Intent

Intelence is an antiviral drug of systemic type of exposure.

The etravirine component is an HIV-1 NNRTI substance. It is directly synthesized by reverse-type transcriptase and blocks the activity of DNA polymerase, which depends on the activity of the DNA along with RNA, which leads to the destruction of the catalytic regions of this enzyme. Etravirin has a flexible structure in space, which allows it to be synthesized with the reverse type transcriptase of at least 2 ways. The drug does not slow down the activity of human DNA polymerase (α, β and γ).

Indications Intense

It is used for infections caused by the action of HIV-1 - with complex treatment in individuals who have not previously received therapy with antiretroviral drugs.

[1], [2]

Release form

The release of drugs is implemented in the form of tablets - 60 pieces inside the bottle; The box contains 1 bottle and 3 special bags containing silica gel desiccant.

Pharmacodynamics

Etravirine rather actively influences clinical isolates, as well as HIV-1 strains bred in laboratory conditions, located inside T-cell lines, human peripheral-type mononuclear cells and macrophages with monocytes.

The drug exhibits an in vitro antiviral effect on HIV-1 category M (subcategories A, B, and C with D, as well as E with F and G), and in addition, the main isolates from category O, in which the average therapeutically effective indicators (EC50) fluctuate in the range of 0.7-21.7 nmol.

Etravirin does not show an antagonistic effect on any of the known antiretroviral drugs. Demonstrates additive antiviral activity when combined with such drugs:

• substances that inhibit protease activity: atazanavir, nelfinavir, amprenavir with saquinavir, and in addition lopinavir, darunavir, ritonavir with indinavir, and tipranavir;
• nucleotides or nucleosides that inhibit the effect of the reverse type of transcriptase: stavudine, zalcitabine, abacavir with didanosine, and tenofovir;
• non-nucleoside agents that inhibit the activity of the reverse type of transcriptase: delavirdine and efavirenz with nevirapine;
• anti-fusion drug: enfuvirtide;
• substance inhibiting the activity of integrase: raltegravir;
• CCR5 chemokine end antagonist: maraviroc.

Etravirin has additive or synergistic antiviral effects when combined with NRTIs - lamivudine, emtricitabine, and zidovudine.

[3], [4], [5]

Pharmacokinetics

Suction.

After oral ingestion with food, plasma Cmax values of etravirine are noted after 4 hours. The simultaneous oral administration of omeprazole or ranitidine, which increases the gastric pH, does not affect the absorption of etravirine.

The type of food consumed does not affect the indicators of etravirine (both with a normal caloric content, which is 561 kcal, and fat dishes - 1160 kcal).

Drug values were lower when used before meals (by 17%) or on an empty stomach (by 51%) compared to after use. Therefore, in order to maintain an optimal plasma level of a substance, one should use the medication after a meal.

Distribution processes.

Approximately 99.9% of the component is synthesized with blood plasma protein (mainly with albumin (by 99.6%), as well as with α1-acid type glycoprotein (by 97.66-99.02%)).

Exchange processes.

The drug is mainly involved in oxidative metabolic processes, using intrahepatic isoenzymes of the structure CYP3A; a smaller part is affected by CYP2C isoenzymes. After that, the processes of glucuronization develop.

Excretion.

After oral ingestion of a portion of the 14C-labeled component inside feces and urine, respectively, 93.7%, as well as 1.2% of this dosage, were noted. The unchanged element inside the feces is within 81.2-86.4% of the injected dose. Inside the urine, unchanged substance is not noted. The final term for the half-life of a drug is approximately 30-40 hours.

[6], [7]

Dosing and administration

Intelence should be used exclusively in combination with other antiretroviral agents. A doctor who has enough experience in performing HIV treatment courses should conduct the therapy.

Persons over the age of 18 years old are required to take orally on the 1st tablet (0.2 g) 2 times a day after eating the food.

People age 6-17 years old.

Calculate the dosage for this category of patients should be based on their weight. Use medication after meals.

The size of the dosage portions, taking into account the weight of the patient:

• within ≥16- <20 kg - 0.1 g 2 times a day;
• in the range of 20- <25 kg - 0.125 g 2-fold per day *;
• In the range of ≥25- <30 kg - 0.15 g 2 times a day *;
• ≥30 kg - 0.2 g twice a day.

* required to use tablets with a volume of 25 mg.

Problems with the work of the liver.

Pharmacokinetics of the drug in case of severe severity of liver failure has not been studied. Because of this, in such disorders, Intelens should not be prescribed.

Reception mode when skipping the next portion.

When a period of less than 6 hours has passed since the intake of the drug, the patient should immediately take the medicine (only after eating the food), and then apply it in the standard mode.

If the pass is more than 6 hours, the skipped portion is not accepted, resuming use according to the standard scheme.

It is necessary to use tablets completely, without chewing, washing down with usual water. If the patient’s swallowing process is difficult, the tablet can be crushed and dissolved in water according to the following scheme:

• tablets are poured with liquid in an amount that will be sufficient for their full coverage (or poured with one teaspoon, equal to 5 ml);
• the medicine must be stirred until the tablet is completely dissolved - the liquid becomes milky white;
• if necessary, this mixture can be diluted with milk or orange juice (at the same time, the drug was initially diluted exclusively in plain water);
• after that you need to immediately drink the resulting solution;
• a glass from under the medicine is rinsed several times with milk or orange juice, then drinking its contents in order to ensure that the maximum dosage of the drug is taken.

For dilution of the drug is prohibited to use carbonated or hot (> 40 ° C) water.

[13], [14], [15], [16], [17], [18]

Use Intense during pregnancy

It is forbidden to use Intelens during pregnancy.

Contraindications

The main contraindications:

• strong personal sensitivity regarding etravirine or other elements of the drug;
• breastfeeding period;
• combination with nelfinavir, efavirenz, ritonavir or tipranavir, and in addition with nevirapine, phenobarbital, rilpivirin, carbamazepine and indinavir. Also on the list is St. John's wort, rifapentin and rifampicin with phenytoin;
• lack of hepatic function in the severe stage.

[8], [9]

Side effects Intense

Often taking the drug causes the development of rashes.

Quite often such signs also appear:

• increase in blood pressure values;
• anemia or thrombocytopenia;
• polyneuropathy, anxiety, myocardial infarction, insomnia, fatigue and headaches;
• vomiting, GERD, gastritis, bloating, pain in the abdominal area, diarrhea, and nausea;
• kidney failure;
• hyperglycemia, α-lipidemia, α-cholesterolemia, triglyceridemia, diabetes mellitus, night sweats and lipohypertrophy;
• an increase in lipase, total Xc, creatinine with triglycerides, and in addition, amylase, ALT and LDL with AST and sugar, as well as a decrease in the number of leukocytes with neutrophils.

The following symptoms are sometimes observed:

• stroke having a hemorrhagic nature, atrial fibrillation or angina pectoris;
• syncope, hypoesthesia, disorientation, convulsions, confusion, paresthesia, amnesia and hypersomnia, and in addition tremor, sleep disorders or drowsiness, nightmares or unusual dreams, nervousness and attention disorder;
• visual misting;
• vertigo;
• dyspnea, appearing during exercise, or bronchial spasm;
• stomatitis, flatulence, emetic urges, constipation, pancreatitis, dry oral mucous membranes and vomiting with blood;
• fatty liver degeneration, hepatomegaly and hepatitis (also of a cytolytic nature);
• lipodystrophy;
• hyperhidrosis, epidermal dryness, facial swelling and prurigo;
• angioedema or erythema polyforme;
• dyslipidemia, drug intolerance, anorexia, a feeling of lethargy and immune recovery syndrome;
• gynecomastia.

Occasionally, the appearance of SSD is observed; single - development of heating elements. It is also possible the occurrence of rhabdomyolysis.

[10], [11], [12]

Overdose

In case of poisoning with Intelens, there may be signs that most often occur as its side effects: among these are diarrhea, rashes, headaches and nausea.

If there are indications, it is possible to excrete unabsorbed active component of the drug with the help of vomiting. Along with this, for this purpose use of activated carbon. Simultaneously, symptomatic measures are taken, among which are monitoring the most important physiological parameters and the clinical picture. There is no antidote for etravirine; dialysis will be ineffective.

[19], [20], [21], [22]

Interactions with other drugs

Drugs that affect plasma etravirine levels.

The drug undergoes metabolic processes using CYP3A4 isoenzymes with CYP2C9, as well as CYP2C19; further metabolic components are involved in glucuronization using uridine-2-phosphate glucuronosyltransferase. The use of drugs that stimulate the activity of CYP3A4 with CYP2C9 or CYP2C19, may cause an increase in etravirine clearance rates, which decrease its plasma values.

Combining the drug with substances that slow down the activity of CYP3A4 with CYP2C9 or CYP2C19, causes a decrease in its clearance values, which leads to an increase in plasma level.

Substances that may be affected by the administration of etravirine.

The drug has a mild inducing effect on CYP3A4 isoenzyme. Combination with drugs, whose metabolic processes occur mainly with CYP3A4, can cause a decrease in their plasma values and reduce their drug effects.

Etravirin also slightly slows down the activity of CYP2C9 isoenzymes with CYP2C19 and P-glycoprotein.

The combination of Intelence with substances whose metabolic processes mostly take place with the participation of CYP2C9 or CYP2C19, and which are also transported under the influence of P-glycoprotein, can increase their plasma values and potentiate or lengthen their drug-induced activity and side effects.

[23], [24], [25], [26], [27]

Storage conditions

Intelens should be kept in a place closed to children. The temperature level is no more than 30 ° С.

Shelf life

Intelens are allowed to use within a 2-year term from the date of manufacture of the drug substance.

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

Application for children

There is no information regarding drug safety and efficacy of the effect when administering the drug to persons under 6 years old or with a weight less than 16 kg.

Analogs

Analogs of drugs are the means Arverenz, Estiva, Neviraton, Viramun, Efavirenz with Nevivir, and in addition Efamath, Nevimun, Favir with Nevipan, Eferven with Efavir and Nevirapin. Also on the list are Stocrin and Efkur with Effachop 600.

[32], [33]