Report immediately

Angioedema (may compromise the airway — a medical emergency), acute kidney injury, severe hyperkalemia.

Persistent dry cough, first-dose hypotension, hyperkalemia, dizziness, mildly rising serum creatinine.

Dose-dependent liver injury/acute liver failure; rare SJS/TEN (FDA warning).

Bradycardia, AV/heart block, and syncope from increased vagal (cholinergic) tone — even without known cardiac disease.

Early/mild nephrotoxicity (rising creatinine), vestibular symptoms (dizziness), injection-site effects.

Proarrhythmia; QT prolongation → torsades de pointes (sotalol, class III); amiodarone thyroid dysfunction.

Potentially fatal pulmonary toxicity, hepatotoxicity, and proarrhythmia — reserve for life-threatening arrhythmias.

Anticholinergic toxicity (hyperthermia, delirium, tachyarrhythmia); acute angle-closure glaucoma; urinary retention (BPH); heat stroke.

Major bleeding (GI, intracranial); heparin-induced thrombocytopenia (HIT); rare warfarin skin necrosis.

Risk of major/fatal bleeding; stopping a DOAC early raises stroke risk; neuraxial anesthesia on a DOAC risks spinal hematoma.

SJS/TEN (HLA-B*1502); carbamazepine hyponatremia & blood dyscrasias; valproate hyperammonemia & thrombocytopenia; phenytoin IV cardiovascular toxicity & "purple glove syndrome."

Carbamazepine — SJS/TEN + HLA-B*1502, and aplastic anemia/agranulocytosis. Valproate — hepatotoxicity, pancreatitis, teratogenicity. Lamotrigine — serious rash. Phenytoin (IV) — cardiovascular risk with rapid infusion.

Dose-dependent QT prolongation → Torsades de Pointes (ondansetron, dolasetron); serotonin syndrome with other serotonergic drugs; hypersensitivity/anaphylaxis (cross-reactive across setrons).

Metoclopramide can cause tardive dyskinesia — often irreversible. Avoid use beyond 12 weeks.

Allopurinol hypersensitivity (SJS/TEN, DRESS); allopurinol–azathioprine/6-MP interaction; colchicine toxicity (marrow suppression, esp. renal/hepatic impairment or CYP3A4/P-gp inhibitors); urate stones.

Neutropenia (→ neutropenic fever/sepsis — an emergency), thrombocytopenia (→ bleeding), anemia; counts lowest at the nadir ~7–14 days.

Doxorubicin: cumulative, dose-dependent cardiotoxicity/heart failure and severe tissue necrosis on extravasation. Vincristine: FATAL if given intrathecally (IV use only). Many agents: severe myelosuppression; must be given by clinicians experienced in cytotoxic therapy.

Impulse-control disorders & sleep attacks (dopamine agonists); hallucinations/psychosis; motor "on-off" fluctuations; NMS-like syndrome if stopped abruptly.

Major bleeding (GI, intracranial); stent thrombosis if stopped early; thrombotic thrombocytopenic purpura (rare, clopidogrel).

Increased mortality when used for dementia-related psychosis in elderly patients (all antipsychotics). NMS is a separate medical emergency.

EPS (acute dystonia, akathisia, parkinsonism, tardive dyskinesia — possibly irreversible); QT prolongation; seizure threshold lowering; clozapine → agranulocytosis, myocarditis.

Hepatotoxicity (INH, rifampin, pyrazinamide); optic neuritis (ethambutol); isoniazid peripheral neuropathy; hyperuricemia/gout (pyrazinamide); rifampin drug interactions (CYP450 induction).

Acyclovir crystalluria/AKI and (in renal impairment) neurotoxicity; valacyclovir TTP/HUS at high doses in the immunocompromised; zanamivir bronchospasm; oseltamivir neuropsychiatric events.

Angioedema (rare — much less than ACE inhibitors), acute kidney injury (bilateral renal artery stenosis), severe hyperkalemia.

Hyperkalemia, dizziness, first-dose/orthostatic hypotension, mildly rising serum creatinine.

Bupropion: seizures (dose-related). Trazodone: priapism (urologic emergency), orthostatic syncope. Serotonin syndrome with serotonergic combinations.

Respiratory depression (dose-dependent, worse with CNS depressants); paradoxical agitation; falls/fractures in the elderly; dependence with life-threatening withdrawal seizures.

Bradycardia, hypotension, fatigue, dizziness, cold extremities.

High-degree AV/heart block, bronchospasm (non-selective agents), masked hypoglycemia.

Esophageal ulceration/erosion/stricture; osteonecrosis of the jaw; atypical femoral fractures (thigh/groin pain prodrome); hypocalcemia; renal toxicity (IV zoledronic acid); rare ocular inflammation (uveitis); severe musculoskeletal pain.

Non-dihydropyridines: bradycardia, AV block, severe hypotension, and worsening of heart failure with reduced EF.

Lowered seizure threshold → seizures, greatest with imipenem, renal impairment, high dose, or pre-existing CNS/seizure disorders.

Carbapenems sharply reduce serum valproic acid, risking loss of seizure control / status epilepticus.

Bradycardia, AV block, and a wide range of dysrhythmias (including PVCs, bigeminy, and life-threatening ventricular arrhythmias).

Anorexia, nausea, vomiting, fatigue, and visual changes — classically yellow-green halos around lights.

Hypersensitivity/anaphylaxis (side-chain cross-reactivity with penicillins); C. difficile colitis; ceftriaxone-calcium precipitation (neonates) + biliary sludge; cefotetan disulfiram-like reaction + hypoprothrombinemia/bleeding; cefepime neurotoxicity/seizures in renal impairment; nephrotoxicity (esp. with aminoglycosides).

Bradycardia, hypotension, bronchospasm/bronchorrhea, and full SLUDGE — a cholinergic crisis. Reversed with atropine.

Clostridioides difficile-associated diarrhea ranging from mild diarrhea to fatal pseudomembranous colitis, from disruption of normal colonic flora.

Sudden cardiac events in structural heart disease; growth suppression (children); new/worsening psychosis, mania, tics; priapism; seizure lowering.

HPA suppression → adrenal crisis; masked infection; osteoporosis; steroid-induced diabetes; peptic ulcer/GI bleed; Cushingoid changes; cataracts/glaucoma; growth suppression.

Fatal hyperkalemia from rapid IV potassium; hypermagnesemia (areflexia → respiratory depression → arrest); fluid overload (isotonic/hypertonic); osmotic demyelination from over-rapid sodium correction.

Increased death, MI, stroke, venous thromboembolism, and vascular-access thrombosis; shortened survival / tumor progression in some cancers.

QT prolongation/torsades (most with moxifloxacin); aortic aneurysm/dissection; hypoglycemia and hyperglycemia; C. difficile colitis; phototoxicity.

Tendinitis/tendon rupture, peripheral neuropathy (may be permanent), CNS effects, and exacerbation of myasthenia gravis — which can occur together. Reserve for patients with no alternative for sinusitis, bronchitis, and uncomplicated UTI.

Local anesthetic systemic toxicity: perioral numbness/tinnitus/metallic taste → seizures → cardiovascular collapse (bupivacaine most cardiotoxic). Antidote: IV 20% lipid emulsion.

Genetic RYR1 trigger: rising end-tidal CO₂ (first sign), rigidity, hyperthermia, rhabdomyolysis, hyperkalemia. Antidote: dantrolene.

Absorbed via the tear duct: bradycardia, hypotension, heart block, and bronchospasm; can mask hypoglycemia. Dangerous in asthma/COPD and cardiac conduction disease.

CYP3A4/P-gp induction lowers levels of contraceptives (unplanned pregnancy), warfarin (clot), cyclosporine/tacrolimus (transplant rejection), digoxin, HIV protease inhibitors, and more.

Ginkgo, garlic, ginger, ginseng, vitamin E, and fish oil raise bleeding risk — additive with anticoagulants/antiplatelets and around surgery.

TNF inhibitors: serious infections (TB, invasive fungal, sepsis) and malignancy (lymphoma, incl. hepatosplenic T-cell lymphoma in young patients). Methotrexate carries multiple boxed warnings (see below).

Oral thrush (candidiasis), dysphonia (hoarseness), throat irritation, cough.

Hypoglycemia, weight gain, and injection-site lipohypertrophy.

Severe hypoglycemia (confusion, seizures, coma); hypokalemia; additive lows with sulfonylureas/alcohol; masked warning signs on beta-blockers.

Serious mood/behavior changes — agitation, depression, sleep disturbance, and suicidal thoughts/behavior.

Profound fluid/electrolyte depletion; ototoxicity (worse with aminoglycosides/rapid IV); severe hypokalemia → arrhythmia & potentiated digoxin toxicity; hyponatremia; hypocalcemia; hypomagnesemia; metabolic alkalosis; hyperuricemia/gout; hyperglycemia; AKI/prerenal azotemia.

QT prolongation / torsades de pointes; hepatotoxicity/cholestasis; serious drug interactions (erythro/clarithro via CYP3A4); infantile pyloric stenosis (erythromycin in neonates).

Loss of deep tendon reflexes (first sign) → respiratory depression → hypotension → cardiac conduction changes/arrest. Reversed with IV calcium gluconate.

Tyramine hypertensive crisis (aged/fermented foods); serotonin syndrome (with serotonergic drugs); many drug interactions.

Tachyarrhythmias, seizures, severe vomiting, hypokalemia, hyperglycemia — at levels > 20 mcg/mL.

Lithium toxicity (ataxia, confusion, slurred speech, seizures, arrhythmia); hypothyroidism; nephrogenic diabetes insipidus / chronic kidney effects.

Respiratory arrest/apnea (always); awareness under inadequate sedation; malignant hyperthermia and hyperkalemia (succinylcholine); prolonged apnea (pseudocholinesterase deficiency).

Rare fatal hyperkalemic rhabdomyolysis/cardiac arrest in children with undiagnosed skeletal myopathy.

Severe hypotension (profoundly worsened by PDE5 inhibitors); syncope; reflex tachycardia worsening ischemia.

GI bleeding/ulcer/perforation; renal impairment/AKI, hyperkalemia, edema, raised BP, worsened heart failure; hypersensitivity/bronchospasm (aspirin-exacerbated respiratory disease); rare hepatotoxicity; Reye syndrome (aspirin in children with viral illness).

NSAIDs increase the risk of serious/fatal cardiovascular thrombotic events (MI, stroke) — contraindicated around CABG surgery — and of serious GI bleeding, ulceration, and perforation, which can be fatal and occur without warning.

Life-threatening respiratory depression; severe hypotension; paralytic ileus; serotonin syndrome with other serotonergics.

Severe sulfonylurea hypoglycemia; SGLT2 euglycemic DKA, Fournier gangrene, volume depletion; DPP-4/GLP-1 pancreatitis; metformin B12 deficiency.

Metformin — lactic acidosis. GLP-1 agonists — thyroid C-cell tumors.

Metformin — diarrhea/nausea; sulfonylureas — hypoglycemia & weight gain; SGLT2 — genital yeast & urinary infections.

First-dose syncope (alpha-1 blockers); rebound hypertension if clonidine stopped abruptly; hydralazine lupus-like syndrome; nitroprusside cyanide toxicity.

Uterine tachysystole → fetal hypoxia/decelerations; uterine rupture; postpartum hemorrhage from atony after overstimulation; water intoxication/hyponatremia (high, prolonged doses) → seizures.

Anaphylaxis / hypersensitivity (the defining risk); C. difficile-associated diarrhea/colitis; acute interstitial nephritis (esp. nafcillin/methicillin); seizures at very high doses in renal impairment; superinfection.

Water retention with continued drinking → dilutional hyponatremia → headache, confusion, cerebral edema, seizures. Highest risk in the elderly, young children, and NSAID users.

Hyperkalemia → fatal arrhythmias (esp. with ACEi/ARB, potassium supplements/salt substitutes, NSAIDs, renal impairment); metabolic acidosis; dehydration/AKI; triamterene — nephrolithiasis/crystalluria.

VTE (DVT/PE — highest in first year), ischemic stroke and MI (esp. with smoking, migraine with aura, hypertension), hypertension, and rare hepatic adenoma / gallbladder disease.

Additive CNS/respiratory depression with opioids/benzodiazepines/alcohol; carisoprodol abuse/dependence (Schedule IV); cyclobenzaprine anticholinergic toxicity + MAOI interaction; tizanidine hypotension, hepatotoxicity, CYP1A2 interactions; dantrolene hepatotoxicity; serotonin syndrome (cyclobenzaprine/metaxalone with serotonergic drugs).

Serotonin syndrome; discontinuation syndrome (abrupt stop); hyponatremia (SIADH); hepatotoxicity (duloxetine); increased bleeding with NSAIDs/anticoagulants.

Serotonin syndrome; hyponatremia/SIADH (esp. elderly); increased bleeding; QT prolongation (citalopram); discontinuation syndrome.

Rhabdomyolysis (muscle breakdown → acute kidney injury) and hepatotoxicity.

Stevens-Johnson syndrome / TEN; blood dyscrasias (agranulocytosis, megaloblastic anemia, thrombocytopenia); severe hyperkalemia; crystalluria/AKI; kernicterus in neonates.

Amphotericin: nephrotoxicity, hypokalemia/hypomagnesemia. Azoles: hepatotoxicity, QT prolongation, major CYP450 drug interactions; voriconazole visual disturbances.

Hypokalemia (arrhythmia, digoxin toxicity); hyponatremia (esp. elderly women — confusion); hyperglycemia; hyperuricemia/gout flare; hypercalcemia; hyperlipidemia; hypomagnesemia; sulfa hypersensitivity; lithium toxicity.

Levothyroxine — signs of over-replacement (palpitations, insomnia, tremor, heat intolerance, weight loss). Antithyroid — rash, GI upset, arthralgia.

Overdose cardiotoxicity (wide QRS, ventricular arrhythmia), seizures, coma; QT prolongation; serotonin syndrome with other serotonergic drugs.

Coronary vasospasm/MI (rare), serotonin syndrome (with serotonergic drugs), medication-overuse headache, marked BP elevation.

Anaphylaxis (rare); vaccine-strain infection if a live vaccine is given to an immunocompromised or pregnant patient.

Vancomycin infusion reaction ("red-man") with rapid infusion — flushing, pruritus, upper-body rash; phlebitis at the IV site.

Extravasation necrosis, severe hypertension, tachy-/dysrhythmias, myocardial and peripheral/organ ischemia (including limb/digit and mesenteric).