Can I take Amitriptyline and Zapain together?
Drug interaction guide
Originally published 25 Jan 2026
Meets Patient’s editorial guidelines
- DownloadDownload
- Share
- Language
- Discussion
Taking these two medicines together can make you feel very drowsy, dizzy, and confused. It can also slow down your breathing and make you more likely to experience constipation or a dry mouth.
In this article:
Continue reading below
Why this happens
Both amitriptyline and Zapain (which contains codeine and paracetamol) affect the central nervous system. Amitriptyline is an antidepressant and Zapain contains an opioid (codeine); when combined, their sedative effects add together. Additionally, both drugs have 'anticholinergic' effects, which can lead to side effects like a dry mouth or constipation.
What you should do
Back to contentsYou should speak to your doctor before taking these together. If your doctor has prescribed both, be aware that you may feel very sleepy. Do not drive or operate machinery until you know how they affect you. Avoid drinking alcohol, as this will make the drowsiness much worse. Seek medical help immediately if you experience extreme sleepiness or difficulty breathing.
Continue reading below
Important precautions
Back to contentsSuicidal 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.
Breathing problems (e.g. asthma, COPD)
Zapain contains codeine, which can cause life-threatening breathing difficulties. You must not take this if you have severe asthma or significant lung disease.
Serotonin syndrome risk
Taking these together increases the risk of a rare but serious reaction called serotonin syndrome. Seek urgent medical help if you experience high fever, agitation, or muscle twitching.
Addiction and withdrawal
Zapain contains codeine, an opioid that can cause addiction if used for more than 3 days. Stopping suddenly after long-term use can cause severe withdrawal symptoms.
Food and drink warnings
Back to contentsAlcohol
You must avoid or strictly limit alcohol while taking these medicines. Both amitriptyline and the codeine in Zapain cause drowsiness and slow your breathing. Alcohol significantly increases these effects, which can lead to dangerous levels of sedation, breathing difficulties, and impaired coordination.
Caffeine (Coffee, tea, energy drinks)
Amitriptyline can sometimes cause a fast or irregular heartbeat. High amounts of caffeine can worsen this effect and may also increase feelings of anxiety or restlessness, potentially counteracting the calming effect of the medication.
Continue reading below
Using other medicines
Back to contentsTaking 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.
Patient picks for Drug interactions

Treatment and medication
Can I take Amlodipine and Atorvastatin together?
Taking amlodipine and atorvastatin together can increase the amount of atorvastatin in your blood. This may increase the risk of side effects, particularly muscle pain, tenderness, or weakness (a condition called myopathy). In rare cases, this can lead to a more serious muscle breakdown called rhabdomyolysis.

Treatment and medication
Can I take Amitriptyline and Zopiclone together?
Taking amitriptyline and zopiclone together can make you feel extremely drowsy, dizzy, and confused. It significantly increases the risk of falling over, especially in the dark or when getting out of bed at night. It can also cause your breathing to become very slow or shallow, and may lead to severe coordination problems.
Continue reading below
Article history
The information on this page is written and peer reviewed by qualified clinicians.
25 Jan 2026 | Originally published

Ask, share, connect.
Browse discussions, ask questions, and share experiences across hundreds of health topics.

Feeling unwell?
Assess your symptoms online for free
Sign up to the Patient newsletter
Your weekly dose of clear, trustworthy health advice - written to help you feel informed, confident and in control.
By subscribing you accept our Privacy Policy. You can unsubscribe at any time. We never sell your data.