Can I take Amitriptyline and Oxycodone together?
Drug interaction guide
Originally published 25 Jan 2026
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Taking amitriptyline and oxycodone together can cause extreme sleepiness, dizziness, and severe breathing difficulties. It may also lead to a rare but serious condition called serotonin syndrome, which can cause confusion, sweating, and muscle twitching.
Why this happens
Both drugs slow down the central nervous system (brain and spinal cord). Amitriptyline also increases serotonin levels, which can be further affected by oxycodone, leading to a dangerous build-up. Additionally, amitriptyline can slow down the body's ability to process oxycodone, making its effects stronger and longer-lasting.
What you should do
You must speak to your doctor before taking these medicines together. If your doctor prescribes both, they will likely start you on the lowest possible doses. Seek immediate medical help if you feel unusually sleepy, have trouble breathing, or feel very confused.
Important precautions
Suicidal thoughts and mood changes
Amitriptyline can increase the risk of suicidal thoughts or self-harm, particularly when first starting treatment or changing doses. Seek immediate medical help if your mood changes or you feel depressed.
Respiratory Depression / Breathing Problems
Both medicines can slow your breathing. Taking them together significantly increases the risk of dangerous, shallow breathing or stopping breathing altogether. Seek emergency help if you feel extremely drowsy or have difficulty breathing.
Opioid Addiction and Dependence
Oxycodone is an opioid that carries a high risk of addiction and physical dependence, even at prescribed doses. Long-term use can lead to withdrawal symptoms if stopped suddenly.
Heart Rhythm Disorders
Amitriptyline can affect your heart rhythm (QT prolongation). It must be used with extreme caution if you have an existing heart condition or a history of heart attacks.
Food and drink warnings
Alcohol
You must avoid or strictly limit alcohol while taking these medicines. Both amitriptyline and Oxycodone cause drowsiness and slow your breathing; alcohol significantly increases these effects, which can lead to dangerous levels of sedation, coordination loss, and respiratory depression.
Grapefruit juice
Avoid drinking grapefruit juice or eating grapefruit. It can increase the amount of oxycodone in your blood to potentially toxic levels, increasing the risk of serious side effects like extreme sleepiness or breathing difficulties.
Caffeine (Coffee, tea, energy drinks)
Amitriptyline can sometimes cause a fast or irregular heartbeat. High intake of caffeine may worsen these heart-related side effects or increase feelings of restlessness and anxiety.
Using other medicines
Taking multiple medicines? Our Medicines Interaction Checker helps you check whether your prescriptions, over-the-counter medicines, and supplements are safe to take together. Simply search for your medicines to see potential interactions and what to do about them.
Disclaimer
This information is for general educational purposes only and should not be relied upon as a substitute for professional medical advice. Always consult your GP, pharmacist, or another qualified healthcare professional before making decisions about your medications. Individual circumstances may vary, and only a healthcare professional who knows your medical history can provide personalised guidance.
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Article history
The information on this page is written and peer reviewed by qualified clinicians.
Article also available in English, German, Spanish, French, Italian, Portuguese, Hindi, Hebrew, Arabic, and Swedish.
25 Jan 2026 | Originally published
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