Drugs with Additive Risk

Serotonergic Toxicity

Meds: Antidepressants (SSRI/SNRIs, TCAs, mirtazapine, trazodone), MAO-I (isocarboxazid, phenelzine, tranylcypromine, linezolid, methylene blue, selegiline, rasagiline), Opioids (fentanyl, meperidine, methadone, tramadol, tapentadol), Triptans, St. John’s wort, buspirone, lithium, dextromethorphan

Sx: autonomic dysfunction (diaphoresis, N/V, hyperthermia), altered mental status (agitation, delirium), and neuromuscular excitation (rigidity, seizures)

Actions: Washout period - Generally 2 weeks between drugs unless longer acting like fluoxetine.

Bleeding

Meds: Anticoagulants, Antiplatelets, NSAIDs, SSRI/SNRIs, Natural Products (5 G’s, Vitamin E, willow bark, fish oils)

Avoid using in combinations with the exception of bridging treatment like enoxaparin + warfarin.

Hyperkalemia

Meds: RAAS (ACE-I, ARBs, Entresto, aliskiren, spironolactone, eplerenone), K-sparring diuretics, salt substitutes, calcineurin inhibitors, Bactrim, canagliflozin, CHC with drospirenone

Sx: weakness, heart palpitation, arrhythmia

QT prolongation

Meds: Anti-arrhythmic, Anti-infective (hydroxychloroquine, azole antifungal, lefamulin, macrolines, fluoroquinolones), Antidepressants (SSRIs, TCAs, mirtazapine, trazodone, venlafaxine), Antipsychotics, Antiemetics (5HT3 receptor antagonists, droperidol, metoclopramide, promethazine), Oncology meds (androgen deprivation therapy, tyrosine kinase inhibitors, arsenic trioxide), cilostazol, donepezil, fingolimod, hydroxyzine, loperamide, ranolazine, solifenacin, methadone

Risk: Torsades de pointes - fatal arrhythmia

CNS depression

Meds: Opioids, Muscle Relaxants, Antiseizure meds, Benzos, Barbiturates, Hypnotics, Antidepressants (mirtazapine, trazodone), Antihypertensive (propranolol, clonidine), Canabis, dronabinol, nabilone, sedating antihistamines, some NSAIDs

Effects: somnolence, dizziness, confusion, cognitive impairment, altered consciousness

Ototoxicity

Meds: aminoglycosides, cisplatin, loop diuretics, salicylates (ASA, salsate, Mg salicylate), vancomycin

Risk: hearing loss, tinntus, vertigo

Nephrotoxicity

Meds: anti-infectives (aminoglycosides, amphotericin B, polymyxins, vanco), cisplatin, calcineurin inhibitors (cyclosporine, tacrolimus), loop diuretics, NSAIDs, radiographic contrast dye

Risk: Increased SCr and BUN.

Actions:

• Use amifostine with cisplatin.

• Maintain adequate hydration.

Anticholinergic Toxicity

Meds: antidepressants/antipsychotics (paroxetine, TCAs, FSAs), sedating antihistamines (benadryl, brompheniramine, doxylamine, hydroxyzine, meclizine), benztropine, muscle relaxants, antimuscarinics for urinary incontinence, atropine, belladonna, dicyclomine

Hypotension/Orthostasis

Meds: PDE5 inhibitors + CYP3A4 inhibitors or nitrates or alpha 1 blockers

Action:

• Start at half the usual dose with CYP3A4 inhibitors or alpha 1 blockers.

• CI: PDE5 inhibitors + nitrates unless it’s in an emergent situation with close monitoring.