Lamivudine

The direct-acting antiviral agent Lamivudine, which belongs to the group of nucleotide and nucleoside reverse transcriptase inhibitors, is marketed by the pharmaceutical company Aurobindo Pharma Ltd., based in India. The international drug code is ATX J05A F05.

HIV infection is a scourge of modern society. But the worst thing is that today there is no effective treatment that can completely rid the patient of this terrible disease. Doctors can only block the further development of the pathology. And such an antiviral drug as Lamivudine can help them with this. But due to its powerful pharmacodynamics, self-medication is absolutely unacceptable. Such liberty can provoke complications, aggravated by mortality. Therefore, it is necessary to maintain mutual communication with your doctor. Only he has the right to prescribe and cancel the drug, adjust its dosage, schedule and duration of treatment.

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Indications Lamivudine

The drug in question, Lamivudine, was developed by the scientific group of the manufacturing company as a medication introduced into the combined treatment of HIV infection (human immunodeficiency virus).

This medication can be used in the treatment of hepatitis, as well as in the treatment of cancerous tumors. It is worth noting that the drug in question does not cure the body of the human immunodeficiency virus, but significantly reduces the risk of further progression of acquired immunodeficiency syndrome (AIDS - a) and other pathologies associated with HIV infection.

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Release form

The drug Lamivudine, which works effectively in tandem with other medications to stop the effects of the retrovirus, is released on the market of medical drugs in the form of an oral solution. This is not the only form of release of this drug. On the shelves of pharmacies you can also find plastic jars in cardboard packaging, inside which there are 60 Lamivudine tablets, covered with a protective shell.

The main active substance, which also denotes the characteristics of the medicine, is the chemical compound lamivudine, the concentration of which is 10 mg, present in 1 ml of solution. One tablet of this substance contains 150 mg.

Additional chemical components contained in the medicinal product are: sucrose, citric acid, methylparaben, propylene glycol, sodium citrate, sodium hydroxide, propyl parahydroxybenzoate, diluted hydrochloric acid, banana or strawberry flavoring, and purified water.

The medicine is a transparent liquid. Its shade can be from colorless to pale yellow. The volume of the bottle is 240 ml.

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Pharmacodynamics

When a retrograde virus, belonging to the lentivirus species, enters the body, it begins to slowly but systematically destroy cellular structures, causing the development of a disease such as HIV infection (AIDS). This process is practically irreversible. It can only be slowed down or blocked.

Therefore, the pharmacodynamics of Lamivudine suggests the ability of the active substance to inhibit the reverse transcriptase of this retrovirus. Lamivudine triphosphate selectively and quite effectively blocks the synthesis of HIV-1 and HIV-2 strains. In combination with zidovudine, the drug qualitatively blocks HIV-1 replication, and at the same time, helps to increase the number of CD4 cell structures. Such a combination as zidovudine and Lamivudine significantly reduces the likelihood of further development of the disease and the risk of mortality from it.

The combined interdependence of these two chemical compounds has a weak cytotoxic effect on peripheral blood lymphocytes, bone marrow cells, monocyte-macrophage cells, lymphocyte cellular structures, which allows us to evaluate the broad possibilities of the therapeutic index of the drug Lamivudine in question.

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Pharmacokinetics

When introducing a particular drug into the treatment protocol, in addition to pharmacodynamics, the attending physician is also interested in the pharmacokinetics of the drug. After all, an important factor in any treatment is the ability of the drug to be quickly absorbed by the mucous membrane, that is, the speed with which the drug is able to bring a positive change to the clinical picture of the disease. And also not the last place is occupied by the ability of the body to effectively remove the remains or metabolites of the drug.

As clinical and laboratory studies have shown, the drug determines its bioavailability within 80 - 85%, which is a good indicator.

The maximum amount of the active ingredient of the drug in the blood plasma is observed already one hour after administration. In case of taking the therapeutic recommended dosage, this indicator (Cmax) is from 1 to 1.9 mcg/ml.

If the drug is taken together with food, the maximum concentration indicator decreases, while the level of bioavailability remains unchanged.

The half-life of the drug (T _1/2 ) on average corresponds to a time interval of five to seven hours. The drug shows a low level of binding to blood proteins. A number of data confirm the fact that the active drug penetrates into both the cerebrospinal fluid (CSF) and the central nervous system. After two to four hours, the concentration of the drug in the CSF (in relation to the same parameter in the blood) is 0.12.

The drug is mainly excreted from the patient's body through the kidneys together with urine (more than 70% of lamivudine). On average, its systemic clearance is approximately 0.32 l / kg per hour.

The active substance of the drug in question (about 10%) is metabolized in the liver into lamivudine triphosphate, which shows a longer half-life, which on average corresponds to a time interval of 16 to 19 hours.

Therefore, if renal function is reduced, the drug dosage must be adjusted.

Pharmacokinetics of the drug during therapeutic therapy in young patients (under twelve years of age) is almost identical to that in an adult patient. The only difference is in the bioavailability of Lamivudine. This indicator is significantly reduced and ranges from 55 to 65%.

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Dosing and administration

A group of pharmacists - developers of any company - manufacturer gives their recommendations on the schedule of administration and dosages of the proposed medicine. But the human body is individual, as is the bouquet of diseases that can bother it. Therefore, the method of application and dosage, in this case of the Medicine, during the course of treatment can be adjusted by the attending physician according to the clinical picture of the disease. At the same time, the specialist prescribing the therapy must have experience working with HIV-infected patients.

The medicine in question can be taken regardless of meal time. It is advisable to swallow the medicine whole, without chewing, with a sufficient amount of liquid.

Adult HIV-infected patients and adolescents whose weight exceeds 30 kg are initially prescribed a dosage of 150 mg, divided into two doses or 300 mg once a day. The duration of treatment is determined by such an indicator as the patient's CD 4 lymphocyte level.

In this case, the dosage of Lamivudine is adjusted based on the patient's creatinine clearance rate.

• If it falls within the range of 30 to 50 ml/min, the recommended dosage is 150 mg. In this case, the maintenance amount is 150 mg (one dose per day).
• If it falls within the range of 15 to 30 ml/min, the recommended dosage is 150 mg. In this case, the maintenance amount is 100 mg (one dose per day).
• If it falls within the range of 5 to 15 ml/min, the recommended dosage is 150 mg. In this case, the maintenance amount is 50 mg (one dose per day).
• If it is below 5 ml/min, the recommended dosage is 50 mg. Similarly, the maintenance dose of the drug is 25 mg (one daily injection).

In complex therapy of HIV infection in young patients whose body weight has not reached 30 kg and whose age is over 3 months, the antiretroviral drug Lamivudine is prescribed in an average daily dose of 4 mg per kilogram of weight, divided into two doses during the day. It is important to ensure that the calculated daily dose of the drug does not exceed 300 mg of lamivudine. The duration of therapeutic treatment is strictly individual and is prescribed by the attending physician. The dosage must be adjusted as the child's weight increases.

As in the adult patient, the Lamivudine dosage may be adjusted based on the creatinine clearance of the pediatric patient.

• If it falls within the range of 30 to 50 ml/min, the recommended dosage is 4 mg per kilogram of weight. In this case, the maintenance amount is 4 mg per kilogram of weight (one dose per day).
• If it falls within the range of 15 to 30 ml/min, the recommended dosage is 4 mg per kilogram of weight. In this case, the maintenance amount is 2.6 mg per kilogram of weight (one dose per day).
• If it falls within the range of 5 to 15 ml/min, the recommended dosage is 4 mg per kilogram of weight. In this case, the maintenance amount is 1.3 mg per kilogram of weight (one dose per day).
• If it is below 5 ml/min, the recommended dosage is 1.3 mg per kilogram of weight. In this case, the maintenance amount is 0.7 mg per kilogram of weight (one dose per day).

For infants under three months of age, there is limited data on the use of this drug.

In case of prophylaxis after contact with HIV-infected patients in adults (for example, medical personnel or close relatives of the patient) no later than 72 hours after contact (cut, sexual contact, injection, etc.), the antiretroviral drug Lamivudine is prescribed at a dosage of 150 mg. Two daily doses are required, taken over the course of a month (four weeks).

If the patient has a history of renal and/or hepatic insufficiency, the dose of the drug in question must be adjusted.

It is necessary to approach the prescribed dosage to patients of pre-retirement and retirement age with great caution. This warning is connected with those age-related changes that invariably affect the organism of this category of patients.

The antiviral drug in question is used only in complex treatment of the disease and is not recommended as a drug for monotherapy.

HIV-infected people and their environment should remember that the therapy taken (including the antiretroviral drug Lamivudine) only suppresses the development of the disease, but in no way prevents the risk of its transmission to another person through blood, sexual contact or an open wound. There is also a high probability, against the background of immunodeficiency, of getting another viral disease, as well as complications of a different kind. Therefore, such patients are under special medical supervision.

If the patient has a history of hepatitis B or C, then against the background of antiviral treatment, such a patient has a high probability of progression of severe complications with potentially high mortality.

Some patients are interested in the question of the possibility, against the background of antiretroviral therapy, to drive vehicles and/or complex mechanisms that require increased attention. To date, there is no data on this issue, but the pharmacodynamics of Lamivudine does not suggest any problems in this matter. Another option is that this may be hindered by the patient's condition itself and the severe clinical picture of the disease.

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Use Lamivudine during pregnancy

During the period of expecting the birth of a child or breastfeeding, the future or current young mother takes all measures to minimize the intake of any pharmacological agent of both traditional and alternative medicine. This is due to her fear of harming the fetus or newborn child. As various studies have shown, the use of Lamivudine during pregnancy is significantly limited.

The results of clinical studies have confirmed the ability of the drug in question to freely penetrate the placental barrier. It is also detected in breast milk.

In this regard, the use of the drug during pregnancy and lactation can only be justified by a severe clinical picture of the woman’s disease.

The introduction of the drug in question to rabbits showed intrauterine death of embryos.

There are a number of documented evidences indicating a delay in the psychological and physiological development of the child, the appearance of convulsive symptoms and the development of neurological diseases. However, a direct connection with the use of the drug has not been established.

However, the ban on taking the drug does not apply to situations where there is a high probability of transmitting the retrograde virus to a child.

The drug in question is also prohibited during lactation. Or the young mother receives treatment, but stops breastfeeding the newborn child, transferring him to artificial feeding.

Contraindications

In order to obtain the expected therapeutic effect of stopping the disease, the medicine must actively affect the areas of the human body that have been damaged. This is the only way to achieve the necessary changes. But the human body is a single whole and its other systems, organs and processes are also affected.

Therefore, based on the above, it can be noted that there are contraindications for the use of Lamivudine.

1. Individual intolerance of the patient's body to lamivudine or one of the minor chemical compounds included in the drug.
2. Should not be used in the treatment protocol for newborns under three months of age.

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Side effects Lamivudine

Individual pharmacodynamics of the drug, its incorrect use, deviation from the schedule or dosage, individual sensitivity to a specific chemical compound - all this can provoke side effects that appear when taking the Medicine. Doctors cannot always clearly state a direct relationship between the administration of the drug and the appearance of pathological symptoms, but, nevertheless, it can manifest itself:

1. Anemia.
2. Sleep disturbance.
3. Paresthesia.
4. Hyperlactatemia.
5. The appearance of a headache.
6. Lactic acidosis.
7. Coughing fits.
8. Thrombocytopenia.
9. Diarrheal manifestations.
10. Neutropenia.
11. Exacerbation of pancreatitis.
12. Increased levels of liver enzymes.
13. True red cell aplasia.
14. Nausea, which sometimes provokes vomiting reflexes.
15. The appearance of cold symptoms.
16. Pain in the upper abdomen.
17. Increased serum amylase levels.
18. Allergic manifestations, including angioedema.
19. Alopecia.
20. Rapid fatigue of the body.
21. Arthralgia.
22. Rhabdomyolysis.
23. Metabolic disorders.
24. Poor general health.
25. And a number of other manifestations.

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Overdose

Due to individual characteristics of the body, weakening of health by other diseases, if carelessness in dosage or protocol of administration, mutual influence of various drugs, an overdose of the drug is possible. Signs of taking high doses of the drug Lamivudine have not been identified to date. There is no specific data on this issue. As there is no data that an overdose of the drug can lead to death.

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Interactions with other drugs

As noted above, the antiretroviral drug Lamivudine is not recommended for monotherapy. It is mainly included in the protocol of complex treatment of patients with HIV infection. Therefore, when prescribing the drug in question, the attending physician should know the specifics of its interaction with other drugs.

When studying the pharmacodynamic characteristics, a low percentage rate of binding of the drug in question to blood protein was found, as well as a low level of metabolic interaction and the ability to quickly excrete unchanged by the kidneys. It is these features of Lamivudine that make it quite inert in working with drugs of other groups, but there are still restrictions in taking it.

As studies and monitoring of such patients have shown, it is impossible to allow the use of Lamivudine together with other drugs that contain one of the chemical compounds: empricitabine or lamivudine

It is necessary to be very careful when introducing it into one protocol with drugs, the main route of excretion of which is through the kidneys (for example, trimethoprim). This is due to the fact that the drug in question is excreted in the same way, unchanged, and this is already a big load on this organ. Especially if the patient's medical history includes disorders in its functioning.

Other drugs (for example, cimetidine or ranitidine) do not completely, but only in small amounts, leave the body with urine through the kidneys. This makes them acceptable partners in tandem administration with the drug in question.

When taken together with its analogue zidovudine, a significant decrease (up to 30%) in the pharmacological characteristics of the latter is observed. No effect on the pharmacokinetics of Lamivudine is observed.

The synthetic antibacterial agent trimethoprim provokes an increase in the concentration of the active substance of the drug in question in the blood by approximately 40%. But if the patient does not suffer from kidney problems, then the dosage of both drugs should not be adjusted.

A similar situation is observed when this drug and sulfamethoxazole are administered together in one treatment protocol.

Lamivudine and zalcitabine should not be co-administered because the pharmacodynamics of the former inhibits intracellular phosphorylation of the latter.

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Storage conditions

In order for the therapy to give the expected result, in addition to following all the recommendations prescribed by the attending physician, it is worth getting acquainted with and following the storage conditions of Lamivudine. Incorrect content of the drug significantly reduces, or even completely cancels its pharmacological characteristics.

If all requirements and recommendations have been met, there is no doubt that the high efficiency of the medicinal product will be maintained throughout its entire shelf life.

Lamivudine must be taken in accordance with the following requirements:

1. The place where the medicine is planned to be kept should be protected from exposure to direct ultraviolet radiation and other spectrum of sunlight.
2. The storage temperature should not exceed 25 degrees above zero.
3. The antiretroviral drug should be kept in places that are inaccessible to teenagers and small children.
4. After opening the package, the medicine must be used within the next month, after which the effectiveness of the drug drops significantly.

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Shelf life

When entering the medical market, any product of pharmaceutical companies is required to have two dates on the packaging material: the first is when the given medicinal product was produced; the other is the end date, after which the drug supplied with these instructions should not be used as an effective antiviral agent for the treatment of HIV infection.

In this case, the shelf life of the antiretroviral drug Lamivudine is two years (or 24 months).