cyp3a4
56 interactions related to cyp3a4
seville orange + red yeast rice
Seville orange contains furanocoumarins that inhibit intestinal CYP3A4, the enzyme that clears the monacolin K in red yeast rice. Because monacolin K is chemically identical to the statin lovastatin and depends on CYP3A4 for its first-pass breakdown, blocking that enzyme raises systemic exposure to the active statin, increasing the risk of muscle-related side effects such as myopathy and, rarely, rhabdomyolysis.
st. john's wort + red yeast rice
St. John's wort is a strong inducer of the CYP3A4 enzyme system that clears the statin-like compound (monacolin K, chemically identical to lovastatin) in red yeast rice. Taking them together speeds up how the body breaks down that compound, lowering its levels and weakening red yeast rice's cholesterol-lowering effect. The concern here is loss of benefit rather than toxicity, and the direction is the opposite of CYP3A4-inhibitor interactions, so it does not raise muscle-injury risk.
pomelo + red yeast rice
Pomelo, like grapefruit, contains furanocoumarins that inhibit the intestinal CYP3A4 enzyme. Red yeast rice's active constituent, monacolin K, is chemically identical to the statin lovastatin, which depends on CYP3A4 for its breakdown. When pomelo blocks that enzyme, more of the monacolin K reaches the bloodstream, amplifying the dose-dependent statin-type risks of muscle injury and, rarely, liver enzyme elevation. Because furanocoumarin inhibition can persist for days, the effect is not reliably avoided by taking the two at different times of day.
clarithromycin + red yeast rice
Clarithromycin is a strong CYP3A4 inhibitor. Red yeast rice's active compound, monacolin K, is chemically identical to the statin lovastatin and is cleared mainly by CYP3A4. Combining them slows clearance of the statin-like compound and raises its blood levels, increasing the risk of muscle injury and, rarely, rhabdomyolysis.
grapefruit + red yeast rice
Grapefruit inhibits intestinal CYP3A4, the enzyme that clears red yeast rice's active constituent monacolin K (the same molecule as the statin lovastatin). Blocking this enzyme lets more monacolin K reach the bloodstream, raising its cholesterol-enzyme-blocking activity and the associated risk of muscle-related side effects. This is a food-drug interaction driven by the grapefruit inhibitor, and because some unregulated red yeast rice products carry near-prescription statin content, the risk can be meaningful.
digoxin + st. john's wort
St. John's wort revs up a gut transporter that digoxin depends on for absorption, so combining them quietly drains digoxin from the bloodstream. Because digoxin has so little room to spare, that drop can leave the drug too weak to control your heart.
apixaban + st. john's wort
St. John's wort strongly induces both CYP3A4 (apixaban's main metabolizing enzyme) and P-glycoprotein (its efflux transporter). Taken together, it speeds apixaban's breakdown and clearance, lowering blood levels and weakening clot protection, which raises the risk of stroke or thromboembolism.
pravastatin + grapefruit
Unlike simvastatin, lovastatin, and atorvastatin, pravastatin is not significantly broken down by the gut enzyme CYP3A4 that grapefruit blocks. Controlled pharmacokinetic studies show grapefruit juice does not meaningfully change pravastatin levels, so grapefruit in normal dietary amounts is fine with this statin.
carvedilol + st. john's wort
Carvedilol is partly broken down by liver enzymes (including CYP2C9 and CYP3A4) and is also a P-glycoprotein substrate. St. John's Wort induces several of these enzymes and P-glycoprotein, which can speed carvedilol clearance and lower its blood levels, potentially weakening its blood-pressure and heart-failure effects. The interaction is mechanism-based and extrapolated from St. John's Wort's effect on similar drugs; no direct human study of this specific pair has been published.
verapamil + st. john's wort
St. John's wort is a potent inducer of intestinal CYP3A4 and P-glycoprotein, the same enzymes that break down verapamil before it reaches the bloodstream. Taking the two together sharply lowers verapamil's systemic exposure and can erase its therapeutic effect on blood pressure, heart rhythm, or migraine prevention.
lovastatin + grapefruit
Grapefruit blocks the intestinal enzyme CYP3A4 that normally limits how much lovastatin reaches your bloodstream. With that enzyme suppressed, lovastatin levels can rise sharply, raising the risk of muscle injury and, rarely, rhabdomyolysis. Spacing the timing does not help because the effect lasts for days.
sertraline + st. john's wort
Sertraline is an SSRI that blocks serotonin reuptake, and St. John's wort independently raises central serotonin through constituents such as hyperforin and hypericin. Combining them can trigger serotonin syndrome, a potentially life-threatening reaction marked by altered mental status, autonomic instability, and neuromuscular hyperactivity. St. John's wort also induces CYP3A4 and CYP2C19, which can lower sertraline levels and undermine treatment.
cyclosporine + st. john's wort
St. John's wort is a potent inducer of CYP3A4 and P-glycoprotein, the enzyme and transporter that clear cyclosporine. Taking the two together markedly lowers cyclosporine blood levels, which can render the drug subtherapeutic. This has caused documented acute organ rejection in transplant recipients, making the combination a contraindication.
grapefruit + sildenafil
Sildenafil is broken down mainly by the gut and liver enzyme CYP3A4. Grapefruit juice contains furanocoumarins that block intestinal CYP3A4, modestly raising sildenafil exposure and delaying its peak. This can amplify the headache, flushing, dizziness, and transient blood-pressure drop that are typical of PDE5 inhibitors.
tramadol + st. john's wort
Tramadol inhibits serotonin and norepinephrine reuptake, and St. John's Wort increases central serotonergic activity, so combining them can add together and raise the risk of serotonin syndrome. St. John's Wort also induces CYP3A4 and CYP2B6, enzymes involved in tramadol metabolism, which may lower levels of tramadol's active M1 metabolite and weaken pain relief.
tacrolimus + grapefruit
Grapefruit furanocoumarins irreversibly inhibit intestinal CYP3A4, the enzyme that limits how much tacrolimus reaches the bloodstream. This can raise tacrolimus blood levels enough to cause kidney and nervous-system toxicity. Because the enzyme inhibition lasts for days, separating dose timing does not prevent it.
oxycodone + st. john's wort
St. John's Wort strongly induces CYP3A4, the main enzyme that clears oxycodone. In a controlled trial, taking St. John's Wort for about two weeks markedly lowered oxycodone blood levels and weakened its pain-relieving effect, so combining the two can leave pain poorly controlled.
oral contraceptives + st. john's wort
St. John's Wort induces CYP3A4 and P-glycoprotein, increasing the clearance of contraceptive hormones and reducing the effectiveness of hormonal contraceptives.
ketoconazole + st. john's wort
St. John's Wort induces CYP3A4 and P-glycoprotein through PXR activation. Because oral ketoconazole is cleared by CYP3A4, regular St. John's Wort use can speed its breakdown, lower antifungal blood levels, and risk reduced effectiveness. The effect is established by mechanism and by analogy with other azole antifungals; topical ketoconazole is not a practical concern.
fluconazole + grapefruit
Fluconazole is a moderate inhibitor of the liver enzyme CYP3A4, and grapefruit irreversibly inhibits intestinal CYP3A4. Their effects overlap on the same enzyme. On their own the pair rarely causes a problem, but together they can further slow the clearance of a third medication that also depends on CYP3A4, allowing its blood levels to rise.
atorvastatin + vitamin d
Vitamin D's active metabolite (calcitriol) can mildly induce CYP3A4, the liver enzyme that breaks down atorvastatin, which can lower atorvastatin blood levels. Despite this, the cholesterol-lowering effect appears largely preserved, so the combination is generally fine. Strip precise dose targets and review high-dose vitamin D regimens with your doctor or pharmacist.
simvastatin + berberine
Simvastatin is activated and cleared by the CYP3A4 enzyme. A human study found that repeated berberine inhibits CYP3A4, which could raise simvastatin levels and increase the risk of muscle-related side effects. Some animal data suggest berberine can also induce CYP3A4 over time, so the net effect on statin exposure is hard to predict. There are no published human case reports of myopathy from this specific combination, so the concern is mechanistic and moderate.
atorvastatin + st. john's wort
St. John's wort induces CYP3A4, the enzyme that metabolizes atorvastatin, lowering statin exposure and weakening cholesterol-lowering efficacy over time.
simvastatin + st. john's wort
St. John's wort induces the CYP3A4 enzyme and the P-glycoprotein transporter that simvastatin depends on, sharply increasing the drug's first-pass breakdown. In a controlled crossover study of healthy volunteers, two weeks of St. John's wort substantially lowered the amount of active simvastatin reaching the bloodstream, weakening its cholesterol-lowering effect.
amlodipine + grapefruit
Amlodipine is a CYP3A4 substrate, but unlike other dihydropyridine calcium channel blockers such as felodipine and nisoldipine, its high oral bioavailability and slow elimination mean grapefruit juice does not meaningfully alter its pharmacokinetics in controlled trials. Some product labels and consumer references still list a theoretical interaction, but the clinical signal at ordinary dietary intakes is small to negligible.
diltiazem + grapefruit
Grapefruit inhibits intestinal CYP3A4, modestly and unpredictably increasing systemic exposure to diltiazem.
grapefruit + carbamazepine
Grapefruit juice inhibits the intestinal CYP3A4 enzyme that performs first-pass metabolism of carbamazepine, allowing more of each oral dose to reach the bloodstream. A human study in epilepsy patients found grapefruit juice raised carbamazepine blood levels, which matters because carbamazepine has a narrow safety margin.
pomelo + tacrolimus
Pomelo contains furanocoumarins that inhibit intestinal CYP3A4 and P-glycoprotein, the systems that limit how much tacrolimus is absorbed. A documented case in a renal transplant patient showed pomelo consumption raised tacrolimus blood levels, and tacrolimus has a narrow therapeutic window where small swings can cause kidney or nervous-system toxicity, or under-immunosuppression and rejection.
grapefruit + methadone
Grapefruit inhibits intestinal CYP3A4, an enzyme that partly clears methadone, which can raise methadone blood levels. The effect is usually modest in stable patients but can become clinically significant with sustained heavy intake.
grapefruit + oxycodone
Oxycodone is broken down mainly by the intestinal enzyme CYP3A4. Grapefruit juice blocks that enzyme, so more active oxycodone reaches the bloodstream and stays there longer, and metabolism shifts toward the more potent metabolite oxymorphone. A controlled study in healthy volunteers confirmed grapefruit juice meaningfully raises oxycodone exposure, increasing the risk of excessive sedation and slowed breathing.
seville orange + atorvastatin
Seville (bitter) orange contains the same furanocoumarins as grapefruit, including bergamottin and 6',7'-dihydroxybergamottin, which inactivate intestinal CYP3A4. A randomized crossover study showed Seville orange juice raised levels of the CYP3A4 drug felodipine to a degree comparable with grapefruit juice, while ordinary sweet orange juice had no effect. Because atorvastatin is metabolised by the same CYP3A4 pathway, Seville orange can raise atorvastatin levels and increase the risk of statin-related muscle injury.
seville orange + cyclosporine
Seville orange (bitter orange, Citrus aurantium) contains furanocoumarins that inhibit intestinal CYP3A4, the enzyme that breaks down cyclosporine in the gut wall. Unlike grapefruit, however, a controlled human study found that Seville orange juice did not meaningfully raise cyclosporine blood levels, because cyclosporine absorption also depends on intestinal P-glycoprotein, which Seville orange spares. Most transplant teams still advise avoiding bitter orange products as a precaution given variable furanocoumarin content and the high stakes of altered immunosuppressant levels.
blood orange + simvastatin
Blood orange (Citrus sinensis var.) is a sweet orange and does not contain the furanocoumarins (such as bergamottin and 6',7'-dihydroxybergamottin) that drive the grapefruit-statin interaction. Reviews of citrus furanocoumarin content place blood orange among the sweet oranges that are essentially free of clinically significant CYP3A4-inhibiting compounds, so it is not expected to meaningfully affect simvastatin levels.
cranberry + tacrolimus
The only human report on cranberry and tacrolimus showed tacrolimus levels falling sharply, not rising; lab studies predict the opposite, so the true direction is genuinely unpredictable. Because tacrolimus has a very narrow therapeutic window, any change in cranberry intake deserves a trough check.
pomegranate + statins
Pomegranate inhibits the drug-metabolizing enzyme CYP3A4 in laboratory and animal studies, raising a theoretical concern that it could increase blood levels of CYP3A4-dependent statins such as simvastatin, atorvastatin, and lovastatin. However, controlled human studies - including ones using simvastatin and a sensitive CYP3A4 probe drug - did not find a meaningful effect, so pomegranate should not be treated like grapefruit. Concentrated pomegranate extract supplements warrant more caution than the whole fruit.
amiodarone + grapefruit
Grapefruit and grapefruit juice inhibit intestinal CYP3A4, the enzyme that metabolizes oral amiodarone. This raises amiodarone blood levels and largely shuts down production of its active metabolite, N-desethylamiodarone. The FDA-approved Pacerone label explicitly states grapefruit juice should not be consumed during oral amiodarone treatment.
venlafaxine + st. john's wort
Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI). St. John's wort independently inhibits serotonin (and to a lesser extent norepinephrine and dopamine) reuptake. Combining them can drive synaptic serotonin higher and trigger serotonin syndrome, and St. John's wort can also reduce venlafaxine exposure by inducing drug-metabolizing enzymes such as CYP3A4.
cbd + tacrolimus
CBD inhibits CYP3A4, CYP3A5, and P-glycoprotein, the main pathways that clear tacrolimus. Case reports and a controlled pharmacokinetic trial show that adding CBD raises tacrolimus blood levels substantially, risking nephrotoxicity, neurotoxicity, and over-immunosuppression in transplant recipients, while stopping CBD abruptly can let levels crash and risk rejection.
cbd + simvastatin
Simvastatin is cleared mainly by the liver enzyme CYP3A4, and CBD inhibits that same enzyme. Combining them is expected to raise simvastatin exposure, which could increase the risk of muscle pain and, rarely, more serious muscle injury. This is a predicted, mechanism-based interaction rather than one confirmed by a direct human study.
grapefruit + lurasidone
Lurasidone is metabolized almost entirely by the CYP3A4 enzyme, which makes it highly sensitive to CYP3A4 inhibitors. The FDA-approved Latuda prescribing information states that grapefruit and grapefruit juice should be avoided in patients taking lurasidone, because they inhibit CYP3A4 and can raise lurasidone concentrations.
phenytoin + vitamin d
Phenytoin induces the liver enzymes that break down vitamin D, accelerating clearance of 25-hydroxyvitamin D and lowering circulating levels over time. The downstream result can be reduced calcium absorption, a compensatory rise in parathyroid hormone, and an increased risk of softened bones (osteomalacia) and fractures with long-term use.
grapefruit + quetiapine
Quetiapine is metabolized primarily by CYP3A4. Grapefruit juice irreversibly inhibits intestinal CYP3A4 and can substantially increase quetiapine plasma concentrations. A published case report describes quetiapine toxicity in a young woman who consumed a large volume of grapefruit juice over a single day while on a stable dose, with sedation, low blood pressure, and ECG changes that resolved once the juice was stopped.
bergamot + statins
Bergamot orange (Citrus bergamia) is the source of bergamottin, the prototype furanocoumarin that inactivates CYP3A4. Bergamot juice and concentrated bergamot polyphenol supplements (often marketed for cholesterol) could in theory raise levels of CYP3A4-metabolized statins (simvastatin, atorvastatin, lovastatin). The mechanism is well established in the lab and in animals, but no direct human pharmacokinetic studies of bergamot with statins exist, so the real-world magnitude is uncertain.
carbamazepine + vitamin d
Carbamazepine activates the pregnane X receptor and induces the liver enzymes (including CYP3A4 and CYP24A1) that break down vitamin D, accelerating the clearance of 25-hydroxyvitamin D into inactive metabolites. A meta-analysis and observational studies consistently show lower 25(OH)D in long-term carbamazepine users, along with a secondary-hyperparathyroidism pattern and reduced bone density that raises fracture risk over years of therapy.
omeprazole + st. john's wort
St. John's wort induces the liver enzymes CYP3A4 and CYP2C19 that break down omeprazole. Taking the two together speeds up omeprazole clearance, lowers its blood levels, and can weaken its acid-suppressing effect — potentially undermining treatment of GERD, ulcers, or H. pylori eradication.
cyclosporine + grapefruit
Grapefruit contains furanocoumarins that irreversibly inhibit intestinal CYP3A4, the enzyme that normally breaks down cyclosporine before it is absorbed. This meaningfully raises cyclosporine blood levels and, because cyclosporine has a narrow safety margin, increases the risk of kidney injury, high blood pressure, and neurological side effects. The effect persists for about a day or longer after a single serving.
pomegranate + warfarin
Pomegranate contains punicalagins and other polyphenols that inhibit the liver enzymes CYP2C9 and CYP3A4 in laboratory and animal studies, which would slow warfarin metabolism. Case reports describe both a raised INR after heavy or newly started pomegranate juice intake and a falling INR after stopping a habitual juice habit. The effect appears to be genuine but infrequent, and consistency of intake matters more than total avoidance.
escitalopram + st. john's wort
Escitalopram is a selective SSRI cleared mainly by CYP2C19 and CYP3A4. St. John's wort independently raises serotonin tone and is a strong inducer of those same enzymes and P-glycoprotein. Taken together, the combination can add to serotonergic effects and, through enzyme induction, lower escitalopram levels and blunt its antidepressant effect. Documented serotonin syndrome cases with St. John's wort involve other SSRIs rather than escitalopram specifically, so the combination is best avoided rather than treated as a guaranteed emergency.
carbamazepine + st. john's wort
Both carbamazepine and St. John's Wort induce CYP3A4, the liver enzyme that primarily breaks carbamazepine down. The combined effect is hard to predict: carbamazepine already induces its own metabolism, so adding the herb may lower exposure most before that self-induction is fully established. The bigger danger comes at transitions — especially stopping St. John's Wort while still on carbamazepine, when the loss of enzyme induction can let carbamazepine levels climb toward toxicity.
tacrolimus + st. john's wort
St. John's wort induces the CYP3A4 enzyme and the P-glycoprotein transporter, which speeds up clearance of tacrolimus and lowers its blood levels, raising the risk of transplant rejection. Stopping the herb after the body has adjusted can let tacrolimus levels rebound, which has been linked to kidney toxicity.
pomelo + simvastatin
Pomelo (Citrus maxima) contains furanocoumarins that inhibit intestinal CYP3A4, the enzyme that breaks down simvastatin during first-pass absorption. With that enzyme suppressed, more simvastatin reaches the bloodstream, raising the risk of muscle-related side effects. This is the same mechanism behind the well-established grapefruit-simvastatin interaction, since pomelo is the parent species of grapefruit and shares its furanocoumarins.
thc + benzodiazepines
THC (the main psychoactive compound in cannabis) and benzodiazepines both depress the central nervous system, so combining them adds up to stronger sedation, impaired coordination, memory problems, and slowed breathing. Cannabinoids, especially CBD, can also inhibit the liver enzyme CYP3A4 that clears several benzodiazepines, raising and prolonging their levels.
grapefruit + sirolimus
Sirolimus is a CYP3A4 and P-glycoprotein substrate with a narrow therapeutic window and high patient-to-patient variability. The FDA-approved Rapamune label states that grapefruit juice inhibits the CYP3A4-mediated metabolism of sirolimus and must not be taken with, or used to dilute, the drug, because unpredictable rises in blood levels can cause toxicity and threaten the transplanted organ.
black pepper + propranolol
Piperine, the active alkaloid in black pepper, can inhibit intestinal P-glycoprotein and several liver enzymes that normally limit how much propranolol reaches the bloodstream. A small human study found that concentrated piperine raised propranolol's blood levels, so a stable dose may behave like a somewhat higher one, slightly amplifying its blood-pressure and heart-rate effects. Culinary pepper is not the concern; concentrated piperine supplements are.
atorvastatin + berberine
In human trials, adding berberine to a statin did not raise muscle or liver side effects, and the two are sometimes studied together for cholesterol. The earlier claim that berberine meaningfully raises atorvastatin levels and risk is not supported by human evidence.
grapefruit + buspirone
Grapefruit irreversibly inhibits intestinal CYP3A4, the enzyme that destroys most of an oral buspirone dose before it reaches the bloodstream. In a controlled human study, grapefruit juice substantially raised buspirone blood levels, markedly amplifying drowsiness, dizziness, and lightheadedness.