Run Detail

{ "rows": [ { "id": "a41f", "significant": true, "mechanism": "CYP2C9 inhibition of S-warfarin clearance (plus CYP3A4/2C19 on R-warfarin)", "effect": "Supratherapeutic INR and major bleeding, sometimes after a single 150 mg dose", "action": "Prefer a topical azole (clotrimazole) for vaginal candidiasis; if fluconazole given, check INR 3-5 days after the dose; for multi-day courses cut warfarin dose empirically 20-30% and recheck INR weekly until off", "numbers": ["INR check 3-5 days after fluconazole", "warfarin dose reduction 20-30% for multi-day courses", "weekly INR while on fluconazole"], "note": "Single 150 mg dose is often tolerated with monitoring alone; the inhibition is dose-dependent and lasts several days after fluconazole stops because of its long half-life." }, { "id": "7c02", "significant": true, "mechanism": "CYP3A4 (and OATP1B1) inhibition raising simvastatin acid exposure roughly 10-fold", "effect": "Myopathy and rhabdomyolysis with acute kidney injury", "action": "Do not co-prescribe; switch to azithromycin or doxycycline, or hold simvastatin for the full clarithromycin course and resume 24-48 h after the last dose", "numbers": ["hold simvastatin for full antibiotic course", "resume simvastatin 24-48 h after last clarithromycin dose"], "note": "Same rule applies to lovastatin; atorvastatin is a lesser but real concern; pravastatin, rosuvastatin and fluvastatin are not CYP3A4 substrates and can continue." }, { "id": "b9d5", "significant": true, "mechanism": "Linezolid is a reversible non-selective MAO inhibitor; additive serotonergic activity with SSRI", "effect": "Serotonin syndrome (hyperthermia, clonus, agitation, autonomic instability)", "action": "Choose a non-MAOI antibiotic (vancomycin, daptomycin) where possible; if elective, stop sertraline 2 weeks before linezolid; if linezolid is urgent, continue sertraline and monitor vitals and neuromuscular signs for 24-72 h and for 2 weeks after linezolid stops", "numbers": ["2-week sertraline washout before elective linezolid", "monitor 24-72 h after starting linezolid", "monitor 2 weeks after stopping linezolid"], "note": "Reported incidence is low (roughly 1-3%) and many clinicians co-administer with monitoring; fluoxetine needs a 5-week washout rather than 2." }, { "id": "3e18", "significant": true, "mechanism": "PDE5 inhibition amplifies nitrate-driven cGMP vasodilation", "effect": "Profound hypotension, syncope, myocardial ischaemia", "action": "Contraindicated; do not prescribe together; if a patient on sildenafil develops chest pain, withhold nitrates for 24 h after the last sildenafil dose (48 h for tadalafil) and treat with non-nitrate agents", "numbers": ["no nitrate within 24 h of sildenafil", "no nitrate within 48 h of tadalafil"], "note": "Applies to sublingual GTN as much as scheduled isosorbide; ask every angina patient about PDE5 inhibitor use before giving nitrates." }, { "id": "c6a7", "significant": true, "mechanism": "ACE inhibition suppresses aldosterone plus direct mineralocorticoid receptor blockade reduces renal potassium excretion", "effect": "Hyperkalaemia and acute kidney injury", "action": "Combination is standard in HFrEF but needs monitoring: start spironolactone 12.5-25 mg daily, check K+ and creatinine at baseline, 3 days, 1 week, then monthly for 3 months; do not start if K+ >5.0 mmol/L or eGFR <30; hold if K+ >5.5", "numbers": ["spironolactone 12.5-25 mg daily", "K+ and creatinine at 3 days and 1 week, then monthly for 3 months", "do not start if K+ >5.0 mmol/L", "do not start if eGFR <30 mL/min", "hold if K+ >5.5 mmol/L"], "note": "Risk climbs sharply with diabetes, age, dehydration, added NSAIDs or potassium supplements (RALES real-world hyperkalaemia admissions); stop potassium supplements when spironolactone is added." }, { "id": "2f4b", "significant": true, "mechanism": "Additive dihydrofolate reductase inhibition by trimethoprim plus reduced renal tubular secretion of methotrexate (OAT/competition) and protein-binding displacement by sulfamethoxazole", "effect": "Pancytopenia, mucositis, sepsis and death, even with low-dose weekly methotrexate", "action": "Avoid; use an alternative antibiotic (nitrofurantoin, cephalexin, doxycycline depending on indication); if unavoidable, ensure folic acid is prescribed and check CBC and creatinine within 5-7 days", "numbers": ["CBC and creatinine within 5-7 days if unavoidable"], "note": "Fatalities are reported with 'low dose' methotrexate; risk is highest in the elderly and with any renal impairment. Dapsone or atovaquone are alternatives for PJP prophylaxis if that is the indication." }, { "id": "8d31", "significant": true, "mechanism": "CYP2C19 inhibition reduces conversion of clopidogrel to its active thiol metabolite", "effect": "Reduced platelet inhibition with possible increase in stent thrombosis and myocardial infarction", "action": "Switch omeprazole (or esomeprazole) to pantoprazole; famotidine if an H2 blocker suffices; do not rely on dose separation because CYP2C19 inhibition persists across the dosing interval", "numbers": [], "note": "Pharmacodynamic effect is consistent but hard clinical outcome data are mixed (COGENT neutral); regulators still advise avoidance and the switch costs nothing. Not an issue with prasugrel or ticagrelor." }, { "id": "5a9e", "significant": false, "mechanism": "none", "effect": "No meaningful loss of clopidogrel antiplatelet effect", "action": "Continue both; pantoprazole is the PPI of choice with clopidogrel", "numbers": [], "note": "Pantoprazole is a weak CYP2C19 inhibitor and platelet-function and outcome studies show no clinically relevant reduction in clopidogrel response." }, { "id": "f072", "significant": true, "mechanism": "Potent CYP3A4 and UGT induction accelerating ethinylestradiol and progestin clearance", "effect": "Breakthrough bleeding and unintended pregnancy", "action": "Use a method unaffected by induction: copper IUD, levonorgestrel IUS, or DMPA injection; if the pill is kept, add condoms for the whole rifampin course and for 28 days after the last rifampin dose", "numbers": ["barrier contraception for the full course plus 28 days after stopping rifampin"], "note": "Rifabutin is a weaker inducer but the same advice applies; implants and combined patch/ring are also compromised. Induction takes about 2 weeks to resolve." }, { "id": "1b6c", "significant": false, "mechanism": "none", "effect": "No reduction in contraceptive efficacy attributable to amoxicillin", "action": "Continue both; no extra precautions required for the antibiotic itself", "numbers": [], "note": "Widely believed but not supported by pharmacokinetic or epidemiological data; only rifamycins (and griseofulvin) matter. If the patient vomits within 3 hours of a pill or has severe diarrhoea, follow standard missed-pill rules." }, { "id": "e3f9", "significant": true, "mechanism": "P-glycoprotein inhibition reducing renal and biliary digoxin clearance, plus additive AV nodal depression", "effect": "Digoxin toxicity: bradycardia, AV block, nausea, visual disturbance, ventricular arrhythmias", "action": "Reduce digoxin dose by 50% when amiodarone is started, check a digoxin level at 1-2 weeks and again at 4-6 weeks, target 0.5-0.9 ng/mL, and reassess whether digoxin is still needed", "numbers": ["reduce digoxin dose by 50%", "digoxin level at 1-2 weeks", "repeat level at 4-6 weeks", "target digoxin 0.5-0.9 ng/mL"], "note": "Amiodarone's very long half-life means the interaction builds over weeks and persists for months after amiodarone is stopped; recheck levels if amiodarone dose changes." }, { "id": "94a2", "significant": true, "mechanism": "NSAID inhibition of renal prostaglandin synthesis reduces renal blood flow and lithium clearance", "effect": "Lithium toxicity: coarse tremor, ataxia, confusion, nephrogenic diabetes insipidus, seizures", "action": "Use acetaminophen instead; if an NSAID is unavoidable, use the lowest dose for the shortest time, check a lithium level 5-7 days after starting and consider a 25% lithium dose reduction if a sustained course is needed", "numbers": ["lithium level 5-7 days after starting NSAID", "lithium dose reduction of about 25% for sustained NSAID use"], "note": "An occasional single ibuprofen dose in a well-hydrated patient rarely causes harm; scheduled courses, dehydration, diuretics and ACE inhibitors are where cases occur. Low-dose aspirin does not have this effect." }, { "id": "6d70", "significant": true, "mechanism": "Xanthine oxidase inhibition blocks 6-mercaptopurine catabolism, shunting to 6-thioguanine nucleotides", "effect": "Severe, sometimes fatal myelosuppression", "action": "Reduce azathioprine to 25-33% of the usual dose (about one-quarter to one-third) and monitor CBC weekly for 4-8 weeks then monthly; or avoid the combination by choosing mycophenolate or a non-xanthine-oxidase urate-lowering strategy", "numbers": ["azathioprine 25-33% of usual dose", "CBC weekly for 4-8 weeks then monthly"], "note": "Febuxostat is also a xanthine oxidase inhibitor and carries the same problem. Check TPMT/NUDT15 status before starting; the combination is sometimes used deliberately in IBD to shift metabolite profile, but only with this dose reduction." }, { "id": "0c85", "significant": true, "mechanism": "Potent CYP1A2 inhibition increasing tizanidine exposure about 10-fold", "effect": "Severe hypotension, bradycardia and profound sedation", "action": "Contraindicated; use an antibiotic that does not inhibit CYP1A2 (levofloxacin, cephalexin, nitrofurantoin as indicated) or replace tizanidine with baclofen for the course", "numbers": [], "note": "Fluvoxamine causes the same problem; smoking cessation modestly raises tizanidine levels by the same pathway." }, { "id": "a7be", "significant": true, "mechanism": "CYP3A4 and P-glycoprotein induction lowering apixaban exposure by roughly half", "effect": "Loss of anticoagulant protection: stroke, systemic embolism or recurrent venous thromboembolism", "action": "Avoid; switch the anticoagulant to warfarin with INR titration (accepting more frequent INR checks while carbamazepine dose is stable), or switch the antiepileptic to levetiracetam or lamotrigine and continue apixaban", "numbers": [], "note": "Applies to all DOACs with carbamazepine, phenytoin, rifampin and St John's wort; there is no validated apixaban dose increase to compensate." }, { "id": "d218", "significant": true, "mechanism": "CYP3A4 and P-glycoprotein inhibition causing colchicine accumulation", "effect": "Colchicine toxicity: diarrhoea, pancytopenia, rhabdomyolysis, multi-organ failure and death", "action": "Avoid; use azithromycin instead; if clarithromycin must be given, for an acute flare give colchicine 0.6 mg once and do not repeat for at least 3 days, and for prophylaxis reduce to 0.3 mg daily; stop colchicine altogether if renal or hepatic impairment", "numbers": ["acute flare: colchicine 0.6 mg single dose, no repeat for 3 days", "prophylaxis: colchicine 0.3 mg daily"], "note": "Fatal cases cluster in patients with renal impairment; the same applies to ketoconazole, itraconazole, ritonavir and cyclosporine." }, { "id": "4f63", "significant": true, "mechanism": "Ibuprofen reversibly occupies the COX-1 acetylation site, blocking aspirin's irreversible platelet inhibition; additive GI mucosal injury", "effect": "Loss of cardioprotective antiplatelet effect plus increased GI bleeding", "action": "Replace ibuprofen with acetaminophen (or celecoxib if an NSAID is essential and GI/CV risk permits); if ibuprofen is kept, take immediate-release aspirin at least 30 minutes before ibuprofen or at least 8 hours after it, and add a PPI", "numbers": ["aspirin at least 30 minutes before ibuprofen", "aspirin at least 8 hours after ibuprofen"], "note": "With ibuprofen three times daily the timing separation is impractical, so switching analgesic is the real answer. Enteric-coated aspirin makes timing unreliable; naproxen shows a similar effect, celecoxib does not." }, { "id": "b5cd", "significant": true, "mechanism": "Combined neprilysin and ACE inhibition blocks both bradykinin degradation pathways", "effect": "Angioedema, potentially airway-threatening", "action": "Contraindicated; stop lisinopril and wait 36 hours before the first sacubitril/valsartan dose; never overlap", "numbers": ["36-hour washout after last ACE inhibitor dose"], "note": "No washout is needed when switching from an ARB. Prior angioedema on an ACE inhibitor is a contraindication to sacubitril/valsartan altogether." }, { "id": "27ea", "significant": false, "mechanism": "none", "effect": "No meaningful risk of lactic acidosis in a patient with normal renal function receiving IV contrast", "action": "Continue metformin without interruption when eGFR is 30 or above and there is no acute kidney injury; hold for 48 hours and recheck creatinine only if eGFR <30, AKI, or intra-arterial contrast with first-pass renal exposure", "numbers": ["eGFR <30 mL/min/1.73 m² triggers a hold", "hold metformin 48 hours and recheck creatinine before restarting"], "note": "The reflex 48-hour hold in everyone is no longer supported (ACR/ESUR); the pathway is contrast nephropathy causing metformin accumulation, so risk is confined to those with existing or expected renal impairment." }, { "id": "ec46", "significant": true, "mechanism": "Indirect sympathomimetic release of noradrenaline that cannot be degraded because of irreversible MAO-A inhibition", "effect": "Hypertensive crisis with risk of intracranial haemorrhage", "action": "Contraindicated; use saline irrigation or an intranasal corticosteroid for congestion; no pseudoephedrine, phenylephrine or ephedrine until 14 days after phenelzine is stopped", "numbers": ["14-day washout after stopping phenelzine"], "note": "Applies to all decongestants including OTC combination cold products; patients on MAOIs should be told to check every over-the-counter purchase with a pharmacist." } ] }