Isentress, 25 mg, 60 pcs.

The active ingredient of Isentress, raltegravir, inhibits the catalytic activity of the enzyme involved in the reproduction (replication) of the HIV virus, HIV integrase. Inhibiting the latter prevents covalent insertion, or integration into the host cell genome of the HIV genome in the early stages of infection. HIV genomes that are not inserted into human DNA cannot produce new viral particles; thus, inhibition of the integration process blocks further spread of the viral infection in the body. Against human phosphotransferases, including DNA polymerases α, β and γ, inhibitory activity of raltegravir is weak.

Indications

Active ingredient

How to take, the dosage

Ingestion. Isentress chewable tablets are prescribed regardless of meals.

The treatment with Isentress should be given by a physician with sufficient experience in HIV therapy.

Because the dosage forms of raltegravir are not bioequivalent, chewable tablets should not be replaced with film-coated tablets of 400 mg.

The maximum daily dose of chewable tablets is 300 mg twice daily.

The treatment with Isentress is carried out in combination with other antiretroviral drugs.

The recommended doses of Isentress in the dosage form of chewable tablets for treatment of HIV-1 infection in children aged 2-11 years are calculated by body weight so that the maximum daily dose of raltegravir does not exceed 300 mg twice daily (see Table 1).

Table 1. Recommended doses* of Isentress in the dosage form of chewable tablets for children aged 2-11 years.

* – Dose recommendations by body weight are based roughly on taking 6 mg/kg/dose 2 times daily.

1- 100 mg chewable tablets – can be divided into two halves.

Patients should be made aware of the need for a dosing schedule, as the dose of Isentress should be adjusted as the child grows.

Contraindications

– hypersensitivity to any of the ingredients of the drug;

– children under 2 years of age and body weight less than 7 kg;

– pregnancy;

– lactation period;

– Sucrose/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption;

– phenylketonuria.

With caution: myopathy and rhabdomyolysis (including in anamnesis); presence of conditions and factors predisposing to their development; severe hepatic insufficiency; concurrent use with strong inducers of UDF-GT1A1 (rifampicin); concurrent use of Isentress with antacids containing aluminum or magnesium; depression, including suicidal ideas and behavior, observed mainly in patients with depression or psychiatric diseases in anamnesis. Caution should be exercised when prescribing Isentress to patients with a history of depression or psychiatric illness.

Side effects

The safety profile of Isentress is based on the results of pooled safety data from clinical trials involving patients previously treated with antiretroviral therapy (ART) and patients not previously treated with ART.

In a pooled analysis of adult clinical trials of antiretroviral therapy in patients previously treated with ART, the discontinuation rate due to adverse reactions was 3.9% in the group of patients receiving Isentress and optimized complementary therapy (OCT) and 4.6% in the group of patients receiving placebo and OCT. The rate of therapy withdrawal due to adverse reactions in adult patients not previously receiving ART was 5.0% in the group of patients taking Isentress concomitantly with emtricitabine and tenofovir and 10.0% in the group of patients taking efavirenz, emtricitabine and tenofovir concomitantly.

The adverse events observed in clinical trials, with varying degrees of probability associated with Isentress or its combination with another ART, are shown below.

The adverse events are listed according to system-organ classes and frequency classification: frequent – >1/100 and <1/10), infrequent – >1/1000 and <1/100.

Infectious and parasitic diseases: infrequent – genital herpes, folliculitis, gastroenteritis, herpes simplex, herpetic infection, shingles, influenza, lymph node abscess, contagious molluscs, nasopharyngitis, upper respiratory infection.

Benign, malignant and unspecified neoplasms (including cysts and polyps): infrequent – skin papillomatosis.

Blood and lymphatic system disorders: infrequent – anemia, iron deficiency anemia, painful lymph nodes, lymphadenopathy, neutropenia, thrombocytopenia1.

Immune system disorders: infrequent – immune reconstitution syndrome, hypersensitivity to the drug, hypersensitivity reactions.

Metabolism and nutrition: frequent – decreased appetite; infrequent – cachexia, diabetes, dyslipidemia, hypercholesterolemia, hyperglycemia, hyperlipidemia, hyperphagia, increased appetite, polydipsia, fat metabolism disorders.

Psychiatric disorders: Frequent – unusual dreams, insomnia, nightmares, conduct disorder2, depression; infrequent – psychotic disorders, suicide attempts, anxiety, confusion, depressed mood, major depressive disorder, midnight insomnia, mood changes, panic attacks, sleep disorders, suicidal ideation1, suicidal behavior1 (especially in patients with a history of psychiatric illness).

Nervous system disorders: Frequent – dizziness, headache, psychomotor hyperreactivity2, infrequent – amnesia, carpal tunnel syndrome, cognitive disorders, attention disorders, postural vertigo, dysgesia, hypersomnia, hypoesthesia, lethargy, memory disorders, migraine, peripheral neuropathy, paresthesias, somnolence, tension headache, tremor, decreased sleep quality.

Visually: infrequent – decrease in visual acuity.

Hearing organ and labyrinth disorders: frequent – vertigo; infrequent – tinnitus.

Heart: infrequent – palpitations, sinus bradycardia, ventricular extrasystole.

Vascular disorders: infrequent – blood rushes to the skin of the face with a feeling of heat, arterial hypertension.

Respiratory system, thoracic and mediastinal organs: infrequent – dysphonia, nasal bleeding, nasal congestion.

Gastrointestinal disorders: frequent – feeling of distention in the abdomen, abdominal pain, diarrhea, flatulence, nausea, vomiting, dyspepsia; infrequent – gastritis, abdominal discomfort, upper abdominal pain, abdominal pain, discomfort in the anus, constipation, dry mouth, discomfort in the epigastric region, erosive duodenitis, belching, gastroesophageal reflux, gingivitis, glossitis, painful swallowing, acute pancreatitis, peptic ulcer, rectal bleeding.

Hepatic and biliary tract disorders: infrequent – hepatitis, steatosis of the liver, alcoholic hepatitis, liver failure1.

Skin and subcutaneous tissue disorders: Frequent – skin rash; infrequent – acne, alopecia, acne-like rash, dry skin, erythema, facial lipoatrophy, hyperhidrosis, lipoatrophy, acquired lipodystrophy, lipohypertrophy, night sweats, prurigo, itching (local and generalized), Macular rash, maculopapular rash, pruritic rash, urticaria, xeroderma, other skin lesions, Stevens-Johnson syndrome1, drug rash with eosinophilia and systemic symptoms1.

Muscular and connective tissue disorders: infrequent – arthralgia, arthritis, back pain, side pain, myalgia, neck pain, osteopenia, pain in the extremities, osteoporosis, polyarthritis, tendinitis, myopathy, rhabdomyolysis1.

Renal and urinary tract disorders: infrequent – renal failure, nephritis, nephrolithiasis, nycturia, renal cysts, renal dysfunction, tubulointerstitial nephritis.

Gender and breast disorders: infrequent – erectile dysfunction, gynecomastia, menopausal symptoms.

General disorders and disorders at the site of administration: frequent – asthenia, weakness, fever; infrequent – chest discomfort, chills, facial edema, increased fatty tissue, restlessness, malaise, submandibular neoplasm, peripheral edema, pain.

Laboratory and instrumental findings: frequent – increased plasma alanine aminotransferase (ALT), aspartate aminotransferase (ACT), pancreatic lipase and amylase activity, increased triglyceride concentration and atypical lymphocyte count; infrequent – reduced absolute plasma neutrophil count; increased plasma alkaline phosphatase, amylase, creatine phosphokinase activity. decrease of albumin concentration; increase of bilirubin, cholesterol, creatinine, glucose concentration (including fasting), urea nitrogen, high density lipoprotein cholesterol, low density lipoprotein cholesterol; increase of international normalized ratio; decrease of platelets and leukocytes count in blood; presence of glucose in urine, presence of red blood cells in urine; increased waist circumference; increase or decrease of body weight.

Injuries, intoxications and complications of manipulations: infrequent – unintentional overdose.

1 Adverse events unrelated to the use of Isentress that were observed in the post-registration period and were not observed in clinical trials.

2 One pediatric patient had adverse reactions associated with Isentress: Grade 3 psychomotor hyperresponsiveness and conduct disorder; this patient also had insomnia.

In clinical trials, there have been cases of malignancies in patients who have and have not received ART when using a combination of Isentress with other antiretrovirals. The characteristics and frequency of malignant neoplasms were consistent with those of patients with severe immunodeficiency. The risk of malignant neoplasms in clinical trials was similar in the groups of patients taking Isentress and in the groups of patients taking comparison drugs.

In patients taking Isentress, an increase in creatine phosphokinase activity of 2-4 degrees was observed. Cases of myopathy and rhabdomyolysis were observed. In patients with a history of myopathy or rhabdomyolysis or with other risk factors (including concomitant therapy) the drug should be prescribed with caution.

The development of osteonecrosis has been reported, particularly in patients with established risk factors, late-stage HIV disease, or long-term exposure to combination ART. The frequency of its development is unknown.

In clinical studies in patients previously treated with ART, cutaneous rash, regardless of etiology, was observed more frequently when Isentress was used concomitantly with darunavir than when the drugs were used alone. Nevertheless, the incidence of drug-related skin rash was comparable in these treatment groups. The skin rash was mild to moderate in severity and did not affect continuation of ART. Patients who had not previously been on ART were less likely to develop a rash when treated with Isentress in combination with emtricitabine and tenofovir than when treated with efavirenz in combination with emtricitabine and tenofovir.

Patients with hepatitis B and/or hepatitis C co-infection

Patients with hepatitis B and/or hepatitis C co-infection. Overall, the safety profile of Isentress in patients both previously and not receiving HRV therapy who were co-infected with chronic (but not acute) active hepatitis B and/or hepatitis C was similar to that in patients without hepatitis B and/or hepatitis C co-infection, although the rate of ALT and ACT activity deviation was sometimes higher in the groups with hepatitis B and/or hepatitis C co-infection.

Children

In clinical studies of the use of raltegravir in recommended doses in combination with other antiretroviral medications in HIV-1-infected children and adolescents 2 to 18 years of age, the frequency, type, and severity of adverse reactions associated with the drug were found to be comparable to those in adults. One patient experienced drug-related adverse reactions: grade 3 psychomotor hyperactivity, conduct disorder, and insomnia. Another patient had a grade 2 serious adverse reaction – an allergic rash. Another patient had a grade 4 ACT and grade 3 ALT elevation that was considered serious.