Juluca (Tablets) Instructions for Use

Marketing Authorization Holder

ViiV Healthcare UK, Limited (United Kingdom)

Manufactured By

Glaxo Operations UK Limited (United Kingdom)

Packaging and Quality Control Release

Glaxo Wellcome, S.A. (Spain)

ATC Code

J05AR21 (Dolutegravir and Rilpivirine)

Active Substances

Rilpivirine (Rec.INN registered by WHO)

Dolutegravir (Rec.INN registered by WHO)

Dosage Form

Juluca

Film-coated tablets, 50 mg+25 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets brownish-pink in color, oval, biconvex, with a bevel and with the inscription “SV J3T” engraved on one side.

Excipients: mannitol, microcrystalline cellulose, silicified microcrystalline cellulose [microcrystalline cellulose, colloidal silicon dioxide], povidone K29/32, povidone K30, sodium carboxymethyl starch, sodium stearyl fumarate, croscarmellose sodium, lactose monohydrate, polysorbate 20, magnesium stearate, film coating Opadry II pink 85 F240164 [polyvinyl alcohol (partially hydrolyzed), titanium dioxide, macrogol/polyethylene glycol, talc, iron oxide yellow dye, iron oxide red dye].

30 pcs. – high-density polyethylene bottles (1) – cardboard packs with first-opening control.

Clinical-Pharmacological Group

Antiviral drug active against HIV

Pharmacotherapeutic Group

Antiviral [HIV] agent

Pharmacological Action

A combined antiviral agent. It contains two active substances used for the treatment of HIV infection: Dolutegravir and Rilpivirine. Dolutegravir belongs to the group of integrase inhibitors (INI). Rilpivirine belongs to the group of non-nucleoside reverse transcriptase inhibitors (NNRTI).

It does not cure HIV infection but maintains the amount of virus in the body at a low level. This helps maintain the number of CD4+ cells in the blood. CD4+ cells are a type of white blood cell that helps the body fight infection.

Pharmacokinetics

Dolutegravir

The pharmacokinetics of dolutegravir in healthy volunteers and HIV-infected patients are the same. The variability of dolutegravir pharmacokinetics was low to moderate.

Dolutegravir is rapidly absorbed after oral administration. The linearity of dolutegravir pharmacokinetics is dose- and formulation-dependent. Food increases the extent and reduces the rate of absorption of dolutegravir. The absolute bioavailability of dolutegravir has not been established.

The binding of dolutegravir to human plasma proteins is approximately 99.3%. The apparent V_d after oral administration of the suspension is approximately 12.5 L. Dolutegravir penetrates into the cerebrospinal fluid and is detected in the male and female genital tracts. The AUC in cervicovaginal fluid, cervical and vaginal tissues was 6-10% of that in plasma at steady state. The AUC in seminal fluid was 7%, and in rectal tissue was 17% of that in plasma at steady state.

It is metabolized mainly by uridine diphosphate-glucuronosyltransferase (UDP-GT) 1A1 with minor involvement of the CYP3A isoenzyme. Dolutegravir is the main compound circulating in plasma. It is excreted by the kidneys unchanged to a minor extent (<1% of the dose). 53% of the total oral dose is excreted unchanged through the intestine. It is unknown whether this is due to complete or partial incomplete absorption of the medicinal dolutegravir or biliary excretion of the glucuronide conjugate, which may further break down to form related compounds in the intestinal lumen. 31% of the total oral dose is excreted by the kidneys in the form of dolutegravir glucuronide ester (18.9% of the total dose), an N-dealkylated metabolite (3.6% of the total dose), and a metabolite formed by oxidation of the benzylic carbon (3.0% of the total dose). The terminal T_1/2 is about 14 hours, clearance is 0.56 L/h.

Rilpivirine

After oral administration, the C_max of rilpivirine in plasma was reached within 4-5 hours. The absolute bioavailability of rilpivirine is unknown. The bioavailability of rilpivirine was approximately 40% lower when the drug was taken on an empty stomach than when taken simultaneously with normal-calorie food (533 kcal) or high-fat food (928 kcal). When taken with a protein-enriched drink, bioavailability was 50% lower than when taken simultaneously with food.

Binding to plasma proteins, predominantly albumin, is 99.7%. The distribution of rilpivirine in biological fluids (cerebrospinal fluid, genital tract secretions) has not been studied.

In vitro studies have shown that Rilpivirine undergoes oxidative metabolism mediated by the CYP3A isoenzyme system.

The terminal T_1/2 of rilpivirine is approximately 45 hours. After a single oral dose of ¹⁴C-rilpivirine, approximately 85% and 6.1% of the radioactively labeled dose was found in feces and urine, respectively.

The amount of rilpivirine found unchanged in feces averaged 25% of the administered dose. Only a negligible amount of unchanged rilpivirine (less than 1% of the dose taken) was detected in urine.

Indications

Treatment of HIV infection in adults over 18 years of age.

ICD codes

Dosage Regimen

Take one tablet orally once daily.

Administer Juluca with a meal to ensure adequate absorption.

Do not crush or chew the tablet; swallow it whole.

If you miss a dose and it is less than 12 hours since the usual time, take the missed dose immediately with food and then resume the normal schedule.

If you miss a dose and it is more than 12 hours since the usual time, skip the missed dose and take the next dose at the regular time.

Do not take a double dose to make up for a forgotten one.

Take antacids containing aluminum, magnesium, or calcium at least 4 hours after or 6 hours before taking Juluca.

Take H2-receptor antagonists (e.g., famotidine, ranitidine) at least 4 hours after or 12 hours before taking Juluca.

Take calcium or iron supplements and multivitamins at least 4 hours after or 6 hours before taking Juluca, or administer them with a meal at the same time as Juluca.

This regimen is indicated for adults (18 years and older) who are virologically suppressed on a stable antiretroviral regimen.

Do not use Juluca in patients with severe hepatic impairment (Child-Pugh Class C).

Discontinue Juluca immediately if a severe skin reaction or hypersensitivity reaction is suspected.

Adverse Reactions

Nervous system disorders very common – headache, dizziness, insomnia; common – drowsiness, sleep disorders, unusual dreams, fatigue, depression, depressed mood, anxiety; uncommon – hepatitis.

Digestive system disorders very common – diarrhea, nausea; common – loss of appetite, abdominal pain or discomfort, pain in the upper abdomen (abdominal cavity), vomiting, flatulence, dry mouth.

Skin and subcutaneous tissue disorders common – rash, skin itching, vomiting.

Investigations very common – increased activity of liver transaminases, increased cholesterol concentration, increased level of pancreatic amylase; common – increased CPK activity,
Decreased platelet count, leukopenia, decreased hemoglobin level, increased triglyceride level, increased lipase level, increased blood bilirubin concentration.

Immune system disorders: uncommon – severe allergic reactions, which may include skin rash, fever, fatigue, swelling, sometimes in the face or mouth area (angioedema), causing difficulty breathing, muscle or joint pain; rare – immune reconstitution syndrome.

Musculoskeletal and connective tissue disorders rare – symptoms of osteonecrosis.

Contraindications

Hypersensitivity to dolutegravir, rilpivirine; simultaneous use of the following medicinal products: ampyridine, carbamazepine, oxcarbazepine, phenobarbital or phenytoin, rifampicin or rifapentine, omeprazole, esomeprazole, lansoprazole, pantoprazole or rabeprazole, dexamethasone for oral or injectable use, except when the drug is used as a single dose, preparations of St. John’s wort.

With caution

Liver diseases, including viral hepatitis B and/or C.

Use in Pregnancy and Lactation

Use is not recommended during planned and confirmed pregnancy.

Use is not recommended during breastfeeding.

Pediatric Use

The safety and efficacy of using this combination in children under 18 years of age have not been established. Use is not recommended.

Special Precautions

During treatment with the drug containing the combination Dolutegravir + Rilpivirine for HIV infection, the development of serious diseases and conditions is possible, including symptoms of infections and inflammatory processes; joint pain, joint stiffness and signs of osteonecrosis.

HIV infection is transmitted through sexual contact with an infected person or through infected blood (for example, through sharing injection needles). It should be borne in mind that when taking this combination, the possibility of transmitting HIV infection to other people remains, although this risk is reduced due to effective antiretroviral therapy.

Antacids should be taken within 6 hours before or at least 4 hours after taking this combination.

Histamine H₂-receptor antagonists (including famotidine, cimetidine, nizatidine, ranitidine) should not be taken within 12 hours before or at least 4 hours after taking this combination.

Use in pediatrics

The use of this combination in children under 18 years of age is not recommended, as the safety and efficacy of this combination in this category of patients have not been established.

Effect on ability to drive vehicles and operate machinery

When using this combination, dizziness, fatigue or drowsiness may occur. Patients experiencing such symptoms should avoid driving vehicles and other potentially hazardous activities during treatment.

Drug Interactions

With simultaneous use with rifabutin, a decrease in the plasma concentration of the combination components is possible, which reduces the therapeutic effectiveness of the combination. In such cases, an additional dose of rilpivirine is recommended.

With simultaneous use with antacids, absorption of the combination components may be impaired, which may reduce its effectiveness.

Calcium- or iron-containing dietary supplements, as well as multivitamins, may interfere with the absorption of the combination components and reduce its effectiveness.

Histamine H₂-receptor blockers (such as famotidine, cimetidine, nizatidine, ranitidine) may interfere with the absorption of the combination components in the body and reduce its effectiveness.

During the use of this combination, a change in the effectiveness of any other drugs for the treatment of HIV infection is possible; rifabutin; the combination of artemether + lumefantrine; clarithromycin, erythromycin; methadone; dabigatran etexilate.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.