Tegvimel (Tablets) Instructions for Use

Marketing Authorization Holder

Izvarino Pharma LLC (Russia)

Manufactured By

Izvarino Pharma LLC (Russia)

Quality Control Release

IZVARINO PHARMA, LLC (Russia)

Or

NANOFARMA DEVELOPMENT, LLC (Russia)

ATC Code

J05AJ01 (Raltegravir)

Active Substance

Raltegravir (Rec.INN registered by WHO)

Dosage Form

Tegvimel

Film-coated tablets, 400 mg: 60 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets from light pink to pink in color, oval in shape, biconvex, with a score on one side and an engraving "f" on the other side.

Excipients: microcrystalline cellulose (type 102), hypromellose (type 2208) (hydroxypropyl methylcellulose), lactose monohydrate, anhydrous dibasic calcium phosphate, sodium stearyl fumarate, magnesium stearate, tablet coating [polyvinyl alcohol, titanium dioxide (E172), talc, macrogol 3350 (polyethylene glycol), yellow iron oxide (E172), red iron oxide (E172), black iron oxide (E172)].

10 pcs. – blister packs (6) – cardboard cartons.

Clinical-Pharmacological Group

Antiviral drug active against HIV

Pharmacotherapeutic Group

Systemic antiviral agents; direct-acting antiviral agents; other antiviral agents

Pharmacological Action

Antiviral agent. 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 during the early stages of infection. 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 capacity of raltegravir against human phosphotransferases, including DNA polymerases a, b, and g, is minimal.

Pharmacokinetics

Raltegravir is rapidly absorbed after administration on an empty stomach; C_max in plasma is reached in approximately 3 hours. AUC and C_max increase proportionally to the dose in the range from 100 to 1600 mg. The absolute bioavailability of raltegravir has not been established. Raltegravir can be taken with or without food.

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

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

After oral administration of raltegravir, approximately 51% and 32% is excreted via the intestine and kidneys, respectively. Only Raltegravir – a hydrolysis product of Raltegravir-glucuronide secreted into the bile – is found in feces. Raltegravir and Raltegravir-glucuronide are detected in urine in proportions of approximately 9% and 23% of the administered dose, respectively, while in 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 in cases of ineffectiveness of other antiretroviral drugs) in combination with other antiretroviral drugs.

ICD codes

Dosage Regimen

Take orally. The recommended dose is 400 mg twice daily approximately every 12 hours.

Take with or without food.

Adhere strictly to the twice-daily schedule to maintain consistent antiviral activity.

The maximum daily dose is 1600 mg.

Always administer in combination with other antiretroviral drugs; do not use as monotherapy.

For patients concurrently receiving strong UDP-GT inducers like rifampicin, consider a dose increase to 800 mg twice daily.

Swallow tablets whole; do not chew or crush.

If a dose is missed, take it as soon as remembered. If it is almost time for the next dose, skip the missed dose and continue the regular schedule. Do not take a double dose.

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, including 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, limb pain, 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, including macular and maculopapular rash, xeroderma, pruritus.

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

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

Effect on ability to drive vehicles and operate machinery

Studies on the effect on the ability to drive vehicles and operate 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 effect 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 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.