Lamivudine

Direct antiviral agent Lamivudine, which belongs to the group of nucleotide and nucleoside reverse transcriptase inhibitors, is released to the pharmacological market by the pharmaceutical company Aurobindo Pharma Ltd., based in India. The international code of the drug is АТХ J05А F05.

HIV infection is a scourge of modern society. But the most terrible thing is that for today there is no effective treatment that can completely relieve the patient of this terrible disease. Physicians are only able to block the further development of pathology. And in this they can help an antiviral drug like lamivudine. But due to its powerful pharmacodynamics, self-medication is absolutely unacceptable. Such liberty can provoke complications, weighed down by lethality. Therefore, it is necessary to keep in touch with your doctor. Only he has the right to prescribe and cancel the drug, adjust its dosage, the schedule of admission and the duration of treatment. 

[1], [2], [3], [4],

Indications Lamivudine

The examined drug Lamivudine was developed by the scientist group of the manufacturer company as a drug introduced into the combined treatment of HIV infection (human immunodeficiency virus).

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

[5], [6], [7]

Release form

Drug Lamivudine, effectively working in tandem of other medications to stop the action of the retrovirus, is released to the market of medical medicines in the form of oral solution. This is not the only form of release of this medication. On the shelves of pharmacies, you can find plastic jars in a cardboard box containing 60 Lamivudine tablets coated with a protective coating.

The main active substance, indicating and characteristics of the medicament, is the chemical compound lamivudine, whose concentration is 10 mg, present in 1 ml of the solution. One tablet of this substance contains 150 mg.

Additional chemical constituents contained in the drug are: sucrose, citric acid, methylparaben, propylene glycol, sodium citrate, sodium hydroxide, propyl parahydroxybenzoate, hydrochloric acid diluted, flavor flavor of banana or strawberry, and purified water.

The drug is a clear liquid. Its shade can be from colorless to pale yellow. The volume of the vial is 240 ml.

[8], [9]

Pharmacodynamics

When a retrograde virus belonging to the lentivirus species enters the body, it starts slowly, but systematically, destroying cellular structures, causing the development of such a disease as HIV infection (AIDS). This process is practically not reversible. It can only be slowed down or blocked.

Therefore, the pharmacodynamics of lamivudine presupposes the presence of the abilities of an active active substance to inhibit the reverse transcriptase of a given retrovirus. Triphosphate lamivudine is selective and effective enough, blocks the synthesis of HIV-1 and HIV-2 strains. In complex treatment with zidovudine, the drug qualitatively blocks the replication of HIV-1, and at the same time, contributes to an increase in the number of cellular structures of CD4. Such combination as zidovudine and lamivudine significantly reduces the likelihood of further development of the disease and the risks of mortality from it.

The joint interdependence of these two chemical compounds has a weak cytotoxic effect on peripheral blood lymphocytes, bone marrow cells, monocyte-macrophage cells, and lymphocyte cell structures, which allows one to assess the wide possibilities of the therapeutic index of the drug Lamivudine.

[10], [11], [12], [13], [14],

Pharmacokinetics

When you enter into the protocol of treatment of a drug, in addition to pharmacodynamics, the attending physician is 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 mucosa, that is, the speed with which the medicine can bring a positive change in the clinical picture of the disease. And as not the last place takes the possibility of the organism, the remnants or metabolites of the medicine are effectively excreted.

As shown by clinical and laboratory studies, the drug determines its bioavailability in the range of 80 - 85%, which is a good indicator. 

The maximum amount of the active active component of the drug in the blood plasma is observed already an hour after administration. In the case of a therapeutic recommended dosage, this value (Cmax) is from 1 to 1.9 μg / ml.

If the drug is taken with food, the maximum concentration is reduced, while the bioavailability level remains unchanged.

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

Mostly, the drug is excreted from the patient through the kidneys together with urine (more than 70% lamivudine). On average, its systemic clearance is approximately marked with a figure of 0.32 l / kg per hour.

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

Therefore, if the function of the kidneys is reduced, an adjustment of the drug dose is necessary.

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

[15], [16], [17], [18]

Dosing and administration

A group of pharmacists - developers of any manufacturer company gives its recommendations on the schedule of administration and dosages of the proposed drug. But the human body is individual, like that bouquet of diseases that can pester it. Therefore, the method of administration and the dose, in this case of the Medication, can be corrected during the course of treatment by the attending physician according to the clinical picture of the disease. In this case, a specialist who prescribes therapy should have experience working with HIV-infected patients.

The medicine in question can be drunk, regardless of the meal time. The drug should be swallowed whole, without chewing, with a sufficient amount of liquid.

Adult HIV-infected patients and adolescents, whose weight exceeds 30 kg, are given a starting dose of 150 mg, divided into two doses or 300 mg once a day during the day. The duration of treatment is predetermined by such an indicator as the level of CD 4 of the patient's lymphocytes.

In this case, the dosage of lamivudine is also adjusted from the patient's creatinine clearance.

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

With complex treatment of HIV infection in small patients whose body weight did not reach a weight of 30 kg and age is more than 3 months, lamivudine antiretroviral drug is prescribed in an average daily dose of 4 mg per kilogram of weight divided into two doses during the day. In this case, it is worthwhile to ensure that the calculated daily amount of the drug does not exceed 300 mg of lamivudine. The duration of therapeutic treatment is highly individual and is prescribed by the attending physician. Dosage should be adjusted during the growth of the weight of the child.

As in the case of an adult patient, the dosage of lamivudine can be adjusted by the creatinine clearance of a small patient.

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

For infants who have not reached the age of three months, data on the admission of the medicine in question are limited.

In the case of prophylaxis, after contact with HIV-infected patients, adults (eg, nursing staff or close relatives of the patient) no later than 72 hours after contact (cut, sex, prick, etc.), antiviral drug Lamivudine is prescribed in a dosage of 150 mg. It takes two daily doses taken during the month (four weeks).

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

It should be very cautious approach the prescribed dosage to patients before retirement and retirement age. This caution is associated with those age-related changes that invariably affect the body of this category of patients.

The antiviral drug under consideration is used only in complex relief of the disease and is not recommended as a medicine for monotherapy.

HIV-infected people and their surroundings should remember that the therapy (including the antiviral drug Lamivudine) only depresses the development of the disease, but in no way prevents the risk of its transmission to another person through blood, sexual contact or open wound. There is still a high probability, against the background of immunodeficiency, to get another viral disease, as well as complications of a different kind. Therefore, such patients are on special control of doctors.

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

Some patients are interested in the issue of the possibility, against antiretroviral therapy, to manage vehicles and / or complex mechanisms requiring 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 can be hampered by the very condition of the patient and the severe clinical picture of the disease.

[25], [26], [27], [28]

Use Lamivudine during pregnancy

In the period of waiting for the birth of a child or breastfeeding it, a future or real young mother makes every effort to minimize the intake of any pharmacological agent of both traditional and non-traditional medicine. This is due to her fear of harming the fetus or newborn baby. As shown by all sorts of studies, the use of lamivudine during pregnancy is significantly limited.

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

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

The introduction of this drug to rabbits showed intrauterine death of embryos.

There are a number of documentary confirmations that indicate a delay in the child's psychological and physiological development, the appearance of convulsive symptoms and the development of neurological diseases. However, a direct connection with the administration of the drug has not been established.

But the ban on taking does not apply to situations where the probability of transmission of a retrograde virus to a child is high.

Prohibited reception of the drug in the lactation period. Either the young mother receives treatment, but interrupts the feeding of the newborn baby with the breast, transferring it to artificial feeding. 

Contraindications

In order to obtain the expected therapeutic effect of arresting the disease, the drug must actively affect the areas of the human body that have been disturbed. 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, proceeding from the above, it can be noted that there are contraindications to the use of Lamivudine.

1. Individual intolerance of the patient's body lamivudine or one of the secondary chemical compounds that make up the drug.
2. Do not use in the protocol of treatment of newborns whose age has not reached three months.

[19], [20], [21]

Side effects Lamivudine

Individual pharmacodynamics of the drug, its wrong reception, deviation from the schedule or dosages, individual sensitivity to a specific chemical compound - all this can provoke side effects manifested when taking the medication. Physicians can not always unequivocally state the direct dependence of the introduction of a medicine 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. Attacks of a cough.
8. Thrombocytopenia.
9. Diarrheal manifestations.
10. Neutropenia.
11. Exacerbation of pancreatitis.
12. Increased level of hepatic enzymes.
13. True erythrocyte aplasia.
14. Nauseated, provoking, at times, vomit reflex.
15. Appearance of cold symptoms.
16. Pain syndrome 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 overall health.
25. And a number of other manifestations.

[22], [23], [24],

Overdose

Due to individual characteristics of the body, the weakening of health by other diseases, with the admission of negligence in the dosage or protocol of admission, the mutual influence of various drugs, an overdose of the drug is possible. There are no signs of taking high doses of Lamivudine today. There is no special information on this issue. As there is no evidence, and that an overdose of the drug can lead to death.

[29], [30], [31]

Interactions with other drugs

As already noted above, the antiretroviral drug Lamivudine is not recommended for use in monotherapy. It is mainly introduced into the protocol of complex treatment of patients with HIV infection. Therefore, when prescribing the medicine in question, the attending physician should know the peculiarities of his interaction with other drugs.

When studying pharmacodynamic characteristics, a low interest rate of the drug's binding to the blood protein was found, as well as a low level of metabolic interaction and the ability to rapidly excrete the kidneys unchanged. It is precisely such features of lamivudine that make it sufficiently inert in the work with the drugs of other groups, but there are still restrictions on admission.

As studies and monitoring of such patients have shown, lamivudine should not be taken together with other drugs that contain one of the chemical compounds: empricitabine or lamivudine

Very carefully it is necessary to enter in one protocol with preparations, the main way of excretion of which passes through the kidneys (for example, trimethoprim). This is due to the fact that in the same way, in the unchanged form, the considered drug is withdrawn, and this is already a great burden on this body. Especially if in the patient's history there are violations in his work.

Other drugs (for example, cimetidine or ranitidine) are not completely, but leave the body with a small amount of urine through the kidneys. This makes them acceptable partners in tandem admission with the medication in question.

With the joint admission with its analog zidovudins, there is a significant reduction (up to 30%) of the pharmacological characteristics of the latter. Effects on the pharmacokinetics of lamivudine are not observed.

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

A similar situation is also observed when the drug and sulfamethoxazole are co-administered in the same treatment protocol.

Do not prescribe a joint method of lamivudine and zalcitabine, since the pharmacodynamics of the first inhibits the intracellular phosphorylation of the latter.

[32], [33], [34]

Storage conditions

To conduct the therapy gave the expected result, in addition to the implementation of all the recommendations prescribed by the treating doctor, it is worth to get acquainted and fulfill the conditions of storage of lamivudine. Incorrect drug content significantly reduces or even completely abolishes its pharmacological characteristics.

If all the requirements and recommendations have been fulfilled, there can be no doubt that the effectiveness of the properties of the medicinal product remains high throughout the life of the product.

Contain lamivudine is necessary, fulfilling such requirements:

1. The place where the medicine is planned to be kept must be protected from direct UV radiation and other spectrum of sun rays.
2. Temperature storage should not exceed 25 degrees above zero.
3. Contain antiretroviral drug is necessary in places that are not available for adolescents and small children.
4. After opening the package, the drug should be used within the next month, then the effectiveness of the drug drops significantly.

[35], [36], [37]

Shelf life

When entering the medical market, any product of pharmaceutical companies must be provided with two dates on the packaging material: the first - when this medicine was produced; the other is the end date, after which, the drug, supplied with this instruction, should not be used as an effective antiviral agent for the treatment of HIV infection, should not be.

In this case, the expiration date of the antiviral drug Lamivudine is two years (or 24 months).