ledipasvir and sofosbuvir

Harvoni is an oral tablet containing two drugs used for the treatment of chronic infection with the hepatitis C virus (HCV), genotype 1 in adults. The components belong to a class of drugs called direct-acting antiviral agents. Similar drugs include:

• boceprevir (Victrelis),
• sofosbuvir (Sovaldi),
• simeprevir (Olysio),
• telaprevir (Incivek), and
• Viekira Pak (ombitasvir, paritaprevir, ritonavir, dasabuvir).

Harvoni contains ledipasvir and sofosbuvir. Sofosbuvir is converted to an active form in the body before it is effective. The active form of sofosbuvir directly blocks replication of the HVC by interfering with a hepatitis C virus enzyme called NS5B. Ledipasvir is an inhibitor of another hepatitis C virus enzyme called NS5A, which also is needed for viral replication. Both drugs in Harvoni interfere with enzymes needed by the hepatitis C virus to multiply and make new viruses, thus reducing the overall viral load. The efficacy of sofosbuvir has been established in subjects with hepatitis C virus genotypes 1, 2, 3, and 4.

Harvoni does not require administration with interferons or ribavirin (Rebetol). In clinical studies, 96%-99% of patients who were not previously treated for their hepatitis C virus were cured after 12 weeks of Harvoni treatment. The cure was defined as undetectable levels of hepatitis C virus in the blood when measured three months after the completion of treatment. Harvoni was approved by the FDA in October 2014.

What brand names are available for Harvoni?

Harvoni

Is Harvoni available as a generic drug?

No

Do I need a prescription for Harvoni?

Yes

WARNING

• There is an increased risk of low heart rate (bradycardia) when Harvoni is combined with amiodarone (Cordarone).
• Harvoni should not be combined with Sovaldi (sofosbuvir) or other drugs containing sofosbuvir.

The recommended treatment dose is one tablet by mouth once daily with or without food. Duration of treatment depends on whether patients have been previously treated with other agents for their infection and the presence or absence of cirrhosis. The usual recommended duration of treatment is as follows:

• Treatment-naïve patients with or without cirrhosis: 12 weeks treatment.
• Eight weeks of treatment may be used for treatment-naïve patients without cirrhosis who have pre-treatment HCV RNA levels of less than 6 million IU/mL
• Previously treated without cirrhosis: 12 weeks of treatment
• Previously treated with cirrhosis: 24 weeks of treatment.

Acid-reducing agents which are commonly used to treat heartburn, indigestion, and GERD may decrease the effectiveness of Harvoni treatment by decreasing blood levels of ledipasvir. Examples of acid-reducing agents include antacids, histamine 2 receptor antagonists, for example, famotidine (Pepcid), and proton pump inhibitors (PPIs), for example, omeprazole (Prilosec).

Antacid and Harvoni administration should be separated by 4 hours. Doses of histamine 2 receptor antagonists equivalent to famotidine 40 mg twice daily or less and doses of proton pump inhibitors equivalent to 20 mg of omeprazole or lower may be given at the same time as Harvoni.

Co-administration of Harvoni and amiodarone is not recommended because the combination may cause serious heart-related side effects including symptomatic bradycardia.

Anti-seizure medications including carbamazepine (Tegretol), phenytoin (Dilantin), phenobarbital (Luminal), and oxcarbazepine (Trileptal) may increase the breakdown of Harvoni, leading to reduced therapeutic effectiveness.

Taking St. John's Wort or rifampin with Harvoni may also reduce the effectiveness of treatment and is not recommended.

Certain medications used to treat tuberculosis (TB) infection may decrease the effectiveness of Harvoni treatment. Patients taking rifampin, rifabutin, or rifapentine should consult with their doctor or pharmacist before starting Harvoni.

Co-administration of Harvoni with rosuvastatin (Crestor), a cholesterol-lowering medication, may significantly increase the blood concentration of rosuvastatin and increase the risk of side effects such as serious muscle injury.

Drug interactions with certain HIV antiretroviral therapies and Harvoni have also been reported. Patients receiving HIV treatment are advised to consult with their doctor or pharmacist before starting Harvoni.

PREGNANCY: Although no fetal adverse events were reported in animal studies, adequate and well-controlled studies of Harvoni treatment in pregnant women are lacking. Therefore, Harvoni should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

NURSING MOTHERS: It is not known whether Harvoni is excreted into human milk. Due to the lack of conclusive safety data, Harvoni should be used cautiously while breastfeeding.

If Harvoni 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 or not Harvoni alone poses a risk to pregnancy outcomes.

It is not known whether ledipasvir or sofosbuvir, the components of Harvoni, 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 Harvoni and any potential adverse effects on the breastfed child from Harvoni or the underlying maternal condition.

If Harvoni is administered with ribavirin, the nursing mother’s information for ribavirin also applies to this combination regimen. Refer to the ribavirin prescribing information for more information on use during lactation.

Oral tablets containing 90 mg ledipasvir and 400 mg sofosbuvir.

Harvoni should be stored in its original container and at room temperature, between 15 C and 30 C (59 F and 86 F).