OBJECT DRUGS
Antipsychotics, Atypical:
- Aripiprazole (Abilify, etc.)
- Brexpiprazole (Rexulti)
- Clozapine (Clozaril, etc.)
- Iloperidone (Fanapt)
- Olanzapine (Zyprexa, etc.)
- Paliperidone (Invega, etc.)
- Perphenazine (Trilafon)
- Risperidone (Risperdal, etc.)
PRECIPITANT DRUGS
Enzyme Inhibitors: (CYP2D6)
- Abiraterone (Zytiga)
- Amiodarone (Cordarone, etc.)
- Cinacalcet (Sensipar)
- Clobazam (Onfi)
- Diphenhydramine (Benadryl, etc.)
- Haloperidol (Haldol)
- Mirabegron (Myrbetriq)
- Propafenone (Rythmol, etc.)
- Propoxyphene*
- Quinidine (Quinidex)
- Ritonavir (Norvir)
- Terbinafine (Lamisil, etc.)
- Thioridazine (Mellaril)
* Propoxyphene (Darvon) was withdrawn from the US market.
Comment:
These antipsychotics are metabolized by CYP2D6. Drugs that inhibit CYP2D6 may lead to accumulation of the antipsychotic. People with "normal" CYP2D6 activity (Extensive Metabolizers) are at the greatest risk. Most of these antipsychotics have multiple pathways of elimination (see CYP3A4 inhibitors, above), and the magnitude of the interactions is likely to vary substantially depending on the specific pair of drugs, and the specific patient characteristics. Note that because terbinafine has an extraordinarily long terminal half-life, the inhibitory effect of terbinafine on CYP2D6 may last for many weeks after terbinafine is discontinued. In one case perphenazine toxicity (akathisia) persisted for 3 weeks after stopping terbinafine. (Perphenazine is not technically an "atypical" antipsychotic.)
Class 3: Assess Risk & Take Action if Necessary
- Consider Alternative:
- Diphenhydramine: Other antihistamines such as desloratadine (Clarinex), fexofenadine (Allegra), loratadine Claritin), and cetirizine (Zyrtec) are not known to inhibit CYP2D6.
- Monitor: Be alert for altered effect of these antipsychotics if CYP2D6 inhibitors are started, stopped, or changed in dosage. The iloperidone product information suggests lowering the iloperidone dose by 50% when it is used with CYP2D6 inhibitors. Due to the long half-lives of some of these drugs, the onset and offset of these interactions may take one to two weeks.