SOFOVIR (SOFOSBUVIR 400MG)
Sofovir (Sofosbuvir 400mg) is a prescription medicine used with other antiviral medicines to treat adults with chronic hepatitis C (Hep C) with or without cirrhosis (compensated). Sofovir recommended with some combination of ribavirin, peginterferon-alfa, simeprevir, ledipasvir, daclatasvir, or velpatasvir to cure genotype 1 to 6 infections. Cure rates are 30 to 97% depending on the type of hepatitis C virus involved. Sofovir is safe and effective in patient who have had a liver transplant.
Sofovir (Sofosbuvir 400mg) inhibits the hepatitis C NS5B protein . Sofovir appears to have a high barrier to the development of resistance. Sofovir is a prodrug. It is metabolized to the active antiviral agent GS-461203 (2'-deoxy-2'-α-fluoro-β-C-methyluridine-5'-triphosphate). GS-461203 serves as a defective substrate for the NS5B protein, which is the viral RNA polymerase, thus acts as an inhibitor of viral RNA synthesis. Although Sofovir has a 3' hydroxyl group to act as a nucleophile for an incoming NTP, a similar nucleotide analogue, 2'-deoxy-2'-α-fluoro-β-C-methylcytidine, is proposed to act as a chain terminator because the 2' methyl group of the nucleotide analogue causes a steric clash with an incoming NTP. Sofovir would act in a similar way.
Sofovir (Sofosbuvir 400mg) is only administered orally. The peak concentration after oral administration is 0.5–2 hours post-dose, regardless of initial dose. Peak plasma concentration of the main circulating metabolite GS-331077 occurs 2–4 hours post-dose. GS-331077 is the pharmacologically inactive nucleoside.
Plasma protein binding of Sofovir is 61–65%, while GS-331077 has minimal binding.
Sofovir (Sofosbuvir 400mg) is activated in the liver to the triphosphate GS-461203 by hydrolysis of the carboxylate ester by either of the enzymes cathepsin A or carboxylesterase 1, followed by cleaving of the phosphoramidate by the enzyme histidine triad nucleotide-binding protein 1 (HINT1), and subsequent repeated phosphorylation. Dephosphorylation creates the inactive metabolite GS-331077. The half life of Sofovir is 0.4 hours, and the half life of GS-331007 is 27 hours.
Following a single 400 mg oral dose of Sofovir , 80% is excreted in urine, 14% in feces, and 2.5% in expired air recovery. However, of the urine recovery 78% was the metabolite (GS-331007) and 3.5% was Sofovir
Sofovir (Sofosbuvir 400mg) has a number of ideal properties, once daily dosing, no meal restrictions, few adverse effects, minimal drug-drug interactions, high genetic barrier to resistance, good safety and efficacy in patients with advanced liver disease, and excellent sustained virologic response rates in patients with unfavorable baseline characteristics
Sofovir (Sofosbuvir 400mg) (in combination with ledipasvir, daclatasvir or simeprevir) should not be used with amiodarone due to the risk of abnormally slow heartbeats.
Sofovir (Sofosbuvir 400mg) is a substrate of P-glycoprotein, a transporter protein that pumps drugs and other substances from intestinal epithelium cells back into the gut. Therefore, inducers of intestinal P-glycoprotein, such as rifampicin and St. John's wort, could reduce the absorption of Hepcinat.
In addition, co administration of Sofovir with anticonvulsants (carbamazepine, phenytoin, phenobarbital, oxcarbazepine), antimycobacterials (rifampin, rifabutin, rifapentine), and the HIV protease inhibitor tipranavir and ritonavir is expected to decrease Sofovir concentration. Thus, coadministration is not recommended.
The interaction between Sofovir and a number of other drugs, such as ciclosporin, darunavir/ritonavir, efavirenz, emtricitabine, methadone, raltegravir, rilpivirine, tacrolimus, or tenofovir disoproxil, were evaluated in clinical trials and no dose adjustment is needed for any of these drugs.
Common side effects include feeling tired, headache, nausea, and trouble sleeping. Side effects are generally more common in interferon-containing regimens. Sofovir may reactivate hepatitis B in those who have been previously infected. In combination with ledipasvir, daclatasvir or simeprevir it is not recommended with amiodarone due to the risk of an abnormally slow heartbeat.
Sofovir (Sofosbuvir 400mg) alone has been assigned a Pregnancy Category B by the FDA (meaning that it there are no adequate and well-controlled studies in pregnant women but animal reproduction studies have not demonstrated a risk to the fetus and, or that adverse effects have been seen in animal studies, but adequate and well-controlled studies in pregnant women have not, in any trimester). However, ribavirin, a medication that is often given together with Sofovir to treat hepatitis C, is assigned a Pregnancy Category X (contraindicated in pregnancy) by the FDA. Pregnant women with hepatitis C who take ribavirin have shown some cases of birth defects and death in their fetus. It is recommended that Sofovir /ribarivin combinations be avoided in pregnant females and their male sexual partners in order to reduce harmful fetal defects caused by ribavirin. Females who could potentially become pregnant should undergo a pregnancy test 2 months prior to starting the Sofovir /ribavirin/peginterferon combination treatment, monthly throughout the duration of the treatment, and 6 months post-treatment to reduce the risk of fetal harm in case of accidental pregnancy.
It is unknown whether Sofovir and ribavirin pass into breastmilk; therefore, it is recommended that the mother does not breastfeed during treatment with Sofovir alone or in combination with ribavirin.
Sofovir ( Sofosbuvir ) is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.
Daclahep ( Daclatasvir)is a NS5A replication complex inhibitor.
Daclahep ( Daclatasvir) is specifically indicated for use with sofosbuvir for the treatment of patients with chronic hepatitis C virus (HCV) of genotype 1, 3, or 4 infections. The other medications used in combination include sofosbuvir, ribavirin, and interferon, vary depending on the virus type and whether the person has cirrhosis.
Daclahep ( Daclatasvir)stops HCV viral RNA replication and protein translation by directly inhibiting HCV protein NS5A. NS5A is critical for HCV viral transcription and translation,
Daclahep ( Daclatasvir) is supplied as tablets for oral administration. It is taken by mouth once a day. The recommended dose is 60 mg taken orally once daily with or without food in combination with sofosbuvir. The recommended treatment duration is 12 weeks. Dose modification: reduce dosage to 30 mg once daily with strong CYP3A inhibitors and increase dosage to 90 mg once daily with moderate CYP3A inducers.
Concomitant use of drugs that are strong inducers of the cytochrome P450 CYP3A is contraindicated due to decreased therapeutic effect and resistance of drug. Some common drugs that are strong CYP3A inducers include dexamethasone, phenytoin, carbamazepine, rifampin and St. John's Wort.
Daclahep ( Daclatasvir) is a CYP3A and p-glycoprotein substrate, therefore, drugs that are strong inducers or inhibitors of these enzyme will interfere with daclatascir levels in the body. Dose modifications are made with concomitant use of daclatasvir and drugs that affect CYP3A or p-gp. When taking daclatasvir with non-nucleoside reverse transcriptase inhibitors, the dose of daclatasvir is increased to overcome CYP3A induction. The dose for daclatasvir should be lowered when taking with antifungals, such as ketoconazole. Currently, there are no required dosage adjustments with concurrent use of daclatasvir and immunosuppressants, narcotic analgesics, antidepressants, sedatives, and cardiovascular agents.
Concurrent use with amiodarone, sofosbuvir and daclatasvir has may result in an increased risk for serious slowing of the heart rate.
Common side effects with sofosubvir and daclatasvir include headache, feeling tired, and nausea. With daclatasvir, sofusbivir, and ribavirin the most common side effects are headache, feeling tired, nausea, and red blood cell breakdown. It should not be used with St. John's wort, rifampin, or carbamazepine. It works by inhibiting the HCV protein NS5A.
It is on the World Health Organization's List of Essential Medicines.