Most antibiotics are polite houseguests. They do their job and leave your other medicines alone. Clarithromycin is different. It is one of the strongest inhibitors of CYP3A4, the liver and gut enzyme that clears a large share of commonly prescribed drugs. While you take it, medicines that normally pass through your system at a steady rate can pile up, sometimes to toxic levels. Statins are the best-known example, but the list stretches to blood pressure pills, gout treatment, blood thinners, sleeping tablets, and heart rhythm drugs.
This guide to clarithromycin drug interactions is organized by how each interaction happens, because once you understand the four mechanisms, the long lists start to make sense. Each section sorts drugs into three actions: Do not combine, Adjust or pause, and Monitor. We finish with a script you can use at the pharmacy counter.
The Four Interaction Mechanisms
| Mechanism | What happens | Typical result |
|---|---|---|
| A. CYP3A4 blockade | Clarithromycin slows the enzyme that breaks down many drugs | The other drug’s level rises, sometimes several-fold |
| B. P-glycoprotein (P-gp) blockade | Clarithromycin blocks a “pump” that pushes some drugs out of cells and into urine or bile | Levels of drugs like digoxin and colchicine rise |
| C. QT stacking | Clarithromycin and the other drug both lengthen the heart’s QT interval | Higher risk of a dangerous rhythm (torsades de pointes) |
| D. Reverse interactions | Other drugs speed up or slow down clarithromycin’s own breakdown | Clarithromycin works less well, or its side effects increase |
The FDA’s reference table of CYP enzyme and transporter interactions lists clarithromycin among its examples of strong CYP3A inhibitors. The effect starts within a day or two of the first dose and can last a few days after the last dose while the enzyme recovers.
The Interaction Timeline: When It Starts and Ends
Clarithromycin does not simply compete with other drugs for CYP3A4. It binds to the enzyme in a way that inactivates it. Your body then has to build new enzyme to restore normal activity. That has practical consequences:
- Onset: interaction effects build over the first one to three days of the course.
- Peak: by the middle of a 7- to 14-day course, enzyme activity is at its lowest.
- Offset: after your last dose, it takes several days for enzyme activity to return to normal, even though clarithromycin itself leaves your blood within a day or two.
This is why pharmacists sometimes advise waiting a few days before restarting a paused medicine, and why an interaction can still matter even if you started the other drug after finishing the antibiotic.
Statins: The Headline Interaction
Statins lower cholesterol, and several of them depend heavily on CYP3A4 for clearance. When clarithromycin blocks that pathway, statin levels can rise high enough to damage muscle. The most severe form, rhabdomyolysis, releases muscle proteins that can injure the kidneys. The US clarithromycin label reports rhabdomyolysis cases with simvastatin, lovastatin, and atorvastatin.
| Statin | Dependence on CYP3A4 | Action during clarithromycin |
|---|---|---|
| Simvastatin (Zocor) | Very high | Do not combine. Pause the statin for the whole course. |
| Lovastatin (Mevacor, Altoprev) | Very high | Do not combine. Pause for the whole course. |
| Atorvastatin (Lipitor) | Moderate to high | Adjust: no more than 20 mg daily if the combination cannot be avoided. |
| Pravastatin (Pravachol) | Low (but transporter effects) | Adjust: no more than 40 mg daily. |
| Rosuvastatin (Crestor) | Minimal | Monitor: generally lower concern. |
| Fluvastatin (Lescol) | Uses CYP2C9 instead | Monitor: the label mentions it as an option not dependent on CYP3A. |
| Pitavastatin (Livalo) | Minimal | Monitor. |
Is it safe to stop my statin for a week or two?
For most people, yes. Pausing a statin for the duration of a short antibiotic course has a negligible effect on long-term heart risk, while continuing simvastatin or lovastatin alongside clarithromycin carries a real risk of muscle injury. Restart the day after your last clarithromycin dose, or as your prescriber advises. If you have had a recent heart attack or stent, ask your cardiologist whether a temporary switch or an alternative antibiotic is better.
Warning signs of statin muscle injury
- Unexplained muscle pain, tenderness, or weakness, especially in the thighs, shoulders, or back.
- Dark, tea- or cola-colored urine.
- Unusual tiredness or reduced urine output.
Stop the statin and seek medical care promptly if these appear.
Mechanism A: Other CYP3A4 “Victim” Drugs
Do not combine
| Drug | Used for | Risk |
|---|---|---|
| Colchicine (in kidney or liver impairment) | Gout, familial Mediterranean fever, pericarditis | Life-threatening colchicine toxicity; deaths reported |
| Ergotamine, dihydroergotamine | Migraine | Severe blood vessel spasm and limb ischemia |
| Pimozide | Tourette syndrome | Dangerous heart rhythms |
| Cisapride | Reflux (largely withdrawn) | Dangerous heart rhythms |
| Lurasidone | Schizophrenia, bipolar depression | Large rise in drug levels and side effects |
| Lomitapide | Familial high cholesterol | Severe liver enzyme elevation |
Several heart medicines are also listed as contraindicated with strong CYP3A4 inhibitors in their own labels, including ranolazine (angina) and ivabradine (heart failure). Ticagrelor (a blood thinner after heart attacks and stents) should be avoided with strong CYP3A inhibitors. If you take any of these, an alternative antibiotic is usually the safer route.
Adjust or pause
- Colchicine (normal kidney and liver function): dose must be reduced, and you should watch for diarrhea, vomiting, muscle weakness, or numbness.
- Calcium channel blockers metabolized by CYP3A4: amlodipine, felodipine, nifedipine, diltiazem, verapamil. See the detailed section below.
- Erectile dysfunction drugs: sildenafil, tadalafil, and vardenafil levels rise. Labels cap tadalafil at 10 mg no more than once every 72 hours with strong CYP3A4 inhibitors. Men with heart disease should also read our Cialis and heart health guide.
- Sedatives: triazolam and midazolam can cause prolonged, deep sedation. Alprazolam levels also rise. Our Xanax vs Ativan comparison explains why lorazepam, which is not cleared by CYP3A4, is sometimes preferred in this situation.
- Quetiapine: levels rise, increasing drowsiness, low blood pressure, and QT risk. Its label recommends a large dose reduction with strong CYP3A4 inhibitors.
- Immunosuppressants: tacrolimus, cyclosporine, sirolimus, and everolimus levels can increase dramatically. Blood levels need close monitoring.
- Carbamazepine: levels rise, with risk of dizziness, double vision, and toxicity.
- Some opioids: oxycodone, fentanyl, and methadone levels can rise, increasing sedation and breathing risk. Methadone also prolongs QT. See our methadone vs tramadol article for background.
- Certain cancer drugs and newer targeted therapies: many kinase inhibitors carry specific dose rules with strong CYP3A4 inhibitors.
Monitor
- Theophylline: modest rise in levels; watch for nausea, tremor, or a racing heart.
- Cilostazol, eletriptan, tolterodine, and others: label-specific advice may apply.
Calcium Channel Blockers: A Common, Underrated Risk
Calcium channel blockers are among the most commonly used blood pressure drugs, which makes this interaction especially relevant. In a large Ontario study published in JAMA in 2013, older adults (average age 76) taking a calcium channel blocker who were prescribed clarithromycin were compared with similar people prescribed azithromycin instead. As reported by ScienceDaily, hospitalization with acute kidney injury within 30 days occurred in 0.44% of the clarithromycin group versus 0.22% of the azithromycin group. Hospitalization for low blood pressure and death from any cause were also higher with clarithromycin. The risk was highest with nifedipine.
The absolute risks are small, but the doubling is consistent, and the study’s authors suggested either pausing the calcium channel blocker during treatment or choosing an antibiotic that does not block CYP3A4. If you take amlodipine, nifedipine, felodipine, diltiazem, or verapamil, ask your prescriber which approach suits you. Signs to watch include dizziness on standing, fainting, swollen ankles, and passing much less urine.
Mechanism B: P-glycoprotein Drugs
- Digoxin: clarithromycin can raise digoxin levels, causing nausea, visual changes (yellow-green halos), confusion, and dangerous rhythms. Levels should be checked.
- Colchicine: affected by both CYP3A4 and P-gp, which is why the interaction is so severe.
- Direct oral anticoagulants (DOACs): apixaban, rivaroxaban, edoxaban, and dabigatran levels can rise moderately. Dose changes are not always required, but bleeding risk increases, particularly in people with kidney impairment. Watch for unusual bruising, nosebleeds, blood in urine, or black stools.
Warfarin
Warfarin is not a P-gp drug, but the clarithromycin label warns of serious bleeding and large rises in INR when the two are combined. If you take warfarin, an INR check within a few days of starting the antibiotic is usually recommended.
Mechanism C: QT-Stacking Drugs
Clarithromycin lengthens the QT interval on its own. Combining it with other QT-prolonging drugs adds up the risk. The label advises avoiding clarithromycin in people taking drugs known to prolong QT, including class IA antiarrhythmics (quinidine, procainamide) and class III antiarrhythmics (amiodarone, dofetilide, sotalol). Other common QT-prolonging medicines include:
- Some antidepressants, such as citalopram at higher doses (see Celexa side effects).
- Some antipsychotics, including haloperidol, quetiapine, and ziprasidone.
- Ondansetron, domperidone, and some other anti-nausea drugs.
- Methadone.
- Other antibiotics and antifungals, such as fluoroquinolones, azithromycin, fluconazole, and ketoconazole.
- Hydroxychloroquine.
Independent databases such as CredibleMeds keep updated lists of QT-prolonging drugs. The heart side of this story, including the FDA’s long-term warning for people with coronary disease, is covered in our clarithromycin heart risks guide. For comparison, see how its cousin behaves in our azithromycin drug interactions article.
Mental Health and Sleep Medicines
Psychiatric and sleep medicines are often overlooked in antibiotic decisions, yet several are cleared by CYP3A4 or prolong QT.
| Medicine | Interaction | Typical action |
|---|---|---|
| Buspirone | Levels can rise substantially | Dose reduction or monitoring for dizziness and drowsiness |
| Trazodone | Levels rise; added QT effect | Monitor; lower dose may be needed |
| Alprazolam, triazolam, midazolam | Levels rise; prolonged sedation | Avoid triazolam/midazolam combinations or adjust |
| Zolpidem | Modest rise | Use lowest dose; avoid alcohol |
| Quetiapine, lurasidone, aripiprazole | Levels rise; quetiapine adds QT risk | Lurasidone contraindicated; quetiapine and aripiprazole doses reduced |
| Pimozide | Levels rise; QT risk | Contraindicated |
| Citalopram, escitalopram | Additive QT effect | Review dose and ECG risk |
| Lorazepam | Not cleared by CYP3A4 | Minimal interaction |
If you take anxiety medicine, our comparison of Ativan vs buspirone explains how these two drugs differ, which can help when discussing short-term adjustments with your prescriber.
Pain Medicines
- Oxycodone, hydrocodone, and fentanyl: CYP3A4 blockade raises levels, increasing drowsiness and the risk of slowed breathing. Extra caution is needed, especially with sedatives or alcohol.
- Methadone: higher levels plus additive QT prolongation. Close monitoring or an alternative antibiotic is usually advised.
- Tramadol: partly cleared by CYP3A4; levels and side effects may change.
- Acetaminophen and ibuprofen: no significant interaction.
Diabetes Medicines and Low Blood Sugar
The label warns that clarithromycin with oral diabetes medicines or insulin can cause significant hypoglycemia. Drugs mentioned include nateglinide, repaglinide, pioglitazone, and rosiglitazone, and in practice sulfonylureas such as glipizide, glyburide, and glimepiride are a frequent concern. If you have diabetes:
- Check your blood glucose more often during the course.
- Keep fast-acting sugar on hand.
- Know the signs: shakiness, sweating, hunger, confusion, irritability, or a fast heartbeat.
- Do not skip meals, especially if you are nauseated.
Mechanism D: Drugs That Change Clarithromycin Itself
| Drug | Effect on clarithromycin | What it means |
|---|---|---|
| Rifampin, rifabutin, efavirenz, nevirapine, etravirine | Speed up clarithromycin breakdown | Lower clarithromycin levels; reduced effectiveness. Rifabutin levels may also rise, causing uveitis or low white cells. |
| Carbamazepine, phenytoin, phenobarbital | Speed up breakdown | Possible reduced effect; carbamazepine levels may also rise |
| St. John’s wort | Speeds up breakdown | Possible reduced effect; avoid during the course |
| Ritonavir, atazanavir | Slow down breakdown | Higher clarithromycin levels; dose cuts needed in kidney impairment |
| Zidovudine | Clarithromycin lowers zidovudine absorption | Separate doses by at least 4 hours |
Supplements and Herbal Products
Supplements rarely appear on medication lists, yet several matter here:
- Red yeast rice: naturally contains monacolin K, which is chemically identical to lovastatin. Treat it like lovastatin and pause it during clarithromycin.
- St. John’s wort: speeds up clarithromycin breakdown, potentially reducing its effectiveness.
- Goldenseal and berberine products: may inhibit drug-metabolizing enzymes; avoid combining without advice.
- Kava and valerian: add sedation, which can compound raised levels of sedative medicines.
- High-dose potassium or magnesium supplements: not harmful here, and correcting real deficiencies can reduce QT risk, but only take them as directed.
Three Real-World Scenarios
Scenario 1: The gout patient with a chest infection
A 68-year-old takes colchicine for gout and has mild kidney impairment. He is offered clarithromycin for a bronchitis flare. Because colchicine with clarithromycin is contraindicated in kidney impairment, his prescriber chooses doxycycline instead. This is the classic case where switching the antibiotic is simpler and safer than adjusting the other drug.
Scenario 2: The H. pylori patient on simvastatin and amlodipine
A 59-year-old woman needs H. pylori treatment and takes simvastatin and amlodipine. Her gastroenterologist chooses bismuth quadruple therapy, which avoids clarithromycin entirely. Had a clarithromycin regimen been necessary, she would have paused simvastatin and been monitored for dizziness from amlodipine.
Scenario 3: The transplant patient
A kidney transplant recipient on tacrolimus develops pneumonia. Clarithromycin could raise tacrolimus to toxic levels within days, damaging the transplanted kidney. The team selects an antibiotic without CYP3A4 effects and checks tacrolimus levels anyway, because illness itself can shift drug levels.
Groups Most at Risk
- Adults over 65 on several medicines: more opportunities for interactions and more sensitivity to low blood pressure, bleeding, and QT effects.
- People with kidney or liver disease: slower clearance of both clarithromycin and the interacting drug.
- Transplant recipients: narrow safety margins for immunosuppressants.
- People with HIV: two-way interactions with antiretrovirals.
- People with heart rhythm conditions: QT stacking.
What About Everyday Medicines?
| Medicine | Concern level | Notes |
|---|---|---|
| Acetaminophen (paracetamol) | Low | Generally fine at normal doses |
| Ibuprofen, naproxen | Low | No major interaction; take with food |
| Antacids, PPIs | Low | PPIs are paired with clarithromycin in H. pylori treatment |
| Hormonal birth control | Low | Clarithromycin is not an enzyme inducer; vomiting or severe diarrhea can still reduce pill absorption. See amoxicillin and birth control for the same principle. |
| Antihistamines (cetirizine, loratadine, fexofenadine) | Low | Older antihistamines terfenadine and astemizole, now withdrawn, were the dangerous ones |
| Levothyroxine | Low | No major interaction |
| Grapefruit juice | Low to moderate | Also inhibits CYP3A4; best avoided in large amounts while taking interacting drugs |
Alcohol has no direct interaction with clarithromycin, but it can magnify sedation from drugs whose levels clarithromycin raises. See clarithromycin and alcohol.
Symptoms That May Signal an Interaction
Interactions often show up as an exaggerated version of the other drug’s side effects. Call your prescriber or pharmacist if, during or shortly after clarithromycin, you notice:
- Muscle pain, weakness, or dark urine (statins).
- Severe diarrhea, vomiting, or numbness (colchicine).
- Dizziness on standing, fainting, or ankle swelling (calcium channel blockers).
- Unusual bruising, nosebleeds, or blood in urine or stool (blood thinners).
- Shakiness, sweating, or confusion (low blood sugar from diabetes medicines).
- Extreme drowsiness or slowed breathing (sedatives, opioids). Call 911 for breathing problems.
- Palpitations or fainting (QT-prolonging combinations). Seek urgent care.
Safer Swaps Your Prescriber Might Consider
When an interaction is serious, the cleanest solution is often a different antibiotic rather than juggling doses:
- Azithromycin is a much weaker CYP3A4 inhibitor, so it avoids most of the interactions above. It still prolongs QT, so it is not a free pass for people with heart rhythm issues. See azithromycin vs clarithromycin.
- Doxycycline covers many of the same respiratory germs without CYP3A4 or QT problems. See azithromycin vs doxycycline.
- Amoxicillin or amoxicillin-clavulanate work for many sinus, ear, and chest infections, with very few interactions. See clarithromycin vs amoxicillin.
- For H. pylori, bismuth quadruple therapy avoids clarithromycin entirely. See clarithromycin for H. pylori.
Your Pharmacy Counter Script
Bring a written list of every prescription, over-the-counter medicine, vitamin, and supplement you take. Then ask:
- “Does clarithromycin interact with anything on this list?”
- “Do I need to stop my statin, and when should I restart it?”
- “Should my blood pressure, blood thinner, or diabetes medicine be adjusted?”
- “Do I need any blood tests, such as INR, kidney function, or drug levels?”
- “Is there an antibiotic with fewer interactions that would work for my infection?”
- “Which symptoms should make me call you or my doctor?”
The NHS also publishes a plain-language list of medicines to check with clarithromycin, which is a useful second reference.
Frequently Asked Questions
Can I take clarithromycin with atorvastatin?
Only with caution. The label advises keeping atorvastatin at 20 mg a day or less if the combination cannot be avoided. Many prescribers simply pause atorvastatin for the course. Report muscle pain or dark urine promptly.
How long after clarithromycin can I restart simvastatin?
Most prescribers advise restarting the day after your last clarithromycin dose. Because enzyme activity takes a little time to recover, some suggest waiting two or three days. Follow your prescriber’s advice.
Is clarithromycin safe with amlodipine?
The combination is not forbidden, but it has been linked with higher rates of low blood pressure and kidney injury in older adults. Your prescriber may pause amlodipine, monitor you closely, or choose a different antibiotic.
Does clarithromycin interact with ibuprofen or acetaminophen?
No significant interactions are known with either at normal doses. They are reasonable choices for fever or aches during treatment.
Can I take clarithromycin with blood pressure medicine?
It depends on the medicine. ACE inhibitors, ARBs, and most diuretics have no major interaction. Calcium channel blockers such as amlodipine, nifedipine, diltiazem, and verapamil need caution because of low blood pressure and kidney injury risk. Never stop a blood pressure medicine without advice.
Does clarithromycin interact with birth control pills?
Clarithromycin does not speed up hormone breakdown the way rifampin does, so it is not expected to reduce pill effectiveness. Vomiting or severe diarrhea can still interfere with absorption, in which case follow your pill’s missed-dose instructions.
Make a Medication-Pause Card
If your prescriber asks you to pause or reduce any medicine during clarithromycin, write it down on a card or phone note so nothing gets forgotten:
| Medicine | Action | Start date | Restart or return-to-normal date |
|---|---|---|---|
| Example: simvastatin 40 mg | Paused | Day 1 of clarithromycin | Day after last clarithromycin dose, or as advised |
| Example: amlodipine 10 mg | Continue; check BP daily | Day 1 | Continue as normal |
| Example: warfarin | Continue; INR check | Day 3 to 5 | Follow anticoagulation clinic advice |
Show the card to anyone who prescribes for you during this period, including urgent care or emergency staff.
The Bottom Line
Clarithromycin’s interaction list is long because it shuts down one of the body’s busiest drug-clearing pathways. The highest-stakes combinations are simvastatin, lovastatin, colchicine, ergot drugs, pimozide, and other QT-prolonging medicines. Calcium channel blockers, blood thinners, sedatives, and diabetes medicines need adjustments or monitoring. The solution is rarely complicated: a full medication list, a quick pharmacist review, and, when needed, a short statin pause or a different antibiotic. For dosing details, see our clarithromycin dosage guide.
This article is for general information. It does not list every possible interaction. Always consult your pharmacist or prescriber before combining medicines.
