Sofosbuvir / Ledipasvir Pharmacology

Here, we take a few minutes to talk about sofosbuvir / ledipasvir pharmacology; an important combination medicine used for antiviral purposes. We learn more about what the medicine is used for, how the medicine works, as well as what prominent side effects and drug interactions the medicine is associated with. We also learn more about the essential clinical implications of this combination medicine.

Let’s take a few minutes to review the fundamental facts you need to know!

Indications

Sofosbuvir / ledipasvir is a combination medicine used to treat just one condition – namely, hepatitis C.

The medicine is most effective against genotype 1 – which makes up just under half of all cases of hepatitis C. After treatment with this medicine, 95-99% of patients with hepatitis C genotype 1 are cured. It has proven enormously effective and remains a vital clinical tool in the battle against this serious viral infection.

It was first introduced to the market in 2014 and has since been listed on the WHO List of Essential Medicines.

Brand names: Harvoni

Mechanism of action

In terms of the mechanism of action of this combination medicine:

  • At the most fundamental level, sofosbuvir / ledipasvir works as inhibitors of NS5 viral proteins.
  • Ledipasvir: NS5A inhibitor
  • Sofosbuvir: NS5B inhibitor
  • The medicine works via hyperphosphorylation of these viral proteins; proteins that are integral to the process of viral assembly. Both NS5A and NS5B are viral polymerases – meaning that using both medicines at the same time has a notable synergistic impact.

Side effects

Clinically significant side effects with sofosbuvir / ledipasvir include:

  • Rash
  • Dark urine / clay-colored stools
  • Jaundice

Other effects include weakness, fatigue, headache, GI effects – nausea, diarrhea, loss of appetite, insomnia, and muscle pain and aches.

Clinical considerations

Clinical considerations of sofosbuvir / ledipasvir pharmacology include:

  • Harvoni is used to treat chronic hepatitis C in adults over the age of 12, or who weigh more than 35 kilograms (77 pounds).
  • Harvoni is often given alongside another antiviral medicine, such as ribavirin.
  • Harvoni increases the probability of hepatitis B relapse. The medicine also worsens existing hepatitis B infection.
  • If Harvoni is taken alongside ribavirin, it’s crucial that 2 forms of contraception be taken for at least 6 months post-treatment. This is due to the teratogenic effects of ribavirin rather than Harvoni. Contraception should also be taken during treatment, too.
  • To be effective, Harvoni is typically taken for 10-24 weeks.
  • Frequent monitoring of liver function tests may be required – particularly if the patient had hepatitis B. These liver function tests are often needed for many months post-treatment.
  • Antacids should be avoided for at least 4 hours after Harvoni has been taken.
  • Solubility of ledipasvir is pH dependent. For this reason, Harvoni should not be taken at the same time as H2 receptor antagonists or proton-pump inhibitors as they alter pH gastric balance.  
  • Risk of bradycardia when sofosbuvir / ledipasvir is taken with amiodarone or other heart rate-lowering medicines.

Sofosbuvir / ledipasvir has revolutionized treatment of hepatitis C, particularly hepatitis C genotype 1. As this genotype is responsible for almost half of hepatitis C cases, Harvoni has had a tremendous clinical impact. The medicine is also safer to use and has a less severe side effect profile than previously used hepatitis C medicines.

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