Sofokast Plus (Sofosbuvir & Daclatasvir )

DESCRIPTION

Sofokast Plus tablets are used in the condition like hepatitis C viral infection. Sofokast Plus tablet containing prime components like Sofosbuvir and Daclatasvir.

Sofokast Plus is first one, comes under the combination of these two most prominent compounds. Daclatasvir is not used alone; it may combine with other anti-viral component like sofosbuvir.

MECHANISM OF ACTION

Sofokast Plus tablet has two component Sofosbuvir & Daclatasvir Sofosbuvir: Sofosbuvir is a prohibitor of nucleotide analogue, especially prohibits HCV non-structural protein 5B RNA dependent RNA polymerase. Sofosbuvir undergo intracellular metabolism, which produce pharmacologically active compound like uridine analog triphosphate. Sofosbuvir interceded into RNA of hepatitis C virus with the help of NS5B polymerase. This may acts as chain eliminator. Daclatasvir: Non structural 5A protein is essential for viral multiplication. Daclatasvir interfere with the activity of NS5A protein, this may leads to viral eradication.

PHARMACOKINETIC

ABSORPTION

The maximum peak plasma concentration time of Daclatasvir reaches within 2 hours; whereas sofosbuvir attains at 0.5 to 2 hours after the dose. There is no effect occurred while taking Sofokast Plus tablet with or without meal. The mean bioavailability of Daclatasvir is reaches at 67%

DISTRIBUTION

Nearly 99% of drug Daclatasvir is highly bound to human plasma protein; whereas sofosbuvir has relatively 61 to 65% protein bounding capacity. Volume of distribution of Daclatasvir is 47L

METABOLISM

Daclatasvir is a CYP3A substrate, which is essential for metabolism of Daclatasvir. Sofosbuvir undergo hepatic metabolism, it may turns to active metabolite like uridine triphosphate required for anti-viral activity. Metabolism of sofosbuvir leads with the help of carboxyl esterase 1 or cathepsin A.

EXCRETION

The elimination of Sofokast Plus tablet occurs through urine; feces or exhaled air. Sofosbuvir: 80% in urine; 14% in feces & 2.5% in exhaled air Daclatasvir: 88% in feces; 6.6% in urine

DOSAGE MANAGEMENT

DOSING CONSIDERATION

Before staring the treatment with Sofokast Plus tablet, patient may examine periodically by taking hepatic function test and analysis the lab values. Examine HBV infection by counting hepatitis B surface antigen & hepatitis B core antibody.

DOSAGE RECOMMENDATION

The usual dose of Sofokast Plus tablet is one tablet should be taken as a single dose by administering with food or without food. On severe condition, Sofokast Plus must be combine with ribavirin. The initial dose of ribavirin is 600mg as a single dose, elevating dose up to 1000mg administrated for In HCV genotype I or III patients with decompensated cirrhosis or post transplantation.

The initial dose of ribavirin should be calculated on the basis of body weight of the suspected patients having with compensated cirrhosis; In patient with weight of at least 75kg: 1200mg of ribavirin should be considered. In patient with weight of less than 75kg: 1000mg of ribavirin should be used.

IN GENOTYPE I

The dose of Sofokast Plus is one tablet should be taken with or without food as a single dose given for Patient suffered without cirrhosis & compensated cirrhosis: In decompensated cirrhosis or post liver transplantation: The recommended dose of Sofokast Plus is one tablet to be taken as a single dose by combining with ribavirin on weight basis manner.

IN GENOTYPE III

Patient struggling without cirrhosis: The usual dose of Sofokast Plus is one tablet to be taken as a single dose. : The usual dose is one Sofokast Plus tablet should be combined with ribavirin as a single dose is given for Patient with compensated, decompensated cirrhosis or post liver transplantation While receiving ribavirin, patient must be administered food. Ribavirin should be taken as twice daily.

SIDE EFFECTS

Side effects occurred in Sofokast Plus tablet receiving patients such as; Fatigue Headache Insomnia Nausea Pruritus Asthenia Anemia Loss of appetite Flu like syndrome Pyrexia Diarrhea Rash Neutropenia Myalgia Irritability Pancytopenia Increase of creatine kinase, bilirubin, lipase, AST & ALT HBV reoccurrence may occurs Serious bradycardia while combining with amiodarone

SAFETY MEASURES TAKEN WHILE UNDERGOING SOFOKAST PLUS THERAPY

Use with caution in the patients are suspected with HBV infection, there is a chance of increasing the risk of HBV reoccurrence in the patient co infected with HCV & HBV Severe bradycardia occurs while concomitant use of Sofokast Plus with amiodarone Exposure of loss of therapeutic effect occurs while concurrently use Sofokast Plus tablet with P-gp inducers or inhibitors Severe adverse effects may occur due to drug interaction, to prevent this problem avoid this type of combinational therapy.

DRUG INTERACTION

Sofokast Plus comprising of two prime component like sofosbuvir & Daclatasvir; Sofosbuvir is a P-gp or BCRP drug transporter substrate, while combining Sofokast Plus tablet with P-gp inducers causes decreasing the plasma concentration of sofosbuvir. This may results as loss of therapeutic effect. Daclatasvir is a CYP3A substrate, while taking Sofokast Plus tablet with CYP3A strong inducers may causes loss of therapeutic effect of Daclatasvir.

Interaction of Sofokast Plus with drugs inhibits the CYP3A may elevates the plasma level of Daclatasvir Interaction with warfarin and Sofokast Plus tablets Alteration in INR or pro thrombin time may occur in patient Sofokast Plus tablet interaction with P-gp or BCRP inhibitors, may leads to cause prolonging the adverse effects of these substrates. Sofokast Plus tablet combined with protease inhibitors causes elevating the effect of concentration of Daclatasvir

Sofokast Plus tablets are concurrently used with non-nucleoside reverse transcriptase inhibitor causes reducing the effect of concentration of Daclatasvir Sofokast Plus tablet combined with amiodarone causes severe bradycardia. Sofokast Plus tablets are concomitantly used with lipid lowering drugs causes increasing concentration of these drugs. Sofokast Plus tablet combined with anti-convulsants, anti-mycobacterials or herbal products like st. Johns wort causes decreasing the effect of concentration of sofosbuvir.

CONTRAINDICATION

Some hypersensitivity reactions may occur, if patients are contraindicated to the components of Sofokast Plus tablets.

WARNING

Serious exposure of hepatitis B virus reactivation occurred in HCV & HBV co infected patients may occur. This serious condition is preventing by; Patients may undergo hepatic function test. Start appropriate patient management for hepatitis B viral infection These cases may occur in patients who are not receiving hepatitis B anti-viral drugs.

PREGNANCY & LACTATION

Sofokast Plus is not contraindicated to pregnancy condition While combined with ribavirin may causes fetal death Breast feeding should not be used while combined with ribavirin.

STORAGE 

Sofokast Plus tablet container should be kept at below 30°C The container should be free from moisture, heat & light