Pharmacology Update
Avinza—A New Long-Acting Morphine Capsule
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
The FDA has approved the first "true once-a-day" oral formulation for morphine. Elan Pharmaceuticals is using a new extended-release (ER) system, the spheroidal oral drug absorption system (SODAS) that results in a slow absorption of the drug over 24 hours. It also releases some drug immediately to maintain blood levels. Elan’s long-acting morphine preparation will be marketed under the tradename Avinza.
Indications
Morphine sulfate ER is indicated for the relief of moderate-to-severe pain requiring continuous, around-the-clock opioid therapy for an extended period of time.1
Dosage
The capsules are intended for once-daily administration. The dose must be titrated individually based on the patient’s previous analgesic regimen, degree of opioid tolerance, concurrent medications, and level of analgesic required. It may be taken without regard to meals. The capsules must be swallowed whole and not be chewed, crushed, or dissolved. The contents of the capsule (beads) may be sprinkled on applesauce. The beads must not be chewed or crushed.1
Avinza is available as 60-mg, 90-mg, and 120-mg capsules.
Potential Advantages
Morphine sulfate ER (Avinza) is the only "truly" once-daily controlled-release oral morphine formulation. Once-daily administration of morphine sulfate ER (Avinza) produces peak and trough plasma concentrations comparable to morphine oral solution administered 6 times a day.1 Other controlled-release formulations (MS Contin, Roxanol SR) are typically dosed every 8-12 hours. Kadian is labeled for once- or twice-daily dosing. Avinza can also be sprinkled on apple sauce for those unable to swallow the capsules and these routes of administration are bioequivalent in terms of the rate and extent of absorption.2
Potential Disadvantages
Fumaric acid is used as an osmotic agent and local pH modifier in SODAS. Due to the potential renal toxicity of fumaric acid, the daily dose of Avinza must be limited to a maximum of 1600 mg daily.1
A potentially fatal dose of morphine may be absorbed if the capsules or the beads are chewed, crushed, or dissolved. Avinza is not intended for as needed (prn) analgesia and is not indicated for postoperative use.1
Comments
Morphine sulfate formulated as Avinza comprises immediate release and extended-release components. The latter component uses the SODAS. The capsules contain numerous ammonio-methacrylate copolymer beads of approximately 1 mm in diameter. In the gastrointestinal tract, fluid enters the beads solubilizing the drug that becomes available for absorption. Plasma concentrations are maintained for a 24-hour period. The efficacy of Avinza was demonstrated in a double-blind, placebo-controlled, fixed-dose (30 mg once daily), parallel group trial in 295 patients with moderate-to-severe pain due to osteoarthritis.1
Avinza will cost about $6-7 per day.
Clinical Implications
Avinza provides an alternative to other controlled-release morphine formulations. Once-daily dosing offers convenience and may improve compliance.
References
1. Avinza Product Information. Ligand Pharmaceuticals. March 2002.
2. Eliot L, et al. Clin Ther. 2002;24(2):260-268.
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Asst. Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.
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