Question 1:
List two reasons why this patient may be at risk for an adverse event.
Answer: This patient may be at risk for an adverse event because of his age, because he is taking multiple medications, has comorbid diseases, and his use of a drug is chronic (use for 8 weeks).
Question 2:
Is a temporal relationship of acute liver failure with drug X reported in this case?
Answer: Yes.
Question 3:
Based on the information on recovery of acute liver failure reported in this case, the patient experienced:
A. Positive rechallenge
B. Negative dechallenge
C. Positive dechallenge
D. Negative rechallenge
Answer: Positive dechallenge.
Question 4:
Name two characteristics in this case that support a causal association of acute liver failure with Drug X.
Answer: Characteristics include temporal association, positive dechallenge, alternate causes (viral hepatitis, alcohol use) ruled out, and no prior history of liver disease.
Question 5:
Based on this case, should regulatory action be taken to add acute liver failure to the label? If not, what additional information may be helpful?
Answer: These decisions are not always easy and straightforward. In this case, additional information would be helpful to understand several unknown factors:
- When were lisinopril and simvastatin started and were they discontinued or continued after the event? Simvastatin is labeled for increase LFTs and lisinopril for hepatic failure: two places to check labels (package inserts or prescribing information) are Drugs@FDA or DailyMed (https://dailymed.nlm.nih.gov/).
- Are there any other cases? Usually more than one case is needed.
- Is there evidence for biologic plausibility? Are other drugs in the same class as Drug X known to cause liver injury?
- What is the exposure to this drug? For example, did this one patient experience liver failure out of only 10 patients exposed to Drug X (10%), or did this one patient experience liver failure out of millions of patients exposed to Drug X?
Presented by the PhRMA Foundation Safe and Effective Prescribing Project
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