Replies to post #188895 on Biotech Values

[dewophile]

I'm still not sure what effect this will have on prescribing habits. May be negligible (see discussion w Peter) or there could be a broader sense that harvoni not great in PTS w severe cardiac comorbidity where you have potential for life threatening drug interaction w a med that may be needed if they go into v tach while on tx.

[frontiers]

GILD: new warning on sovaldi/harvoni label

from GILD website --

Serious Risk of Symptomatic Bradycardia With Co-Use of Amiodarone with Either Harvoni or With Sovaldi in Combination with Another Direct Acting Antiviral (DAA)

• Postmarketing cases of symptomatic bradycardia, as well as one fatal cardiac arrest and cases requiring pacemaker insertion, have been reported in patients taking amiodarone and Harvoni, or amiodarone andSovaldi in combination with another DAA.
• Bradycardia was observed within hours to days of starting Harvoni, or Sovaldi in combination with another DAA, but cases have been observed up to 2 weeks after initiating HCV treatment.
• Risk factors for the development of symptomatic bradycardia in patients receiving amiodarone may include coadministration of a beta blocker, or those with underlying cardiac comorbidities and/or advanced liver disease.
• Similar cases have not been reported in patients receiving Sovaldi with ribavirin or with pegylated interferon and ribavirin.

Warning and Precaution
Coadministration of amiodarone with either Harvoni or with Sovaldi in combination with another DAA is not recommended.

Further Information

Nine cases of symptomatic bradycardia have been reported during postmarketing in patients receiving amiodarone with either Harvoni, or Sovaldi in combination with another DAA (daclatasvir, an investigational DAA, or Olysio (simeprevir)). Seven patients were also receiving a beta blocker.

• Six cases occurred within the first 24 hours and the remaining 3 cases occurred within the first 2-12 days following HCV treatment initiation.
• One case was a fatal cardiac arrest and 3 cases required pacemaker intervention.
• In 3 cases, rechallenge with HCV treatment in the setting of continued amiodarone therapy resulted in recurrence of symptomatic bradycardia.
• In one case discontinuation of amiodarone followed by rechallenge of HCV treatment after 8 weeks did not result in recurrent bradycardia.
• Three of the 9 cases were in patients receiving Harvoni, 5 cases were in patients receiving Sovaldi plus an investigational agent (daclatasvir) and 1 case was in a patient receiving Sovaldi with Olysio (simeprevir).

The mechanism of the potential interaction between amiodarone and Harvoni, or Sovaldi in combination with another DAA is unknown.

Because the number of patients taking amiodarone who have been exposed to Harvoni or Sovaldi in combination with another DAA is unknown, it is not possible to estimate the incidence of occurrence of these events.

Prescriber Action
For patients taking amiodarone who have no other alternative, viable treatment options and who will be co-administered Harvoni, or Sovaldi in combination with another DAA:
• Counsel patients about the risk of serious symptomatic bradycardia
• Cardiac monitoring in an in-patient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.

Patients who are taking Harvoni or Sovaldi in combination with another DAA who need to start amiodarone therapy due to no other alternative, viable treatment options should undergo similar cardiac monitoring as outlined above.

Due to amiodarone’s long half-life, patients discontinuing amiodarone just prior to starting Harvoni or Sovaldi in combination with a DAA should also undergo similar cardiac monitoring as outlined above.