Xtampza ER - Drug Monograph

Introduction

Xtampza ER (oxycodone) extended-release capsules are an opioid analgesic formulation designed for around-the-clock management of severe pain requiring daily, continuous, long-term opioid treatment when alternative treatment options are inadequate. This abuse-deterrent formulation utilizes a microsphere-in-capsule delivery system that resists common methods of tampering while providing extended pain relief.

Mechanism of Action

Xtampza ER contains oxycodone, a full opioid agonist with relative selectivity for mu-opioid receptors, though it can bind to other opioid receptors in the central nervous system. The drug's primary therapeutic effects occur through activation of opioid receptors in various brain regions, resulting in:

• Modulation of pain perception in the brain and spinal cord
• Alteration of the emotional response to pain
• Production of analgesia through decreased propagation of pain signals

The microsphere delivery system provides a controlled release of oxycodone over approximately 12 hours, maintaining relatively constant plasma concentrations.

Indications

Xtampza ER is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

• Not for use as an as-needed analgesic
• Not for postoperative pain management unless the patient was already receiving chronic opioid therapy prior to surgery
• Not for mild or intermittent pain

Dosage and Administration

• Opioid-naïve patients: Initiate with 9 mg every 12 hours with food
• Patients converting from other opioids: Use equianalgesic conversion tables and reduce dose by 25-50% to account for incomplete cross-tolerance
• Patients switching from other oxycodone formulations: Use the same total daily oxycodone dose divided into two equal doses administered every 12 hours

• Titrate gradually based on pain control and adverse effects
• May increase dose every 1-2 days
• Do not exceed 288 mg total daily dose (144 mg every 12 hours)

• Administer every 12 hours with food
• Swallow capsules whole; do not crush, chew, or dissolve
• For patients with difficulty swallowing, capsules may be opened and contents sprinkled on soft food or through feeding tubes

• Hepatic impairment: Use caution; consider reduced initial doses
• Renal impairment: Use caution; consider reduced initial doses
• Elderly: Initiate at lower end of dosing range
• Pediatric: Safety and effectiveness not established

Pharmacokinetics

• Bioavailability: Approximately 60-87% when administered with food
• Time to peak concentration: 4.5-8 hours
• Food effect: Administration with high-fat meal increases AUC by 50% and Cmax by 65%

• Protein binding: 38-45%
• Volume of distribution: 2.6 L/kg
• Crosses placenta and blood-brain barrier; present in breast milk

• Primarily metabolized in liver via CYP3A4 to noroxycodone (less active)
• Minor pathway via CYP2D6 to oxymorphone (more potent)
• Noroxycodone and oxymorphone contribute to analgesic effects

• Half-life: Approximately 4.5-8 hours
• Excretion: Primarily renal (50-70% as metabolites)
• Clearance: 0.8 L/min

Contraindications

• Significant respiratory depression
• Acute or severe bronchial asthma in unmonitored settings or absence of resuscitative equipment
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Hypersensitivity to oxycodone or any component of the formulation

Warnings and Precautions

• Addiction, abuse, and misuse risk
• Life-threatening respiratory depression
• Accidental ingestion can be fatal
• Neonatal opioid withdrawal syndrome
• Risks from concomitant use with benzodiazepines or other CNS depressants
• Opioid analgesic risk evaluation and mitigation strategy (REMS)

• Interactions with alcohol: Contraindicated due to risk of fatal overdose
• Increased intracranial pressure: Use with caution in head injury patients
• Seizure disorders: May exacerbate condition
• Adrenal insufficiency: Cases reported with opioid use
• Severe hypotension: May occur in volume-depleted patients
• Gastrointestinal effects: May cause spasm of sphincter of Oddi

Drug Interactions

• May increase oxycodone plasma concentrations
• Monitor for respiratory depression and sedation
• Consider dose reduction

• May decrease oxycodone plasma concentrations
• May reduce efficacy
• Consider dose increase

• May alter oxycodone metabolism
• May decrease oxymorphone formation

• Additive CNS depression
• Reserve concomitant use for patients with no alternatives
• Limit dosages and durations to minimum required

• Risk of serotonin syndrome
• Monitor closely when coadministered with SSRIs, SNRIs, MAOIs

• Enhanced neuromuscular blocking action
• Increased respiratory depression

Adverse Effects

• Constipation (28%)
• Nausea (23%)
• Somnolence (15%)
• Headache (14%)
• Pruritus (11%)

• Respiratory depression
• Apnea
• Circulatory depression
• Hypotension
• Shock
• Adrenal insufficiency
• Severe hypotension
• Anaphylaxis
• Seizures
• Serotonin syndrome
• Withdrawal symptoms

Monitoring Parameters

• Pain intensity and relief
• Respiratory rate, depth, and pattern
• Blood pressure, especially during initiation and titration
• Bowel function (constipation management)
• Signs of misuse, abuse, or addiction
• Mental status changes
• Signs of adrenal insufficiency
• Signs of hypersensitivity reactions
• Signs of serotonin syndrome

Patient Education

• Take exactly as prescribed; do not adjust dose without consulting provider
• Swallow capsules whole; do not crush, chew, or dissolve
• Take with food to ensure consistent absorption
• Report any difficulty breathing or unusual drowsiness
• Avoid alcohol and other CNS depressants
• Be aware of potential for impaired mental and physical abilities
• Do not share medication with others
• Store securely to prevent theft or accidental ingestion
• Properly dispose of unused medication
• Inform all healthcare providers of opioid use
• Report signs of allergic reaction or severe constipation
• Understand risks of dependence, addiction, and withdrawal

References

1. Xtampza ER [package insert]. Collegium Pharmaceutical, Inc.; 2022. 2. Webster L, Henningfield J, Buchhalter AR, et al. Human abuse potential of oxycodone DETERx® (Xtampza® ER) compared to immediate-release oxycodone. Pain Med. 2018;19(6):1225-1236. 3. Gudin J, Levy-Cooperman N, Kopecky EA, et al. Comparing the effect of tampering on the oral pharmacokinetic profiles of two extended-release oxycodone formulations with abuse-deterrent properties. Pain Med. 2015;16(11):2142-2151. 4. US Food and Drug Administration. FDA approves first extended-release, abuse-deterrent opioid pain medication with properties that are expected to reduce abuse. April 2016. 5. Pergolizzi JV Jr, Raffa RB, Taylor R Jr, et al. A review of abuse-deterrent opioids for chronic nonmalignant pain. Pain Pract. 2018;18(7):935-951. 6. Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain. Journal of Pain. 2009;10(2):113-130.