Odefsey

For the treatment of HIV-1 infection or for use in Pre-Exposure Prophylaxis (PrEP), the standard adult dosage of Emtricitabine is 200 mg taken orally once daily. In the context of PrEP, it is vital that the medication is taken every single day to maintain protective levels in the body tissues. Clinical trials have shown that the efficacy of PrEP is highly dependent on adherence; missing doses significantly increases the risk of HIV acquisition. When used for HIV treatment, Emtricitabine must be used as part of a multi-drug antiretroviral regimen. Your healthcare provider will select the specific combination based on your medical history and viral resistance testing.

Emtricitabine is approved for use in pediatric patients, including neonates. The dosage for children is typically calculated based on body weight to ensure safety and efficacy.

• Infants (0 to 3 months): The recommended dose using the oral solution is 3 mg/kg once daily.
• Children (3 months through 17 years): The recommended dose is 6 mg/kg once daily, up to a maximum of 200 mg.
• Children weighing more than 33 kg (73 lbs): May be prescribed the 200 mg capsule once daily if they are able to swallow capsules whole.

Healthcare providers must carefully monitor pediatric growth and development while the child is on this medication.

Renal Impairment

Because Emtricitabine is primarily cleared by the kidneys, patients with decreased kidney function require dosage interval adjustments to prevent drug accumulation and toxicity. According to the FDA-approved labeling, the following adjustments are recommended based on Creatinine Clearance (CrCl):

• CrCl 30–49 mL/min: 200 mg every 48 hours.
• CrCl 15–29 mL/min: 200 mg every 72 hours.
• CrCl <15 mL/min (including patients on hemodialysis): 200 mg every 96 hours.

For patients on hemodialysis, the dose should be administered after the dialysis session if the dose falls on a dialysis day.

Hepatic Impairment

No dosage adjustment is typically required for patients with hepatic (liver) impairment. However, since many patients taking Emtricitabine may also have chronic Hepatitis B or C, liver function must be monitored closely.

Elderly Patients

Clinical studies did not include enough subjects aged 65 and over to determine if they respond differently than younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Emtricitabine should be taken at the same time every day to maintain a consistent level of the drug in your system.

• With or Without Food: You may take the capsule or solution with or without a meal.
• Swallowing: Capsules should be swallowed whole. If you are using the oral solution, use a calibrated measuring device (not a household spoon) to ensure the correct dose.
• Storage: Store the capsules and solution at room temperature (25°C or 77°F). Brief excursions to 15-30°C are permitted. Keep the container tightly closed and out of reach of children.

If you miss a dose of Emtricitabine, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and continue with your regular schedule. Do not double the dose to catch up. Consistency is the most important factor in preventing viral resistance and ensuring the effectiveness of PrEP.

There is no specific antidote for Emtricitabine overdose. If an overdose occurs, the patient should be monitored for evidence of toxicity, and standard supportive treatment should be applied as necessary. Hemodialysis can remove approximately 30% of an Emtricitabine dose over a 3-hour period. If you suspect an overdose, contact your local poison control center or seek emergency medical attention immediately. Symptoms of overdose may include severe nausea, vomiting, or an intensification of common side effects.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop taking the medication without medical guidance, as this can lead to viral resistance or a 'flare-up' of underlying conditions like Hepatitis B.

In clinical trials, Emtricitabine was generally well-tolerated, but some patients experienced side effects, particularly during the first few weeks of treatment. Common side effects (occurring in more than 10% of patients) include:

• Headache: Often mild to moderate and may diminish over time.
• Diarrhea and Nausea: Gastrointestinal upset is common when starting ART. Taking the medication with food may help alleviate these symptoms.
• Fatigue and Dizziness: Some patients report feeling unusually tired or lightheaded.
• Insomnia and Abnormal Dreams: Difficulty sleeping or vivid dreams are occasionally reported, though these are more common when Emtricitabine is combined with Efavirenz.
• Rash: A mild skin rash may occur. If the rash becomes severe or is accompanied by fever, contact your doctor immediately.

• Hyperpigmentation: This is a unique side effect of Emtricitabine, characterized by darkening of the skin, particularly on the palms of the hands or the soles of the feet. It is more frequently observed in non-white patients and is generally considered harmless (cosmetic), though it can be distressing to some.
• Digestive Issues: Dyspepsia (indigestion), abdominal pain, and vomiting.
• Increased Cough and Rhinitis: Some patients may experience cold-like symptoms.
• Muscle Pain (Myalgia): General aches and pains in the muscles or joints.

• Anemia: A decrease in red blood cell count, which can lead to weakness and shortness of breath.
• Neutropenia: A decrease in white blood cells, which may increase the risk of infection.
• Pancreatitis: Inflammation of the pancreas, which presents as severe upper abdominal pain radiating to the back, often accompanied by nausea.

> Warning: Stop taking Emtricitabine and call your doctor immediately if you experience any of the following serious symptoms:

1. 1Lactic Acidosis: This is a rare but life-threatening buildup of acid in the blood. Symptoms include unusual tiredness, unexpected muscle pain, stomach pain with nausea and vomiting, feeling cold (especially in arms and legs), feeling dizzy or lightheaded, and a fast or irregular heartbeat.
2. 2Hepatotoxicity (Liver Toxicity): Signs include yellowing of the skin or whites of the eyes (jaundice), dark 'tea-colored' urine, light-colored bowel movements, and loss of appetite for several days.
3. 3Severe Allergic Reaction (Anaphylaxis): Symptoms include swelling of the face, lips, or tongue; difficulty breathing; or a severe, blistering skin rash.
4. 4Immune Reconstitution Inflammatory Syndrome (IRIS): In some patients with advanced HIV, the immune system may 'wake up' and begin to fight hidden infections, leading to a sudden onset of inflammatory symptoms. This requires medical evaluation but is often a sign that the medication is working.

• Fat Redistribution (Lipodystrophy): Long-term use of antiretroviral therapy has been associated with the redistribution of body fat. This may include loss of fat from the legs, arms, and face (lipoatrophy) and increased fat in the abdomen, neck ('buffalo hump'), and breasts.
• Bone Loss: While more commonly associated with Tenofovir (often taken with Emtricitabine), some studies suggest a potential for decreased bone mineral density over years of treatment.
• Kidney Function Changes: Prolonged use requires regular monitoring of serum creatinine and calculated creatinine clearance to ensure the kidneys are processing the drug safely.

Emtricitabine carries a FDA Black Box Warning regarding the post-treatment exacerbation of Hepatitis B. In patients co-infected with HIV-1 and HBV, stopping Emtricitabine has been associated with severe, acute exacerbations of Hepatitis B. These 'flare-ups' can lead to liver failure. If you have Hepatitis B and stop taking Emtricitabine, your doctor will need to monitor your liver function closely for several months through both clinical and laboratory follow-ups. If necessary, initiation of anti-hepatitis B therapy may be warranted.

Report any unusual symptoms or changes in your health to your healthcare provider immediately. Regular blood tests are necessary to monitor for these side effects.

Emtricitabine is a potent medication that requires careful medical supervision. It is not a cure for HIV-1 infection or AIDS. Patients must remain under the care of a physician experienced in treating infectious diseases. It is also important to understand that while taking Emtricitabine for PrEP reduces the risk of getting HIV, it does not protect against other sexually transmitted infections (STIs) such as syphilis, chlamydia, or gonorrhea. Consistent condom use and regular STI testing remain essential components of a comprehensive sexual health strategy.

Warning: Post-Treatment Exacerbation of Hepatitis B.

All patients should be tested for the presence of chronic Hepatitis B virus (HBV) before initiating antiretroviral therapy or PrEP. Emtricitabine is not approved for the treatment of chronic HBV infection. In patients co-infected with HIV-1 and HBV, severe acute exacerbations of Hepatitis B have been reported after the discontinuation of Emtricitabine. Liver function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are co-infected with HIV-1 and HBV and discontinue Emtricitabine. If appropriate, initiation of anti-Hepatitis B therapy may be warranted.

• Lactic Acidosis and Severe Hepatomegaly with Steatosis: Though rare, cases of lactic acidosis (buildup of acid in the blood) and severe liver enlargement with fat (steatosis) have been reported with the use of nucleoside analogs. This condition is more common in women and obese patients. Treatment should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.
• New Onset or Worsening Renal Impairment: Emtricitabine is eliminated through the kidneys. Impairment of renal function, including cases of acute renal failure and Fanconi syndrome (renal tubular injury), has been reported, particularly when used in combination with Tenofovir. Your doctor will assess your kidney function (CrCl) before and during treatment.
• Immune Reconstitution Syndrome: Patients with advanced HIV infection may experience an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia, or tuberculosis) shortly after starting ART. Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution.

To ensure the safe use of Emtricitabine, your healthcare provider will require regular laboratory monitoring, including:

• HIV Testing: For those on PrEP, HIV status must be confirmed every 3 months. Taking Emtricitabine while already having an undiagnosed HIV infection can lead to the development of drug-resistant virus.
• Renal Function: Serum creatinine and calculated creatinine clearance should be checked at baseline and periodically during treatment.
• Liver Function Tests (LFTs): Especially for patients with known Hepatitis B or C co-infection.
• Viral Load and CD4 Count: To monitor the effectiveness of HIV treatment.

Emtricitabine generally does not interfere with the ability to drive or operate machinery. However, some patients have reported dizziness or fatigue. If you experience these symptoms, avoid hazardous activities until you know how the medication affects you.

There are no known direct interactions between Emtricitabine and alcohol. However, excessive alcohol consumption can strain the liver and may interfere with your ability to adhere to a daily medication schedule. Discuss your alcohol intake with your doctor.

Never stop taking Emtricitabine without consulting your doctor. Sudden discontinuation can lead to a 'rebound' in viral load, increasing the risk of illness and transmission. For patients with Hepatitis B, stopping the drug can cause a life-threatening liver flare-up. If the drug must be stopped, your doctor will provide a specific plan for monitoring and potentially starting alternative medications.

> Important: Discuss all your medical conditions, especially kidney or liver disease, with your healthcare provider before starting Emtricitabine.

Emtricitabine should not be administered concurrently with other medications that contain Emtricitabine or its close chemical relative, Lamivudine (3TC). Because Lamivudine and Emtricitabine are both cytidine analogs and work via the same mechanism, taking them together provides no additional benefit and significantly increases the risk of toxicity. Common brand names containing these ingredients include Epivir, Combivir, Trizivir, and Epzicom.

While Emtricitabine does not interact with the Cytochrome P450 enzyme system, it is primarily excreted by the kidneys via glomerular filtration and active tubular secretion. Therefore, drugs that reduce renal function or compete for active tubular secretion may increase the concentration of Emtricitabine in the blood.

• Ganciclovir, Valganciclovir, and Cidofovir: These antiviral drugs are also renally cleared and may compete with Emtricitabine for excretion, potentially increasing the levels of both drugs and the risk of side effects.
• Acyclovir and Valacyclovir: Similar to ganciclovir, these may compete for renal elimination pathways.
• NSAIDs (Non-Steroidal Anti-Inflammatory Drugs): High doses or chronic use of drugs like ibuprofen or naproxen can impair kidney function, which in turn can slow the clearance of Emtricitabine.

• Orlistat: This weight-loss medication may decrease the absorption of antiretroviral drugs, potentially reducing their efficacy. Patients taking Orlistat should be monitored for changes in viral load.
• Aminoglycoside Antibiotics: Drugs like gentamicin or amikacin can be toxic to the kidneys (nephrotoxic), which may affect how the body processes Emtricitabine.

Emtricitabine has no significant interactions with specific foods. It can be taken with or without meals. Unlike some other HIV medications, it does not require a high-fat meal for absorption, nor is it affected by dairy or caffeine. However, maintaining a healthy, balanced diet is recommended to support overall immune health while managing HIV.

• St. John's Wort: While St. John's Wort is a potent inducer of CYP3A4 (which Emtricitabine does not use), it is often contraindicated with the other drugs that are typically paired with Emtricitabine in combination tablets (like Protease Inhibitors or NNRTIs). If you are taking a combination pill, you must avoid St. John's Wort.
• Creatine Supplements: High doses of creatine can affect serum creatinine laboratory readings, which your doctor uses to estimate your kidney function. Inform your doctor if you use these supplements.

Emtricitabine does not typically interfere with standard laboratory tests, other than the intended effects on viral load and CD4 counts. However, it can cause asymptomatic increases in creatine kinase (CK), which is an enzyme released when muscle tissue is damaged. If your CK levels are elevated, your doctor will investigate whether it is due to the medication, intense exercise, or another underlying cause.

For each major interaction, the management strategy usually involves either avoiding the combination or increasing the frequency of kidney function monitoring.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter pain relievers and vitamins.

Emtricitabine is absolutely contraindicated in patients with a known hypersensitivity (severe allergy) to Emtricitabine or any of the inactive ingredients in the formulation. An allergic reaction may manifest as a severe skin rash, hives, swelling of the face or throat, or difficulty breathing. If a hypersensitivity reaction occurs, the drug must be discontinued immediately and never restarted.

Another absolute contraindication is the use of Emtricitabine as monotherapy for the treatment of HIV-1 infection. Using only one drug to treat HIV allows the virus to quickly develop mutations that make it resistant to the medication. Once resistance develops, the drug will no longer work for that patient, and they may pass a resistant strain of the virus to others. For treatment, Emtricitabine must always be part of a complete antiretroviral regimen.

Relative contraindications require a careful risk-benefit analysis by a healthcare professional:

• Severe Renal Impairment (CrCl < 15 mL/min): While not an absolute contraindication, use in these patients requires significant dose interval adjustments and intense monitoring. In some cases, alternative medications with different clearance pathways may be preferred.
• Chronic Hepatitis B Co-infection: As mentioned in the Black Box Warning, the presence of HBV is not a reason to avoid Emtricitabine, but it is a reason for extreme caution. The risk of a severe liver flare-up upon discontinuation means that the patient must be committed to long-term adherence and follow-up.
• Lactic Acidosis Risk Factors: Patients with existing liver disease, obesity, or those taking other medications known to cause mitochondrial toxicity should be monitored more closely for the development of lactic acidosis.

There is a potential for cross-sensitivity between Emtricitabine and Lamivudine. Because these two drugs are chemically very similar, a patient who has had a severe allergic reaction to Lamivudine should not take Emtricitabine unless specifically directed by an allergist or infectious disease specialist under controlled conditions.

> Important: Your healthcare provider will evaluate your complete medical history, including any previous drug allergies and your current kidney and liver function, before prescribing Emtricitabine.

Emtricitabine is generally considered one of the safer antiretroviral drugs to use during pregnancy. It is classified as Pregnancy Category B (under the old FDA system). Extensive data from the Antiretroviral Pregnancy Registry (APR) has shown no increase in the risk of major birth defects when Emtricitabine is used during the first, second, or third trimesters compared to the background rate in the general population.

For pregnant individuals living with HIV, maintaining an undetectable viral load is the most effective way to prevent mother-to-child transmission of the virus. Therefore, healthcare providers often recommend continuing Emtricitabine-based therapy throughout pregnancy. There is no evidence of teratogenicity (harm to the fetus) in animal studies at doses much higher than human therapeutic levels.

In the United States and other regions where safe infant formula and clean water are available, the CDC and many medical associations recommend that individuals with HIV avoid breastfeeding to eliminate the risk of postnatal HIV transmission. Emtricitabine is known to pass into human breast milk. While the effects on the nursing infant are generally considered low-risk, the primary concern remains the potential for the infant to acquire HIV through breast milk or to develop drug-resistant HIV if they are infected. If you are taking Emtricitabine for PrEP and are HIV-negative, discuss the risks and benefits of breastfeeding with your doctor.

Emtricitabine is FDA-approved for use in pediatric patients from birth through adolescence. It is available in an oral solution specifically for infants and children who cannot swallow pills. Clinical trials have demonstrated that the safety and efficacy profile in children is similar to that in adults. The most common side effect reported in children is hyperpigmentation (skin darkening). Pediatric patients must have their doses adjusted as they grow and gain weight to ensure they continue to receive an effective amount of the medication.

There is limited data on the use of Emtricitabine specifically in patients over the age of 65. However, older adults are more likely to have decreased kidney function (reduced GFR). Since Emtricitabine is cleared by the kidneys, elderly patients are at a higher risk of drug accumulation and toxicity. Healthcare providers should assess renal function before starting the drug and monitor it frequently. Additionally, older patients may be taking multiple other medications (polypharmacy), increasing the potential for drug interactions involving the kidneys.

Renal impairment is a significant consideration for Emtricitabine. For patients with a Creatinine Clearance (CrCl) below 50 mL/min, the dosing interval must be extended (e.g., taking the pill every 48, 72, or 96 hours instead of every 24 hours). For patients on hemodialysis, the drug is partially removed during the procedure, so the dose should be administered after the dialysis session. Failure to adjust the dose in renal impairment can lead to high blood levels of the drug, increasing the risk of side effects like headache and gastrointestinal distress.

No dose adjustment is required for patients with liver impairment. However, as noted, patients with Hepatitis B must be monitored for liver 'flares' if the drug is stopped. The pharmacokinetics of Emtricitabine have not been specifically studied in patients with severe hepatic impairment (Child-Pugh Class C), so caution is still advised in this population.

> Important: Special populations require individualized medical assessment and frequent monitoring to ensure the safest possible treatment outcome.

Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI). Its molecular structure is 5-fluoro-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. The addition of the fluorine atom at the 5-position of the cytidine ring increases its potency and extends its intracellular half-life compared to older analogs like Lamivudine.

Once inside the host cell, Emtricitabine is phosphorylated by cellular kinases (deoxycytidine kinase, cytidylate kinase, and nucleoside diphosphate kinase) into its active form: emtricitabine 5'-triphosphate. This active metabolite inhibits the HIV-1 reverse transcriptase enzyme by competing with the natural deoxycytidine 5'-triphosphate. Once the enzyme incorporates emtricitabine 5'-triphosphate into the viral DNA, the lack of a 3'-OH group prevents the formation of a 5' to 3' phosphodiester bond. This causes obligate chain termination, effectively stopping the synthesis of viral DNA and preventing the virus from integrating into the host genome.

Emtricitabine shows high antiviral activity against HIV-1, with IC50 values (the concentration needed to inhibit 50% of viral replication) in the low micromolar range. It is also active against the Hepatitis B virus (HBV). The relationship between the concentration of the drug in the blood and its effect is well-established; however, the intracellular concentration of the triphosphate form is the most accurate predictor of antiviral efficacy. Because of its high potency and long intracellular half-life, the drug provides sustained suppression of viral replication throughout a 24-hour dosing interval.

| Parameter | Value |

|---|---|

| Bioavailability | ~93% |

| Protein Binding | < 4% |

| Half-life (Plasma) | ~10 hours |

| Half-life (Intracellular) | ~39 hours |

| Tmax | 1–2 hours |

| Metabolism | Minimal (not CYP dependent) |

| Excretion | Renal (86%), Fecal (14%) |

• Molecular Formula: C8H10FN3O3S
• Molecular Weight: 247.24 g/mol
• Solubility: Soluble in water (approx. 112 mg/mL at 25°C).
• Structure: It is a white to off-white crystalline powder. It is the (-) enantiomer of a thio analog of cytidine.

Emtricitabine is a Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor [EPC]. It is closely related to Lamivudine (3TC) but is generally considered more potent. It is a core component of many 'single-tablet regimens' (STRs) used in modern HIV management. Within the NRTI class, it is often paired with a nucleotide analog like Tenofovir to provide a 'backbone' for antiretroviral therapy.