P & T PORTFOLIO

September 27, 2004

FDA-approved indication

FDA-approved indication

Treatment of pain following major surgery

Pharmacology

Morphine is an opioid analgesic that is relatively selective for the mu-receptor, although it can interact with other opiate receptors at higher doses. While its exact mechanism of analgesic action is unknown, morphine appears to produce analgesia by interacting with opioid receptors in the CNS, perhaps mimicking enkephalins and endorphins. This extended-release formulation consists of lipid-based particles containing discrete water-filled chambers dispersed through the lipid matrix, which contain the active drug. The small amount of lipid in the formulation is cleared rapidly in the body as the particles deliver morphine into the epidural space, providing pain relief for up to 48 hours following surgery.

Efficacy

The efficacy of morphine extended-release liposome epidural injection was demonstrated in four controlled clinical trials involving 876 patients undergoing surgical procedures such as hip arthroplasty, prostatectomy, colon resection, and cesarean section. Efficacy in these studies was assessed by a reduction in pain intensity using Visual Analog Scores (VAS) and/or a reduction in rescue pain medication over 48 hours. Study results showed that morphine extended-release liposome epidural injection significantly reduced pain intensity and/or cumulative rescue pain medication usage, compared with placebo or standard epidural morphine injection.

Pharmacokinetics

Protein binding20%-35%
Volume of distribution1-4 L/kg
MetabolismHepatic glucuronidation, sulfation,and demethylation. Glucuronideproducts include morphine-3-glucuronide (50%) and morphine-6-glucuronide (5%-15%)
ExcretionUrine (2%-12%)Feces (7%-10%)
Half-lifeEpidural morphine extended-releaseliposome, 3.8-32.9 hours (5- to 25-mg doses); standard epidural morphine, 2.2 hours (5-mg dose)

Contraindications

  • Hypersensitivity to morphine, morphine salts, or any product component
  • Respiratory depression, acute or severe bronchial asthma, or upper airway obstruction
  • Paralytic ileus
  • Head injury or increased intracranial pressure
  • Circulatory shock

Warnings

  • Due to a risk of severe adverse effects during epidural administration, the facility administering the drug must be equipped to resuscitate patients with severe opiate overdosage, and personnel must be familiar with the use and limitations of specific narcotic antagonists.
  • Morphine extended-release liposome epidural injection is indicated for epidural administration at the lumbar levels only.
  • Prior to drug administration, the physician should be familiar with any patient conditions that call for special evaluation of the benefit-versus-risk potential.
  • Morphine extended-release liposome is a Schedule II controlled substance, and abuse or diversion is possible.
  • Morphine extended-release liposome epidural injection should not be administered to patients with GI obstruction.

Conclusion/comments

Morphine extended-release liposome injection is an opioid analgesic that has demonstrated efficacy in the treatment of pain following major surgery for up to 48 hours after a single epidural injection. After major surgery, the level of pain is usually very high for the first 24-48 hours, but the intensity gradually subsides, allowing for oral analgesic control. This extended-release epidural morphine formulation does not require an indwelling or IV catheter for continuous infusion or patient-controlled analgesia. A catheter can fall out, interfere with patient mobility, or increase the risk of infection. For patients who require anticoagulants prior to or during surgery, this new long-acting formulation will reduce the risk of bleeding into the spinal column that can be associated with epidural catheters. DepoDur was previously referred to as DepoMorphine.

Published September 2004. Content based on medical literature and product information available at that time.