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Nelfiner
Last reviewed: 23.04.2024
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Nelfiner is an antiviral drug with direct therapeutic effects. Included in the group of agents that slow down the activity of the protease.
HIV protease is an enzyme required to perform a proteolytic separation that occurs with polyprotein viral precursors, after which proteins are formed that are constituent elements of active HIV. The processes of separation of such polyproteins are paramount for the subsequent formation of the virus.
The nelfinavir component is synthesized with the active region of the HIV protease and prevents the breakdown of polyproteins. As a result, immature particles of the virus are formed that cannot infect the surrounding cells.
Release form
The release of drugs is implemented in the form of tablets with a volume of 0.25 g.
Pharmacodynamics
The administration of the medication together with other antiviral substances weakens the intra-serum viral load and increases the number of CD4 cells. An analysis of earlier and current testing confirms that Nelfiner decreases the rate of pathology progression.
The antiviral effect of the drug in vitro was noted during the chronic or active phase of HIV infection in the line of lymphocytes with monocytes, and besides lymphoblastic cells with macrophages inside peripheral blood. The nelfinavir component affects a large number of clinical isolates, as well as laboratory strains of HIV-1 subtypes with HIV-2, and in addition to this, a strain of the ROD type.
The drug demonstrates synergistic and additive effects as an element of 2 and 3 complex treatment regimens (including substances that slow down the effect of reverse transcriptase), while not potentiating their cytotoxicity.
In vitro processes formed HIV isolates with reduced sensitivity to nelfinavir. When genotyping a viral form, whose sensitivity was attenuated by half, a specific replacement of aspartic acid (type D) with asparagine (type N) was found within the HIV protease supplemented with amino acid fragments 30 (type D30N).
Cross-resistance between reverse transcriptase retarding agents and nelfinavir is unlikely, because these drugs have different target enzymes. HIV isolates that are resistant to nucleoside analogs, as well as non-nucleoside components that slow down reverse transcriptase, retain their sensitivity to nelfinavir for in vitro tests.
Pharmacokinetics
When administered once or repeatedly, 0.5-0.75 g of the substance (2 or 3 tablets) with food, it usually takes 2-4 hours to obtain the level of plasma Cmax. After repeated administration of 0.75 g at 8-hour intervals for 28 days (equilibrium indices), plasma Cmax values were 3-4 mcg / ml, and Cmin (just before using a new batch) - 1-3 mcg / ml
Indicators of bioavailability of the drug are unknown, but tests using a radioactive label, given the large volumes of metabolic elements observed inside the urine, suggest that approximately 78% of the ingested dosage is absorbed.
The use of medication with food increases its plasma level twice / threefold (in comparison with the introduction on an empty stomach). The fat content of food does not affect the intensity of the increase in plasma drug values when used with food.
The calculated indicator of distribution volume (in the range of 2-7 l / kg) is higher than the general indicator of the volume of fluid inside the body, from which it can be concluded that nelfinavir in large quantities penetrates into the tissues. Inside the serum, the substance is almost fully (98%) undergoes protein synthesis. High plasma saquinavir values increase free-form nelfinavir.
With a single injection of 0.75 g of 14C-nelfinavir, its unchanged element was 82–86% of intraplasma radioactivity. Inside the plasma, the main metabolic component and several additional ones formed during oxidation are recorded. In vitro, the main oxymetabolite has an antiviral effect similar to the original element. In vitro metabolic processes of drugs are implemented using a variety of hemoprotein P450 isoenzymes, including CYP3A.
The level of clearance at 1-time (in the range of 24-33 l / h) and re-introduction (within 26-61 th l / h) indicates a high intrahepatic bioavailability of drugs. The term plasma half-life (terminal stage) is usually 2.5-5 hours. A substantial portion of the 0.75 g oral dose, which contains 14C-nelfinavir, is found inside feces (87%); fecal radioactivity is associated with the labeled active element (22%), as well as many of its oxymetabolites. Inside the urine, only 1-2% of the used portion is noted (mostly unchanged nelfinavir).
In children 2-13 years old, the level of clearance is approximately twice / three times the adult level. The use of Nelfiner tablets in portions of about 20-30 mg / kg 3 times daily with food leads to equilibrium plasma values similar to those in adults taking 3 times daily for 0.5-0.75 g of drug.
Dosing and administration
The medication is taken orally, often with food. Adolescents over the age of 13 and adults are prescribed 0.75 g of medication per day (3 times a day, 1 tablet each).
Children aged 2-13 years old need to apply 3 times a day for 20-30 mg / kg.
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Use Nelfinera during pregnancy
There is no information about the use of nelfinavir during pregnancy, so the prescription of the drug in the specified period is allowed only with strict indications.
Information regarding the removal of the drug with mother's milk is not available. When using Nelfiner breastfeeding is not performed.
Contraindications
It is contraindicated to appoint persons with severe intolerance against the elements of the drug.
Side effects Nelfinera
The side effects of the medication are generally weak. Most often marked diarrhea.
Occasionally, disorders such as bloating, abdominal pain, nausea, asthenia, epidermal rash, an increase in the number of lymphocytes, a decrease in the number of neutrophils and an increase in the activity of ALT and CPK develop.
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Overdose
There is only limited information regarding acute Nelfiner poisoning.
Antidote medication is missing. It can be removed by gastric lavage and induction of vomiting. The unabsorbed substance is excreted with activated carbon. Because a substantial portion of nelfinavir is synthesized with intraplasma protein, the likelihood of dialysis effectiveness is extremely low.
Interactions with other drugs
The metabolism processes of nelfinavir are partially realized with the help of the hemoprotein P450 3A (element CYP3A). Although nelfinavir does not significantly inhibit the effect of CYP3A (in comparison with other inhibitors - ritonavir, indinavir or ketoconazole), it must be very carefully combined with substances that induce CYP3A, or with potentially toxic drugs whose metabolism is produced with the participation of CYP3A.
Other antiviral substances.
Because didanosine should be taken on an empty stomach, Nelfiner is taken along with food 2 hours before didanosine is given or 1 hour after it.
Means inducing the action of enzymes of metabolic processes.
Medicines with a potent inducing effect on the CYP3A element (nevirapine, phenytoin, and rifampicin with carbamazepine, as well as phenobarbital) can lower the plasma values of nelfinavir. Therefore, if a person using Nelfiner needs therapy using the above drugs, they need to find an alternative.
Combined administration of the drug with rifabutin requires reducing the dosage of the latter by half.
Other likely interactions.
The drug increases plasma indicators of terfenadine, so they can not be combined - to prevent the development of life-threatening or severe arrhythmia.
Because there is a possibility of a similar interaction of drugs with cisapride and astemizole, they are also not used in combination.
Although appropriate testing was not performed, it is forbidden to use the drug together with sedatives whose metabolic processes are implemented with the participation of CYP3A (among them midazolam or triazolam), because a prolongation of their sedative effect may occur.
The drug is able to increase the plasma values of other drug-substrates of the element CYP3A (among those substances that block the action of the Ca channels), so patients in such situations should be carefully examined to diagnose the toxicity symptoms of these drugs.
The drug reduces the performance of oral contraception with their combined use.
Storage conditions
Nelfiner should be kept in a closed area from small children and sunlight. Temperature values - not more than 25 ° С.
Shelf life
Nelfiner can be used for a 24-month period from the date of sale of the drug product.
Use in children
There are no data on the safety and drug efficacy of drugs when used in children under 2 years of age, so it is used in this group only in situations where the benefits of its administration are more likely than the risks of complications.
Attention!
To simplify the perception of information, this instruction for use of the drug "Nelfiner" translated and presented in a special form on the basis of the official instructions for medical use of the drug. Before use read the annotation that came directly to medicines.
Description provided for informational purposes and is not a guide to self-healing. The need for this drug, the purpose of the treatment regimen, methods and dose of the drug is determined solely by the attending physician. Self-medication is dangerous for your health.