Rolnavir^® (Tablets) Instructions for Use

Marketing Authorization Holder

Promomed Rus LLC (Russia)

Manufactured By

Biokhimik, JSC (Russia)

ATC Code

J05AJ01 (Raltegravir)

Active Substance

Raltegravir (Rec.INN WHO registered)

Dosage Form

Rolnavir®

Film-coated tablets, 400 mg: 30 or 60 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets pink in color, oval, biconvex; the core on the cross-section is white or almost white with gray specks.

Excipients: microcrystalline cellulose (type 102) – 169.4 mg, lactose monohydrate – 26.06 mg, calcium hydrogen phosphate – 69.5 mg, hypromellose – 43.44 mg, poloxamer 407 – 104.3 mg, sodium stearyl fumarate – 8.688 mg, magnesium stearate – 13.03 mg.

Film coating partially hydrolyzed polyvinyl alcohol – 10.424 mg (40 %), titanium dioxide (E171) – 6.224 mg (23.88 %), macrogol 4000 (polyethylene glycol 4000) – 5.264 mg (20.2 %), talc – 3.856 mg (14.8 %), iron oxide red dye (E172) – 0.276 mg (1.06 %), iron oxide yellow dye (E172) – 0.016 mg (0.06 %)
Or ready-made film coating Opadry^® II 85F240280 pink – 26.06 mg [partially hydrolyzed polyvinyl alcohol – 40 %; titanium dioxide (E171) – 23.88 %; macrogol 4000 (polyethylene glycol 4000) – 20.2 %; talc – 14.8 %; iron oxide red (E172) – 1.06 %; iron oxide yellow (E172) – 0.06 %].

10 pcs. – contour cell packaging (3) – cardboard packs (1).
10 pcs. – contour cell packaging (6) – cardboard packs (1).
30 pcs. – jars (1) – cardboard packs (1).
60 pcs. – jars (1) – cardboard packs (1).

Clinical-Pharmacological Group

Antiviral drug active against HIV

Pharmacotherapeutic Group

Antiviral [HIV] agent

Pharmacological Action

Antiviral agent. It inhibits the catalytic activity of HIV integrase, an enzyme involved in viral replication. Inhibition of integrase prevents the covalent insertion of the HIV genome into the host cell genome at the early stages of infection development. HIV genomes not integrated into human DNA are unable to induce the production of new viral particles, thereby suppressing the integration process and preventing further spread of the viral infection in the body. The inhibitory ability of raltegravir against human phosphotransferases, including DNA polymerases a, b, and g, is insignificant.

Pharmacokinetics

Raltegravir is rapidly absorbed after administration on an empty stomach; C_max in blood plasma is reached in approximately 3 hours. AUC and C_max increase proportionally to the dose in the dose range from 100 to 1600 mg. The absolute bioavailability of raltegravir has not been established. Raltegravir can be taken regardless of food intake.

When administered twice daily, steady state is reached rapidly, within approximately 2 days after the start of treatment. The AUC and C_max values indicate minimal accumulation of raltegravir; the plasma concentrations at 12 hours indicate insignificant accumulation.

In the concentration range from 2 to 10 µmol, the binding of raltegravir to plasma proteins is 83%. Raltegravir easily crosses the placental barrier. It does not cross the blood-brain barrier.

After oral administration of raltegravir, approximately 51% and 32% are excreted via the intestine and kidneys, respectively. Only Raltegravir – a hydrolysis product of Raltegravir-glucuronide secreted into bile – is found in feces. Raltegravir and Raltegravir-glucuronide are determined in urine in proportions of approximately 9% and 23% of the administered dose, respectively, while in blood plasma, 70% is Raltegravir and 30% is Raltegravir-glucuronide. The main metabolic pathway of raltegravir is glucuronidation mediated by the enzyme uridine diphosphate glucuronosyltransferase.

Indications

Treatment of HIV-1 infection (even with the ineffectiveness of other antiretroviral drugs) in combination with other antiretroviral drugs.

ICD codes

Dosage Regimen

Administer orally. The recommended adult dose is 400 mg twice daily.

Take tablets with or without food. Do not exceed the maximum daily dose of 1600 mg.

Always use Rolnavir^® in combination with other antiretroviral agents. Never use as monotherapy.

For patients concurrently receiving rifampicin, increase the dosage to 800 mg twice daily.

Swallow tablets whole; do not chew, crush, or split them.

Adhere strictly to the twice-daily schedule. If a dose is missed by less than 6 hours, take the missed dose immediately and resume the normal schedule. If more than 6 hours have passed, skip the missed dose and continue with the next scheduled dose.

In patients with severe renal impairment or end-stage renal disease, no dosage adjustment is required. Use with caution in patients with pre-existing muscle disorders or those at risk for elevated creatine phosphokinase.

Discontinuation of therapy may increase the risk of therapeutic failure; do not interrupt treatment without consulting a physician.

Adverse Reactions

From the digestive system diarrhea, nausea, abdominal pain; rarely – vomiting, discomfort and pain in the upper abdomen, constipation, dyspepsia, flatulence, gastritis, glossitis, gastroesophageal reflux, hepatitis, hepatomegaly, hyperbilirubinemia, increased activity of AST, ALT and ALP in serum.

From the central and peripheral nervous system headache, dizziness, asthenia, weakness; rarely – irritability, peripheral neuropathy, paresthesia, polyneuropathy, drowsiness, depression, insomnia, unusual dreams, anxiety.

From the hematopoietic system rarely – anemia, incl. macrocytic anemia, neutropenia.

From the cardiovascular system rarely – myocardial infarction, palpitations, ventricular extrasystole.

From the sensory organs rarely – blurred vision.

From metabolism rarely – increased appetite, decrease or increase in body weight, lipomatosis, lipid metabolism disorder, diabetes mellitus, hyperglycemia, hyperlactatemia, hyperlipidemia, hypertriglyceridemia.

From the musculoskeletal system rarely – arthralgia, myalgia, pain in the extremities, back pain, muscle spasms, myositis, muscle atrophy, increased CPK activity.

From the urinary system rarely – toxic nephropathy, nephrotic syndrome, nocturia, pollakiuria, renal failure, tubular necrosis.

From the reproductive system rarely – erectile dysfunction, gynecomastia.

Allergic reactions hypersensitivity reactions.

Dermatological reactions rarely – acquired lipodystrophy, hyperhidrosis, erythema, rash, incl. macular and maculopapular rash, xeroderma, itching.

Other rarely – chest discomfort, chills, fever, phlegmon, infections caused by Herpes simplex virus, nosebleeds.

Contraindications

Children and adolescents under 16 years of age; pregnancy, lactation (breastfeeding); hypersensitivity to raltegravir.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation (breastfeeding).

Pediatric Use

Contraindicated in children and adolescents under 16 years of age.

Special Precautions

Use with caution in patients at risk of developing myopathy, rhabdomyolysis, and increased serum CPK concentration.

At the initial stages of combined therapy with antiretroviral agents in HIV-infected patients, an inflammatory reaction to asymptomatic or residual opportunistic infections (cytomegalovirus or pneumocystis pneumonia caused by Pneumocystis jirovecii, tuberculosis or paratuberculosis caused by Mycobacterium avium) may develop, which may manifest as a worsening of the clinical condition and intensification of existing symptoms. Usually, such reactions are observed in the first weeks or months after the start of therapy. In such cases, additional diagnostic and therapeutic measures may be required.

Since it is unknown whether Raltegravir is removed by dialysis, administration is not recommended immediately before a dialysis session.

Effect on the ability to drive vehicles and operate machinery

Studies on the effect on the ability to drive vehicles and use machinery have not been conducted. Given the possibility of dizziness, weakness, drowsiness, and blurred vision during therapy, patients should exercise particular caution when engaging in potentially hazardous activities.

Drug Interactions

With simultaneous use with inducers of uridine diphosphate glucuronosyltransferase 1A1 (UDP-GT1A1), such as rifampicin, the plasma concentration of raltegravir decreases. The influence of other enzyme inducers – such as phenytoin, phenobarbital, involved in the metabolism of raltegravir, on UDP-GT1A1, is unknown.

With simultaneous use of raltegravir with inhibitors of UDP-GT1A1 (including atazanavir), a moderate increase in the plasma concentration of raltegravir is observed.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°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.