For example, fatigue and headache are nearly reduced by half, influenza-like symptoms are reduced to 3–6% as compared to 16–18%, and neutropenia is almost absent in interferon-free treatment. : 7 Sofosbuvir may reactivate hepatitis B in those who have been previously infected. The European Medicines Agency (EMA) has recommended screening all people for hepatitis B before starting sofosbuvir for hepatitis C in order to minimize the risk of hepatitis B reactivation. Interactions
Sofosbuvir (in combination with ledipasvir, daclatasvir or simeprevir) should not be used with amiodarone due to the risk of abnormally slow heartbeats.Sofosbuvir 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. Johns wort, could reduce the absorption of sofosbuvir.In addition, coadministration of sofosbuvir with anticonvulsants (carbamazepine, phenytoin, phenobarbital, oxcarbazepine), antimycobacterials (rifampin, rifabutin, rifapentine), and the HIV protease inhibitor tipranavir and ritonavir is expected to decrease sofosbuvir concentration. Thus, coadministration is not recommended.The interaction between sofosbuvir 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. Pharmacology
Mechanism of action
Sofosbuvir inhibits the hepatitis C NS5B protein. Sofosbuvir appears to have a high barrier to the development of resistance.Sofosbuvir is a prodrug of the Protide type, whereby the active phosphorylated nucleotide is granted cell permeability and oral bioavailability. It is metabolized to the active antiviral agent GS-461203 (2-deoxy-2-α-fluoro-β-C-methyluridine-5-triphosphate).
Microtubules are structural components of the cytoskeleton that lengthen and shrink for important cell functions. Colchicine binds to β- tubulin and forms tubulin-colchicine complexes., These complexes interfere with microtubule formation microtubules. Low doses of colchicine can inhibit the formation of microtubules, while high doses depolymerize or break down a polymer to a monomer. Therefore, any process involving cytoskeleton change, including mitosis and motility of white blood cells, are highly impacted.Microtubule disruption decrease neutrophil adhesion, an important step for inflammation. Neutrophils are recruited to the target location of inflammation via signals from the endothelium where they adhere and play a role in the inflammatory response. Colchicine diminishes neutrophil adhesion by decreasing expression of selectins, a family of cell adhesion molecules. In addition, colchicine prevents the movement and secretion of intercellular granules, substances, proinflammatory enzymes from neutrophils, thus making a significant impact on inflammatory processes within the body. The high concentration of colchicine in neutrophils, sixteen times greater compared the plasma levels, can account for the positive therapeutic effects.Many mediators are altered to assist neutrophils during inflammation, including the monokine tumor necrosis factor-alpha (TNFα). Cytokines help stimulate the acute phase reaction in response to inflammation. Colchicine inhibits macrophage production of TNFα, leading to the interference between TNFα and neutrophil interaction. There are many more effects of colchicine that are currently under research, and some aspects of this metabolite are not fully understood.There was great hope that Colchicine could be a primary preventive measure in treating Post-Pericardiotomy Syndrome due to its anti-inflammatory effects.