Resof L is an anti-viral drug which is effective against chronic hepatitis C viral infection. Resof L containing anti-viral agents known as Sofosbuvir & ledipasvir which two prime components are approved by FDA. Sofosbuvir is an inhibitor of hepatitis C virus nucleoside polymerase NS5B and it is a uridine monophosphate analogue. Sofosbuvir is available as orally nucleotide prodrug, with potential HCV prohibitor activity. Ledipasvir is pharmacologically categorized as NS5A inhibitor of HCV
Sofosbuvir & Ledipasvir
400mg & 90mg
Therapeutical indication of Resof L tablets
Resof L tablets are clinical indicated for the treatment of advanced hepatitis C viral infection.
Resof L is applicable in; Genotype I, IV, V or VI along with infection without cirrhosis or with compensated cirrhosis. Genotype I associated infection with decompensated cirrhosis by combining with ribavirin Genotype I or IV associated infection in liver transplant patients without cirrhosis or with compensated cirrhosis by combining with ribavirin.
Resof L is used in pediatric patients with the age of 12 years or older & weighing of at least 35kg. Resof L is effective only in HCV caused by genotype I, IV, V, or VI infection without cirrhosis or with compensated cirrhosis.
Working of Resof L
Sofosbuvir is a prodrug, which is converted into active form in vivo.
After oral administration of Resof L , sofosbuvir is metabolized to form a metabolite known as 2’ deoxy 2’ alpha fluoro beta C methyluridine 5’ monophosphate.
Then further conversion of this metabolite into an active form such as triphosphate nucleotide which is responsible for prohibition of NS5B polymerase. NS5B polymerase is essential for viral production, this inhibition causes stopping viral multiplication.
HCV non structural 5B protein is an RNA dependent RNA polymerase enzyme which is responsible for viral HCV RNA genome multiplication. Ledipasvir, after an oral administration the cell are uptake the ledipasvir and leads to blockade the effect of NS5A protein.
This inhibition concludes as interruption of RNA multiplication complex of virus. Thus results as blocking the HCV RNA formation and causes obstruction of viral proliferation. NS5A protein is belongs to zinc binding & proline high hydrophilic phosphoprotein important for viral formation.
After oral uptake of Resof L tablet, the maximum plasma concentration time of sofosbuvir is occurs between 0.5 to 2 hours. Ledipasvir maximum plasma concentration is occurs between 4 to 4.5 hours.
Ledipasvir is largely bound to human plasma protein by 99.8%. The blood to plasma ratio is occurs between 0.51 & 0.66. Sofosbuvir is binds to human plasma protein by 61 to 65%. The blood to plasma ratio is almost 0.7.
The metabolism of sofosbuvir is mediated by cathepsin A, or carboxyl esterase 1. The metabolism of ledipasvir is occurred by CYP1A2, 2C8, 2C9, 2C19, 2D6, & 3A4.
Ledipasvir dose are eliminated via feces & urine by almost 87% The terminal half life period of ledipasvir is 47 hours Sofosbuvir is eliminated via urine in 80%, feces in 14% & exhaled air in 2.5%. The major route of excretion is occurs via kidneys. The terminal half life period of sofosbuvir is 0.4 hours.
Before starting the Resof L treatment, patient should be tested by counting the HBsAg & anti-HBc levels for reducing the chance of occurring the HBV reactivation.
In adult patients
Resof L containing 400mg of sofosbuvir & 90mg of ledipasvir The prescribed dose of Resof L is one tablet should be administered as a single dose by taking with or without food. Patient co infected with HCV/HIV-1infection, the dosage recommendation is;
Newly commenced patients without cirrhosis or with compensated cirrhosis & therapy experienced without cirrhosis: The prescribed dose of Resof L is one tablet to be administered orally as a single dose. Newly commenced & therapy experienced with decompensated cirrhosis One Resof L tablet should be combined with ribavirin as a single dose. By combining with ribavirin, it should be administered with food.
Genotype I or IV
Therapy naïve & therapy experienced in liver transplant patients without cirrhosis or with compensated cirrhosis; One Resof L tablet should be administered with weight based ribavirin.
Genotype IV, V or VI
Therapy naïve & therapy experienced without cirrhosis or with compensated cirrhosis; One Resof L tablet should be administered as a single dose.
The prescribed dose of Resof L in pediatric patient with the age of 12 years or older & weight of at least 35kg is one tablet should be administered as a single dose.
Therapy naïve without cirrhosis or with compensated cirrhosis: The advised dose of Resof L is one tablet should be taken orally as a single dose. Therapy experienced without cirrhosis: The advised dose of Resof L is one tablet should be taken orally as a single dose. Compensated cirrhosis: The advised dose of Resof L is one tablet should be taken orally as a single dose.
Genotype IV, V, or VI
In all condition, the suggested dose of Resof L is one tablet should be administered orally as a single dose.
No special antidote is applicable for treating the over dosage of Resof L . Patient should be provided with supportive measures Investigate the manifestation occurs due to over dosage of Resof L Ledipasvir is difficult to eliminate from the body because it has high binding capacity. Sofosbuvir circulating metabolite is eliminated by hemodialysis with the range of 53%.
The most worsening effect occur during the treatment of Resof L is; Severe bradycardia due to concomitant use of Resof L with amiodarone
Common side effects
Fatigue, Headache, Nausea, Diarrhea, Insomnia, Asthenia, Myalgia, Irritability, Dizziness, Cough, Bilirubin elevation, Lipase elevation, Creatine kinase elevation, Rashes, Angioedema
The major adverse effect occurs during the therapy using with Resof L is
Exposure of hepatitis B virus reoccurrence in patients who are co infected with HCV & HBV This adverse condition may have suspected in patient who are receiving HCV directly acting anti-viral agents and not getting HBV therapy. This may conclude as hepatic failure and finally death.
To avoid this problem, patient must be
Examine for prior hepatitis B virus infection before initiating the treatment. Investigate the HCV/HBV co infected patients for hepatitis flare or HBV reoccurrence during the HCV therapy & after completion o treatment. Commence appropriate patient management of HBV infection.
Exposure of hepatitis B viral infection in patient co infected with HCV & HBV
This adverse effect will be overcome by examining the patients by counting the HBsAg & anti-HBc before starting the anti-viral treatment. Monitor the laboratory manifestation of hepatitis flare during & completion of anti-viral medication.
Bradycardia during concomitant use with amiodarone
Anti-viral agent combined with amiodarone, leads to cause serious bradycardia which results as cardiac arrest. Avoid the concomitant use and in severe condition discontinue the therapy. Counsel the patient before starting the therapy with anti-viral drugs. Monitor the ECG frequently
Loss of therapeutic effect during concurrent use of Resof L with P-gp inducers
During concomitant use of Resof L with strong P-gp inducers causing decreased plasma concentration of sofosbuvir & ledipasvir which may results as reducing the effectiveness of Resof L tablets.
Exposure of risk during concurrent use of Resof L with ribavirin
This combinational study leads to cause adverse effects in pregnancy condition.