minutes) 2.5 to 15 mg diluted in 4 to 5 ml water for injection. May also administer controlled-release tablets 15 to 30 mg q 12 hours. As an intermittent epidural injection, 5 mg via an epidural catheter q 24 hours. For continuous epidural infusion (device not implanted surgically), initial dose is 2 to 4 mg per 24 hours. May increase 1 to 2 mg daily, as needed. For a surgically implanted device, 3.5 to 7.5 mg daily or 4.5 to 10 mg daily if opiate tolerant. Intrathecal dose is one-tenth epidural dose; 0.2 to 1 mg may provide adequate relief in patients not tolerant to opiates.
 Extended-released capsules are given q 24 hours.
Children: 0.1 to 0.2 mg/kg S.C. or I.M. q 4 hours. Maximum dose is 15 mg. May also give 0.05 to 0.1 mg/kg I.V. very slowly. In some situations, morphine may be administered by continuous I.V. infusion or by intraspinal and intrathecal injection.
 Severe chronic pain related to cancer.
Adults: Initial loading dose of 15 mg I.V. push followed by 0.8 to 10 mg /hour continuous I.V. or S.C. infusion. Adjust to effect.
Children: 0.025 to 2.6 mg/kg/hour by I.V. infusion or 0.025 to 1.79 mg/kg/hour by S.C. infusion.
 Preoperative sedation and adjunct to anesthesia. Adults: 8 to 10 mg I.M., S.C., or I.V.
 Postoperative analgesia.
Children: 0.01 to 0.04 mg/kg/hour by continuous I.V. infusion.
Neonates: 0.015 to 0.02 mg/kg/hour by continuous I.V. infusion.
 Control of pain caused by acute MI. Adults: Initially, 2 to 15 mg I.M., S.C., or I.V. Additional doses of 1 to 4 mg I.V. may be given q 5 minutes, p.r.n.
 Control of angina pain. Adults: 2 to 5 mg I.V. q 5 to 30 minutes, p.r.n., in pain unrelieved by three doses of S.L. nitroglycerin.
 Adjunctive treatment of acute pulmonary edema. Adults: 10 to 15 mg I.V. at a rate not exceeding 2 mg/minute.
 Analgesia during labor. Adults: 10 mg I.M. or S.C.

Pharmacodynamics
Analgesic action: Morphine is the principal opium alkaloid, the standard for opiate agonist analgesic activity. Mechanism of action is thought to be via the opiate receptors, altering patient’s perception of pain. Morphine is particularly useful in severe, acute pain or severe, chronic pain. Morphine also has a central depressant effect on respiration and on the cough reflex center.

Pharmacokinetics
Absorption: Absorption is variable from the GI tract.
Distribution: Distributed widely through the body; low protein-binding.
Metabolism: Metabolized primarily in the liver. One metabolite, morphine 6-glucuromide, is active.
Excretion: Excreted in the urine and bile. Morphine 6-glucuromide may accumulate after continuous dosing in patients with renal failure, leading to enhanced and prolonged opiate activity.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and patients with conditions that would preclude administration of opioids by I.V. route (acute bronchial asthma or upper airway obstruction).
  Use cautiously in geriatric or debilitated patients and in those with head injury, increased intracranial pressure, seizures, pulmonary disease, prostatic hyperplasia, hepatic or renal disease, acute abdominal conditions, hypothyroidism, Addison’s disease, or urethral strictures.

Interactions
Drug-drug. Anticholinergics: May cause paralytic ileus. Monitor patient carefully.
Cimetidine: Increases respiratory and CNS depression. Reduced dosage of morphine is usually needed.
CNS depressants, such as antihistamines, barbiturates, benzodiazepines, general anesthetics, narcotic analgesics, MAO inhibitors, muscle relaxants, phenothiazines, sedative-hypnotics, tricyclic antidepressants: Potentiates respiratory and CNS depression, sedation, and hypotensive effects of drug. Use together cautiously.
General anesthetics: May cause severe CV depression. Use together cautiously.
Narcotic antagonist: Patients who become physically dependent on this drug may experience acute withdrawal syndrome if given a narcotic antagonist. Avoid use together.
Zidovudine: May cause toxicity of either or both drugs. Monitor patient for toxicity.
Drug-lifestyle. Alcohol use: Potentiates effects of drug. Discourage alcohol use.

Adverse reactions
CNS: sedation, somnolence, clouded sensorium, euphoria, seizures (with large doses), dizziness, nightmares (with long-acting oral forms), light-headedness, hallucinations, nervousness, depression, syncope.
CV: hypotension, bradycardia, shock, cardiac arrest, tachycardia, hypertension.
GI: nausea, vomiting, constipation, ileus, dry mouth, biliary tract spasms, anorexia.
GU: urine retention.
Hematologic: thrombocytopenia.
Respiratory: respiratory depression, apnea, respiratory arrest.
Skin: pruritus, skin flushing (with epidural administration); diaphoresis; edema. Other: physical dependence, decreased libido.

Effects on lab test results
• May increase amylase levels.
• May decrease platelet count.

Overdose and treatment
Rapid I.V. administration may result in overdose because of the delay in maximum CNS effect (30 minutes). The most common effects of morphine overdose are respiratory depression, with or without CNS depression, and miosis (pinpoint pupils). Other acute toxic effects include hypotension, bradycardia, hypothermia, shock, apnea, cardiopulmonary arrest, circulatory collapse, pulmonary edema, and seizures.
 To treat acute overdose, first establish adequate respiratory exchange by way of a patent airway and ventilation, as needed; administer a narcotic antagonist (naloxone) to reverse respiratory depression. (Because duration of action of morphine is longer than that of naloxone, repeated naloxone dosing is needed.) Naloxone shouldn’t be given in the absence of clinically significant respiratory or CV depression. Monitor vital signs closely.
 If patient is seen within 2 hours of ingestion of an oral overdose, empty the stomach immediately by inducing emesis (ipecac syrup) or using gastric lavage. Use cautiously to avoid risk of aspiration. Administer activated charcoal via nasogastric tube for further removal of drug in an oral overdose.
 Provide symptomatic and supportive treatment (continued respiratory support, correction of fluid or electrolyte imbalance). Monitor laboratory parameters, vital signs, and neurologic status closely.

Special considerations
 ALERT Don’t confuse morphine with hydromorphone. Don’t confuse Avinza (extended-release morphine sulfate) with Invanz (ertapenem).
• Morphine is the drug of choice in relieving pain of MI; it may cause transient decrease in blood pressure.
• Regimented (around-the-clock) scheduling is beneficial in severe, chronic pain.
• Oral solutions of various levels are available as well as a new intensified oral solution.
• There’s a greater fluctuation in pain control with extended-release preparations.
• Note the disparity between oral and parenteral doses.
 ALERT For continuous epidural or intrathecal infusion, morphine is administered via a controlled-infusion device. Take care when refilling the reservoir of such devices to ensure that medication is instilled into the proper port. A technical error could result in life-threatening respiratory depression.
• Morphine sulfate 10 or 25 mg/ml injections are intended for use with continuous, controlled microinfusion devices.
• For I.V. use, morphine 25 mg/ml is diluted to 0.1 to 1 mg/ml in D₅W. A higher concentration may be used for patients with fluid restriction.
• Long-term therapy in patients with advanced renal disease may lead to toxicity as a result of accumulation of the active metabolite.
• Some morphine injections contain sulfites which may cause allergic-type reactions.
• For S.L. administration, measure oral solution with tuberculin syringe, and administer dose a few drops at a time to allow maximal S.L. absorption and to minimize swallowing.
• Refrigeration of rectal suppositories isn’t needed. In some patients, rectal and oral absorption may not be equivalent.
• Preservative-free preparations are available for epidural and intrathecal administration. The use of the epidural route is increasing.
• Epidural morphine has proven to be an excellent analgesic for patients with postoperative pain. After epidural administration, monitor patient closely for respiratory depression up to 24 hours after the injection. Check respiratory rate and depth according to protocol (such as every 15 minutes for 2 hours, then hourly for 18 hours). Some clinicians advocate a dilute naloxone infusion of 5 to 10 mcg/kg/hour during the first 12 hours to minimize respiratory depression without altering pain relief.
• Morphine may worsen or mask gallbladder pain.
Breast-feeding patients
• Morphine appears in breast milk. Breast-feeding women should wait 2 to 3 hours after last dose before breast-feeding to avoid sedating infant.
Pediatric patients
• Safety and efficacy of epidural and intrathecal dosing in children haven’t been established.
• Safety and efficacy of morphine in neonates haven’t been established. Children may be more sensitive to opiates on a body-weight basis.
Geriatric patients
• Lower doses are usually indicated for geriatric patients, who may be more sensitive to the therapeutic and adverse effects of drug.

Patient education
• Tell patient that oral liquid form of morphine may be mixed with a glass of fruit juice immediately before it’s taken, if desired, to improve the taste.
• Tell patient taking long-acting morphine tablets to swallow them whole. Tablets shouldn’t be broken, crushed, or chewed before swallowing.
• Tell patient to take with food to lessen GI upset.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use