Beers Criteria - Criteria 4
Beers Criteria (Criteria 4)
NAV Top A B C D E F G H I L M N O P Q R S T V W Z

American Geriatrics Society 2023 updated AGS Beers Criteria®
for potentially inappropriate medication use in older adults. Reference
Criteria 4: Potentially clinically important drug-drug interactions that should be avoided in older adults. (Table 5) Back to All Criteria View
 A
 acetaminophen-codeine (Tylenol #3)
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 acetaminophen-HYDROcodone (Lortab, Norco, Vicodin)
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 acetaminophen-oxyCODONE (Percocet, Roxicet, Tylox)
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 acetaminophen-traMADol (Ultracet)
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 alfuzosin (Uroxatral)
Data are limited for selective peripheral alpha-1 blockers (e.g., tamsulosin, silodosin, and others) but may apply as well.
 
Interacting drug(s) or class(es) selective peripheral alpha-1 blockers ⇄ Loop diuretics
Risk Rationale Increased risk of urinary incontinence in older women.
Recommendation Avoid in older women, unless conditions warrant both drugs.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 aliskiren (Tekturna)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 ALPRAZolam (Xanax)
Interacting drug(s) or class(es) benzodiazepines ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 aMILoride (Midamor)
Interacting drug(s) or class(es) potassium-sparing diuretics ⇄ RAS inhibitors (ACEIs, ARBs, ARNIs, aliskiren)
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 aMILoride-hydroCHLOROthiazide (Moduretic)
Interacting drug(s) or class(es) potassium-sparing diuretics ⇄ RAS inhibitors (ACEIs, ARBs, ARNIs, aliskiren)
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 amitriptyline (Elavil)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 amoxapine (Asendin)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 ARIPiprazole (Abilify)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 asenapine (Saphris)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 atropine
excludes ophthalmic
 
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 azilsartan (Edarbi)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 B
 baclofen (Lioresal)
Interacting drug(s) or class(es) skeletal muscle relaxants ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 benazepril (Lotensin)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 benztropine (Cogentin)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 brexpiprazole (Rexulti)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 brivaracetam (Briviact)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 brompheniramine (Dimetane, Dimetapp)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 C
 candesartan (Atacand)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 cannabidiol (Epidiolex)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 captopril (Capoten)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 carBAMazepine (Carbatrol, TEGretol)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 cariprazine (Vraylar)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 carisoprodol (Soma)
Interacting drug(s) or class(es) skeletal muscle relaxants ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 cenobamate (Xcopri)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 chlordiazePOXIDE (Librium)
alone or in combination with amitriptyline or clidinium
 
Interacting drug(s) or class(es) benzodiazepines ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 chlorpheniramine (Chlor-Trimeton)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 chlorproMAZINE (Thorazine)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 chlorzoxazone (Parafon Forte DSC)
Interacting drug(s) or class(es) skeletal muscle relaxants ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 citalopram (CeleXA)
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 clidinium-chlordiazePOXIDE (Librax)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 cloBAZam (Onfi, Sympazan)
Interacting drug(s) or class(es) benzodiazepines ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 clomiPRAMINE (Anafranil)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 clonazePAM (KlonoPIN)
Interacting drug(s) or class(es) benzodiazepines ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 clorazepate (Tranxene)
Interacting drug(s) or class(es) benzodiazepines ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 cloZAPine (Clozaril)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 codeine
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 cyclobenzaprine (Flexeril)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) skeletal muscle relaxants ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 cyproheptadine (Periactin)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 D
 dantrolene (Dantrium)
Interacting drug(s) or class(es) skeletal muscle relaxants ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 darifenacin (Enablex)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 desipramine (Norpramin)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 desvenlafaxine (Pristiq)
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 diazePAM (Valium)
Interacting drug(s) or class(es) skeletal muscle relaxants ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) benzodiazepines ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 dicyclomine (Bentyl)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 dimenhyDRINATE (Dramamine)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 diphenhydrAMINE (Benadryl)
diphenhydrAMINE (oral) Use of diphenhydrAMINE in situations such as acute treatment of severe allergic reactions may be appropriate.
 
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 divalproex (Depakote)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 doxazosin (Cardura)
Interacting drug(s) or class(es) non-selective peripheral alpha-1 blockers ⇄ Loop diuretics
Risk Rationale Increased risk of urinary incontinence in older women.
Recommendation Avoid in older women, unless conditions warrant both drugs.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 doxepin (SINEquan)
>6 mg/day
 
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 doxylamine (Unisom)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 droperidol (Inapsine)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 DULoxetine (Cymbalta)
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 E
 enalapril (Vasotec)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 epleronone (Inspra, Espler)
Interacting drug(s) or class(es) potassium-sparing diuretics ⇄ RAS inhibitors (ACEIs, ARBs, ARNIs, aliskiren)
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 escitalopram (Lexapro)
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 eslicarbazepine (Aptiom)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 estazolam (Prosom)
Interacting drug(s) or class(es) benzodiazepines ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 eszopiclone (Lunesta)
Interacting drug(s) or class(es) nonbenzodiazepine benzodiazepine-receptor agonist hypnotics (i.e., "Z-drugs") ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 ethosuximide (Zarontin)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 everolimus (Afinitor, Zortress)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 F
 felbamate (Felbatol)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 fenfluramine (Fintepla)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 fentaNYL (Sublimaze)
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 fesoterodine (Toviaz)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 finerenone (Kerendia)
Interacting drug(s) or class(es) potassium-sparing diuretics ⇄ RAS inhibitors (ACEIs, ARBs, ARNIs, aliskiren)
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 flavoxATE (Urispas)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 FLUoxetine (PROzac)
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 fluPHENAZine (Prolixin)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 fLuvoxaMINE (Luvox)
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 fosinopril (Monopril)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 G
 gabapentin (Neurontin)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 ganaxolone (Ztalmy)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 H
 haloperidol (Haldol)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 homatropine (Hycodan, Hydromet)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 HYDROmorphone (Dilaudid)
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 hydrOXYzine (Atarax, Vistaril)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 hyoscyamine (Hyosyne, Levsin, Levsinex)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 I
 iloperidone (Fanapt)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 imipramine (Tofranil)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 irbesartan (Avapro)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 L
 lacosamide (Vimpat)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 lamoTRIgine (LaMICtal)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 levETIRAcetam (Keppra)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 levomilnacipran (Fetzima)
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 lisinopril (Prinivil, Zestril)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 lithium (Eskalith, Lithobid)
Interacting drug(s) or class(es) lithium ⇄ ACEIs, ARBs, ARNIs
Risk Rationale Increased risk of lithium toxicity.
Recommendation Avoid; monitor lithium concentrations.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) lithium ⇄ Loop diuretics
Risk Rationale Increased risk of lithium toxicity.
Recommendation Avoid; monitor lithium concentrations.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 LORazepam (Ativan)
Interacting drug(s) or class(es) benzodiazepines ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 losartan (Cozaar)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 loxapine (Loxitane)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 lurasidone (Latuda)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 M
 meclizine (Antivert)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 meperidine (Demerol)
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 metaxalone (Skelaxin)
Interacting drug(s) or class(es) skeletal muscle relaxants ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 methadone (Dolophine)
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 methocarbamol (Robaxin)
Interacting drug(s) or class(es) skeletal muscle relaxants ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 midazolam (Versed)
Interacting drug(s) or class(es) benzodiazepines ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 milnacipran (SavElla)
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 moexipril (Univasc)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 morphine (Oramorph SR, Roxanol)
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 N
 nortriptyline (Pamelor)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 O
 OLANZapine (ZyPREXA)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 olmesartan (Benicar)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 orphenadrine (Norflex)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) skeletal muscle relaxants ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 oxazepam (Serax)
Interacting drug(s) or class(es) benzodiazepines ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 OXcarbazepine (Oxtellar XR)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 oxybutynin (Ditropan)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 oxyCODONE (Oxaydo, OxyCONTIN, Oxyfast, Oxy-IR, Percodan, Roxicodone, Roxybond, Xtampza)
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 oxyMORphone (Numorphan, Opana)
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 P
 paliperidone (Invega)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 PARoxetine (Paxil)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 perampanel (Fycompa)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 perindopril (Aceon)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 perphenazine (Trilafon)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 PHENobarbital (Luminal)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 phenytoin (Dilantin, Phenytek)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) phenytoin ⇄ trimethoprim-sulfamethoxazole
Risk Rationale Increased risk of phenytoin toxicity
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 pimavanserin (Nuplazid)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 pimozide (Orap)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 prazosin (Minipress)
Interacting drug(s) or class(es) non-selective peripheral alpha-1 blockers ⇄ Loop diuretics
Risk Rationale Increased risk of urinary incontinence in older women.
Recommendation Avoid in older women, unless conditions warrant both drugs.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 pregabalin (Lyrica)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 primidone (Mysoline)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 prochlorperazine (Compazine)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 promethazine (Phenadoz, Phenergan)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 Q
 QUEtiapine (SEROquel)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 quinapril (Accupril)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 R
 ramipril (Altace)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 risperiDONE (RisperDAL)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 rufinamide (Banzel)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 S
 sacubitril-valsartan  (Entresto)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 scopolamine (Transderm Scop)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 sertraline (Zoloft)
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 silodosin (Rapaflo)
Data are limited for selective peripheral alpha-1 blockers (e.g., tamsulosin, silodosin, and others) but may apply as well.
 
Interacting drug(s) or class(es) selective peripheral alpha-1 blockers ⇄ Loop diuretics
Risk Rationale Increased risk of urinary incontinence in older women.
Recommendation Avoid in older women, unless conditions warrant both drugs.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 solifenacin (Vesicare)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 spironolactone (Aldactone, Carospir)
Interacting drug(s) or class(es) potassium-sparing diuretics ⇄ RAS inhibitors (ACEIs, ARBs, ARNIs, aliskiren)
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 spironolactone-hydroCHLOROthiazide (Aldactazide)
Interacting drug(s) or class(es) potassium-sparing diuretics ⇄ RAS inhibitors (ACEIs, ARBs, ARNIs, aliskiren)
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 stiripentol (Diacomit)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 SUFentanil (Sufenta)
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 T
 tamsulosin (Flomax)
Data are limited for selective peripheral alpha-1 blockers (e.g., tamsulosin, silodosin, and others) but may apply as well.
 
Interacting drug(s) or class(es) selective peripheral alpha-1 blockers ⇄ Loop diuretics
Risk Rationale Increased risk of urinary incontinence in older women.
Recommendation Avoid in older women, unless conditions warrant both drugs.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 telmisartan (Micardis)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 temazepam (Restoril)
Interacting drug(s) or class(es) benzodiazepines ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 terazosin (Hytrin)
Interacting drug(s) or class(es) non-selective peripheral alpha-1 blockers ⇄ Loop diuretics
Risk Rationale Increased risk of urinary incontinence in older women.
Recommendation Avoid in older women, unless conditions warrant both drugs.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 theophylline
Interacting drug(s) or class(es) theophylline ⇄ cimetidine
Risk Rationale Increased risk of theophylline toxicity
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) theophylline ⇄ ciprofloxacin
Risk Rationale Increased risk of theophylline toxicity
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 thioridazine (MEllaril)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 thiothixine (Navane)
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 tiaGABine (Gabitril)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 tiZANidine (Zanaflex)
Interacting drug(s) or class(es) skeletal muscle relaxants ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 tolterodine (Detrol)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 topiramate (Qudexy XR, Topamax)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 traMADol (Ultram)
Interacting drug(s) or class(es) opioids ⇄ benzodiazepines
Risk Rationale Increased risk of overdose and adverse events.
Recommendation Avoid
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 
Interacting drug(s) or class(es) opioids ⇄ gabapentin, pregabalin
Risk Rationale Increased risk of severe sedation-related adverse events, including respiratory depression and death.
Recommendation Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 trandolapril (Mavik)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 triamterene (Dyrenium)
Interacting drug(s) or class(es) potassium-sparing diuretics ⇄ RAS inhibitors (ACEIs, ARBs, ARNIs, aliskiren)
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 triamterene-hydroCHLOROthiazide (Dyazide, Maxzide)
Interacting drug(s) or class(es) potassium-sparing diuretics ⇄ RAS inhibitors (ACEIs, ARBs, ARNIs, aliskiren)
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 triazolam (Halcion)
Interacting drug(s) or class(es) benzodiazepines ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 trifluoperazine (Stelazine)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 trihexyphenidyl (Artane)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 triprolidine (Histex, Zymine)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 trospium (Sanctura)
Interacting drug(s) or class(es) anticholinergics ⇄ anticholinergics
Risk Rationale Use of more than one medication with anticholinergic properties increases the risk of cognitive decline, delirium, and falls or fractures.
Recommendation Avoid; minimize the number of anticholinergic drugs Click for list.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 V
 valproic acid (Depacon, Stavzor)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 valsartan (Diovan)
Interacting drug(s) or class(es) RAS inhibitors (ACEIs ARBs, ARNIs, aliskiren) ⇄ Another RAS inhibitor or a potassium-sparing diuretic
Risk Rationale Increased risk of hyperkalemia.
Recommendation Avoid routinely using 2 or more RAS inhibitors, or a RAS inhibitor and potassium-sparing diuretic, concurrently in those with chronic kidney disease Stage 3a or higher.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 venlafaxine (Effexor)
Interacting drug(s) or class(es) antidepressants (TCAs, SSRIs, and SNRIs) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 vigabatrin (Sabril)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 W
 warfarin (Coumadin, Jantoven)
Interacting drug(s) or class(es) warfarin ⇄ amiodarone, ciprofloxacin, macrolides (excluding azithromycin), trimethoprim-sulfamethoxazole, SSRIs
Risk Rationale Increased risk of bleeding.
Recommendation Avoid when possible; if used together, monitor INR closely.
 Quality of evidence: Moderate, Strength of Recommendation: Strong
 Z
 zaleplon (Sonata)
Interacting drug(s) or class(es) nonbenzodiazepine benzodiazepine-receptor agonist hypnotics (i.e., "Z-drugs") ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 ziprasidone (Geodon)
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health and neuropsychiatric conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
 
Interacting drug(s) or class(es) antipsychotics ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 zolpidem (Ambien)
Interacting drug(s) or class(es) nonbenzodiazepine benzodiazepine-receptor agonist hypnotics (i.e., "Z-drugs") ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong
 zonisamide (Zonegran)
Interacting drug(s) or class(es) antiepileptics (including gabapentinoids) ⇄ CNS-active agents
Risk Rationale Increased risk of falls and of fracture with the concurrent use of ≥3 CNS-active agents (antiepileptics including gabapentinoids, antidepressants, antipsychotics, benzodiazepines, Nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants).
Recommendation Avoid concurrent use of ≥3 CNS-active drugs Click for list; minimize the number of CNS-active drugs.
 Quality of evidence: High, Strength of Recommendation: Strong

Pharmacy Contact Info:

Main Inpatient Pharmacy: ext 4599, 3503
Fax: 704-878-7283

Director of Pharmacy - Randi Raynor, PharmD: ext 4501
Clinical Coordinator - Laura Rollings, PharmD: ext 4597
Pharmacy Informaticist - Stephen Pringle, PharmD: ext 7645
Pharmacy Technician Supervisor - Amy Wingler, CPhT: ext 7385
Pharmacy Automation Coordinator (Omnicell) - Melissa Fulford, CPhT: ext 3556



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