Run Detail

{ "rows": [ { "id": "a41f", "significant": true, "mechanism": "Fluconazole inhibits CYP2C9-mediated clearance of S-warfarin.", "effect": "Excess anticoagulation and bleeding, potentially even after a single fluconazole dose.", "action": "Notify the anticoagulation service; check INR about 3 days and again 5–7 days after fluconazole. Adjust or temporarily withhold warfarin according to INR and bleeding, rather than applying an automatic dose reduction.", "numbers": [ "INR approximately 3 days after fluconazole", "Repeat INR 5–7 days after fluconazole" ], "note": "A single 150 mg dose is not interaction-free. The magnitude varies, so an automatic warfarin hold can also cause harm." }, { "id": "7c02", "significant": true, "mechanism": "Clarithromycin strongly inhibits CYP3A4-mediated simvastatin clearance.", "effect": "Myopathy and rhabdomyolysis, potentially causing acute kidney injury.", "action": "Do not coadminister. Replace clarithromycin with azithromycin if appropriate for the infection, or withhold simvastatin throughout the clarithromycin course and restart after the course is completed.", "numbers": [], "note": "Simply lowering the simvastatin dose is not the recommended solution; this combination is contraindicated." }, { "id": "b9d5", "significant": true, "mechanism": "Linezolid's reversible MAO inhibition combines with sertraline's serotonin-reuptake inhibition.", "effect": "Serotonin syndrome, including agitation, clonus, hyperreflexia, hyperthermia and autonomic instability.", "action": "Prefer an infection-appropriate alternative such as vancomycin when suitable. If urgent linezolid is essential, stop sertraline immediately without delaying necessary antibiotic treatment; monitor for serotonin toxicity for 14 days or until 24 hours after the last linezolid dose, whichever comes first. Restart sertraline no sooner than 24 hours after the last linezolid dose.", "numbers": [ "Monitor for 14 days after stopping sertraline or until 24 hours after the last linezolid dose, whichever comes first", "Restart sertraline no sooner than 24 hours after the last linezolid dose" ], "note": "The absolute incidence appears low, and this is not an absolute prohibition when linezolid is necessary. Specialist-supervised concurrent treatment is sometimes justified; also watch for antidepressant discontinuation symptoms." }, { "id": "3e18", "significant": true, "mechanism": "Nitrate-driven cGMP production combines with sildenafil's inhibition of PDE5-mediated cGMP breakdown.", "effect": "Profound hypotension, syncope and potentially myocardial ischemia.", "action": "Do not prescribe sildenafil while nitrate therapy is required; consider alprostadil for erectile dysfunction. After sildenafil exposure, withhold nitrates for at least 24 hours; chest pain requires emergency assessment rather than self-administration of a nitrate.", "numbers": [ "Minimum nitrate-free interval after sildenafil: 24 hours" ], "note": "The interval is a minimum, not a guarantee of safety; impaired clearance or strong metabolic inhibitors can prolong sildenafil exposure. Do not independently interrupt necessary chronic nitrate treatment to use sildenafil." }, { "id": "c6a7", "significant": true, "mechanism": "ACE inhibition and mineralocorticoid-receptor blockade additively reduce renal potassium excretion.", "effect": "Hyperkalemia, potentially causing fatal arrhythmias, and worsening renal function.", "action": "Check potassium and creatinine before treatment, 3–7 days after initiation or dose changes, at 1 month, then every 3 months. Avoid potassium supplements and potassium-containing salt substitutes. Do not initiate spironolactone if potassium is ≥5.0 mmol/L or eGFR is ≤30 mL/min/1.73 m²; reduce or hold it and reassess promptly if potassium reaches ≥5.5 mmol/L.", "numbers": [ "Potassium and creatinine 3–7 days after initiation or dose changes", "Repeat at 1 month", "Ongoing monitoring every 3 months", "Do not initiate spironolactone at potassium ≥5.0 mmol/L", "Do not initiate spironolactone at eGFR ≤30 mL/min/1.73 m²", "Reduce or hold spironolactone at potassium ≥5.5 mmol/L" ], "note": "This is often an intentional, beneficial heart-failure combination, not a blanket contraindication. Acute illness, dehydration, NSAIDs and declining kidney function require additional monitoring." }, { "id": "2f4b", "significant": true, "mechanism": "Additive folate antagonism plus reduced renal clearance of methotrexate.", "effect": "Severe mucositis, pancytopenia, infection, bleeding and potentially fatal marrow suppression.", "action": "Avoid trimethoprim-sulfamethoxazole; use a non-antifolate antibiotic such as cephalexin when appropriate for the infection and susceptibility. If exposure has occurred, stop trimethoprim-sulfamethoxazole, withhold methotrexate pending urgent review, and obtain CBC and creatinine promptly; arrange follow-up blood counts because toxicity can be delayed.", "numbers": [], "note": "Low-dose weekly methotrexate does not eliminate this risk, and routine folic acid does not reliably prevent it. Prophylactic trimethoprim-sulfamethoxazole is a separate specialist-managed situation." }, { "id": "8d31", "significant": true, "mechanism": "Omeprazole inhibits CYP2C19-dependent formation of clopidogrel's active metabolite.", "effect": "Reduced platelet inhibition, with possible loss of protection against myocardial infarction or stent thrombosis; increased clinical events have not been consistently demonstrated.", "action": "If acid suppression is needed, replace omeprazole with pantoprazole. Do not attempt to solve the interaction by separating administration times.", "numbers": [], "note": "The pharmacokinetic and platelet-function interaction is established, but its clinical outcome significance remains disputed. Regulatory recommendations and the availability of pantoprazole make this actionable without claiming proven excess cardiovascular events." }, { "id": "5a9e", "significant": false, "mechanism": "none", "effect": "No established clinically meaningful loss of clopidogrel's cardiovascular protection.", "action": "Continue both when indicated; no interaction-specific dose adjustment, separation or platelet-function testing is needed.", "numbers": [], "note": "Pantoprazole is generally a preferred PPI when clopidogrel users need gastroprotection; the omeprazole warning should not be indiscriminately applied to every PPI." }, { "id": "f072", "significant": true, "mechanism": "Rifampin induces CYP3A4 and other hormone-metabolizing enzymes, accelerating estrogen and progestin clearance.", "effect": "Contraceptive failure and unintended pregnancy; breakthrough bleeding may occur.", "action": "Use an unaffected method such as a copper IUD, levonorgestrel IUD or depot medroxyprogesterone. Treat the combined pill as unreliable during rifampin and for 28 days after its last dose; use condoms or abstain until the alternative method is effective.", "numbers": [ "Combined pill remains unreliable for 28 days after the last rifampin dose" ], "note": "Absence of breakthrough bleeding does not establish contraceptive protection. Oral emergency contraception can also be compromised by enzyme induction." }, { "id": "1b6c", "significant": false, "mechanism": "none", "effect": "No demonstrated increase in contraceptive failure attributable to amoxicillin itself.", "action": "Continue the combined pill normally; no antibiotic-specific backup contraception is needed. If vomiting or severe diarrhea occurs, follow the particular pill's missed-dose and gastrointestinal-illness instructions.", "numbers": [], "note": "The proposed gut-flora/enterohepatic-recycling interaction has not translated into a clinically meaningful interaction with ordinary non-enzyme-inducing antibiotics." }, { "id": "e3f9", "significant": true, "mechanism": "Amiodarone inhibits P-glycoprotein-mediated digoxin transport and adds AV-nodal suppression.", "effect": "Digoxin toxicity, including nausea, confusion, visual disturbance, bradycardia, AV block and ventricular arrhythmias.", "action": "When adding amiodarone, reduce the maintenance digoxin dose by approximately 50%. Check digoxin concentration, creatinine and electrolytes after 7 days and again after 2–4 weeks; draw the digoxin sample at least 6 hours after a dose. Monitor pulse and obtain an ECG for bradycardia or toxicity symptoms.", "numbers": [ "Reduce maintenance digoxin dose by approximately 50%", "Check digoxin, creatinine and electrolytes after 7 days", "Repeat after 2–4 weeks", "Draw digoxin concentration at least 6 hours after a dose" ], "note": "Further adjustment depends on the indication, concentration and clinical response. Amiodarone's interaction can evolve and persist because of its long tissue half-life." }, { "id": "94a2", "significant": true, "mechanism": "Ibuprofen inhibits renal prostaglandin synthesis, reducing renal perfusion and lithium clearance.", "effect": "Lithium toxicity, including vomiting, coarse tremor, ataxia, confusion and potentially seizures.", "action": "Prefer acetaminophen instead of ibuprofen. If ibuprofen is necessary, obtain baseline lithium and renal function, repeat 5–7 days after starting and after stopping it, and adjust lithium according to results. Use a lithium trough drawn 12 hours after the preceding dose.", "numbers": [ "Repeat lithium and renal function 5–7 days after starting ibuprofen", "Repeat lithium and renal function 5–7 days after stopping ibuprofen", "Lithium trough sample 12 hours after the preceding dose" ], "note": "The effect varies substantially between patients and can occur with normal baseline kidney function. Dehydration and sodium depletion increase risk." }, { "id": "6d70", "significant": true, "mechanism": "Allopurinol inhibits xanthine oxidase-mediated inactivation of azathioprine-derived mercaptopurine.", "effect": "Profound myelosuppression, potentially causing severe infection, bleeding and death.", "action": "Avoid unadjusted coadministration. If deliberately combined under specialist supervision, reduce azathioprine to 25–33% of its usual dose; monitor CBC and liver tests weekly for the first 4 weeks, every 2 weeks for the next 8 weeks, then monthly.", "numbers": [ "Azathioprine dose: 25–33% of the usual dose", "CBC and liver tests weekly for the first 4 weeks", "CBC and liver tests every 2 weeks for the next 8 weeks", "CBC and liver tests monthly thereafter" ], "note": "This combination is sometimes intentionally used in inflammatory bowel disease with markedly reduced thiopurine dosing. Febuxostat is not a safe substitute to escape the interaction." }, { "id": "0c85", "significant": true, "mechanism": "Ciprofloxacin strongly inhibits CYP1A2-mediated tizanidine clearance.", "effect": "Profound hypotension, bradycardia, excessive sedation and impaired consciousness.", "action": "Do not coadminister. Replace ciprofloxacin with an antibiotic such as amoxicillin if appropriate for the infection and susceptibility, or arrange a supervised switch off tizanidine; separating doses does not solve the interaction.", "numbers": [], "note": "This combination is contraindicated. Long-term high-dose tizanidine may require a supervised taper to avoid withdrawal-associated rebound hypertension." }, { "id": "a7be", "significant": true, "mechanism": "Carbamazepine induces CYP3A4 and P-glycoprotein, reducing apixaban exposure.", "effect": "Loss of anticoagulant protection, causing stroke, systemic embolism or recurrent venous thromboembolism.", "action": "Avoid the combination. If carbamazepine must continue, use warfarin with INR-guided dosing or an indication-appropriate low-molecular-weight heparin rather than empirically increasing apixaban.", "numbers": [], "note": "Carbamazepine also increases warfarin dose requirements, but INR permits titration; monitor closely when carbamazepine is started or stopped. Apixaban concentration testing does not provide a validated dose-escalation strategy." }, { "id": "d218", "significant": true, "mechanism": "Clarithromycin strongly inhibits both CYP3A4-mediated metabolism and P-glycoprotein transport of colchicine.", "effect": "Colchicine toxicity with severe gastrointestinal illness, neuromyopathy, rhabdomyolysis, marrow suppression and potentially fatal multiorgan failure.", "action": "Avoid the combination; replace clarithromycin with an infection-appropriate noninhibiting antibiotic such as amoxicillin or doxycycline.", "numbers": [], "note": "Fatal toxicity can occur even with initially normal renal function. Concomitant use is contraindicated in renal or hepatic impairment; normal organ function does not make routine coadministration safe." }, { "id": "4f63", "significant": true, "mechanism": "Reversible platelet COX-1 occupancy by ibuprofen can block aspirin's irreversible acetylation, while both drugs increase gastrointestinal bleeding risk.", "effect": "Possible loss of aspirin's protection against recurrent myocardial infarction or ischemic stroke, plus increased gastrointestinal ulceration and bleeding.", "action": "Avoid scheduled ibuprofen; use acetaminophen for pain and continue aspirin. For a single occasional ibuprofen dose with immediate-release aspirin, take ibuprofen at least 8 hours before or at least 30 minutes after aspirin; do not rely on this timing workaround for repeated daily ibuprofen or enteric-coated aspirin.", "numbers": [ "Occasional ibuprofen: at least 8 hours before immediate-release aspirin", "Alternatively, occasional ibuprofen: at least 30 minutes after immediate-release aspirin" ], "note": "The familiar timing rule is not a reliable solution for the scheduled regimen in this pair. Gastroprotection can reduce gastrointestinal risk but does not restore aspirin's platelet effect." }, { "id": "b5cd", "significant": true, "mechanism": "Combined neprilysin and ACE inhibition impairs bradykinin degradation.", "effect": "Angioedema, potentially involving life-threatening airway obstruction.", "action": "Never coadminister. Allow at least 36 hours between the last lisinopril dose and the first sacubitril/valsartan dose, and the same interval when switching in the reverse direction.", "numbers": [ "Minimum washout in either switching direction: 36 hours" ], "note": "A history of ACE-inhibitor- or ARB-associated angioedema is also a contraindication to sacubitril/valsartan. The ACE-inhibitor washout rule does not apply to an ARB alone, although duplicate ARB treatment must be avoided." }, { "id": "27ea", "significant": false, "mechanism": "none", "effect": "No clinically meaningful interaction with routine intravenous iodinated contrast in an adult with normal renal function and no acute kidney injury.", "action": "Continue metformin under contemporary radiology guidance; no routine postcontrast renal test is required solely because of metformin. If acute kidney injury is present or eGFR is <30 mL/min/1.73 m², withhold metformin at or before contrast, reassess renal function after 48 hours, and restart only if renal function is stable, eGFR is ≥30 mL/min/1.73 m² and metformin remains appropriate.", "numbers": [ "eGFR <30 mL/min/1.73 m² changes the plan to withholding metformin", "Reassess renal function after 48 hours when metformin has been withheld", "Restart requires stable renal function and eGFR ≥30 mL/min/1.73 m²" ], "note": "The concern is metformin accumulation and lactic acidosis if acute kidney injury develops, not a direct metformin–contrast interaction. FDA labeling and some local protocols are more conservative; intra-arterial contrast has different rules." }, { "id": "ec46", "significant": true, "mechanism": "Irreversible MAO inhibition potentiates pseudoephedrine's sympathomimetic norepinephrine effects.", "effect": "Hypertensive crisis, potentially causing intracranial hemorrhage, myocardial ischemia or arrhythmia.", "action": "Avoid pseudoephedrine and other sympathomimetic decongestants during phenelzine treatment and for at least 14 days after stopping it. Use saline nasal spray or intranasal fluticasone for allergic congestion; severe headache, chest pain or neurologic symptoms require emergency assessment.", "numbers": [ "Avoid sympathomimetic decongestants for at least 14 days after stopping phenelzine" ], "note": "Phenylephrine is not a safe workaround, and topical sympathomimetic decongestants should not be assumed safe. MAO inhibition persists after phenelzine has left the circulation." } ] }