Sofosbuvir and ledipasvir

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 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 genotype 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. 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.

Harvoni

GENERIC AVAILABLE: No

: 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 medication 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 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.

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).