STEPTRACKERPHARMACOLOGY | INTERACTIONS & SAFETY | RAPID-FIRE REVIEW

Interactions, Contraindications & Special Populations

The combinations, diseases and patient groups that turn a safe drug into a dangerous one — in one table, each linked to its full page.

FOCUS ON
Interactions come in a few patterns: CYP induction (rifampin, carbamazepine, phenytoin, St John's wort → partner fails), CYP inhibition (azoles, macrolides, ritonavir, grapefruit, amiodarone → partner toxicity), additive pharmacodynamics (QT, serotonin, CNS depression, bleeding, hyperkalemia), renal competition (probenecid, NSAIDs, thiazides with lithium/methotrexate) and absorption (cations chelating tetracyclines and fluoroquinolones). Special populations: pregnancy, children, elderly, G6PD, renal and hepatic failure. Detailed pages: 1.03 and 1.05.
SITUATION
DRUGS
RESULT · ACTION
PAGE
Rifampin + OCP, warfarin, ART, tacrolimus
CYP induction
Contraceptive failure, clotting, viral rebound, rejection
1.03
Macrolide/azole + simvastatin
CYP3A4 inhibition
Rhabdomyolysis
3.06
TMP-SMX, fluconazole, metronidazole + warfarin
CYP2C9 inhibition, displacement
↑ INR, bleeding
5.01
Thiazide, ACEi, NSAID + lithium
↑ Proximal reabsorption
Lithium toxicity
10.03
Allopurinol + azathioprine/6-MP
Xanthine oxidase inhibition
Marrow failure — cut dose by ~75%
11.02
SSRI + MAOI, linezolid, tramadol, meperidine, triptan
Additive 5-HT
Serotonin syndrome
10.01
MAOI + tyramine foods or sympathomimetics
Unmetabolized tyramine releases NE
Hypertensive crisis → phentolamine
10.01
Nitrate + PDE5 inhibitor
Additive cGMP
Severe hypotension
3.03
ACEi/ARB + K⁺-sparing diuretic, TMP, NSAID
↓ K⁺ excretion
Hyperkalemia
4.02
Loop diuretic + aminoglycoside
Additive ototoxicity
Hearing loss
4.01
Verapamil, amiodarone, quinidine + digoxin
↓ Digoxin clearance (P-gp)
Digoxin toxicity
3.02
β-blocker + verapamil/diltiazem
Additive nodal block
Bradycardia, heart block
3.05
Antacids, iron, calcium + tetracycline/fluoroquinolone
Chelation
Treatment failure — separate doses
1.01
Probenecid + penicillin, methotrexate
↓ Tubular secretion
↑ Levels (useful or toxic)
1.02
Opioids + benzodiazepines/alcohol
Additive CNS depression
Respiratory arrest
9.04
Multiple QT drugs
Additive hERG block
Torsades
14.03
Pregnancy — avoid
ACEi/ARB, warfarin, valproate, isotretinoin, methotrexate, lithium, tetracyclines, statins
Teratogenesis
1.05
Children — avoid
Aspirin (Reye), tetracyclines (< 8 y), fluoroquinolones (cartilage), codeine/tramadol
Developmental toxicity
11.01
Elderly — avoid
First-gen antihistamines, TCAs, long-acting benzodiazepines, glyburide, muscle relaxants
Delirium, falls, hypoglycemia
1.05
Renal failure — avoid or adjust
Metformin, NSAIDs, nitrofurantoin, LMWH, gabapentinoids, morphine, meperidine, aminoglycosides
Accumulation, toxicity
4.02
Asthma — avoid
Nonselective β-blockers, aspirin/NSAIDs (AERD), adenosine
Bronchospasm
2.06
Myasthenia gravis — avoid
Aminoglycosides, fluoroquinolones, macrolides, magnesium, β-blockers
Weakness, crisis
12.02
Parkinson disease — avoid
Haloperidol, metoclopramide, prochlorperazine
Worsened rigidity
9.02
Gout — avoid
Thiazides, loops, low-dose aspirin, pyrazinamide, niacin, cyclosporine
↑ Uric acid
11.02

Mechanism — inducer vs inhibitor timing

Inhibitor addedEffect within days
→
Partner toxicity
Inducer addedNew enzyme over 1–2 weeks
→
Partner failure— and toxicity when inducer stops

The usual suspects

ROLE
DRUGS
PAGE
Inducers
Rifampin, carbamazepine, phenytoin, phenobarbital, St John's wort
Inhibitors
Azoles, macrolides, ritonavir, grapefruit, amiodarone, cimetidine
Victims
Warfarin, OCPs, statins, tacrolimus, theophylline

How it's tested

COMMON CONFUSIONNot all macrolides inhibit CYP3A4 — azithromycin barely does; clarithromycin and erythromycin strongly do.
THE TRAPA stable patient on a narrow-index drug who suddenly becomes toxic or fails therapy usually started or stopped another drug — look at the medication list first.
YOUR APPROACHVictim (narrow index) → perpetrator (inducer/inhibitor/additive) → direction of change → monitor or switch.

If you see… think…

Pregnancy on OCP during TB therapy → rifampin induction
Rhabdomyolysis after adding clarithromycin → statin interaction
Lithium toxicity after new BP pill → thiazide or ACEi
Pancytopenia after gout drug in transplant patient → allopurinol + azathioprine
Clonus and fever after adding linezolid → serotonin syndrome
Syncope after nitroglycerin, recent erectile drug → PDE5 + nitrate
Tacrolimus toxicity after antifungal → azole CYP3A4 inhibition
Ciprofloxacin fails when taken with milk → chelation
Myasthenic crisis after antibiotic → aminoglycoside or fluoroquinolone
Bleeding after fluconazole in a warfarin user → CYP2C9 inhibition