Brand Name : Ledihep
Active components : sofosbuvir & Ledipasvir
Strength of the components : 400mg & 90mg
Manufactured by : Zydus Cadila
Category : Anti-hepaciviral drugs
Package : 28 tablets in a container
Ledihep tablet should be used for both adults & pediatric patients with the age of 12 years or older or weight of at least 35kg. Used for; Genotype I, 4, 5, or 6 with compensated cirrhosis or without cirrhosis Genotype 1 infection with compensated cirrhosis or without cirrhosis Liver transplantation condition, genotype 1 with decompensated cirrhosis by use of ribavirin Genotype 1 or 4 without cirrhosis or with compensated cirrhosis by use of ribavirin Pediatric patients, HCV infection related to genotype 1, 4, 5, or 6 without cirrhosis or with compensated cirrhosis.
The usual advised dose of Ledihep is one tablet should be administered as once a day. In HIV-1 co infected patients, Ledihep dosage consideration is; Patient without cirrhosis: (adult or pediatric of 12 years of age or older with genotype I, IV, V or VI Chronic HCV) The prescribed dose of Ledihep is one tablet should be taken orally as a single dose for 12 weeks
Without cirrhosis or compensated cirrhosis:
Ledihep should be taken alone as a single dose followed for 12 weeks
Therapy experienced without cirrhosis: Ledihep should be taken as a single agent for once a day for 12 weeks
Therapy experienced with compensated cirrhosis: Ledihep tablet should be used for 24 weeks
In decompensated cirrhosis: Ledihep should be combined with ribavirin to be used, followed for 12 weeks
Genotype I to IV
In liver transplantation patients with compensated cirrhosis or without cirrhosis: Ledihep tablet should be combined with ribavirin for 12 weeks.
Genotype IV, V or VI :
Ledihep tablets should be administered alone for 12 weeks for Without cirrhosis or with compensated cirrhosis patients: On the basis of body weight the dose of ribavirin should be calculated <75kg: 1000mg; ≥75kg: 1200mg Ribavirin should be administered with food. Ledihep should be administered with or without food.
Peak plasma concentration of Ledihep :
Sofosbuvir: 0.8 to 1 hour & GS331007: 3.5 to 4 hours; ledipasvir: 4 to 4.5 hours No effect produced, while Ledihep should be administered with or without food.
Plasma protein binding capacity of Ledihep :
Sofosbuvir: 61 to 65% & GS-331007: minimal binding effect, ledipasvir: >99.8%
Metabolism of Ledihep :
Sofosbuvir: hepatic metabolism with cathepsin A, or carboxyl esterase 1 & ledipasvir: mediated by CYP1A2, 2C8, 2C9, 2C19, 2D6 & 3A4.
Elimination of Ledihep :
Major route of elimination is through urine & feces. Ledipasvir through urine by 87%; sofosbuvir through urine by 80%, feces by 14% & exhaled air by 3.5%
Half life period of Ledihep :
Sofosbuvir 0.4%, GS-331007: 27 hours & ledipasvir: 47 hours.
Ledipasvir is a solid prohibitor of perpetual hepatitis C viral relating non structural 5A protein which is a viral phosphoprotein. The essential part of ledipasvir in hostile to viral action instrument; Restraint of; Replication Virion assembly Secretion The mechanism of sofosbuvir associated with against viral movement is; Sofosbuvir is prohibitor of nucleotide analogue of hepatitis C viral disease identified with non basic 5B polymerase. This catalyst is in charge of interceding the HCV RNA duplication. The dynamic type of sofosbuvir is in triphosphate shape, which included diminishing the common cell uridine nucleotide and is coordinated by HCV RNA polymerase into the broadened RNA preliminary strand, which is closed in viral chain end.
Hepatitis B reoccurrence :
This condition is mostly occurs in patients who are undergoing anti-viral therapy & fail to receive the anti-hepatitis B viral treatment. Monitor the HBsAg & anti-HBc counts before the therapy Hepatic function test should be performed Start the anti-hepatitis B treatment.
This severity is due to combination of amiodarone with Ledihep treatment. To avoid the problem patient ECG should be monitored. Patient should be counseled before initiate the treatment about the exposure of risk due to amiodarone. Provide supportive management.
Drug interactions :
The combination of Ledihep with P-gp inducers (potent), causes decreasing the plasma concentration of component of Ledihep.
Risk due to ribavirin :
Ribavirin causes fetal damage and leads to death. Contraindicated to pregnancy
Without cirrhosis or with compensated cirrhosis: Ledihep should be administered orally afor 12 weeks. Therapy experienced without cirrhosis: Ledihep should be administered orally for 12 weeks. Therapy experienced compensated cirrhosis: Ledihep tablet should be administered orally for 12 weeks.
Genotype IV, V or VI
Therapy naïve or experienced without cirrhosis or with compensated cirrhosis: Ledihep tablet should be administered orally for 12 weeks. Renal impairment patients; Ledihep dosage adjustment should not be allowed in severe renal damaged condition. Due to greater exposure of sofosbuvir metabolite causes final stage of renal disease (ERSD).
Ledihep, an inhibition of P-gp or BCRP drug transporters, this concomitant use causes increase intestinal absorption of these substrates. Ledihep + P-gp strong inducers lead to diminish the Ledihep plasma concentration causes loss of therapeutic efficacy of Ledihep. Ledihep + warfarin causes alteration in INR values, monitor the prothrombin time during this combination. Ledihep + gastric regulators, causes diminishing ledipasvir plasma concentration, do not administer Ledihep tablet concurrently with gastric regulators. Ledihep + anti-arrhythmic agents lead to produce plasma concentration elevation of these drugs. Ledihep + anti-convulsants or anti-mycobacterials may cause depletion of plasma concentration of Ledihep. Ledihep + anti-retroviral drugs, increases the plasma concentration of these drugs. Ledihep + st Johns wort causes decreasing the plasma concentration of Ledihep. Ledihep + HMG CoA reductase inhibitors cause elevation of plasma concentration of these drugs.
The over dosage condition should be overcome by; Provide supportive management. Monitor the manifestations. Treated by Hemodialysis Ledipasvir does not eliminate by hemodialysis process, because of ledipasvir has large protein binding capacity. The circulating metabolite of sofosbuvir is eliminated from the body by processing with hemodialysis with the range of 54%.
Ledihep with ribavirin is contraindicated to pregnancy condition Hypersensitivity reactions produces, if patients are contraindicated to the component present in the Ledihep.
In case of missed dose occurrence during the therapy, patient must be consult with medical practitioner and follow the instructions. Maintain the regular dosing schedule.
Fatigue, Headache, Nausea, Diarrhea, Insomnia, Elevation of bilirubin, Elevation of lipase, Elevation of creatine kinase, Severe bradycardia, HBV reactivation, Chest pain, Dizziness, Trouble in breathing.
The regular antagonistic delivered amid or after finish of treatment are; Introduction of HBV restoration in HCV/HBV co contaminated patients. To avoid the problem by counting the patients HBsAg & anti-HBc values before initiate the treatment with Ledihep. Monitor the hepatic function test periodically before, during & after completion of treatment. Patient should be provided with supportive management for preventing the hepatitis B viral infection reoccurrence.