Oxycodone (OxyContin)
oxycodone hydrochloride (Roxicodone, OxyContin, Oxaydo)
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Acute and chronic pain severe enough to require opioid analgesia (IR) | Adults; some formulations ≥18 yr | As-needed or around-the-clock; for pain where alternatives are inadequate | FDA Approved |
| Chronic pain requiring continuous around-the-clock opioid (ER/OxyContin) | Adults and children ≥11 yr (opioid-tolerant, already receiving ≥20 mg oxycodone/day) | Around-the-clock q12h; not for as-needed use | FDA Approved |
Oxycodone is a semi-synthetic opioid derived from thebaine with approximately 1.5 times the oral potency of morphine. Its notably high oral bioavailability (60–87%) compared with morphine (20–40%) makes it particularly well-suited for oral pain management. It occupies a central role in the treatment of moderate-to-severe pain across oncologic, post-surgical, and chronic non-cancer pain settings. The availability of both immediate-release and extended-release formulations allows flexibility for both acute titration and sustained chronic pain management. Oxycodone is the reference opioid in many equianalgesic conversion tables alongside morphine and is commonly combined with acetaminophen or ibuprofen in fixed-combination products.
Restless legs syndrome (refractory): Oxycodone/naloxone combination has been studied for severe RLS refractory to dopaminergic agents and gabapentinoids. Evidence quality: Moderate (based on one pivotal RCT).
Dosing
Immediate-Release (IR) Tablets, Capsules, and Oral Solution
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Moderate-to-severe pain — opioid-naive adult | 5–15 mg PO q4–6h | Titrate to adequate analgesia | No absolute ceiling; titrate to effect | Typical starting dose is 5–10 mg; higher initial doses only if pain severity warrants May take with or without food |
| Conversion from other opioids to IR oxycodone | Calculate equianalgesic dose, reduce by 25–50% | Titrate per response | Individualize | Oxycodone 20 mg PO ≈ morphine 30 mg PO; always underestimate and provide rescue Inter-patient variability is substantial |
| Elderly or debilitated patients | 2.5–5 mg PO q6h | Titrate cautiously | Individualize | Plasma concentrations ~15% higher in elderly >65; start at 1/3 to 1/2 usual dose in debilitated patients Monitor closely for respiratory depression |
| Renal impairment (CrCl <60 mL/min) | 2.5–5 mg PO q6–8h | Titrate conservatively | Individualize | Higher plasma concentrations; prolonged half-life in end-stage renal disease; titrate slowly |
| Hepatic impairment | 1/3 to 1/2 usual starting dose | Titrate cautiously | Individualize | Clearance reduced; CYP3A4 metabolism impaired in liver disease Follow conservative approach per FDA PI |
Extended-Release (ER) — OxyContin
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Chronic pain — opioid-naive (new to ER) | 10 mg PO q12h | Titrate q1–2 days | No ceiling; 80 mg and above for opioid-tolerant only | Swallow whole; never crush/chew/dissolve (fatal dose dump); steady state in 24–36 h Not for as-needed use |
| Conversion from IR oxycodone to OxyContin | Same total daily dose divided q12h | Titrate per response | Individualize | May lead to peak sedation initially; provide IR rescue for breakthrough Round down to nearest available ER strength |
| Conversion from other opioids to OxyContin | 10 mg PO q12h (opioid-naive); calculate equianalgesic for tolerant | Titrate q1–2 days | Individualize | No established conversion ratios from clinical trials; always underestimate; monitor closely |
| Pediatric ≥11 yr (opioid-tolerant, ≥20 mg oxycodone/day equivalent) | Calculate from prior opioid; use conversion table | Titrate per response | Individualize | Not appropriate if total daily dose <20 mg; close monitoring required |
Oxycodone’s oral bioavailability of 60–87% is substantially higher than morphine’s 20–40%, meaning a greater proportion of each oral dose reaches the systemic circulation. This accounts for the approximately 1.5:1 oral potency ratio (20 mg oxycodone ≈ 30 mg morphine orally). When converting between these agents, this difference in bioavailability — not receptor affinity — drives the equianalgesic ratio. The higher bioavailability also means oral-to-parenteral dose conversions for oxycodone are less dramatic than for morphine.
Pharmacology
Mechanism of Action
Oxycodone is a pure mu-opioid receptor agonist whose principal therapeutic action is analgesia. Like morphine, it activates mu-receptors in the brain, spinal cord, and peripheral tissues, triggering inhibitory G-protein signaling that reduces neuronal excitability and nociceptive transmission. In the gastrointestinal tract, mu-receptor activation inhibits peristalsis and increases smooth muscle tone, producing the characteristic opioid-induced constipation. Oxycodone also produces peripheral vasodilation, histamine release (to a lesser extent than morphine), and dose-dependent respiratory depression. Its metabolite oxymorphone (formed via CYP2D6) has 3–5-fold greater mu-receptor affinity but circulates at very low plasma concentrations, and the primary analgesic activity is attributed to the parent compound oxycodone itself. Unlike morphine, oxycodone does not appear to have significant immunosuppressive effects.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Oral bioavailability 60–87% (high due to low pre-systemic/first-pass metabolism compared to other opioids); Tmax ~1 h (IR); dose-proportional absorption; food delays Tmax to ~3 h but does not reduce AUC | Higher oral bioavailability than morphine means more predictable dose-response relationship; 20 mg oxycodone PO ≈ 30 mg morphine PO in equianalgesic tables |
| Distribution | Vss 2.6 L/kg (IV); protein binding ~45%; detected in breast milk; crosses placenta | Moderate protein binding means some displacement interaction potential; breast milk excretion requires risk-benefit assessment in nursing mothers |
| Metabolism | Hepatic: CYP3A4 → noroxycodone (major, AUC ratio 0.6 relative to oxycodone, weak activity); CYP2D6 → oxymorphone (minor, very low plasma levels, 3–5x more potent at mu-receptor); conjugation to glucuronides and sulfates | CYP3A4 inhibitors (ketoconazole, ritonavir, voriconazole) can increase oxycodone AUC up to 3.6-fold — clinically critical; CYP3A4 inducers (rifampin, carbamazepine) reduce efficacy; CYP2D6 poor metabolizers have minimal clinical impact on oxycodone |
| Elimination | t½ 3.5–4 h (IR), 4.5 h (ER/OxyContin); total plasma clearance 0.8 L/min; renal excretion: free oxycodone up to 19%, conjugated oxycodone up to 50%, conjugated oxymorphone ≤14%; steady state in 24–36 h | Short half-life necessitates q4–6h dosing for IR; ER formulation extends effective duration to 12 h; renal impairment increases exposure; elderly have ~15% higher plasma concentrations |
Side Effects
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Constipation | 23% | Does not habituate; proactive bowel regimen required from day 1; can lead to bowel perforation if untreated |
| Nausea | 23% | Typically improves within 3–5 days; can be minimized by slow titration and co-administration of anti-emetics |
| Somnolence/Drowsiness | 23% | Dose-related; tolerance develops within days; warn about driving and hazardous activities |
| Dizziness | 13% | Related to orthostatic hypotension and central opioid effects; advise slow position changes |
| Pruritus | 13% | Histamine-mediated and centrally mediated; less histamine release than morphine; antihistamines may help |
| Vomiting | 12% | CTZ-mediated; usually habituates; assess for dehydration if persistent |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Headache | 7% | Usually mild; may improve with continued therapy |
| Dry mouth | 6% | Encourage oral hydration; long-term xerostomia can increase dental caries risk |
| Sweating/Diaphoresis | 5% | Opioid class effect; rarely treatment-limiting |
| Asthenia/Fatigue | 3–6% | Usually improves after the initial titration period |
| Insomnia | 3–5% | May be related to pain control or opioid effects on sleep architecture |
| Abdominal pain | 1–5% | May be related to constipation or direct GI effects; evaluate for obstruction if severe |
| Orthostatic hypotension | 1–5% | Due to peripheral vasodilation; worse with hypovolemia; advise slow position changes |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Respiratory depression | Dose-dependent; highest in opioid-naive | First 24–72 h or after dose increase; higher risk with CYP3A4 inhibitors | Naloxone; ventilatory support; dose reduction; discontinue CYP3A4 inhibitor if applicable |
| Serotonin syndrome | Rare | Hours to days with concurrent serotonergic drugs | Discontinue all serotonergic agents; cyproheptadine; supportive care |
| Adrenal insufficiency | Rare; with chronic use | After ≥1 month of chronic use | Cortisol testing; taper opioid; physiologic steroid replacement |
| Severe hypotension / Circulatory depression | Uncommon | At initiation or dose increase; worse with hypovolemia | IV fluids; vasopressors; reduce dose; avoid in circulatory shock |
| Neonatal opioid withdrawal syndrome | Expected with prolonged maternal use | Hours to days after delivery | Neonatal monitoring; supportive care per neonatology protocols; do not abruptly discontinue in pregnant patients |
Opioid-induced constipation occurs in up to 41–81% of patients on chronic opioid therapy and does not improve with tolerance. Initiate a stimulant laxative (senna or bisacodyl) at the same time as oxycodone therapy. If conventional laxatives are insufficient, peripherally acting mu-opioid receptor antagonists (PAMORAs) such as naloxegol, methylnaltrexone, or the oxycodone/naloxone fixed-combination product may be considered. Counsel patients that constipation management is a mandatory component of opioid therapy.
Drug Interactions
Oxycodone’s primary metabolism through CYP3A4 makes it highly susceptible to pharmacokinetic interactions with CYP3A4 inhibitors and inducers. This is the most clinically important distinction from morphine (which is glucuronidated). CYP2D6 plays a minor metabolic role, and CYP2D6 polymorphism has minimal clinical impact on oxycodone efficacy.
Monitoring
- Respiratory StatusContinuous at initiation
RoutineMonitor respiratory rate, oxygen saturation, and sedation level during first 24–72 h, after dose increases, and when CYP3A4 inhibitors are started. - Pain AssessmentEach visit
RoutineValidated pain scale; re-evaluate benefit vs risk at least every 3 months for chronic use; document functional outcomes. - Bowel FunctionEach visit
RoutineInitiate bowel regimen at day 1. Constipation does not habituate; assess at every visit. - Signs of Misuse / OUDEach visit
RoutinePDMP check before prescribing and periodically; risk assessment at baseline; urine drug testing as indicated. - CYP3A4 Drug InteractionsAt each medication change
Trigger-basedReview medication list for CYP3A4 inhibitors/inducers at every visit. Starting or stopping a CYP3A4 inhibitor requires dose reassessment. - Renal & Hepatic FunctionBaseline; periodically
RoutineOxycodone clearance reduced in hepatic impairment; higher plasma concentrations in renal impairment. - Blood PressureAt initiation
RoutineMonitor for orthostatic hypotension, especially in hypovolemic patients or those on antihypertensives.
Contraindications & Cautions
Absolute Contraindications
- Significant respiratory depression — in settings without monitoring or resuscitative equipment
- Acute or severe bronchial asthma — in unmonitored settings
- Known or suspected GI obstruction, including paralytic ileus
- Hypersensitivity to oxycodone — includes cross-sensitivity with other phenanthrene opioids (codeine, morphine)
Relative Contraindications (Specialist Input Recommended)
- Concurrent strong CYP3A4 inhibitors — can increase oxycodone AUC up to 3.6-fold, causing potentially fatal respiratory depression
- Severe hepatic impairment — reduced clearance; start at reduced dose and titrate cautiously
- Severe renal impairment — higher plasma concentrations; prolonged half-life
- History of substance use disorder — Schedule II; high abuse potential
Use with Caution
- Elderly or debilitated patients — ~15% higher plasma concentrations; start at 1/3 to 1/2 usual dose
- Head injury or raised ICP — respiratory depression elevates ICP; miosis may obscure neurological assessment
- COPD or cor pulmonale — reduced respiratory reserve
- Circulatory shock — vasodilation may worsen hypotension
- Biliary tract disease — sphincter of Oddi spasm
Addiction, abuse, and misuse: Oxycodone exposes patients to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess risk before prescribing.
Life-threatening respiratory depression: Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely during initiation and dose escalation.
Accidental ingestion: Accidental ingestion of even one dose, especially by children, can result in fatal overdose.
Neonatal opioid withdrawal syndrome: Prolonged use during pregnancy can cause life-threatening neonatal withdrawal.
CNS depressant interactions: Concomitant use with benzodiazepines or other CNS depressants may result in profound sedation, respiratory depression, coma, and death.
ER formulation risk: OxyContin 60 mg and above are for opioid-tolerant patients only. Crushing, chewing, or dissolving ER tablets releases a potentially fatal dose.
Patient Counselling
Purpose of Therapy
Oxycodone is a strong opioid pain medication prescribed when other, less powerful painkillers have not provided adequate relief. It works by activating pain receptors in the brain to reduce the sensation of pain. While effective, oxycodone carries significant risks including dependence, side effects, and the potential for misuse. Your prescriber has carefully weighed the benefits against these risks for your specific condition.
How to Take
Take oxycodone exactly as prescribed. For immediate-release tablets, take the prescribed dose every 4–6 hours as directed. For extended-release tablets (OxyContin), take every 12 hours at the same times each day. Swallow extended-release tablets whole — never crush, break, chew, or dissolve them, as this releases a dangerous amount of medication at once. You may take oxycodone with or without food. Store securely out of reach of children and others.
Sources
- Oxycodone Hydrochloride Tablets — FDA-Approved Prescribing Information (Roxicodone). dailymed.nlm.nih.govPrimary reference for IR dosing, adverse reaction incidence data, pharmacokinetics (bioavailability, half-life, metabolism), and contraindications.
- OxyContin (oxycodone HCl controlled-release) — FDA-Approved Prescribing Information. accessdata.fda.govSource for ER dosing, opioid-tolerant restrictions, CYP3A4 interaction data, conversion guidelines, and pediatric use in patients ≥11 years.
- Oxycodone Hydrochloride Capsules — FDA-Approved Prescribing Information. accessdata.fda.govReference for capsule formulation dosing, boxed warnings including REMS, and tapering guidance.
- Oxycodone Hydrochloride Oral Solution — FDA-Approved Prescribing Information. accessdata.fda.govSource for oral solution formulation, volume of distribution (2.6 L/kg), protein binding (45%), and food effect data.
- Salzman RT, Roberts MS, Wild J, et al. Can a controlled-release oral dose form of oxycodone be used as readily as an immediate-release form for titrating to stable pain control? J Pain Symptom Manage. 1999;18(4):271–279. doi:10.1016/S0885-3924(99)00079-2Pivotal trial comparing CR and IR oxycodone titration demonstrating equivalent pain control and similar adverse effect profiles between formulations.
- Trenkwalder C, Benes H, Grote L, et al. Prolonged release oxycodone-naloxone for treatment of severe restless legs syndrome after failure of previous treatment. BMC Neurol. 2013;13:78. doi:10.1186/1471-2377-13-78RCT supporting oxycodone/naloxone for refractory RLS, relevant to off-label indication.
- Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022. MMWR Recomm Rep. 2022;71(No. RR-3):1–95. doi:10.15585/mmwr.rr7103a1Current CDC guideline on opioid prescribing for pain; framework for dosing limits (MME), monitoring, and risk mitigation applicable to oxycodone.
- American Geriatrics Society 2023 Updated AGS Beers Criteria. J Am Geriatr Soc. 2023;71(7):2052–2081. doi:10.1111/jgs.18372Classifies opioids as potentially inappropriate in older adults; relevant for oxycodone dosing in elderly patients.
- Lalovic B, Kharasch E, Hoffer C, Risler L, Liu-Chen LY, Shen DD. Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites. Clin Pharmacol Ther. 2006;79(5):461–479. doi:10.1016/j.clpt.2006.01.009Key study establishing that oxycodone’s analgesic activity is primarily from the parent compound, with minimal contribution from oxymorphone or noroxycodone metabolites.
- Hagelberg NM, Nieminen TH, Saari TI, et al. Voriconazole drastically increases exposure to oral oxycodone. Eur J Clin Pharmacol. 2009;65(3):263–271. doi:10.1007/s00228-008-0568-5Published study demonstrating 3.6-fold increase in oxycodone AUC with voriconazole, establishing the clinical significance of CYP3A4 inhibition.
- Nieminen TH, Hagelberg NM, Saari TI, et al. Rifampin greatly reduces the plasma concentrations of intravenous and oral oxycodone. Anesthesiology. 2009;110(6):1371–1378. doi:10.1097/ALN.0b013e31819faa54Study documenting the significant reduction in oxycodone exposure with rifampin co-administration, confirming the importance of CYP3A4 induction.
- Oxycodone — StatPearls [Internet]. National Library of Medicine. Updated February 20, 2024. ncbi.nlm.nih.govComprehensive clinical reference covering indications, dosing, adverse effects (>5% incidence data), CYP3A4/CYP2D6 interactions, and special populations.
- Camilleri M. Opioid-induced constipation: challenges and therapeutic opportunities. Am J Gastroenterol. 2011;106(5):835–842. doi:10.1038/ajg.2011.30Review establishing the prevalence of OIC (41–81%) and PAMORA therapeutic approaches relevant to oxycodone-induced constipation management.
- Leppert W. CYP2D6 in the metabolism of opioids for mild to moderate pain. Pharmacology. 2011;87(5–6):274–285. doi:10.1159/000326085Review clarifying that CYP2D6 polymorphism has minimal clinical impact on oxycodone efficacy, unlike its role in codeine and tramadol metabolism.