Drug-drug interactions

Dual RAAS blockade: ACE-I blocks angiotensin II formation, ARB blocks its receptors.

Rifampicin is the most potent CYP3A4 inducer in clinical practice.

Escitalopram (SSRI) raises synaptic serotonin; tramadol blocks serotonin and norepinephrine reuptake.

Apixaban directly inhibits factor Xa; clopidogrel blocks the platelet P2Y12 receptor.

Carbamazepine induces CYP3A4 – the main simvastatin metabolic route.

Dual mechanism: aspirin competes with furosemide for organic anion tubular secretion in the renal tubules (so furosemide does not reach its target in the loop of Henle lumen), and concurrently suppresses renal prostaglandin synthesis supporting glomerular perfusion.

Additive QT prolongation.

Carbamazepine induces CYP3A4 – the main atorvastatin metabolic route.

Additive CNS depression, sedation, and anticholinergic effect.

Additive slowing of atrioventricular (AV) conduction and lowered heart rate.

Additive hypotension with sublingual or parenteral nitroglycerin.

Both drugs prolong QT.

Haloperidol prolongs QT, moxifloxacin too.

An early study (Lau et al.

ACE inhibitors improve tissue insulin sensitivity and potentiate metformin's glucose-lowering effect.

Target combination in heart failure and arterial hypertension.

Omeprazole weakly inhibits intestinal OCT1, the transporter mediating metformin absorption.

Amoxicillin taken concurrently may slightly impair intestinal levothyroxine absorption.

Both can cause hyponatraemia: furosemide via natriuresis, sertraline via SIADH-like mechanism.

No direct pharmacokinetic interaction.

Carbamazepine induces CYP3A4 – the main cyclosporine metabolic route.

Voriconazole inhibits CYP3A4.

Hypothyroidism itself raises LDL.

Strong CYP3A4 inhibitor.

Rifampicin is a strong CYP3A4 + P-gp inducer.

Both prolong QT.

Doxycycline forms non-absorbable chelates with calcium in the gut (and with other polyvalent cations — magnesium, iron, aluminium).

Target combination in triple and quadruple Helicobacter pylori eradication (Maastricht VI/Florence Consensus 2022, Kyoto Global Consensus).

Rifampicin induces enterocyte P-glycoprotein.

Additive CNS depression and mild hypotension.

Itraconazole is the strongest CYP3A4 inhibitor.

Fluoxetine blocks CYP2D6 (strongly) and CYP3A4 (moderately).

Antacids accelerate renal aspirin elimination via urinary alkalinisation.

Esomeprazole inhibits CYP2C19, the key enzyme that converts clopidogrel to its active metabolite.

Dual mechanism.

Carbamazepine induces CYP3A4 and CYP2D6; amitriptyline plasma levels fall by 50–60%.

No direct pharmacokinetic or pharmacodynamic interaction.

Rifampicin strongly induces CYP3A4 – the main amlodipine metabolic route.

No clinically significant direct interaction.

Additive QT prolongation.

ARBs, like ACE inhibitors, improve tissue insulin sensitivity.

No clinically significant direct interaction.

Target combination in angina and hypertension.

No clinically significant direct interaction.

Clopidogrel blocks platelet aggregation via the P2Y12 receptor; sertraline impairs primary haemostasis by inhibiting platelet serotonin reuptake.

Spironolactone moderately inhibits P-glycoprotein; digoxin levels rise by 20–30%.

Historical theory of reduced combined oral contraceptive efficacy via gut flora suppression.

Thiazides are one of the most common drug causes of hyponatraemia in older patients via SIADH-like mechanism and natriuresis.

Trimethoprim (a co-trimoxazole component) blocks sodium channels in the collecting duct epithelium (amiloride-like mechanism) and reduces potassium secretion.

Omeprazole inhibits CYP2C19, the enzyme responsible for sertraline metabolism.

Dual QT prolongation.

No direct pharmacokinetic interaction.

Additive QT prolongation.

Dual risk: both drugs lower the seizure threshold.

The historical theory of reduced combined oral contraceptive efficacy via gut flora suppression is rejected by meta-analyses.

Aspirin irreversibly blocks platelet cyclooxygenase; rivaroxaban directly inhibits factor Xa.

Alprazolam and tramadol depress the central nervous system and respiratory centre.

Doxycycline does not affect hepatic ethinylestradiol metabolism.

Proton pump inhibitors raise gastric pH, reducing levothyroxine absorption.

No direct pharmacokinetic interaction.

Carbamazepine induces CYP3A4 – a partial haloperidol clearance route.

Escitalopram (SSRI) is a citalopram enantiomer with dose-dependent QT prolongation.

Beta-blockers mask adrenergic hypoglycaemia symptoms (tachycardia, tremor), leaving only sweating.

Strong CYP3A4 inhibitor – lovastatin rises 20+ fold.

Azithromycin has minimal effect on CYP3A4 (unlike clarithromycin and erythromycin).

Fluoroquinolones disturb glucose homeostasis — they can cause both hypoglycaemia (especially in older patients on glucose-lowering therapy) and hyperglycaemia.

Furosemide is a loop diuretic that increases urinary loss of potassium and magnesium.

Target combination in hypertension: synergistic BP lowering via different mechanisms (calcium channel blockade plus RAAS suppression).

Carbamazepine is a CYP3A4 inducer.

Metronidazole does not induce CYP3A4 and does not affect hepatic ethinylestradiol metabolism.

Thiazide diuretics reduce glycaemic control via hypokalaemia-driven suppression of insulin secretion.

Furosemide (loop diuretic) increases potassium and magnesium loss.

Trimethoprim blocks collecting duct sodium channels (amiloride-like mechanism) and reduces potassium secretion.

Linezolid is a reversible MAO inhibitor.

Azithromycin has minimal effect on CYP3A4 and does not affect hepatic oestradiol metabolism.

Additive GI bleeding risk: anticoagulant (rivaroxaban) + ulcerogenic NSAID (diclofenac).

Fluconazole weakly inhibits CYP3A4 and CYP2C19.

Fluoxetine is a strong CYP2D6 inhibitor.

Celecoxib (a selective COX-2 inhibitor) reduces renal blood flow via prostaglandin suppression.

Dual mechanism.

Linezolid is a reversible MAO inhibitor and may mildly potentiate opioid CNS depression.

Strong CYP3A4 inducer.

Both lower the seizure threshold.

Tramadol is a serotonergic opioid; mirtazapine raises serotonergic transmission via α2-blockade.

Additive ulcerogenic effect.

At high doses, aspirin weakens verapamil's antihypertensive effect via vasodilator prostaglandin suppression.

Additive hypotension and fall risk.

Additive hypotension.

Indapamide (thiazide-like diuretic) raises allopurinol and oxypurinol levels, increasing hypersensitivity risk.

No direct interaction.

Valproate weakly suppresses hepatic alprazolam metabolism; alprazolam plasma levels may rise slightly.

Additive sedation and fall risk in older patients.

No clinically significant direct interaction.

Loratadine causes minimal QT prolongation at standard doses, but with CYP3A4 blockade by amiodarone, loratadine levels rise, potentially amplifying cardiac effects in predisposed patients.

Linezolid mildly prolongs QT, additively with amiodarone.

No direct interaction.

Additive orthostatic hypotension and hypokalaemia risk.

Additive bradycardia and orthostatic hypotension.

Levetiracetam is not metabolised by the CYP system; no pharmacokinetic interaction with amitriptyline.

No clinically significant direct interaction.

Same as the ethinylestradiol pair: meta-analyses did not confirm clinically significant reductions in hormone therapy efficacy with broad-spectrum antibiotics.

Serotonergic load from combining two drugs with different mechanisms.

Linezolid is a reversible MAO inhibitor.

Ciprofloxacin weakly affects CYP3A4 and P-glycoprotein — the main clearance routes of apixaban.

IV methylene blue inhibits MAO-A.

Clarithromycin inhibits CYP3A4 – lovastatin (sensitive substrate) rises 8-fold.

Additive myopathy and rhabdomyolysis risk.

'California rocket fuel' augmentation – mirtazapine (5-HT2/3 blocker) + venlafaxine (SNRI).

Strong CYP3A4 inhibitor.

Norfloxacin does not induce CYP3A4 and does not affect ethinylestradiol metabolism.

Doxycycline does not induce CYP3A4 and does not affect oestradiol metabolism.

Rosuvastatin is minimally metabolised by CYP2C9 and excreted mainly unchanged via the liver and kidneys.

Magnesium theoretically antagonises lithium-driven neuronal excitability, but no clinical cases of efficacy loss at standard magnesium doses (up to 400 mg/day) have been described.

Simethicone is a surface-active silicone agent that is not absorbed in the gastrointestinal tract.

Paracetamol and bisoprolol are metabolised by different pathways.

Calcium carbonate and sertraline are metabolised by different pathways.

Echinacea purpurea modulates CYP1A2 and CYP3A4 in vitro, but the in vivo effect is minimal.

Azithromycin does not clinically significantly inhibit CYP3A4 (Indiana Flockhart Table).

Dexamethasone stimulates gluconeogenesis and reduces tissue insulin sensitivity.

Esomeprazole suppresses gastric acidity, reducing release of B12 from food (which requires HCl and pepsin).

Loratadine rarely causes sedation at standard doses.

Azithromycin does not significantly inhibit CYP3A4, unlike clarithromycin and erythromycin (the FDA labels these as absolute contraindications with simvastatin due to rhabdomyolysis risk).

Allopurinol inhibits xanthine oxidase, the enzyme that inactivates 6-mercaptopurine (the active metabolite of azathioprine).

Ciclosporin inhibits P-glycoprotein in gut and renal tubules, reducing digoxin clearance.

Prednisolone is ulcerogenic; escitalopram reduces platelet aggregation via serotonin uptake.

Gabapentin reduces morphine clearance and potentiates CNS depression.

Both cause hypokalaemia: glucocorticoids via mineralocorticoid effect and muscle catabolism; furosemide via direct urinary potassium loss.

Febuxostat is a selective xanthine oxidase inhibitor; like allopurinol it blocks the conversion of 6-mercaptopurine to its inactive metabolite.

Both drugs are mineralocorticoid receptor antagonists.

Similar to tramadol + gabapentin: additive CNS depression, seizure risk (tramadol lowers threshold).

Rosuvastatin is excreted mainly unchanged and minimally metabolised by CYP.

Dual risk.

Trimethoprim in co-trimoxazole blocks epithelial sodium channels in renal collecting ducts via the same mechanism as amiloride.

Sildenafil inhibits PDE-5; isosorbide mononitrate releases nitric oxide.

Iron forms non-absorbable chelates with tetracyclines in the gut (as with the doxycycline-calcium pair).

Dual NSAID therapy – additive GI bleeding and nephrotoxicity risk.

Erythromycin inhibits CYP3A4.

Itraconazole is the strongest CYP3A4 inhibitor in clinical use.

Carbamazepine induces CYP1A2, which partly metabolises theophylline.

Itraconazole inhibits CYP3A4 and P-glycoprotein.

Voriconazole is a strong CYP3A4 inhibitor, the main enzyme for sirolimus.

Two SSRIs simultaneously – serotonin syndrome without therapeutic rationale.

Voriconazole inhibits CYP3A4.

Fluconazole inhibits CYP2C9, the main enzyme of S-warfarin (the more active isomer).

Additive serotonergic effect of SSRIs and lithium (lithium enhances synaptic serotonergic transmission).

Carbamazepine is a strong CYP3A4 and P-glycoprotein inducer.

NSAID (meloxicam) + nephrotoxic calcineurin inhibitor (tacrolimus) – additive acute kidney injury risk in transplant patients.

Same mechanism as with apixaban: CYP3A4 and P-gp induction by carbamazepine drops rivaroxaban levels by 50%.

Venlafaxine (SNRI) + tramadol – serotonin syndrome plus additive seizure risk.

Rifampicin is the strongest clinical inducer of CYP3A4 and P-glycoprotein.

Rifampicin induces CYP2C9, CYP3A4 and CYP1A2 – all main warfarin metabolism pathways.

Non-dihydropyridine calcium channel blocker (diltiazem) + beta-blocker (carvedilol) – additive AV node blockade and negative inotropic effect.

Ibuprofen reduces methotrexate renal elimination by inhibiting proximal tubular secretion.

NSAIDs reduce renal blood flow via prostaglandin blockade.

Diclofenac, like other NSAIDs, reduces methotrexate renal clearance.

Additive bradycardia and atrioventricular (AV) block.

Ibuprofen reduces lithium renal clearance by inhibiting prostaglandin synthesis in the proximal tubule.

Fluvoxamine blocks CYP1A2 and CYP2C19 – the main amitriptyline demethylation routes.

Enalapril and other ACE inhibitors reduce renal blood flow and glomerular filtration, decreasing lithium excretion.

Hydrochlorothiazide increases sodium and lithium reabsorption in the distal tubule.

Amitriptyline (TCA) causes orthostatic hypotension via α1-adrenergic blockade.

Losartan, like ACE inhibitors, reduces lithium renal clearance via angiotensin blockade of the efferent arteriole.

Escitalopram is a citalopram enantiomer with the same effects.

Bupropion blocks CYP2D6 – the route converting tramadol to its active M1 metabolite.

Clarithromycin inhibits intestinal and renal P-glycoprotein and suppresses gut flora that inactivates part of the digoxin dose.

Haloperidol is a CYP2D6 substrate; bupropion is a potent CYP2D6 inhibitor.

High morphine doses cause opioid-induced myoclonus, raising seizure risk.

Additive seizure threshold reduction.

Dihydropyridine calcium channel blocker (amlodipine) + cardioselective beta-blocker (bisoprolol) – additive bradycardia and hypotension.

Both drugs prolong QT by blocking hERG potassium channels.

Additive QT prolongation (both prolong QT).

Fluconazole inhibits CYP3A4 and CYP2B6 – the main methadone metabolism enzymes.

Bupropion blocks CYP2D6.

Two SSRIs simultaneously – serotonin syndrome without therapeutic purpose.

Linezolid is a reversible MAO inhibitor.

SSRI + SNRI – serotonin syndrome, additive QT prolongation at high venlafaxine doses.

Clarithromycin is a strong CYP3A4 inhibitor.

Erythromycin is a moderate-to-strong CYP3A4 inhibitor.

Abrupt clonidine withdrawal on a beta-blocker triggers a hypertensive crisis: the α2 effect is lost while β-blockade persists – an 'unopposed' α1 effect develops with a sharp blood pressure rise.

Rifampicin is the most potent available CYP3A4 inducer.

Itraconazole is the strongest clinical CYP3A4 inhibitor.

Mirtazapine + SNRI – augmentation in resistant depression ('California rocket fuel').

Ketoconazole is a strong CYP3A4 inhibitor.

SSRI + SNRI – serotonin syndrome.

Voriconazole is a strong CYP3A4 inhibitor and itself a QT prolonger.

Additive QT prolongation.

Posaconazole is a strong CYP3A4 inhibitor.

Dual antipsychotic therapy – additive risk of extrapyramidal symptoms, sedation, QT prolongation, and metabolic side effects.

Dual NSAID therapy – sharp rise in GI bleeding risk (3- to 5-fold), acute kidney injury, and cardiovascular events.

Additive bradycardia and hypotension.

Ritonavir is the strongest ARV CYP3A4 inhibitor.

Cobicistat is a strong CYP3A4 inhibitor (potency similar to ritonavir).

Fluconazole is a moderate CYP3A4 inhibitor.

Omeprazole blocks CYP2C19.

NSAIDs reduce renal methotrexate clearance.

Quinidine is a strong CYP2D6 inhibitor (secondary pimozide pathway) and itself a QT prolonger.

Amiodarone is a moderate CYP3A4 inhibitor and the strongest clinical QT prolonger.

Phenelzine irreversibly inhibits MAO; fluoxetine blocks serotonin reuptake.

Additive CNS depression plus seizure threshold reduction (tramadol lowers it, quetiapine at high doses).

Calcium carbonate as an antacid mildly reduces lithium intestinal absorption, but no clinically significant drop in blood concentration has been documented.

Spironolactone retains potassium via aldosterone receptor blockade.

Sertraline is an SSRI.

Citalopram is an SSRI.

Escitalopram is an SSRI.

Paroxetine is an SSRI with additional antimuscarinic activity.

High aspirin doses (above 1 g/day) may reduce the ARB's antihypertensive effect via vasodilator prostaglandin suppression.

Additive CNS depression and hypotension.

Paracetamol and cetirizine are metabolised by different pathways.

Celecoxib is a CYP2C9 substrate.

Additive orthostatic hypotension.

Additive CNS depression.

Paracetamol and loratadine are metabolised by different pathways.

TCA blocks α1-adrenoceptors — additive orthostatic hypotension with carvedilol (α/β-blocker).

Additive hypotension, especially orthostatic.

Ritonavir is a strong CYP2D6 and CYP3A4 inhibitor.

NSAIDs antagonise amlodipine's antihypertensive effect via renal prostaglandin-dependent sodium regulation suppression.

Venlafaxine is an SNRI with strong serotonin effect.

The selective COX-2 inhibitor celecoxib gives lower GI risk than non-selective NSAIDs, but with a direct factor Xa inhibitor additive bleeding risk persists.

Fluconazole is a moderate CYP3A4 inhibitor.

Metronidazole does not block CYP3A4 but increases myopathy risk with statins (mechanism not fully established; reported in post-marketing data).

Tramadol inhibits serotonin reuptake (secondary mechanism).

Methadone is an opioid with serotonergic activity and QT prolongation.

Pantoprazole is the most CYP-neutral PPI.

Tacrolimus is a weak CYP3A4 inhibitor and P-glycoprotein substrate.

Linezolid is a reversible MAO inhibitor.

Linezolid is associated with rhabdomyolysis in combination with statins (rare post-marketing cases; mechanism not fully established).

Ciprofloxacin is a weak CYP3A4 inhibitor.

Mirtazapine is a dual-mechanism antidepressant (α2 + 5-HT2 blockade).

Systemic (oral) budesonide causes sodium retention and weakens the antihypertensive effect of the beta-blocker.

Tranylcypromine is an irreversible MAOI.

Antibiotics may affect methotrexate gut absorption.

Additive QT prolongation (venlafaxine prolongs QT at doses above 150 mg).

Tranylcypromine irreversibly inhibits MAO.

Cumulative MAO inhibition (irreversible tranylcypromine + reversible linezolid).

Standard combination in hypertension – additive antihypertensive effect.

Additive bradycardia.

Additive hypotension and sedation.

Standard combination in heart failure with reduced ejection fraction.

Glucocorticoid plus NSAID — additive risk of GI ulcers and bleeding.

Fluvoxamine is a CYP3A4 inhibitor; budesonide is a CYP3A4 substrate.

Systemic budesonide retains sodium and water, blunting the beta-blocker's antihypertensive effect.

Dual QT prolongation (amiodarone extends 30–50 ms, quinidine 20–40 ms) plus amiodarone inhibits CYP3A4 (quinidine metabolism).

Quinidine inhibits renal and intestinal P-glycoprotein – digoxin clearance drops 50%.

Additive QT prolongation (sotalol extends 30 ms, quinidine 20–40 ms).

Clopidogrel is a prodrug.

Glucocorticoid plus NSAID — additive GI ulcer and bleeding risk with systemic budesonide.

Phenytoin is a strong CYP3A4 + P-gp inducer.

Same as apixaban: CYP3A4 + P-gp induction by phenytoin drops rivaroxaban by 50%.

Phenytoin induces CYP3A4.

Phenytoin induces CYP3A4.

Cobicistat is a strong CYP3A4 inhibitor.

Lovastatin is a CYP3A4 sensitive substrate (like simvastatin).

Sirolimus is a CYP3A4 sensitive substrate, P-gp substrate, NTI.

Cobicistat inhibits CYP3A4 (quinidine metabolism) and itself prolongs PR via MATE1 inhibition.

Amitriptyline, a tricyclic antidepressant, blocks serotonin and norepinephrine reuptake.

Diclofenac (NSAID) inhibits platelet aggregation, injures the gastric mucosa, and weakly displaces warfarin from albumin binding.

Clarithromycin inhibits CYP3A4.

Erythromycin is a CYP3A4 inhibitor.

Itraconazole is the strongest CYP3A4 inhibitor.

Bupropion inhibits dopamine and norepinephrine reuptake.

Naproxen (NSAID) inhibits platelet aggregation and injures the gastric mucosa.

Ketoconazole is a strong CYP3A4 inhibitor.

Voriconazole is a strong CYP3A4 inhibitor.

Posaconazole is a strong CYP3A4 inhibitor.

Ritonavir is the strongest CYP3A4 inhibitor.

Cobicistat is a strong CYP3A4 inhibitor.

Both drugs are 5-HT1B/1D vasoconstrictors.

IV methylene blue is a potent reversible MAO-A inhibitor.

Posaconazole is a strong CYP3A4 inhibitor.

Posaconazole is a strong CYP3A4 inhibitor.

Posaconazole is a strong CYP3A4 inhibitor.

Ketorolac is the most potent available NSAID.

Erythromycin inhibits CYP3A4 (disopyramide metabolism) and itself prolongs QT.

Clarithromycin is a strong CYP3A4 inhibitor; disopyramide rises 3-fold.

Amiodarone is the strongest clinical QT prolonger and CYP3A4 inhibitor.

Verapamil inhibits renal OCT2 transporter that clears dofetilide.

Hydrochlorothiazide causes hypokalaemia and hypomagnesaemia; combined with dofetilide leads to torsades de pointes.

Fluvoxamine inhibits CYP2C19 and CYP1A2 – minor warfarin clearance routes.

Trimethoprim inhibits renal OCT2 transporter clearing dofetilide.

Ketoconazole inhibits CYP3A4 (dofetilide metabolism) and OCT2.

Both drugs prolong QT (pimavanserin 5-8 ms, ondansetron 10-15 ms).

Clarithromycin inhibits CYP3A4 – pimavanserin rises 2-3 fold.

Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI).

Additive QT prolongation (amiodarone 30-50 ms, pimavanserin 5-8 ms).

Clarithromycin inhibits CYP3A4 – cisapride rises 5-7 fold.

Itraconazole is the strongest CYP3A4 inhibitor.

Both are potassium-sparing diuretics.

Enalapril suppresses aldosterone – less potassium excreted.

Omeprazole raises gastric pH – atazanavir solubility drops, bioavailability falls 75%.

Atazanavir inhibits CYP3A4.

CYP3A4 inhibition by atazanavir raises pimozide – torsades de pointes.

CYP3A4 inhibition – fatal ergotism.

Darunavir inhibits CYP3A4.

CYP3A4 inhibition – fatal ergotism.

Carbamazepine is a strong CYP3A4 inducer.

Efavirenz induces CYP3A4 and P-gp.

Efavirenz induces CYP3A4.

Trimethoprim blocks ENaC in collecting ducts – potassium retention.

Dual K+-sparing effect: enalapril suppresses aldosterone, trimethoprim blocks ENaC.

Both inhibit ALDH.

Disulfiram inhibits CYP2C9 and CYP2C19.

Clarithromycin inhibits CYP3A4 – dihydroergotamine accumulates 5-10 fold.

Strongest CYP3A4 inhibitor – dihydroergotamine rises 20+ fold.

Ritonavir is the strongest ARV CYP3A4 inhibitor.

Both are 5-HT1B/1D vasoconstrictors.

Both raise cGMP in vascular smooth muscle.

Cyclosporine inhibits both CYP3A4 and P-glycoprotein – the clearance routes of colchicine.

Synergistic systemic vasodilation.

Ritonavir inhibits CYP3A4 – tadalafil rises 5-fold.

Both raise cGMP.

Same as tadalafil-nitrate.

Ritonavir – CYP3A4 inhibitor.

Sildenafil and isosorbide dinitrate via cGMP – synergistic hypotension.

Both activate cGMP pathway.

Riociguat activates sGC independently of NO.

Erythromycin inhibits CYP3A4 – bromocriptine rises 4-5 fold.

CYP3A4 inhibition – bromocriptine rises 4-5 fold.

Itraconazole is the strongest CYP3A4 inhibitor.

Meperidine inhibits serotonin reuptake.

Same pharmacodynamics – fatal serotonin syndrome.

Linezolid is a reversible MAO inhibitor.

Ritonavir inhibits CYP3A4 (meperidine metabolism) while inducing formation of neurotoxic normeperidine.

Itraconazole inhibits CYP3A4 and P-gp.

Same CYP3A4 + P-gp pharmacodynamics.

Strong CYP3A4 inhibitor.

Both cause renal potassium loss.

Both nephrotoxic.

Amphotericin B causes hypokalaemia, which enhances digoxin binding to cardiomyocyte Na-K-ATPase and potentiates digoxin toxicity.

Clarithromycin is a strong CYP3A4 and P-glycoprotein inhibitor.

Quinidine is a strong CYP2D6 inhibitor; flecainide is a CYP2D6 substrate.

Clarithromycin inhibits CYP3A4 (main sirolimus pathway) and P-gp.

Ketoconazole is a strong CYP3A4 inhibitor.

Ritonavir is the strongest CYP3A4 inhibitor.

Both are mTOR inhibitors.

Erythromycin inhibits CYP3A4.

Itraconazole is a strong CYP3A4 inhibitor.

Posaconazole is a strong CYP3A4 inhibitor.

Clarithromycin inhibits CYP3A4 and P-gp.

Strong CYP3A4 inhibitor – everolimus rises 9-fold.

Strongest CYP3A4 inhibitor.

Cobicistat is a strong CYP3A4 inhibitor (similar to ritonavir).

Rifampicin is a strong CYP3A4 inducer.

Strong CYP3A4 inhibitor.

Rifampicin induces CYP3A4 and CYP2B6.

Strong CYP3A4 induction – atazanavir falls 80%.

Strong CYP3A4 induction – darunavir falls 80%.

Strong CYP3A4 inhibitor.

Ritonavir has dual action: inhibits CYP3A4 (raises methadone) and induces CYP2B6 (lowers methadone).

IV methylene blue inhibits MAO-A.

Linezolid is a reversible MAO inhibitor with antibacterial activity.

Clarithromycin inhibits CYP3A4 (raises methadone) and itself prolongs QT.

Strong CYP3A4 inducer.

Strong CYP3A4 inducer.

Strong CYP3A4 + P-gp inducer.

Ritonavir is the most potent CYP3A4 and P-glycoprotein inhibitor in clinical use (a pharmacokinetic booster in HIV regimens).

Ritonavir strongly inhibits CYP3A4 and P-glycoprotein – the clearance routes of rivaroxaban.

Same pharmacodynamics – synergistic hypotension.

Riociguat activates sGC independently of NO.

Both activate cGMP pathway.

Tramadol is a weak opioid with additional serotonin–norepinephrine reuptake inhibition.

Sumatriptan is a 5-HT1B/1D agonist, partly metabolised by MAO-A.

Tranylcypromine irreversibly inhibits MAO-A.

Rizatriptan is a MAO-A substrate.

MAO-A inhibition by tranylcypromine + rizatriptan – fatal serotonin syndrome.

Zolmitriptan is MAO-A + CYP1A2 substrate.

MAO-A inhibition + zolmitriptan – fatal serotonin syndrome.

Almotriptan is CYP3A4 + CYP2D6 substrate.

MAO-A inhibition + triptan – fatal serotonin syndrome.

Naratriptan is a serotonin agonist.

Frovatriptan is a serotonin agonist, CYP1A2 substrate.

Eletriptan is a serotonin agonist, CYP3A4 substrate.

Selegiline at high doses loses MAO-B selectivity and inhibits MAO-A.

Both strongly prolong QT (amiodarone 30-50 ms, sotalol 30 ms).

Both prolong QT (moxifloxacin 10-20 ms, citalopram dose-dependent).

Methadone prolongs QT (especially above 80 mg/day).

Sertraline (SSRI) blocks serotonin reuptake into platelets, depleting the platelet serotonin pool and impairing primary haemostasis.

Ziprasidone prolongs QT clinically (15-20 ms).

Dual QT prolongation, torsades risk.

Ondansetron prolongs QT 10-15 ms, amiodarone 30-50 ms.

Additive QT prolongation from two strong QT prolongers + amiodarone inhibits CYP3A4 (methadone rises).

Fluconazole prolongs QT (5-10 ms) + inhibits CYP3A4 and CYP2C9 (amiodarone metabolism).

Apixaban inhibits factor Xa; ibuprofen (NSAID) injures the gastric mucosa and transiently inhibits platelet aggregation.

Clopidogrel blocks the platelet P2Y12 receptor; rivaroxaban directly inhibits factor Xa.

CYP3A4 inhibition – lovastatin rises 5-fold.

Amiodarone inhibits CYP3A4.

Erythromycin inhibits CYP3A4.

Voriconazole inhibits CYP3A4.

Atazanavir inhibits CYP3A4.

Cyclosporine inhibits OATP1B1 – pitavastatin rises 5-7 fold.

Cyclosporine inhibits OATP1B1.

Clarithromycin inhibits CYP3A4.

Strong CYP3A4 inhibitor.

Strong CYP3A4 inhibitor.

Ritonavir is the strongest CYP3A4 inhibitor.

Strong CYP3A4 + P-gp inducer.

Fluoxetine inhibits CYP2C19, the enzyme converting clopidogrel into its active metabolite.

Ritonavir inhibits CYP3A4 (and weakly CYP2D6).

Paroxetine is a strong CYP2D6 inhibitor.

Fluconazole inhibits CYP2C19, the key enzyme converting clopidogrel into its active metabolite.

Fluvoxamine is a strong CYP1A2 inhibitor.

Dual QT prolongation (ziprasidone 15-20 ms + moxifloxacin 10-20 ms).

Sotalol + citalopram – additive QT prolongation.

Dual QT prolongation (amiodarone 30-50 ms, droperidol 10-20 ms).

Dual QT prolongation.

Additive QT prolongation (ondansetron 10-15 ms + droperidol 10-20 ms).

Dual RAAS blockade (ACE-I + ARB).

Dual QT prolongation, especially with methadone above 80 mg/day.

Dual QT prolongation, additive hypotension (chlorpromazine alpha-1 block).

Additive QT prolongation.

Rifampicin is a strong CYP3A4 inducer.

Carbamazepine is a strong CYP3A4 inducer.

Dual RAAS blockade (ACE-I + ARB).

Strong CYP3A4 induction.

Losartan (ARB) reduces aldosterone synthesis and angiotensin-dependent constriction of glomerular afferent arterioles.

Trimethoprim blocks collecting duct sodium channels (amiloride-like mechanism) and reduces potassium secretion.

Isavuconazole is a moderate CYP3A4 inhibitor.

Rifabutin is a moderate CYP3A4 + P-gp inducer (2-3 fold weaker than rifampicin).

Ritonavir inhibits CYP3A4.

Clarithromycin inhibits CYP3A4.

Propafenone inhibits renal P-glycoprotein.

Aspirin suppresses renal prostaglandin synthesis that maintains glomerular perfusion.

Propafenone inhibits CYP2C9 (S-warfarin metabolism).

Additive AV node slowing and QT prolongation.

Tamoxifen is a prodrug activated to endoxifen via CYP2D6.

Bupropion is a strong CYP2D6 inhibitor.

Gentamicin (an aminoglycoside) is directly oto- and nephrotoxic.

Trimethoprim in co-trimoxazole inhibits CYP2C9.

Clarithromycin inhibits CYP3A4 and CYP2C9.

Hydrochlorothiazide (thiazide diuretic) increases potassium and magnesium loss.

Additive QT prolongation.

Amoxicillin may reduce gut flora vitamin K synthesis – INR mildly rises.

Additive AV slowing and reduced contractility.

Ibuprofen reversibly binds platelet COX-1 and blocks aspirin's access to its irreversible acetylation site.

Dual mechanism: tramadol weakly prolongs QT (additive with amiodarone) and lowers the seizure threshold.

SSRIs reduce platelet serotonin uptake – impaired aggregation.

Dual mechanism: both prolong QT, and amitriptyline (TCA) additionally blocks cardiac sodium channels – His-Purkinje conduction is depressed.

SSRI + NSAID – increased GI bleeding risk.

SSRI + NSAID – GI bleeding.

Theoretical serotonin syndrome risk with SSRI + triptan.

Indapamide (thiazide-like diuretic) increases potassium and magnesium loss.

Brivudine irreversibly inhibits dihydropyrimidine dehydrogenase (DPD) – the enzyme degrading 5-FU.

Capecitabine is a 5-FU prodrug, same fatal mechanism via brivudine DPD inhibition.

Additive QT prolongation.

Additive QT prolongation.

5-FU inhibits CYP2C9 (S-warfarin metabolism) and impairs vitamin K-dependent clotting factor synthesis through direct myelotoxicity.

Capecitabine raises INR 4-fold or more via CYP2C9 inhibition – EMA Xeloda Section 4.

5-FU inhibits CYP2C9 – phenytoin rises 2-fold.

Additive nephrotoxicity.

Valproate inhibits UGT1A4 – the lamotrigine glucuronidation enzyme.

Carbamazepine induces UGT1A4.

Phenytoin induces UGT1A4.

St John's wort contains hypericin and hyperforin – serotonergic activators and strong inducers of CYP3A4 and P-glycoprotein.

Dual mechanism.

Rifampicin induces UGT1A4.

Ketoconazole inhibits CYP3A4.

Strong CYP3A4 inhibitor – ticagrelor rises 5-7 fold.

Clarithromycin is a strong CYP3A4 inhibitor.

Dual risk.

Strongest CYP3A4 inhibitor.

Strong CYP3A4 inhibitor.

Strong CYP3A4 inducer – ticagrelor falls 86%.

Two SSRIs simultaneously raise synaptic serotonin activity.

Ticagrelor inhibits P-glycoprotein.

Ticagrelor inhibits renal P-glycoprotein.

Erythromycin inhibits CYP3A4 and CYP1A2.

Rifampicin induces CYP1A2 and CYP3A4.

Phenytoin induces CYP1A2.

Prednisolone (a systemic glucocorticoid) suppresses muscle glucose uptake and stimulates hepatic gluconeogenesis – steroid-induced diabetes develops or existing type 2 diabetes decompensates.

Methylprednisolone (a systemic glucocorticoid) modestly lowers the seizure threshold and induces CYP3A4.

Additive nephrotoxicity.

Prednisolone (a systemic glucocorticoid) modestly lowers the seizure threshold; bupropion also lowers it.

Diclofenac (NSAID) suppresses renal prostaglandin synthesis maintaining glomerular perfusion.

Tacrolimus prolongs the QT interval, especially with hypomagnesaemia (common on calcineurin inhibitors).

Tacrolimus prolongs the QT interval, especially with hypomagnesaemia (typical on calcineurin inhibitors).

Additive QT prolongation.

Additive bradycardia and AV block.

Abrupt clonidine withdrawal on a beta-blocker triggers a hypertensive crisis: the α2 effect is lost while β-blockade persists – an 'unopposed' α1 effect develops with a sharp blood pressure rise.

Amitriptyline (TCA) blocks α2-receptors and antagonises clonidine.

Both drugs prolong QT.

Additive seizure threshold reduction (both drugs do this).

Dual risk.

Clarithromycin prolongs QT and is a potent CYP3A4 inhibitor.

Ketoconazole is a potent CYP3A4 inhibitor.

SSRI (sertraline) + SNRI (venlafaxine) – additive serotonergic load.

SSRI (fluvoxamine) + tramadol – serotonin syndrome.

Additive seizure threshold reduction plus elevated synaptic norepinephrine (bupropion is a norepinephrine-dopamine reuptake inhibitor; duloxetine is an SNRI).

Fluvoxamine is a weak CYP2D6 inhibitor but a strong CYP2C19 and CYP1A2 inhibitor.

Additive seizure threshold reduction plus elevated synaptic norepinephrine.

Clopidogrel is a prodrug, activated by CYP2C19.

SSRI + SNRI – serotonergic load rises, serotonin syndrome risk.

SSRI (sertraline) + SNRI (duloxetine) – additive serotonergic load, serotonin syndrome risk without therapeutic rationale.

Bupropion is a potent CYP2D6 inhibitor, the main amitriptyline metabolic route.

Tramadol lowers seizure threshold and prolongs QT.

Ciprofloxacin blocks CYP1A2 and lowers seizure threshold itself.

Fluoxetine is a potent CYP2D6 inhibitor.

Mirtazapine lowers the seizure threshold less than bupropion, but the effect is additive.

Quetiapine lowers the seizure threshold, especially at doses above 300 mg/day.

Additive CNS depression.

Additive serotonergic effect.

SSRI augmentation with mirtazapine in resistant depression is possible ('California rocket fuel').

Hydrochlorothiazide (thiazide diuretic) increases urinary potassium loss.

Additive QT prolongation.

Additive suppression of sinus node and atrioventricular (AV) conduction.

Additive bradycardia and AV conduction suppression.

Metronidazole prolongs the QT interval.

Additive bradycardia and AV conduction suppression.

Additive bradycardia and AV block.

Dual calcium channel blockade: amlodipine is a dihydropyridine blocker, verapamil is non-dihydropyridine.

Carbamazepine is a potent CYP3A4 inducer.

Additive GI bleeding risk: anticoagulant (rivaroxaban) + ulcerogenic NSAID with antiplatelet effect (ibuprofen).

Ketorolac inhibits platelet aggregation and strongly injures the gastric mucosa.

Similar to ibuprofen – additive GI bleeding risk.

Naproxen reduces methotrexate renal clearance by 30–40%.

Ketorolac is the most nephrotoxic NSAID, limited to 5 days of use.

Non-dihydropyridine calcium channel blocker (verapamil) + beta-blocker (carvedilol) – additive AV node blockade and negative inotropic effect.

Trimethoprim in co-trimoxazole blocks the epithelial sodium channel (ENaC) like amiloride – potassium retention.

Empagliflozin (SGLT2 inhibitor) causes osmotic diuresis and mild hypovolaemia.

Dexamethasone causes sodium and water retention via mineralocorticoid effect, reducing the antihypertensive effect of the beta-blocker.

Rifampicin strongly induces CYP3A4, which partly metabolises fluconazole.

Rifampicin strongly induces CYP3A4 – the main haloperidol metabolic route.

Dual CYP3A4 inhibition (clarithromycin + ritonavir).

Non-dihydropyridine calcium channel blocker (diltiazem) + beta-blocker (bisoprolol) – additive AV node blockade and negative inotropic effect.

Diltiazem slows AV conduction + inhibits CYP3A4 (metoprolol metabolism).

Non-dihydropyridine calcium channel blocker (diltiazem) + non-selective beta-blocker (propranolol) – marked additive bradycardia, AV block, negative inotropic effect.

Non-dihydropyridine calcium channel blocker (verapamil) + non-selective beta-blocker (propranolol) – marked additive bradycardia, AV block, negative inotropic effect.

Verapamil and metoprolol slow AV conduction via independent paths.

Dual potent CYP3A4 inhibition.

Ritonavir blocks CYP3A4 and CYP2C19, through which clopidogrel becomes its active metabolite.

Beta-blockers mask adrenergic hypoglycaemia symptoms (tachycardia, tremor, sweating), leaving only neuroglycopenic symptoms (confusion, weakness).

Standard combination in heart failure and hypertension.

Additive bradycardia and atrioventricular (AV) conduction slowing.

Additive hypotension (haloperidol blocks α1-adrenoceptors) and QT prolongation risk (haloperidol is a known QT prolonger).

Standard combination in hypertension – additive antihypertensive effect.

Additive hypotension (quetiapine blocks α1-adrenoceptors) and additive bradycardia.

Standard combination in heart failure with reduced ejection fraction – additive antihypertensive effect.

Rifampicin induces CYP3A4, modestly lowering bisoprolol plasma levels (bisoprolol is metabolised 50% via CYP3A4 and 50% renally).

Vitamin D increases intestinal calcium absorption by activating calbindin in enterocytes.

Synergistic blood pressure reduction – a target hypertension combination.

SGLT2 inhibitors (empagliflozin) cause osmotic diuresis and mild hypovolaemia.

Additive hypotension and sedation.

Fluconazole at high doses (200 mg/day or above) blocks CYP3A4 – the main amlodipine metabolic route.

Fluoxetine and its active metabolite norfluoxetine moderately block CYP3A4 – the main amlodipine metabolic route.

Additive hypotension (haloperidol blocks α1-adrenoceptors) and sedation.

Additive bradycardia and hypotension.

Additive hypotension via different mechanisms – calcium channel blockade (amlodipine) + PDE5 blockade (sildenafil).

Prednisolone causes sodium and water retention via mineralocorticoid effect, antagonising amlodipine's antihypertensive action.

Additive hypotension.

Similar to amlodipine + prednisolone.

Tacrolimus and amlodipine are both CYP3A4 substrates competing for the enzyme.

High aspirin doses (above 1 g/day) weaken the hypotensive and cardioprotective effects of the ACE-I via vasodilator prostaglandin suppression.

High aspirin doses (above 1 g/day) weaken the ARB's antihypertensive effect via vasodilator prostaglandin suppression.

Old experimental data suggested NSAIDs combined with fluoroquinolones increase CNS excitability and seizure risk (via GABAergic suppression).

At analgesic doses (above 1 g/day), aspirin suppresses vasodilator prostaglandins and weakens the ACE-I's hypotensive effect.

High aspirin doses can reduce renal digoxin clearance via prostaglandin-dependent renal blood flow suppression.

Analgesic aspirin doses weaken the ARB's antihypertensive effect via vasodilator prostaglandin suppression.

Similar to ASA + fluvoxamine.

Additive hypotension and fall risk in older patients.

Additive hypotension.

Additive hypotension.

Omeprazole weakly blocks CYP3A4; alprazolam plasma levels may rise slightly.

Naproxen competes with aspirin for platelet COX-1 similar to ibuprofen.

Additive hypotension and fall risk in older patients.

Additive bradycardia and sedation.

Additive bradycardia, hypotension, and sedation.

Additive sedation.

Additive CNS depression and sedation.

Additive CNS depression and sedation.

Azithromycin weakly prolongs QT, additively with the TCA amitriptyline (a pronounced QT prolonger).

Dual macrolide therapy – doubled QT effect and redundant antibacterial activity without clinical rationale.

Both prolong QT.

Additive QT prolongation – both drugs prolong QTc dose-dependently.

Additive QT prolongation.

Additive QT prolongation (tacrolimus prolongs QT in hypomagnesaemia, common on calcineurin inhibitors).

Additive QT prolongation (tramadol weakly prolongs QT).

Additive QT prolongation (fluoxetine weakly prolongs QT at high doses).

Additive QT prolongation (mirtazapine weakly prolongs QT, especially above 30 mg).

Additive QT prolongation (quetiapine prolongs QT at high doses).

Additive QT prolongation (sertraline minimally prolongs QT at standard doses, azithromycin dose-dependently).

Additive sedation, anticholinergic effect, and weight gain.

TCAs may mask hypoglycaemia symptoms (tremor, tachycardia) via anticholinergic effect.

Amitriptyline is metabolised via CYP2C9 (a minor route) – weak competition with warfarin is possible.

Additive orthostatic hypotension.

Additive orthostatic hypotension.

Additive orthostatic hypotension via different mechanisms.

Additive orthostatic hypotension.

Additive orthostatic hypotension.

Amitriptyline is a CYP2D6 substrate, as is metoprolol.

Verapamil blocks CYP3A4 (one of the amitriptyline metabolic routes).

Fluconazole weakly blocks CYP2C19 and CYP3A4 – amitriptyline metabolic routes.

Ketoconazole blocks CYP3A4 (one of the amitriptyline metabolic routes).

Additive CNS depression and sedation.

Valproate weakly blocks hepatic amitriptyline metabolism; TCA plasma levels may rise.

Omeprazole weakly blocks CYP3A4 – atorvastatin exposure rises modestly (by 10–20%).

Dexamethasone induces CYP3A4.

Esomeprazole weakly affects CYP3A4 (mainly via CYP2C19).

Paracetamol at doses above 3 g/day for more than 7 days raises INR by 1–1.

Simvastatin weakly inhibits CYP3A4 and partly displaces warfarin from protein binding.

Allopurinol weakly inhibits CYP2C9 and reduces metabolism of the more active S-warfarin enantiomer.

Tramadol indirectly affects CYP2C9-mediated warfarin metabolism via CYP2D6.

Dexamethasone is a weak CYP3A4 inducer and a potential weak CYP2C9 inhibitor.

Amiodarone weakly inhibits CYP2C19, the key enzyme that converts clopidogrel to its active metabolite.

Ibuprofen blocks platelet aggregation via COX-1 inhibition, additively with clopidogrel.

Fluvoxamine impairs primary haemostasis by inhibiting platelet serotonin reuptake.

Citalopram, like other SSRIs, impairs primary haemostasis by inhibiting platelet serotonin reuptake.

Diltiazem moderately inhibits CYP3A4 and P-glycoprotein; apixaban is substrate for both.

Duloxetine (SNRI) moderately impairs primary haemostasis by inhibiting platelet serotonin reuptake.

Fluoxetine, like other SSRIs, impairs primary haemostasis by inhibiting platelet serotonin reuptake.

No direct pharmacokinetic interaction.

Venlafaxine (SNRI) moderately impairs primary haemostasis by inhibiting platelet serotonin reuptake.

Verapamil moderately inhibits CYP3A4 and P-glycoprotein.

Thiazide diuretic causes hypokalaemia and hypomagnesaemia, increasing myocardial sensitivity to digoxin.

Spironolactone moderately inhibits P-glycoprotein; digoxin levels rise by 20–30%.

Telmisartan moderately inhibits intestinal P-glycoprotein.

In 10–15% of patients, gut flora (mainly Eubacterium lentum) metabolises part of digoxin to inactive products.

Additive antihypertensive effect; in hypovolaemic patients it can trigger acute kidney injury.

Additive antihypertensive effect.

Target combination in heart failure with reduced ejection fraction and in arterial hypertension.

Glucocorticoids retain sodium and water via mineralocorticoid effect, blunting the ACE inhibitor's antihypertensive effect.

Prednisolone retains sodium and water via mineralocorticoid effect, blunting the ARB's antihypertensive effect.

Dexamethasone has minimal mineralocorticoid activity but, at high doses and prolonged use, blunts the ACE inhibitor's antihypertensive effect.

Opposing effects on potassium: furosemide depletes it via the loop of Henle, spironolactone retains it by blocking aldosterone in collecting ducts.

Opposing effects on potassium: thiazide depletes it, spironolactone retains it.

Sequential nephron blockade: furosemide acts at the loop of Henle, the thiazide at the distal tubule.

Prednisolone is ulcerogenic — suppresses prostaglandin synthesis and gastric mucosal turnover.

Calcium binds levothyroxine in the gut as insoluble complexes, reducing absorption by 20–25%.

Metformin suppresses calcium-dependent absorption of the B12-intrinsic factor complex in the terminal ileum.

Pantoprazole reduces gastric acidity and B12 release from food.

Thiazide diuretics raise allopurinol and oxypurinol metabolite levels, increasing hypersensitivity risk, including allopurinol hypersensitivity syndrome (DRESS).

Dexamethasone is a weak CYP3A4 inducer and may slightly reduce amiodarone levels in long-term therapy.

Rosuvastatin is minimally metabolised by CYP3A4, so amiodarone's CYP3A4 inhibition has limited effect.

No direct pharmacokinetic interaction.

Amiodarone contains 37% iodine in its structure.

No direct pharmacokinetic interaction.

Amiodarone inhibits CYP1A2 and CYP3A4 — the key enzymes of theophylline metabolism.

Fluvoxamine is a strong CYP1A2 inhibitor and moderate CYP3A4 inhibitor.

Additive bradycardia and QT effect from amiodarone, on top of carvedilol's negative chronotropy.

Duloxetine is a CYP1A2 and CYP2D6 substrate.

Amiodarone is a weak CYP3A4 inhibitor.

Amiodarone inhibits CYP3A4 — the enzyme responsible for budesonide metabolism.

Dual immunomodulation.

Additive GI ulcer and bleeding risk with systemic budesonide.

Oestrogens raise corticosteroid-binding globulin, increasing the bound budesonide fraction, but the effective free fraction changes minimally.

Oestradiol raises corticosteroid-binding globulin, increasing the bound budesonide fraction.

Systemic budesonide retains sodium and water via mineralocorticoid effect (weaker than prednisolone), antagonising the ACE inhibitor's antihypertensive effect.

Glucocorticoid plus NSAID — additive GI ulcer risk with systemic budesonide.

Fluoroquinolone plus systemic glucocorticoid — tendinitis and tendon rupture risk (mainly Achilles tendon).

Systemic budesonide retains sodium and water via mineralocorticoid effect, blunting clonidine's antihypertensive effect.

Additive hypotension and sedation.

Diltiazem moderately inhibits CYP3A4; alprazolam is a CYP3A4 substrate.

Additive hypotension.

Tacrolimus is a weak CYP3A4 inhibitor; alprazolam is a CYP3A4 substrate.

Fluvoxamine inhibits CYP3A4 and CYP1A2.

Additive CNS depression via different mechanisms: alprazolam (GABAergic) and gabapentin (α2δ calcium channel inhibition).

Additive CNS depression.

Additive CNS depression via different mechanisms (GABAergic for alprazolam, α2δ calcium channel blockade for pregabalin).

Additive CNS and respiratory depression.

Additive CNS depression (minimal for venlafaxine, mainly from alprazolam).

Bupropion lowers seizure threshold, especially at high doses (above 300 mg/day) or in predisposition.

Additive anticholinergic effect (amitriptyline pronounced, celecoxib mild).

Diltiazem weakly inhibits CYP2D6 and CYP3A4; amitriptyline is metabolised by both.

Tacrolimus prolongs QT; the TCA does the same independently via a quinidine-like effect on cardiomyocyte Na/K channels.

Additive orthostatic hypotension.

Additive CNS depression via different mechanisms.

Similar to amitriptyline plus gabapentin — additive CNS depression.

Additive anticholinergic and QT effects.

Ciprofloxacin absorbs better in acidic gastric environment.

Calcium forms insoluble chelates with ciprofloxacin in the gut.

Ciprofloxacin is a weak P-glycoprotein inhibitor and may slightly raise colchicine levels.

Spironolactone is a weak P-glycoprotein inhibitor and may slightly raise colchicine levels.

Additive nephrotoxicity.

Additive nephrotoxicity.

Escitalopram is metabolised mainly by CYP2C19 and partly by CYP3A4.

Metoprolol is cardioselective but at high doses antagonises theophylline's bronchodilator effect.

Propranolol is non-selective, blocks bronchial β2 receptors, and antagonises theophylline's bronchodilator effect.

A bacteriostatic agent (doxycycline) suppresses the bactericidal action of a beta-lactam (amoxicillin), which requires active bacterial division.

Loratadine is a second-generation antihistamine with minimal blood-brain barrier penetration.

Cetirizine penetrates the blood-brain barrier at higher doses.

Paracetamol does not interact significantly with ciclosporin in short courses.

Metoprolol is mainly metabolised by CYP2D6; clarithromycin does not clinically significantly inhibit CYP2D6.

Carbamazepine is a strong CYP3A4 inducer.

Phenobarbital is a strong CYP3A4 inducer; it lowers oestradiol levels by 40–60%.

Beta-blockers mask adrenergic hypoglycaemia symptoms (tachycardia, tremor, sweating).

Metformin on long-term use (over 5 years) moderately reduces blood B12 (by 10–30%).

Ascorbic acid raises gastric acidity and improves levothyroxine absorption in patients with atrophic gastritis or hypochlorhydria.

Calcium carbonate slightly reduces metformin intestinal absorption when taken together.

Calcium carbonate as an antacid may theoretically reduce metronidazole absorption, but no clinically significant effect on antibacterial efficacy has been described.

Paracetamol is metabolised by CYP2E1 (5%) and predominantly by glucuronidation; metoprolol by CYP2D6.

Curcumin (Curcuma longa extract) theoretically weakly inhibits CYP2E1, which produces paracetamol's hepatotoxic metabolite NAPQI.

Ascorbic acid does not affect cetirizine metabolism.

Zinc theoretically competes with metformin for renal tubular organic cation secretion, but no clinically significant hyperglycaemia has been described on the combination.

St John's wort is a CYP3A4 inducer and a weak CYP2E1 inducer.

Proton pump inhibitors suppress gastric acidity and reduce B12 release from food (which requires HCl and pepsin).

Simethicone is a surface-active silicone agent that is not absorbed in the gastrointestinal tract.

Fluoxetine (SSRI) depletes the platelet serotonin pool, impairing primary haemostasis.

Sertraline (SSRI) depletes the platelet serotonin pool, weakening platelet aggregation.

Clarithromycin blocks CYP3A4 – the main quetiapine metabolic route.

Carbamazepine induces P-glycoprotein, the main dabigatran clearance route.

Dual risk.

Clarithromycin inhibits CYP3A4, the carbamazepine metabolism enzyme.

Ciprofloxacin is a strong CYP1A2 inhibitor.

Clarithromycin blocks CYP3A4 – the main alprazolam metabolic route.

Amiodarone blocks CYP3A4 and the P-glycoprotein transporter – two colchicine clearance routes.

Ketoconazole strongly blocks CYP3A4 – the main alprazolam metabolic route.

Fluconazole at 200 mg/day or above blocks CYP3A4 – the main colchicine clearance route.

Linezolid is a reversible monoamine oxidase (MAO) inhibitor.

Additive nephrotoxicity.

Fluoxetine and its active metabolite norfluoxetine moderately block CYP3A4.

Fluconazole at 200 mg/day or above moderately inhibits CYP3A4; at 400 mg/day, strongly.

Warfarin blocks vitamin K-dependent clotting factor synthesis; dabigatran is a direct thrombin inhibitor.

Simvastatin is metabolised by CYP3A4; colchicine uses the same route and inhibits it.

Clarithromycin blocks CYP3A4 – the main sildenafil metabolic route.

NSAIDs reduce renal lithium clearance via prostaglandin-dependent renal blood flow blockade.

Clonidine is an α2-agonist that reduces sympathetic tone.

Fluvoxamine blocks CYP2C19 and CYP3A4 – both diazepam metabolic routes.

Diltiazem blocks CYP3A4 – the main carbamazepine metabolic route.

Clarithromycin blocks CYP3A4 – the main tamsulosin metabolic route.

Esomeprazole is the S-isomer of omeprazole, the same CYP2C19 inhibitor.

Additive nephrotoxicity via two distinct mechanisms.

Ketoconazole is a potent CYP3A4 inhibitor – the main tamsulosin metabolic route.

Amiodarone inhibits CYP3A4 and P-glycoprotein.

Diltiazem moderately inhibits CYP3A4 – a partial atorvastatin metabolic route.

Dronedarone strongly inhibits intestinal P-glycoprotein, the clearance route of dabigatran.

Cyclosporine is a strong CYP3A4 and P-glycoprotein inhibitor.

Cyclosporine inhibits OATP1B1 – rosuvastatin hepatic uptake falls, plasma concentration rises 7-fold.

Colchicine is a CYP3A4 and P-glycoprotein substrate with narrow therapeutic window.

Tacrolimus is almost entirely cleared via hepatic CYP3A4.

Quetiapine is cleared via hepatic CYP3A4.

Linezolid is an oxazolidinone antibiotic that also reversibly inhibits monoamine oxidase (MAO).

Amiodarone and dronedarone are class III antiarrhythmics with overlapping mechanism and additive QT prolongation.

Amitriptyline (tricyclic antidepressant) prolongs QT.

Tacrolimus (a post-transplant immunosuppressant) is cleared via hepatic CYP3A4.

Dual mechanism: ritonavir strongly inhibits CYP3A4, the partial clearance route of amiodarone, raising amiodarone levels.

Clarithromycin blocks CYP3A4 – the main hepatic metabolic route for budesonide.

Ketoconazole strongly blocks CYP3A4 – the main budesonide metabolic route.

Captopril (ACE-I) reduces aldosterone synthesis, while spironolactone directly blocks aldosterone receptors.

Intravenous iodinated contrast media (iopromide) can cause acute kidney injury via osmotic load and direct toxicity.

Sertraline (SSRI) raises synaptic serotonin; tramadol blocks serotonin and norepinephrine reuptake.

Dual mechanism.

Both drugs raise serotonergic transmission and prolong QT.

Additive QT prolongation and anticholinergic effect.

Fluconazole at 200 mg/day or above blocks CYP3A4 – the main alprazolam metabolic route.

Clarithromycin blocks CYP3A4 – the main methylprednisolone metabolic route.

Contrast-induced nephropathy lowers renal methotrexate clearance.

Ketoconazole strongly blocks CYP3A4 – the main methylprednisolone metabolic route.

Ritonavir is the most potent CYP3A4 inhibitor available – the main methylprednisolone metabolic route.

Strong CYP3A4 inhibitor – tacrolimus rises 4-5 fold.

Amiodarone blocks CYP3A4 and P-glycoprotein – two key tacrolimus clearance routes.

Tacrolimus and colchicine are both P-glycoprotein substrates.

Dronedarone blocks the P-glycoprotein transporter – the main tacrolimus clearance route.

Esomeprazole inhibits CYP2C19.

Fluconazole at 200 mg/day or above blocks CYP3A4 – the main tacrolimus metabolic route.

Propranolol is a non-selective beta-blocker (β1 and β2).

Ritonavir is the most potent CYP3A4 inhibitor available – the main alprazolam metabolic route.

Ritonavir is the most potent CYP3A4 inhibitor available.

Both drugs prolong QT and are serotonergic.

Fluvoxamine is the strongest clinical CYP1A2 inhibitor.

Ketoconazole is a potent CYP3A4 inhibitor – the main quetiapine metabolic route.

Fluoxetine is a potent CYP2D6 inhibitor, the main carvedilol metabolic route.

Ketoconazole is a potent CYP3A4 and P-glycoprotein inhibitor – two main cyclosporine clearance routes.

Clarithromycin blocks CYP1A2 and CYP3A4 – theophylline metabolic routes.

Diltiazem blocks CYP3A4 and P-glycoprotein – cyclosporine clearance routes.

Tamsulosin is a CYP3A4 substrate.

Amlodipine weakly inhibits CYP3A4 – a partial atorvastatin metabolic route.

Dual calcium channel blockade: amlodipine (dihydropyridine), diltiazem (non-dihydropyridine).

Azithromycin is a weak P-glycoprotein inhibitor; rivaroxaban is a P-glycoprotein substrate.

Atorvastatin blocks intestinal P-glycoprotein (one of the digoxin clearance routes).

Carbamazepine induces CYP3A4; alprazolam plasma levels fall by 50%.

Carbamazepine induces CYP3A4 – the main amlodipine metabolic route.

Rifampicin strongly induces CYP3A4 – the main N-deethylation pathway of amiodarone.

Additive bradycardia and hypotension.

Additive CNS depression, sedation, and anticholinergic effect (constipation, urinary retention).

Dexamethasone is a potent CYP3A4 inducer and weak CYP2B6 inducer (which metabolises bupropion).

Rifampicin is the most potent CYP3A4 inducer available.

Additive hypotensive effect.

Theophylline at toxic doses causes seizures by itself.

Dronedarone is a strong CYP3A4 inhibitor, the main alprazolam metabolic route.

Sildenafil is a vasodilator via PDE5 blockade.

Additive sedation.

Azithromycin is a weak CYP1A2 inhibitor (theophylline is a substrate).

Additive anticholinergic effect and sedation.

Rifampicin strongly induces CYP3A4 and the OATP1B1 transporter – two atorvastatin clearance routes.

Azithromycin inhibits the P-glycoprotein transporter less than clarithromycin but still blocks a colchicine clearance route.

Carvedilol is a moderate P-glycoprotein inhibitor; colchicine is a P-glycoprotein substrate with a narrow therapeutic window.

Carbamazepine is a strong CYP3A4 inducer.

Rifampicin strongly induces CYP3A4 and the OATP1B1 transporter – the routes of simvastatin activation and hepatocyte uptake.

Diltiazem is a moderate CYP3A4 and P-glycoprotein inhibitor.

Dual antibiotic therapy with additive QT prolongation.

Rifampicin is a potent CYP3A4 inducer.

Colchicine is cleared via CYP3A4 and P-glycoprotein.

Sildenafil is cleared via hepatic CYP3A4.

Colchicine is cleared via hepatic CYP3A4 and the P-glycoprotein transporter.

Sildenafil blocks phosphodiesterase-5, slowing breakdown of cGMP – the intracellular mediator of vascular relaxation.

Dual mechanism: amiodarone blocks CYP3A4 – a partial sildenafil metabolic route – and both drugs prolong QT.

Dronedarone strongly blocks both P-glycoprotein and CYP3A4 – two colchicine clearance routes.

Verapamil blocks CYP3A4 and the P-glycoprotein transporter – two colchicine clearance routes.

Additive hypotension with sublingual nitroglycerin.

Additive orthostatic hypotension with sublingual nitroglycerin.

Additive QT prolongation.

Two SSRIs simultaneously raise synaptic serotonin activity.

Apixaban inhibits factor Xa; diclofenac injures the gastric mucosa and reduces platelet aggregation.

Additive serotonergic effect.

Indapamide (thiazide-like diuretic) increases urinary potassium loss.

Dual RAAS blockade (ACE-I + ARB).

Dual QT prolongation.

Mirtazapine prolongs QT dose-dependently, additively with haloperidol (especially parenteral).

Sertraline at high doses prolongs QT, additively with haloperidol.

Dexamethasone is a weak CYP3A4 inducer.

NSAIDs weaken amlodipine's antihypertensive effect via renal prostaglandin suppression.

Additive gastroesophageal ulcer and bleeding risk.

Similar to naproxen + lithium.

Amiodarone prolongs QT and weakly blocks CYP3A4 (the main quetiapine metabolic route).

Similar to apixaban + meloxicam.

Dual RAAS blockade (ACE-I + ARB).

Dual NSAID therapy – additive GI bleeding, nephrotoxicity, and cardiovascular event risks.

Additive QT prolongation.

Contrast and NSAID (naproxen) – additive nephrotoxicity, especially in chronic kidney disease and dehydration.

Direct oral anticoagulant (rivaroxaban) + NSAID (naproxen) – additive GI bleeding risk.

Glucocorticoids damage the gastric mucosa and suppress protective prostaglandin production.

Meloxicam is preferentially COX-2 selective and weakly displaces aspirin from COX-1.

NSAIDs weaken the antihypertensive effect of beta-blockers.

Celecoxib is metabolised by CYP2C9 – the same route as S-warfarin (the more active form).

IV methylene blue inhibits MAO-A.

IV methylene blue reversibly inhibits MAO-A.

Rivaroxaban blocks factor Xa; dabigatran blocks thrombin.

Ketoconazole strongly inhibits both CYP3A4 and P-glycoprotein – the clearance routes of apixaban.

Mirtazapine increases serotonin release by blocking presynaptic α2-adrenergic autoreceptors.

Venlafaxine is a serotonin–norepinephrine reuptake inhibitor (SNRI).

Methylene blue (methylthioninium chloride) given intravenously is a potent reversible MAO-A inhibitor.

IV methylene blue is a reversible MAO-A inhibitor.

Aspirin irreversibly blocks platelet cyclooxygenase; apixaban directly inhibits factor Xa.

Sertraline (SSRI) depletes the platelet serotonin pool and impairs primary haemostasis.

Enalapril (an angiotensin-converting enzyme inhibitor, ACE-I) reduces aldosterone synthesis, while spironolactone directly blocks aldosterone receptors.

Losartan (angiotensin II receptor blocker, ARB) suppresses the renin-angiotensin-aldosterone system and reduces aldosterone release.

Valsartan (ARB) suppresses the RAAS, while spironolactone blocks aldosterone receptors.

Mirtazapine prolongs QT dose-dependently.

Additive QT prolongation.

SSRI + SNRI – serotonergic load rises, serotonin syndrome risk.

Two SSRIs simultaneously.

Mirtazapine increases serotonergic transmission via α2-adrenergic blockade and blocks 5-HT2A/2C.

Quetiapine prolongs QT at high doses.

Dual SNRI – doubling the same pharmacological effect without therapeutic benefit.

SSRI + SNRI – serotonin syndrome without therapeutic rationale.

Pregabalin acts via the α2δ subunit of calcium channels and depresses the central nervous system.

Additive QT risk.

Additive CNS and respiratory centre depression.

Additive CNS and respiratory depression.

Sertraline at high doses (above 150 mg/day) moderately prolongs QT.

Mirtazapine prolongs QT dose-dependently (especially above 30 mg/day).

Dronedarone is a strong CYP3A4 inhibitor, the main amlodipine metabolic route.

Additive QT prolongation at high quetiapine doses.

NSAIDs reduce renal blood flow via prostaglandin blockade.

Similar to ibuprofen + losartan.

NSAIDs reduce renal methotrexate clearance (both selective and non-selective COX inhibitors).

Similar to enalapril + celecoxib.

Similar to losartan + ibuprofen.

Apixaban is a direct factor Xa inhibitor; meloxicam blocks platelet function and injures the GI mucosa.

Contrast (iopromide) and an NSAID (celecoxib) are both nephrotoxic.

Ibuprofen reduces renal blood flow via PGE2 inhibition.

Direct oral anticoagulant (rivaroxaban) + NSAID (meloxicam) – additive GI bleeding risk via combined anticoagulation, mucosal injury, and platelet dysfunction.

NSAID (naproxen) + nephrotoxic calcineurin inhibitor (tacrolimus) – additive acute kidney injury risk in transplant patients.

Contrast (iopromide) and nephrotoxic immunosuppressant (tacrolimus) – high contrast-induced nephropathy risk.

Similar to iopromide + naproxen.

Additive hyperkalaemia.

Dual RAAS blockade – increased hyperkalaemia, hypotension, and acute kidney injury without outcome improvement (ONTARGET).

Trimethoprim blocks sodium channels via an amiloride-like mechanism, additively with an ARB (losartan) causing hyperkalaemia.

Prednisolone causes sodium and water retention via mineralocorticoid effect, reducing bisoprolol's antihypertensive effect.

NSAIDs weaken the antihypertensive effect of beta-blockers via prostaglandin-dependent renal regulation (natriuresis).

Similar to bisoprolol + ketorolac.

Methylprednisolone causes sodium and water retention via mineralocorticoid effect, reducing the antihypertensive effect of the beta-blocker.

Beta-blockers can make treating anaphylaxis to iodinated contrast harder – adrenaline becomes less effective due to β-blockade.

NSAIDs weaken the antihypertensive effect of beta-blockers via renal prostaglandin suppression.

At high aspirin doses (above 1 g/day), vasodilator prostaglandins are suppressed, weakening amlodipine's antihypertensive effect.

Ketorolac suppresses vasodilator prostaglandins, weakening amlodipine's antihypertensive effect.

NSAIDs weaken amlodipine's antihypertensive effect via renal prostaglandin suppression.

Diltiazem impairs platelet function via calcium channel blockade; aspirin is an antiplatelet.

Similar to ASA + methylprednisolone.

Venlafaxine (SNRI) depletes the platelet serotonin pool, impairing primary haemostasis.

Azithromycin suppresses vitamin K-producing gut flora, raising INR.

Dual statin therapy – doubling the same pharmacological class with additive myopathy risk and no therapeutic benefit.

Dual statin therapy – additive myopathy and rhabdomyolysis risk.

Fluvoxamine blocks CYP3A4 – a partial atorvastatin metabolic route.

Ciprofloxacin disrupts insulin secretion from pancreatic β-cells and concurrently inhibits CYP2C9 – the glibenclamide metabolic route.

Dual mechanism: both prolong QT, and clarithromycin blocks CYP3A4 – a partial amiodarone clearance route.

Verapamil inhibits P-glycoprotein, which clears digoxin via kidney and intestine.

Dual mechanism.

Additive QT prolongation.

Ketoconazole strongly blocks P-glycoprotein, the main transporter of dabigatran.

Carbamazepine induces CYP3A4 and accelerates hepatic doxycycline metabolism.

Amiodarone blocks P-glycoprotein in the intestine and renal tubules – the main dabigatran-style clearance route of digoxin.

Amoxicillin and other penicillins compete with methotrexate for renal tubular secretion.

Verapamil blocks CYP3A4 – the main carbamazepine metabolic route.

Additive tendon injury risk.

The combination raises risk of hypersensitivity reactions and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema).

Aspirin suppresses tubular secretion of methotrexate and displaces it from albumin binding.

Both drugs cause benign intracranial hypertension (pseudotumor cerebri).

Ketoconazole strongly blocks CYP3A4 – the N-deethylation pathway of amiodarone.

Atorvastatin weakly inhibits CYP3A4 and CYP2C9 – the warfarin clearance route.

Amiodarone moderately blocks CYP3A4 – a partial atorvastatin metabolic route.

Dual mechanism.

Amlodipine moderately inhibits CYP3A4 – the main simvastatin metabolic route.

Ketorolac reduces renal methotrexate clearance and suppresses tubular secretion.

Additive ulcerogenic effect with oral budesonide (used in inflammatory bowel disease).

Clarithromycin blocks CYP3A4 and prolongs QT itself.

Cyclosporine blocks the OATP1B1 transporter and CYP3A4 – two atorvastatin clearance routes.

Dronedarone is a strong P-glycoprotein and CYP3A4 inhibitor – two apixaban clearance routes.

Additive myopathy and rhabdomyolysis risk.

Cyclosporine blocks two simvastatin clearance routes: the OATP1B1 transporter (uptake into hepatocytes) and CYP3A4.

Ketoconazole strongly inhibits CYP3A4 – the main atorvastatin metabolic route.

Dronedarone inhibits CYP3A4 – the main simvastatin metabolic route.

Ketorolac is the most potent oral and parenteral NSAID.

Dexamethasone is a CYP3A4 and P-glycoprotein inducer.

Additive tendon injury risk.

Fluconazole at 200 mg/day or above moderately inhibits CYP3A4 – the main simvastatin metabolic route.

Ciprofloxacin blocks CYP1A2 and, to a lesser extent, CYP3A4 – warfarin clearance routes.

Amiodarone blocks intestinal P-glycoprotein – the main route of dabigatran absorption and elimination.

Dual QT-prolongation risk.

Venlafaxine (SNRI) has serotonin and noradrenergic activity; amitriptyline (TCA) acts the same way.

Verapamil inhibits CYP3A4 and P-glycoprotein.

Escitalopram is the S-enantiomer of citalopram.

Linezolid is a reversible monoamine oxidase (MAO) inhibitor.

Additive QT prolongation (both prolong QTc).

Ritonavir is the most potent CYP3A4 inhibitor available – the main amlodipine metabolic route.

Macrolides suppress the gut bacteria Eggerthella lenta that inactivate digoxin.

Verapamil is a moderate CYP3A4 inhibitor.

Diltiazem inhibits CYP3A4.

Ibuprofen and warfarin compete for plasma protein (albumin) binding.

Escitalopram (SSRI) raises synaptic serotonin.

Meloxicam (preferential COX-2 NSAID) inhibits platelet aggregation less than non-selective NSAIDs but still injures the gastric mucosa.

Citalopram (SSRI) raises synaptic serotonin.

Warfarin blocks vitamin K-dependent clotting factor synthesis (II, VII, IX, X); apixaban directly inhibits factor Xa.

Warfarin blocks vitamin K-dependent clotting factor synthesis; rivaroxaban directly inhibits factor Xa.

Clarithromycin is a strong CYP3A4 inhibitor and prolongs QT itself.

Ketoconazole is a strong CYP3A4 inhibitor, the main dronedarone clearance route.

Ritonavir is the most potent CYP3A4 inhibitor available.

Amiodarone blocks the P-glycoprotein transporter and renal tubular secretion of digoxin.

Dronedarone blocks intestinal P-glycoprotein – the main route of digoxin absorption and elimination.

Simvastatin is cleared via hepatic CYP3A4.

Atorvastatin uses hepatic CYP3A4 for ~70% of its clearance.

Diltiazem blocks intestinal P-glycoprotein – a key digoxin absorption route.

Morphine and diazepam act on different receptors (μ-opioid and GABA-A) but both depress the central nervous system and the medullary respiratory centre.

Alprazolam and morphine depress the central nervous system and respiratory centre through different routes (GABA-A and μ-opioid).

Fluoxetine is a potent CYP2D6 inhibitor, the main metoprolol metabolic route.

Phenazepam is a long-acting benzodiazepine with an active metabolite persisting for several days.

Ketorolac and diclofenac are both NSAIDs.

Ketorolac and ibuprofen are both NSAIDs.

Bupropion is a potent CYP2D6 inhibitor, the main metoprolol metabolic route.

Thyroid hormones accelerate catabolism of vitamin K-dependent clotting factors.

Aspirin irreversibly blocks platelet cyclooxygenase and reduces platelet aggregation.

Prednisolone (a systemic glucocorticoid) raises fibrinogen and clotting factors but can also alter warfarin metabolism through liver enzymes.

Tramadol is an opioid with serotonin–norepinephrine reuptake inhibition.

Ketoconazole is a potent inhibitor of hepatic CYP3A4 and the P-glycoprotein transporter.

Ketorolac is a potent non-selective NSAID; nimesulide is a selective COX-2 inhibitor.

Co-trimoxazole contains trimethoprim, a dihydrofolate reductase inhibitor.

Amiodarone prolongs the QT interval.

Apixaban inhibits factor Xa, while ketorolac is the most potent available NSAID.

Clarithromycin blocks intestinal P-glycoprotein, the main transporter of dabigatran.

Clarithromycin blocks CYP3A4 and P-glycoprotein – the two main rivaroxaban clearance routes.

Clarithromycin blocks CYP3A4 and P-glycoprotein – two apixaban clearance routes.

Amiodarone moderately blocks P-glycoprotein and CYP3A4 – two apixaban clearance routes.

Metronidazole stereospecifically inhibits CYP2C9, the clearance route for S-warfarin.

A thiazide diuretic plus an ARB synergistically lower blood pressure: the thiazide reduces circulating volume, losartan vasodilates by suppressing the RAAS.

Metronidazole inhibits CYP2C9 – S-warfarin (more active isomer) accumulates.

Indapamide is a thiazide-like diuretic.

Furosemide (loop diuretic) lowers circulating volume and, via subclinical volume depletion, increases lithium reabsorption in the proximal tubules.

Omeprazole blocks the renal BCRP transporter and reduces methotrexate clearance.

Dual mechanism.

Additive QT prolongation.

Fluoxetine blocks CYP2D6 (a minor amiodarone clearance route) and modestly prolongs QT.

Both prolong QT, and clarithromycin blocks CYP3A4 (a minor escitalopram metabolic route).

Dual mechanism: both prolong QT (additively), and ciprofloxacin blocks CYP1A2 – a partial haloperidol clearance route.

Ketoconazole strongly blocks CYP3A4 – the main sildenafil metabolic route.

The combination raises risk of hypersensitivity reactions and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema).

Carbamazepine strongly induces CYP3A4 and P-glycoprotein.

Complex mechanism.

Escitalopram (SSRI) depletes the platelet serotonin pool, impairing primary haemostasis.

Escitalopram (SSRI) depletes the platelet serotonin pool, impairing primary haemostasis.

Omeprazole is a potent CYP2C19 inhibitor, the main citalopram metabolic route.

Dronedarone prolongs QT (FDA Multaq carries a boxed warning).

Dual risk.

Dual mechanism.

Ciprofloxacin is a potent CYP1A2 inhibitor, the main duloxetine metabolic route.

Dual risk.

Fluvoxamine blocks CYP1A2 (a minor venlafaxine metabolic route).

Duloxetine moderately blocks CYP2D6 (an amitriptyline metabolic route); amitriptyline plasma levels rise.

Additive QT prolongation.

Fluoxetine is a potent CYP2D6 inhibitor; duloxetine is minorly metabolised by CYP2D6.

Additive CNS depression and sedation.

Furosemide (loop diuretic) increases urinary potassium loss.

Amiodarone moderately blocks CYP3A4 and P-glycoprotein – two rivaroxaban clearance routes.

Clarithromycin blocks CYP3A4 – the main amlodipine metabolic route.

Ketoconazole is a strong CYP3A4 inhibitor – the main amlodipine metabolic route.

Proton pump inhibitors block the renal BCRP transporter and reduce methotrexate clearance.

Proton pump inhibitors block the renal BCRP transporter, reducing methotrexate clearance.

Diclofenac competitively inhibits platelet cyclooxygenase-1 and blocks aspirin's access for COX-1 acetylation.

NSAIDs (including selective COX-2 inhibitors like celecoxib) reduce renal lithium clearance.

Calcium carbonate may reduce bisoprolol GI absorption when taken simultaneously.

Fluconazole at 200 mg/day or above blocks CYP2C9 – the main glibenclamide metabolic route.

Ketoconazole is a potent CYP3A4 inhibitor – the main haloperidol metabolic route.

Additive tendon injury risk.

Bupropion blocks CYP2D6.

High aspirin doses displace glibenclamide from albumin binding and suppress hepatic gluconeogenesis.

Additive antiplatelet effect via different targets: aspirin irreversibly blocks platelet cyclooxygenase; clopidogrel inhibits the P2Y12 receptor.

Aspirin displaces valproate from albumin binding and suppresses its metabolism.

SSRIs block serotonin reuptake into platelets, impairing primary haemostasis.

Duloxetine (SNRI) depletes the platelet serotonin pool, impairing primary haemostasis.

Celecoxib is a selective COX-2 inhibitor and does not displace aspirin from COX-1 (unlike ibuprofen/naproxen).

Dronedarone blocks CYP3A4 – a partial atorvastatin metabolic route.

Atorvastatin blocks OATP1B1 – the hepatic methotrexate uptake route.

Tacrolimus is a weak CYP3A4 inhibitor; atorvastatin is a substrate.

Fluoxetine (SSRI) raises synaptic serotonin.

Apixaban and rivaroxaban are both direct factor Xa inhibitors.

Apixaban inhibits factor Xa; dabigatran inhibits thrombin.

Dual immunosuppression plus additive nephrotoxicity.

NSAIDs weaken the antihypertensive effect of beta-blockers via renal prostaglandin suppression.

NSAIDs weaken amlodipine's antihypertensive effect via prostaglandin suppression.

Warfarin acts via two stereoisomers: S-warfarin (5-fold more active) and R-warfarin.

Warfarin blocks vitamin K-dependent clotting factor synthesis; clopidogrel inhibits platelet aggregation via the P2Y12 receptor.

Rifampicin strongly induces P-glycoprotein, the main dabigatran clearance route.

Carbamazepine strongly induces CYP2C9 and CYP3A4.

Carbamazepine induces CYP3A4 and accelerates ethinylestradiol metabolism.

Bisoprolol is cardioselective, but at high doses (above 10 mg/day) partially blocks β2-receptors and may weaken theophylline's bronchodilator effect in asthma or COPD.

Rosuvastatin barely uses CYP3A4 but is a substrate of OATP1B1 and BCRP transporters, both inhibited by ritonavir.

Aspirin irreversibly blocks platelet cyclooxygenase and reduces aggregation.

Simvastatin clearance is 98% via hepatic CYP3A4.

Simvastatin clearance is 98% dependent on hepatic CYP3A4.

Warfarin blocks vitamin K-dependent clotting factor synthesis; clopidogrel inhibits platelet aggregation via the P2Y12 receptor.

Ibuprofen (NSAID) suppresses prostaglandin synthesis maintaining glomerular perfusion at lower blood pressure.

Additive QT prolongation.

Carvedilol blocks β2-adrenergic receptors (non-selective beta-blocker) and causes bronchoconstriction in asthma or COPD.

Additive hypotension and peripheral oedema.