MSL

Approved Indications:

• Moderate to Severe Pain:
  Relief of moderate to severe acute pain (e.g., post-operative, trauma, renal colic) and chronic pain not responsive to non-opioid therapy.
• Chronic Cancer Pain:
  Long-term pain management in advanced malignancies requiring continuous opioid analgesia.
• Palliative Care:
  Management of intractable pain in terminally ill patients; also used to relieve dyspnea in end-of-life settings.
• Myocardial Infarction (MI):
  Adjunct therapy for acute MI to relieve pain and anxiety and reduce myocardial oxygen demand.

Off-label (Clinically Accepted) Uses:

• Dyspnea associated with pulmonary edema or chronic heart failure.
• Sedation in mechanically ventilated ICU patients (as part of multimodal sedation).
• Epidural or intrathecal analgesia for labor or postoperative pain.

Important: Dosage must be individualized based on severity of pain, patient response, previous opioid exposure, and risk of adverse events.

Adults

Oral (Immediate-Release):

• Initial: 10–30 mg every 4 hours as needed for pain.
• Adjust dose every 1–2 days based on efficacy and tolerability.

Oral (Extended-Release Tablets/Capsules):

• Starting: 15–30 mg every 12 hours for opioid-naïve patients.
• Titrate every 1–2 days to achieve adequate pain control.

Parenteral (IV, IM, SC):

• IV: 2–10 mg every 3–4 hours as needed (slow injection over 4–5 minutes).
• IM/SC: 5–20 mg every 3–4 hours as needed.

Patient-Controlled Analgesia (PCA):

• Common settings: 1 mg demand dose, 6-minute lockout, no basal rate initially.

Epidural (Preservative-Free):

• Bolus: 2–5 mg, may repeat every 24 hours.
• Continuous infusion: 2–4 mg/day.

Intrathecal:

• Single dose: 0.2–1 mg.

Pediatrics

Oral:

• 0.2–0.5 mg/kg/dose every 4–6 hours (immediate-release).

IV:

• 0.05–0.1 mg/kg/dose every 4 hours; titrate carefully.

Epidural/Intrathecal:

• Requires specialist dosing; only under close supervision.

Elderly

• Start at 30–50% of usual adult dose.
• Titrate slowly and monitor for respiratory depression and sedation.

Renal Impairment

• Use with caution. Reduce dose and extend dosing intervals.
• Accumulation of active metabolites (e.g., morphine-6-glucuronide) can cause respiratory depression and sedation.

Hepatic Impairment

• Use caution in moderate impairment.
• Avoid in severe hepatic dysfunction due to altered metabolism and clearance.

Morphine Sulfate is a potent opioid analgesic that exerts its effects by binding to mu-opioid receptors (μ-receptors) in the central nervous system (CNS). These receptors are located in the brain, spinal cord, and peripheral tissues. Activation of μ-receptors inhibits adenylate cyclase, decreases intracellular cAMP, suppresses the release of substance P and other neurotransmitters, and blocks nociceptive transmission. Morphine also hyperpolarizes neurons by increasing potassium efflux and decreasing calcium influx, which reduces neuronal excitability and pain perception. This leads to analgesia, sedation, and euphoria, but also to side effects like respiratory depression and constipation.

• Absorption:
  Well absorbed orally; subject to significant first-pass metabolism.
  Bioavailability: 20–40% (oral); nearly 100% (IV).
• Distribution:
  Widely distributed, including CNS and placenta.
  Protein binding: ~30–35%.
  Volume of distribution: 1–4 L/kg.
• Metabolism:
  Primarily hepatic via UGT2B7 to morphine-3-glucuronide (inactive) and morphine-6-glucuronide (active, more potent).
• Elimination:
  Primarily renal excretion of glucuronide metabolites.
  Half-life:
• Immediate-release: 2–4 hours
• Extended-release: 8–12 hours
• Epidural/intrathecal: Prolonged effect (up to 24 hours)
• Onset:
• IV: 5–10 minutes
• IM/SC: 10–30 minutes
• Oral: 30–60 minutes
• Epidural: 15–30 minutes
• Duration:
• Oral/Parenteral: 3–5 hours
• Extended-release: 8–12 hours
• Epidural: Up to 24 hours

• Pregnancy:
  Previously FDA Pregnancy Category C.
  Risk of fetal harm not ruled out; prolonged use during pregnancy can lead to neonatal opioid withdrawal syndrome (NOWS). Use only if benefits justify potential risks.
• Lactation:
  Morphine is excreted in breast milk. Small doses for short-term use are generally compatible with breastfeeding. Monitor infant for sedation, feeding difficulties, or apnea. Avoid chronic use or high doses in lactating mothers.

• Primary Class: Opioid Analgesic (Narcotic)
• Subclass: Full μ-opioid receptor agonist
• Drug Schedule: Controlled Substance – Schedule II (under US DEA regulations)

• Hypersensitivity to morphine or formulation components.
• Significant respiratory depression (in absence of resuscitative equipment).
• Acute or severe bronchial asthma.
• Paralytic ileus or known gastrointestinal obstruction.
• Concurrent use of MAO inhibitors (or within 14 days).
• Head injuries or increased intracranial pressure (relative contraindication).
• Acute alcoholism or delirium tremens.

• Respiratory Depression:
  Most serious risk, especially in opioid-naïve, elderly, or renally impaired patients.
• Addiction, Abuse & Misuse:
  Risk of misuse and dependence; prescribe only when necessary and at the lowest effective dose.
• Neonatal Opioid Withdrawal Syndrome (NOWS):
  Can occur in infants of mothers using morphine long-term during pregnancy.
• Hypotension:
  Use caution in patients with hypovolemia or cardiovascular disease.
• CNS Depression:
  May impair mental and physical abilities; avoid driving or operating machinery.
• Seizures:
  Rarely reported, especially in high doses or with interacting medications.
• Intrathecal/Epidural Use:
  Use preservative-free formulations only; monitor for delayed respiratory depression.

Common:

• CNS: Sedation, dizziness, confusion, headache
• GI: Nausea, vomiting, constipation, dry mouth
• Dermatologic: Sweating, pruritus
• Respiratory: Mild respiratory depression

Serious:

• Respiratory depression
• Hypotension, bradycardia
• Severe constipation, paralytic ileus
• Addiction and physical dependence
• Anaphylaxis (rare)

Timing & Severity:

• Dose-dependent; respiratory depression more likely in first 24–72 hours or after dose increases.

• CNS Depressants (e.g., benzodiazepines, alcohol):
  Increased risk of profound sedation, respiratory depression, coma, or death.
• MAO Inhibitors:
  Contraindicated; risk of serotonin syndrome or severe hypotension.
• Anticholinergics:
  May exacerbate constipation or urinary retention.
• CYP450 Interactions:
  Although morphine is mainly glucuronidated, some metabolism via CYP3A4 may occur; caution with strong inhibitors or inducers.
• Muscle Relaxants:
  Enhanced CNS depression.

• Black Box Warnings Updated:
  Emphasis on addiction, abuse potential, and risks of combining opioids with benzodiazepines or alcohol.
• CDC Guidelines (2022):
  Recommend careful opioid use only after non-opioid options are exhausted. Morphine is no longer first-line for chronic non-cancer pain.
• FDA REMS Program:
  Morphine ER products are subject to Risk Evaluation and Mitigation Strategy to ensure safe use.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C.
• Humidity & Light: Protect from excessive moisture and light.
• Handling Precautions:
• Keep out of reach of children.
• High potential for abuse—store securely.
• Destroy unused portions properly (do not flush unless instructed).
• Reconstitution Needs (Injectables):
  Use sterile water or normal saline; preservative-free formulations required for epidural/intrathecal use.