Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir is a combination medication used to treat the symptoms of Hepatitis C Virus Infection. 

• Ledipasvir-Sofosbuvir is available under the following different brand names: Harvoni

Common side effects of Ledipasvir-Sofosbuvir include:

• Weakness,
• Headache, and
• Tired feeling

Serious side effects of Ledipasvir-Sofosbuvir include:

• Hives,
• Difficulty breathing,
• Swelling of your face, lips, tongue, or throat,
• Right-sided upper stomach pain,
• Vomiting,
• Loss of appetite,
• Yellowing of the skin or eyes (jaundice), and
• General feeling of unwellness  

Rare side effects of Ledipasvir-Sofosbuvir include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet

• 45 mg/200 mg
• 90 mg/400 mg

Oral pellets

• 33.75 mg/150 mg per packet

Hepatitis C Virus Infection

Adult dosage

• 1 tablet (90 mg/400 mg) orally once a day

Ribavirin dosing

• Below 75 kg with or without decompensated cirrhosis: 1000 mg orally every 12 hours
• Above 75 kg with or without decompensated cirrhosis: 1200 mg orally every 12 hours
• If the initial dose is not well tolerated, reduce the dose as clinically indicated based on hemoglobin levels; refer to the ribavirin prescribing information for further information

Pediatric dosage

• Below 3 years: Safety and efficacy not established
• Above 3 years
  • Below 17 kg: 1 packet (33.75 mg/150 mg) of pellets orally once a day
  • Children between 17 to below 35kg: 1 tablet or packet (45 mg/200 mg) orally once a day
• Children above 35 kg: 1 tablet (90 mg/400 mg) orally once a day or 2 tablets or packets (45 mg/200 mg) orally once a day

Treatment duration

Ribavirin dosing

• Below 47 kg: 15 mg/kg/day orally (divided dose morning and evening)
• 47-49 kg: 600 mg/day orally (. e, 200 mg morning, 400 mg evening)
• 50-65 kg: 800 mg/day orally (. e, 400 mg morning, 400 mg evening)
• 66-80 kg: 1000 mg/day orally (. e, 400 mg morning, 600 mg evening)
• Above 80 kg: 1200 mg/day orally (. e, 600 mg morning, 600 mg evening)

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Ledipasvir-Sofosbuvir has severe interactions with the following drugs
  • carbamazepine
  • fosphenytoin
  • oxcarbazepine
  • phenobarbital
  • phenytoin
  • rifabutin
  • rifampin
  • rifapentine
  • St John's Wort
  • tipranavir
• Ledipasvir-Sofosbuvir has serious interactions with the following drugs
  • colchicine
  • darolutamide
  • edoxaban
  • erdafitinib
  • lasmiditan
  • rimegepant
  • sotorasib
  • lapatinib
  • topotecan
  • venetoclax
• Ledipasvir-Sofosbuvir has moderate interactions with at least 48 other drugs.
• Ledipasvir-Sofosbuvir has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• If coadministered with ribavirin, the contraindications to ribavirin also apply to this combination regimen

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ledipasvir-Sofosbuvir?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ledipasvir-Sofosbuvir?”

Cautions

• HCV and HBV Coinfection
  • Hepatitis B virus (HBV) reactivation reported in HCV/HBV coinfected patients undergoing or who had completed treatment with HCV direct-acting antivirals, and who were not receiving HBV antiviral therapy
  • Some cases have resulted in fulminant hepatitis, hepatic failure, and death; cases have been reported in patients who are HBsAg positive and in patients with serologic evidence of resolved HBV infection (. g, HBsAg negative and anti-HBc positive)
  • HBV reactivation was also reported in patients receiving certain immunosuppressants or chemotherapeutic agents
  • The risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients
  • HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level; in patients with resolved HBV infection, the reappearance of HBsAg can occur
  • Reactivation of HBV replication may be accompanied by hepatitis. g, increases in aminotransferase levels and, in severe cases, increases in bilirubin levels, liver failure, and death can occur
  • Test all patients for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc before initiating HCV therapy
  • In patients with serologic evidence of HBV infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up; initiate appropriate patient management for HBV infection as clinically indicated
• Drug interaction overview
  • The concomitant use of drug combination and P- GP inducers may significantly decrease ledipasvir and sofosbuvir plasma concentrations and may lead to a reduced therapeutic effect; use of drug combination with P- GP inducers (. g, rifampin, St. John’s wort) not recommended
  • If drug combinations ion administered with ribavirin, the warnings, and precautions for ribavirin the pregnancy avoidance warning, apply to this combination regimen; refer them to the ribavirin prescribing information for a full list of warnings and precautions for ribavirin
  • Ledipasvir and sofosbuvir are substrates of P-GP and BCRP; coadministration with P-GP inducers (. g, rifampin, St. John’s wort) is not recommended; may significantly decrease ledipasvir and sofosbuvir plasma concentrations and the reduce therapeutic effect
  • Ledipasvir is an inhibitor of P-GP and BCRP; may increase intestinal absorption of coadministered substrates for these transporters
  • Coadministration of ledipasvir with acid-reducing agents may decrease ledipasvir solubility, resulting in decreased serum concentrations
  • Frequent monitoring of relevant laboratory parameters (. g, International Normalized Ratio [INR] in patients taking warfarin, blood glucose levels in diabetic patients) or drug concentrations of concomitant medications such as cytochrome P450 substrates with a narrow therapeutic index (. g, certain immunosuppressants) is recommended to ensure safe and effective use; dose adjustments of concomitant medications may be necessary
• Bradycardia with amiodarone coadministration
  • Postmarketing cases of symptomatic bradycardia, as well as fatal cardiac arrest and cases requiring pacemaker intervention, reported when the drug combination is administered with amiodarone
  • Bradycardia has generally occurred within hours to days, but cases reported 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 is not recommended; for patients taking amiodarone with no other alternative, viable treatment options should 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 the which outpatient or self-monitoring of the heart rate should occur daily through at least first 2 weeks of treatment; patients on the drug combination who need to take amiodarone should use the same approach as described above
  • Due to amiodarone’s long half-life, patients discontinuing amiodarone should undergo cardiac monitoring before starting therapy; patients who develop signs or symptoms of bradycardia, including near-fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pains, confusion or memory problems should seek medical evaluation immediately

Pregnancy and Lactation

• If the drug combination is administered with ribavirin, the combination regimen is contraindicated in pregnant women and in men whose female partners are pregnant; refer to the ribavirin prescribing information for more information on ribavirin-associated risks of use during pregnancy
• No adequate human data are available to establish whether the drug combination poses a risk to pregnancy outcomes; in animal reproduction studies, no evidence of adverse developmental outcomes was observed with the drug combination ledipasvir or sofosbuvir at exposures greater than those in humans at the recommended human dose (RHD).
• Lactation
  • It is not known whether ledipasvir or sofosbuvir, the drug combination, or their metabolites are present in human breast milk, affect human milk production, or have effects on the breastfed infant.
  • The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug combination and any potential adverse effects on the breastfed child from the drug combination or the underlying maternal condition