Lazid

The antiviral drug for systemic use Lazid, manufactured by the Indian corporation Emcure Pharmaceuticals Ltd, has long confirmed its high efficiency in the fight against the damaging infection caused by various pathogenic strains. Its international name is Zidovudine and lamivudine.

Indications Lazid

The active ingredients of the drug are such compounds as zidovudine, lamivudine, which determine the focus of the drug. Hence the indications for the use of Lazid. This drug is prescribed as part of a combination antiviral treatment course for HIV infection for older patients and adolescents over 12 years of age.

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Release form

The modern pharmacological market offers Lazid for use, the release form of which is represented by white oval-shaped tablets covered with a protective self-dissolving film. On one surface of each tablet, the embossing "LZD" is visible, the other side is provided with a dividing line. One unit of the product contains two basic substances, which give this drug its properties: 0.15 g of lamivudine, as well as 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 drug is coated with a shell consisting of polyethylene glycol 6000, talc, hydroxypropyl methylcellulose, methylparaben, titanium dioxide E 171, propylparaben.

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Pharmacodynamics

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

Lazid is perfectly metabolized by intracellular kinases from its primary form to 5M-triphosphate (TP). The active substances of the drug in question are an excellent basis for the retrograde transcriptase of the human immunodeficiency virus infection and highly effective inhibitors of this enzyme.

The antiviral action of Lazid is characterized by the preferential introduction of the monophosphate section into the structure of the viral DNA genome. The inhibitory effect of the drug leads to a break in the structural chain of DNA. And, as a result, the pathologically affected cell dies.

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Pharmacokinetics

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

On average, the maximum amount of active chemical compounds in the blood plasma is observed: lamivudine - after a period of time from half an hour to two hours, the quantitative concentration is from 1.3 to 1.8 mg / ml, while zidovudine - from fifteen minutes to two hours with a 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, work characteristics and the severity of the pathology present in his body.

The pharmacokinetics of lamivudine are linear, its Vd (distribution volume) is on average 1.3 l/kg (based on the therapeutic dosage). Zidovudine's Vd is 1.6 l/kg. Both of these chemical compounds bind to blood plasma albumin rather weakly (less than 36%). The main components of Lazid easily enter the elements of the central and peripheral nervous system, as well as the cerebrospinal fluid.

Lamivudine has a fairly low metabolism, so it is excreted from the body almost unchanged through the kidneys with urine. Metabolic indices in the liver are quite low and amount to 5 to 10%.

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

The average T1/2 (half-life) of lamivudine is between five and seven hours, with renal clearance of about 70% and occurs with the assistance of the cationic transport system. If the patient has a history of a disease characterized by creatinine clearance of less than 50 ml / min, then, accordingly, the amount of Lazid administered to the body should be reduced.

If it is necessary to administer the drug intravenously, the half-life T1/2 is on average about one hour and ten minutes. Renal clearance of this component of Lazid is determined to be 0.34 l/h/kg. This indicator is formed from glomerular filtration and the level of activity of the renal tubular secretion. Therefore, if the patient has a history of renal dysfunction, the quantitative indicator of zidovudine in the blood plasma increases significantly.

The pharmacokinetics of Lazid in children is absolutely identical to that of adult patients. The pregnancy of a woman does not affect these characteristics.

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Dosing and administration

It is worth remembering that the treatment must be prescribed, carried out and monitored only by a qualified specialist with experience in stopping HIV infection. The drug is taken without chewing and regardless of the time of food consumption. If it is physically difficult for the patient to swallow the drug whole, it is allowed to crush it and take it together with food of a semi-liquid or liquid consistency. The method of administration and dosage is prescribed by the attending physician who is monitoring the disease. The recommended basic dosage is taking one unit of Lazid twice a day.

If the patient suffers from renal enzyme deficiency (creatinine clearance below 50 ml per minute), then the concentration of active substances of the drug in question 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 selecting a dosage is necessary, and it is best to select two drugs: lamivudine separately with its dosage and zidovudine separately. This will make it easier to select the quantitative component of each chemical compound.

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

If the patient's body, when taking Lazid, gives side symptoms in the form of obvious anemia (hemoglobin level in the blood below 9 g / dl or 5.59 mmol / l), as well as neutropenia (neutrophil count less than 1.0 x 109 / l), then the doctor needs to adjust the dosage of zidovudine. In this case, it is also recommended to prescribe drugs separately containing lamivudine and zidovudine.

There are no special comments regarding the use of Lazid by elderly people, but it is still worth clarifying that any drug should be prescribed to this category of patients with special caution. This is due to the age-related changes that are already present in the patient's body.

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Use Lazid during pregnancy

Monitoring of the drug Lazid showed that if the mother took this drug during pregnancy, the level of its concentration in the mother's serum corresponded to its quantitative and qualitative composition in the fetus's blood, as well as in the umbilical cord blood during obstetrics. Such indicators confirm the easy permeability of the drug's components through the hematoplacental barrier.

It has been documented that the use of Lazid during pregnancy, more specifically its component zidovudine, as well as administration to a newborn after birth, can significantly reduce the risk of HIV infection from the mother to her child, but the likelihood of side effects increases significantly. No data on similar characteristics have yet been found for lamivudine.

You should take Lazid very carefully while breastfeeding your baby. Only your doctor can give permission to administer the drug; you may have to exclude breastfeeding during drug therapy.

Contraindications

Any drug, in addition to its "positive" qualities aimed at relieving a particular problem, also has its negative characteristics. There are also contraindications to the use of Lazid.

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

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Side effects Lazid

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

• Pain symptoms in the head area.
• Nausea.
• Leukopenia, neutropenia, which invariably lead to anemia. The anemia indicators may be such that a blood transfusion may be required.
• Problems with sleep.
• Dizziness.
• Decreased overall tone of the body.
• Manifestations of fever.
• Attacks of pain in the epigastrium, leading to vomiting.
• Rhinorrhea (the nasal cavity is filled with a significant amount of mucous fluid).
• Coughing fits.
• Diarrhea.
• Transient increase in the level 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.
• Cramps.
• Thrombocytopenia (low platelet count in peripheral blood).
• Cardiomyopathy (inflammation of the heart muscle).
• Digestive upset.
• Pigment changes in the skin and nail plates.
• Increased sweating.
• Frequent urge to urinate.
• Hives.

It is not clear whether these side effects are caused by Lazid or are manifestations of the disease itself, but in any case, the symptoms that appear should be reported to the attending physician. To date, there is no data indicating additive toxicity of this drug.

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Overdose

If the required amount of the drug is significantly exceeded, the body reacts with unpleasant symptoms. An overdose of the drug Lazid, the active substances of which are lamivudine and zidovudine, can lead to general intoxication of the patient's body. In case of detection of the first symptoms of poisoning, it is necessary to carry out standard measures for such a picture: cleansing the victim's body (intermittent hemodialysis may be used) and introducing maintenance therapy. No fatal cases have been recorded with an overdose of Lazid. There is no single antidote, so the therapy is purely symptomatic.

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Interactions with other drugs

Based on the fact that the basic components of the drug in question are two components, lamivudine and zidovudine, 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, interacting with plasma proteins), the main, unchanged part of the chemical substance is excreted from the body through the kidneys.

Zidovudine also interacts to a low degree with the protein fraction of the blood, but, unlike lamivudine, its metabolism occurs mainly in the liver, degenerating into an inactive glucuronide.

Below are some drugs or classes of drugs that should be used more carefully together with Lazid in drug therapy. If we consider the mutual influence of the two main components, it is worth noting that zidovudine itself does not have any effect on the pharmacokinetics of lamivudine. While the opposite effect is still observed: an increase (approximately 13%) in the duration of zidovudine action on the patient's body is noted, and there is an increase in its maximum quantitative component in the blood (up to 28%).

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

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

Taking lamivudine during treatment with trimethoprim (one of the components of co-trimoxazole) is accompanied by an increase (up to 40%) in the concentration of the former in the blood (in the case of taking therapeutic doses). Lamivudine itself does not affect co-trimoxazole and its derivatives. No effect of trimethoprim on zidovudine has been recorded. Caution should be exercised when combining these two drugs, especially in patients with renal insufficiency.

The mutual use of Lazid with aspirin, indomethacin, codeine, reduces the metabolism of zidovudine, inhibiting its ability to transform into glucuronides, and a direct blockade of liver microsomal enzymes is also observed. The combined use of Lazid and ribavirin (analog of nucleosides) is not recommended, since the latter drug inhibits the antiviral characteristics of zidovudine in vitro. There is evidence that probenecid prolongs the half-life of zidovudine from the patient's body and blocks its transformation into glucuronides.

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

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Storage conditions

The medicine should be kept in a dark place at a room temperature of 15 to 25 °C. Storage conditions for Lazid do not allow the temperature to rise to 30 °C and do not shake the medicine, since in this situation the transformation of the surface shell of the medicine into a gel-like structure begins. Store Lazid in places inaccessible to children!

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Shelf life

The pharmaceutical product Lazid is available at the pharmacy with a prescription. Its expiration date is indicated on the package and is two years. It is not recommended to use the drug after the expiration date.

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