Company: Gilead Sciences Ltd.
Legal category: Prescription. Hospital only. Sport permitted.
Active ingredient: Ledipasvir/sofosbuvir 90/400mg.
Description: Orange, diamond-shaped, film-coated tablet marked GSI on one side and 7985 on reverse.
Presentation: 28, price available on request.
Indications: Treatment of chronic hepatitis C in patients with genotypes 1, 3 or 4.
Pharmacology: Ledipasvir is a HCV inhibitor targeting the HCV NS5A protein, which is essential for both RNA replication and the assembly of HCV virions. Sofosbuvir, a nucleotide prodrug, is a pan-genotypic inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication. It undergoes intracellular metabolism to form the pharmacologically active uridine analogue triphosphate (GS-461203), which can be incorporated into HCV RNA by the NS5B polymerase and acts as a chain terminator.
Dosage: Adult: Swallow whole. One tablet once daily. If vomiting occurs within 5 hours take another. For specialist use only. Genotype 1/4 (including HIV co-infection): Patients without cirrhosis, Harvoni only for 12 weeks (may consider 8 weeks in treatment-naïve patients with genotype 1; consider 24 weeks for previously treated patients with uncertain subsequent retreatment options); patients with compensated cirrhosis, Harvoni only for 24 weeks (may consider 12 weeks for patients at low risk of disease progression with subsequent retreatment options); patients with decompensated cirrhosis/who are pre-/post-liver transplant (assess risk/benefit), Harvoni + ribavirin for 24 weeks. Genotype 3 (including HIV co-infection): With cirrhosis/prior treatment failure, Harvoni + ribavirin for 24 weeks. See Ribavirin SPC. Elderly: As per adults. Children: Under 18 years, not recommended.
Contraindications: Hypersensitivity to the active substances or to any of the excipients. Pregnancy, lactation. Women or their male partners must use contraception during treatment (see ribavirin SPC if used).
Special precautions: Do not use in patients with HCV genotypes 2, 5 and 6. If a potentially ribavirin-related serious adverse reaction occurs, modify dose (see SPC) or discontinue ribavirin. Retreatment of patients who failed with either a subsequent NS5A inhibitor-containing regimen or prior therapy that included an NS3/4A protease inhibitor (no data). Severe renal impairment or end stage renal disease requiring haemodialysis (safety not established). HCV genotype 3/4 (limited data). HCV/HBV co-infection (no data). Creatinine clearance <50mL/min using ribavirin. See SPC of ribavirin if used in combination with Harvoni. Contains lactose, sunset yellow FCF aluminium lake.
Drug interactions: Contraindicated: Rosuvastatin, St. John’s wort. Do not use proton pump inhibitors (before Harvoni), other medicines containing sofosbuvir, potent P-gp inducers (e.g. rifampicin, carbamazepine, phenytoin), phenobarbital, oxcarbazepine. Not recommended: Rifabutin, rifapentine, simeprevir, tipranavir (ritonavir boosted). Caution: CYP3A4/ CYP2C/ UGT1A1 substrates with a narrow therapeutic range, digoxin, pharmacokinetic enhancers (e.g. ritonavir, cobicistat). P-gp or breast cancer resistance protein substrates. Antacids (within 4 hours), tenofovir disoproxil fumarate, HMG-CoA reductase inhibitors, pravastatin, dabigatran etexilate. H2-receptor antagonists (do not exceed doses comparable to famotidine 40mg twice daily).
Adverse drug reactions: Headache, fatigue.
Full prescribing information and references available from Gilead Sciences Ltd. Telephone: (01) 2078156. Fax: +441223 897281. E-mail: ukmedinfo@gilead.com