Edurant

/ Janssen

The recommended dose of EDURANT is one 25 mg tablet once daily taken orally with a meal.
Rifabutin Co-administration: For patients concomitantly receiving rifabutin, the EDURANT dose should be increased to 50 mg (two tablets of 25 mg each) once daily, taken with a meal. When rifabutin co-administration is stopped, the EDURANT dose should be decreased to 25 mg once daily, taken with a meal.

EDURANT™, in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-naïve adult patients with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy.

Hypersensitivity to the active substance or to any of the excipients.
EDURANT is not recommended for patients less than 18 years of age.
This drug should not be co-administered with the following drugs, as significant decreases in rilpivirine plasma concentrations may occur due to CYP3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance to the drug  or to the class of NNRTIs:
– Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin.
– Antimycobacterials: rifabutin, rifampin, rifapentine.
– PPIs:  esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole.
– Systemic use of glucocorticoid dexamethasone (more than a single dose).
– St John’s wort (Hypericum perforatum).

Immune reactivation syndrome
In HIV infected patients with severe immune deficiency at the time of initiation of CART, an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions or aggravation of symptoms. Typically, such reactions have been observed within the first weeks or months of initiation of CART. Any inflammatory symptoms should be evaluated and treatment instituted when necessary. Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to
occur in the setting of immune reactivation; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment
Pregnancy
Should be used during pregnancy only if the potential benefit justifies the potential risk. Lower exposures of rilpivirine were observed during pregnancy, therefore viral load should be monitored closely. Alternatively, switching to another ART regimen could be considered.
See prescribing information for full details.

Common: Nausea, Abdominal pain, Vomiting, Fatigue, Headache, Dizziness,
Depressive disorders, Insomnia, Abnormal Dreams, Rash. 
See prescribing information for full details.

Rilpivirine is primarily metabolized by cytochrome P450 (CYP)3A, and drugs that induce or inhibit CYP3A may thus affect the clearance of rilpivirine. Co-administration of EDURANT and drugs that induce CYP3A may result in decreased plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs. Co-administration of EDURANT and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine.
Co-administration of EDURANT with drugs that increase gastric pH may result in decreased plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs.
EDURANT at a dose of 25 mg once daily is not likely to have a clinically relevant effect on the exposure of drugs metabolized by CYP enzymes.
See prescribing information for full details.

Pregnancy: Lower exposures of rilpivirine were observed during pregnancy, therefore viral load should be monitored closely.
Should be used during pregnancy only if the potential benefit justifies the potential risk. Lower exposures of rilpivirine were observed during pregnancy, therefore viral load should be monitored closely. Alternatively, switching to another ART regimen could be considered.
Lactation: The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. It is not known whether rilpivirine is secreted in human milk. Because of both the potential for HIV transmission and the potential for adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving this drug.
See prescribing information for full details.

There is no specific antidote for overdose with this drug. Human experience of overdose with EDURANT is limited. Treatment of overdose consists of general supportive measures including monitoring of vital signs and ECG (QT interval) as well as observation of the clinical status of the patient. If indicated, elimination of unabsorbed active substance may be achieved by gastric lavage. Administration of activated charcoal may also be used to aid in removal of unabsorbed active substance. Since rilpivirine is highly bound to plasma protein, dialysis is unlikely to result in significant removal of the active substance.