drug interaction
44 interactions related to drug interaction
St. John's Wort + SSRI
St. John's Wort is pharmacologically active, not a harmless herb, and it interacts with SSRIs in two overlapping and hard-to-predict ways. The result is a combination most clinicians prefer to avoid rather than manage.
alcohol + lithium
Lithium has a narrow therapeutic window and is cleared almost entirely by the kidneys. Alcohol promotes urination and dehydration, which can reduce renal lithium clearance and push serum lithium levels higher — toward the toxic range (tremor, confusion, unsteadiness, vomiting). Alcohol also independently destabilizes mood in bipolar disorder, and its early intoxication signs can mask the early warning signs of lithium toxicity.
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.
alcohol + warfarin
Alcohol affects warfarin in two opposing directions: acute heavy drinking slows the liver's metabolism of warfarin, which can raise INR and bleeding risk, while sustained heavy drinking induces those same enzymes and can lower INR, increasing clot risk. Alcohol also impairs platelets and can damage the liver where clotting factors are made, and intoxication raises fall risk, all of which compound the bleeding hazard.
metronidazole + alcohol
Metronidazole is traditionally said to cause a disulfiram-like reaction with alcohol — flushing, nausea, and headache. Controlled human studies have not reproduced a true disulfiram reaction, so the effect appears real but uncommon and usually mild. Most product labels still advise avoiding alcohol during treatment and for a short period afterward as a precaution.
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.
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.
cranberry + warfarin
Cranberry contains flavonoids and polyphenols that may slow CYP2C9, the liver enzyme that clears the more potent S-enantiomer of warfarin. Multiple human case reports describe a rising INR and serious bleeding in patients who took up cranberry juice or supplements while stably anticoagulated, and the effect appears to depend on how much cranberry is consumed: randomized trials using a modest daily amount have not consistently reproduced it.
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.
noni juice + warfarin
Noni juice (Morinda citrifolia) products vary widely in vitamin K content, and one published case of warfarin resistance was attributed to a high-vitamin K noni preparation. Noni has also been linked to drug-induced liver injury, which can secondarily destabilize warfarin. The interaction is real but rests on case reports rather than large studies.
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.
alcohol + duloxetine
Duloxetine (Cymbalta) can occasionally cause liver injury, and its FDA label advises against prescribing it to people with substantial or chronic alcohol use or existing liver disease, because both substances stress the liver. Documented cases have generally been reversible after stopping the drug, with no clear pattern of alcohol-linked liver failure in the published case series.
alcohol + amitriptyline
Amitriptyline is a sedating tricyclic antidepressant with strong antihistaminic and anticholinergic effects. Combining it with alcohol — also a central nervous system depressant — produces additive drowsiness, impaired coordination and reaction time, and a greater risk of falls and accidents. The FDA label warns explicitly that amitriptyline may enhance the response to alcohol.
alcohol + pregabalin
Pregabalin and alcohol are both central nervous system depressants. Taken together their sedative effects add up, increasing drowsiness, dizziness, and impaired coordination, and at the serious end can cause life-threatening respiratory depression — a risk highlighted by FDA and MHRA safety warnings.
caffeine + ciprofloxacin
Ciprofloxacin inhibits the liver enzyme CYP1A2, which is the main pathway that clears caffeine. As a result, caffeine is broken down more slowly, its blood levels stay higher for longer, and its stimulant effects are amplified and prolonged while you are on the antibiotic.
smoking + clozapine
Polycyclic aromatic hydrocarbons in tobacco smoke (not nicotine) strongly induce CYP1A2, the liver enzyme that handles most clozapine metabolism, so smokers tend to have lower clozapine levels and need higher doses. The greater danger is stopping smoking: levels can climb sharply over a few days as the enzyme returns to baseline, risking sedation, seizures, and toxicity unless the dose is reviewed.
smoking + olanzapine
Polycyclic aromatic hydrocarbons in cigarette smoke induce CYP1A2, the main enzyme that breaks down olanzapine, so smokers clear the drug faster and run lower blood levels. When someone quits, levels rise over the following days to weeks and side effects can emerge on a previously stable dose. The effect is driven by combustion products, not nicotine.
smoking + theophylline
Combustion products in tobacco smoke induce the liver enzyme CYP1A2, speeding up how fast the body clears theophylline. Smokers therefore tend to need more theophylline to stay in range, and stopping smoking can reverse this within days and push levels into a toxic range unless the dose is reviewed.
smoking + propranolol
Cigarette smoking induces hepatic metabolism of propranolol (mainly via CYP1A2 and glucuronidation), increasing its clearance and lowering propranolol blood levels in smokers compared with non-smokers. Nicotine also independently raises heart rate, blood pressure, and circulating catecholamines, partly counteracting propranolol's beta-blocking effect. Both effects reverse when a person quits smoking.
smoking + caffeine
Polycyclic aromatic hydrocarbons in tobacco smoke induce CYP1A2, the main liver enzyme that breaks down caffeine, so smokers clear caffeine faster and feel it less. When you quit smoking, that fast clearance fades within a few days and your usual caffeine can build up, contributing to jitters, anxiety, palpitations, and poor sleep that can be mistaken for nicotine withdrawal.
smoking + insulin
Smoking worsens insulin resistance through nicotine-driven catecholamine release, oxidative stress, and inflammation, and slows subcutaneous insulin absorption through vasoconstriction, so people with diabetes who smoke typically need more insulin to reach the same glucose control. Quitting improves insulin sensitivity within days to weeks, so insulin doses often need to come down to avoid hypoglycemia.
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 + sertraline
CBD inhibits CYP2C19, one of several enzymes that help break down sertraline, so adding CBD can raise sertraline exposure. A single published case report describes low sodium (hyponatremia) and cognitive decline in an older intermediate-metabolizer patient who added over-the-counter CBD to long-standing sertraline. The evidence is limited to this one report, so treat it as a reason for caution and prescriber discussion rather than a strong contraindication.
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.
cbd + beta-blockers
CBD weakly inhibits CYP2D6, the liver enzyme that clears beta-blockers such as metoprolol, propranolol, and carvedilol, so in theory it could nudge their plasma levels up. CBD also has a mild blood-pressure-lowering effect of its own. Both actions point in the same direction as the beta-blocker, but the CYP2D6 effect is weak and its real-world clinical significance has not been demonstrated in humans.
chamomile tea + warfarin
Chamomile contains naturally occurring coumarin-type compounds and may slow the liver enzymes that clear warfarin, so heavy or sudden chamomile use could add to warfarin's blood-thinning effect. A published case report linked frequent chamomile tea and lotion use to a dangerously high INR and severe internal bleeding in an older woman whose warfarin had previously been stable.
salt substitute + spironolactone
Most salt substitutes replace ordinary table salt with potassium chloride, so they act as concentrated potassium supplements. Spironolactone is a potassium-sparing diuretic that reduces how much potassium the kidneys excrete. Using the two together can drive potassium high enough to cause dangerous, sometimes life-threatening heart rhythm problems (hyperkalemia).
probiotics + antifungals
Systemic antifungals (such as fluconazole, itraconazole, amphotericin B, and the echinocandins) can kill yeast-based probiotics such as Saccharomyces boulardii, blunting their benefit. Bacterial probiotics like Lactobacillus and Bifidobacterium are generally unaffected, because their cell structure differs from fungi.
cocoa + warfarin
Cocoa flavanols can modestly reduce platelet activity in people, which in theory could add to warfarin's anticoagulant effect. In practice the evidence is mechanistic only: no case reports or clinical studies show actual bleeding or a change in INR from cocoa in people taking warfarin. Keeping cocoa intake small and consistent is a sensible precaution rather than a response to a proven interaction.
chocolate + lithium
Chocolate contains caffeine, a mild diuretic that increases how much lithium the kidneys clear. Because lithium has a narrow therapeutic window, a large, sustained change in caffeine intake can nudge serum lithium levels — adding a steady caffeine habit can lower them, while abruptly stopping one can raise them. Chocolate is a relatively minor caffeine source compared with coffee or tea, so the effect matters most for heavy, consistent chocolate consumers who make a sudden change.
methotrexate + nsaids
Methotrexate is cleared almost entirely by the kidneys. NSAIDs reduce renal blood flow by blocking prostaglandins and compete with methotrexate at renal tubular transporters, both of which slow methotrexate elimination and raise its blood levels. The danger is greatest with high-dose methotrexate (cancer chemotherapy) or pre-existing kidney impairment, where the buildup can cause bone marrow suppression, mouth and gut ulceration, liver injury, and acute kidney injury. In low-dose weekly methotrexate for autoimmune disease with healthy kidneys, the interaction is usually more modest and often manageable under prescriber supervision.
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.
alcohol + sertraline
Sertraline (Zoloft) and alcohol both act on the central nervous system. Controlled studies in healthy volunteers did not show sertraline worsening alcohol's effects on thinking or coordination, but the FDA label still advises against drinking on sertraline because alcohol can deepen depression and anxiety, worsen drowsiness and sleep, and blunt the medication's benefit in people being treated for a mood disorder.
alcohol + fluoxetine
Fluoxetine (Prozac) is an SSRI antidepressant, and alcohol is a central nervous system depressant. The FDA-approved Prozac label states that alcohol use is not recommended while taking fluoxetine. Fluoxetine and its active metabolite norfluoxetine also have unusually long half-lives, so the drug stays in your system for weeks once you reach steady state — there is no simple "timing window" that avoids the interaction. Notably, a controlled human study found that alcohol did not measurably increase fluoxetine's psychomotor impairment, so the combined sedative effect is more modest than once assumed; the precaution remains sensible but is not an emergency.
alcohol + gabapentin
Gabapentin and alcohol are both central nervous system depressants. Combining them increases drowsiness, dizziness, impaired coordination, and the risk of serious, potentially life-threatening respiratory depression, especially in older adults and people with lung disease, sleep apnea, kidney impairment, or who take opioids or other sedatives.
cbd + clobazam
CBD inhibits CYP2C19, the enzyme that clears N-desmethylclobazam, the active metabolite of clobazam. Taking the two together raises N-desmethylclobazam levels substantially, increasing sedation, drowsiness, drooling, and unsteadiness. This interaction is documented in the FDA-approved Epidiolex prescribing information and in clinical studies in children with epilepsy.
salt substitute + lisinopril
Most salt substitutes replace sodium chloride with potassium chloride, making them a concentrated source of potassium. Lisinopril and other ACE inhibitors lower aldosterone and reduce the kidneys' ability to clear potassium. Used together, they can raise blood potassium to dangerous levels (hyperkalemia), especially in people with reduced kidney function, diabetes, older age, or who take other potassium-raising medicines.
caffeine + clozapine
Caffeine and clozapine are both broken down by the liver enzyme CYP1A2, and caffeine competitively inhibits it. Large changes in caffeine intake - especially starting or stacking energy drinks - can raise clozapine to toxic levels, with a documented case report of severe toxicity and multiorgan failure.
coffee + propranolol
Caffeine in coffee acutely raises heart rate and blood pressure, which can partly counteract the heart-rate and blood-pressure-lowering effects of propranolol, a non-selective beta-blocker. Propranolol does not fully block this caffeine pressor response. Older claims that propranolol slows caffeine clearance appear to be wrong: a human study found propranolol slightly speeds caffeine elimination rather than slowing it.
cbd + valproate
Taking CBD (including prescription Epidiolex and over-the-counter products) together with valproate raises the chance of liver enzyme elevations well above either drug alone, and the combination has been linked to high blood ammonia that can cause confusion or worsening seizures even when liver tests look only mildly abnormal. This pairing should be managed by the prescribing neurologist with baseline and follow-up liver testing.
caffeine + oral contraceptives
Ethinyl estradiol in combined oral contraceptives inhibits CYP1A2, the liver enzyme that clears caffeine. This slows caffeine's breakdown and prolongs its half-life, so the same cup of coffee can leave more caffeine circulating for longer and intensify jitteriness, insomnia and palpitations.
coffee + ciprofloxacin
Ciprofloxacin inhibits CYP1A2, the liver enzyme that clears caffeine, slowing caffeine metabolism so a normal amount of coffee produces higher, longer-lasting caffeine levels and stronger stimulant effects.
cbd + warfarin
CBD inhibits the liver enzymes (notably CYP2C9, and also CYP3A4) that clear warfarin, especially its more potent S-enantiomer. Adding CBD to a stable warfarin regimen can slow warfarin breakdown, raise its blood level, push the INR upward, and increase bleeding risk. A published case report described a patient who needed a meaningful warfarin dose reduction after starting CBD.
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.