Zerit

Zerit is an antiviral drug with systemic use. It belongs to the category of nucleoside and nucleotide reverse transcriptase inhibitors.

Indications Zerit

Indicated for the treatment of people with the HIV virus.

Release form

Available in capsules of 30 or 40 mg. One blister contains 14 capsules. One package contains 4 blister strips – a total of 56 capsules per package.

Pharmacodynamics

Stavudine is an artificial analogue of thymidine (nucleoside) that has antiviral properties. It is active in vitro against HIV inside human cells. The action of cellular kinases promotes its phosphorylation and conversion into stavudine triphosphate. This element inhibits the activity of HIV revertase because it competes with the natural substrate TTP.

The drug also inhibits the process of viral DNA synthesis – induces DNA chain termination. This is explained by the absence of the 3'-hydroxyl category required for the DNA elongation process. In vitro, the substance stavudine triphosphate inhibits DNA polymerase cells, exerting a suppressive effect on the process of mtDNA binding. The active effects on DNA polymerase cells "a" and "b" are a hundred times less than the effects on HIV revertase. The in vitro passivation process, as well as examination of isolated patients after treatment, made it possible to identify HIV-1 strains that have reduced sensitivity to stavudine. However, information on the development of HIV resistance to stavudine in vivo is quite limited, as well as on cross-resistance to other analogs of nucleoside substances.

Pharmacokinetics

In adults, the bioavailability index is 86±18%. When taken orally in doses of 0.5-0.67 mg/kg, the peak concentration of the substance will be 810±175 ng/ml. When taking the capsule of the drug orally, the peak and AUC values increase in accordance with the dosage in the range of 0.033-4.0 mg/kg.

The half-life is not related to the dosage and is 1.3±0.2 hours with a single dose, and 1.4±0.2 hours with multiple doses of the drug. The intracellular half-life of stavudine triphosphate in vitro lasts 3.5 hours in CEM lymphocytes, and in addition in PBMC. This allows the drug to be used twice a day.

The overall clearance rate of stavudine is 600±90 ml/min, and the clearance within the kidney is 240±50 ml/min. This is evidence of active tubular secretion, as well as glomerular filtration.

The excretion of the substance occurs in urine in unchanged form (approximately 34±5% with single use; or 40±12% with repeated use). The remainder, in the form of 60% of the drug, is probably excreted via endogenous pathways.

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Dosing and administration

To improve the absorption of the drug, it is advisable to take it at least 1 hour before meals, washing it down with water (at least 100 ml of liquid). If it is impossible to follow this recommendation, it is allowed to take the drug with a light meal. If problems with swallowing capsules occur, it is allowed to transfer the patient to a soluble form of the drug or carefully open the capsule and then mix its contents with food.

The daily dosage is selected taking into account the patient’s weight and other individual indicators.

For children aged 12 and over and adults:

• for weight less than 60 kg, the dosage is 30 mg twice a day every 12 hours;
• for weight over 60 kg – 40 mg twice a day every 12 hours.

Children 6-12 years old:

• for weight less than 30 kg – dosage is 1 mg/kg twice a day, every 12 hours;
• for weight 30-60 kg – 30 mg twice a day, every 12 hours.

For adults with renal pathologies, the dosage should be reduced proportionally to the creatinine clearance coefficient:

• if the clearance rate is less than 50 ml/minute – 30 mg every 12 hours (for weight less than 60 kg) and 40 mg in the same regimen (for weight over 60 kg);
• with a CC rate of 26-50 ml/minute – 15 mg every 12 hours (weight less than 60 kg) and 20 mg in the same regimen (weight over 60 kg);
• with a CC value of less than 25 ml/minute – 15 mg every 24 hours (weight less than 60 kg) and 20 mg every 24 hours (weight from 60 kg); also, if hemodialysis is performed with such a CC value, it is recommended to take the prescribed dose immediately after its completion. On days when there is no dialysis, the intake is carried out in the above-mentioned regimen.

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Use Zerit during pregnancy

Before starting to use the drug, the doctor needs to know about the patient’s possible pregnancy or planning, since this drug is allowed to be prescribed only when the potential benefit to the woman is higher than the possible risk of negative consequences for the fetus.

If a woman is breastfeeding or plans to do so, she should be warned that this will cause the baby to become infected with HIV. Doctors forbid women with HIV from breastfeeding. Breastfeeding must be stopped before starting the treatment course.

Contraindications

The use of the drug is contraindicated for people who are intolerant to stavudine or other components included in the drug. In addition, it cannot be prescribed to children under 6 years of age (the use of capsules as a drug at this age is not recommended).

Side effects Zerit

During the treatment of HIV, it is difficult to distinguish between adverse reactions in patients caused by the use of Zerit, from negative effects due to other drugs that are used in combination with the drug, as well as from manifestations that develop in a person due to the pathology itself.

Observations of the patients' condition during the period of using the drug showed the development of the following negative reactions:

• General: chills, headaches, abdominal pain, malaise. In addition, flu-like allergic manifestations, various neoplasms and asthenia developed;
• digestive organs: vomiting, diarrhea and nausea, dyspeptic symptoms and anorexia; occasionally – constipation;
• respiratory system: development of dyspnea; occasionally – pneumonia;
• nervous system organs: depression, dizziness, anxiety, sleep disorders;
• skin: itching, redness, heavy sweating; benign tumors occurred less frequently;
• bone structure and muscles: joint pain, muscle pain;
• cardiovascular system: the appearance of pain in the chest;
• lymphatic and hematopoietic systems: development of lymphadenopathy.

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Overdose

A single accidental overdose of the drug should not have serious consequences (there is information that with a 12-fold excess of the required daily dosage, no symptoms of acute poisoning were observed). In the case of chronic overdose, the development of peripheral nephropathy or liver dysfunction is possible. In this case, medical supervision will be required, and non-specific detoxification procedures may also be necessary. The hemodialysis coefficient of stavudine purification is 120 ml/minute, but there is no information on the effectiveness of this procedure in case of an overdose of this substance. There is also no information on the effectiveness of the peritoneal dialysis procedure.

Interactions with other drugs

Since zidovudine is capable of inhibiting the process of stavudine phosphorylation inside cells, it is prohibited to combine it with Zerit.

Combined use with lamivudine, didanosine, and nelfinavir does not affect the properties of the drug.

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Storage conditions

The medicine must be kept in a dark place, inaccessible to small children, at a temperature of no more than 30°C.

Shelf life

Zerit is permitted to be used for 2 years from the date of release of the drug.