It is also recommended that, while on the drug, one should avoid those having recently received oral polio vaccine. This drug was formerly not recommended during pregnancy and early evidence indicated pregnant women on the drug (or the related azathioprine) showed a seven-fold incidence of fetal abnormalities as well as a 20-fold increase in miscarriage. There were also anecdotal reports linking mercaptopurine with spontaneous abortion, leading to the US FDA rating both AZA and mercaptopurine as category D drugs. However, Davis et al. 1999 found mercaptopurine, compared to methotrexate, was ineffective as a single-agent abortifacient; every woman in the mercaptopurine arm of the study had fetal cardiac activity at follow-up (two weeks later) and was given a suction abortion. A more recent, larger study, however, performed by the Cancers et Surrisque Associe aux Maladies inflamatoires intestinales En France (CESAME) indicated an overall rate of congenital malformations not significantly greater than the general population in France. The European Crohns and Colitis Organisation (ECCO) concluded in a consensus paper in 2010 that while AZA and mercaptopurine have an FDA rating of D, new research in both animals and humans indicates that "thiopurines are safe and well tolerated during pregnancy. "Mercaptopurine causes changes to chromosomes in animals and humans, though a study in 1990 found, "while the carcinogenic potential of 6-MP cannot be precluded, it can be only very weak or marginal." Another study in 1999 noted an increased risk of developing leukemia when taking large doses of 6-MP with other cytotoxic drugs.
After injection into the muscle, the substance reaches highest plasma levels after three to four days.Independently of the mode of application, rilpivirine is almost completely bound to plasma proteins (99.7%), mostly to albumin. It is metabolised mainly by the liver enzyme CYP3A4. Metabolites include several oxidation products, glucuronides, and glucuronides of oxidized metabolites. The biological half-life is approximately 45 hours for the tablets and 13 to 28 weeks for the injection.Elimination has only been studied for oral administration: Most of the drug is excreted via the faeces (85%), partly in unchanged form (25%), partly in form of its metabolites (60%). A minor amount is excreted via the urine (6%), almost exclusively as metabolites. Fixed-dose combinations
A fixed-dose medication combining rilpivirine with emtricitabine and tenofovir disoproxil (TDF) was approved by the U.S. Food and Drug Administration (FDA) in August 2011 under the brand name Complera, and was approved for use in the European Union with the brand name Eviplera in November 2011. This combination has been shown to have higher rates of virologic failure than emtricitabine/tenofovir/efavirenz in people with baseline HIV viral loads greater than 100,000 copies/mm3.A fixed-dose medication combining rilpivirine with emtricitabine and tenofovir alafenamide (TAF) was approved for use in the US in March 2016 with the brand name Odefsey.Dolutegravir/rilpivirine, sold under the brand name Juluca, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It was approved for use in the United States in November 2017 and for use in the European Union in May 2018.