What Is Abacavir Sulfate?

Abacavir sulfate tablets, the indication is to treat adults infected with human immunodeficiency virus (HIV), with antiretroviral combination therapy. The confirmation of the efficacy of this product is mainly based on the results of studies with patients who have never received treatment before in combination with lamivudine and zidovudine.

Abacavir sulfate tablets, the indication is to treat adults infected with human immunodeficiency virus (HIV), with antiretroviral combination therapy. The confirmation of the efficacy of this product is mainly based on the results of studies with patients who have never received treatment before in combination with lamivudine and zidovudine.

Drug Name

Abacavir sulfate

Drug type

Prescription medicines, essential medicines, medicines for medical workers' injuries

Use classification

Reverse transcriptase inhibitor

Abacavir sulfate tablets ingredients

The main ingredient of this product is abacavir sulfate, and its chemical name is: (1S, cis) -4- [2-amino-6- (cyclopropylamino) -9Hpurine-9-yl] -2-cyclo Pentene-1-methanol sulfate (2: 1). Molecular formula: C ₁₄ H ₁₈ N ₆ O ₂ · H ₂ SO ₄ , molecular weight: 670.76.

Traits of Abacavir Sulfate

This product is a yellow, biconvex, capsule film-coated tablet with "GX 623" engraved on one side.

Indications of abacavir sulfate

Human immunodeficiency virus (HIV) infected adults are treated with antiretroviral combination therapy.
The confirmation of the efficacy of this product is mainly based on the results of studies with patients who have never received treatment before in combination with lamivudine and zidovudine.

Abacavir sulfate tablets dosage

The recommended adult dose is 300 mg (1 tablet) twice daily. Can be taken with or without food. For patients who should not take tablets, oral solutions are available.
Renal damage: Patients with poor renal function do not need to adjust the dose, but patients with advanced kidney disease should avoid taking it.
Liver damage: Abacavir is mainly metabolized by the liver. No dose adjustment is necessary for patients with mild liver impairment. For patients with moderate liver damage, there is no supporting information on taking this product, so the above patients should be avoided. Patients with severe liver impairment should not take it.

Adverse effects of abacavir sulfate tablets

For many adverse reactions, it is unclear whether they are related to this product, or to many other drugs used to treat HIV diseases, or are the result of the disease progression itself.
The following adverse reactions occur in more than 10% of patients and may be related to this product: nausea, vomiting, lethargy and fatigue. Other common adverse reactions are: fever, headache, diarrhea, and anorexia. In short, adverse reactions are transient and do not limit treatment. Most are mild or moderate.
In controlled clinical studies, laboratory examinations related to the treatment of this product are rare and their incidence is not different between the treated patients and the control group.
There have been cases of lactic acidosis with nucleoside analogs that are sometimes fatal and are usually associated with severe hepatomegaly and hepatic steatosis.
Allergic reactions: In clinical studies, approximately 3% of subjects receiving abacavir treatment experienced allergic reactions, some of which were life-threatening and, despite caution, caused fatal consequences. Allergic reactions are characterized by symptoms that indicate involvement of multiple organs or multiple systems in the body. Fever and / or rash (usually maculopapular and urticaria) are part of the syndrome in all patients with allergic reactions. Other common symptoms and signs include gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain), lethargy, and discomfort. Allergic reactions without rash and fever have also occurred.
Other symptoms and signs may include respiratory symptoms (dyspnea, cough, shortness of breath), musculoskeletal symptoms (myalgia, arthralgia), headache, paresthesia, and edema. Physical examination revealed lymphangular disease, occasional mucosal damage (conjunctivitis and oral ulcers), and hypotension.
Laboratory abnormalities associated with abacavir allergic reactions include liver function tests, creatine phosphokinase, elevated creatinine, or decreased lymphocytes. Allergic reactions have been reported with renal failure and sensitization. Some allergic reactions are initially thought to be viral infections, such as flu-like symptoms, gastroenteritis, and respiratory symptoms, so patients with these symptoms need to be closely monitored. Symptoms usually occur within the first 6 weeks of initiating abacavir therapy (on average, on the 11th day after initiating treatment), and can also occur at any time during the course of treatment. It is necessary to monitor the patient closely during the first two months of treatment, with consultations every 2 weeks.
The risk factors for the occurrence of abacavir allergic reactions and their severity have not been confirmed, but intermittent treatment is likely to increase the risk of sensitization and cause clinically significant allergic reactions. Patients should be informed about the importance of taking this product regularly.
Continue to receive this product for treatment, symptoms related to allergic reactions will worsen, and usually recover after stopping the drug.
Restarting treatment after an allergic reaction can cause symptoms to reappear within hours. This relapse of an allergic reaction is usually more severe than when it first appears, and life-threatening hypotension and death can occur.
Patients with the above-mentioned allergic reactions must stop using this product and must not restart it. All patients should be warned of an allergic reaction to abacavir.

Abacavir sulfate taboo

This product is contraindicated in any patient who is known to be allergic to abacavir, or allergic to any of the ingredients in abacavir tablets. Disabled in patients with severe liver impairment.

Precautions for Abacavir Sulfate

This product should be prescribed by a physician experienced in treating HIV infection.
Allergic reactions In clinical studies, about 3% of the subjects receiving abacavir experienced an allergic reaction, which was life-threatening in some cases, and despite careful measures, it still caused fatal consequences. An allergic reaction is indicated by symptoms of multiple organ involvement. Most allergic reactions are manifested as fever and / or rash. Other common symptoms and signs of allergic reactions include gastrointestinal symptoms such as nausea, vomiting, diarrhea or abdominal pain, lethargy and discomfort (see Adverse Reactions).
Symptoms of an allergic reaction usually occur within the first 6 weeks of treatment with abacavir, and can occur at any time during the treatment. Close medical monitoring of patients receiving abacavir should be conducted, especially in the first 2 months, with consultations every two weeks.
Special care should be taken when receiving abacavir and other drugs known to cause skin toxicity (such as non-nucleoside reverse transcriptase inhibitors). Because it is difficult to tell whether the rash is caused by other medicines or an allergy to abacavir.
If the patient is diagnosed with an allergic reaction during treatment, abacavir must be stopped immediately.
Patients who have discontinued this product due to an allergic reaction should never use this product again. Restarting the product after an allergic reaction will cause symptoms to quickly reappear within hours. The recurrence of an allergic reaction is usually more severe than when it first occurs and can be life threatening or fatal.
The doctor must ensure that the patient is fully informed of the following allergic reactions:
Patients should be aware that an allergic reaction to abacavir may cause life-threatening or death.
Inform patients of the importance of taking this product regularly.
Patients must contact a doctor immediately if they develop signs and symptoms that may be related to an allergic reaction.
All patients should be reminded to read the instructions in the box of this product. A warning card is included in the box. Patients should be reminded to always carry this card with them.
To avoid re-taking this product, patients with allergic reactions should be required to return the remaining tablets and oral liquids to the pharmacy.
Patients received nucleoside drugs for treatment. There were reports of lactic acidosis (hypoxemia), usually accompanied by severe hepatomegaly and fatty liver, and sometimes death. Taking nucleosides should be discontinued when there is a rapid rise in transaminase, progressive hepatomegaly, or unexplained metabolic / lactic acidosis. Benign gastrointestinal symptoms, such as nausea, vomiting, and abdominal pain, suggest the possibility of lactic acidosis. Patients with hepatomegaly, hepatitis and other liver diseases with known risk factors (especially obese women) should be careful with nucleosides. These patients should be followed closely.
The current data does not support the use of this product in patients with moderate hepatic impairment, so the above patients should be avoided.
Patients with advanced kidney disease should not take it.
Patients receiving this product or any other antiretroviral treatment may still experience opportunistic infections and other complications of HIV infection. Therefore, close clinical monitoring of patients should be maintained by experienced physicians treating HIV-related diseases.
Patients should be informed that current antiretroviral therapies, including this product, have not been shown to prevent the danger of HIV transmission to others through sexual contact or blood contamination. Appropriate precautions should continue to be taken.
Impact on the ability to drive or manipulate a machine Abacavir's study on the ability to drive or manipulate a machine has not been conducted.

Abacavir sulfate tablets for pregnant and lactating women

Pregnancy: The safety of human use of abacavir during pregnancy has not been established. Animal experiments have shown that abacavir and / or its related metabolites can be transmitted through the placenta. Toxicity to developing embryos and fetuses has been shown in rat experiments, but not in rabbits. These toxicity manifestations include reduced fetal weight, fetal edema and bone changes / malformations, early intrauterine death and stillbirth. This product is not recommended for pregnant women.
Lactation: Abacavir and its metabolites can be secreted into the milk of lactating rats. The drug and its metabolites are expected to be secreted into human milk, but this conclusion has not been confirmed. There are no safety data on the use of abacavir in infants younger than 3 months. It is therefore recommended that mothers receiving abacavir not breastfeed their babies. At the same time, to avoid transmission of HIV, mothers who may be infected with HIV are advised not to breastfeed their babies.

Abacavir sulfate tablets for children

There is no sufficient information, so this product is not recommended for children. It is difficult to identify allergic reactions in these patients.

Abacavir sulfate tablets for elderly

Abacavir pharmacokinetic studies have not been performed in patients over 65 years of age.

Abacavir sulfate tablets drug interactions

Based on the results of abacavir in vitro tests and its main metabolic pathways, it is unlikely that P450 mediates its interaction with other drugs. The cytochrome P450 enzyme system does not play an important role in the metabolism of abacavir, and abacavir does not inhibit CYP 3A4-mediated metabolism. Abacavir did not inhibit the activity of CYP 3A4, CYP 2C9 or CYP 2D6 enzymes at clinical dose concentrations in vitro. No clinically induced effects on liver metabolism. As a result, there is very little possibility of interaction between abacavir and antiretroviral protease inhibitors or other drugs that are primarily metabolized by P450. No clinically significant interactions between abacavir, zidovudine, and lamivudine have been seen in clinical studies.
Strong enzyme inducers, such as rifampicin, phenobarbital, and phenytoin, can slightly reduce the plasma concentration of abacavir by acting on UDP-glucuronyltransferase.
When used with ethanol, it affects the metabolism of abacavir, resulting in an increase in AUC of about 41%. It is not considered clinically significant. Abacavir does not alter the metabolism of ethanol.
Resin-like compounds are eliminated by the action of alcohol dehydrogenase and may interact with abacavir, but this has not been studied. [Drug overdose]
In clinical studies, patients have been given a single dose of 1200 mg and a daily dose of 1800 mg of this product, and no unexpected adverse reactions have been reported. The effect of larger doses is unknown. If overdose occurs, the patient should be monitored for toxic effects (see Adverse Reactions) and symptomatic supportive therapy if necessary. It is unknown whether abacavir can be removed by peritoneal or hemodialysis.

Pharmacology and Toxicology of Abacavir Sulfate Tablets

Pharmacological effects Abacavir is a nucleoside reverse transcriptase inhibitor. It is a selective HIV-1 and HIV-2 antiviral agent, including HIV-1 isolates with reduced sensitivity to zidovudine, lamivudine, zalcitabine, didanosine, or nevirapine. In vitro studies have confirmed that the mechanism of abacavir's effect on HIV is to inhibit HIV's reverse transcriptase, and this process leads to the termination of the chain and interrupts the cycle of virus replication. Abacavir has been shown to be synergistic in vitro when used in combination with nevirapine and zidovudine. Abacavir has also been shown to have an additive effect when used in combination with didanosine, zalcitabine, lamivudine, and stavudine.
HIV-1 isolates resistant to abacavir have been screened in vitro, and these isolates are associated with changes in specific genotypes in the reverse transcriptase coding regions (encoding M184V, K65R, L74V, and Y115F). In vitro and in vivo tests, the process of virus resistance to abacavir is relatively slow, and multiple mutations must occur before its IC50 can be 8 times higher than that of wild type, which may be a clinically significant level. Abacavir-resistant isolates may also have reduced susceptibility to lamivudine, zalcitabine, and / or didanosine, but zidovudine and stavudine remain sensitive.
Cross-resistance between abacavir, a protease inhibitor, and a non-nucleoside reverse transcriptase inhibitor is unlikely. In clinically isolated patients who received other nucleoside inhibitors in advance and became resistant to them, virus replication could not be controlled, and it has been confirmed that these patients have reduced sensitivity to abacavir.
Clinical application experience. For patients who have never received antiretroviral therapy, the combination of abacavir, lamivudine, and zidovudine has resulted in about 70% (analysis of the intention-to-treat population at 48 weeks) of patients. Viral load was undetectable ([400 copies / mL), and CD4 cells increased correspondingly.
A clinical study of patients who have never been treated for more than 48 weeks. The antiviral efficacy of a combination of abacavir, lamivudine, and zidovudine is comparable to indinavir and lamivudine. The effect is similar to that of zidovudine.
For patients receiving moderate antiretroviral therapy, combined antiretroviral therapy plus abacavir can reduce the viral load appropriately (median change at week 16 is 0.44 log10 copies / mL). Abacavir is very ineffective in patients who have previously received intensive treatment with nucleoside reverse transcriptase inhibitors. The extent to which the new combination will benefit patients will depend on the nature and duration of previous treatments that may have been screened to form HIV-1 variants that are cross-resistant to abacavir.
The safety and efficacy of this product have not been fully evaluated in many different multiple drug combinations (especially in combination with non-nucleoside reverse transcriptase inhibitors).
Abacavir penetrates into the cerebrospinal fluid and reduces HIV-1 RNA levels in the cerebrospinal fluid. But for patients with AIDS dementia syndrome, this product has no neuropsychological effect.
Toxicity studies Abacavir has no mutagenicity in bacterial tests, but has shown activity in in vitro human chromosome aberration tests, mouse lymphoma tests, and in vivo micronucleus tests. This is consistent with the effect of other nucleoside analogs. These results indicate that abacavir has a weak potential to cause chromosomal damage in vitro and in vivo at high test concentrations. There is no information on whether abacavir poses a carcinogenic risk to animals. Therefore, a trade-off must be made between any potential danger to humans and the expected benefits of treatment with this drug.
In preclinical toxicology studies, abacavir can cause liver weight gain in rats and monkeys, and its clinical relevance is unclear, and there is no evidence of hepatotoxicity in abacavir in clinical studies. In addition, the auto-induced metabolism of abacavir or the metabolism of other drugs by the liver has not been observed.
Studies of fertility in rats have shown that abacavir has no effect on male or female fertility.

Pharmacokinetics of Abacavir Sulfate Tablets

Absorption: Abacavir is quickly and fully absorbed after oral administration. The absolute bioavailability of oral abacavir in adults is about 83%. After oral administration, the mean peak time (tmax) of abacavir plasma concentration was approximately 1.5 hours for tablets and approximately 1 hour for oral solutions. There was no difference between the AUC of the tablet and the solution. At a therapeutic dose (300 mg, twice daily), the steady-state Cmax of abacavir tablets is about 3 mg / mL, and the AUC is about 6 mg / h / mL at a 12-hour dosing interval. . Cmax values for oral solutions are slightly higher than for tablets.
Eating delayed absorption and reduced Cmax, but did not affect overall plasma concentration (AUC). Therefore, this product can be taken with or without food.
Distribution: After intravenous administration, the apparent volume of distribution is about 0.8 L / kg, indicating that abacavir can penetrate freely into the tissue. Studies on HIV-infected patients have shown that abacavir penetrates well into the cerebrospinal fluid, and the ratio of cerebrospinal fluid to serum AUC is between 30-44%. When abacavir was administered twice daily at 600 mg, the peak concentration observed was 9 times greater than the IC50 of abacavir, ie 0.08 mg / mL or 0.26 mM.
In vitro plasma protein binding studies have shown that at therapeutic concentrations, abacavir binds to human plasma proteins only low and moderately (about 49%). This indicates that the possibility of these drugs interacting with other drugs through plasma protein conversion is low.
Metabolism: Abacavir is mainly metabolized by the liver. Approximately 2% of the dose taken is eliminated by the kidney through the prototype. The main metabolic pathway of this drug in humans is to produce about 5'-carboxylic acid and 5'-glucuronide through the urine through the dehydrogenase and glucuronidation.
Clearance: The average half-life of abacavir is approximately 1.5 hours. After oral administration of 300 mg twice daily, there was no significant accumulation of abacavir. Abacavir's elimination is first metabolized by the liver, and then metabolites are mainly excreted by the urine. Metabolites and prototypes in the urine accounted for 83% of the abacavir dose, and the rest were cleared through feces.
Liver damage in special populations: Abacavir is mainly metabolized by the liver. Safety analysis data support the use of abacavir 300 mg twice a day in patients with mild liver injury. There is no supporting information on the recommendation of taking abacavir in patients with moderate liver injury. Therefore, the above patients should avoid taking this product. For patients with severe liver impairment, this product is prohibited.
Kidney damage: Abacavir is mainly metabolized by the liver, and about 2% of abacavir is excreted in the urine as it is. Patients with advanced kidney disease and those with normal renal function have similar pharmacokinetics, so patients with renal impairment do not need to reduce their doses. Due to limited experience, patients with advanced kidney disease should avoid taking this product.
Children: According to clinical trials conducted in children, abacavir oral solution is absorbed quickly and adequately. Children's overall pharmacokinetic parameters are similar to those of adults, but there are large differences in plasma concentrations. In clinical trials, the dose for children from 3 months to 12 years is 8 mg / kg twice daily. Safety information recommending abacavir for children is insufficient.
Elderly patients: Pharmacokinetic studies of abacavir have not been performed in patients over 65 years of age.

Abacavir sulfate tablets storage

Store below 30 ° C.

Validity of Abacavir Sulfate Tablets

2 years ^[1]