Raltegravir - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Means for the treatment of HIV infection

Included in the formulation

Isentress®

pills inwards

Merck Sharp and Doum B.V. Netherlands

Isentress®

pills inwards

Merck Sharp and Doum B.V. Netherlands

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

АТХ:

J.05.A.X Other antiviral drugs

J.05.A.X.08 Raltegravir

Pharmacodynamics:An antiviral agent. Inhibits the catalytic activity of HIV integrase, an enzyme involved in viral replication. Inhibition of integrase prevents the covalent introduction of the HIV genome into the genome of the host cell in the early stages of infection. The HIV genomes not included in human DNA are not capable of inducing the production of new viral particles, as a result of which the integration process is suppressed and the further spread of the viral infection in the body is prevented. The inhibitory ability of raltegravir in relation to human phosphotransferase, including DNA polymerase, is negligible.

Pharmacokinetics:

Raltegravir is rapidly absorbed after taking the drug on an empty stomach, the maximum concentration in the blood plasma is reached after about 3 hours. AUC and maximum concentration increase proportionally in the dose range from 100 to 1600 mg. The absolute bioavailability of raltegravir is not established. Raltegravir can be taken regardless of the mode of food intake.

With the introduction of 2 times a day, the equilibrium state is reached quickly, approximately 2 days after the start of treatment. The values of AUC and maximum concentration indicate a minimal cumulation of raltegravir, plasma concentrations in 12 hours indicate a slight cumulation.

In the concentration range from 2 to 10 μmol, the binding of raltegravir to plasma proteins is 83%. Raltegravir easily penetrates the placental barrier. Does not penetrate the blood-brain barrier.

After ingestion of raltegravir, approximately 51% and 32% are excreted through the intestine and kidneys, respectively. In the stool is found only raltegravir - product of hydrolysis of raltegravir-glucuronide, secreted in bile. In the urine is determined raltegravir and raltegravir-glucuronide in proportions of approximately 9% and 23% of the administered dose, while in blood plasma 70% is raltegravir, and 30% - raltegravir-glucuronide. The main way of metabolism of raltegravir is represented by the process of glucuronization mediated by the enzyme uridine-diphosphate-glucuronosyltransferase.

Indications:Treatment of HIV-1 infection (even if other antiretroviral drugs are ineffectivex preparations) in combination with other antiretroviral drugsth preparations.

ICD-10

I.B20-B24 Disease caused by the human immunodeficiency virus [HIV]

Contraindications:Children and adolescence under 16; pregnancy, lactation (breastfeeding); increased sensitivity to raltegravir, a deficiency of sugar / isomalbasins, intolerance to fructose, glucose-galactosemalabsorption; phenylketonuria.

Carefully:Severe hepatic insufficiency, concomitant hepatitis C, concomitant use with powerful UGT1A1 inducers (including rifampicin); patients with predispositionto the development of myopathy or rhabdomyolysis or with these conditions in the anamnesis, the simultaneous use of the drug with antacids containing aluminum or magnesium. Care should be taken when prescribing the drug to patients with depression or psychiatric illnesses in history.

Pregnancy and lactation:Recommendations for FDA - Category C. Contraindicated in pregnancy, during lactation (breastfeeding).

Dosing and Administration:

Accepted inside. The recommended dose is 400 mg twice a day. The maximum dose is 1600 mg / day.

The maximum daily dose of chewing tablets is 300 mg 2 times a day.

Treatment is carried out in combination with other antiretroviral drugs.

Side effects:

From the side 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 alkaline phosphatase in the serum.

From the side CNS and peripheral nervous system: headache, dizziness, asthenia, weakness; rarely - irritability, peripheral neuropathy, paresthesia, polyneuropathy, drowsiness, depression, insomnia, unusual dreams, feelings of anxiety.

From the side hematopoiesis system: rarely - anemia, including macrocytic anemia, neutropenia.

From the side of cardio-vascular system: rarely - myocardial infarction, palpitations, ventricular extrasystole.

From the side sense organs: rarely - blurred vision.

From the side metabolism: rarely - increased appetite, decrease or increase in body weight, lipomatosis, impaired fat metabolism, diabetes mellitus, hyperglycemia, hyperlactatemia, hyperlipidemia, hypertriglyceridemia.

From the side musculoskeletal system: rarely - arthralgia, myalgia, pain in extremity, back pain, muscle cramps, myositis, muscular atrophy, increased creatine kinase activity.

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

From the side reproductive system: rarely - erectile dysfunction, gynecomastia.

Allergic reactions: hypersensitivity reactions.

Dermatological reactions: rarely - acquired lipodystrophy, rash, erythema, rash, including macular and maculo-papular rash, dermatoxerasia itching.

Other: rarely - a feeling of discomfort in the chest, chills, fever, phlegmon, infections caused by the Herpes simplex virus, nosebleeds.

Overdose:No data.
Treatment: removal of non-sucking drug from the gastrointestinal tractth track, monitoring of vital signsand, including ECG, the appointment of symptomatic therapy.

Interaction:

With the simultaneous use with uridine diphosphate inducers of glucuronosyltransferase 1A1 (UDF-GT1A1), such as rifampicin, the concentration of raltegravir in blood plasma is reduced.

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

The simultaneous use of raltegravir with drugs that increase the pH of gastric juice (for example, omeprazole or famotidine) can increase the absorption rate of raltegravir and, accordingly, the concentration of raltegravir in blood plasma.

Special instructions:

Use with caution in patients at risk of developing myopathy, rhabdomyolysis, and increasing the concentration of creatine phosphokinase in the blood serum.

In the initial stages of combination therapy with antiretrovirals, HIV-infected patients may develop an inflammatory response to asymptomatic or residual opportunistic infections (cytomegalovirus or pneumocystis pneumonia caused by Pneumocystis jiroveci, tuberculosis or paratuberculosis,caused by Mycobacterium avium), which can manifest itself as a worsening of the clinical condition and strengthening of the existing symptoms. Usually such reactions are observed in the first weeks or months after the initiation of therapy. In such cases, additional diagnostic and treatment measures may be required.

Since it is not known whether raltegravir when dialysis is not recommended before the dialysis session.

Impact on the ability to drive vehicles and manage mechanisms

Studies to study the impact on the ability to drive vehicles and the use of mechanisms were not carried out. Given the possibility of developing dizziness, weakness, drowsiness and blurred vision on the background of therapy, patients should exercise special care when engaging in potentially hazardous activities.

Instructions

Raltegravir (Raltegravirum)