FDA APPROVES TEMBEXA-AN ORAL ANTIVIRAL FOR SMALLPOX TREATMENT

FDA APPROVES TEMBEXA(BRINCIDOFOVIR), AN ORAL ANTIVIRAL FOR THE TREATMENT OF SMALLPOX 

Edited by, JASPER VICTORIA

     Small pox is a deadly, contagious disease caused by Variola virus, Known to be completely eradicated. It is of two types variola minor, the less common type in which only 1% of the affected individuals died and the variola major, the more common type in which 30% of the affected patients were fatal. Small pox was prevalent in two rare and often fatal forms, the haemorrhagic form and the malignant form.

    The incubation period of smallpox is 7-17 days, during which is not transmissible. The symptoms start to show up 10-14 days after the infection. The flu-like symptoms of small pox include fever, discomfort, vomiting, severe fatigue and back pain. Flat, red spots start to appear a fewdays later on the face, hands, forearm and trunk.These lesions then develop into small blisters. The blisters initially contain a clear fluid which then turns into pus. The blisters turn into scabs in eight or nine days and gradually fall off, leaving scars looking deep and pitted. The lesions that develop in the mucous membrane of the nose and mouth turn into sores and break open.

    The small pox infection caused by the variola virus is transmitted directly or indirectly from infected person airborne or through droplets, contaminated clothing or bedding, or as a biological weapon. Small pox patients are usually isolated to prevent transmission.

    Previously no cure existed for small pox. Though vaccines are available for small pox, routine vaccination was not possible for people at low risk of exposure, due to the side effects associated with the vaccine.

   The FDA granted approval to the chimerix for their production of Tembexa(Brincidofovir) as tablets and suspension to be taken orally for the treatment of small pox.

   Tembexa is an oral antiviral available in two dosage forms such as 100 mg tablets and 10 mg/ml oral suspensions. It should be taken once a week for 2 weeks. It is indicated for the adults and pediatric patients including the neonates having smallpox.

    Tembexa is a nucleotide analogue lipid conjugate. It is designed in such a way that it mimics a natural mono-acyl phospholipid, in order to achieve effective intracellular concentrations of cidofovir diphosphate, the active antiviral metabolite. Cidofovir acts as an alternate substrate inhibitor in viral DNA polymerase-mediated synthesis of viral DNA and hence exerts its antiviral action.

   Tembexa is not studied in human due to the inability to induce small pox a fatal and deadly disease just for the purpose of trial. However it's efficacy in immune deficient animals were reduced and hence is expected to also have reduced efficacy in immuno-compromized patients.

   The label of Tembexa warns that it should not be taken for longer duration, as it may cause mortality if taken for longer periods. The following are the warnings and precautions of the Tembexa,

❌ It is necessary to monitor liver parameters such as Serum transaminases and bilirubin, before and during the treatment, as they may be elevated.

❌ The patients must be monitered for gastrointestinal adverse effects such as diarrhoea, nausea, vomiting, abdominal pain.

❌ It should not be admisnistered along with intravenous cidofovir.

❌ It is a potential human carcinogen and hence direct contact with crush tablets or oral suspension should be avoided.

❌ It may cause infertility in men.

❌ It may cause teratogenic effect and hence an alternative therapy must be sought for pregnant women, if possible.

    The FDA approved Tembexa based on the efficacy in 2 animal models such as the Rabbit pox model and mouse Pox model.