Carbamazepine Interactions: Drugs to Avoid and Safer Alternatives

One medicine can wreck a dozen others-and vice versa. Carbamazepine (Tegretol/Teril) is that kind of drug. It speeds up how your liver clears meds and also gets pushed around by antibiotics, antifungals, HIV boosters, and even grapefruit. If you’re on it for seizures, trigeminal neuralgia, or bipolar, the biggest risk isn’t missing a dose; it’s mixing it with the wrong thing. I’ll keep it simple: what to avoid, what you can pair with careful monitoring, and the exact steps to stay safe. I live in Perth and coach patients through this every week. Here’s the playbook I use at home and in clinic.

carbamazepine interactions - TL;DR

• Red-zone “do not mix”: strong 3A4 inhibitors (clarithromycin/erythromycin, ketoconazole/itraconazole/voriconazole/posaconazole), cobicistat/ritonavir, nefazodone, grapefruit juice; plus clozapine, MAOIs, St John’s wort, and direct oral anticoagulants (apixaban/rivaroxaban) without specialist input.
• Biggest everyday trap: hormones. Carbamazepine can make pills, patches, rings, implants, and morning-after pills fail. Use a copper or levonorgestrel IUD, or discuss depot medroxyprogesterone.
• Antibiotics/antifungals: choose azithromycin over clarithromycin; terbinafine for skin fungus rather than azoles; avoid voriconazole with carbamazepine.
• Monitoring matters: check levels, sodium, liver, and blood counts when adding or stopping inducers/inhibitors. Dose changes are common.
• When unsure: ask your pharmacist or prescriber to run an interaction check before you start anything-prescription, OTC, or herbal.

Red‑zone interactions to avoid (and what to use instead)

These are the combos that most often lead to seizures returning, serious side effects, ER visits, or treatment failure. If one of these is suggested for you, flag your carbamazepine right away and ask for an alternative.

• Macrolide antibiotics that spike carbamazepine levels: clarithromycin and erythromycin can double or triple carbamazepine, causing dizziness, blurred vision, nausea, ataxia, or confusion within days. Safer pick: azithromycin for many chest/ear infections. If azithromycin isn’t right, your prescriber can choose a non-macrolide like doxycycline (note: carbamazepine lowers doxycycline a bit-see the next section).
• Strong azole antifungals: voriconazole is a hard “no”-carbamazepine drops voriconazole exposure by up to ~90%, and voriconazole drives carbamazepine up. Itraconazole, ketoconazole, and posaconazole also cause trouble. Safer picks: for skin/nail infections, terbinafine; for vaginal thrush, topical clotrimazole or a clinician-guided short course of fluconazole with monitoring.
• HIV boosters and some antiretrovirals: cobicistat and ritonavir swing levels both ways. Avoid without an HIV specialist. Many antiretrovirals are impacted by enzyme induction-there are better regimens to use with carbamazepine.
• Nefazodone: raises carbamazepine; avoid.
• MAOIs: avoid within 14 days. Risk of serious CNS and blood pressure effects.
• Clozapine: both drugs can suppress the bone marrow. The combo is generally contraindicated due to agranulocytosis risk. If an antipsychotic is needed, quetiapine or olanzapine are common alternatives, but both may run low because carbamazepine induces their clearance-doses often need to be higher under supervision.
• Direct oral anticoagulants (DOACs): apixaban and rivaroxaban often underperform with carbamazepine; bleeding protection can collapse. Use warfarin with close INR monitoring or a non-enzyme-induced plan guided by cardiology/haematology.
• St John’s wort: it’s an inducer like carbamazepine, so it can wipe out the effect of many drugs (including birth control, HIV meds, anticoagulants). Leave it on the shelf.
• Grapefruit juice: even a glass can raise carbamazepine levels. Swap for orange or apple juice.

Why this list? Carbamazepine is a strong inducer of CYP3A4, UGTs, and P‑glycoprotein, and it’s also metabolized by CYP3A4. That means some drugs speed carbamazepine up or slow it down, and carbamazepine speeds a lot of other drugs up. I’ve seen people end up toxic after a GP quite reasonably chose clarithromycin for a chest infection. One phone call and a switch to azithromycin fixed it.

Sources doctors trust for these calls include the Tegretol Product Information (FDA/TGA), the Australian Medicines Handbook (2025), and specialist guidance for DOACs (e.g., EHRA). No links here-ask your clinician to check their current copy.

Manageable combinations: adjust, monitor, and stay in range

Some pairings aren’t instant deal-breakers, but they need a plan. Here’s how I walk people through it.

1. Get your baseline right. Autoinduction means carbamazepine speeds up its own clearance over 2-5 weeks after you start or change dose. Target blood level: roughly 4-12 mg/L (17-51 micromol/L), but the “right” level is where your symptoms are controlled without side effects.
2. When adding a 3A4 inhibitor (e.g., diltiazem, verapamil, fluconazole): expect carbamazepine to rise within 2-5 days. Rule of thumb: consider lowering the carbamazepine dose 25-50% and check a level after 3-5 days, then again at 7-10 days. Watch for dizziness, double vision, unsteady gait, nausea.
3. When adding a 3A4 inducer (e.g., rifampicin, phenytoin, phenobarbital, primidone): expect carbamazepine to fall. You might need a big dose increase. Check a level after 1-2 weeks and adjust in steps.
4. When stopping an inducer: the liver “calms down” slowly. The interaction can persist 1-3 weeks. Rebound carbamazepine toxicity is common if you don’t lower the dose.
5. Check labs smartly. At baseline and with any big change: carbamazepine level, sodium (hyponatremia is a real risk, especially with SSRIs, diuretics, and in older adults), liver enzymes, and full blood count. In Australia, this is standard pathology your GP can order.

Specific drug groups you’ll run into:

• Antidepressants: fluoxetine and fluvoxamine can increase carbamazepine; sertraline and citalopram are milder but watch sodium. Mirtazapine is generally easier. Start low, go slow, check sodium at 1-2 weeks.
• Antipsychotics: quetiapine and lurasidone levels often plunge with carbamazepine; the med may “stop working.” Olanzapine and aripiprazole are also induced. Doses sometimes need to be higher-or a different mood stabilizer may be better for bipolar.
• Other antiseizure meds:
  • Valproate: raises the active carbamazepine-epoxide metabolite; can trigger neuro side effects. Valproate levels may also shift. If you must combine, monitor both levels and watch for tremor, sedation, or confusion.
  • Lamotrigine: carbamazepine cuts lamotrigine exposure about in half. The lamotrigine dose usually needs to be higher, with careful titration to lower rash risk.
  • Topiramate and oxcarbazepine: mild to moderate induction; watch for reduced effect and more hyponatremia with oxcarbazepine.
• Pain medicines:
  • Tramadol: lowers seizure threshold and relies on metabolism pathways that carbamazepine changes. I avoid it in people with epilepsy.
  • Codeine: may underperform; consider simple analgesia (paracetamol) or an alternative opioid if needed, supervised.
  • Methadone: levels can drop; coordinate with the prescriber to adjust.
  • NSAIDs: fine from an interaction standpoint; mind GI/kidney risks.
• Anticoagulants and antiplatelets:
  • DOACs (apixaban, rivaroxaban, edoxaban, dabigatran): generally avoid. Go to warfarin with tight INR checks or another strategy.
  • Warfarin: carbamazepine can lower INR; dose often needs to go up. Check INR more often when starting or stopping carbamazepine.
  • Clopidogrel/aspirin: no direct clash, but don’t forget bleeding risks if you go toxic on carbamazepine and get unsteady.
• Thyroid hormone: carbamazepine can lower T4; you might need a higher levothyroxine dose. Recheck TSH 6-8 weeks after starting carpamazepine or any big dose change.
• Diuretics and SSRIs: additive risk of hyponatremia with carbamazepine. Check sodium at 1-2 weeks and with any symptoms (headache, confusion, nausea, falls).

Small Perth‑specific note: brand names you’ll hear include Tegretol and Teril. Pharmacies will offer generics; keep the formulation consistent (IR vs CR) to avoid level swings.

Everyday traps: antibiotics, antifungals, pain, hormones, herbs, and food

Real life is messy. You catch a bug, you need a tooth pulled, you’re sorting birth control, or someone hands you a “natural” sleep aid. Here’s how I talk people through common scenarios.

• I got a chest or sinus infection. What antibiotic is okay?
  • Often fine: amoxicillin, amoxicillin-clavulanate, cephalexin, trimethoprim-sulfamethoxazole (watch sodium/potassium as usual), azithromycin.
  • Caution/avoid: clarithromycin, erythromycin (toxic carbamazepine levels), doxycycline (may be less effective-use if appropriate and finish the full course), rifampicin (strong inducer-avoid unless specialist says otherwise).
• I have thrush or tinea. Which antifungal?
  • Skin/nails: terbinafine is the go-to instead of strong azoles.
  • Vaginal thrush: topical clotrimazole works well. Fluconazole single-dose may be okay with monitoring, but check with your prescriber.
  • Avoid: voriconazole with carbamazepine, full stop.
• I need pain relief or a cough-and-cold fix.
  • Pain/fever: paracetamol is safe. NSAIDs like ibuprofen are fine interaction-wise. Avoid tramadol if you have seizures.
  • Cold/flu: plain antihistamines (e.g., cetirizine) are okay but can add drowsiness. Decongestants (pseudoephedrine) don’t clash with carbamazepine but can raise blood pressure. Cough suppressants like dextromethorphan are usually okay; just avoid combo packs with too many extras.
  • Sleep aids: sedating antihistamines can stack drowsiness with carbamazepine. Go easy.
• I’m on hormonal contraception.
  • Carbamazepine can cut ethinyl estradiol and progestin levels by 50-80%. Pills, patches, rings, implants, and many emergency contraception options can fail.
  • Best picks: copper IUD or levonorgestrel IUD. Depot medroxyprogesterone injection is an option but discuss timing and bleeding.
  • Emergency contraception: a copper IUD is most reliable. If an oral option is your only route, guidance often suggests a double dose levonorgestrel (3 mg) within 72 hours, but effectiveness is uncertain with enzyme induction; ulipristal isn’t recommended with enzyme inducers.
• I take supplements and herbal products.
  • Avoid: St John’s wort. It’s the classic inducer.
  • Be cautious: ginkgo can increase seizure risk; kava and valerian add sedation.
  • Folic acid: if you’re trying for pregnancy or could become pregnant, discuss a higher-dose folate plan with your GP.
• Food and drink.
  • Skip grapefruit and Seville oranges. Regular oranges, apples, berries are fine.
  • Alcohol adds sedation and fall risk. If you drink, keep it light and consistent; avoid binges.

Numbers give context. Clarithromycin has been shown to increase carbamazepine levels 2-3× in small clinical series, while carbamazepine can slash quetiapine exposure by over 80%-no wonder mood symptoms break through. Rifampicin can push carbamazepine levels down so low that seizures return. These aren’t rare “maybe” effects; they show up in day-to-day practice.

Quick reference: checklists, decision rules, mini‑FAQ, and next steps

Here’s the tight, practical stuff I give patients-and keep on my own fridge. Abigail insists it saves us calls to the on‑call pharmacist.

Fast checklists

• Before starting any new med or herbal:
  • Tell the prescriber you’re on carbamazepine and why.
  • Ask: “Is this a 3A4 inhibitor or inducer?”
  • Plan for a carbamazepine level check if yes.
  • Set an alarm to watch for symptoms (dizziness, blurred vision, unsteady gait) in the first week.
• When you stop an inducer or inhibitor:
  • Book a level check 1-2 weeks later (inducers), 3-5 days (inhibitors).
  • Ask if your carbamazepine dose should change the same day you stop the other med.
• Contraception decisions:
  • On carbamazepine? Prefer an IUD or depot. Don’t rely on standard pills/patch/ring/implant.
  • EC needed? Copper IUD best. Oral EC under enzyme induction is less reliable.
• Lab monitoring timing:
  • Baseline when you start or change dose.
  • 3-5 days after starting/stopping inhibitors; 1-2 weeks after inducers.
  • Anytime symptoms change.

Simple decision rules

• If it’s a strong macrolide (clarithro/erythro) or strong azole (voriconazole/itraconazole/ketoconazole/posaconazole), avoid and choose a different class.
• If it’s St John’s wort or grapefruit, skip it.
• If the drug “needs steady blood levels to work” (anticoagulants, antiretrovirals, antipsychotics, hormones), assume carbamazepine will mess with it until proven otherwise.
• If you can’t avoid an inducer/inhibitor, build a monitoring plan before you take the first dose.

Mini‑FAQ

• Can I take cold and flu meds? Yes, but keep it simple. Paracetamol for fever. A plain decongestant or a non-drowsy antihistamine if needed. Avoid multi-symptom packs that hide dextromethorphan, sedating antihistamines, and a decongestant in one hit.
• Is ibuprofen safe? Interaction-wise, yes. Mind stomach/kidneys if you use it often.
• How long do interactions last after stopping carbamazepine? The enzyme induction effect can linger 1-3 weeks. Other drugs you were taking may “bounce back” to higher levels during that time.
• Do vaccines interact? No metabolic clashes. If you spike a fever after a vaccine, that can lower seizure threshold briefly, so keep paracetamol handy.
• Pregnancy plans? Carbamazepine can be used in pregnancy with specialist care, but folate needs are higher and drug levels can shift. Loop in your GP/obstetrician early and lock in a contraception plan until then.
• What if I feel off-balance or see double? That’s classic carbamazepine toxicity. Call your prescriber the same day. If it’s severe or you’re vomiting, seek urgent care.

Next steps and troubleshooting

• If you’re starting carbamazepine for the first time: ask your prescriber to schedule a level check around week 2-3 (as autoinduction kicks in) and again at week 4-6.
• If you need an antibiotic today: tell the clinic you’re on carbamazepine and ask them to avoid clarithromycin/erythromycin. Azithromycin or amoxicillin are common safe bets for many infections.
• If you’re on a DOAC: don’t add carbamazepine without a plan from cardiology/haematology. The stroke risk isn’t theoretical.
• If mood meds feel like they stopped working: check if carbamazepine was added or the dose went up. You may need to raise the antipsychotic/antidepressant dose or switch to a less-affected option.
• If sodium runs low: review SSRIs, diuretics, and fluid intake. You might need a dose cut, med switch, or salt strategy.
• If you live remote or can’t get quick labs: ask your GP for a standing pathology form and a written “dose-adjustment” plan that spells out when to change and when to test.

Why I’m confident about this advice: it’s anchored in primary sources clinicians use daily-the Tegretol/Teril Product Information (FDA and TGA), the Australian Medicines Handbook 2025 edition, guidance from the European Heart Rhythm Association on DOAC interactions, and reviews in Lexicomp/Micromedex and the UK Specialist Pharmacy Service. On the ground in WA, these rules prevent problems. They’re not theory.

One last human tip: keep an updated med list in your wallet and on your phone. I put a bold line under “Avoid clarithromycin/erythromycin, strong azole antifungals, St John’s wort, grapefruit.” It’s saved more than one weekend.