How long do opiates (opioid analgesics) stay in the system?

How Long Opiates Stay in the System

The detection time of opiates in the body varies significantly by specific drug, with most short-acting opioids detectable in urine for 1-4 days after a single dose, while long-acting opioids like methadone can persist much longer due to their extended half-lives and tissue accumulation.

Detection Times by Biological Matrix

Urine Detection (Most Clinically Relevant)

• Short-acting opioids (morphine, heroin, hydromorphone): Detectable for 1-1.5 days after relatively low doses (3-12 mg heroin via IV/IM/intranasal routes) using a 300 ng/mL cut-off 1
• Single dose of most opioids: Detection window of 1.5-4 days in urine 2
• Chronic users: Drugs can be detected for approximately 1 week after last use, and in extreme cases even longer 2
• Codeine/morphine metabolites: Using immunoassays calibrated with morphine at 300 ng/mL cut-off, heroin (which rapidly metabolizes to 6-acetylmorphine and morphine) shows detection times of 1-1.5 days for low doses 1

Blood/Plasma Detection

• Most opioids: Detectable at low nanogram per milliliter levels for only 1-2 days 2
• Blood detection times are significantly shorter than urine, making blood less useful for detection of prior use 2

Oral Fluid Detection

• Detection window: 5-48 hours at low nanogram per milliliter levels 2
• Shorter detection time compared to urine but useful for recent use 2

Pharmacokinetic Factors Affecting Duration

Half-Life Considerations

Methadone (longest duration):

• Plasma elimination half-life: 8-59 hours, substantially longer than morphine (1-5 hours) 3
• Clinical implications: With repeated dosing, methadone accumulates in the liver and is slowly released, prolonging duration of action despite low plasma concentrations 3
• Steady-state: Not attained until 3-5 days of dosing 3
• Average half-life: Approximately 24 hours with a range of 17 to over 100 hours due to pronounced interindividual differences 4

Fentanyl (transdermal):

• After patch removal, serum levels take approximately 16 hours to drop to 50% due to intradermal depot formation 4
• Steady state achieved at 72 hours with continuous use 4

Morphine and typical short-acting opioids:

• Plasma elimination half-life: 2-4 hours 4
• Steady state achieved within 24 hours (4-5 half-lives) 4

Factors Influencing Detection Time

Dose-dependent variables:

• Higher doses extend detection times proportionally 2, 1
• Route of administration affects both peak levels and duration 2

Individual patient factors:

• Hepatic metabolism: Most opioids undergo hepatic oxidation or glucuronidation; liver disease significantly prolongs clearance 5
• Renal excretion: Impaired renal function extends duration, particularly for morphine metabolites 5
• Chronic vs. acute use: Tissue accumulation with chronic use dramatically extends detection windows 2

Assay sensitivity:

• Lower cut-off values (e.g., 300 ng/mL vs. 1000 ng/mL for amphetamines) extend detection by approximately one day 1
• Method sensitivity directly impacts reported detection times 2

Clinical Antagonist Considerations

Naloxone Duration

• Half-life: 30-45 minutes after IV administration (range 30-81 minutes) 6
• Duration of clinical effect: 45 minutes to 3-4 hours depending on dose and route, often longer than elimination half-life 4, 6
• Critical pitfall: Patients may experience re-sedation after initial reversal because most opioids have much longer half-lives than naloxone 6
• Monitoring requirement: Extended observation for up to 2 hours minimum to watch for re-emergence of opioid toxicity 6

Naltrexone Duration

• Oral naltrexone half-life: 4 hours 4
• Active metabolite (6-β-naltrexol) half-life: 13 hours 4
• Antagonist effects: May persist for 2-3 days after stopping due to metabolite accumulation 4
• Extended-release formulation: Effects persist for 24-30 days after last injection 4, 7

Common Clinical Pitfalls

• Methadone accumulation: The discrepancy between methadone's analgesic duration (4-8 hours) and its elimination half-life (8-59 hours) creates significant overdose risk during the first 3-5 days of treatment 3
• Incomplete cross-tolerance: High opioid tolerance does not eliminate the possibility of methadone overdose during conversion from other opioids 3
• Drug interaction effects: CYP 2D6 and 3A4/5 enzyme interactions can significantly alter opioid metabolism and duration 8
• Hepatic impairment: Reduced clearance and increased oral bioavailability in cirrhosis necessitates dose reduction or extended intervals 5