Can I take Amitriptyline and Modafinil together?
Drug interaction guide
Originally published 25 Jan 2026
Meets Patient’s editorial guidelines
- DownloadDownload
- Share
- Language
- Discussion
- Audio Version
- Add to preferred sources on Google
Taking amitriptyline and modafinil together can increase the levels of amitriptyline in your body. This may lead to an increased risk of side effects such as extreme sleepiness, dry mouth, blurred vision, constipation, or a fast heartbeat. In some cases, it can also increase the risk of heart rhythm problems or seizures.
Why this happens
Modafinil can slow down the liver enzymes (specifically CYP2C19) that are responsible for breaking down amitriptyline. Because the body cannot clear the amitriptyline as quickly as usual, the drug builds up in your system. Additionally, both drugs can affect heart rate and brain activity, which may lead to additive effects.
What you should do
You should consult your doctor before taking these two medicines together. Your doctor may need to adjust your dose of amitriptyline or monitor you more closely for side effects. Seek medical help immediately if you experience a very fast or irregular heartbeat, severe dizziness, or fainting.
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.
Heart conditions
Do not take amitriptyline if you have recently had a heart attack or have heart rhythm problems (arrhythmias), as it can affect the electrical signals in your heart.
Hormonal contraception (Pill, patch, or implants)
Modafinil makes hormonal contraceptives less effective. You must use an additional barrier method (like condoms) during treatment and for 2 months after stopping.
Severe skin rash
Stop taking modafinil and seek urgent medical help if you develop a rash, skin peeling, or mouth sores, as it can cause rare but life-threatening skin reactions.
Food and drink warnings
Alcohol
You should avoid or strictly limit alcohol while taking amitriptyline. Both substances cause drowsiness and slow your reactions; combining them can lead to dangerous levels of sedation, impaired coordination, and increased risk of falls. Alcohol can also worsen the side effects of the medication.
Caffeine (Coffee, tea, energy drinks)
Limit your intake of caffeine while taking modafinil. Because both are stimulants, combining them can increase the risk of side effects such as a racing heart (palpitations), anxiety, jitters, high blood pressure, and difficulty sleeping.
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.
Patient picks for Drug interactions

Drug interactions checker
Can I take Ashwagandha and Vitamin B12 together?
There are no known clinical interactions between ashwagandha and vitamin B12. It is generally considered safe to take these two supplements together.

Drug interactions checker
Can I take Mounjaro and Metformin together?
When taken together, Mounjaro and Metformin can increase the risk of your blood sugar levels dropping too low (hypoglycaemia). While both drugs work to lower blood sugar, they do so in different ways, which can sometimes lead to an additive effect. Additionally, Mounjaro slows down how quickly your stomach empties, which might slightly change how your body absorbs Metformin, though this is usually not a major concern.
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
Join the conversation
Share your thoughts or experiences with others in our patient communities.

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.
More in drug interactions checker
- Can I take Alcohol and Candesartan together?
- Can I take Allopurinol and Candesartan together?
- Can I take Amitriptyline and Paracetamol together?
- Can I take Anastrozole and Simvastatin together?
- Can I take Ashwagandha and Vitamin B12 together?
- Can I take Atorvastatin and Cardioace together?
- Can I take Atorvastatin and Levothyroxine together?
- Can I take Atorvastatin and Mirabegron together?
- Can I take Atorvastatin and Pyridostigmine together?
- Can I take Atorvastatin and Turkey tail together?
- Can I take Calcium and Doxycycline together?
- Can I take Clarithromycin and Paracetamol together?
- Can I take Clopidogrel and Gabapentin together?
- Can I take Clopidogrel and Naproxen together?
- Can I take Codeine and Morphine together?
- Can I take Cordyceps and Turkey tail together?
- Can I take Danazol and Tramadol together?
- Can I take Evana heavy period relief and Mefenamic acid together?
- Can I take Rivaroxaban and Tamsulosin together?
- Can I take Statins and Grapefruit together?