Rilpivirine

Unless your doctor tells you otherwise, continue your normal diet.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from light, excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to rilpivirine.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Rilpivirine is usually taken once per day with a meal. Always take the medicine with food.

Use rilpivirine regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

While using rilpivirine, you may need frequent blood tests at your doctor's office.

If you have ever had hepatitis B or C, rilpivirine can cause this condition to come back or get worse. You will need frequent blood tests to check your liver function during treatment.

HIV/AIDS is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.

Store rilpivirine in its original container at room temperature away from moisture, heat, and light.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

If you are less than 12 hours late in taking your medicine, take the missed dose with food as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Rilpivirine is a prescription medicine used in combination with other medications to treat human immunodeficiency virus (HIV) in certain patients. Rilpivirine is in a class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs).  It blocks an enzyme that the virus needs in order to reproduce.

Rilpivirine can cause depressive disorders (depressed mood, depression, dysphoria, major depression, altering of mood, negative thoughts, suicide thoughts, and suicidal attempt). If you have severe depressive symptoms, tell your doctor immediately. Your doctor will determine if these symptoms are related to rilpivirine and will determine what the best course of action is for you. 

Do not take rilpivirine if your HIV infection has been previously treated with HIV medicines.

Rilpivirine does not cure HIV infection or AIDS. You must stay on continuous HIV therapy to control HIV infection and decrease HIV-related illnesses.

Avoid doing things that can spread HIV-1 infection to others.

• Do not share or re-use needles or other injection equipment.
• Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades
• Do not have any kind of sex without protection. Always practice safer sex by using a latex or polyurethane condom to lower the chance of sexual contact with any body fluids such as semen, vaginal secretions, or blood.

Ask your doctor if you have any questions about how to prevent passing HIV to other people.

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As a non-nucleoside reverse transcriptase inhibitor, rilpivirine has activity against HIV-1 by binding to reverse transcriptase. It consequently blocks the RNA-dependent and DNA-dependent DNA polymerase activities, including HIV-1 replication. It does not require intracellular phosphorylation for antiviral activity.

Absorption

Increased 40% with a meal (normal-to-high calorie)

Metabolism

Hepatic, primarily by CYP3A4

Excretion

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

Time to Peak

Plasma: 4 to 5 hours

Half-Life Elimination

~50 hours

Protein Binding

99.7% (primarily albumin)

HIV-1 infection: Treatment of HIV-1 infections in antiretroviral treatment-naive patients with HIV-1 RNA ≤100,000 copies/mL at the start of therapy in combination with at least 2 other antiretroviral agents

HIV-1 infection, treatment: Children ≥12 years and Adolescents ≥35 kg: Refer to adult dosing.

Dosage adjustment for concomitant therapy with rifabutin: Children ≥12 years and Adolescents (≥35 kg): Refer to adult dosing.

Swallow tablet whole with water. Administer with a normal- to high-calorie meal. Taking with a protein supplement drink alone does not increase absorption.

Concerns related to adverse effects:

• Depressive disorders: May cause depression, depressed mood, dysphoria, mood changes, negative thoughts, suicide attempts, or suicidal ideation; if changes are noted, seek professional intervention immediately; reevaluate risk versus benefit of continued rilpivirine therapy.

• Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).

• Hepatotoxicity: Has been reported during use. Patients with significant transaminase elevations or hepatitis B or C prior to treatment may be at greater risk for hepatic adverse events. Hepatotoxicity has occurred in a few adult patients with no prior hepatic disease or risk factors. Baseline and periodic laboratory LFT evaluation during therapy is recommended for patients with pre-existing risk factors; also consider LFT monitoring in patients without identifiable hepatic disease risk.

• Hypersensitivity: Hypersensitivity and severe skin reactions have been reported, including severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis or eosinophilia, or drug reaction with eosinophilia and systemic symptoms (DRESS) with rilpivirine-containing regimens. Some skin reactions were accompanied by constitutional symptoms (eg, fever); other skin reactions were associated with organ dysfunction (eg, hepatic serum biochemistry elevations). In clinical trials, treatment-related rashes ≥ Grade 2 were reported in 3% of patients. Most rashes were Grade 1 or 2 and occurred within the first 4 to 6 weeks of therapy. No Grade 4 rashes were reported. Monitor laboratory parameters and clinical status; discontinue if any hypersensitivity or skin rash develop.

• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• QTc prolongation: Doses >25 mg daily (ie, 75 mg daily, 300 mg daily) have been associated with QTc prolongation; use caution when coadministering with a drug with a known risk of torsades de pointes (HHS [adult] 2015).

Other warnings/precautions:

• Appropriate use: Do not use in adolescent and adult HIV-1 patients with a pre-ART of CD4 count <200 cells/mm3 and/or HIV RNA >100,000 copies/mL (HHS [adult] 2015).

Adverse events have not been observed in animal reproduction studies. Rilpivirine has moderate to high placental transfer. Available data in pregnant women are insufficient to evaluate the overall risk of birth defects. Maternal antiretroviral therapy may increase the risk of preterm delivery, although available information is conflicting possibly due to variability of maternal factors (disease severity; initiation of therapy); however, maternal antiretroviral medication should not be withheld due to concerns of preterm birth. Information related to stillbirth, low birth weight, and small for gestational age infants is limited. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children who develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction. Hypersensitivity reactions (including hepatic toxicity and rash) are more common in women on NNRTI therapy; it is not known if pregnancy increases this risk.

Combination antiretroviral therapy (cART) therapy is recommended for all HIV-infected pregnant women to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. When HIV is diagnosed during pregnancy in a woman who has never received antiretroviral therapy, cART should begin as soon as possible after diagnosis. The Health and Human Services (HHS) Perinatal HIV Guidelines recommend rilpivirine as a component in alternative regimens for initial use in antiretroviral-naïve pregnant women with a pre-treatment HIV RNA ≤100,000 copies/mL and CD4 cell count ≥200 cells/mm3. The pharmacokinetics are variably altered in pregnancy and although routine dosing adjustment is not suggested for all women, close monitoring is recommended. In general, women who become pregnant on a stable cART regimen may continue that regimen if viral suppression is effective, appropriate drug exposure can be achieved, contraindications for use in pregnancy are not present, and the regimen is well tolerated. Monitoring during pregnancy is more frequent than in non-pregnant adults; cART should be continued postpartum.

For HIV-infected couples planning a pregnancy, maximum viral suppression with cART is recommended prior to conception for the HIV-infected partner(s) and expert consultation is recommended; modification of therapy (if needed) and optimization of the woman’s health should be done prior to conception. HIV-infected women not planning a pregnancy may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. In addition, consistent use of condoms is also recommended (even during pregnancy) to prevent transmission of HIV or other sexually transmitted diseases.

Health care providers are encouraged to enroll pregnant women exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Health care providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2016).

Mild or moderate renal dysfunction: No adjustment recommended.
Severe renal dysfunction, end-stage renal disease: Caution and increased monitoring for side effects are recommended.