Lazid

Issued by the Indian corporation EmCure Pharmaceuticals Co., Ltd. Antiviral drug systemic use Lazid has long been proven to be highly effective in combating a striking infection caused by various pathogenic strains. Its international name is Zidovudine and lamivudine.

Indications Lazid

The active substances of the drug are such compounds as zidovudine, lamivudine, which determine the direction of the drug. Hence the indication for the use of Lazid. This drug is prescribed as part of the combinatorial antiviral treatment course of HIV infection for older patients and adolescents, whose age has exceeded 12 years.

[1], [2], [3], [4], [5], [6], [7]

Release form

The modern pharmacological market offers Lazid, the form of which is represented by white tablets in the form of an oval, covered with a protective self-dissolving film. On one of the surfaces of each tablet, one can see "LZD" embossing, the other side is provided with a dividing line. The structure of one unit of the product includes two basic substances that give this medicine its properties: 0.15 grams of lamivudine, and twice as many grams of zidovudine. There are also auxiliary components, which include colloidal silicon dioxide, microcrystalline cellulose, lactose, sodium starch glycolate, starch, magnesium stearate.

The preparation is coated with a coating consisting of polyethylene glycol 6000, talc, hydroxypropyl methylcellulose, methylparaben, titanium dioxide E 171, propylparaben.

[8], [9]

Pharmacodynamics

Lamivudine and zidovudine, which form the basis of the drug Lazid, are classified as high-performance chemical compounds, selective inhibitors of reverse revertase HIV-1 and HIV-2. Both of these substances have a synergistic effect, mutually reinforcing each other's actions. Therefore, lamivudine helps zidovudine to inhibit the replication of HIV infection in the patient's body.

Lazid perfectly metabolizes intracellular kinases from its primary form and up to 5M-triphosphate (TF). The active substances of the drug under consideration are an excellent basis for the retrograde transcriptase of human immunodeficiency virus infection and inhibitors of this high-efficiency enzyme.

The antiviral effect of Lazide is characterized by the preferred introduction of a monophosphate section into the structure of the viral DNA genome. The oppressive effect of the drug leads to the rupture of the structural chain of DNA. And, as a result, a pathologically affected cell dies.

[10], [11], [12],

Pharmacokinetics

Physicians note that the pharmacokinetics of Lazid is quite high. The active substances of the preparation are perfectly passed through the mucosa of the gastrointestinal tract, showing excellent bioavailability: the percentage of lamivudine absorption is about 85%, the bioavailability of zidovudine absorption is somewhat lower, but nevertheless also quite high - up to 70%.

On average, the maximum number of active chemical compounds in the blood plasma is observed: lamivudine - after a period of time from half an hour to two hours, the concentration is 1.3 to 1.8 mg / ml, whereas zidovudine - from fifteen minutes to two hours with present concentration of 1.5 to 2.2 mg / ml. The time interval and the level of the components of the drug Lazid directly depend on the patient's age, the features of the work and the severity of the pathology present in his body.

The pharmacokinetics of lamivudine obeys linear laws, its Vd (volume of distribution) averages 1.3 l / kg (if based on the therapeutic dosage). Vd of zidovudine is characterized by a figure of 1.6 l / kg. At the same time, both these chemical compounds are weakly (lower than 36%) tied to the albumin of the blood plasma. The main components of Lazid easily fall into the elements of the central and peripheral nervous system, as well as into the fluid of the spinal secretion.

Lamivudine shows a fairly low metabolism, therefore, almost unchanged is excreted from the body through the kidneys with urine. The metabolic parameters in the liver are rather low and range from 5 to 10%.

The basic metabolite of zidovudine in blood and urine is 5-glucuronide. Up to 80% of this component is removed from the body by a kidney route. If the drug was administered intravenously, then the product of zidovudine transformation is 3-amino-3deoxythymidine, which after renal excretion is found in the urine.

The averaged T1 / 2 (half-life) of lamivudine is between five and seven hours, with a kidney clearance of about 70% and is facilitated by the cationic transport system. If there is a disease in the patient's history, indicated by a creatinine clearance less than 50 ml / min, then, accordingly, the amount of Lazid injected into the body must be reduced.

If it is necessary to administer the drug to the vein, the half-life of T1 / 2 is approximately one hour and ten minutes on average. The renal clearance of this component of Lasid is determined at 0.34 l / h / kg. This indicator is formed from glomerular filtration and the level of activity of the renal tubular secretion. Therefore, in the presence of a patient with a history of renal dysfunction, the quantitative index of zidovudine in blood plasma is significantly increased.

Pharmacokinetics Lazid in children is absolutely identical with that of adult patients. Has no effect on these characteristics and pregnancy of a woman.

[13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23]

Dosing and administration

It is worth remembering that only qualified specialists with experience of arresting HIV infection should prescribe, conduct and supervise therapy. The drug is taken without chewing and regardless of the time of consumption of food. If the patient is physically difficult to swallow the whole drug, it is allowed to break and take with the food a semi-liquid or liquid consistency. The method of application and dose is prescribed by the attending physician, the leading disease. The recommended basic dosage is a single unit dose of Lazid twice a day.

If the patient suffers from a deficiency of the renal enzyme (creatinine clearance below 50 ml per minute), then the concentration of active substances of the drug in the patient's blood increases due to a decrease in the rate of their utilization and removal from the body. In this situation, a private approach to the choice of dosage is necessary, and it is best to select two drugs: separately lamivudine with its dosage and separately zidovudine. This will make it easier to select the quantitative component of each chemical compound.

If the patient suffers from a pathology of liver function, physicians note a significant cumulation of zidovudine in the patient's body, which invariably affects the decrease in its interaction with glucuronic acid. Such patients are recommended to appoint lamivudine and zidovudine as separate drugs. This will allow to select a quantitative dosage for zidovudine.

If the patient's body, when taking Lazid, gives a side symptomatology in the form of obvious anemia (hemoglobin level in the blood below 9 g / dl or 5.59 mmol / l), as well as with neutropenia (the number of neutrophils is less than 1.0х109 / l) doctor to adjust the dosage of zidovudine. In this case, the administration of drugs separately containing lamivudine and zidovudine is also recommended.

There are no special comments about the use of Lazid by elderly people, but it is still necessary to specify that such a category of patients should be prescribed with special care with any drug. This is due to those age changes that are already present in the patient's body.

[32], [33], [34], [35]

Use Lazid during pregnancy

Monitoring of Lazid's drug intake showed that if the mother took this medication while the baby is pregnant, then the level of its concentration in the mother's serum was consistent with its quantitative and qualitative composition in the fetal blood, as well as in the cord blood during the delivery. Such indicators confirm the easy permeability of the constituents of the drug through the hematoplacental barrier.

It has been documented that the use of Lazid during pregnancy, more specifically its zidovudine component, as well as the introduction of a newborn after its birth, significantly reduces the risk of HIV infection from the mother giving birth to her child, but the likelihood of side effects is significantly increased. Data on similar characteristics of lamivudine has not yet been found.

Very cautiously it is necessary to take Lazidum and during feeding of the kid by a breast. Only the attending physician can give permission to administer the drug, it may be necessary to exclude breastfeeding at the time of drug therapy.

Contraindications

Any drug, in addition to its "positive" qualities, aimed at stopping this or that problem, has its own negative characteristics. There are also contraindications to the use of Lazid.

• Excessive sensitivity to the components of the drug.
• Renal dysfunction (creatinine clearance less than 50ml / min).
• Neutropenia is a pathology characterized by a decreased number of neutrophils in the blood plasma. In this case, less than 0.75 x10 ⁹ / l.
• The period of bearing and breastfeeding of a child in women.
• Anemia (digital hemoglobin is less than 4.65 mmol / l or 7.5 g / dL).
• The drug is contraindicated in children and adolescents under the age of 18 years.

[24], [25], [26]

Side effects Lazid

Depending on the severity of the pathology and general condition of the patient's body, side effects of Lazid can show the following:

• Pain symptomatology in the head.
• Nausea.
• Leukopenia, neutropenia, which invariably entails anemia. The indicators of anemia may be such that a blood transfusion may be required.
• Problems with sleep.
• Dizziness.
• Decrease in the general tone of the body.
• Manifestations of fever.
• Painful seizures in the epigastrium, contributing to the occurrence of vomiting.
• Rinorrhea (nasal cavity is filled with a significant amount of mucous fluid).
• Coughing attacks.
• Diarrhea.
• Transient growth in the number of liver enzymes: aspartate aminotransferase (AST), bilirubin and alanine aminotransferase (ALT).
• Joint and muscle pain.
• Itching and rash on the skin.
• Anorexia.
• Depressive state, excitability.
• Flatulence.
• Decreased mental activity.
• Convulsions.
• Thrombocytopenia (reduced platelet count in peripheral blood).
• Cardiomyopathy (inflammation of the heart muscle).
• Indigestion disorder.
• Pigmentary changes in the skin and nail plates.
• Increased sweating.
• Frequent urge to urinate.
• Hives.

There is not enough certainty whether these side effects are caused by Lazid or are manifestations of the disease itself, but in any case, the treating physician should be informed of the symptoms that appear. To date, there is no data indicating the additive toxicity of this drug.

[27], [28], [29], [30], [31]

Overdose

With a significant excess of the required amount of the drug taken, the body responds with a response to unpleasant symptoms. Overdose of a drug Lazid, active substances of which are lamivudine and zidovudine, can lead to general intoxication of the patient's body. In the case of detection of the first symptoms of poisoning, it is necessary to conduct standard measures in such a pattern: purification of the organism of the victim (possible use of discontinuous hemodialysis) and the introduction of maintenance therapy. When Lazid overdosed, no cases of death were recorded. There is no single-agent antidote, so therapy is symptomatic.

[36],

Interactions with other drugs

Proceeding from the fact that the two components of lamivudine and zidovudine are the basic components of the drug in question, the interactions of Lazid with other drugs directly depend on the characteristics of these components. If we consider lamivudine, then, due to its low metabolism (only a small part of it metabolizes by interacting with plasma proteins), the main, unchanged, part of the chemical is excreted from the body through the kidneys.

Zidovudine also interacts poorly with the protein fraction of the blood, but unlike lamivudine, its metabolism mainly occurs in the liver, rebuilding into an inactive glucuronide.

Below are sounded some drugs or classes of drugs that should be used more cautiously with Lazid in drug therapy. If we consider the mutual influence of the two main components, it is worth noting that zidovudine does not directly affect the pharmacokinetics of lamivudine. While the reverse effect is still observed: growth (about 13%) of the duration of action of zidovudine on the patient's organism is noted, and an increase in its maximum quantitative component in the blood (up to 28%) also occurs.

During the interaction of Lazid with phenytoin, a decrease in the quantitative component of the latter in plasma was observed (one case gave the opposite indicator - the phenytoin accumulation in the blood increased). This feature of the drug indicates the need to constantly monitor the amount of concomitant Lazide substance in the plasma.

In the case of using zidovudine against the background of a therapeutic course with paracetamol, there is an increased risk of neutropenia. This is especially true with a long course of treatment. Paracetamol does not affect the plasma concentration of zidovudine and its metabolism.

The use of lamivudine against the background of therapy with trimethoprim (one of the constituents of co-trimoxazole) is accompanied by an increase (up to 40%) of the concentration of the first in the blood (in the case of therapeutic doses). Lamivudine itself does not affect the co-trimoxazole and its derivatives. The effects of trimethoprim on zidovudine have not been documented. One should be careful when combining these two drugs, especially those with kidney failure.

Mutual use of Lasid with aspirin, indometacin, codeine, reduces the metabolism of zidovudine, inhibiting its ability to transform into glucuronides, as well as direct blockade with microsomal enzymes of the liver. It is not recommended joint use of Lazide and ribavirin (nucleoside analogue), since the latter drug depresses the antiviral characteristics of zidovudine in vitro. There is evidence that the probenicide prolongs the half-life of T ½ zidovudine from the patient's body and blocks its transformation into glucuronides.

Therefore, before the introduction of drugs into the protocol of treatment, it is necessary to thoroughly study the interaction of Lazid with other drugs, especially if it concerns a sufficiently long course of therapeutic therapy.

[37], [38], [39], [40], [41], [42]

Storage conditions

The drug should be kept in a dark place at room temperature from 15 to 25 ° C. Lazid storage conditions do not allow an increase in temperature to 30 ° C and shaking of the drug, since in this situation the transformation of the surface of the drug into a gel-like structure begins. Keep Lazid in places that are not accessible to children!

[43], [44]

Shelf life

Pharmacological drug Lazid is released at the pharmacy if a prescription is available. Its shelf life is indicated on the packaging and is two years. It is not recommended to use the drug after the expiration of the storage period.

[45]