Emtricitabine: A Powerful Ally Against HIV Infection

Overview:

Emtricitabine is a nucleoside reverse-transcriptase inhibitor (NRTI) generally prescribed for the prevention and treatment of human immunodeficiency virus (HIV) infection in both pediatric and adult populations. This medication is mostly used in combination with other antiretroviral agents. Emtricitabine is to be taken orally once daily. This drug works by decreasing the amount of viral load in the bloodstream.

This drug received its Food and Drug Administration (FDA) approval on July 2, 2003. Emtricitabine is considered the 49th most commonly prescribed medicine in 2019 in the United States, accounting for more than three thousand prescriptions.

Drug Group:

Nucleoside reverse transcriptase inhibitors (NRTIs) are known to be the first class of antiretroviral agents to receive approval from the FDA. They are usually taken as prodrugs as it is to be taken into the host body and get phosphorylated even before they become active. The cellular kinase will begin the activation of the drug once it gets inside the host cell.

Available Doses and Dosage Forms:

Emtricitabine is available as an oral solution and an oral capsule.

• Capsule: 200 mg (milligrams) of Emtricitabine with the size of one hard gelatinous capsule.

• Oral Solution: Clear and orange to dark orange liquid containing ten milligrams of Emtricitabine per milliliter.

For Patients:

What Is HIV Infection?

Human immunodeficiency virus (HIV) is a serious infection that attacks the immune system in the human body, especially the white blood cells known as the CD4 cells. This infection influences and ruins the CD4 cells, declining the individual’s potential and immunity towards opportunistic infections like tuberculosis, fungal infections, certain bacterial infections, and some cancerous conditions.

Many people with HIV infection do not experience symptoms during the first few months following an infection and even go unaware of their infection. Other people might encounter influenza-like symptoms such as fever, headache, sore throat, and rash. Nevertheless, the first few months manifest as the most severe infectious disease.

The symptoms get more pronounced as the condition progresses. The symptoms include weight loss, fever, cough, diarrhea, and swollen lymph nodes. Human immunodeficiency virus substantially weakens the body’s potential to combat other infections. Without proper care and treatment, people will become more susceptible to severe illnesses like cryptococcal meningitis, tuberculosis, bacterial infections, and certain cancerous conditions such as Kaposi’s sarcoma and lymphoma.

How Does Emtricitabine Work?

Emtricitabine is administered in combination with other medications for the treatment of human immunodeficiency virus (HIV) infection. Emtricitabine belongs to the class of drugs called nucleoside reverse transcriptase inhibitors (NRTIs). This drug functions by reducing the amount of virus in the blood. Though Emtricitabine does not have a role in the cure of HIV, it might decrease the possibility of developing a deadly condition called acquired immunodeficiency syndrome (AIDS) and other HIV-related diseases like cancer and serious infections. Taking Emtricitabine medication alone with safer sex practices and lifestyle modifications might decrease the likelihood and risk of transmitting the human immunodeficiency virus to partners and other people.

What Is the Dosage of Emtricitabine?

Emtricitabine is available in two forms and associated strengths. The recommended dosage of Emtricitabine in the treatment of HIV infection includes the following. The form and dosage can vary between the adult and pediatric population, considering weight and certain factors.

• Capsule: 200 milligrams orally once every day.

• Oral Solution: 240 milligrams or 24 milliliters orally once daily.

What Are the Things to Inform the Doctor Before Taking Emtricitabine?

• Inform the doctor if one is allergic or hypersensitive to Emtricitabine or other ingredients in the prescribed formulation.

• Tell the doctor about the health status, past medical history, and underlying medical conditions.

• Be certain to inform the doctor if one has any liver problems, especially hepatitis B virus infection.

• It is crucial to inform the doctor in case of the presence of kidney problems and kidney dialysis treatment.

• Inform the healthcare providers about all the medications one takes or plans to take. This includes prescription medicine, over-the-counter medication, vitamins, nutritional supplements, and herbal products.

• Certain medications are more likely to interact with Emtricitabine, causing undesirable reactions. So, one must keep a list of medications and show it to the healthcare provider before getting treatment.

• Inform the doctor if one is pregnant or has plans to get pregnant. It is not determined whether Emtricitabine could harm the unborn baby. Inform the healthcare provider if one becomes pregnant during the treatment of Emtricitabine.

• There is a pregnancy registry for female patients who take Emtricitabine during the time of pregnancy. This registry's significance is gathering information about the health status of women and babies.

• Inform the doctor if one is breastfeeding or has any breastfeeding plan. Emtricitabine could be passed to the infant through breast milk. Hence, it is advised not to breastfeed if one has an HIV-1 infection due to the risk of passing the infection to the baby. Discuss with the healthcare provider regarding the safest way to feed the infant.

How Is Emtricitabine Administered?

• Take the Emtricitabine medication exactly per the healthcare provider's instructions and labeled guidelines.

• Only take in smaller or larger amounts for a shorter time than recommended.

• Emtricitabine medication is advised to be taken by mouth once daily. The dosage differs for adults and children. The form (capsule or oral solution) and dosage for the pediatric population are given based on the healthcare provider’s calculations of the child's weight.

• Emtricitabine medication might be taken with or without food intake.

• One should take a dose of Emtricitabine. Missing the dosage can lower the amount of medication in the blood. Hence, be cautious and refill the Emtricitabine prescription before anyone runs out of the medicine.

• Do not change the dosage and bring it to a stop of taking Emtricitabine without the doctor’s consent. One must stay under the care and supervision of a healthcare provider while on Emtricitabine therapy.

• The disease might become resistant to the Emtricitabine drug if one stops taking the medication, even for the short term.

• During Emtricitabine treatment, one might need frequent blood, liver, and kidney function tests.

• Do not take Emtricitabine as the only HIV medicine. Human immunodeficiency virus (HIV) or Acquired immunodeficiency syndrome (AIDS) are usually targeted with a combination of the drugs. So, one should take all the medicines as the healthcare provider directs.

Emtricitabine Capsule:

• Swallow the Emtricitabine capsule as a whole with water.

• It is advised not to crush, chew, or break the Emtricitabine capsules.

Emtricitabine Oral Solution:

• Measure the oral solution with the dosing syringe provided with the medication or using a specified dose-measuring spatula or medicine cup.

• Then, administer the appropriate dosage of Emtricitabine gradually using a syringe or dispensing tool.

What Are the Side Effects of Emtricitabine?

Emtricitabine is a safe and effective drug for pediatrics, adolescent, and adult populations. It can induce certain undesirable reactions in several people that sometimes require medical attention and prompt treatment.

Common Side Effects:

The common side effects associated with Emtricitabine intake are listed below. The following less severe side effects can be temporary and resolved independently. However, one must inform the doctor and get appropriate intervention if it is not cured, distressing the daily functions.

• Headaches.

• Weakness.

• Dizziness.

• Stomach pain.

• Nausea.

• Vomiting.

• Diarrhea.

• Distorted dreams.

• Abnormal sleep patterns.

• Skin discoloration.

• Rashes.

• Changes in the size and shape of the body part, particularly in the arms, face, legs, breasts, and waist.

Serious Side Effects:

Serious side effects can occur with Emtricitabine treatment. One should inform the doctor immediately and receive appropriate and prompt care.

Allergic Reaction:

Individuals who are allergic or hypersensitive to Emtricitabine can develop certain unwanted reactions. One must seek professional help if one has any of the following signs.

• Hives.

• Rashes.

• Difficulty breathing.

• Swelling of the lips, face, and throat.

Lactic Acidosis:

This form of metabolic disease results when lactic acid accumulates in the blood. The early symptoms associated with this condition could worsen over time, turning into fatal. Hence, one should get medical help with even milder symptoms.

• Muscle pain or weakness.

• Difficulty breathing.

• Nausea and vomiting.

• Stomach pain.

• Numbness or cold feelings in the extremities.

• Rapid or abnormal heart rate.

• Dizziness.

• Tiredness.

Liver Problems:

Inform the doctor if one has any symptoms of the liver problem. They include:

• Upper stomach pain.

• Swelling around the midsection of the abdomen.

• Dark urine.

• Loss of appetite.

• Nausea.

• Jaundice (yellowish discoloration of the skin and mucous membrane).

Emtricitabine might increase the risk of autoimmune disorders and certain infections by influencing the mechanism of the immune system. One could experience the symptoms in weeks or months following the initiation of Emtricitabine therapy. The signs include the following.

• Signs of new infection include night sweats, fever, mouth sores, swollen glands, stomach pain, diarrhea, and weight loss.

• Chest pain during breathing, wheezing, dry cough, and shortness of breath.

• Cold sores, sores on the anal or genital area.

• Rapid heart rate, irritability, weakness, balance problems, and problems with eye movement.

• Difficulty speaking, lower back pain, loss of bladder control.

• Swelling in the neck or throat, impotence, menstrual changes, and loss of interest in sex.

Dietetic and Other Restrictions:

Follow the usual dietary habits unless the healthcare professionals utter any control or restrictions. One should know that taking Emitricibitane medication will not usually prevent one from passing HIV infection to other people. So, one should not have unprotected sex and not share razors and toothbrushes. Discuss with the doctor about the safe ways to prevent human immunodeficiency (HIV) transmission during sex. Moreover, sharing the medicine needles and drugs is considered unsafe, even for healthier people.

Missed Dose:

One can take the missed dosage as soon as one has the thought. However, skip the missed dosage if it is nearly time for the subsequent dose of Emtricitabine. One should not take the double dosage of Emtricitabine medication to compensate for the forgotten dose.

Overdose:

In case of overdosage, seek emergency medical services or the poison helpline at the earliest. Call the healthcare provider or reach out to the nearest emergency room straight away if one takes too much Emtricitabine. Overdosage of Emtricitabine can cause serious effects, sometimes resulting in fatal. The healthcare professionals will monitor the individual for evidence of toxicity and start with a standard supportive intervention as required.

Storage

• Keep the Emtricitabine medication in its original packaging and keep the container firmly closed.

• Do not use the Emtricitabine medication if the seal over the container opening is missing or broken.

• Keep the Emtricitabine medication away from heat, sunlight, and moisture. Any medication should be stored away from the sight and reach of the children.

• Emtricitabine capsules should be stored at a room temperature of 68 to 77 degrees Fahrenheit.

• Emtricitabine oral solution should be stored in the refrigerator at 36 to 46 degrees Fahrenheit.

• One might also store Emtricitabine at room temperature within 68 to 77 degrees Fahrenheit for up to three months.

For Doctors:

Clinical Data of Emtricitabine

• Drug Name: Emtricitabine.

• Generic Name: Emtricitabine.

• Route of Administration: Oral.

• Drug Class: Nucleoside reverse transcriptase inhibitors (NRTIs).

• Molar Mass: 247.24 g.mol -1.

• Chemical Formula: C8H10FN3O3S.

Indication:

Emtricitabine, in combination with other medication, is indicated in the following conditions:

• Treatment of human immunodeficiency virus (HIV)-1 infection.

• Treatment of HIV-1 infection in pediatric populations of 25 to 35 kg (kilogram).

• Treatment of HIV-1 disease in adults of greater than 35 kg.

• Pre-exposure prophylaxis of HIV-1 in both adolescents and adults, except for those having receptive vaginal sex.

• Treatment of HIV-1 infection in children and adults of greater than 17 kg.

• Pre-exposure prophylaxis in both adolescents and adults greater than 35 kg.

• Treatment of HIV-1 infection in individuals greater than 12 years, weighing more than 35 kg, 25 kg, and 40 kg.

Associated Conditions:

• HIV transmission.

• Human immunodeficiency virus (HIV) infections.

• Human immunodeficiency virus type 1 infection.

• Pre-exposure prophylaxis.

Dose:

Testing the patients before the initiation of Emtricitabine treatment is required. So, test them for hepatitis B virus infection before the initial dosage. Emtricitabine is advised to be taken by mouth without regard to food. It is usually taken once daily.

Pediatric Patients (0 to 3 Months of Age):

• The recommended dosage for capsule form is one 200 mg (milligrams) capsule once daily orally.

• For oral solution form, the recommended dosage of Emtricitabine is 240 mg (24 milliliters) once daily orally.

Pediatric Patients (3 Months Through 17 Years):

• The recommended dosage for oral solution form is 3 mg per kg once daily.

Adult Patients:

• For oral solution form, the recommended dosage is 6 mg per kilogram up to a maximum range of 240 mg (24 milliliters) once daily orally.

• For Emtricitabine capsules, one 200 mg capsule once daily orally for pediatric patients weighing over 33 kilograms who could swallow the intact capsule.

Dosing Considerations:

The following dosing adjustments are considered in various stages associated with renal impairment.

• Creatinine clearance of 50 mL/min and more, 200 mg capsule once daily; 240 mg oral solution once daily.

• Creatinine clearance of 30 to 49 mL/min, 200 mg orally once 48 hours; 120 mg oral solution once daily.

• Creatinine clearance of 15 to 29 mL/min, 200 mg orally once in 72 hours; 80 mg oral solution orally once daily.

• Creatinine clearance of less than 15 mL/min, 200 mg capsule orally once in 96 hours; 60 mg oral solution once daily.

• For Emtricitabine administration on the day of hemodialysis, it is always recommended to administer it after the dialysis.

What Are the Pharmacological Aspects of Emtricitabine?

Pharmacodynamics:

Emtricitabine is typically a cytidine analog that contends with the natural substrate of the human immunodeficiency virus (HIV) -1 reverse transcriptase to be integrated into a new deoxyribonucleic acid (DNA), resulting in the termination of its transcription. Emtricitabine is generally administered once daily. Hence, it has a prolonged duration of action. Cautioning the patients about the risks associated with lactic acidosis and hepatomegaly is recommended.

Mechanism of Action:

Emtricitabine is a cytidine analog that generally competes with the deoxycytidine 5-triphosphate intended for HIV-1 reverse transcripts after being phosphorylated to Emtricitabine 5-triphosphate. Since HIV-1 reverse transcriptase integrates Emtricitabine with the newly formed DNA strands, new nucleotides could not be incorporated. This results in the termination of the viral DNA chain. In addition, reverse transcriptase inhibition circumvents the transcription of viral ribonucleic acid (RNA) into DNA. Hence, the virus loses the potential to incorporate its DNA with the host DNA, replicating host cell machinery. As a result, the virus load is reduced.

Pharmacokinetics:

Absorption:

• Emtricitabine attains a maximum od peak serum concentration (Cmax) of 1.8 mg/mL with a time-to-peak concentration of one to two hours.

• The area under the curve (AUC) of Emtricitabine is determined to be 10mg*hr/mL.

• The bioavailability of Emtricitabine capsules is about 93 percent, and that of the oral solution form is 75 percent.

• Intake of Emtricitabine with food could decrease the Cmax by 29 percent.

Distribution:

• The evident central volume of distribution of Emtricitabine is 42.3 liters, and the peripheral volume of distribution is around 55.4 liters.

• The plasma protein binding capacity of Emtricitabine is four percent.

• Emtricitabine binds chiefly with serum albumin.

Metabolism:

• Emtricitabine is not adequately metabolized. So, it is approximately 86 percent unmetabolized.

• Nearly nine percent of the dosage is metabolized to form 3-sulfoxide diastereomers, four percent into 2-O-glucuronide, and a minor proportion converts into 5-fluorocytosine.

Elimination:

• Nearly 86 percent of Emtricitabine is recovered in urine and 14 percent in feces.

• About 13 percent of the dosage is recovered in the urine through metabolites, nine percent as 3-sulfoxide diastereomers, and four percent as 2-O-glucuronide.

Half-Life and Clearance:

• The half-life period of Emtricitabine is nearly ten hours.

• Emtricitabine has an evident elimination rate of 15.1 liters/hour.

• The rate of elimination of Emtricitabine is closely related to creatinine clearance.

Toxicity:

• The median lethal dose (LD50) of the drug Emtricitabine is not readily available.

• The symptoms of toxicity of Emtricitabine include lactic acidosis as well as hepatotoxicity with steatosis.

• The treatment of overdosage includes symptomatic and supportive measures, encompassing hemodialysis.

Adverse Effects:

Emtricitabine can cause adverse effects. The following are the potential adverse effects based on the frequencies with the combination treatment.

Greater Than 10 Percent:

• Diarrhea.

• Headache.

• Dizziness.

• Rash.

• Insomnia.

• Nausea.

• Asthenia.

• Abdominal pain.

• Abnormal sleep patterns and dreams.

• Rhinitis.

• Increased creatinine kinase.

• Neuritis.

• Paresthesia.

• Cough.

One to Ten Percent:

• Dyspepsia.

• Symptoms associated with depression.

• Myalgia.

• Increased triglycerides level.

• vomiting.

Less Than One Percent:

• Severe lactic acidosis.

• Hepatomegaly with steatosis even with fatal cases.

• Severe and acute exacerbation of hepatitis B in individuals with co-infection of HIV-1 and Hepatitis B virus infection.

What Are the Contraindications of Emtricitabine?

The drug Emtricitabine is strictly contraindicated in individuals with hypersensitivity to Emtricitabine and any other components of the product.

Warnings and Precautions:

HBV Infection:

Every patient with HIV-1 infection should be tested for the manifestation of chronic hepatitis B virus (HBV) infection before the initiation of antiretroviral therapy. The safety and efficacy of Emtricitabine have not been established in people with coinfection of HIV-1 and HBV. For people infected with HBV infection, the exacerbations of hepatitis B were noticed in association with liver dysfunction and liver failure when treated with Emtricitabine. Hence, hepatic function should be closely monitored with laboratory and clinical follow-ups for a minimum of several months in people who are coinfected with both HBV and HIV-1. Discontinue the therapy if there is any change. Initiation of anti-hepatitis B treatment might be warranted if appropriate.

Lactic Acidosis and Hepatomegaly:

The clinical findings show the incidence of lactic acidosis and severe degrees of hepatomegaly with steatosis, even with fatal incidents when at nucleoside analogs, either solely or in conjugation with other antiretroviral drugs. It is recommended to suspend the treatment in any individual developing clinical or laboratory manifestations suggestive of lactic acidosis or hepatotoxicity. Hepatotoxicity markedly includes hepatomegaly and steatosis even without significant transaminase elevation.

Coadministration:

It should not be co-administered with the specified combination of antiretroviral agents constituting Lamivudine or Emtricitabine.

Renal Function:

Depending on the creatinine clearance rate, dosage adjustment and reduction are recommended in people with impaired renal function.

Immune Reconstitution Syndrome:

The risk and occurrence of immune reconstitution syndrome when combined with certain other antiretroviral drugs have been reported. The autoimmune disorders determined include polymyositis, Grace’s disease, and Guillain-Barré syndrome. Such problems have been reported to manifest in the setting of immune reconstitution. Nevertheless, the onset time is variable, occurring many months after initiating Emtricitabine therapy.

Specific Considerations:

• Geriatrics: The data does not provide adequate evidence showing the effect of Emtricitabine on geriatric patients. It is not determined whether the geriatric population responds differently from the adults. Generally, dosage selection for elderly patients should be cautiously made, considering the greater risk and frequency of renal, hepatic, and cardiac dysfunctions, concomitant conditions, and other drug treatments.

• Pregnancy: The clinical data from the registry shows that there is no increase in the overall risks of significant birth defects with the very first-trimester exposure to Emtricitabine. However, Emtricitabine should be prescribed considering the potential benefits and risks to the mother and the unborn baby.

• Lactation: It is recommended that HIV-1-infected women should not breastfeed to prevent the risk of postnatal transmission of HIV-1 infection. Hence, instruct mothers not to breastfeed during Emtricitabine treatment due to the risk of passing the virus into the infant.

• Renal Impairment: Modification of the dosage and dosing interval of Emtricitabine is recommended for people with creatinine clearance of less than 59 milliliters per minute and people with end-stage renal disorder requiring hemodialysis.