olanzapine / samidorphan

What is in it

Each ingredient has its own full page with the FDA label, side-effect reports, recalls, evidence, and payments. Open them for the detail behind this grade.

Score breakdown (47/100)

Safety: 35

• Graded by its riskiest ingredient, olanzapine (35)
• Carries an FDA boxed warning, the strongest warning the FDA issues (-30)
• FDA issued 2 Drug Safety Communication(s) naming this drug since 2010, most recently 2016 (-16)
• 4,328 FDA reports naming it as the suspect drug per million Medicare fills, 1.6x the median drug on this site (-4)
• Subject to a REMS safety program: FDA requires special controls to use it (-10)
• Death share in reports is near or below the FAERS average (1.2x)
• Off-label use is among the five most-reported items: widely used beyond its approved evidence (-5)

Evidence: 38

• Graded by its riskiest ingredient, samidorphan (38)
• 21 randomized trials and 3 systematic reviews/meta-analyses indexed in PubMed
• No Cochrane review found (-5)

Regulatory history: 73

• Graded by its riskiest ingredient, olanzapine (73)
• Recalls since 2016: 0 Class I, 2 Class II, 2 Class III across 46 generic makers (-4)
• REMS program in force (-10)
• 10 label changes approved since 2021: the safety story is still moving (-8)
• Label lists recent major changes to warnings or indications (-5)

Money & lawsuits: 70

• Graded by its riskiest ingredient, olanzapine (75)
• Maker paid $1.4 billion in 2009 to settle federal allegations naming this drug (Off-label promotion) (-25)
• Pharma paid doctors $0 tied to this drug last year: negligible
• Not named in any pending federal MDL
• For the combination product itself:
• Pharma paid doctors $4,877,809 tied to this drug last year (-30)
• Not named in any pending federal MDL

Options: 40

• Graded by its riskiest ingredient, samidorphan (40)
• No generic version approved: brand-only pricing (-30)
• No same-class alternatives found: little leverage to switch (-30)

Money and lawsuits

In 2024, drug companies reported $4,877,809 in payments to US physicians and hospitals tied to this combination's brands across 16,955 transactions (Lybalvi $4,877,809).

No pending federal MDL names this combination or its brands.

The ingredients' own payments and lawsuits are on their pages and already count toward this grade.

Who takes it and what it costs

Not in the Medicare Part D spending file.

Questions to ask your prescriber

1. This is a fixed combination of olanzapine and samidorphan. Why both together, instead of only the one I need?
2. In 2016 the FDA issued a safety communication about this drug (FDA warns about rare but serious skin reactions with mental health drug olanzapine (Zyprexa, Zyprexa Zydis, Zy). Does that risk apply to me?
3. The maker paid $1.4 billion in 2009 to settle federal allegations about how this drug was marketed. Is my use one of the uses that was promoted improperly?
4. This drug carries a boxed warning. Which specific risk does it cover, and does it apply to me?
5. This drug has a REMS safety program. What monitoring does that require from us?
6. The most-reported problems in FDA's adverse event data are weight increased, toxicity to various agents. How would we recognize and handle those?
7. Off-label use is among the most-reported items for this drug. Is my use on-label, and if not, what evidence supports it?
8. Why this one over asenapine, clothiapine, clozapine? What would make you pick one of those instead?
9. What result are we expecting, by when, and what is the plan if it does not happen?
10. If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)
11. The most-reported problems in FDA's adverse event data are abdominal discomfort, blood creatine phosphokinase increased, diarrhoea, drug interaction. How would we recognize and handle those?
12. There is no generic. Is there an older generic in the same class that works as well for my situation?