Fluvoxamine XR Drug Interactions You Need to Know About

Fluvoxamine XR is an effective medication for OCD and social anxiety, but it's also one of the SSRIs with the most drug interactions. This isn't to scare you — it's to make sure you and your doctor are on the same page about what's safe to take together.

Fluvoxamine is a potent inhibitor of several liver enzymes (especially CYP1A2 and CYP2C19) that your body uses to break down other medications. When those enzymes are blocked, other drugs can build up in your system to dangerous levels. That's what makes Fluvoxamine's interaction profile so important to understand.

How Drug Interactions Work

Your liver processes most medications using a family of enzymes called cytochrome P450 (CYP) enzymes. Fluvoxamine strongly blocks two of these:

• CYP1A2 — Used to break down caffeine, Theophylline, Clozapine, Tizanidine, and others
• CYP2C19 — Used to break down Diazepam, Omeprazole, and others

It also moderately inhibits CYP3A4 and CYP2C9, which affect Alprazolam, Warfarin, and many other drugs.

When Fluvoxamine blocks these enzymes, other medications metabolized by them stay in your body longer and at higher levels — potentially causing side effects or toxicity.

Medications That Interact with Fluvoxamine XR

Contraindicated (Do NOT Combine)

The following medications should never be taken with Fluvoxamine XR:

• MAOIs (Phenelzine/Nardil, Tranylcypromine/Parnate, Isocarboxazid/Marplan, Selegiline/Emsam) — Risk of life-threatening serotonin syndrome. Must wait 14 days between stopping one and starting the other.
• Tizanidine (Zanaflex) — Fluvoxamine can increase Tizanidine levels dramatically, causing severe drops in blood pressure, excessive sedation, and impaired psychomotor function.
• Thioridazine — Combination can cause dangerous heart rhythm changes (QTc prolongation) that may be fatal.
• Pimozide (Orap) — Similar risk of QTc prolongation and cardiac arrhythmias.
• Alosetron (Lotronex) — Fluvoxamine markedly increases Alosetron levels.
• Ramelteon (Rozerem) — Fluvoxamine can increase Ramelteon levels by over 100-fold via CYP1A2 inhibition.

Major Interactions (Use with Extreme Caution)

• Theophylline (Theo-Dur, Elixophyllin) — Fluvoxamine can increase Theophylline levels 3-fold or more, potentially causing seizures, nausea, and cardiac arrhythmias. If you must take both, your doctor needs to closely monitor Theophylline levels.
• Warfarin (Coumadin) — Fluvoxamine increases Warfarin levels, raising the risk of serious bleeding. INR monitoring must be more frequent.
• Clozapine (Clozaril) — Fluvoxamine can increase Clozapine levels by 5 to 10 times, leading to sedation, seizures, and dangerous drops in blood pressure.
• Triptans (Sumatriptan/Imitrex, Rizatriptan/Maxalt, etc.) — Risk of serotonin syndrome when combined with Fluvoxamine. Use with caution under medical supervision.
• Lithium — Enhanced serotonergic effects; monitor for signs of serotonin syndrome and lithium toxicity.
• Benzodiazepines metabolized by CYP3A4 — Alprazolam (Xanax), Triazolam (Halcion), and Midazolam (Versed) can build up to excessive levels, causing profound sedation.

Moderate Interactions (Monitor Closely)

• Other SSRIs/SNRIs — Combining serotonergic medications increases the risk of serotonin syndrome. Your doctor should avoid prescribing Fluvoxamine XR alongside Sertraline (Zoloft), Fluoxetine (Prozac), Venlafaxine (Effexor), or Duloxetine (Cymbalta).
• Tramadol (Ultram) — Increased risk of seizures and serotonin syndrome.
• Methadone — Fluvoxamine can increase Methadone levels, potentially causing QTc prolongation or excessive sedation.
• Cyclosporine — Increased Cyclosporine levels; monitor drug levels closely.
• Carbamazepine (Tegretol) — Fluvoxamine may increase Carbamazepine levels.
• Olanzapine (Zyprexa) — Metabolized by CYP1A2; Fluvoxamine can increase Olanzapine levels significantly.
• NSAIDs and Aspirin — Ibuprofen (Advil), Naproxen (Aleve), and Aspirin increase bleeding risk when combined with any SSRI, including Fluvoxamine XR.

Supplements and OTC Medications to Watch

It's not just prescription drugs you need to worry about. Several common supplements and over-the-counter products interact with Fluvoxamine XR:

• St. John's Wort — A popular herbal supplement for mood. Combining it with Fluvoxamine XR significantly increases the risk of serotonin syndrome. Do not take them together.
• Tryptophan supplements — L-Tryptophan and 5-HTP increase serotonin and should be avoided.
• Melatonin — Fluvoxamine inhibits the enzyme that breaks down melatonin (CYP1A2), so melatonin levels can increase significantly. If you take melatonin for sleep, use a lower dose and mention it to your doctor.
• NSAIDs — Over-the-counter pain relievers like Ibuprofen (Advil, Motrin) and Naproxen (Aleve) increase bleeding risk. Acetaminophen (Tylenol) is generally a safer choice for pain relief.
• Cold and flu medications — Some contain Dextromethorphan (DXM), which can increase serotonin levels. Check labels carefully.

Food and Drink Interactions

Caffeine

This is a big one. Fluvoxamine is one of the most potent inhibitors of CYP1A2, the enzyme your body uses to break down caffeine. When you take Fluvoxamine XR, caffeine levels in your body can increase up to 5-fold.

One cup of coffee can feel like five. This can cause jitteriness, rapid heartbeat, insomnia, and anxiety — the exact symptoms you're trying to treat.

What to do: Significantly reduce your caffeine intake. Switch to decaf or limit yourself to half a cup of regular coffee. This applies to coffee, tea, energy drinks, chocolate, and caffeinated sodas.

Alcohol

Alcohol adds to the sedative effects of Fluvoxamine XR and can worsen depression and anxiety. It's best to avoid alcohol entirely or limit it significantly while taking this medication.

Grapefruit Juice

Grapefruit juice has a minor interaction with Fluvoxamine XR. While not as critical as with some other medications, it's generally a good idea to limit grapefruit consumption.

What to Tell Your Doctor

Before starting Fluvoxamine XR, give your doctor a complete list of:

• All prescription medications you currently take
• Over-the-counter medications you use regularly (pain relievers, cold medicine, sleep aids)
• Supplements and herbal products (especially St. John's Wort, melatonin, tryptophan, and fish oil)
• Your caffeine intake — how much coffee, tea, or energy drinks you consume daily
• Alcohol use
• Any medications you've recently stopped — especially MAOIs, which require a 14-day washout period

Also tell your doctor if you've experienced serotonin syndrome in the past, have a history of seizures, or take blood thinners.

Final Thoughts

Fluvoxamine XR is an effective medication, but its drug interaction profile requires more attention than many other SSRIs. The strong CYP1A2 and CYP2C19 inhibition means everyday substances like caffeine and common medications like Tizanidine or Theophylline can become problems.

The good news: most interactions are manageable with the right information and communication with your healthcare team. Keep your doctor and pharmacist in the loop about everything you take, and don't be afraid to ask questions.

For more on what to expect when taking this medication, check out our guides on Fluvoxamine XR side effects and how Fluvoxamine XR works. If you're having trouble finding the medication, Medfinder can help you locate it near you.