Elpida capsules 20 mg, 30 pcs.

Treatment of HIV-1 infection in adults as part of combination antiretroviral therapy.

Active ingredient

Composition

1 capsule contains:

the active ingredient:

elsulfavirin sodium 20.7 mg (in terms of elsulfavirin 20.0 mg);

excipients:

Lactose monohydrate,

croscarmellose sodium,

p> povidone-K30,

magnesium stearate;

hard gelatin capsule:

Titanium dioxide (E171), crimson [Ponceau 4R] dye (E124), red iron oxide dye (E172), gelatin.

How to take, the dosage

The drug Elpida is taken orally. It is recommended to take the drug on an empty stomach 15 minutes before a meal. The capsule should be swallowed whole without chewing, with plenty of water.

Elpida should be prescribed by a doctor who has experience in treating HIV infection.

Elpida must be prescribed in combination with other antiretroviral medicines.

Adults

Elpida is prescribed in a dose of 20 mg once daily in combination with other antiretroviral medicines.

If another dose of Elpida is missed at the usual time and less than 6 hours have passed since the scheduled time of administration, the missed capsule should be taken as soon as possible. The next capsule should be taken at the prescribed time.

If more than 6 hours have passed since the scheduled appointment, continue the next day at the scheduled time.

Dose adjustment

There are no dose adjustments for Elpida or concomitant therapy.

Patients with impaired renal function

Elpida is contraindicated in patients with moderate to severe renal impairment (GFR < 60 ml/min).

Patients with impaired liver function

Elpida is contraindicated in patients with moderate to severe impaired liver function (Child-Pugh grades B and C).

Interaction

Antiretroviral drugs

In a phase 3 clinical trial, Elpida was used as part of a complex APT with a fixed combination of 2 NRTIs – tenofovir and emtricitabine. This drug combination was well tolerated by patients.

In a clinical trial evaluating drug-drug interactions, the use of Elpida in combination with the HIV protease inhibitors darunavir and ritonavir and the integrase inhibitor raltegravir was studied. In general, coadministration was well tolerated. Changes in pharmacokinetic parameters and drug exposure were insignificant and did not require changes in the standard dosing regimen of these drugs. Administration of atazanavir after completion of therapy with Elpida in another clinical trial resulted in severe adverse gastrointestinal reactions (nausea, vomiting) characteristic of atazanavir.

Other drugs

The drug Elpida induces the activity of CYP2B6 and CYP3A4 isoenzymes and can decrease the plasma concentration and, therefore, the activity of drugs that are substrates of these isoenzymes. Concomitant use of these drugs should be treated with caution.

The substrates of CYP2B6 and CYP3A4 isoenzymes whose activity can be reduced by co-administration of Elpida

The substrates of CYP2B6 and CYP3A4:

Immunosuppressors (cyclosporine, tacrolimus, sirolimus).

. Chemotherapy drugs (docetaxel, tamoxifen, paclitaxel, cyclophosphamide, doxorubicin, erlotinib, etoposide, ifosfamide, teneposide, vinblastine, vincristine, vindesin, imatinib, sorafenib, sunitinib, vemurafenib, temsirolimus, anastrozole, genfatinib).

The azole antifungal drugs (ketoconazole, itraconazole).

Macrolides (clarithromycin, erythromycin, telithromycin; except azithromycin). Tricyclic antidepressants (amitriptyline, clomipramine, imipramine, cyclobenzaprine).

Selective serotonin reuptake inhibitors (citalopram, norfluoxetine, sertraline).

Other antidepressants (mirtazapine, nefazodone, reboxetine, venlafaxine, trazodone). Antipsychotics (haloperidol, aripiprazole, risperidone, ziprasidone, pimozide).

Opiate analgesics (alfentanil, buprenorphine, codeine, fentanyl, hydrocodone, methadone, levacetylmethadol, tramadol).

Benzodiazepines (alprozolam, midazolam, triazolam, diazepam).

Sleeping pills (zopiclone, zaleplon, zolpidem).

Statins (atorvastatin, lovastatin, simvastatin, cerivastatin; except pravastatin and rosuvastatin).

Calcium channel blockers (diltiazem, feldipine, nifedipine, verapamil, amlodipine, lercanidipine, nitrandipine, nisoldipine, bepridil).

Antiorhythmics (amiodarone, dropedarone, quinidine).

Phosphodiesterase-5 inhibitors (sildenafil, tadalafil).

Gender hormone agonists and antagonists (finasteride, estradiol, progesterone, ethinyl estradiol, testosterone, toremifene, bicalutamide).

H1-receptor antagonists (terfenadine, astemizole, chlorphenamine).

HIV protease inhibitors (indinavir, ritonavir, saquinavir, nelfinavir).

Some glucocorticosteroids (budesonide, hydrocortisone, dexamethasone).

Other CYP2B6 substrates:

Bupropion, valproic acid, methoxetamine, propofol, efavirenz.

Other CYP3A4 substrates:

. Aprepitant, buspirone, warfarin, dapsone, domperidone, donepezil, caffeine, clopidogrel, lidocaine, montelukast, nateglinide, nevirapine, omeprazole, ondansetron, propranolol, salmeterol, cisapride, eplerenone, ergot alkaloids (ergotamine, dihydroergotamine, ergonovine, methyl ergonovine).

Special Instructions

Patients should be warned that current antiretroviral drugs do not cure HIV infection or prevent HIV transmission to others through blood or sexual contact. Patients should continue to take appropriate precautions during treatment with Elpida.

Elpida is not used as monotherapy to treat HIV infection (may lead to the development of virus resistance) or as the only drug added to an ineffective treatment. Treatment should be given by a physician with sufficient experience in treating HIV infection.

Given the tropicity of the active metabolite to blood cells, caution should be exercised when prescribing Elpida in patients with severe anemia and pancytopenia.

Companion APT

If any antiretroviral drug in the combination APT is withdrawn due to suspected intolerance, all antiretroviral drugs should be considered for simultaneous withdrawal. All antiretrovirals that have been discontinued should be resumed as soon as the symptoms of intolerance have disappeared. Interrupted monotherapy and sequential re-treatment with antiretrovirals are not recommended because of the increased likelihood of emergence of therapy-resistant virus.

The effects of food

Eating affects the absorption kinetics of Elpid, significantly reducing absorption, so it is recommended that Elpid be taken on an empty stomach.

Allergic reactions

No allergic reactions have been reported while taking Elpida in the clinical studies conducted.

Immune reconstitution syndrome

In HIV-infected patients with severe immunodeficiency, an inflammatory response in response to activation of pathogens of asymptomatic or residual opportunistic infections may occur at the start of combination APT, which may result in serious clinical conditions or increased symptomatology. These reactions usually occur within the first weeks or months after initiation of complex APT. Typical examples are cytomegalovirus retinitis, generalized and/or focal mycobacterial infection and pneumonia caused by Pneumocystis jiroveci (P. carinii). The appearance of any symptoms of inflammation requires evaluation and, if necessary, treatment. Autoimmune diseases (such as Graves’ disease) have also been observed against the background of immune reconstitution, but the timing of the initial manifestations varied and the disease could occur many months after the start of therapy.

Body weight and metabolic parameters

An increase in body weight and an increase in blood glucose and lipid concentrations may be seen against the background of APT. These changes may be partly related to the disease itself and lifestyle. In some cases, the effect of therapy on an increase in lipid concentration has been proven, but there is no conclusive evidence of the effect of therapy on an increase in body weight. Blood glucose and lipid concentrations should be monitored according to the guidelines for the treatment of HIV infection. Lipid metabolism disorders should be corrected if clinically necessary.

Lipodystrophy and metabolic disorders

Combination APT is associated with redistribution of subcutaneous body fat (lipodystrophy) in HIV-infected patients. The long-term effects of this phenomenon are still unknown and the mechanism of its development is poorly understood. It has been suggested that visceral lipomatosis is associated with the use of HIV protease inhibitors and lipoatrophy with the use of NIOT. The increased risk of lipodystrophy may be due to both individual factors, such as advanced age, and factors associated with drug administration, such as prolonged APT and associated metabolic disorders. Therefore, during the clinical examination of a patient, a physical examination should be performed, paying attention to the redistribution of subcutaneous fat, as well as determining the serum lipid concentration and fasting plasma glucose concentration. Abnormalities should be corrected according to clinical manifestations.

Osteonecrosis

While the etiology of this disease is recognized as multifactorial (including glucocorticosteroid use, alcohol abuse, severe immunosuppression, increased body mass index), cases of osteonecrosis have been observed primarily in patients with long-term HIV infection and/or in patients who have received long-term combination APT. Patients should immediately consult a physician if they experience joint pain, decreased joint mobility or difficulty walking. No such reactions have been reported in clinical studies of Elpida.

Contraindications

– Hypersensitivity to elsulfavirin sodium or any other component of the drug.

– Lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome (the drug contains lactose).

– Children under 18 years of age.

– Pregnancy and breastfeeding period.

– Patients with renal dysfunction of moderate to severe degree (GFR < 60 ml/min).

Patients with moderate to severe hepatic dysfunction (Child-Pugh grades B and C).

With caution:

– Patients with severe anemia and pancytopenia.

– Simultaneous use with drugs whose metabolism occurs with participation of CYP2B6 and CYP3A4 cytochrome P450 isoenzymes (see section “Interaction with other medicinal products”).

– Patients with mild hepatic dysfunction (class A according to Child-Pugh) (see section “Special Precautions”).

Side effects

The frequency of adverse drug reactions by organs and systems is given according to the World Health Organization (WHO) classification and taking into account the size of the general population of patients with HIV infection treated with Elpida in the clinical trials conducted: very common (≥ 1/10) – more than 10 cases; common (≥ 1/100, <1/10) – 2 to 10 cases, infrequent (≥ 1/1000, <1/100) – a single case, rare (≥ 1/10000, <1/1000) – not applicable, very rare (<1/10000) – not applicable.

Infectious and parasitic diseases: often – herpes simplex; infrequently – genital herpes, oral herpes, fungal infection.

Blood and lymphatic system disorders: frequently – leukopenia and neutropenia.

Endocrine system disorders: infrequent – autoimmune thyroiditis.

Psychiatric disorders: frequently – sleep disorders, depressive states (depressed mood), anxiety, apathy, irritability; infrequently – aggression, mood swings, attention deficit, intrusive thoughts, nightmares.

Nervous system disorders: very frequently – headache; frequently – dizziness, unusual dreams, somnolence; infrequently – decreased concentration, memory disturbance, insomnia, decreased quality of sleep, disorder of taste sensitivity, paresthesia.

Hearing and labyrinth disorders: infrequent – hyperacusis, tinnitus.

Respiratory system, chest and mediastinum disorders: infrequent – cough, shortness of breath, pain in the oropharynx, rhinorrhea, olfactory disorders.

Gastrointestinal disorders: frequently – nausea, diarrhea, dry mouth. vomiting; infrequently – abdominal discomfort, abdominal pain, belching, glossalgia, colitis.

Skin and subcutaneous tissue disorders: frequently – rash, itching; infrequently – hair loss, furunculosis.

Muscular and connective tissue disorders: infrequent – arthralgia.

Renal and urinary tract disorders: frequently – mild proteinuria, polyuria; infrequently – urolithiasis, leukocyturia.

Gender and mammary gland disorders: infrequent – menstrual delay, polymenorrhea, sexual dysfunction.

General disorders and disorders at the site of administration: often – asthenia, weakness, decreased appetite, increased body temperature; infrequently – pain in the chest.

Laboratory and instrumental data: very common – increase of gamma-glutamyl transferase (GGT) activity; common – increase of alanine aminotransferase (ALT) activity, increase of creatine phosphokinase (CPK) activity, increase of blood glucose level; infrequent – increase of aspartataminotransferase (ACT) activity, increased blood pressure, weight loss. If any of the side effects listed in the instructions worsen, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose