Rilpivirine (Edurant) is a non-nucleoside reverse transcriptase inhibitor that inhibits viral replication by inhibiting RNA-dependent and DNA-dependent DNA polymerases.

Rilpivirine (Edurant) Indications:

• HIV-1 infection:

  • It is indicated for the treatment of HIV-1 infections in antiretroviral treatment-naive patients who are 12 years of age or older and weighing 35 kgs or more, with HIV-1 RNA ≤100,000 copies/mL at the start of therapy.
  • It should be given in combination with other antiretroviral therapies.

Rilpivirine (Edurant) Dose in Adults

Rilpivirine (Edurant) Dose in the treatment of HIV-1 infection:

• Patients ≥35 kg:

  • 25 mg orally once a day.

Rilpivirine (Edurant) Dose in Pregnancy:

• 25 mg once a day in patients on a stable regimen before pregnancy and who are virologically suppressed

• Dosage adjustment for concomitant therapy with rifabutin:

  • Increase the dose to 50 mg once a day in patients on concomitant rifabutin.
  • Decrease the dose to 25 mg once a day when rifabutin is stopped.

Rilpivirine (Edurant) Dose in Childrens

Rilpivirine (Edurant) Dose in the treatment of HIV-1 infection:

Note: It is not indicated as monotherapy (Use in combination with other antiretroviral agents).

• Infants and Children <12 years or <35 kg:

  • No dosing recommendations are available. Avoid using it in these patients.

• Children and Adolescents ≥12 years and ≥35 kg:

  • 25 mg orally once a day.

• Dosage adjustment for concomitant therapy with rifabutin:

  • Children ≥12 years and Adolescents:

    • Increase the dose to 50 mg orally once a day in patients on concomitant rifabutin.
    • The dose may be decreased to 25 mg once a day when rifabutin is stopped.

Pregnancy Risk Category: Not Assigned

• Rilpivirine crosses the placental barrier.
• It has been proven that there is no increase in the risk of birth defects when it's administered in the first trimester.
• Although maternal ART has been shown to reduce the risk of preterm births, data is not available and could be confounded with other risk factors, such as advanced maternal years and severe disease.
• Some studies also found an increase in stillbirths, low birth weights, and a small gestational age.
• Maternal ART should not be stopped during pregnancy. However, it is important to monitor infants who were born to mothers who are on ART. 
• For children with neurological disorders, it is important to check for mitochondrial disease.
• The use of rilpivirine is considered as an alternative treatment in pregnant patients who are antiretroviral-naive, who have had ART therapy in the past but are restarting, who require a new ART regimen, and who are planning to conceive.
• If a female becomes pregnant while taking Edurant (Rilpivirine), she can continue the treatment as long as the virus is under control and tolerated.
• Pregnancy can affect the pharmacokinetics and drug efficacy. Therefore, it is important to monitor viral loads regularly.
• According to the HHS Health and Human Services Perinatal HIV Guidelines, rilpivirine is recommended as an alternative treatment for females with HIV RNA levels of =100,000. copies/mL and CD4 cells >=200.

NOTE:

• All pregnant women should receive ART and continue treatment after giving birth to reduce vertical transmission.

Rilpivirine use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk.
• Breastfeeding is not advised as viral transmission can occur during breastfeeding. Maternal ART cannot completely eliminate the possibility of viral transmission.

Rilpivirine (Edurant) Dose in Kidney Disease:

• Mild or moderate renal impairment:

  • Adjustment in the dose is not necessary.

• Severe or end-stage renal impairment (ESRD):

  • Adjustment is not necessary but use with caution.

• Hemodialysis and peritoneal dialysis:

  • The drug is not dialyzable because of significant protein-binding.

Rilpivirine (Edurant) Dose in Liver disease:

• Mild to moderate impairment (Child-Pugh class A or B):

  • Adjustment in the dose is not necessary.

• Severe impairment (Child-Pugh class C):

  • It has not been studied in patients with severe liver disease.
  • Canadian labeling recommends avoiding it in severe hepatic impairment.

Common Side Effects of Rilpivirine (Edurant):

• Central Nervous System:

  • Depression
  • Headache
  • Drowsiness

• Endocrine & Metabolic:

  • Decreased Plasma Cortisol
  • Increased Serum Cholesterol
  • Increased LDL Cholesterol

• Gastrointestinal:

  • Nausea

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST

Less Common Side Effects of Rilpivirine (Edurant):

• Central Nervous System:

  • Dizziness
  • Insomnia
  • Abnormal Dreams
  • Fatigue

• Dermatologic:

  • Skin Rash

• Endocrine & Metabolic:

  • Increased Serum Triglycerides

• Gastrointestinal:

  • Abdominal Pain
  • Vomiting

• Hepatic:

  • Increased Serum Bilirubin

• Renal:

  • Increased Serum Creatinine

Contraindication to Rilpivirine Include:

• Allergy reactions to any component of the drug or the drug itself
• With:
  • anticonvulsants drugs (carbamazepine, oxcarbazepine, phenobarbital, phenytoin),
  • antimycobacterial drugs (rifampin, rifapentine),
  • proton pump inhibitors (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole),
  • Systemic dexamethasone (or
  • St John's Wort.

Warnings and precautions

• Depressive disorders:

  • Patients receiving Rilpivirine (Edurant), treatment may experience neuropsychiatric symptoms.
  • Patients can experience depression, low mood, disphoria and mood changes.
  • It may be necessary to consult a psychiatrist promptly.
  • If the suicide risk is greater, it may be necessary to change the antiviral treatment regimen.

• Fat redistribution

  • Fat distribution can occur as a result of the treatment. This could manifest as a buffalo-hump, peripheral waste, increased abdominal girth and cushingoid appearance.

• Hepatotoxicity:

  • Rilpivirine, Edurant, may cause hepatotoxicity in patients who have had hepatitis B or C or other liver-related illnesses before the treatment.
  • Hepatotoxicity refers to a significant increase in liver enzymes. It can occur in patients who have no other risk factors for liver disease.
  • It is important to monitor the liver function test results at baseline as well as periodically, if necessary.

• Hypersensitivity

  • It is possible to experience severe hypersensitivity reactions or skin reactions such as a rash, blisters, mucosal involvement and conjunctival injection. Also, there may be facial and lip swelling.
  • Sometimes, skin reactions can be accompanied with constitutional symptoms such as fever or organ dysfunction like hepatic transaminitis.
  • Patients should be closely monitored, and treatment must be stopped if hypersensitivity reactions develop.

• Immune reconstitution syndrome:

  • After antiretroviral treatment, immunorestitution syndrome can occur.
  • It's characterized by an exaggerated reaction to indolent infection such as tuberculosis or fungal infections, after ART has been initiated.
  • In therapy, other immune-mediated diseases such as Graves disease and polymysitis may also develop.
  • It may be necessary to provide the appropriate treatment.

Rilpivirine: Drug Interaction

Monitoring parameters:

• Cholesterol and triglycerides,
• Hepatic transaminases;
• Monitor for allergic reactions, skin rash, and a fever
• Observe the signs and symptoms of infection.

How to administer Rilpivirine (Edurant)?

• The tablets should be swallowed whole with water.
• Preferably, it should be administered with a normal or a high-calorie meal.
• The absorption of the drug is not increased when the drug is administered with a protein supplement drink alone.

Mechanism of action of Rilpivirine (Edurant):

• Rilpivirine, a non-nucleoside inhibitor of reverse transcriptase, inhibits HIV-1 replication.
• It does this by inhibiting DNA-dependent and RNA-dependent DNA polymerase.

Absorption is increased by 40% when taken with a meal.

Protein binding: 99.7% of the drug is protein-bound, primarily to albumin.

Metabolism: It is metabolized by the liver, primarily by CYP3A4

Half-life elimination: The half-life elimination of the drug is about 50 hours

Time to peak plasma concentration: 4 to 5 hours

Excretion:

• Feces (85%, ~25% as unchanged drug);
• urine (~6%; <1% as unchanged drug)

International Brands of Rilpivirine:

• Edurant

Rilpivirine Brands Names in Pakistan:

No Brands Available in Pakistan.