Run Detail

{ "rows": [ { "id": "a41f", "significant": true, "mechanism": "CYP2C9 and CYP3A4 inhibition by fluconazole reduces warfarin (S- and R-enantiomer) clearance", "effect": "Elevated INR with risk of major bleeding (GI, intracranial)", "action": "Check INR 3–5 days after the fluconazole dose; reduce warfarin by 25–50 % if INR rises >2 above the patient's usual range", "numbers": ["INR check at 3–5 days post-dose", "reduce warfarin 25–50 % if INR >2 above baseline"], "note": "A single 150 mg dose still inhibits CYP2C9 for ~5–7 days (t½ ≈ 30 h), so the interaction is real even for one-dose thrush treatment." }, { "id": "7c02", "significant": true, "mechanism": "Potent CYP3A4 inhibition by clarithromycin blocks simvastatin oxidation", "effect": "Markedly elevated simvastatin exposure → myopathy and rhabdomyolysis with renal failure", "action": "Hold simvastatin for the entire clarithromycin course; if a statin is essential, substitute rosuvastatin or pravastatin (non-3A4 substrates)", "numbers": [], "note": "FDA lists this as a contraindication. The 40 mg dose is in the range where rhabdomyolysis risk is highest; even 10 mg simvastatin is contraindicated with strong 3A4 inhibitors." }, { "id": "b9d5", "significant": true, "mechanism": "Additive serotonergic effect: reversible MAO-A/B inhibition (linezolid) plus serotonin reuptake inhibition (sertraline)", "effect": "Serotonin syndrome: hyperthermia, clonus, agitation, diaphoresis, tachycardia, autonomic instability", "action": "Avoid the combination. If linezolid is essential, stop sertraline and observe for 2 weeks before starting linezolid; if linezolid is started emergently, stop sertraline and monitor for 2 weeks", "numbers": ["2-week sertraline washout before linezolid"], "note": "Linezolid's MAO inhibition is weak and reversible, so the risk is lower than with a true MAOI, but case reports of full serotonin syndrome exist. An alternative antibiotic (e.g., vancomycin, daptomycin) is preferred when feasible." }, { "id": "3e18", "significant": true, "mechanism": "Additive NO/cGMP pathway activation: PDE-5 inhibition (sildenafil) + nitrate-derived NO (isosorbide mononitrate) → unopposed vasodilation", "effect": "Profound, refractory hypotension with syncope, myocardial ischaemia, or cardiovascular collapse", "action": "Absolute contraindication. Do not co-administer. If the patient requires chronic nitrate therapy, PDE-5 inhibitors cannot be used; if erectile dysfunction is the indication, manage with non-NO-based therapy", "numbers": [], "note": "No dose of sildenafil is safe with any nitrate. This is not a 'monitor closely' situation—it is a hard stop." }, { "id": "c6a7", "significant": true, "mechanism": "Additive reduction of renal potassium excretion: ACE-inhibitor–mediated aldosterone suppression plus direct aldosterone-receptor blockade by spironolactone", "effect": "Hyperkalaemia → peaked T-waves, bradycardia, ventricular arrhythmia, cardiac arrest", "action": "Check serum K⁺ and creatinine 1–2 weeks after starting or changing either agent, then every 3–6 months; avoid the combination if baseline K⁺ >5.0 mEq/L or eGFR <30 mL/min; limit spironolactone to 25 mg/day", "numbers": ["K⁺ and Cr at 1–2 weeks after initiation or dose change", "avoid if baseline K⁺ >5.0 mEq/L", "spironolactone ≤25 mg/day"], "note": "Risk is highest in the first 2 weeks and in elderly, volume-depleted, or diabetic patients. The combination is used intentionally in heart failure (e.g., RALES protocol) but demands the monitoring cadence above." }, { "id": "2f4b", "significant": true, "mechanism": "Additive folate-pathway blockade: methotrexate inhibits dihydrofolate reductase; trimethoprim inhibits DHFR (human and bacterial) and sulfamethoxazole inhibits dihydropteroate synthase", "effect": "Bone-marrow suppression (leukopenia, thrombocytopenia, anaemia) and mucositis", "action": "Avoid the combination when an alternative antibiotic exists. If TMP-SMX is unavoidable (e.g., short PCP course), use single-strength (80/400 mg) and check a CBC 1–2 weeks after the TMP-SMX course", "numbers": ["CBC at 1–2 weeks after TMP-SMX course if combination unavoidable"], "note": "At 15 mg/week (RA dose) the interaction is less dramatic than at oncologic doses, but pancytopenia cases are well documented. The risk is dose- and duration-dependent for the TMP-SMX." }, { "id": "8d31", "significant": true, "mechanism": "CYP2C19 inhibition by omeprazole reduces conversion of clopidogrel to its active thiol metabolite", "effect": "Reduced platelet inhibition → increased risk of stent thrombosis or recurrent ischaemic event (absolute risk increase is small)", "action": "Switch acid suppression to pantoprazole or famotidine; if omeprazole must continue, consider switching antiplatelet to prasugrel or ticagrelor", "numbers": [], "note": "The COGENT trial did not show a statistically significant rise in ischaemic events, and the FDA warning rests largely on PK/PD data. The interaction is real but the absolute clinical impact is modest; still, the prescribing change (switch PPI) is standard of care." }, { "id": "5a9e", "significant": false, "mechanism": "none", "effect": "none", "action": "No action needed; pantoprazole is the preferred PPI when acid suppression is required with clopidogrel", "numbers": [], "note": "Pantoprazole is a weak CYP2C19 inhibitor and does not meaningfully reduce clopidogrel's active metabolite. This pair is the recommended solution to the omeprazole problem." }, { "id": "f072", "significant": true, "mechanism": "CYP3A4 and UGT induction by rifampin accelerates hepatic and intestinal clearance of ethinylestradiol and progestin", "effect": "Subtherapeutic hormone levels → contraceptive failure and unintended pregnancy", "action": "Use a non-hormonal backup method (condom, diaphragm) throughout rifampin therapy and for 1 month after the last dose; consider a non-enzyme-inducing antibiotic if the indication allows", "numbers": ["backup contraception for 1 month after stopping rifampin"], "note": "This is one of the highest-yield interactions in primary care. The 1-month tail reflects the time for CYP3A4/UGT enzyme levels to normalise after rifampin is stopped." }, { "id": "1b6c", "significant": false, "mechanism": "none", "effect": "none", "action": "No action needed; amoxicillin does not reduce OCP efficacy", "numbers": [], "note": "The 'antibiotics make the pill fail' teaching is a myth for non-enzyme-inducing antibiotics. The only antibiotics with proven OCP interaction are rifamycins (CYP3A4/UGT induction). Gut-flora reabsorption theory has not held up clinically." }, { "id": "e3f9", "significant": true, "mechanism": "P-glycoprotein inhibition by amiodarone reduces renal and biliary digoxin efflux, raising serum digoxin", "effect": "Digoxin toxicity: nausea, visual halos, bradycardia, AV block, ventricular arrhythmia", "action": "Reduce digoxin dose by 50 % when starting amiodarone; check a digoxin level at 7–10 days and again at 4–6 weeks (amiodarone t½ ≈ 40–55 days, so the interaction evolves slowly)", "numbers": ["reduce digoxin dose by 50 %", "digoxin level at 7–10 days and at 4–6 weeks"], "note": "Because amiodarone's half-life is 40–55 days, the interaction persists for weeks after amiodarone is stopped. Do not 're-chase' the digoxin dose upward until amiodarone has fully cleared." }, { "id": "94a2", "significant": true, "mechanism": "Inhibition of renal prostaglandin synthesis by ibuprofen reduces renal blood flow and lithium tubular clearance", "effect": "Elevated lithium → tremor, nausea, ataxia, confusion, seizures, renal impairment", "action": "Prefer acetaminophen for analgesia. If an NSAID is essential, use the lowest effective dose for the shortest course and check a lithium level 3–5 days after starting ibuprofen", "numbers": ["lithium level at 3–5 days after starting ibuprofen"], "note": "Risk is amplified in the elderly, volume-depleted, or those on concurrent diuretics. Even a 3-day course of ibuprofen can push a lithium level from 0.7 to >1.2 mEq/L." }, { "id": "6d70", "significant": true, "mechanism": "Xanthine oxidase inhibition by allopurinol blocks the primary inactivation pathway of 6-mercaptopurine (active metabolite of azathioprine)", "effect": "Severe, potentially fatal myelosuppression (pancytopenia) and hepatotoxicity", "action": "If the combination is unavoidable (e.g., gout in a transplant patient), reduce azathioprine to 25–33 % of the original dose before starting allopurinol and check a CBC weekly for the first 4 weeks", "numbers": ["reduce azathioprine to 25–33 % of original dose", "CBC weekly × 4 weeks"], "note": "This is a 'do not miss' interaction. The dose reduction must be applied prospectively; waiting for a falling CBC is too late. Febuxostat has the same interaction and the same dose-reduction rule." }, { "id": "0c85", "significant": true, "mechanism": "CYP1A2 inhibition by ciprofloxacin blocks the sole major metabolic pathway of tizanidine", "effect": "Markedly elevated tizanidine → severe hypotension, profound sedation, bradycardia, syncope", "action": "Contraindicated. Do not co-administer. Use levofloxacin (not a CYP1A2 inhibitor) or another non-fluoroquinolone antibiotic; if a muscle relaxant is needed, use a non-CYP1A2 agent (e.g., cyclobenzaprine, methocarbamol)", "numbers": [], "note": "Listed as a contraindication on the tizanidine label. The interaction is not dose-dependent in a reassuring way—any ciprofloxacin dose can push tizanidine into the toxic range." }, { "id": "a7be", "significant": true, "mechanism": "CYP3A4 and P-glycoprotein induction by carbamazepine increases apixaban hepatic and intestinal clearance", "effect": "Subtherapeutic anticoagulation → stroke, systemic embolism, or recurrent VTE", "action": "Avoid the combination. If carbamazepine cannot be stopped, switch anticoagulation to warfarin with INR monitoring; if a DOAC is preferred, note that all four DOACs are CYP3A4/P-gp substrates and are similarly affected", "numbers": [], "note": "The problem is class-wide for DOACs, not specific to apixaban. Carbamazepine is one of the strongest inducers; phenytoin and phenobarbital cause the same issue. Lamotrigine and levetiracetam are non-inducing AED alternatives." }, { "id": "d218", "significant": true, "mechanism": "CYP3A4 and P-gp inhibition by clarithromycin reduces colchicine hepatic metabolism and biliary/renal efflux", "effect": "Colchicine accumulation → pancytopenia, multi-organ failure, death (narrow therapeutic index)", "action": "Avoid the combination. If both are essential and renal/hepatic function is normal, reduce colchicine dose by 50 % and check a CBC at 1–2 weeks; in renal or hepatic impairment the combination is contraindicated", "numbers": ["reduce colchicine dose by 50 %", "CBC at 1–2 weeks"], "note": "Colchicine's therapeutic window is extremely narrow. Fatal cases have been reported with macrolide co-administration, particularly in the elderly or those with any degree of renal impairment." }, { "id": "4f63", "significant": true, "mechanism": "Ibuprofen competitively occupies the COX-1 active site on platelets, physically blocking aspirin's irreversible acetylation of Ser-530", "effect": "Loss of aspirin's antiplatelet effect → increased risk of MI, stent thrombosis, or ischaemic stroke", "action": "Instruct the patient to take aspirin at least 30 minutes before the first daily ibuprofen dose, or take ibuprofen at least 8 hours after aspirin; preferably substitute acetaminophen for routine analgesia", "numbers": ["aspirin ≥30 min before ibuprofen", "ibuprofen ≥8 h after aspirin"], "note": "This is a pharmacodynamic, not pharmacokinetic, interaction. The 400 mg TID regimen makes the window of COX-1 occupancy long, so timing separation is critical. Naproxen has the same problem." }, { "id": "b5cd", "significant": true, "mechanism": "Additive RAAS and neprilysin blockade: sacubitril (neprilysin inhibitor) + valsartan (ARB) + lisinopril (ACE inhibitor) → excessive bradykinin accumulation and dual angiotensin-pathway blockade", "effect": "Angioedema (laryngeal, potentially fatal) and severe hypotension", "action": "Contraindicated. Do not co-administer. If transitioning from an ACE inhibitor to sacubitril/valsartan, enforce a 36-hour washout after the last lisinopril dose before the first Entresto dose", "numbers": ["36-hour washout after last ACE-inhibitor dose before starting sacubitril/valsartan"], "note": "The 36-hour gap is specifically to allow the ACE inhibitor to clear and reduce the bradykinin-mediated angioedema risk. This is not a 'monitor closely' pair—it is a hard contraindication to concurrent use." }, { "id": "27ea", "significant": false, "mechanism": "none", "effect": "none", "action": "No action needed in a patient with normal renal function; continue metformin through the contrast study", "numbers": [], "note": "The old blanket 'hold metformin 48 h around all contrast' is outdated. ACR and KDIGO guidance: in eGFR >60 with no acute kidney injury, metformin may be continued. The hold-and-recheck protocol applies to eGFR 30–60 or known renal impairment." }, { "id": "ec46", "significant": true, "mechanism": "Irreversible MAO-A/B inhibition by phenelzine prevents degradation of norepinephrine released by pseudoephedrine → unopposed sympathetic surge", "effect": "Hypertensive crisis: severe hypertension, pounding headache, tachycardia, risk of intracranial haemorrhage", "action": "Contraindicated. Do not use pseudoephedrine (or any sympathomimetic decongestant) with an MAOI. Use topical oxymetazoline nasal spray or a non-sympathomimetic antihistamine for congestion", "numbers": [], "note": "Applies to all MAOIs (phenelzine, tranylcypromine, selegiline ≥10 mg) and all indirect-acting sympathomimetics. The interaction is not dose-dependent in a reassuring way—any amount of pseudoephedrine can trigger a crisis." } ] }