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Oxycodone + Naloxone

Fixed-dose combination: long-acting opioid analgesic plus peripheral opioid receptor antagonist

ATC code: N02AA55(Oxycodone and naloxone)

Updated · Methodology

Indications

B

Chronic pain

Third line

Severe chronic pain requiring long-term opioid analgesia with established or anticipated opioid-induced constipation. Per EAU 2024 and SED 2024, used mainly for cancer pain and severe neuropathic pain refractory to standard therapy. Dose: 10/5, 20/10, 40/20 mg every 12 hours. Not first-line for chronic non-cancer pain – see CDC 2022 opioid limits. Before starting, exclude severe hepatic impairment (raised naloxone bioavailability).

Sources

  1. AEMPS: Ficha técnica de Oxicodona (2024)

ICD-10: R52 · ICD-11: MG30.Z

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

D

Acute pain

Not recommended

Acute postoperative and post-traumatic pain. A strong opioid with fixed 12-hour dosing is not suited for variable acute pain – flexible titration with immediate-release agents is needed. Per SED 2024, acute pain is managed with short-course immediate-release oxycodone or morphine. If Targin was prescribed for 1–2 weeks of postoperative pain, consider getting a second opinion.

Sources

  1. AEMPS: Ficha técnica de Oxicodona (2024)

ICD-10: R52.0 · ICD-11: MG31

How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

Oxycodone provides analgesia through μ-opioid receptors. Oral naloxone has very low systemic bioavailability (<3% due to first-pass metabolism) but blocks intestinal μ-receptors, reducing opioid-induced constipation. No systemic naloxone effect; opioid analgesia is preserved. RCTs show 40–50% reduction in constipation vs oxycodone monotherapy.

Safety

Boxed warning

FDA Black Box: risk of addiction and fatal respiratory depression; neonatal opioid withdrawal syndrome; fatal interactions with benzodiazepines and alcohol.

Contraindications

  • Hypersensitivity to oxycodone or naloxone
  • Respiratory depression, severe COPD, asthma exacerbation
  • Paralytic ileus
  • Severe hepatic impairment (Child-Pugh B-C)
  • Acute alcohol or psychotropic intoxication
  • MAOI use <2 weeks

Serious adverse effects

  • Respiratory depression and death
  • Opioid dependence
  • Acute adrenal insufficiency
  • Acute biliary colic
  • Serotonin syndrome

Common adverse effects

  • Constipation (still occurs but less than with monotherapy)
  • Nausea, vomiting
  • Drowsiness
  • Dry mouth
  • Dizziness
  • Pruritus
  • Decreased appetite

Pregnancy: can you take Oxycodone + Naloxone?

Not recommended in pregnancy. Long-term use causes neonatal opioid withdrawal. Taper 1–2 months before planned conception.

Breastfeeding: can you take Oxycodone + Naloxone?

Long-term use not recommended – infant sedation risk. Hale L3. Short course under supervision if acutely necessary.

RID, infant dose via milk
9%
Calculate RIDFull profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Drug interactions

With benzodiazepines, gabapentinoids, alcohol – fatal respiratory depression ( Black Box). CYP3A4 inhibitors raise oxycodone levels. With SSRIs and MAOIs – serotonin syndrome risk.

Monitoring

BP, respiratory rate, sedation, and bowel transit at every visit. In moderate hepatic impairment, start at minimum doses and check liver function every 3–6 months.

Drug–nutrient interactions

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Frequently asked

What is Oxycodone + Naloxone used for?

Oxycodone + Naloxone is evaluated for the following indications with varying evidence strength: Chronic pain (evidence tier B), Acute pain (evidence tier D). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Oxycodone + Naloxone?

Common side effects of Oxycodone + Naloxone (≥ 1 in 100): Constipation (still occurs but less than with monotherapy), Nausea, vomiting, Drowsiness, Dry mouth, Dizziness, Pruritus. See the Safety section for uncommon and serious reactions.

Is Oxycodone + Naloxone safe during pregnancy?

Not recommended in pregnancy. Long-term use causes neonatal opioid withdrawal. Taper 1–2 months before planned conception.

Is Oxycodone + Naloxone compatible with breastfeeding?

Long-term use not recommended – infant sedation risk. Hale L3. Short course under supervision if acutely necessary.

Can you drink alcohol while taking Oxycodone + Naloxone?

With benzodiazepines, gabapentinoids, alcohol – fatal respiratory depression (FDA Black Box).

Who should not take Oxycodone + Naloxone?

Oxycodone + Naloxone is contraindicated in: Hypersensitivity to oxycodone or naloxone; Respiratory depression, severe COPD, asthma exacerbation; Paralytic ileus; Severe hepatic impairment (Child-Pugh B-C); Acute alcohol or psychotropic intoxication. Full list in the Safety section.

Does Oxycodone + Naloxone carry an FDA boxed warning?

FDA Black Box: risk of addiction and fatal respiratory depression; neonatal opioid withdrawal syndrome; fatal interactions with benzodiazepines and alcohol.

Other drugs in this group

Paracetamol, Palmitoylethanolamide, Rizatriptan, Sumatriptan, Zolmitriptan, Eletriptan, Meperidine, Tapentadol