Abamat

"Abamat" will not change the human attitude towards the disease, but it is an excellent antiviral drug, specially developed by medical scientists for children and adults with HIV infection.

Indications Abamat

"Abamat", whose international name is "Abacavir", is intended for the treatment of the virus - HIV in adults and children.

Treatment with the drug requires special caution, since HIV infection affects the entire human body, which means that the drug should be taken under the strict supervision of a doctor who has the necessary experience in treating patients with AIDS and HIV. During treatment, the patient's viral load and the number of CD4 lymphocytes should be assessed. Patients should be informed that the use of "Abamat" does not prevent the transmission of the immunodeficiency virus through blood or intimate contact.

[ 1 ]

Release form

"Abamat" is presented in the form of peach-colored tablets, which are coated with a round biconvex shell, with the inscription "M20" on one side, on the other side there is a "strip" for breaking into two parts, each part of which is a dose of 60 mg.

"Abamat" "M110" is almost identical to "Abamat" "M20", but the release form of "M110" - capsules are also peach-colored, logically, have the inscription "M110" on one side, the other side is smooth, the dose of which is 300 mg.

The difference between the first and second types of the drug is the dosage, which is discussed, first of all, with the attending physician.

Pharmacodynamics

"Abamate" is rapidly absorbed from the gastrointestinal tract. Bioavailability in adults is 83%. The maximum concentration in the blood serum is reached after 1.5 hours after taking the drug in tablets. When taking the drug in therapeutic doses (600 mg), the maximum concentration is approximately 3 mcg / ml, and the AUC is taken at intervals of 12 hours - 6 mcg / h / ml.

Taking the drug during meals slows down the time of peak serum concentration, but does not affect the overall plasma concentration. Therefore, Abamat can be taken regardless of food intake.

Abacavir, another name for Abamata, freely penetrates into various tissues of the body, including the CSF. The average ratio of abacavir levels in the cerebrospinal fluid to serum is approximately 30-44%. When used in therapeutic doses, the level of protein binding is approximately 49%.

With regard to metabolism, abacavir undergoes primary metabolism in the liver, with less than 2% of the administered dose excreted unchanged in the urine.

The main metabolites are 5'-carboxylic acid and 5'-glucuronide, the transformation of which occurs with the help of alcohol dehydrogenase or by glucuronidation.

The half-life of abacavir is 1.5 hours. No significant accumulation occurs after repeated dosing of 300 mg twice daily. Metabolites and unchanged abacavir, approximately 83% of the dose taken, are excreted in the urine, the remainder in the feces.

As for carcinogenesis, mutagenesis, there are data on the occurrence of malignant and benign tumors. In most cases, these tumors occurred with the use of high doses of "Abamate" - 330 mg / kg / day and 600 mg / kg / day. These doses are equivalent to a level that is 24-32 times higher than the level of systemic distribution of the drug in humans. Although the carcinogenic potential of the drug in humans is unknown, these data allow us to believe that the potential benefit from the use of the drug outweighs the carcinogenic risk for humans.

Liver lesions

Abamat is metabolized primarily in the liver. The pharmacokinetics of Abamat were studied in patients with moderate liver impairment (Child-Pugh score 5-6) receiving a single 600 mg daily dose. The results showed a mean increase of 1.89-fold [1.32; 2.70] in abacavir AUC and 1.58-fold [1.22; 2.04] in half-life.

Kidney damage

Abamat is primarily metabolized in the liver, with approximately 2% of the dose excreted unchanged via the kidneys. The pharmacokinetics of abacavir in patients with end-stage renal disease are similar to those in patients with normal renal function. Therefore, dose adjustment is necessary for patients with renal impairment.

Based on short-term experience, Abamate should be discontinued in patients with end-stage renal disease.

Pharmacokinetics in children

In children, Abamat is rapidly and easily absorbed from oral solutions. Overall pharmacokinetic parameters in children are similar to those in adults, with greater variability in plasma concentrations.

If we talk about babies under 3 months, there is no necessary information on safe use.

Pharmacokinetics

Active ingredient: 1 film-coated tablet contains: abacavir in the form of sulfate 60 mg or 300 mg.

Excipients include:

• colloidal silicon dioxide,
• microcrystalline cellulose,
• sodium starch (type A),
• magnesium stearate,
• film coating "Opadry yellow" 03B82849 (titanium dioxide - E171, hypromellose),
• iron oxide red - E172,
• iron oxide yellow - E172,
• polyethyleneglycol.

"Abamat" is a systemic antiviral agent.

"Abamate" is a nucleoside reverse transcriptase inhibitor, and is also a potent inhibitor of HIV-1 - HIV-2, including HIV-1 isolates with reduced sensitivity to zidovudine, lamivudine, zalcitabine, nevirapine or didanosine. In the cell, this drug is converted into an active metabolite, carbovir triphosphate, which acts by inhibiting HIV reverse transcriptase, resulting in a disruption of the necessary connection in the viral DNA system and its replication is stopped.

Dosing and administration

Treatment should be carried out by a physician who has experience in treating patients with HIV infection.

"Abamat" is taken orally, regardless of food intake.

Adults and children over 12 years of age (weighing at least 30 kg): 300 mg twice daily or 600 mg once daily.

When switching from a twice-daily regimen to a once-daily schedule, in the morning, the first dose of 600 mg should be taken in the morning. If an evening regimen is preferred, then on the day of the switch, 300 mg should be taken in the morning and 600 mg in the evening.

When switching from once daily to twice daily dosing, the first 300 mg should be taken in the morning.

Children from 3 years (whose weight is not less than 14 kg) to 12 years, the recommended dose is 8 mg/kg 2 times a day; the maximum daily dose is up to 600 mg per day. "Abamat" should be prescribed only to those children who can swallow a tablet. For patients who cannot swallow a tablet, "Abacavir" in the form of an oral solution may be offered.

Recommendations for the use of 60 mg tablets for children weighing from 14 to 30 kg.

Dose adjustment in case of renal failure is not required, since the process of metabolism of "Abamate" occurs mainly in the liver, patients with mild liver failure (Child-Pugh index - 5-6) are recommended to take 200 mg of "Abamate" twice a day. For such dosing, "Abamate" should be used in the form of a solution for oral use.

Dose adjustment for elderly patients. When prescribing the drug to elderly patients, it is necessary to take into account the higher frequency of cardiac, hepatic and renal dysfunction, the presence of concomitant diseases and the use of drugs.

[ 3 ]

Use Abamat during pregnancy

"Abamat" has a whole range of contraindications and side effects. But the safety of using "Abamat" during pregnancy has not been established, hence, there are no recommendations for pregnant women. But a doctor can prescribe this drug only if the expected benefit to the mother during this period exceeds the risk to the fetus.

"Abamat" for nursing HIV-infected mothers, as well as during pregnancy, is not recommended, as its effect on the child is unknown. Studies have not established the penetration of the drug into the mother's milk, therefore, during the process of taking it, breastfeeding should be stopped.

But in any case, a pregnant woman or a woman who has already given birth must follow the doctor’s strict instructions, especially since this medicine is sold in pharmacies only upon presentation of a prescription.

Contraindications

"Abamat" has several contraindications, which include:

• Hypersensitivity to the components that make up the drug.
• Moderate or severe liver impairment.
• End-stage kidney disease.
• Positive test for the presence of the HLA-B allele * 5701.

"Abamat" in addition to contraindications also has side effects, which are also indicated in the instructions, and which the attending physician must take into account during therapy. Predisposition to contraindications can be established using diagnostics: laboratory tests and ultrasound examination.

Side effects Abamat

There is evidence that approximately 5% of patients receiving Abamate developed hypersensitivity reactions, which were characterized by the appearance of multiorgan symptoms with or without fever and/or the appearance of rashes (maculopapular or urticaria), and were rarely fatal.

Symptoms may occur at any time during treatment, but usually appear within the first six weeks of starting treatment (average time of onset is 11 days).

Symptoms and signs of allergic reactions are listed below. Those occurring with a frequency of more than 10% are highlighted in bold.

From the skin: rash (maculopapular or urticarial).

From the digestive system: abdominal pain, diarrhea, nausea, vomiting, gastroenteritis, ulcers on the oral mucosa.

From the respiratory system: cough, shortness of breath, respiratory depression syndrome, sore throat, respiratory failure, changes in the chest X-ray (mainly infiltrates, which can be localized) general manifestations: fever, fatigue, malaise, lymphadenopathy, edema, conjunctivitis, arterial hypotension, anaphylaxis.

From the nervous system: headaches, paresthesia.

From the hematopoietic system: lymphopenia.

From the digestive system: increased levels of functional liver tests, hepatitis, liver failure.

Musculoskeletal system: muscle pain, isolated cases of myolysis, arthralgia, increased CPK levels.

In addition, creatinine levels may increase, renal failure, rash and gastrointestinal side effects were more common in children than in adults. Skin rashes were a common isolated symptom of hypersensitivity reactions. Some patients with hypersensitivity reactions are initially perceived as having respiratory diseases (pneumonia, pharyngitis, bronchitis), flu-like illnesses, gastroenteritis or reactions to other medications.

Delay in diagnosis of hypersensitivity results in patients continuing to use abacavir, which may cause severe exacerbation of allergic reactions and even death. Therefore, the possibility of a hypersensitivity reaction should always be considered if patients experience the above symptoms. If the risk of such a reaction cannot be excluded, the use of Abamat or other drugs containing abacavir should be discontinued and not resumed. With continued treatment, the symptoms of a hypersensitivity reaction worsen and usually disappear after discontinuation of the drug. Patients who have developed a hypersensitivity reaction should stop treatment and never resume it with any drug containing Abamat.

There are isolated reports of hypersensitivity reactions occurring after repeated administration of the drug, when this was preceded by the appearance of one of the main signs of hypersensitivity (skin rash, fever, fatigue, malaise, gastrointestinal or respiratory symptoms).

In rare cases, hypersensitivity reactions have occurred in patients who have resumed treatment, but this was not preceded by hypersensitivity symptoms. For many other adverse reactions, it remains unclear whether they are related to the use of Abamat or other drugs used to treat HIV infection, or are the result of the disease itself.

Many of the above symptoms (nausea, vomiting, diarrhea, fever, fatigue, rash) occur as part of a hypersensitivity reaction. Therefore, patients with any of these symptoms should be carefully examined for allergic reactions. If treatment is stopped due to the presence of at least one of these symptoms, resumption of treatment is possible only under the direct supervision of a physician.

[ 2 ]

Overdose

In case of overdose, it is necessary to first make sure that the patient does not have an allergic reaction to Abamate or its components, and, if necessary, to conduct standard supportive therapy. In other cases, treatment is symptomatic. It is unknown whether this drug is eliminated by peritoneal dialysis or hemodialysis.

In order to avoid overdose, you should strictly follow the doctor's recommendations. In case of any unexpected symptoms, you should inform your doctor. It is quite possible that the symptoms may be associated with an allergic reaction.

Interactions with other drugs

The likelihood of P450-mediated interactions of Abamate with other medicinal products is low. Abamate inhibits CYP3A4, CYP2C9 and CYP2D6 enzymes at clinically relevant concentrations.

Interactions between protease inhibitors and other drugs that are metabolized by major P450 enzymes are unlikely.

There is no interaction between Abamat, Zidovudine and Lamivudine.

Taking the drug with "Ethanol" leads to the development of the scale under the pharmacokinetic curve "concentration / time" (AUC) of "Abamate" by almost 41%. "Abamate" does not affect the metabolism of "Ethanol".

Concomitant administration of 600 mg of Abamate twice daily and Methadone reduces the maximum concentration (Cmax) of Abamate by 35% and delays the time to reach the maximum concentration (tmax) by one hour, but the AUC remains unchanged. This antiviral agent increases the average systemic exposure of Methadone by 22%. Adult patients taking Methadone and Abamate should be monitored for signs of withdrawal syndrome, indicating low dosage, as Methadone dosage adjustment may be necessary.

Retinoid components are eliminated by alcohol dehydrogenase. Interaction with Abamate is possible, but has not been studied.

[ 4 ], [ 5 ], [ 6 ], [ 7 ], [ 8 ]

Storage conditions

"Abamat" has standard storage rules, i.e. in a dark, dry place, inaccessible to children, the temperature of which should not exceed 30°C. Moreover, it should be stored in the original packaging together with the insert - instructions.

It should be remembered that failure to comply with storage standards can significantly reduce the shelf life of the drug, since most substances that are active or additional components lose their therapeutic properties at too high a temperature or when exposed to sunlight.

It is for these reasons that “Abamat”, the insert of which contains all the information on this matter, should be stored in accordance with all instructions.

Shelf life

"Abamat", if stored according to the instructions, is valid for 2 years from the date of manufacture. But, otherwise, it is impossible to name the exact expiration date.

When buying "Abamat", do not be shy, look at the date of manufacture and the name of the manufacturer. Why check the date is clear. As for the manufacturer, the only one who can produce it is "Matrix Laboratories Limited" India. There were no counterfeits among pharmacies. But, if we talk about "virtual" delivery methods, then everything is possible, even delivery of an expired drug.