Abacavir

For the treatment of HIV-1 infection in adults, the standard recommended dosage of Abacavir is 600 mg daily. This can be administered in one of two ways, depending on patient preference and adherence history:

• Once-Daily Dosing: 600 mg (two 300 mg tablets) taken once per day.
• Twice-Daily Dosing: 300 mg (one tablet) taken twice per day.

Clinical trials have shown that both dosing schedules are equally effective in maintaining viral suppression. Your healthcare provider will help you decide which schedule fits your lifestyle best. If you are taking a fixed-dose combination (like Epzicom), the dosage is typically one tablet once daily.

Abacavir is approved for use in infants and children at least 3 months of age. Dosing in children is highly individualized and is based on the child's body weight.

• Infants (3 months and older) and Children: The standard dose is 8 mg per kg of body weight, administered twice daily.
• Maximum Dose: The total pediatric dose should not exceed 300 mg twice daily (600 mg total per day).
• Formulation: For children who cannot swallow tablets, the oral solution (20 mg/mL) should be used to ensure accurate measurement. Healthcare providers often recommend using a calibrated oral syringe rather than a household teaspoon for dosing.

Renal Impairment

For patients with kidney dysfunction (renal impairment), no dosage adjustment of Abacavir is typically required. Because Abacavir is primarily metabolized by enzymes and not cleared as an unchanged drug by the kidneys, even patients with end-stage renal disease (ESRD) can usually take the standard dose. However, your doctor will monitor your overall health closely.

Hepatic Impairment

Because the liver is the primary site of Abacavir metabolism, patients with liver disease require careful management:

• Mild Hepatic Impairment (Child-Pugh Class A): The dose is reduced to 200 mg twice daily. Since the 300 mg tablets cannot be easily split into this specific dose, the oral solution is often required for these patients.
• Moderate to Severe Hepatic Impairment (Child-Pugh Class B or C): Abacavir is contraindicated (should not be used) in these patients due to the risk of drug accumulation and toxicity.

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, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

• Consistency: Take Abacavir at the same time(s) every day. Consistency is vital for maintaining a steady level of the drug in your system to prevent the virus from mutating and becoming resistant.
• Food: You may take Abacavir with or without food. If the medication causes an upset stomach, taking it with a meal may help.
• Swallowing: Tablets should ideally be swallowed whole with water. If you have difficulty swallowing, discuss using the oral solution with your pharmacist.
• Storage: Store Abacavir at room temperature (20°C to 25°C or 68°F to 77°F). Keep the bottle tightly closed and away from moisture.

If you miss a dose of Abacavir, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and return to your regular schedule. Do not double the dose to catch up. Frequent missed doses can lead to treatment failure and drug resistance, making the HIV harder to treat in the future.

There is no specific antidote for an Abacavir overdose. If an overdose occurs, the patient should be monitored for signs of toxicity (specifically the hypersensitivity reaction or lactic acidosis) and provided with standard supportive care. If you suspect an overdose, contact your local poison control center or seek emergency medical attention immediately.

> 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 cause the virus to become resistant to treatment.

Most patients tolerate Abacavir well, but some may experience mild to moderate side effects, especially during the first few weeks of therapy. Common side effects include:

• Nausea and Vomiting: This is the most frequently reported side effect. It usually subsides as the body adjusts to the medication.
• Headache: Often described as a dull ache, this typically improves over time.
• Malaise and Fatigue: A general feeling of being unwell or tired. If this is accompanied by a fever, it must be reported to a doctor immediately.
• Dreams and Sleep Disturbances: Some patients report vivid dreams or difficulty falling asleep.

• Insomnia: Persistent difficulty sleeping.
• Dizziness: A feeling of lightheadedness or spinning.
• Fever and Chills: These can occur independently but are also hallmark signs of the more serious hypersensitivity reaction.
• Gastrointestinal Distress: Including diarrhea, abdominal pain, and loss of appetite (anorexia).

• Pancreatitis: Inflammation of the pancreas, characterized by severe upper abdominal pain that radiates to the back.
• Erythema Multiforme: A skin reaction that can cause 'target' lesions.
• Stevens-Johnson Syndrome (SJS): A very rare but life-threatening skin condition.

> Warning: Stop taking Abacavir and call your doctor immediately if you experience any of these symptoms. These may be signs of a life-threatening reaction.

1. 1Hypersensitivity Reaction (HSR): This is the most critical risk associated with Abacavir. It typically occurs within the first six weeks of treatment. Symptoms usually appear in at least two of the following groups:

• Group 1: Fever.
• Group 2: Rash.
• Group 3: Gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain).
• Group 4: Constitutional symptoms (generalized malaise, fatigue, achiness).
• Group 5: Respiratory symptoms (shortness of breath, cough, sore throat).

1. 1Lactic Acidosis: A buildup of lactic acid in the blood. Symptoms include unusual tiredness, unexpected muscle pain, stomach pain with nausea/vomiting, feeling cold, dizziness, or a fast/irregular heartbeat.
2. 2Hepatotoxicity (Liver Toxicity): Signs include yellowing of the skin or eyes (jaundice), dark urine, light-colored stools, and pain on the right side of the stomach area.
3. 3Immune Reconstitution Inflammatory Syndrome (IRIS): When the immune system recovers, it may respond aggressively to previously hidden infections (like tuberculosis or fungal infections), causing new inflammatory symptoms.

• Lipodystrophy: Changes in body fat distribution, such as loss of fat from the legs, arms, and face, and increased fat in the abdomen or back of the neck ('buffalo hump').
• Cardiovascular Risk: Some observational studies (such as the D:A:D study) have suggested a potential link between Abacavir use and an increased risk of myocardial infarction (heart attack). While this remains a subject of clinical debate, patients with existing heart disease risk factors should be monitored closely.

Abacavir carries two prominent FDA Black Box Warnings:

1. 1Hypersensitivity Reactions: Fatal hypersensitivity reactions have been associated with Abacavir. Patients who carry the HLA-B5701 allele are at high risk. Screening for this allele is mandatory. If a reaction is suspected, Abacavir must be discontinued immediately and NEVER* restarted, as re-exposure can cause a fatal drop in blood pressure (anaphylaxis) within hours.
2. 2Lactic Acidosis and Severe Hepatomegaly with Steatosis: Though rare, these conditions can be fatal. They occur more frequently in women and obese patients. Treatment should be suspended if clinical or laboratory findings suggest these conditions.

Report any unusual symptoms to your healthcare provider. You are encouraged to report negative side effects of prescription drugs to the FDA at 1-800-FDA-1088.

Before starting Abacavir, it is imperative that you and your healthcare provider discuss your complete medical history. Abacavir is a potent medication that requires strict adherence and specific genetic screening to ensure safety. The most critical safety requirement is the HLA-B*5701 genetic test. This test identifies individuals who are genetically predisposed to a severe, potentially fatal allergic reaction to Abacavir. If you test positive for this marker, you must not take Abacavir.

1. Hypersensitivity Reactions:

Serious and sometimes fatal hypersensitivity reactions have occurred with Abacavir. These reactions usually involve multiple organ systems. Symptoms often include fever, rash, nausea, vomiting, malaise, or shortness of breath. If you develop symptoms from two or more of these groups while taking Abacavir, stop the drug immediately and contact your doctor. Never restart Abacavir if you have had a hypersensitivity reaction to it, as the second exposure can cause life-threatening hypotension (low blood pressure) and death.

2. Lactic Acidosis and Liver Enlargement:

Lactic acidosis (acid buildup in the blood) and severe liver enlargement with fat (steatosis) have been reported with the use of NRTIs like Abacavir. This is a medical emergency that requires immediate hospitalization.

• Allergic Reactions / Anaphylaxis: Beyond the specific HLA-B*5701 reaction, standard allergic reactions can occur. Always carry your 'Abacavir Warning Card' provided by your pharmacist.
• Hepatotoxicity: Patients with pre-existing liver conditions, such as Hepatitis B or C, are at a higher risk for liver-related complications. Liver function tests (LFTs) will be monitored regularly.
• Cardiovascular Risk: There is ongoing clinical discussion regarding whether Abacavir increases the risk of heart attacks. If you have high blood pressure, high cholesterol, diabetes, or smoke, discuss these risks with your cardiologist before starting Abacavir.
• Immune Reconstitution Syndrome: As your immune system strengthens, it may begin to fight 'opportunistic infections' that were already in your body, leading to sudden inflammation. This is not a reason to stop the drug, but it requires medical management.

Your healthcare provider will require regular blood tests to ensure the medication is working and that you are staying healthy. These include:

• Viral Load (HIV-1 RNA): To measure how much virus is in your blood.
• CD4+ Cell Count: To measure the strength of your immune system.
• Liver Function Tests (ALT, AST, Bilirubin): To monitor for hepatotoxicity.
• Basic Metabolic Panel: To check kidney function and electrolyte balance.
• Lactate Levels: If symptoms of lactic acidosis appear.

Abacavir is not generally known to cause significant impairment in the ability to drive or operate heavy machinery. However, side effects like dizziness or fatigue can occur. You should assess how you feel on the medication before engaging in potentially dangerous activities.

Alcohol (ethanol) significantly interacts with Abacavir. Alcohol is processed by the same enzyme (alcohol dehydrogenase) that breaks down Abacavir. Consuming alcohol while taking Abacavir can increase the concentration of Abacavir in your blood by about 41%. While this is not usually toxic, it may increase the risk of side effects. It is best to limit alcohol consumption.

Never stop taking Abacavir without consulting your doctor. Stopping the medication suddenly can cause the HIV virus to 'rebound,' leading to a rapid increase in viral load and a drop in CD4 cells. Furthermore, if you stop Abacavir because of a suspected allergic reaction, restarting it can be fatal.

> Important: Discuss all your medical conditions, including any history of liver disease, heart disease, or kidney problems, with your healthcare provider before starting Abacavir.

While Abacavir has fewer drug interactions than many other HIV medications, certain combinations are strictly avoided:

• Other Abacavir-containing products: Do not take Abacavir (Ziagen) if you are already taking a combination pill that contains abacavir, such as Epzicom, Trizivir, or Triumeq. This leads to an overdose.
• Riociguat: Some studies suggest that Abacavir may increase the levels of Riociguat (used for pulmonary hypertension), potentially leading to dangerously low blood pressure. Use with extreme caution or avoid if possible.

• Methadone: Abacavir may slightly increase the clearance of methadone in some patients. While most people do not need a dose adjustment, some may experience mild withdrawal symptoms and require a higher dose of methadone. Your doctor should monitor you closely during the first few weeks of co-administration.
• Ethanol (Alcohol): As mentioned, alcohol increases the 'Area Under the Curve' (AUC) of Abacavir by approximately 41%. This occurs because alcohol competes for the enzyme alcohol dehydrogenase. While the dose of Abacavir does not typically need to be changed, the risk of side effects is higher.

• Tipranavir/Ritonavir: This combination of protease inhibitors may slightly decrease the plasma concentrations of Abacavir. Usually, this is not clinically significant enough to change the dose, but viral load should be monitored.
• Phenytoin: There is a theoretical risk that Abacavir could alter the levels of this anti-seizure medication. Monitoring of phenytoin levels is recommended.

• General Meals: Abacavir can be taken with or without food. High-fat meals do not significantly alter the absorption of the drug.
• Grapefruit: Unlike many other medications, Abacavir is not affected by grapefruit juice because it does not rely on the CYP3A4 enzyme system.

• St. John's Wort: While St. John's Wort is a potent inducer of CYP enzymes, it does not have a major direct effect on Abacavir metabolism. However, it does interact with many other HIV drugs often taken alongside Abacavir (like Protease Inhibitors or Integrase Inhibitors). Therefore, St. John's Wort is generally avoided in HIV-positive patients to prevent overall treatment failure.
• Sorbitol: Some liquid medications or sugar-free supplements contain sorbitol. Co-administration of sorbitol-containing solutions with Abacavir oral solution may slightly decrease Abacavir levels. This is usually only a concern with chronic, high-volume use of sorbitol.

• Creatine Phosphokinase (CPK): Abacavir can occasionally cause elevations in CPK levels, which might be misinterpreted as a sign of muscle injury or heart attack.
• Liver Function Tests: As noted, elevations in ALT, AST, and bilirubin may occur and require clinical correlation with the patient's liver health.

Mechanism of Interactions

Most interactions with Abacavir occur through enzymatic competition. Because Abacavir is metabolized by alcohol dehydrogenase and glucuronyltransferase, drugs that inhibit or induce these specific pathways can change how much Abacavir stays in your system. Unlike many other drugs, Abacavir does not significantly inhibit or induce the Cytochrome P450 system, which is why it has a relatively 'clean' interaction profile compared to other antiretrovirals.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. This includes over-the-counter vitamins and 'natural' remedies, as they can still interfere with your HIV treatment.

There are several situations where Abacavir must NEVER be used due to the extreme risk of life-threatening complications:

1. 1HLA-B*5701 Positive Status: Any patient who tests positive for the HLA-B*5701 genetic allele must never be prescribed Abacavir. Clinical data shows that nearly 100% of patients with this marker who are exposed to Abacavir will develop a serious hypersensitivity reaction. Screening is a mandatory standard of care globally.
2. 2Previous Hypersensitivity Reaction to Abacavir: If a patient has ever had a suspected or confirmed allergic reaction to Abacavir (or any product containing it, like Epzicom), they must never take it again. Re-challenging a patient with Abacavir after a reaction can lead to fatal anaphylaxis and cardiovascular collapse within minutes to hours.
3. 3Moderate to Severe Hepatic Impairment: Patients with Child-Pugh Class B or C liver disease should not use Abacavir. Because the liver is responsible for the drug's metabolism, impaired function leads to toxic accumulation of the drug in the blood, significantly increasing the risk of lactic acidosis and liver failure.

These are conditions where the use of Abacavir requires a careful risk-benefit analysis by a specialist:

• High Cardiovascular Risk: For patients with a high risk of heart attack (e.g., those with multiple risk factors like smoking, uncontrolled hypertension, or recent cardiac events), healthcare providers may prefer alternative NRTIs like Tenofovir, provided they are suitable for the patient's renal profile.
• Mild Hepatic Impairment: Requires a specific dose reduction (200 mg twice daily) and frequent monitoring. If the patient cannot be monitored closely, Abacavir may be avoided.

There is no known cross-sensitivity between Abacavir and other classes of HIV medications (like Protease Inhibitors or NNRTIs). However, there is a strong cross-sensitivity between different brands of Abacavir. If you are allergic to Ziagen, you are also allergic to Epzicom, Trizivir, and Triumeq. Always inform all healthcare providers, including dentists and surgeons, of your Abacavir allergy status.

> Important: Your healthcare provider will evaluate your complete medical history, including genetic testing and liver function, before prescribing Abacavir to ensure it is safe for you.

Abacavir is commonly used during pregnancy to prevent mother-to-child transmission of HIV.

• Pregnancy Category: While the FDA has transitioned away from letter categories, Abacavir is generally considered safe when the benefits of controlling the HIV infection outweigh the risks.
• Antiretroviral Pregnancy Registry (APR): Data from thousands of pregnancies have shown no significant increase in the risk of major birth defects with Abacavir compared to the general population.
• Clinical Considerations: It is vital for pregnant women to maintain an undetectable viral load to protect the health of the infant. Abacavir is often a preferred component of pregnancy-safe HIV regimens.

• Transmission Risk: In the United States and other regions where safe infant formula and clean water are available, the CDC and medical guidelines generally recommend that women with HIV avoid breastfeeding to eliminate the risk of postnatal HIV transmission.
• Drug Passage: Abacavir is excreted into human breast milk. The effects of this exposure on the nursing infant are not fully known, but the primary concern remains the transmission of the virus itself.

• Approved Age: Abacavir is FDA-approved for infants as young as 3 months of age.
• Dosing: Pediatric dosing must be carefully calculated based on weight (mg/kg). As children grow, their dose must be adjusted frequently by their pediatrician.
• Safety: The safety profile in children is similar to that in adults, though gastrointestinal side effects may be more common in younger children using the oral solution.

• Pharmacokinetics: Older adults may have age-related declines in liver or kidney function. While Abacavir doesn't require renal adjustment, the overall 'pill burden' and potential for drug interactions in seniors (polypharmacy) require careful management.
• Cardiac Health: Since seniors are at higher risk for cardiovascular disease, the potential link between Abacavir and myocardial infarction should be discussed thoroughly.

• Adjustment: No dose adjustment is needed for patients with kidney disease or those on hemodialysis. This makes Abacavir a useful option for HIV patients who cannot take Tenofovir (which is associated with kidney toxicity).

• Mild (Child-Pugh A): Requires a dose reduction to 200 mg twice daily. This requires the use of the oral solution for precise dosing.
• Moderate/Severe (Child-Pugh B/C): Use is contraindicated. The risk of lactic acidosis is significantly elevated in these patients.

> Important: Special populations, particularly pregnant women and those with liver disease, require individualized medical assessment and frequent monitoring by an HIV specialist.

Abacavir is a carbocyclic synthetic nucleoside analogue. Its primary target is the HIV-1 Reverse Transcriptase enzyme.

1. 1Intracellular Uptake: Abacavir enters the host cell (CD4+ T-cell) via passive diffusion.
2. 2Triphosphorylation: It is converted by cellular kinases into its active metabolite, carbovir triphosphate (CBV-TP).
3. 3Competitive Inhibition: CBV-TP competes with the natural substrate deoxyguanosine triphosphate (dGTP) for incorporation into the viral DNA chain.
4. 4Chain Termination: Once incorporated, the lack of a 3'-OH group on the Abacavir molecule prevents the formation of a phosphodiester bond with the next incoming nucleotide. This stops the synthesis of viral DNA, effectively 'breaking' the replication cycle.

• Antiviral Effect: The relationship between Abacavir plasma concentrations and the antiviral effect is complex because the active form is intracellular.
• Resistance: Resistance to Abacavir typically develops through mutations in the HIV reverse transcriptase gene, most notably the K65R, L74V, F115N, and M184V mutations. Regular viral load monitoring ensures the drug remains effective.

| Parameter | Value |

|---|---|

| Bioavailability | ~83% (Oral) |

| Protein Binding | ~49% to 50% |

| Half-life (Plasma) | ~1.5 hours |

| Half-life (Intracellular) | ~12 to 20 hours |

| Tmax (Time to peak) | 0.6 to 1.0 hours |

| Metabolism | Alcohol dehydrogenase & Glucuronyltransferase |

| Excretion | Renal 83% (as metabolites), Fecal 16% |

• Molecular Formula: (C14H18N6O)2 · H2SO4 (as sulfate)
• Molecular Weight: 670.76 g/mol (Sulfate salt); 286.33 g/mol (Base)
• Solubility: Soluble in water (approx. 77 mg/mL at 25°C).
• Structure: A guanosine analogue where the ribose ring is replaced with a cyclopentene ring, providing greater stability against enzymatic degradation.

Abacavir is classified as a Nucleoside Reverse Transcriptase Inhibitor (NRTI). It is often grouped with other NRTIs like Lamivudine (3TC), Tenofovir (TDF/TAF), and Emtricitabine (FTC). Within the EPC classification, it is noted as a Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor.