Oxycodone vs Hydromorphone

## Overview

Oxycodone and hydromorphone are both semi-synthetic opioids used for moderate-to-severe pain. Hydromorphone is ~4–5× more potent by oral route. Oxycodone has the advantage of both immediate-release and extended-release oral formulations and higher oral bioavailability.

## Mechanism of Action

Both are full mu-opioid receptor agonists. Hydromorphone may also have delta-opioid receptor activity at high concentrations, which is pharmacologically relevant in some pain contexts.

## Pharmacokinetics

Oxycodone: oral bioavailability 60–87%, CYP3A4 (→ noroxycodone, less active) and CYP2D6 (→ oxymorphone, active, minor). Half-life 4–6 h (IR). Hydromorphone: oral bioavailability 24%, half-life 2–3 h, H3G metabolite (neuroexcitatory at high doses).

## Equianalgesic Conversion

Oral oxycodone 10 mg ≈ oral hydromorphone 2–4 mg (approximately 4-5× potency difference PO).

## Clinical Selection

Oxycodone IR/ER (OxyContin) are widely used for outpatient chronic pain. Hydromorphone PO is used when opioid rotation is needed for patients developing tolerance. Hydromorphone IV/SC is preferred for high-dose palliative care (high water solubility).

## Key Takeaways

- Oxycodone: higher oral bioavailability, established ER formulation
- Hydromorphone: higher potency per mg, better SC/IV suitability
- Both avoid M6G problem of morphine in CKD