Intelens

Intelence is a systemic antiviral medication.

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

Indications Intelensa

It is used for infections caused by HIV-1 – in complex treatment of individuals who have not previously undergone therapy using antiretroviral agents.

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Release form

The drug is released in the form of tablets - 60 pieces in a bottle; a box contains 1 such bottle and 3 special bags containing silica gel desiccant.

Pharmacodynamics

Etravirine is quite active against clinical isolates, as well as laboratory-derived HIV-1 strains located within T-cell lines, human peripheral mononuclear cells, and macrophages with monocytes.

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

Etravirine does not exhibit antagonistic effects with respect to any of the known antiretroviral drugs. It demonstrates additive antiviral activity when combined with the following drugs:

• substances that inhibit protease activity: atazanavir, nelfinavir, amprenavir with saquinavir, and also lopinavir, darunavir, ritonavir with indinavir and tipranavir;
• nucleotides or nucleosides that inhibit the action of reverse transcriptase: stavudine, zalcitabine, abacavir with didanosine and tenofovir;
• non-nucleoside reverse transcriptase inhibitors: delavirdine and efavirenz with nevirapine;
• fusion inhibitor drug: enfuvirtide;
• integrase inhibitor: raltegravir;
• CCR5 chemokine terminal antagonist: maraviroc.

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

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Pharmacokinetics

Suction.

After oral administration with food, plasma Cmax values of etravirine are observed after 4 hours. The absorption of etravirine is not affected by the simultaneous oral administration of omeprazole or ranitidine, which increase gastric pH values.

The type of food consumed does not affect etravirine levels (either normal calorie foods, 561 kcal, or fatty foods, 1160 kcal).

The drug values were lower when taken before meals (by 17%) or on an empty stomach (by 51%) compared to after. Therefore, to maintain optimal plasma levels of the substance, the medication should be taken after meals.

Distribution processes.

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

Exchange processes.

The drug is mostly involved in oxidative metabolic processes, with the help of intrahepatic isoenzymes of the CYP3A structure; a smaller part is affected by CYP2C isoenzymes. After this, glucuronidation processes develop.

Excretion.

After oral administration of a portion of the labeled 14C component, 93.7% and 1.2% of this dose were recovered in the feces and urine, respectively. The unchanged element in the feces constitutes 81.2-86.4% of the administered dose. No unchanged substance was observed in the urine. The terminal half-life of the drug is approximately 30-40 hours.

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Dosing and administration

Intelence should only be used in combination with other antiretroviral agents. Therapy should be administered by a physician with sufficient experience in administering HIV treatment courses.

Persons over 18 years of age are required to take orally 1 tablet (0.2 g) 2 times a day after meals.

People aged 6-17 years.

The dosage for this category of patients must be calculated taking into account their weight. The medication is taken after meals.

Dosage portion sizes based on patient weight:

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

*requires use of 25 mg tablets.

Problems with liver function.

The pharmacokinetics of the drug in cases of severe liver failure have not been studied. Therefore, Intelence should not be prescribed in such disorders.

Mode of administration when missing a dose.

If less than 6 hours have passed since the missed dose, the patient should take the medicine immediately (only after eating), and then use it in the standard mode.

If the interval is more than 6 hours, the missed dose is not taken, and the standard regimen is resumed.

The tablets must be taken whole, without chewing, with plain water. If the patient has difficulty swallowing, the tablet can be crushed and dissolved in water as follows:

• the tablets are filled with liquid in an amount sufficient to completely cover them (or one teaspoon is added, equal to 5 ml);
• the medicine must be stirred until the tablet is completely dissolved - the liquid will acquire a milky white hue;
• if necessary, this mixture can be diluted with milk or orange juice (in this case, the medicine is initially diluted exclusively in plain water);
• After this, you need to immediately drink the resulting solution;
• The medicine glass is rinsed several times with milk or orange juice, then its contents are drunk – to ensure that the maximum dosage of the medicine is taken.

It is prohibited to use carbonated or hot (>40°C) water to dilute the medication.

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Use Intelensa during pregnancy

It is prohibited to use Intelence during pregnancy.

Contraindications

Main contraindications:

• strong personal sensitivity to etravirine or other components of the drug;
• breastfeeding period;
• combination with nelfinavir, efavirenz, ritonavir or tipranavir, as well as nevirapine, phenobarbital, rilpivirine, carbamazepine and indinavir. Also on the list are St. John's wort, rifapentine and rifampicin with phenytoin;
• severe liver failure.

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Side effects Intelensa

Often, taking medication causes the development of rashes.

Quite often, the following symptoms also appear:

• increase in blood pressure values;
• anemia or thrombocytopenia;
• polyneuropathy, anxiety, myocardial infarction, insomnia, fatigue and headaches;
• vomiting, GERD, gastritis, bloating, abdominal pain, diarrhea and nausea;
• renal failure;
• hyperglycemia, -lipidemia, -cholesterolemia, -triglyceridemia, diabetes mellitus, night sweats and lipohypertrophy;
• an increase in the values of lipase, total cholesterol, 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:

• hemorrhagic stroke, atrial fibrillation or angina;
• fainting, hypoesthesia, disorientation, seizures, confusion, paresthesia, amnesia and hypersomnia, as well as tremor, sleep disturbances or drowsiness, nightmares or unusual dreams, nervousness and attention disorder;
• visual blurring;
• vertigo;
• dyspnea that occurs during physical exertion, or bronchial spasm;
• stomatitis, flatulence, vomiting, constipation, pancreatitis, dry mouth and vomiting of blood;
• fatty liver degeneration, hepatomegaly and hepatitis (also cytolytic);
• lipodystrophy;
• hyperhidrosis, epidermal dryness, facial swelling and prurigo;
• Quincke's edema or erythema multiforme;
• dyslipidemia, drug intolerance, anorexia, fatigue and immune reconstitution syndrome;
• gynecomastia.

Occasionally, the development of SSc is observed; in isolated cases, the development of TEN. Rhabdomyolysis may also occur.

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Overdose

In case of poisoning with Intelence, symptoms may be observed that most often occur as its side effects: among them are diarrhea, rashes, headaches and nausea.

If indicated, unabsorbed active ingredient of the drug can be excreted by vomiting. Activated carbon can also be taken for this purpose. Symptomatic measures are taken at the same time, including monitoring of the most important physiological parameters and clinical picture. Etravirine has no antidote; dialysis will be ineffective.

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Interactions with other drugs

Medicines that affect plasma levels of etravirine.

The drug is metabolized by CYP3A4 isoenzymes with CYP2C9 and CYP2C19; the metabolic components are then glucuronidated by uridine-2-phosphate glucuronosyltransferase. Use of drugs that induce CYP3A4 with CYP2C9 or CYP2C19 may increase etravirine clearance rates, resulting in decreased plasma levels.

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

Substances that may be affected by etravirine administration.

The drug has a weak inducing effect on the isoenzyme CYP3A4. Combination with drugs whose metabolism processes occur mainly with the help of CYP3A4 may cause a decrease in their plasma values and reduce their medicinal effect.

Etravirine also slightly inhibits the activity of CYP2C9 isoenzymes with CYP2C19 and P-glycoprotein.

The combination of Intelence with substances whose metabolism is largely mediated by CYP2C9 or CYP2C19 and which are also transported by P-glycoprotein may increase their plasma levels and potentiate or prolong their medicinal activity and side effects.

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Storage conditions

Intelence should be stored in a place inaccessible to children. The temperature level should not exceed 30°C.

Shelf life

Intelence is permitted to be used within a 2-year period from the date of manufacture of the medicinal substance.

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Application for children

There is no information regarding the drug's safety and effectiveness when administered to individuals under 6 years of age or weighing less than 16 kg.

Analogues

The analogs of the drug are Arverenz, Estiva, Neviraton, Viramun, Efavirenz with Nevivir, and also Efamat, Nevimun, Favir with Nevipan, Eferven with Efavir and Nevirapine. Also on the list are Stocrin and Efcur with Effachop 600.

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