FDA approved changes to the Olysio (simeprevir) package insert to include two new Warnings and Precautions;
--serious symptomatic bradycardia when co-administered with sofosbuvir and amiodarone
--hepatic decompensation and hepatic failure.
FDA - Safety Announcement
Facts about Harvoni and Sovaldi
More Info for Patients
More Info for Health Care Professionals
Data Summary
March 21:
Serious and Life-Threatening Cases of Symptomatic Bradycardia as well as One Case of Fatal Cardiac Arrest Reported with Coadministration of amiodarone with either Harvoni® (ledipasvir and sofosbuvir fixed-dose combination) or with Sovaldi® (sofosbuvir) in combination with another direct acting antiviral.
Please see Gilead Sciences has issued a Dear Healthcare Provider letter:
SVD HVN - DHCP Letter 20March15 - FINAL.DOCX - COPY provided below......
On March 20, 2015, FDA approved changes to the Harvoni (ledipasvir/sofosbuvir fixed dose combination) and Sovaldi (sofosbuvir) labels to update the WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS, and DRUG INTERATIONS sections of the labeling and the patient package insert with information on post-marketing cases of symptomatic bradycardia when co-administered with amiodarone. Additionally, Gilead Sciences has issued a Dear Healthcare Provider letter (see below).
The specific changes to the each label are summarized below.
Harvoni label changes:
5 WARNINGS AND PRECAUTIONS
5.1 Serious Symptomatic Bradycardia When Coadministered with Amiodarone
Postmarketing cases of symptomatic bradycardia, including fatal cardiac arrest and cases requiring pacemaker intervention, have been reported when amiodarone is coadministered with HARVONI. Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. Bradycardia generally resolved after discontinuation of HCV treatment. The mechanism for this effect is unknown.
Coadministration of amiodarone with HARVONI is not recommended. For patients taking amiodarone who have no other alternative, viable treatment options and who will be coadministered HARVONI:
• 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 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 should also undergo similar cardiac monitoring as outlined above.
Patients who develop signs or symptoms of bradycardia should seek medical evaluation immediately.
6 ADVERSE REACTIONS
6.2 Postmarketing Experience
Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been identified during post approval use of HARVONI.
7 DRUG INTERACTIONS
Added amiodarone information to Table 3, Potentially Significant Drug Interactions: Alterations in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction.
Sovaldi Label Changes:
5 WARNINGS AND PRECAUTIONS
IMPORTANT DRUG WARNING
Subject: Serious and Life-Threatening Cases of Symptomatic Bradycardia as well as One Case of Fatal Cardiac Arrest Reported with Coadministration of Amiodarone With Either Harvoni® (ledipasvir and sofosbuvir fixed-dose combination) or With Sovaldi® (sofosbuvir) in Combination with Another Direct Acting Antiviral.
Dear Health Care Provider,
The purpose of this letter is to inform you of new important safety information for Harvoni and Sovaldi
· Harvoni is indicated for the treatment of chronic hepatitis C genotype 1 infection in adults.
· Sovaldi is indicated for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen.
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 and Sovaldi 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.
Tell your patients if they develop signs or symptoms that might suggest symptomatic bradycardia they should seek medical evaluation immediately. Symptoms may include:
· Near-fainting or fainting
· Excessive tiredness
· Dizziness or lightheadedness
· Shortness of breath
· Malaise
· Chest pains
· Weakness
· Confusion or memory problems
Patients should not stop taking any of their medicines without talking to their healthcare provider.
This information is based on currently available data and recommendations may change. Additionally, the product labeling will be updated.
Reporting Adverse Events
Please report all adverse events, following or coincident with the use of Harvoni or Sovaldi, to Gilead Global Drug Safety at 1-800-GILEAD-5, option 3; or to FDA's MedWatch program by telephone at 1-800-332-1088; by fax at 1-800-332-0178; via www.FDA.gov/medwatch; or by mail to MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20857 (use postage-paid FDA Form 3500).
Please refer to the accompanying full prescribing information and approved patient information for a complete description of the risk profile for Harvoni or Sovaldi.
Contact Gilead Medical Information at 1-800-GILEAD-5, option 2 if you have additional questions.
This information is being sent in agreement with the FDA.
Sincerely,
John McHutchison, MD
Executive Vice President, Clinical Research
Gilead Sciences, Inc.
Download - SVD HVN - DHCP Letter 20March15 - FINAL.DOCX
FDA update and Gilead Sciences issued letter to Healthcare Providers;
FDA Hepatitis Update - Important safety information: Harvoni , and Sovaldi
FDA Hepatitis Update - Important safety information: Harvoni , and Sovaldi
Serious and Life-Threatening Cases of Symptomatic Bradycardia as well as One Case of Fatal Cardiac Arrest Reported with Coadministration of amiodarone with either Harvoni® (ledipasvir and sofosbuvir fixed-dose combination) or with Sovaldi® (sofosbuvir) in combination with another direct acting antiviral.Please see Gilead Sciences has issued a Dear Healthcare Provider letter:
SVD HVN - DHCP Letter 20March15 - FINAL.DOCX - COPY provided below......
On March 20, 2015, FDA approved changes to the Harvoni (ledipasvir/sofosbuvir fixed dose combination) and Sovaldi (sofosbuvir) labels to update the WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS, and DRUG INTERATIONS sections of the labeling and the patient package insert with information on post-marketing cases of symptomatic bradycardia when co-administered with amiodarone. Additionally, Gilead Sciences has issued a Dear Healthcare Provider letter (see below).
The specific changes to the each label are summarized below.
Harvoni label changes:
5 WARNINGS AND PRECAUTIONS
5.1 Serious Symptomatic Bradycardia When Coadministered with Amiodarone
Postmarketing cases of symptomatic bradycardia, including fatal cardiac arrest and cases requiring pacemaker intervention, have been reported when amiodarone is coadministered with HARVONI. Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. Bradycardia generally resolved after discontinuation of HCV treatment. The mechanism for this effect is unknown.
Coadministration of amiodarone with HARVONI is not recommended. For patients taking amiodarone who have no other alternative, viable treatment options and who will be coadministered HARVONI:
• 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 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 should also undergo similar cardiac monitoring as outlined above.
Patients who develop signs or symptoms of bradycardia should seek medical evaluation immediately.
6 ADVERSE REACTIONS
6.2 Postmarketing Experience
Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been identified during post approval use of HARVONI.
7 DRUG INTERACTIONS
Added amiodarone information to Table 3, Potentially Significant Drug Interactions: Alterations in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction.
Concomitant Drug Class: Drug Name
|
Effect on Concentration
|
Clinical Comment
|
Antiarrhythmics:
amiodarone
|
Effect on amiodarone, ledipasvir, and sofosbuvir concentrations unknown
|
Coadministration of HARVONI with amiodarone may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. Coadministration of amiodarone with HARVONI is not recommended; if coadministration is required, cardiac monitoring is recommended [see Warnings and Precautions (5.1)]
|
Sovaldi Label Changes:
5 WARNINGS AND PRECAUTIONS
5.1 Serious Symptomatic Bradycardia When Coadministered with Amiodarone and Another HCV Direct Acting Antiviral
Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with SOVALDI in combination with an investigational agent (NS5A inhibitor) or simeprevir. A fatal cardiac arrest was reported in a patient receiving a sofosbuvir-containing regimen (HARVONI (ledipasvir/sofosbuvir)). Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. Bradycardia generally resolved after discontinuation of HCV treatment. The mechanism for this effect is unknown.
Coadministration of amiodarone with SOVALDI in combination with another direct acting antiviral (DAA) is not recommended. For patients taking amiodarone who have no other alternative, viable treatment options and who will be coadministered SOVALDI and 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 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 SOVALDI in combination with a DAA should also undergo similar cardiac monitoring as outlined above.
Patients who develop signs or symptoms of bradycardia should seek medical evaluation immediately. Symptoms may include near-fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pains, confusion or memory problems [See Adverse Reactions (6.2), Drug Interactions (7.2)].
6 ADVERSE REACTIONS
6.2 Postmarketing Experience
The following adverse reactions have been identified during post approval use of SOVALDI. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiac Disorders
Serious symptomatic bradycardia has been reported in patients taking amiodarone who initiate treatment with SOVALDI in combination with another HCV direct acting antiviral [See Warnings and Precautions (5.1), Drug Interactions (7.2)].
7 DRUG INTERACTIONS
Added amiodarone information to Table 5, Potentially Significant Drug Interactions: Alterations in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction.
Updated labeling will be posted soon at DailyMed
Concomitant Drug Class: Drug Name
|
Effect on Concentration
|
Clinical Comment
|
Antiarrhythmics:
amiodarone
|
Effect on amiodarone and sofosbuvir concentrations unknown
|
Coadministration of amiodarone with SOVALDI in combination with another DAA may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. Coadministration of amiodarone with SOVALDI in combination with another DAA is not recommended; if coadministration is required, cardiac monitoring is recommended [See Warnings and Precautions (5.1), Adverse Reactions (6.2)].
|
Please see Gilead Sciences has issued a Dear Healthcare Provider letter:
SVD HVN - DHCP Letter 20March15 - FINAL.DOCX - COPY provided below......
Harvoni and Sovaldi are products of Gilead Sciences.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
Steve Morin
Office of Special Health Issues
Food and Drug Administration
Gilead Sciences issued letter to Healthcare Providers
FDA Hepatitis Update - Important safety information: Harvoni , and Sovaldi
IMPORTANT DRUG WARNING
Subject: Serious and Life-Threatening Cases of Symptomatic Bradycardia as well as One Case of Fatal Cardiac Arrest Reported with Coadministration of Amiodarone With Either Harvoni® (ledipasvir and sofosbuvir fixed-dose combination) or With Sovaldi® (sofosbuvir) in Combination with Another Direct Acting Antiviral.
Dear Health Care Provider,
The purpose of this letter is to inform you of new important safety information for Harvoni and Sovaldi
· Harvoni is indicated for the treatment of chronic hepatitis C genotype 1 infection in adults.
· Sovaldi is indicated for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen.
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 and Sovaldi 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.
Tell your patients if they develop signs or symptoms that might suggest symptomatic bradycardia they should seek medical evaluation immediately. Symptoms may include:
· Near-fainting or fainting
· Excessive tiredness
· Dizziness or lightheadedness
· Shortness of breath
· Malaise
· Chest pains
· Weakness
· Confusion or memory problems
Patients should not stop taking any of their medicines without talking to their healthcare provider.
This information is based on currently available data and recommendations may change. Additionally, the product labeling will be updated.
Reporting Adverse Events
Please report all adverse events, following or coincident with the use of Harvoni or Sovaldi, to Gilead Global Drug Safety at 1-800-GILEAD-5, option 3; or to FDA's MedWatch program by telephone at 1-800-332-1088; by fax at 1-800-332-0178; via www.FDA.gov/medwatch; or by mail to MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20857 (use postage-paid FDA Form 3500).
Please refer to the accompanying full prescribing information and approved patient information for a complete description of the risk profile for Harvoni or Sovaldi.
Contact Gilead Medical Information at 1-800-GILEAD-5, option 2 if you have additional questions.
This information is being sent in agreement with the FDA.
Sincerely,
John McHutchison, MD
Executive Vice President, Clinical Research
Gilead Sciences, Inc.
Download - SVD HVN - DHCP Letter 20March15 - FINAL.DOCX
Can you point to an official statement directly from either FDA or Gilead on this?
ReplyDeletePlease see the first paragraph in the post, click to download. Text reads; Please see Gilead Sciences has issued a Dear Healthcare Provider letter:
ReplyDeleteSVD HVN - DHCP Letter 20March15 - FINAL.DOCX. I received the safety update because I am a subscriber to the FDA hepatitis electronic list serve. As noted in the release; Updated labeling will be posted soon at DailyMed
Hope this helps, added Healthcare Provider letter from Gilead at the bottom of the post.
ReplyDelete