Intelens

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Intelens: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Intelence

ATX code: J05AG04

Active ingredient: etravirine (etravirine)

Manufacturer: Janssen-Cilag SpA (Italy)

Description and photo updated: 2018-16-08

Intelens is an antiviral drug that is active against the human immunodeficiency virus (HIV).

Release form and composition

The drug is produced in the form of tablets: almost white or white; dosage 100 mg - oval, engraved on one side "T125", on the other - engraved "100"; dosage 200 mg - biconvex, oblong, engraved on one side "T200" [120 pcs. 100 mg or 60 pcs. 200 mg in a polyethylene bottle with 3 bags with desiccant (silica gel), 2 g each, in a cardboard box 1 bottle and instructions for use of Intelens].

1 tablet contains:

active substance: etravirine - 100/200 mg;
additional components: microcrystalline cellulose, colloidal silicon dioxide, hypromellose, magnesium stearate, croscarmellose sodium, lactose monohydrate (100 mg tablets), microcrystalline silicon cellulose (200 mg tablets).

Pharmacological properties

Pharmacodynamics

Etravirine is an antiviral agent related to HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). The active substance directly communicates with reverse transcriptase and suppresses the DNA-dependent and RNA-dependent activity of DNA polymerase, leading to the destruction of the catalytic sites of this enzyme. Demonstrates activity against laboratory strains and clinical isolates of HIV-1 wild type in acutely infected T-cell lines, in monocytes / macrophages and human peripheral mononuclear cells.

Etravirine has an in vitro antiviral effect against a wide range of HIV-1 group M members (including subtypes A, B, C, D, E, F, G) and primary group O isolates, for which the mean effective concentration (EC ₅₀) can be in the range of 0.7-21.7 nM.

The agent is not included in the antagonist group of any of the antiretroviral drugs studied. Intelens is characterized by additive antiviral activity in combination with the following drugs:

protease inhibitors (PIs): atazanavir, amprenavir, indinavir, darunavir, nelfinavir, lopinavir, tipranavir, ritonavir, saquinavir;
NNRTIs: delavirdine, efavirenz, nevirapine;
nucleoside reverse transcriptase inhibitors (NRTIs) or nucleotide reverse transcriptase inhibitors (NRTIs): didanosine, zalcitabine, abacavir, stavudine, tenofovir;
fusion inhibitor: enfuvirtide;
integrase inhibitor: raltegravir;
CCR5 receptor antagonist: maraviroc.

An additive or synergistic antiviral effect of etravirine has been reported in combination with NRTIs such as lamivudine, emtricitabine, and zidovudine.

Etravirine exhibits pronounced antiviral activity against 56 out of 65 HIV-1 strains with one amino acid substitution at the RT positions, which causes resistance to NNRTIs, including strains carrying the most common mutations Y181C and K103N. The mutations Y181V (17-fold change in EC ₅₀ value) and Y181I (13-fold change in EC ₅₀ value) are among the amino acid substitutions that cause the highest resistance to the active substance in cell culture.

The antiviral effect of etravirine in cell cultures against 24 strains of HIV-1, including multiple amino acid substitutions associated with resistance to PI and / or NNRTIs, is similar to the effect against the wild strain of HIV-1. The most frequently developing mutations in patients with unsuccessful virological results of therapy with combinations including etravirine were V179I, V179F, Y181I, Y181C.

In vitro studies have found limited cross-resistance between the active substance and efavirenz in 3 out of 65 mutant HIV-1 strains with a mutation that confers resistance to NNRTIs. The amino acid positions in other strains associated with poor sensitivity to etravirine and efavirenz were different. Etravirine exhibits an EC _{50 of} <10 nmol in contrast to 83% of the 6171 clinical isolates resistant to delavirdine, efavirenz and / or nevirapine. Patients whose etravirine regimen is virologically ineffective are not recommended to use delavirdine, efavirenz and / or nevirapine.

Pharmacokinetics

After oral administration with food, the maximum plasma concentration of etravirine (C _max) is reached within 4 hours. Plasma concentrations of a substance do not depend on the type of food consumed (with a high fat content - 1160 kcal, or normal calorie content - 561 kcal). The level of content of the product was lower in those cases when Intelens was used on an empty stomach (by 51%) or before meals (by 17%). Consequently, to achieve better absorption, the drug should be taken after meals.

In healthy volunteers, the absorption of etravirine did not change against the background of concomitant oral administration of omeprazole or ranitidine, which increased the pH of the stomach contents.

In vitro, etravirine almost completely (approximately 99.9%) binds to blood plasma proteins, mainly with α ₁ -oxidized glycoprotein (97.66-99.02%) and albumin (99.6%). In other biological fluids, including cerebrospinal fluid, the distribution of the active substance in humans has not been studied. In in vitro experiments with human liver microsomes, it was found that etravirine is predominantly subjected to oxidative metabolism with the participation of hepatic isoenzymes of the CYP3A family and, to a lesser extent, with the participation of isoenzymes of the CYP2C family, followed by glucuronization.

After oral administration of labeled ¹⁴ C-etravirine, 93.7% and 1.2% of the taken dose were detected in feces and urine, respectively. In feces, the proportion of unchanged etravirine was 81.2–86.4% of the dose taken; in urine, the substance in this form was not detected. The final elimination period of etravirine can vary from 30 to 40 hours.

In patients with renal failure, the pharmacokinetics of etravirine has not been studied. Less than 1.2% of an ingested dose of a substance is excreted in the urine. In an unchanged form, the agent was not found in the urine, so the effect of impaired renal activity on its excretion may be extremely insignificant. Etravirine is characterized by a very high degree of binding to plasma proteins, therefore, its elimination from the body in any significant quantities using hemodialysis or peritoneal dialysis is unlikely.

The process of metabolic transformation and elimination of etravirine occurs primarily in the liver. The pharmacokinetics of Intelens in the presence of mild and moderate disorders of its activity (classes A or B on the Child-Pugh scale) did not change, therefore the dose of the drug in such patients does not need to be reduced. In patients with severe hepatic impairment (class C on the Child-Pugh scale), the pharmacokinetics of the drug have not been studied.

In patients infected with HIV-1 and at the same time with hepatitis B and / or C virus, Intelens' clearance is reduced. Patients in this group should be careful, since they have an increased risk of increased activity of liver enzymes.

It was found that the race of the patient does not affect the pharmacokinetic parameters of Intelens.

There were no significant differences in the pharmacokinetics of the substance between women and men.

Indications for use

Intelens is recommended for the treatment of HIV-1 infection in adult patients receiving antiretroviral drugs, including in patients with NNRTI resistance as part of combination therapy.

Contraindications

malabsorption of glucose-galactose or lactose intolerance, galactose - for 100 mg (1 tablet contains 160 mg of lactose);
age up to 18 years;
pregnancy and lactation;
severe liver dysfunctions (class C according to the Child-Pugh classification) - for 200 mg;
combined use with drugs that affect the plasma level of etravirine in the blood, and drugs whose plasma levels change when combined with etravirine: NNRTIs (delavirdine, nevirapine, efavirenz, rilpivirine), PIs without the simultaneous use of low-dose ritonavir (atazanavir, nelfinavir, saquinavir, indinavir and others, except for fosamprenavir), anti-tuberculosis drugs (rifapentin, rifampicin), anticonvulsants (phenobarbital, carbamazepine, phenytoin), drugs containing St. John's wort (Hypericum perforatum), ritonaviravir / once a day at a dose of 600 mg;
hypersensitivity to any of the constituents of the antiviral agent.

With caution, Intelens tablets at a dosage of 200 mg should be used by elderly patients and patients simultaneously infected with hepatitis B and / or C.

Intelens, instructions for use: method and dosage

Intelens is taken orally after a meal; it is recommended to swallow the tablets whole with water. If the patient has difficulty swallowing, the tablets can be crushed and mixed thoroughly in a glass of water, and then immediately drink the resulting solution. In order to ensure that the full dose is taken, the glass must be rinsed with water several times and its contents must be completely drunk. In this case, warm (over 40 ° C) water and carbonated drinks cannot be used.

Intelens always needs to be given in combination with other antiretroviral drugs.

Adults are recommended to take Intelens 2 times a day, 200 mg, the maximum daily dose of etravirine should not exceed 400 mg.

If the patient has forgotten to take a dose, and it has not yet passed more than 6 hours after the usual time of administration, then it can be taken after meals as soon as possible, and the next dose can be used as usual. If more than 6 hours have passed after the usual time of admission, then you should not use the missed dose, and you should continue taking Intelens according to the previously used scheme.

Side effects

hematopoietic system: often - anemia, thrombocytopenia;
cardiovascular system: often - increased blood pressure, myocardial infarction; infrequently - angina pectoris, atrial fibrillation, hemorrhagic stroke;
nervous system: often - insomnia, anxiety, headache, peripheral neuropathy; infrequently - drowsiness, nervousness, sleep disturbances (including hypersomnia), nightmarish / unusual dreams, tremors, confusion, paresthesia, hypoesthesia, disorientation, impaired concentration, amnesia, fainting, convulsions;
urinary system: often - renal failure;
digestive system: often - nausea, flatulence, vomiting, diarrhea, abdominal pain, gastritis, gastroesophageal reflux; infrequently - stomatitis, dry mouth, constipation, urge to vomit, bloody vomiting, bloating, pancreatitis, hepatitis, cytolytic hepatitis, hepatomegaly, fatty liver degeneration;
metabolism: often - hyperglycemia, diabetes mellitus, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, hyperlipidemia; infrequently - anorexia;
sense organs: infrequently - vertigo, blurred vision;
respiratory organs: infrequently - shortness of breath during physical activity, bronchospasm;
skin and subcutaneous tissue: often - night sweats, skin rash, lipohypertrophy; infrequently - dry skin, facial edema, pruritus, hyperhidrosis, lipodystrophy;
reproductive system: gynecomastia;
allergic reactions: infrequently - erythema multiforme, angioedema, Stevens-Johnson syndrome;
immune system: infrequently - hypersensitivity to the drug, immune restoration syndrome;
laboratory indicators: increased activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), pancreatic amylase, lipase, an increase in total cholesterol, creatinine, low density lipoproteins, glucose, triglycerides, a decrease in the number of leukocytes, neutrophils;
general reactions: often - fatigue; infrequently - lethargy.

The most common adverse reactions reported were skin rash, nausea, diarrhea, and hypertriglyceridemia.

Cancellation of Intelens in most cases occurred due to the appearance of a rash. This adverse reaction was usually mild to moderate, macular, erythematous, or maculopapular. The rash, as a rule, appeared in the second week of treatment and was rarely observed after the fourth, usually did not require the appointment of special therapy and disappeared within 1–2 weeks of the continued course. During therapy, the incidence of rash was higher in women.

In the post-marketing period, the following disorders were recorded: hypersensitivity reactions, including DRESS symptom (drug-induced hypersensitivity syndrome with eosinophilia), accompanied by fever, rash and systemic manifestations (including rash with fever, severe rash, fatigue, general malaise, pain in muscles and joints, conjunctivitis, lesions of the oral mucosa, eosinophilia, hepatitis), on the part of the musculoskeletal tissue - rhabdomyolysis.

Overdose

There is no sufficient data on Intelens overdose. The most likely signs of an overdose may be undesirable effects often observed during the treatment period, such as nausea, rash, diarrhea, and headache. There is no specific antidote. If an overdose is suspected, supportive symptomatic therapy is prescribed, including monitoring the patient's condition and monitoring the basic physiological parameters. If necessary, the removal of etravirine from the stomach can be carried out by washing the latter, as well as by artificial vomiting or taking activated carbon.

special instructions

Patients should be aware that the use of modern antiretroviral drugs does not cure HIV infection and does not reduce the risk of HIV transmission through blood or through sexual intercourse to others. During treatment with Intelens, you must continue to observe all appropriate safety measures.

Therapy with the drug should be prescribed and carried out by a doctor with sufficient experience in treating HIV infection.

When prescribing and using Intelens, it is required to be guided by a therapeutic history and, if possible, by the results of determining the sensitivity of HIV-1 to antiretroviral drugs. If patients have had virologic failure in the treatment of NNRTIs and NRTIs or NRTIs, it is not recommended to carry out combination therapy with Intelens only with NRTIs or NRTIs.

You should immediately stop using Intelens if symptoms or signs of severe hypersensitivity reactions or severe skin reactions occur, by establishing observation of the patient's clinical condition, including monitoring the activity of hepatic transaminases, with further, if necessary, appropriate therapy. Severe hypersensitivity reactions and severe skin reactions, as a rule, occur at 3-6 weeks of therapy and in most cases disappear after discontinuation of the drug and at the beginning of the use of glucocorticosteroids. If the above complications have arisen during treatment with Intelens, you cannot continue taking the drug in the future. After a severe rash is detected, a delay in stopping the antiviral can cause a life-threatening reaction.

During the period of combination antiretroviral therapy, HIV-infected patients may experience lipodystrophy - a redistribution of adipose tissue in the body. This disorder is accompanied by the loss of facial and peripheral subcutaneous fat tissue, an increase in visceral and intra-abdominal fat mass, mammary gland hypertrophy, and fat accumulation in the dorsocervical region (fat hump formation). The mechanism of this phenomenon is currently poorly understood and its long-term consequences have not been established. There is a hypothesis about the existing relationship between PI and visceral lipomatosis, as well as between NRTI and lipoatrophy. The risk of this phenomenon is aggravated in the presence of such factors as concomitant metabolic disorders, advanced age, and long-term antiretroviral therapy. When conducting a clinical examination of HIV-infected patients, an assessment of physical signs of adipose tissue redistribution should be included.

During the initial period of combination antiretroviral therapy in HIV-infected patients with severe immunodeficiency, inflammatory reactions to asymptomatic / residual opportunistic infections may develop, the manifestations of which may be a worsening of the clinical condition and aggravation of existing symptoms. Such reactions in most cases are observed during the first weeks or months after starting therapy. Examples of this complication may be generalized and / or focal mycobacterial infections, cytomegalovirus retinitis, pneumonia caused by Pneumocystis jirovecii. If any symptoms of inflammation occur, you must immediately undergo an examination and carry out appropriate treatment. There have also been reports of the development of autoimmune diseases against the background of restoration of immunity, incl.diffuse toxic goiter. According to the available data, the timing of the onset of these diseases varies widely, and they can develop many months after the start of combination treatment.

Influence on the ability to drive vehicles and complex mechanisms

There are currently no data on the negative impact of Intelens on the ability to drive a car or any other complex equipment. At the same time, the profile of side reactions of this agent should be taken into account.

Application during pregnancy and lactation

In pregnant women, taking Intelens is contraindicated.

Well-controlled and adequate clinical studies of the safety of using Intelens during pregnancy have not been conducted. In the course of animal studies, no negative effect of the drug on the course of pregnancy, childbirth, intrauterine and postnatal development was found.

Data on the effect of Intelens on human fertility are currently lacking.

It is not known whether etravirine passes into breast milk in women. Due to the threat of mother-to-infant transmission of HIV during breastfeeding and the development of possible unwanted effects of etravirine in lactating women themselves, HIV-infected mothers should refrain from breastfeeding during treatment.

Pediatric use

Intelens tablets are contraindicated in patients under 18 years of age.

With impaired renal function

In the presence of functional disorders of the kidneys, there is no need to adjust the dose of Intelens.

For violations of liver function

The pharmacokinetics of Intelens in the presence of mild and moderate liver disorders (classes A or B on the Child-Pugh scale) does not change, and therefore it is not required to adjust the dose in this group of patients. Caution should be exercised when using the drug in patients with moderate liver dysfunction.

Patients with severe hepatic impairment (class C on the Child-Pugh scale) are contraindicated to take Intelens at a dosage of 200 mg.

In patients infected with HIV-1 and at the same time with hepatitis B and / or C virus, Intelens' clearance is reduced. Given the safety profile of etravirine, dose adjustment is not required in this case. Patients in this group should be careful, since they have an increased risk of increased activity of liver enzymes.

Use in the elderly

The pharmacokinetic characteristics of etravirine do not depend on the age of the patients (from 18 to 77 years). Elderly people do not need to change the dose of the drug. Patients of this age group have limited experience with Intelens treatment, so they should take it with caution.

Drug interactions

drugs that induce CYP2C19, CYP2C9 or CYP3A4: the concentration of etravirine in plasma decreases due to the acceleration of its clearance, since these isoenzymes are involved in the metabolic transformation of etravirine, and its metabolites under the influence of the enzyme uridine diphosphate glucuronosyltransferase undergo glucuronization;
drugs that suppress CYP2C19, CYP2C9 or CYP3A4: the plasma concentration of etravirine increases due to a slowdown in its clearance;
drugs that are metabolized mainly by the CYP3A4 isoenzyme: plasma levels decrease and their therapeutic effects weaken or shorten (etravirine refers to weak inducers of the CYP3A4 isoenzyme);
drugs that are metabolized predominantly by CYP2C19 or CYP2C9 isoenzymes, or which are transported using P-glycoprotein: the plasma concentration of such drugs increases and, as a result, their therapeutic or side effects increase or lengthen (etravirine is a weak inhibitor of P-glycoprotein, CYP2C19 isoenzymes and CYP2C9).

Drug interactions while using etravirine with other antiretroviral drugs:

NRTIs: didanosine (400 mg once a day), tenofovir (300 mg once a day) - dose adjustment can be omitted; since didanosine should be used on an empty stomach, it is recommended to take it 1 hour before or 2 hours after taking Intelens; emtricitabine, abacavir, stavudine, zidovudine, lamivudine and others - it is believed that etravirine does not interact with these drugs, since they are excreted mainly by the kidneys;
PI with simultaneous ritonavir: atazanavir / ritonavir (once a day, 300/100 mg), saquinavir / ritonavir (gelatin soft capsules; 2 times a day, 1000/100 mg), lopinavir / ritonavir (gelatin soft capsules, tablets; 2 times a day, 400/100 mg), darunavir / ritonavir (2 times a day, 600/100 mg) - Intelens can be used in combination with each of these combinations without changing doses; fosamprenavir / ritonavir (2 times a day, 700/100 mg) - it may be necessary to change the doses of drugs of this combination and etravirine;
two PI drugs with simultaneous administration of ritonavir: lopinavir / saquinavir / ritonavir (2 times a day, 400/800–1000 / 100 mg): this combination does not require dose adjustment;
antagonists of CCR5 receptors: maraviroc - a change in the dose of etravirine is not required, the doses of maraviroc are adjusted in accordance with the instructions, given that Intelens has the properties of an inducer of CYP3A isoenzymes;
integrase inhibitors: raltegravir (2 times a day, 400 mg) - used without dose adjustment; dolutegravir (1 time per day, 50 mg) - can be used simultaneously with etravirine only while taking such combinations as darunavir / ritonavir, atazanavir / ritonavir or lopinavir / ritonavir;
fusion inhibitors: enfuvirtide (2 times a day, 90 mg) - the interaction presumably does not occur.

Interactions of etravirine with some other drugs / substances:

flecainide, amiodarone, disopyramide, bepridil, mexiletine, intravenous lidocaine (i.v.), quinidine, propafenone (antiarrhythmics): their concentration may decrease; the use of etravirine in combination with these agents requires caution, if possible with the control of the plasma content of these drugs;
digoxin (0.5 mg once): with this combination, dose adjustment of both drugs is not required; monitoring of plasma digoxin concentration is necessary;
warfarin (anticoagulants): there may be a change in the level of its content, monitoring of the international normalized ratio (INR) is recommended;
itraconazole, ketoconazole, posaconazole: an increase in the plasma concentration of etravirine and a decrease in the concentration of itraconazole and ketoconazole are possible, simultaneous treatment with these agents is carried out without changing doses;
fluconazole (200 mg once a day in the morning), voriconazole (200 mg twice a day): the combination is prescribed without dose adjustment;
azithromycin: this agent is eliminated by the kidneys and presumably does not interact;
clarithromycin (2 times a day, 500 mg): its concentration decreases by 53%, but the concentration of 14-hydroxy-clarithromycin (active metabolite) increases by 46%, and since the latter has a reduced activity against the Mycobacterium avium complex (MAC), the total activity of the agent and its metabolite against MAC may change; in this case, it is advisable to use substances alternative to clarithromycin (azithromycin);
artemether / lumefantrine (80/480 mg, 6 doses according to the scheme: 0 h, 8 h, 24 h, 36 h, 48 h, 60 h): no dose adjustment is necessary, but the combination should be carried out with caution, since. it is not known whether a decrease in exposure to artemether or dihydroartemisinin (its active metabolite) can cause a decrease in antimalarial activity;
rifabutin (300 mg once a day): etravirine alone with PIs, boosted ritonavir can be used with rifabutin without changing doses; if etravirine is used with lopinavir, darunavir, or saquinavir in combination with ritonavir, rifabutin should be used with caution because of the increased risk of a significant decrease in plasma levels of etravirine; Rifabutin is prescribed at a dose that is consistent with the instructions for use of the PI;
diazepam (benzodiazepines): its concentration in plasma may increase;
ribavirin: excreted by the kidneys, therefore interaction with etravirine is unlikely;
telaprevir (750 mg every 8 hours), boceprevir (800 mg 3 times a day) (antiviral agents): no dose adjustment required; when combined with boceprevir, caution must be exercised due to the risk of a decrease in the plasma concentration of etravirine, careful monitoring of the virological response to treatment for hepatitis C virus and HIV should be carried out;
dexamethasone (glucocorticosteroids for systemic use): the plasma level of etravirine may decrease and its therapeutic effect may be weakened; the combination requires caution, especially with a long course;
atorvastatin (40 mg once a day): to achieve the desired effect, it is recommended to adjust its dose;
rosuvastatin, lovastatin, simvastatin (substrates of CYP3A4): a decrease in plasma concentrations of these agents is possible;
Pravastatin: Presumably no interaction with etravirine;
fluvastatin, pitavastatin, rosuvastatin: metabolized with the participation of the CYP2C9 isoenzyme, their plasma level may increase, dose adjustment may be necessary;
sirolimus, cyclosporine, tacrolimus (systemic immunosuppressants): changes in their plasma concentrations are possible; these combinations require caution;
clopidogrel: the disintegration of this agent is suppressed to the formation of its active metabolites; the possibility of alternative treatment options should be considered;
vardenafil, sildenafil, tadalafil [phosphodiesterase type 5 inhibitors (PDE-5)] at a daily dose of 50 mg: it may be necessary to change their doses to achieve the desired therapeutic effect;
omeprazole, paroxetine (both drugs 1 time per day, 40 mg), methadone (60–130 mg per day), ranitidine (2 times a day, 150 mg), norethisterone and ethinyl estradiol (a combination of estrogen and / or progesterone-based contraceptives): No dose adjustments are required for all drugs.

Analogs

The analogue of Intelens is Etravirine.

Terms and conditions of storage

Store out of the reach of children, at a temperature not exceeding 30 ° C, in a well-closed bottle to prevent moisture ingress; Do not discard desiccant bags.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Intelens

There are very few reviews about Intelens. Doctors point out that the drug is a modern effective drug intended for the treatment of infection caused by HIV, and against the background of treatment with a minimum number of adverse reactions. According to patient reviews, Intelens in combination therapy with other antiretroviral drugs has shown good results in most cases. Side effects, mainly from the nervous system, occurred most often at the beginning of treatment, then their frequency and severity decreased. All patients recommend taking the drug only after meals.

Price for Intelens in pharmacies

Approximate prices for Intelens can leave:

200 mg tablets: 5980–6480 rubles per bottle containing 60 pieces;
tablets 100 mg: 7900–9500 rubles per bottle containing 120 pcs.

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!