Pharm Foundations: DDI/Additive Effects Flashcards
Amiodarone DDI
- Warfarin and Digoxin
- If using amiodarone first, start warfarin/digoxin at a lower dose (=<5 mg/0.125 mcg QD, respectively)
- If adding amiodarone, lower the established warfarin/digoxin dose (30-50%/50%)
- Monitor INR and HR (inform if using for rate control)
Other HR Lowering Meds
- B-blockers
- Clonidine
- Verapamil
- Diltiazem
- Precedex
- Amiodarone
- Digoxin
Digoxin + Loop Diuretics
- Monitor electrolyte and correct if abnormal
- Renal impairment => decrease digoxin dose or frequency, or discontinue
Statins + Strong CYP3A4 Inhibitors
(Think G PACMAC)
- Increased levels of CYP3A4 substrates like lovastatin, simvastatin, and atorvastatin (increases myopathy risk)
- CI Sim/lovastatin with these agents
Warfarin + CYP2C9 Inhibitors/Inducers
- Inhibitors: Azoles, SMZ/TMP, amiodarone, metronidazole
- Inducers: Rifampin, St. John’s Wort
- Decreased or increases warfarin levels respectively to increase/decrease bleeding risk
- Monitor INR
CYP 3A4 Inhibitors + Substrates
- Increase drug levels and potential toxicities
- Don’t use with an opioid since with inhibitors, could increase ADRs like sedation
- Don’t take with grapefruit juice: amiodarone, sim/lovastatin, nifedipine, and tacrolimus
Valproate + Lamotrigine
- Valproate decreases lamotrigine metabolism and increases risk of ADRs like skin reactions (SJS/TEN)
- Initiate lamotrigine using a starter kit and begin at lower levels
MAOI + Catecholamine or 5HT drugs
- Blocking MAO with inhibitor will increase Epi/NE/DA/5HT
- High catecholamines could cause hypertensive crisis
- High 5HT could cause serotonin syndrome
- Don’t use certain antidepressants, stimulants, pain medications, and common inhibitors/inducers together for these reasons
- 2 week washout period between MAOI and serotonergic drugs (fluoxetine, 5 weeks)
- Avoid tyramine rich foods (aged cheese, air-dried meets, sauerkraut)
CYP2D6 Inhibitors
- Amiodarone, fluoxetine, paroxetine, and fluvoxamine
- Don’t use together with the many CYP2D6 substrates (Decreased drug metabolism and increased ADRs)
CYP3A4/P-gp Inhibitors/Inducers
- Calcineurin Inhibitors (CNIs- tacrolimus, cyclosporine) or mTOR kinase inhibitors (sirolimus, everolimus)
- Avoid using together (decreased metabolism, increased ADRs)
- With inducers increased drug metabolizing and potential risk for transplant organ rejection
Antiepileptic CYP Inducers + Other CYP Metabolizers
- Phenytoin, phenobarbital, carbamazepine, oxcarbamazepine + OCDs, carbamazepine, etc.
- If substrate is lamotrigine, use starter kit/low doses
- Decrease drug levels and effects, loss of seizure control with AEDs
Rifampin + CYP/p-gp substrates
- Substrate will greatly decrease
- Increase dose of substrate as necessary and monitor as needed
CYP Inducers + Opioids
- Fentanyl, Hydrocodone, Oxycodone, Methadone
- Increased metabolism, decreased [opioid], pain
CYP2D6 UM + CYP2D6 Prodrugs
- Codeine and tramadol
- Convert prodrug more rapidly, increase active [drug] to potential dangerous levels => toxicity
- Don’t use in children <12 years old or in a breast-feeding mother
Smoking/Quitters
- Quitters - drug concentrations can increase as an CYP1A2 inducer is removed, increased toxicities
- Encourage cessation, but also monitor for toxicities/necessary monitoring parameters
- Nicotine replacement doesn’t induce
- Current smokers - decreased levels of substrate drug, may need to start at a higher initial dose (some antipsychotics, antidepressants, warfarin, anxiolytics)
5 Gs
- Garlic
- Ginger
- Ginkgo biloba
- Ginseng
- Glucosamine
Natural products that can increase bleeding risk
(Also Vitamin E, willow bark, and high dose fish oils)
Additive SE: Serotonergic Toxicity
- Antidepressants - SSRIs, SNRIs, TCAs, mirtazapine, trazodone
- MAOI
- Opioids
- Triptans
- Natural products - St. John’s wort, I-tryptophan
- Other: buspirone, lithium, dextromethorphan (in excess/abuse)
Look for agitation, N/V, hyperthermia, and rigidity
Additive SE: Bleeding
- Anticoagulants
- Antiplatelets
- NSAIDs
- SSRIs/SNRIs
Additive SE: Hyperkalemia
- Renin/Angiotensin/Aldosterone system drugs
- K-sparing diuretics (amiloride, triamterene)
- Others: Salt substitutes, SMX/TMP, canagliflozin, CNIs
Additive SE: QT Prolongation
- Antiarrhythmics - amiodarone, dronedarone, dofetilide, sotalol
- Antibiotics/fungals - Quinolones, macrolides, azoles
- Antidepressants - Citalopram and escitalopram are highest risk, avoid citalopram >20 mg QD and escitalopram >10 mg QD in elderly (>60 yo)
- Antipsychotics (most)
- Antiemetics
- Other: Donepezil, methadone, fingolimod
Additive SE: Ototoxicity
- Aminoglycosides: gent, tobramycin, amikacin
- Cisplatin
- Loop diuretics
- Salicylates: ASA, magnesium salicylate
- Vanco
Additive SE: Nephrotoxicity
- Anti-infectives: aminoglycosides, amphotericin B, polymixins, vanco
- Cisplatin => use amifostine to protect kidneys
- CNIs (tacrolimus, cyclosporine)
- Loop diuretics
- NSAIDs
- Radiographic dye
Additive SE: Anticholinergic toxicity
- Antidepressants/psychotics: 1st gen, paroxetine, TCAs
- Sedating antihistamines: Benadryl, hydroxyzine, meclizine
- Centrally-actin anticholinergics: benztropine, trihexyphenidyl
- Muscle relaxants: baclofen, carisoprodol, cyclobenzapine
- Antimuscarinics: oxybutynin, tolterodine
- Other: Atropine, belladonna, dicyclomine
Highest risk in elderly
Additive SE: Hypotension/Orthostasis
PDE5-i
+
-CYP3A4i - start PDE5-i at half usual starting dose
-Nitrates - severe, CI
-Alpha-1 blockers - tamsulosin, doxazosin, or terazosin; start at lower dose of either drug (1/2 if adding PDE5-i)
