Side effects with Shingrix are greater than those with Zostavax and occur more frequently in individuals aged 50 to 69 years compared with those 70 years and older. Zostavax
The live vaccine (Zostavax) is very safe; one to a few percent of people develop a mild form of chickenpox, often with about five or six blisters around the injection site, and without fever. The blisters are harmless and temporary. In one study 64% of the Zostavax group and 14% of the controls had some adverse reaction. However, the rates of serious adverse events were comparable between the Zostavax group (0.6%) and those receiving the placebo (0.5%). A study including children with leukaemia found that the risk of getting shingles after vaccination is much lower than the risk of getting shingles for children with natural chicken pox in their history. Data from healthy children and adults point in the same direction.Zostavax is not used in people with compromised immune function. Composition
Shingrix
Shingrix is a suspension for intramuscular injection consisting of a lyophilized recombinant varicella zoster virus glycoprotein E antigen that is reconstituted at the time of use with AS01B suspension as an immunological adjuvant. The antigen is a purified truncated form of the glycoprotein, expressed in Chinese hamster ovary cells. The AS01B adjuvant suspension is composed of 3-O-desacyl-4-monophosphoryl lipid A (MPL) from Salmonella (Minnesota strain) and a saponin molecule (QS-21) purified from Quillaja saponaria (soap bark tree) extract, combined in a liposomal formulation consisting of dioleoyl phosphatidylcholine (DOPC) and cholesterol in phosphate-buffered saline solution.
Interactions
When combined with intravenous agalsidase alfa or beta, which are recombinant versions of the enzyme α-GalA, migalastat increases tissue concentrations of functional α-GalA compared to agalsidase given alone up to fivefold.Migalastat is not intended to be combined with agalsidase.Migalastat does not inhibit or induce cytochrome P450 liver enzymes or transporter proteins and is therefore expected to have a low potential for interactions with other drugs. Pharmacology
Mechanism of action
Fabry disease is a genetic disorder caused by various mutations of the enzyme α-GalA, which is responsible for breaking down the sphingolipid globotriaosylceramide (Gb3), among other glycolipids and glycoproteins. Some of these mutations result in misfolding of α-GalA, which subsequently fails protein quality control in the endoplasmic reticulum and is decomposed. Lack of functional α-GalA leads to accumulation of Gb3 in blood vessels and other tissues, with a wide range of symptoms including kidney, heart, and skin problems.Migalastat is a potent, orally available inhibitor of α-GalA (IC50: 4 μM). When binding to faulty α-GalA, it shifts the folding behaviour towards the proper conformation, resulting in a functional enzyme provided the mutation is amenable. Molecules with this type of mechanism are called pharmacological chaperones.When the enzyme reaches its destination, the lysosome, migalastat dissociates because of the low pH and the relative abundance of Gb3 and other substrates, leaving α-GalA free to fulfill its function. Depending on the mutation, the EC50 is between 0.8 μM and over 1 mM in cellular models.