emtricitabine, rilpivirine, tenofovir DF

Action and Spectrum

Actions and spectrum: 

• emtricitabine: emtricitabine belongs to the class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs). It acts by inhibiting the reverse transcriptase enzyme, which is necessary for the replication of the HIV virus. emtricitabine has activity against both HIV-1 and HIV-2. 
• rilpivirine: rilpivirine is the non-nucleoside reverse transcriptase inhibitor. It works by binding to and inhibiting the reverse transcriptase enzyme, thereby blocking the replication of the HIV virus. rilpivirine is primarily active against HIV-1. 
• tenofovir DF: tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor (NtRTI). It acts by inhibiting the reverse transcriptase enzyme, preventing the conversion of viral RNA into viral DNA. tenofovir DF has activity against both HIV-1 and hepatitis B virus (HBV). 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% (rilpivirine) 

total bilirubin Increased (Grade 1: 5%) 

Insomnia (2%) 

Nausea (1%) 

Abnormal dreams (1%) 

Increased creatinine (5%) 

Headache (2%) 

Dizziness (1%) 

Depressive disorder (1%) 

Rash (1%)  

>10% (rilpivirine) 

AST Increased (Grade 1: 13%) 

ALT Increased (Grade 1: 16%) 

LDL cholesterol Increased (Grade 1: 11%) 

total cholesterol Increased (Grade 1: 13%)  

1-10% (tenofovir or emtricitabine) 

Dyspepsia 

Fever 

Nasopharyngitis 

Sinusitis 

Arthralgia 

Myalgia 

Peripheral neuropathy 

Increased cough 

Skin discoloration 

Abdominal pain 

Vomiting 

Pain 

Pneumonia 

URTI 

Back pain 

Paresthesia 

Anxiety 

Rhinitis  

>10% (tenofovir or emtricitabine) 

Diarrhea 

Fatigue 

Dizziness 

Insomnia 

Rash 

Nausea 

Headache 

Depression 

Abnormal dreams  

Post marketing Reports  

tenofovir 

Nutrition and Metabolism disorders: hypokalemia, Lactic acidosis, hypophosphatemia 

Gastrointestinal disorders: increased amylase, Pancreatitis, abdominal pain 

subcutaneous tissue and skin disorders:  Rash 

Respiratory, mediastinal and thoracic disorders: Dyspnea 

Hepatobiliary disorders: hepatitis, Hepatic steatosis, increased liver enzymes 

connective tissue and Musculoskeletal disorders: osteomalacia, Rhabdomyolysis 

Rilpivirine 

subcutaneous tissue and skin disorders: DRESS 

Urinary and Renal disorders: Nephrotic syndrome 

Black Box Warning

Black Box Warning: 

The black box warning for emtricitabine, rilpivirine, and tenofovir DF combination includes the risk of severe and potentially fatal side effects, such as lactic acidosis (excess lactic acid buildup) and hepatotoxicity (liver damage). Close monitoring of liver function and lactate levels is advised to prevent these complications. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: The combination is contraindicated in individuals with a known hypersensitivity or allergic reaction to emtricitabine, rilpivirine, tenofovir, or any of the components of the formulation. 
• Coadministration with certain drugs: The combination should not be coadministered with drugs that are known to significantly reduce the exposure of rilpivirine, such as rifampin or certain anticonvulsants (e.g., carbamazepine, phenytoin). 
• Pregnancy: The use of this combination is contraindicated during pregnancy. It is recommended to avoid use in the first trimester and assess the benefits and risks during the second and third trimesters. 
• Breastfeeding: The combination is contraindicated in breastfeeding women due to the HIV transmission and potential adverse effects on the infant.

Caution: 

• Drug Interactions: The combination can interact with other medications, including those that induce or inhibit certain enzymes responsible for drug metabolism. It is important to review the individual drug profiles and consult with a healthcare professional for potential drug interactions before initiating or changing therapy. 
• Immune Reconstitution Syndrome: In HIV-infected individuals with severe immune deficiency, such as those starting antiretroviral therapy, an inflammatory response to opportunistic infections or other diseases may occur. This is known as immune reconstitution syndrome, and caution is advised during the initial phase of therapy. 
• Resistance: Resistance to the individual components of the combination can develop, which may affect treatment efficacy. Regular monitoring of viral load and clinical response is recommended to detect any signs of treatment failure or development of resistance. 
• Bone Health: tenofovir DF has been associated with decreased bone density and the risk of bone fractures. This is a particular concern in individuals with underlying risk factors for osteoporosis or bone loss. Monitoring of bone health and considering interventions to reduce the risk of bone loss may be necessary. 

Comorbidities: 

• Hepatitis B Virus (HBV) Coinfection: emtricitabine and tenofovir DF have activity against HBV, so they can be used to treat both HIV and HBV coinfection. However, caution is needed as discontinuation of therapy may result in exacerbation of HBV. Regular monitoring of liver function and HBV viral load is recommended. 
• Renal Impairment: tenofovir DF is primarily eliminated by the kidneys, so caution should be exercised in individuals with pre-existing renal impairment. Dose adjustments may be necessary in those with reduced kidney function. Regular monitoring of renal function and serum phosphorus levels is advised. 
• Hepatic Impairment: rilpivirine is metabolized by the liver, so caution should be exercised in individuals with pre-existing liver impairment. Dose adjustments may be necessary in patients with moderate to severe hepatic impairment. 
• Mental Health Disorders: rilpivirine has been associated with psychiatric symptoms such as depression, mood changes, and suicidal ideation. It is important to monitor individuals with a history of mental health disorders or those at risk for such conditions. 
• Cardiovascular Disease: Some antiretroviral medications, including rilpivirine, have an increased risk of cardiovascular events. Caution should be exercised in individuals with pre-existing cardiovascular disease or risk factors. Regular monitoring of cardiovascular health parameters is recommended. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned. 

Lactation: Excreted into human milk: Yes (emtricitabine, tenofovir); Unknown (rilpivirine)  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI). It is phosphorylated within cells to its active form, which competitively inhibits the reverse transcriptase enzyme, preventing the replication of the HIV virus. 

rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). It binds directly to the reverse transcriptase enzyme and blocks its activity, thereby inhibiting HIV replication. 

tenofovir DF is a nucleotide reverse transcriptase inhibitor (NtRTI). It is converted to its active form, tenofovir diphosphate, which inhibits reverse transcriptase and terminates the viral DNA chain during viral replication.  

Pharmacodynamics: 

The pharmacodynamics results in the inhibition of HIV replication, reduction of viral load, and preservation of immune function. They are used in combination regimens to achieve optimal viral suppression and improve the health outcomes of individuals living with HIV. emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI). It inhibits the activity of reverse transcriptase, an enzyme necessary for the replication of the human immunodeficiency virus (HIV).

By blocking reverse transcriptase, emtricitabine prevents the conversion of viral RNA into DNA, thereby inhibiting viral replication. rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). It binds to the reverse transcriptase enzyme and inhibits its activity. By doing so, rilpivirine prevents the conversion of viral RNA into DNA, leading to the inhibition of HIV replication.

tenofovir DF is a nucleotide reverse transcriptase inhibitor (NtRTI). It is converted into its active form, tenofovir diphosphate, within cells. tenofovir diphosphate competes with natural nucleotides and incorporates itself into the growing viral DNA chain, causing premature termination of the viral DNA synthesis and inhibiting reverse transcriptase.  

Pharmacokinetics: 

emtricitabine: 

• Absorption: emtricitabine is well absorbed orally, and its bioavailability is approximately 93%. 
• Distribution: It has a high distribution volume, and it can penetrate various tissues, including the central nervous system (CNS). 
• Metabolism: emtricitabine undergoes minimal metabolism in the liver, with approximately 13% of the dose being metabolized to an inactive form. 
• Excretion: The majority of emtricitabine is excreted unchanged in the urine. The elimination half-life is approximately 10 hours. 

rilpivirine: 

• Absorption: rilpivirine is well absorbed after oral administration, with a bioavailability of approximately 85%. 
• Distribution: It has a high distribution volume, and it can penetrate various tissues, including the CNS. 
• Metabolism: rilpivirine undergoes extensive metabolism in the liver primarily via the CYP3A4 enzyme. The metabolites are mostly inactive. 
• Excretion: The metabolites of rilpivirine are primarily excreted in the feces, while a small amount is eliminated in the urine. The elimination half-life is approximately 50 hours. 

tenofovir DF: 

• Absorption: tenofovir DF is rapidly absorbed following oral administration, and its bioavailability is approximately 25%. 
• Distribution: It has a high distribution volume, and it can penetrate various tissues, including the kidneys. 
• Metabolism: tenofovir DF undergoes minimal metabolism in the liver, and the majority of the drug remains unchanged. 
• Excretion: The primary route of elimination is renal excretion, with 70-80% of the dose being excreted unchanged in the urine. The elimination half-life is approximately 17 hours. 

Adminstartion

Administration: 

emtricitabine, rilpivirine, and tenofovir disoproxil fumarate (DF) are usually administered together as part of a fixed-dose combination medication for the treatment of HIV infection. The specific administration instructions may vary depending on the brand and formulation of the medication. 

emtricitabine/rilpivirine/tenofovir DF Fixed-Dose Combination Tablet: 

• The medication is typically taken orally by mouth. 
• It is usually taken once daily, preferably with a meal. 

Other Formulations: 

• emtricitabine, rilpivirine, and tenofovir DF may also be available in separate formulations or combinations with different dosing instructions. 
• For specific administration instructions, it is important to refer to the prescribing information provided by the manufacturer. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: emtricitabine, rilpivirine, tenofovir DF 

Pronounced: em-trye-SYE-ta-been- ril-PIV-ir-een- ten-oh-FOH-veer dee-eff  

Why do we use emtricitabine, rilpivirine, tenofovir DF? 

• Treatment of HIV-1 Infection: emtricitabine/rilpivirine/tenofovir DF is used to treat HIV-1 infection in adults and adolescents who have not previously received antiretroviral treatment. It helps to suppress the replication of the HIV virus and reduce the viral load in the body, thus improving immune function and slowing down the progression of the disease. 
• Maintenance Therapy: emtricitabine/rilpivirine/tenofovir DF is also used as a maintenance therapy for individuals with HIV-1 infection who have achieved viral suppression on a stable antiretroviral regimen. It is used to maintain viral suppression and prevent the development of drug resistance.