Report immediately

Hypersensitivity with organ involvement (myocarditis, pericarditis, nephritis, hepatitis, pneumonitis, blood changes); liver failure in pre-existing liver disease; SJS/TEN, DRESS, AGEP.

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.

With captopril, neutropenia with bone-marrow (myeloid) hypoplasia — report sore throat or fever at once.

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

Risk of medication errors and hepatotoxicity with acetaminophen injection.

Lowering or blocking cortisol can cause sometimes life-threatening adrenal insufficiency — nausea, vomiting, fatigue, abdominal pain, loss of appetite, dizziness, hypotension, hypoglycemia.

Mifepristone terminates pregnancy. Pregnancy must be excluded before Korlym is started, and again if treatment is interrupted for more than 14 days in females of reproductive potential.

Fludrocortisone (mineralocorticoid excess), osilodrostat (11-deoxycorticosterone build-up) and mifepristone (hypokalemia).

Both prolong the QTc interval in a dose-related way.

Myocardial infarction, cerebrovascular spasm and occlusion have followed phentolamine, usually with marked hypotension; tachycardia and arrhythmias also occur.

Rarely, a persistent painful erection unrelated to sexual activity.

Postural hypotension with dizziness, and possible syncope — especially when starting, and in older patients.

Stop alfuzosin if angina appears or worsens; use caution with QT prolongation or QT-prolonging drugs.

Moderate to severe sedation in almost all patients; drooling, speech difficulty and tremor in about 10%; diarrhea; crystals in the urine.

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.

Serious pulmonary oil microembolism (POME) reactions and anaphylaxis can occur during or immediately after any injection of testosterone undecanoate, including the first.

Danazol is contraindicated in pregnancy; thromboembolism, peliosis hepatis and benign hepatic adenoma, and benign intracranial hypertension have been reported.

Depression and suicidal ideation have occurred in clinical trials of these products.

Virilization has been reported in children who were secondarily exposed to testosterone gel; children should avoid contact with unwashed or unclothed application sites.

Testosterone raises hematocrit; an increase in red cell mass may increase the risk of thromboembolic events, and DVT and PE have been reported.

Testosterone can increase blood pressure, which can increase cardiovascular risk over time.

Men with BPH may have worsening urinary symptoms, and androgens may increase the risk of prostate cancer.

Prolonged high-dose use of oral 17-α-alkyl androgens such as methyltestosterone has been associated with peliosis hepatis, hepatic neoplasms, cholestatic hepatitis and jaundice.

Testosterone has been abused, typically at doses above those recommended and with other anabolic androgenic steroids.

Liver failure, hospitalization and death; about half of cases occurred in the first 3 months.

Exertional dyspnea, cough, chest pain and fever; mostly in the first 3 months, usually reversible on stopping.

Seizure with enzalutamide, apalutamide and darolutamide; falls and fractures with enzalutamide and apalutamide; PRES with enzalutamide.

Ischemic heart disease with enzalutamide and darolutamide; cerebrovascular and ischemic cardiovascular events with apalutamide, including fatal events.

Hypertension, hypokalemia and fluid retention; QT prolongation and torsades with hypokalemia; adrenocortical insufficiency after steroid interruption or stress.

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

Positive ANA with or without a lupus-like syndrome; increased mortality in non-life-threatening arrhythmias (CAST); potentially fatal blood dyscrasias such as agranulocytosis.

Increased mortality with antiarrhythmic therapy for non-life-threatening arrhythmias — reserve for life-threatening ventricular arrhythmias; propafenone carries proarrhythmic risk in structural heart disease.

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

Start (or restart) only in a facility for at least 3 days, with creatinine clearance calculation, continuous ECG monitoring and cardiac resuscitation.

Can cause potentially fatal arrhythmias — give only with continuous ECG monitoring and staff trained to treat polymorphic VT.

Doubles the risk of death in recently decompensated or NYHA class IV heart failure, and of death, stroke and heart-failure hospitalization in permanent atrial fibrillation.

Immune thrombocytopenia (can cause fatal hemorrhage); cinchonism — tinnitus, hearing loss, vertigo, blurred vision, headache, confusion; QT prolongation and torsades; rare hepatotoxicity.

Urinary retention (especially with prostatic hypertrophy), glaucoma risk, worsening heart failure or severe hypotension, hypoglycemia, QRS/QT prolongation and torsades.

Drowsiness, dizziness, paresthesia, tinnitus, twitching or tremor progressing to convulsions and respiratory depression; bradycardia, hypotension, worsening conduction.

New or worsened arrhythmias; may unmask Brugada syndrome; heart failure (negative inotropy plus β-blockade); conduction block; agranulocytosis; altered pacemaker thresholds.

Hypotension with rapid IV administration; QRS widening, PR and QT prolongation, heart block; accumulation in renal insufficiency.

Diarrhea, nausea, abdominal pain, bradycardia and rash are most common; hepatocellular liver injury, interstitial lung disease and new or worse heart failure are labeled warnings.

Swelling of the face, lips, tongue or larynx with oxybutynin — possible from the first dose.

Absorbed eye drops can cause psychotic reactions and behavioral disturbances (ataxia, restlessness, hallucinations, seizures) and, in children, vasomotor or cardiorespiratory collapse; infants are especially prone.

Stopping or cutting the dose abruptly can flare parkinsonism or trigger neuroleptic malignant syndrome; angle-closure glaucoma (sometimes with blindness) and fatal hyperthermia have been reported.

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

Constipation is common and dose-limiting and can progress to intestinal pseudo-obstruction (abdominal distention, pain, nausea or vomiting); new diarrhea, especially with an ileostomy or colostomy, may be an early sign of incomplete obstruction.

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

Risk of major/fatal bleeding (warfarin); stopping a DOAC (apixaban, rivaroxaban, edoxaban, dabigatran) early raises stroke risk; neuraxial anesthesia on a DOAC, enoxaparin or fondaparinux risks spinal hematoma.

In nonvalvular atrial fibrillation with creatinine clearance above 95 mL/min, edoxaban had more ischemic strokes than warfarin — it should not be used in these patients.

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.

Torsades de pointes, cardiac arrest, and death have been reported with higher-than-recommended doses.

Chest pain from myocardial ischemia with ondansetron — mostly with IV doses, sometimes right after the dose; PR/QRS prolongation, AV block and fatal arrhythmias with dolasetron.

Extended-release granisetron injection: serious injection-site reactions (infection such as abscess or cellulitis, prolonged bleeding, bruising, hematoma, nodules, pain) and hypersensitivity, including anaphylaxis, that can begin days after the dose.

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 — potentially 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.

Gout patients with established cardiovascular disease treated with febuxostat (Uloric) had a higher rate of cardiovascular death than those treated with allopurinol in a CV outcomes study.

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

Doxorubicin: cardiomyopathy (risk rises with cumulative dose — 1%–20% at 300–500 mg/m²), secondary AML/MDS, severe tissue necrosis on extravasation, and severe myelosuppression. Vincristine: FATAL if given by any route other than IV; given only by clinicians experienced in its administration. Cisplatin: nephrotoxicity, peripheral neuropathy, severe nausea/vomiting, and myelosuppression.

Impulse-control disorders & sleep attacks (dopamine agonists); hallucinations/psychosis; depression with suicidal tendencies; vitamin B6 deficiency with seizures (carbidopa-levodopa); motor “on-off” fluctuations; NMS-like syndrome if stopped abruptly.

Diarrhea, which can start late; prolonged watery, non-bloody diarrhea may be drug-induced microscopic colitis, sometimes with dehydration, abdominal pain, weight loss, and low potassium.

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

Eptifibatide and tirofiban: bleeding (most often at the arterial access site) and acute, sometimes profound thrombocytopenia.

Cilostazol: headache, diarrhea and abnormal stools, palpitations and dizziness are common; tachycardia, angina and rare agranulocytosis.

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, ethambutol); rifampin drug interactions (CYP450 induction).

Severe and sometimes fatal hepatitis, which can develop even after many months of treatment; the risk rises with age and with daily alcohol use.

Acyclovir crystalluria/AKI and (in renal impairment) neurotoxicity; valacyclovir and valganciclovir acute renal failure (elderly, nephrotoxins, poor hydration); valacyclovir TTP/HUS at high doses in the immunocompromised; zanamivir bronchospasm; oseltamivir neuropsychiatric events and serious skin reactions (SJS/TEN); symptomatic bradycardia with sofosbuvir + amiodarone.

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.

In women with pre-existing ischemic heart disease, ischemic cardiovascular events were more frequent with anastrozole than with tamoxifen.

Angioedema, urticaria and anaphylaxis have been reported, as have severe skin reactions and hepatitis.

All three can decrease bone mineral density; fractures were more common with anastrozole and letrozole than with tamoxifen, and so was osteoporosis with letrozole.

All three can cause fetal harm; letrozole is contraindicated in pregnancy.

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.

Severe liver injury is rare but can be fatal — labetalol is stopped for jaundice or lab evidence of liver injury.

Irritation and inflammation at the IV site; extravasation can cause thrombophlebitis, necrosis, or blistering.

Fecal impaction or bowel obstruction, and esophageal obstruction from the large tablets.

Colesevelam can raise triglycerides, and hypertriglyceridemia can cause acute pancreatitis.

Reduced absorption of vitamins A, D, E and K and folate, with a bleeding tendency from vitamin K deficiency.

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

Denosumab (Prolia) — severe hypocalcemia in advanced kidney disease. Romosozumab — myocardial infarction, stroke and cardiovascular death. Raloxifene — venous thromboembolism and death from stroke.

Hypocalcemia (denosumab, cinacalcet, calcitonin); hypercalcemia (PTH analogs, calcitriol); osteonecrosis of the jaw and atypical femur fractures (denosumab, romosozumab); multiple vertebral fractures after stopping denosumab; serious infections (denosumab); anaphylaxis (calcitonin, PTH analogs); nasal ulceration (calcitonin spray); upper GI bleeding and adynamic bone disease (cinacalcet).

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

IV clevidipine or nicardipine: hypotension and reflex tachycardia with rapid upward titration; headache, nausea and vomiting; infusion-site phlebitis (nicardipine); raised triglycerides (clevidipine’s lipid emulsion).

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

Carbapenems significantly reduce serum valproic acid, risking loss of seizure control (breakthrough seizures).

Rarely fatal Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias, and anaphylaxis.

Serious reactions, including anaphylaxis, hypotension and dyspnea that have led to cardiac arrest and death.

Metabolic acidosis and electrolyte imbalance with both drugs; acetazolamide’s label names hypokalemia and hyponatremia, and methazolamide increases potassium excretion at first.

Hypervolemia that can cause or worsen heart failure and pulmonary edema; or dehydration and hypovolemia from the osmotic diuresis.

Acute kidney injury, osmotic nephrosis and, rarely, irreversible renal failure.

Confusion, lethargy and coma, some fatal; a rebound rise in intracranial pressure several hours after the infusion.

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, full SLUDGE and, with cholinesterase inhibitors, increasing muscle weakness — a cholinergic crisis. Treated with atropine.

Severe bronchoconstriction can follow inhaled methacholine, even at the lowest dose of the challenge test.

Bradycardia, excess salivation with breathing difficulty, and seizures when the IV injection is too rapid; an overdose can cause a cholinergic crisis.

Blurred or dim vision, eye pain, stinging and redness; rarely retinal detachment. With echothiophate, also iris cysts (more often in children) and lens opacities.

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

Acute kidney injury has been reported — clindamycin is potentially nephrotoxic.

Sudden cardiac events in structural heart disease; growth suppression (children); new/worsening psychosis, mania, tics; priapism; seizure lowering; peripheral vasculopathy incl. Raynaud’s; serotonin syndrome with serotonergic drugs (amphetamines).

Splenic rupture (LUQ/shoulder pain); acute respiratory distress syndrome; serious allergic reactions; sickle cell crisis (in SCD); glomerulonephritis; capillary leak syndrome; aortitis/large-vessel arteritis; alveolar hemorrhage; very high white counts; MDS/AML.

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.

Rapid injection can cause vasodilation, low blood pressure, bradycardia, arrhythmias, syncope and cardiac arrest.

Undiluted, bolus or rapid infusion has caused cardiac arrest, arrhythmias, hyperkalemia and death; hyperphosphatemia forms calcium phosphate, causing hypocalcemia, tetany and nephrocalcinosis with acute kidney injury.

Calcium gluconate can cause calcinosis cutis (calcium deposits in the skin) with or without extravasation; tissue necrosis, ulceration and secondary infection are the most serious complications.

Overly aggressive therapy causes metabolic alkalosis (muscle twitching, irritability, tetany) and hypernatremia; extravasation causes chemical cellulitis with tissue necrosis, ulceration or sloughing.

Both can cause fluid overload with pulmonary edema; excess 3% saline causes hypernatremia (seizures, coma, cerebral edema), and lactated Ringer’s can cause hyponatremia.

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

Anaphylaxis, angioedema and severe skin reactions (SJS, TEN, DRESS) with fenofibrate.

Muscle pain, tenderness or weakness with raised CK — rhabdomyolysis can follow, especially with a statin.

Serious drug-induced liver injury with fenofibrate; raised liver tests with gemfibrozil.

Gallstones (cholelithiasis) with either fibrate; pancreatitis reported with fenofibrate.

QT prolongation/torsades; aortic aneurysm/dissection; hypoglycemia and hyperglycemia; C. difficile colitis; phototoxicity.

Serious, sometimes fatal hypersensitivity (anaphylaxis) can follow even the first dose; severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) and severe, sometimes fatal hepatotoxicity also occur.

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, chronic-bronchitis flares, and uncomplicated UTI.

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

Cyanosis or dark, abnormally colored blood, immediately or hours after exposure; oxygen saturation that does not improve with oxygen (benzocaine, prilocaine).

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

Bladder and urinary-tract damage (cystitis, reduced bladder capacity, ureteral stenosis, hydronephrosis) with long-term use or abuse; possible long-term cognitive effects in children ≤ 3 years with exposures over 3 hours or repeated exposures.

Absorbed via the tear duct: bradycardia, hypotension, heart block, and bronchospasm; can worsen heart failure; can mask hypoglycemia and the signs of hyperthyroidism (e.g., tachycardia). Dangerous in asthma/COPD, cardiac conduction disease, and overt heart failure.

Catecholamine release with pheochromocytoma; exaggerated insulin release and hypoglycemia with insulinoma; serious allergic reactions.

Increased blood pressure, pulse and myocardial oxygen demand in cardiac disease; hyperglycemia in diabetes; secondary hypoglycemia with glucagonoma; necrolytic migratory erythema with continuous infusion.

Testosterone rises about 50% in the first weeks: bone pain, urinary obstruction, neurologic symptoms, spinal cord compression.

Anaphylaxis and angioedema (all classes); severe cutaneous adverse reactions with leuprolide and goserelin; in children, a flare of puberty signs, psychiatric events, convulsions and pseudotumor cerebri.

QT prolongation (agonists and antagonists); hyperglycemia and diabetes and an increased risk of MI, sudden cardiac death and stroke in men (agonist labels).

Loss of bone mineral density (some not reversible); depression and mood changes; suicidal ideation with elagolix; ALT elevations with elagolix.

Angioedema with sacubitril/valsartan — laryngeal involvement can be fatal.

Symptomatic hypotension, a fall in renal function and hyperkalemia with sacubitril/valsartan.

Bradycardia, sinus arrest, heart block and atrial fibrillation with ivabradine.

CYP3A4/P-gp induction lowers levels of contraceptives (unplanned pregnancy), warfarin (clot), cyclosporine/tacrolimus (transplant rejection), digoxin, HIV protease inhibitors, anticonvulsants (phenytoin, carbamazepine), some cancer drugs, ivabradine, simvastatin, 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).

New or worsening demyelinating disease (multiple sclerosis, optic neuritis, Guillain-Barré syndrome); lupus-like syndrome or autoimmune hepatitis; new or worsening heart failure.

Tacrolimus (Prograf): increased risk of serious infections and malignancies that may lead to hospitalization or death. Cyclosporine (Neoral, Gengraf, Sandimmune): increased susceptibility to infection and possible lymphoma and other neoplasms; only physicians experienced in immunosuppressive therapy should prescribe it.

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.

Injectafer — severe, prolonged hypophosphatemia (osteomalacia, fractures).

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.

Anaphylaxis, angioedema, and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, acute generalized exanthematous pustulosis); fatalities have been reported.

QT prolongation / torsades de pointes; hepatotoxicity/cholestasis; serious drug interactions (erythro/clarithro via CYP3A4); infantile pyloric stenosis (neonates given erythromycin, or azithromycin in the first 42 days of life); hearing loss (usually reversible).

Loss of deep tendon reflexes (first sign) → respiratory depression → hypotension → cardiac arrest (heart block can occur at or below the reflex-loss level). Reversed with IV calcium gluconate.

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

Endometrial cancer with unopposed estrogen; stroke and DVT with estrogen alone; stroke, DVT, PE, MI and invasive breast cancer with estrogen plus progestin; probable dementia at 65 or older.

Serious and sometimes fatal infection or bleeding, very rarely, after abortion; REMS.

Gallbladder disease; severe hypercalcemia in breast cancer with bone metastases; retinal vascular thrombosis; pancreatitis with pre-existing hypertriglyceridemia; recurrence of cholestatic jaundice; anaphylaxis and angioedema.

Hepatotoxicity, reported after marketing.

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

Toxic epidermal necrolysis, Stevens-Johnson syndrome, DRESS, and acute generalized exanthematous pustulosis — potentially life-threatening.

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

Lithium toxicity is closely related to serum lithium levels and can occur at doses close to therapeutic levels.

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

Succinylcholine: rare fatal hyperkalemic rhabdomyolysis/cardiac arrest in children with undiagnosed skeletal myopathy.

Anaphylaxis and other hypersensitivity reactions; marked bradycardia, sometimes with cardiac arrest, within minutes of the dose; recurrence of neuromuscular blockade.

Severe hypotension (profoundly worsened by PDE5 inhibitors); syncope; paradoxical bradycardia with increased angina.

GI bleeding/ulcer/perforation; renal impairment/AKI, hyperkalemia, edema, raised BP, worsened heart failure; hypersensitivity/bronchospasm (aspirin-exacerbated respiratory disease); serious skin reactions (SJS/TEN, DRESS); 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.

Ketorolac: short-term use only (up to 5 days in adults, IV/IM and oral combined) for moderately severe acute pain needing opioid-level analgesia — not for minor or chronic pain and not for children.

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. Semaglutide, liraglutide, dulaglutide, tirzepatide — thyroid C-cell tumors.

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

Rare cholestatic jaundice and hepatitis; hyponatremia; serious hypoglycemia with renal or hepatic insufficiency.

Pancreatitis; severe joint pain; bullous pemphigoid; serious hypersensitivity; sitagliptin acute renal failure; alogliptin liver failure.

Nausea, vomiting, diarrhea; kidney injury from dehydration; pancreatitis; gallbladder disease; aspiration under anesthesia.

Dose-related QTc prolongation from IKr block.

Acute renal failure in patients with severe renal impairment (creatinine clearance < 30 mL/min).

Tremor, myoclonus, abnormal coordination, paresthesia and hallucinations, often after a dose increase or higher exposure.

Glinides can cause hypoglycemia, especially with a skipped meal; pioglitazone, acarbose and miglitol add to the hypoglycemia risk of insulin or a sulfonylurea, and pramlintide to that of insulin.

Pioglitazone — congestive heart failure. Pramlintide — severe hypoglycemia with insulin.

Dose-related edema and weight gain; more fractures in women; possible bladder cancer; rare hepatic failure; macular edema.

Acarbose can raise serum transaminases, rarely with jaundice or fulminant hepatitis; pneumatosis cystoides intestinalis has been reported.

Aliskiren can cause angioedema or anaphylaxis at any time and, like other RAAS drugs, can raise potassium and impair renal function.

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

Methyldopa can cause a positive direct Coombs test (10–20% on prolonged therapy) that rarely progresses to hemolytic anemia, and liver injury (fever, abnormal liver tests or jaundice; rarely fatal hepatic necrosis).

Anaphylaxis and angioedema have been reported with inclisiran, bempedoic acid (angioedema) and ezetimibe.

Liver injury with niacin — severe, even fulminant, when sustained-release niacin replaced immediate-release at the same dose — and raised glucose and uric acid.

Muscle pain, tenderness or weakness — mainly when ezetimibe or niacin is combined with a statin (or ezetimibe with a fibrate).

Bempedoic acid raises uric acid (gout) and increases the risk of tendon rupture.

Icosapent ethyl increases atrial fibrillation or flutter requiring hospitalization, and bleeding.

Severe diarrhea with volume depletion, reduced absorption of fat-soluble vitamins and fatty acids, and embryo-fetal toxicity with lomitapide.

Swelling of the face, lips, tongue or larynx has been reported with all seven drugs; anaphylactic reactions with several.

Inability to empty the bladder — with antimuscarinics, especially with bladder outlet obstruction; with mirabegron and vibegron, in outlet obstruction or when combined with an antimuscarinic.

Dizziness, somnolence, headache, confusion and hallucinations with the antimuscarinics — most likely after starting or increasing the dose.

Mirabegron can raise blood pressure and worsen pre-existing hypertension; it can also raise blood pressure in children.

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

Mother: anaphylaxis, cardiac arrhythmias (including premature ventricular contractions), hypertensive episodes, subarachnoid hemorrhage, pelvic hematoma, and afibrinogenemia (fatal cases reported). Fetus/newborn: bradycardia and other arrhythmias, low 5-minute Apgar scores, neonatal jaundice, retinal hemorrhage, seizures, permanent brain damage, and fetal death.

Serious hypersensitivity reactions, including angioedema; with alirocumab also hypersensitivity vasculitis and reactions requiring hospitalization.

PDE5 inhibitors potentiate the hypotensive effects of nitrates and guanylate cyclase stimulators, and add to α-blockers, other antihypertensives and substantial alcohol.

Erections lasting more than 4 hours and priapism (painful erections over 6 hours) have been reported.

Sudden loss of vision in one or both eyes may be a sign of non-arteritic anterior ischemic optic neuropathy, reported rarely with all PDE5 inhibitors.

Sudden decrease or loss of hearing, sometimes with tinnitus and dizziness, has been reported in temporal association with PDE5 inhibitors.

Treatments for erectile dysfunction should generally not be used in men for whom sexual activity is inadvisable because of their cardiovascular status.

Vardenafil increases the QTc interval; patients with congenital QT prolongation or taking class IA or III antiarrhythmics should avoid it.

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

Water retention with continued drinking → dilutional hyponatremia → headache, confusion, cerebral edema, seizures. Greater risk in the elderly, young children, and with other drugs that can lower sodium — tricyclic antidepressants, SSRIs, chlorpromazine, opioid analgesics, NSAIDs, lamotrigine, carbamazepine (the injection label adds thiazide diuretics, chlorpropamide and other sulfonylureas, and oxybutynin) — which call for more frequent sodium checks.

DDAVP Injection — hyponatremia, which can be severe and life-threatening.

Sudden deaths have been reported in children with Prader-Willi syndrome who were severely obese or had severe respiratory impairment.

Reduced gallbladder contractility and bile secretion lead to sludge and stones; cholecystitis, cholangitis, biliary obstruction and pancreatitis have been reported.

Heart rate may fall; octreotide has caused bradycardia, conduction abnormalities, arrhythmias and, given intravenously, complete heart block.

Intracranial hypertension, fluid retention (edema, arthralgia, carpal tunnel), slipped capital femoral epiphysis and scoliosis progression in children, unmasked hypothyroidism or hypoadrenalism, pancreatitis, and second neoplasms in childhood cancer survivors.

Transaminase elevations, occasionally with raised bilirubin, have been reported.

Cardiac valve disease and pericardial, pleural, pulmonary or retroperitoneal fibrosis.

Intestinal necrosis, which may be fatal, and other serious GI events (bleeding, ischemic colitis, perforation) reported with SPS, most often when sorbitol was given at the same time.

Hypokalemia: any binder can remove too much potassium.

Edema and sodium load from the sodium that SPS and SZC deliver (SZC’s edema was mostly mild to moderate and more common at higher doses).

Patiromer and SZC are avoided in severe constipation, bowel obstruction or impaction, because they may not work and may worsen the condition. SPS is contraindicated in obstructive bowel disease.

Inhaled SPS particles have caused acute bronchitis or bronchopneumonia.

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

Severe skin reactions (erythema multiforme, SJS/TEN, DRESS, AGEP); cutaneous or systemic lupus (new or flared); fundic gland polyps with long-term use.

Stopping suddenly, an infusion interruption, or a large dose cut can cause rebound PAH — potentially fatal.

Chronic IV infusion through a central venous catheter carries a risk of bloodstream infection and sepsis, which may be fatal.

Non-arteritic anterior ischemic optic neuropathy (NAION), sudden hearing loss, and priapism.

Pulmonary vasodilators can badly worsen PVOD; new pulmonary edema after starting suggests it.

Fetal harm with bosentan, ambrisentan, macitentan and riociguat — all are contraindicated in pregnancy.

Bosentan can raise liver aminotransferases and cause liver failure, so it is available only through the Bosentan REMS.

Sildenafil, tadalafil, riociguat, epoprostenol and treprostinil dilate systemic vessels and lower blood pressure — lightheadedness, dizziness, chest pain.

Peripheral edema and fluid retention; hemoglobin and hematocrit decrease early, then stabilize.

Treprostinil and epoprostenol inhibit platelet aggregation; riociguat caused serious bleeding; sildenafil increases epistaxis.

Like other inhaled prostaglandins, inhaled treprostinil can cause acute bronchospasm; cough and throat irritation are common.

Uterine malignancies (endometrial adenocarcinoma, uterine sarcoma), stroke and pulmonary embolism, including fatal cases.

Endometrial cancer (estrogen-agonist effect in the endometrium) and cardiovascular disorders (stroke, DVT).

QT prolongation that can cause torsade de pointes, syncope, seizure or death.

Ovarian enlargement and ovarian hyperstimulation syndrome; multiple pregnancy; visual blurring, spots or flashes that may rarely persist.

Cataracts and other ocular changes; liver enzyme changes and, rarely, fatty liver, cholestasis, hepatitis or necrosis; thrombocytopenia and leukopenia; hypercalcemia with bone metastases.

VTE (DVT/PE — highest in the first year and on restarting after a break of 4 weeks or more), ischemic stroke and MI (esp. with smoking, migraine with aura, hypertension), hypertension, and rare hepatic adenoma / gallbladder disease.

Medroxyprogesterone injection (Depo-Provera CI, depo-subQ provera 104): loss of bone mineral density. Etonogestrel implant (Nexplanon): complications of improper insertion and removal.

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.

Severe, symptomatic hyponatremia (especially with high-dose treatment of Pneumocystis pneumonia); hypoglycemia in patients without diabetes (rare, usually after a few days); hemophagocytic lymphohistiocytosis (HLH), a life-threatening immune activation.

Anaphylaxis has been reported with amphotericin B products, including the liposomal form.

Amphotericin: nephrotoxicity, hypokalemia/hypomagnesemia. Azoles: hepatotoxicity, QT prolongation, major CYP450 drug interactions; voriconazole visual disturbances (optic neuritis and papilledema reported with prolonged use).

Conventional amphotericin B: use primarily for progressive, potentially life-threatening fungal infections — not for noninvasive disease such as oral thrush or vaginal/esophageal candidiasis in patients with normal neutrophil counts. Do not exceed 1.5 mg/kg.

Exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS; fixed drug eruptions can worsen with each re-exposure.

A rare idiosyncratic sulfonamide reaction: sudden decreased vision or eye pain, typically within hours to weeks of starting hydrochlorothiazide. Untreated angle-closure glaucoma can cause permanent vision loss.

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

Intracranial hemorrhage and serious internal bleeding — sometimes fatal.

Angioedema (often orolingual) and anaphylaxis — during or soon after treatment.

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

Swelling of the salivary glands, nausea, vomiting, diarrhea, stomach ache, fever, headache, metallic taste, and allergic reactions (rash, swelling, fever with joint pain, trouble breathing).

Terbutaline has not been approved and should not be used for prolonged tocolysis beyond 48 to 72 hours (injection) or for acute or maintenance tocolysis (oral), and never for maintenance tocolysis at home.

NSAIDs increase the risk of serious cardiovascular thrombotic events and of gastrointestinal bleeding, ulceration and perforation, which can be fatal.

NSAIDs at about 30 weeks of gestation and later increase the risk of premature closure of the fetal ductus arteriosus; from about 20 weeks they can cause fetal renal dysfunction and oligohydramnios.

β-agonists can raise pulse and blood pressure and produce ECG changes; terbutaline is used with caution in cardiovascular disorders, hyperthyroidism and diabetes.

Occasional patients have had excessive and poorly tolerated hypotension, usually during initial titration or dose increases.

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, seizures.

Dinoprostone can cause uterine tachysystole with or without fetal heart rate changes; misoprostol used in labor can cause tachysystole progressing to uterine tetany, rupture or amniotic fluid embolism.

Induction of labor, including with dinoprostone, raises the risk of postpartum disseminated intravascular coagulation; dinoprostone can also cause amniotic fluid embolism syndrome.

Misoprostol given to pregnant women can cause birth defects, abortion, premature birth or uterine rupture; it must not be taken by pregnant women to reduce the risk of NSAID ulcers.

Hypertension — sometimes with seizure or headache — is its most common adverse reaction; IV use risks sudden hypertensive and cerebrovascular accidents.

Carboprost may cause transient bronchoconstriction; wheezing, coughing, dyspnea and asthma are reported.

Anaphylaxis (rare); vaccine-strain infection if a live vaccine is given to an immunocompromised patient (in pregnancy, a theoretical fetal risk).

Nephrotoxicity (acute kidney injury — also reported with oral vancomycin, especially over age 65), ototoxicity, true anaphylaxis, severe skin reactions (SJS/TEN, DRESS, AGEP, linear IgA bullous dermatosis), reversible neutropenia, and C. difficile-associated diarrhea.

Vancomycin infusion reaction with rapid infusion — flushing, pruritus, upper-body rash; less often, phlebitis at the IV site.

Osmotic demyelination from correcting hyponatremia too fast — Samsca is started and restarted only in a hospital where serum sodium can be monitored closely, and it is not for ADPKD outside the FDA-approved REMS.

Anaphylaxis, including anaphylactic shock, and generalized rash have been reported.

Serious and potentially fatal liver injury with Jynarque, including acute liver failure requiring transplantation — it is available only through the Tolvaptan for ADPKD Shared System REMS.

Liver injury with either brand, signaled by fatigue, anorexia, nausea, right upper abdominal discomfort, dark urine or jaundice.

The copious aquaresis can dehydrate the patient and push sodium too high, especially with diuretics or fluid restriction.

A sudden rise in urine volume can cause acute retention when outflow is partly obstructed — for example, prostatic hypertrophy.

Allergic-type reactions, including anaphylactic symptoms and asthma attacks, from the sodium metabisulfite in Levophed, dopamine, and dobutamine.

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

Midodrine can cause marked supine hypertension — reserved for patients whose lives are considerably impaired despite standard care.

Ventricular arrhythmias (about 12% in trials, including nonsustained VT) and vasodilator hypotension; not shown safe beyond 48 hours.

Tachycardia and palpitations are common; arrhythmias and myocardial ischemia can follow, especially with coronary artery disease or cardiomyopathy.

Nausea, vomiting and tachycardia are the most common effects; palpitations, reactive hypertension, bradycardia and ventricular ectopy also occur. Serious postpartum hypertension, sometimes with stroke, has followed its use with an oxytocic.