OBJECT DRUGS
- Ramelteon (Rozerem)
- Tasimelteon (Hetlioz)
PRECIPITANT DRUGS
Enzyme Inhibitors:
- Atazanavir (Reyataz)
- Cimetidine (Tagamet, etc.)
- Ciprofloxacin (Cipro, etc.)
- Enoxacin (Penetrex)
- Fluvoxamine (Luvox, etc.)
- Mexiletine (Mexitil)
- Tacrine (Cognex)
- Zileuton (Zyflo, etc.)
Comment:
Ramelteon is metabolized by CYP1A2, and inhibitors of CYP1A2 can produce dramatic increases in ramelteon plasma concentrations. Fluvoxamine is one of the post potent CYP1A2 inhibitors known, and it can cause an almost 200-fold increase in ramelteon plasma concentrations. Given the apparently high sensitivity of ramelteon to CYP1A2 inhibitors, even weaker inhibitors may be expected to produce substantial increases in ramelteon plasma concentrations. Although ramelteon does not appear to have much dose-related toxicity in normal dose ranges, it is possible that toxicity may occur following the dramatically increased concentrations found after concurrent use of CYP1A2 inhibitors. Tasimelteon is also metabolized by CYP1A2, but is not as sensitive to CYP1A2 inhibitors as ramelteon.
Class 2: Use only if benefit felt to outweigh risk
- Use Alternative: Given the magnitude of the increases in ramelteon plasma concentrations, it would be prudent to avoid these combinations.
- Ramelteon or Tasimelteon: Eszopiclone (Lunesta), zaleplon (Sonata), zolpidem (Ambien), and zopiclone (Imovane) are metabolized primarily by CYP3A4, and are probably less likely to interact with CYP1A2 inhibitors than is ramelteon.
- Cimetidine: Famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac) do not appear to affect CYP1A2 activity.
- Fluoroquinolones: Gemifloxacin (Factive), levofloxacin (Levaquin), lomefloxacin (Maxaquin), moxifloxacin (Avelox), norfloxacin (Noroxin), and ofloxacin (Floxin) appear to have little effect on CYP1A2.
- Fluvoxamine: Citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and venlafaxine (Effexor), are not known to inhibit CYP1A2.
- Monitor: If ramelteon or tasimelteon is used with a CYP1A2 inhibitor, monitor for evidence of ramelteon toxicity.