Overview:
Rilpivirine is an antiviral medication used to treat HIV or AIDS (acquired immunodeficiency syndrome). Rilpivirine belongs to second-generation non-nucleoside reverse transcriptase inhibitors (NNRTI). It is a highly potent drug with a longer half-life and minimal side effects compared with older NNRTIs like Efavirenz. However, the Rilpivirine drug is not a cure for HIV or AIDS.
Tibotec, a pharmaceutical company, developed Rilpivirine. In the United States, this drug is approved for treatment in patients with a viral load of 100,000 copies/milliliter or less during the initiation of the therapy. This drug is used in combination with other antiviral drugs to treat HIV. In addition, the European Union approved the combined use of Rilpivirine with Cabotegravir for maintenance therapy in adults with a viral load of fewer than 50 copies/milliliter, which is undetectable in the blood.
How Does Rilpivirine Work?
When HIV enters a cell, reverse transcriptase converts the viral single-stranded RNA genome into a double-stranded viral DNA. The viral DNA then integrates into the host chromosomal DNA and allows cellular processes such as transcription and translation to reproduce the virus in the host.
Rilpivirine is a diaryl pyrimidine non-nucleoside reverse transcriptase inhibitor. It interferes with viral RNA (ribonucleic acid) and DNA (deoxyribonucleic acid)-directed polymerase activities of reverse transcriptase and inhibits the replication of HIV-1. It blocks HIV-1 replication by preventing reverse transcriptase from completing the reverse transcription of the viral single-stranded RNA genome into DNA.
What Are the Uses of Rilpivirine?
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Rilpivirine treats HIV-1 infection in adults and adolescents over 12 years with plasma HIV-1 levels greater than 100,000 copies/mL. It is used in combination with other antiretroviral drugs.
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It is used in postexposure prophylaxis following occupation exposure, like needle stick injury, cutting with sharp objects, or mucous membrane contact with blood, tissue, or other body fluids contaminated with HIV.
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It is used in postexposure prophylaxis following nonoccupational exposure, like exposure to blood, genital secretions, or other infectious body secretions contaminated with HIV.
What Is the Dosage of Rilpivirine?
Rilpivirine is available as a tablet and as long-acting intramuscular injections. The intramuscular injections are given once a month or every two months. Before giving an injection, the tablets are given for four weeks to assess tolerability.
Pediatric Dose for the Treatment of HIV infection:
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25 mg (milligram) Rilpivirine is given once a day in adolescents more than the age of 12 years with a body weight greater than 35 kg (kilograms).
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Emtricitabine (200 mg)/ Rilpivirine (25 mg) / Tenofovir Afenamide (25 mg); 1 tablet once a day in adolescent patients of age 12 or more with a body weight of 35 kgs or more.
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Emtricitabine 200mg/ Rilpivirine 25 mg/ Tenofovir DF 300 mg; one tablet is given once a day in adolescents of age 12 or more with a body weight of 35 kg or more.
Adult Dose for the Treatment of HIV Infection:
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25 mg (milligram) Rilpivirine is given once a day.
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Emtricitabine (200 mg)/ Rilpivirine (25 mg) / Tenofovir Afenamide (25 mg); one tablet once a day.
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Emtricitabine 200 mg/ Rilpivirine 25 mg/ Tenofovir DF (Complera) 300 mg; one tablet is given once a day.
Postexposure Prophylaxis for HIV Infection Following Occupational Exposure:
Postexposure prophylaxis should be initiated immediately within 72 hours following the exposure. For example, 25 mg (milligram) of Rilpivirine is given once daily in conjunction with two NRTIs. Emtricitabine 200mg / Rilpivirine 25 mg / Tenofovir 300 mg; one tablet is given once daily for four weeks as a complete postexposure prophylaxis (PEP) regimen.
Postexposure Prophylaxis for HIV Infection Following Non-Occupational Exposure:
Emtricitabine 200mg/Rilpivirine 25 mg/Tenofovir DF 300 mg; 1 tablet is given daily for 28 days to prevent HIV infection following nonoccupational exposure. It is not recommended if the exposed individual seeks care after 72 hours of exposure.
Warnings:
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Hypersensitivity Reactions: Severe hypersensitivity reactions, such as drug reactions with eosinophilia and systemic symptoms (DRESS), were reported. It also caused organ dysfunction with elevated hepatic serum enzyme concentrations. In addition, skin reactions like rashes, blisters, facial edema, mucosal involvement, conjunctivitis, and angioedema are observed.
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Depressive Disorders: Depressive disorders such as depression, dysphoria, major depression, altered mood, and suicidal thoughts were reported.
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Hepatotoxicity: Adverse hepatotoxic effects were reported in some patients without an underlying hepatic disease.
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Adipogenic Effects: Redistribution or accumulation of boy fat, namely central obesity, peripheral wasting, breast enlargement, facial wasting, and general cushingoid appearance, were observed.
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Immune Reconstitution Syndrome: Autoimmune disorders such as Grave's disease, polymyositis, and Guillain-Barre syndrome occurs in the setting of immune reconstitution. It occurs after several months of initiation of antiretroviral therapy.
For Patients
What Is HIV-1 Infection?
HIV-1 is a viral infection. HIV-1 is the common human immunodeficiency virus that attacks the body's immune system. HIV-1 and HIV-2 are two types of HIV infections, of which HIV-1 is more common. Both types result in AIDS, but HIV-2 has lower transmissibility and a reduced rate of progression to cause AIDS. HIV-1 destroys the CD4 (clusters of differentiation 4) cells that are essential for fighting against infections. This virus severely attacks the body's immune system and results in acquired immunodeficiency syndrome (AIDS), which has no effective treatment. Individuals infected with HIV-1 carry it for a lifetime. If left untreated, the virus constantly depletes the body's CD4 cells, weakens the immune system, and makes it hard to deal with infections and certain types of cancers.
What Causes HIV-1 Infection?
Individuals can contract HIV-1 when they come into contact with body fluids containing the virus. It enters the host through the blood or mucous membrane found in regions like the genitals, anus, or mouth. The infection can be transmitted through the blood, semen, pre-seminal fluid, vaginal fluid, rectal fluids, and breast milk. The transmission occurs during unprotected anal or vaginal sex, reusing or sharing infected needles, from a mother who is not receiving antiretroviral therapy for this infection to a child during pregnancy, labor, or through breastfeeding.
What Happens in HIV-1 Infection?
HIV infection progresses in three different stages.
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Acute: Acute stage is the period shortly after exposure to HIV-1. A high viral load is present in this stage, and the individual experiences flu-like symptoms.
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Chronic: A person at this stage does not experience any symptoms. However, the virus attacks the immune system if antiretroviral drugs are not given.
Acquired Immunodeficiency Syndrome (AIDS) occurs when the CD4 count is below 200 cells per cubic millimeter. As a result, the immune system is severely damaged, and the person develops opportunistic infections.
Learn More About Rilpivirine
Facts to Know Before Starting Rilpivirine:
When and Why Switch to Rilpivirine?
Various drug regimens are followed in antiretroviral therapy. Rilpivirine is a second-generation non-nucleoside reverse transcriptase inhibitor that should be consumed once daily. It is a highly potent drug with a longer half-life and minimal side effects compared with older NNRTIs like Efavirenz. Efavirenz, an NNRTI, is the first-line antiretroviral therapy for HIV infection. A switch to a Rilpivirine-based regimen should be considered in patients fully suppressed on antiretroviral therapy only in the absence of previous virological failure or resistant mutations to nucleoside and non-nucleoside reverse transcriptase inhibitors to avoid virological failures.
How Effective Is Rilpivirine?
Antiretroviral therapy with Rilpivirine in conjunction with other antiretrovirals has proven to be effective, even in individuals with advanced HIV infection, low CD4 level, history of virological failure, and previous non-suppressive antiretroviral therapy. In addition, it is better tolerated, less toxic, highly potent, and more durable than Efavirenz in first-line antiretroviral therapy.
Things to Inform the Doctor Before Rilpivirine Is Prescribed
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After taking Rilpivirine, it is essential to inform the doctor if skin rashes or allergic reactions are present.
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The presence of liver diseases should be informed because Rilpivirine worsens the liver diseases like Hepatitis B or C.
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The presence of kidney diseases should be informed.
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If depression or mental illness is present, it should be informed.
Starting Rilpivirine:
How to Take Rilpivirine?
Rilpivirine should be consumed as directed by the physician. All instructions on the prescription label regarding Rilpivirine should be followed. It is usually taken once per day with a full meal. Frequent medical tests are required while under this medication. If Rilpivirine and Cabotegravir are given together, it is usually prescribed once a day for 28 days before switching to the injectable combination.
Do's and Don'ts While Under Rilpivirine:
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It is important to visit the doctor regularly to check the improvements in the disease.
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The dose should remain the same, and the medication should only be skipped with the doctor's advice.
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Taking the tablet with food is important because it enhances this drug's absorption.
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Rilpivirine will not prevent the spread of the disease. Having unprotected sex and sharing razors, toothbrushes, and needles are unsafe.
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It is important to consult the doctor if allergic reactions, liver problems, or mood changes like depression occurs.
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Rilpivirine can cause various adverse effects; if any unwanted effects are present, it should be informed to the doctor.
Advise for Caregivers:
The caregivers should inform the doctor if the patient develops symptoms of hypersensitivity reactions like rashes, hives, breathing difficulties, or any other symptoms like chest pain, skin reactions, depression, or any other unwanted effects.
Things to Do After Taking Rilpivirine:
After taking Rilpivirine, it is essential to inform the doctor if any noticeable symptoms are present. For example, any signs of allergic reactions, skin reactions, or symptoms like chest pain should be immediately informed to the doctor.
Diet Modifications:
Diet modifications are not necessary unless recommended by the doctor. A healthy and balanced diet can be followed during antiviral therapy. The use of alcohol or tobacco is not recommended during the treatment.
Look Out for the Side Effects:
The patients should familiarize themselves with Rilpivirine's common and rare side effects of Rilpivirine so that the symptoms can be easily recognized. If side effects are present, they should be consulted with the doctor. Rilpivirine may cause some other side effects that are not listed here.
The common side effects include the following:
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Insomnia (sleep problems).
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Allergic reactions like hives, rashes, breathing difficulties, and swelling of the face or throat.
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Skin reactions like peeling and blistering.
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Mood changes, anxiety, and depression.
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Liver problems like jaundice, dark urine, and right-sided upper stomach pain.
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Headache.
The less common side effects are
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Indigestion.
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Stomach pain.
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Irritability.
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Lack of appetite.
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Recurrent fever.
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Blurred vision.
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Chest tightness.
Staying on Rilpivirine:
Tips to Stay on Track:
Improvement in the symptoms of HIV can be experienced after taking Rilpivirine. However, if any side effects occur during treatment, it is important to inform the doctor. Rilpivirine is prescribed on a fixed schedule; it should not be skipped without informing the doctor.
Things to remember,
1) Sticking to the dosage schedule of Rilpivirine is important because skipping the dose will affect the treatment outcome.
2) It is vital to follow up regularly with the doctor and inform them about the improvement in the symptoms of HIV.
For Doctors
Indications:
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Rilpivirine is used in the treatment of HIV-1 infection in adults and adolescents who are more than 12 years of age. It is used in combination with other antiretroviral drugs.
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It is used in postexposure prophylaxis following occupation exposure, like needlestick injury, cutting with sharp objects, or mucous membrane contact with blood, tissue, or other body fluids contaminated with HIV.
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It is also used in postexposure prophylaxis following nonoccupational exposure, like exposure to blood, genital secretions, or other infectious body secretions contaminated with HIV.
Mechanism of Action:
When HIV enters a cell, reverse transcriptase converts the viral single-stranded RNA genome into a double-stranded viral DNA. The viral DNA then integrates into the host chromosomal DNA and allows cellular processes such as transcription and translation to reproduce the virus in the host.
Rilpivirine is a diaryl pyrimidine non-nucleoside reverse transcriptase inhibitor. It interferes with viral RNA (ribonucleic acid) and DNA (deoxyribonucleic acid)-directed polymerase activities of reverse transcriptase and inhibits the replication of HIV-1. It blocks HIV-1 replication by preventing reverse transcriptase from completing the reverse transcription of the viral single-stranded RNA genome into DNA.
Pharmacodynamics:
The subinhibitory concentrations of Rilpivirine cause loss of virological response and development of resistance to Rilpivirine or cross-resistance to other drugs in this group. Rilpivirine should be used in conjunction with other antiretroviral drugs to prevent resistance. Information regarding the post-antiviral effects of Rilpivirine is not available.
Absorption:
Rilpivirine reached peak plasma concentrations within four to five hours. If it is administered in fasting conditions or with a protein drink, the systemic availability decreases by 30 to 40 percent compared with administration with a full meal.
Distribution:
Rilpivirine is bound to plasma proteins, mainly albumin, by 99.7 percent. However, the distribution of this drug into compartments other than plasma, such as cerebrospinal fluid and genital secretions, is unknown.
Metabolism:
Rilpivirine undergoes oxidative metabolism mediated by the liver's cytochrome P450 (CYP) 3A system.
Elimination:
The elimination half-life is approximately 50 hours for Rilpivirine. Following oral administration, 85 percent of Rilpivirine is eliminated in feces, and 6 % is eliminated in urine. Since Rilpivirine is bound to plasma proteins, removal by peritoneal or hemodialysis is impossible.
What Are the Warnings and Precautions for the Drug?
1) Hypersensitivity Reactions: Severe hypersensitivity reactions, such as drug reactions with eosinophilia and systemic symptoms (DRESS), were reported. It also caused organ dysfunction with elevated hepatic serum enzyme concentrations. Skin reactions like rashes, blisters, facial edema, mucosal involvement, conjunctivitis, and angioedema are observed.
2) Depressive Disorders: Depressive disorders such as depression, dysphoria, major depression, altered mood, and suicidal thoughts were reported.
3) Hepatotoxicity: Adverse hepatotoxic effects were reported in some patients without an underlying hepatic disease.
4) Adipogenic Effects: Redistribution or accumulation of boy fat, namely central obesity, peripheral wasting, breast enlargement, facial wasting, and general cushingoid appearance, were observed.
5) Immune Reconstitution Syndrome: Autoimmune disorders such as Grave's disease, polymyositis, and Guillain-Barre syndrome occurs in the setting of immune reconstitution. It occurs after several months of initiation of antiretroviral therapy.
Indications and Uses:
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Rilpivirine treats HIV-1 infection in adults and adolescents over 12 years with plasma HIV-1 levels greater than 100,000 copies/mL. It is used in combination with other antiretroviral drugs.
-
It is used in postexposure prophylaxis following occupation exposure, like needlestick injury, cutting with sharp objects, or mucous membrane contact with blood, tissue, or other body fluids contaminated with HIV.
-
It is used in postexposure prophylaxis following nonoccupational exposure, like exposure to blood, genital secretions, or other infectious body secretions contaminated with HIV.
Dosage Strength and Forms:
Rilpivirine is a 25 mg white to off-white, film-coated, round tablet. A single tablet contains 27.5 mg of Rilpivirine hydrochloride, equivalent to 25 mg of Rilpivirine. It is available as a tablet and as long-acting intramuscular injections. The intramuscular injections are given once a month or every two months. Before giving an injection, the tablets are given for four weeks to assess tolerability.
Dosage:
Pediatric Dose for the Treatment of HIV infection:
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25 mg (milligram) Rilpivirine is given once a day in adolescents more than the age of 12 years with a body weight greater than 35 kg (kilograms).
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Emtricitabine (200 mg) / Rilpivirine (25 mg) / Tenofovir Afenamide (25 mg); one tablet once a day in adolescent patients of age 12 or more with a body weight of 35 kgs or more.
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Emtricitabine 200mg/Rilpivirine 25 mg / Tenofovir DF 300 mg one tablet is given once a day in adolescents of age 12 or more with a body weight of 35 kg or more.
Adult Dose for the Treatment of HIV Infection:
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25 mg (milligram) Rilpivirine is given once a day.
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Emtricitabine (200 mg)/Rilpivirine (25 mg)/Tenofovir Afenamide (25 mg); one tablet once a day.
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Emtricitabine 200mg/Rilpivirine 25 mg/Tenofovir DF (Complera) 300 mg; one tablet is given once a day.
Postexposure Prophylaxis for HIV Infection Following Occupational Exposure:
Postexposure prophylaxis should be initiated immediately within 72 hours following the exposure. 25 mg (milligram) Rilpivirine is given once daily in conjunction with two NRTIs. Emtricitabine 200mg/Rilpivirine 25 mg/Tenofovir 300 mg; 1 tablet is given once daily for four weeks as a complete postexposure prophylaxis (PEP) regimen.
Postexposure Prophylaxis for HIV Infection Following NonOccupational Exposure:
Emtricitabine 200mg/Rilpivirine 25 mg/Tenofovir DF (Complera) 300 mg; 1 tablet is given once a day for 28 days to prevent HIV infection following nonoccupational exposure. It is not recommended if the exposed individual seeks care after 72 hours of exposure.
Considerations for Administration:
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Rilpivirine should not be given if skin rashes or allergic reactions were present previously after taking Rilpivirine.
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Rilpivirine worsens the liver diseases like Hepatitis B or C, and it should be avoided in patients with hepatic impairment.
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It should not be given to patients with kidney diseases.
Contraindication:
Rilpivirine worsens the underlying liver disease. Therefore, it is highly contraindicated in patients with liver disease.
Results from Clinical Trials:
Phase 3 clinical trials showed that most adverse drug reactions occurred within 48 weeks of treatment. It was also observed that Rilpivirine is a highly potent drug with a longer half-life and minimal side effects compared with Efavirenz. Subinhibitory concentrations of Rilpivirine caused the loss of virological response and the development of resistance to Rilpivirine or cross-resistance to other drugs. Hence, Rilpivirine should be used with other antiretroviral drugs to prevent resistance.
Drug Interactions:
Interactions With Other Drugs:
Drug interactions occur with Rilpivirine and the drugs in fixed-dose combinations. Drug interactions occur with the following drugs:
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Drugs that affect hepatic enzymes or those metabolized by hepatic micro enzymes.
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Drugs affected by P-glycoprotein transport.
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Drugs that increase gastric pH.
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Drugs that prolong the QT (QT wave in electrocardiogram) interval.
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Nephrotoxic drugs or drugs that are eliminated by renal excretion.
Other Specifications:
1) Hypersensitivity Reactions: Severe hypersensitivity reactions, such as drug reactions with eosinophilia and systemic symptoms (DRESS), were reported. It also caused organ dysfunction with elevated hepatic serum enzyme concentrations. Skin reactions like rashes, blisters, facial edema, mucosal involvement, conjunctivitis, and angioedema are observed.
2) Depressive Disorders: Depressive disorders such as depression, dysphoria, major depression, altered mood, and suicidal thoughts were reported.
3) Hepatotoxicity: Adverse hepatotoxic effects were reported in some patients without an underlying hepatic disease.
4) Adipogenic Effects: Redistribution or accumulation of boy fat, namely central obesity, peripheral wasting, breast enlargement, facial wasting, and general cushingoid appearance, were observed.
5) Immune Reconstitution Syndrome: Autoimmune disorders such as Grave's disease, polymyositis, and Guillain-Barre syndrome occurs in the setting of immune reconstitution. It occurs after several months of initiation of antiretroviral therapy.
6) Pregnancy: Insufficient data is available to assess the risk of birth defects in pregnant women regarding using Rilpivirine.
7) Lactation: HIV-infected women should not breastfeed the baby because of the risk of transmission. The distribution of Rilpivirine in breast milk is not known.
8) Pediatric use: The safety and efficacy of Rilpivirine in pediatric patients below 12 years of age are not established.
9) Geriatric Use: The safety and efficacy of Rilpivirine in pediatric patients above 65 years of age are unknown.
10) Renal Impairment: Rilpivirine should be used cautiously in patients with severe renal impairment or end-stage renal disease.
