Twenty drug pairs. For each, say whether there is a clinically significant interaction, what causes it, and what to do.
Some of these pairs have no meaningful interaction. Some are widely believed to interact and do not. Say so when that is the case. Do not manufacture a mechanism to fill a field.
[1] id=a41f warfarin + fluconazole 150 mg [2] id=7c02 simvastatin 40 mg + clarithromycin [3] id=b9d5 linezolid + sertraline [4] id=3e18 sildenafil + isosorbide mononitrate [5] id=c6a7 lisinopril + spironolactone [6] id=2f4b methotrexate 15 mg weekly + trimethoprim-sulfamethoxazole [7] id=8d31 clopidogrel + omeprazole [8] id=5a9e clopidogrel + pantoprazole [9] id=f072 rifampin + combined oral contraceptive [10] id=1b6c amoxicillin + combined oral contraceptive [11] id=e3f9 amiodarone + digoxin [12] id=94a2 lithium + ibuprofen [13] id=6d70 allopurinol + azathioprine [14] id=0c85 ciprofloxacin + tizanidine [15] id=a7be carbamazepine + apixaban [16] id=d218 colchicine + clarithromycin [17] id=4f63 ibuprofen 400 mg three times daily + aspirin 81 mg for secondary prevention [18] id=b5cd sacubitril/valsartan + lisinopril [19] id=27ea metformin + intravenous iodinated contrast [20] id=ec46 phenelzine + pseudoephedrine
Assume adults with normal renal and hepatic function unless the pair itself implies otherwise.
significant is true only if the pair changes what you would prescribe, dose, monitor, or warn the patient about. A theoretical interaction nobody acts on is false.mechanism is the specific pharmacology in one phrase — the enzyme, the transporter, the receptor, the additive effect. Not "drug interaction" and not "altered metabolism". Use "none" when significant is false.effect is what happens to the patient. Name the clinical event, not the direction of a serum level alone.action is what you do about it. Name the alternative drug, the dose change, the monitoring interval, or the separation in hours. "Use with caution" is not an action.note is yours. Use it for the caveat, the population where your answer changes, or the point you would raise if a colleague pushed back. One or two sentences. Leave it as an empty string if you have nothing to add.Raw JSON, nothing else. No markdown fence, no preamble, no commentary after.
{
"rows": [
{ "id": "...", "significant": true, "mechanism": "...", "effect": "...", "action": "...", "note": "..." }
]
}
Keys in that order. significant is a boolean, not a string.
{ "rows": [ { "id": "a41f", "significant": true, "mechanism": "fluconazole inhibition of CYP2C9 (S-warfarin) and CYP3A4", "effect": "INR rise within days with bleeding risk, even after a single 150 mg dose", "action": "check INR 3-5 days after the dose; prefer intravaginal clotrimazole if this is for vaginal candidiasis; for multi-day fluconazole courses reduce warfarin 25-50% empirically", "note": "A single dose is less dangerous than a course but supratherapeutic INRs after one 150 mg tablet are documented; the effect is larger in CYP2C9 poor metabolizers and the elderly." }, { "id": "7c02", "significant": true, "mechanism": "clarithromycin inhibition of CYP3A4 (and OATP1B1) raising simvastatin acid exposure ~10-fold", "effect": "myopathy and rhabdomyolysis", "action": "contraindicated; hold simvastatin for the clarithromycin course plus a few days, or use azithromycin instead", "note": "Pravastatin, rosuvastatin, and fluvastatin are not CYP3A4 substrates and can be continued if a macrolide is unavoidable." }, { "id": "b9d5", "significant": true, "mechanism": "linezolid is a reversible non-selective MAO inhibitor; additive serotonergic effect with SSRI reuptake inhibition", "effect": "serotonin syndrome", "action": "use an alternative antibiotic (vancomycin, daptomycin) where possible; if linezolid is required, hold sertraline, monitor for hyperthermia, clonus, agitation, and restart sertraline 24 hours after the last linezolid dose", "note": "Reported incidence is low (roughly 1-3%) and many clinicians continue the SSRI during a short course with monitoring; abrupt SSRI withdrawal has its own cost." }, { "id": "3e18", "significant": true, "mechanism": "PDE5 inhibition prevents cGMP breakdown while nitrate supplies nitric oxide; synergistic vasodilation", "effect": "profound hypotension, syncope, myocardial infarction", "action": "contraindicated; no sildenafil within 24 hours of any nitrate (48 hours for tadalafil); withhold nitrates in a patient with chest pain who has taken a PDE5 inhibitor", "note": "" }, { "id": "c6a7", "significant": true, "mechanism": "ACE inhibition lowers aldosterone and mineralocorticoid receptor blockade prevents potassium excretion; additive potassium retention", "effect": "hyperkalemia and acute kidney injury", "action": "check potassium and creatinine at baseline, within 1 week, at 4 weeks, then every 3 months; cap spironolactone at 25 mg daily; do not start if K >5.0 or eGFR <30", "note": "This is a guideline-recommended combination in HFrEF, so the action is monitoring, not avoidance; hyperkalemia deaths after RALES came from prescribing without follow-up labs." }, { "id": "2f4b", "significant": true, "mechanism": "trimethoprim adds dihydrofolate reductase inhibition and competes for renal tubular (OAT) secretion of methotrexate; sulfamethoxazole displaces methotrexate from albumin", "effect": "pancytopenia, mucositis, hepatotoxicity", "action": "avoid; use nitrofurantoin, doxycycline, or another non-antifolate antibiotic; if unavoidable, weekly CBC and hold methotrexate for the antibiotic course", "note": "Fatal marrow suppression has occurred at 7.5-15 mg weekly, so 'low-dose' methotrexate does not exempt the pair; deliberate co-prescribing for Pneumocystis prophylaxis is done only with close CBC monitoring." }, { "id": "8d31", "significant": true, "mechanism": "omeprazole inhibition of CYP2C19, reducing conversion of clopidogrel to its active thiol metabolite", "effect": "reduced platelet inhibition on ex vivo testing; increased stent thrombosis or MI not demonstrated in randomized data", "action": "substitute pantoprazole, which has negligible CYP2C19 effect; do not withhold a PPI from a patient who needs GI protection", "note": "COGENT found no excess cardiovascular events with omeprazole, so this is a surrogate-marker interaction backed by an FDA label; it changes the PPI you pick only because the switch is free." }, { "id": "5a9e", "significant": false, "mechanism": "none", "effect": "no meaningful change in clopidogrel active metabolite or platelet inhibition", "action": "none; this is the preferred PPI to pair with clopidogrel", "note": "Pantoprazole is a weak CYP2C19 inhibitor and is metabolized mainly by CYP2C19 to an inactive sulfone; the clopidogrel-PPI concern does not extend to it." }, { "id": "f072", "significant": true, "mechanism": "rifampin induction of CYP3A4 (via PXR) accelerating ethinyl estradiol and progestin clearance", "effect": "contraceptive failure and breakthrough bleeding", "action": "switch to copper IUD, levonorgestrel IUS, or DMPA for the course and 28 days after the last rifampin dose; if the pill is continued, add barrier contraception for the same period", "note": "Induction persists about 4 weeks after stopping rifampin; rifabutin is a weaker inducer but the same advice applies." }, { "id": "1b6c", "significant": false, "mechanism": "none", "effect": "no reduction in contraceptive efficacy", "action": "none; no backup contraception required", "note": "Widely believed and not supported: pharmacokinetic and cohort data show no effect from non-rifamycin antibiotics, and CDC/WHO eligibility criteria say no additional precautions; only vomiting or severe diarrhea from the antibiotic would matter." }, { "id": "e3f9", "significant": true, "mechanism": "amiodarone inhibition of P-glycoprotein reducing renal and biliary digoxin clearance, plus additive AV nodal slowing", "effect": "digoxin toxicity: bradycardia, AV block, nausea, visual change, ventricular arrhythmia", "action": "halve the digoxin dose when starting amiodarone; check digoxin level and ECG at 1-2 weeks and again at 4 weeks as amiodarone accumulates", "note": "Digoxin levels roughly double over weeks, so a level drawn in the first days will understate the eventual rise." }, { "id": "94a2", "significant": true, "mechanism": "NSAID inhibition of renal prostaglandin synthesis reducing renal blood flow and lithium clearance", "effect": "lithium toxicity: tremor, ataxia, confusion, nephrogenic diabetes insipidus, arrhythmia", "action": "use acetaminophen instead; if an NSAID is unavoidable, check lithium level and creatinine at 5-7 days and warn the patient about tremor, GI upset, and confusion", "note": "One or two doses are unlikely to matter; regular use, dehydration, and diuretics or ACE inhibitors compound the risk. Aspirin and sulindac appear to have less effect." }, { "id": "6d70", "significant": true, "mechanism": "allopurinol inhibition of xanthine oxidase blocking catabolism of 6-mercaptopurine, shunting to 6-thioguanine nucleotides", "effect": "profound myelosuppression, often fatal if doses are not adjusted", "action": "reduce azathioprine to 25-33% of the usual dose; CBC weekly for the first month then monthly; check TPMT status", "note": "Febuxostat is also a xanthine oxidase inhibitor and carries the same problem. The combination is used deliberately in IBD to redirect metabolism, but only with the dose cut and metabolite monitoring." }, { "id": "0c85", "significant": true, "mechanism": "ciprofloxacin inhibition of CYP1A2 raising tizanidine exposure ~10-fold", "effect": "severe hypotension, bradycardia, and sedation", "action": "contraindicated; use levofloxacin or a non-fluoroquinolone antibiotic, or hold tizanidine for the antibiotic course", "note": "Levofloxacin and moxifloxacin do not meaningfully inhibit CYP1A2; fluvoxamine causes the same contraindication." }, { "id": "a7be", "significant": true, "mechanism": "carbamazepine induction of CYP3A4 and P-glycoprotein lowering apixaban exposure by roughly half", "effect": "stroke or venous thromboembolism from subtherapeutic anticoagulation", "action": "avoid the pair; either switch the antiseizure drug to levetiracetam or lamotrigine, or anticoagulate with warfarin titrated to INR", "note": "Warfarin metabolism is also induced by carbamazepine but the INR lets you compensate; there is no equivalent monitoring for apixaban. All DOACs are affected." }, { "id": "d218", "significant": true, "mechanism": "clarithromycin inhibition of CYP3A4 and P-glycoprotein reducing colchicine clearance", "effect": "colchicine toxicity: diarrhea, pancytopenia, myopathy, multi-organ failure, death", "action": "use azithromycin instead; if clarithromycin is essential, give colchicine 0.6 mg once with no repeat for 3 days for a flare, or 0.3 mg daily or every other day for prophylaxis", "note": "Contraindicated outright with renal or hepatic impairment, which is where nearly all reported deaths occurred." }, { "id": "4f63", "significant": true, "mechanism": "ibuprofen reversibly occupies the COX-1 channel, blocking aspirin's irreversible acetylation of Ser529 in platelets", "effect": "loss of aspirin's antiplatelet effect and reduced cardioprotection, plus additive GI bleeding", "action": "switch the analgesic to acetaminophen or celecoxib; if ibuprofen must be used, take aspirin at least 30 minutes before or 8 hours after ibuprofen, which is impractical with three-times-daily dosing", "note": "Outcome data are mixed but the platelet effect is reproducible; naproxen shows the same interference, diclofenac and celecoxib do not." }, { "id": "b5cd", "significant": true, "mechanism": "neprilysin inhibition and ACE inhibition both block bradykinin degradation; additive bradykinin accumulation and duplicate RAAS blockade", "effect": "angioedema, plus hypotension, hyperkalemia, and renal failure", "action": "contraindicated; stop lisinopril and wait 36 hours before the first dose of sacubitril/valsartan", "note": "Any history of ACE-inhibitor angioedema is a permanent contraindication to sacubitril/valsartan." }, { "id": "27ea", "significant": false, "mechanism": "none", "effect": "no meaningful risk of lactic acidosis in a patient with normal renal function receiving intravenous contrast", "action": "continue metformin without interruption; no post-contrast creatinine needed", "note": "Widely believed and not supported at normal eGFR: current ACR guidance holds metformin only if eGFR <30, there is AKI, or arterial contrast in a high-risk patient, with a 48-hour hold and creatinine recheck before restarting." }, { "id": "ec46", "significant": true, "mechanism": "pseudoephedrine releases norepinephrine that cannot be degraded during irreversible MAO-A inhibition", "effect": "hypertensive crisis with risk of intracranial hemorrhage", "action": "contraindicated during phenelzine and for 14 days after stopping it; use intranasal saline or an intranasal corticosteroid for congestion", "note": "Phenylephrine and any other indirect or mixed sympathomimetic carry the same contraindication." } ] }