Oxycodone

Generic Name

Oxycodone hydrochloride

Brand Names

OxyContin

Endone

Roxicodone

Oxynorm

Percocet (oxycodone + acetaminophen)

Targin (oxycodone + naloxone)

Combunox (oxycodone + ibuprofen)

Xtampza ER (abuse-deterrent extended-release formulation)

Many generic formulations available in immediate-release (IR), extended-release (ER), and combination products

Drug Class

Opioid analgesic

Phenanthrene derivative

Schedule II controlled substance (USA)

Narcotic analgesic

Mechanism of Action

Oxycodone acts primarily as a full agonist at μ-opioid receptors in the central nervous system

It also exhibits weak activity at κ- and δ-opioid receptors

Binding to the μ-receptor produces analgesia, euphoria, sedation, and respiratory depression

Oxycodone inhibits ascending pain pathways and alters the perception and response to pain

It also increases pain threshold

No ceiling effect on analgesia, but dose escalation increases adverse effects and risks

Indications

Approved Indications

Moderate to severe acute pain (e.g., post-operative, injury-related)

Chronic pain requiring continuous opioid therapy (e.g., cancer pain, palliative care, chronic musculoskeletal pain)

Pain not adequately controlled by non-opioid analgesics

Off-Label Uses

Refractory cough in palliative care

Dyspnea management in terminal illness (e.g., COPD, cancer)

Procedural sedation (in combination)

Neuropathic pain (when other treatments fail)

Dosage and Administration

Adults

Immediate-Release (IR) Tablets/Capsules

Start: 5–15 mg orally every 4–6 hours as needed

Severe pain: higher doses (up to 30 mg) may be required

Maximum: individualized based on tolerance

Extended-Release (ER) Tablets (e.g., OxyContin)

Start: 10 mg orally every 12 hours in opioid-naive patients

Titrate every 1–2 days based on pain control and tolerance

Maximum: no defined ceiling dose

Combination Formulations (e.g., Percocet)

Oxycodone 2.5–10 mg with acetaminophen 325–650 mg every 4–6 hours

Limit acetaminophen to <4000 mg/day

Oral Liquid Formulations

Often 1 mg/mL or 5 mg/5 mL

Used in pediatrics, geriatrics, or patients with swallowing difficulties

Rectal Administration

Suppositories (rare use): same doses as oral IR

Intravenous (IV)/Subcutaneous (SC)/Intramuscular (IM)

Oxycodone parenteral formulations are available in some countries

IV: 1–2 mg every 4–6 hours, titrated based on response

Pediatric Use

Use limited to specialist settings

Not approved in many jurisdictions for children

Doses based on weight and opioid tolerance

Geriatric Dosing

Start at lowest dose (e.g., 2.5–5 mg IR)

Titrate slowly due to increased risk of respiratory depression

Renal Impairment

Use with caution

Dose reduction or extended dosing interval may be necessary

Hepatic Impairment

Start at lower doses due to decreased metabolism

Monitor for respiratory depression

Administration Notes

Extended-release tablets must not be crushed, chewed, or broken

Immediate-release can be administered with or without food

Ensure consistent dosing intervals for ER formulations

Pharmacokinetics

Absorption

High oral bioavailability (60–87%)

Onset: 10–30 minutes (IR), 1 hour (ER)

Peak: 1 hour (IR), 3–4 hours (ER)

Distribution

Widely distributed

Plasma protein binding ~45%

Crosses placenta and blood-brain barrier

Metabolism

Primarily metabolized in liver via CYP3A4 and CYP2D6

Converted to noroxycodone (inactive) and oxymorphone (active metabolite)

Metabolic variability affects individual response

Elimination

Excreted in urine, mostly as metabolites

Half-life: 3–4 hours (IR), 4.5–6.5 hours (ER)

Prolonged in renal or hepatic dysfunction

Contraindications

Hypersensitivity to oxycodone or other opioids

Significant respiratory depression

Acute or severe bronchial asthma in unmonitored settings

Paralytic ileus

GI obstruction

Known or suspected GI motility disorder

Use of monoamine oxidase inhibitors (MAOIs) within 14 days

Warnings and Precautions

Respiratory Depression

Dose-dependent and potentially fatal

Greatest risk at initiation and dose escalation

Monitor closely, especially in elderly and opioid-naïve patients

Addiction, Abuse, and Misuse

Schedule II substance with high abuse potential

Abuse-deterrent formulations reduce tampering but do not eliminate risk

Risk of opioid use disorder (OUD) with prolonged use

Accidental Ingestion

One dose can be fatal in children

Keep out of reach of children and untrained individuals

Opioid-Induced Hyperalgesia

Chronic use may paradoxically increase sensitivity to pain

Interactions with CNS Depressants

Increased risk of profound sedation, coma, and death when used with benzodiazepines, alcohol, or antipsychotics

Avoid or use with extreme caution

Seizure Risk

May lower seizure threshold

Use with caution in seizure-prone patients

Gastrointestinal Effects

Slows gastric motility

Increased risk of constipation, ileus, and nausea

Endocrine Effects

Chronic use suppresses HPA axis

Decreased testosterone and cortisol levels

May cause sexual dysfunction and infertility

Pregnancy and Lactation

Pregnancy (Category C)

Crosses placenta

Risk of neonatal opioid withdrawal syndrome (NOWS)

Avoid use during labor unless benefits outweigh risks

Lactation

Present in breast milk

May cause sedation or respiratory depression in infants

Avoid or monitor infant closely

Adverse Effects

Very Common

Constipation

Nausea

Vomiting

Sedation

Drowsiness

Dizziness

Dry mouth

Common

Headache

Pruritus

Sweating

Euphoria or dysphoria

Abdominal pain

Anorexia

Confusion

Less Common

Hypotension

Tachycardia or bradycardia

Urinary retention

Rash

Depression

Visual disturbances

Serious

Respiratory depression

Apnea

Severe hypotension

Anaphylaxis

Seizures

Addiction

Overdose

Neonatal withdrawal

Overdose

Symptoms

Pinpoint pupils

Severe respiratory depression

Hypotension

Bradycardia

Coma

Cyanosis

Death

Management

Naloxone (opioid antagonist) IV/IM/SC

Airway and ventilatory support

Activated charcoal if ingestion within 1 hour

Continuous monitoring and supportive care

Drug Interactions

CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir, clarithromycin)

Increase oxycodone plasma levels

Risk of respiratory depression

Reduce dose and monitor closely

CYP3A4 Inducers (e.g., rifampin, carbamazepine, phenytoin)

Decrease efficacy

Avoid or adjust dose accordingly

CYP2D6 Inhibitors (e.g., fluoxetine, paroxetine)

Reduce conversion to active metabolite oxymorphone

Possible reduction in analgesic effect

Benzodiazepines and CNS Depressants

Additive CNS and respiratory depression

Avoid or use with extreme caution

Warn patients not to consume alcohol

MAO Inhibitors

Contraindicated within 14 days of use

Risk of hypertensive crisis and serotonin syndrome

SSRIs and SNRIs

Serotonin syndrome possible with combined use

Anticholinergic drugs

Additive risk of urinary retention and constipation

Use in Special Populations

Elderly

Increased sensitivity

Use lowest effective dose

Monitor for sedation, confusion, respiratory effects

Renal Impairment

Reduced clearance of active metabolites

Dose adjustment or alternative agent may be required

Hepatic Impairment

Reduced metabolism

Start at lower doses and titrate cautiously

Monitoring Parameters

Pain control and functional improvement

Respiratory rate and oxygen saturation

Signs of sedation or overdose

Bowel function (especially constipation)

Signs of opioid use disorder

Endocrine function in long-term therapy

Blood pressure and heart rate

Signs of CNS toxicity

Formulations Available

Immediate-release tablets: 5 mg, 10 mg, 15 mg, 20 mg, 30 mg

Extended-release tablets: 10 mg, 20 mg, 40 mg, 80 mg

Oral solution: 1 mg/mL, 5 mg/5 mL

Oral concentrate: 20 mg/mL

Rectal suppository (rare)

Combination with acetaminophen (Percocet): 2.5–10 mg oxycodone with 325–650 mg acetaminophen

Combination with naloxone (Targin): mitigates opioid-induced constipation

Parenteral oxycodone available in select regions

Comparative Pharmacology

Oxycodone vs Morphine

Oxycodone has higher oral bioavailability

More potent per oral dose

Better tolerated in terms of GI effects for some patients

Oxycodone vs Hydrocodone

Both effective in acute and chronic pain

Hydrocodone usually combined with acetaminophen

Oxycodone available alone or in multiple combinations

Oxycodone vs Fentanyl

Fentanyl is more potent and used for severe chronic pain

Oxycodone is more flexible for oral administration

Oxycodone vs Tramadol

Tramadol is less potent, dual mechanism (opioid + SNRI)

Lower abuse potential but more serotonergic side effects

Regulatory and Legal Status

Controlled Substance

Schedule II (United States)

Class A (UK), Schedule 8 (Australia), Category B (EU)

Subject to strict prescription controls

Abuse-deterrent formulations (ADF) increasingly favored