Serious and Life-Threatening Cases for use Harvoni and Sovaldi with amiodarone
Serious and Life-Threatening Cases for use Harvoni and Sovaldi with amiodarone
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.The specific changes to each label are summarized below.
Harvoni label changes:
WARNINGS AND PRECAUTIONS
Serious Symptomatic Bradycardia When Coadministered with AmiodaronePostmarketing 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.
• 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.
ADVERSE REACTIONS
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.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.Effect on amiodarone, ledipasvir, and sofosbuvir concentrations unknown
Coadministration of HARVONI with amiodarone may result in serious symptomatic bradycardia. The mechanism for this effect is unknown. Coadministration of amiodarone with HARVONI is not recommended; if coadministration is required, cardiac monitoring is recommended.
Sovaldi Label Changes:
WARNINGS AND PRECAUTIONS
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 inpatient 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.
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.
ADVERSE REACTIONS
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.Serious symptomatic bradycardia has been reported in patients taking amiodarone who initiate treatment with SOVALDI in combination with another HCV direct-acting antiviral.
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.Coadministration of amiodarone with SOVALDI in combination with another DAA may result in serious symptomatic bradycardia. The mechanism for 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.
source: https://drive.google.com/file/d/0B5vxpvyLa6CGb21aaDdwMVA0S0g1MHJXSzg3cWw4ZGNTeEFv/view?usp=sharing
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