Morphine Sulfate

Pronunciation: (moRE-feen SULL-fate)

Class: Opioid analgesic

Trade Names:

Astramorph PF

- Injection 0.5 mg/mL

- Injection 1 mg/mL

Trade Names:

Duramorph

- Injection 0.5 mg/mL

- Injection 1 mg/mL

Trade Names:

Infumorph

- Injection 10mg/mL

- Injection 25 mg/mL

Trade Names:

Kadian

- Capsules, sustained-release 20 mg

- Capsules, sustained-release 50 mg

- Capsules, sustained-release 100mg

Trade Names:

MS Contin

- Tablets, controlled-release 15mg

- Tablets, controlled-release 30 mg

- Tablets, controlled-release 60mg

- Tablets, controlled-release 100 mg

- Tablets, controlled-release 200mg

Trade Names:

MSIR

- Solution 10 mg per 5 mL

- Solution 20 mg per 5 mL

- Solution 20 mg/mL

Trade Names:

Oramorph SR

- Tablets, controlled-release 15mg

- Tablets, controlled-release 30 mg

- Tablets, controlled-release 60 mg

- Tablets, controlled-release 100 mg

Trade Names:

OMS Concentrate

- Solution 20 mg/mL

Trade Names:

RMS

- Rectal Suppositories 5 mg

- Rectal Suppositories 10 mg

- Rectal Suppositories 20 mg

- Rectal Suppositories 30 mg

Trade Names:

Roxanol

- Solution 20 mg/mL

Trade Names:

Roxanol Rescudose

- Solution 10 mg per 2.5 mL

Trade Names:

Roxanol 100

- Solution 100 mg per 5 mL

Trade Names:

Roxanol T

- Solution 20 mg/mL

Trade Names:

Roxanol UD

- Solution 10 mg per 2.5 mL

- Solution 20 mg per 5 mL

- Solution 30 mg per 1.5 mL

M.O.S.-Sulfate (Canada)

Morphine HP Injection (Canada)

Morphine LP Epidural (Canada)

PMS-Morphine Sulfate SR (Canada)

ratio-Morphine SR (Canada)

Pharmacology

Relieves pain by stimulating opiate receptors in CNS; also causes respiratory depression, peripheral vasodilation, inhibition of intestinal peristalsis, sphincter of Oddi spasm, stimulation of chemoreceptors that cause vomiting and increased bladder tone.

Pharmacokinetics

Absorption

Mean T max is 3.7 h and mean C max is 9.9 to 27.4 ng/mL (dose dependent) for sustained-release form. Bioavailability is approximately 40%.

Distribution

Morphine distributes to skeletal muscle, kidneys, liver, intestinal tract, lungs, spleen, and brain; crosses the placental membrane and is found in breast milk.

Metabolism

Virtually all converted into glucuronide metabolites; small fraction is demethylated in the liver. Major metabolite is morphine-3-glucuronide (55% to 75%).

Elimination

The t ½ is approximately 2 to 4 h.

Onset

Onset is 15 to 60 min (intrathecal/epidural).

Duration

Duration is 3 to 7 h.

Indications and Usage

Relief of moderate to severe acute and chronic pain; relief of pain in patients who require opioid analgesics for more than a few days (sustained-release only); management of pain not responsive to nonnarcotic analgesics; dyspnea associated with acute left ventricular failure and pulmonary edema; preoperative sedation; adjunct to anesthesia; analgesia during labor.

Contraindications

Hypersensitivity to opiates; upper airway obstruction; acute asthma; diarrhea caused by poisoning or toxins.

Injection

Heart failure secondary to chronic lung disease; cardiac arrhythmias; brain tumor; acute alcoholism; delirium tremens; idiosyncrasy to the drug; convulsive states (eg, status epilepticus, tetanus, strychnine poisoning).

Immediate-release oral solution

Respiratory insufficiency; severe CNS depression; heart failure secondary to chronic lung disease; cardiac arrhythmias; increased intracranial or cerebrospinal pressure; head injuries; brain tumor; acute alcoholism; delirium tremens; convulsive disorders; after biliary tract surgery; suspected surgical abdomen; surgical anastomosis; idiosyncrasy to the drug; concomitantly with MAOIs or within 14 days of such treatment.

Intrathecal/epidural

Infection at injection site; anticoagulation; bleeding condition; parenteral corticosteroids within past 2 wk; any other drug or condition that would contraindicate intrathecal/epidural therapy.

Dosage and Administration

Adults

PO 10 to 30 mg every 4 h as needed. Subcutaneous/IM 5 to 20 mg/70 kg every 4 h as needed. IV 2.5 to 15 mg per 70 kg in water for injection 4 to 5 mL over 5 min as needed. IV (open-heart surgery) 0.5 to 3mg/kg. IV (MI pain) 8 to 15 mg; for very severe pain, additional smaller doses may be given every 3 to 4 h. PR 10 to 20 mg every 4 h as needed. Epidural Initial injection of 5 mg may provide pain relief for up to 24 h; if pain is not controlled within 1 h, give incremental doses of 1 to 2 mg. Do not exceed 10mg per 24h. Intrathecal Usual dose is 10% of epidural dose. Single injection of 0.2 to 1 mg may provide pain relief for 24 h. Do not inject more than 2 mL of 5 mg per 10 mL ampule or 1 mL of 10 mg per 10 mL ampule. Repeat injections not recommended.

Children

Subcutaneous/IM 0.1 to 0.2 mg/kg every 4 h.

Max dose

15 mg.

Storage/Stability

Store at room temperature (59° to 86°F).

Drug Interactions

Morphine has the following interaction information:

Esmolol morphine possibly increases plasma concentration of esmolol
Ritonavir plasma concentration of morphine possibly reduced by ritonavir
Morphine belongs to Opioid Analgesics and will have the following interactions:

Alcohol enhanced hypotensive and sedative effects when opioid analgesics given with alcohol
Antidepressants, Tricyclic sedative effects possibly increased when opioid analgesics given with tricyclics
Antipsychotics enhanced hypotensive and sedative effects when opioid analgesics given with antipsychotics Increased risk of toxicity with myelosuppressive drugs
Anxiolytics and Hypnotics increased sedative effect when opioid analgesics given with anxiolytics and hypnotics
Cimetidine metabolism of opioid analgesics inhibited by cimetidine (increased plasma concentration)
Ciprofloxacin avoidance of premedication with opioid analgesics advised by manufacturer of ciprofloxacin (reduced plasma concentration of ciprofloxacin) when ciprofloxacin used for surgical prophylaxis
Domperidone opioid analgesics antagonise effects of domperidone on gastro-intestinal activity
MAOIs possible CNS excitation or depression (hypertension or hypotension) when opioid analgesics given with MAOIs —avoid concomitant use and for 2 weeks after stopping MAOIs For interactions of reversible MAO-A inhibitors (RIMAs) see Moclobemide, and for interactions of MAO-B inhibitors see Rasagiline and Selegiline; the antibacterial Linezolid is a reversible, non-selective MAO inhibitor
Metoclopramide opioid analgesics antagonise effects of metoclopramide on gastro-intestinal activity
Mexiletine opioid analgesics delay absorption of mexiletine
Moclobemide possible CNS excitation or depression (hypertension or hypotension) when opioid analgesics given with moclobemide
Sodium Oxybate opioid analgesics enhance effects of sodium oxybate (avoid concomitant use)


Adverse Reactions

Cardiovascular

Hypotension; orthostatic hypotension; bradycardia; tachycardia; palpitations.

CNS

Lightheadedness; dizziness; drowsiness; sedation; euphoria; dysphoria; delirium; disorientation; incoordination.

Dermatologic

Sweating; pruritus; urticaria.

EENT

Blurred vision; miosis.

GI

Nausea; vomiting; constipation; abdominal pain.

Genitourinary

Urinary retention or hesitancy.

Respiratory

Respiratory depression; apnea; respiratory arrest; laryngospasm; depression of cough reflex.

Miscellaneous

Tolerance; psychological and physical dependence with chronic use; pain at injection site; local irritation and induration following subcutaneous use.

Precautions

Warnings

Monitor patient for at least 24 h after initial dose because of reports of severe adverse reactions with epidural/intrathecal use. Improper substitution of Infumorph for regular Duramorph may result in serious overdose.

Pregnancy

Category C

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Dosage reduction may be necessary.

Labor and Delivery

Therapeutic morphine doses have increased duration of labor.

Renal Function

May need to reduce dose.

Hepatic Function

May need to reduce dose.

Special Risk Patients

Use drug with caution in patients with myxedema, acute alcoholism, acute abdominal conditions, ulcerative colitis, decreased respiratory reserve, head injury or increased intracranial pressure, hypoxia, supraventricular tachycardia, depleted blood volume or circulatory shock.

Asthma and other respiratory conditions

Bisulfites and morphine may potentiate each other, preventing use by cause severe adverse reactions.

Drug dependence

Has abuse potential.

Overdosage

Symptoms

Miosis, respiratory and CNS depression, circulatory collapse, seizures, cardiopulmonary arrest, death.

Patient Information

* Instruct patient to take oral preparations with food or juice if GI upset occurs.
* Tell patient not to crush or chew controlled-release tablets.
* Explain that full effectiveness of drug may not occur for 30 to 60 min after administration. Emphasize that drug is more effective if taken regularly to prevent pain rather than to treat pain after it occurs.
* If patient is to receive patient-controlled analgesia (PCA), instruct on use of PCA pump.
* Explain that physical dependency may occur with long-term therapy and that dosage will be tapered slowly before stopping to prevent withdrawal symptoms (nausea, vomiting, cramps, fever, faintness, anorexia).
* Encourage patient to turn, cough and breathe deeply every 2 h to prevent atelectasis.
* Advise patient to consult with health care provider if excessive sedation occurs or if pain relief is inadequate.
* Inform patient that drug may cause constipation. Stool softener, fiber laxative, increased fluid intake and bulk in diet may help alleviate problem.
* Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
* Instruct patient to avoid intake of alcoholic beverages and other CNS depressants.
* Advise patient that drug may cause drowsiness, dizziness or blurred vision and to use caution while driving or performing other tasks requiring mental alertness.