Guidance note:


Merck Sharp and Doum BV, Netherlands Merk Sharp &Dohme B.V

Composition of Isendress

Active substance : raltegravir.1 tablet, coated, contains 400 mg of raltegravir.
Excipients .Microcrystalline cellulose, lactose monohydrate, calcium hydrophosphate anhydrous;Hydroxypropylmethylcellulose;Poloxamer;Sodium stearyl fumarate;Magnesium stearate;Fill gray( composition: polyvinyl alcohol partially hydrolyzed, polyethylene glycol, talc, titanium dioxide( E 171), iron oxide black( E172).

Issue Issue of

Tablets coated with 400 mg No. 60.

To whom Isentress is shown?

Treatment of HIV-1 infection with ineffectiveness of other antiretroviral drugs, that is, patients with persistent replication of HIV, despite ongoing antiretroviral therapy( in combination with other antiretroviral drugs).

How to use Isentress

LecheThe Isentress drug should be given by a doctor who has sufficient experience in HIV therapy. The dose of Isentress, recommended for the treatment

of HIV-1 infection, is 400 mg twice a day. The drug can be taken irrespective of food intake. With other antiretroviral drugs. As tablets are coated, it is not recommended to chew them, break them, crush them.

Features of the use of Isentress

Patients should be warned that the treatment does not cure HIV infection and does not prevent the transmission of the human immunodeficiency virus to others through blood or sexual contact. During treatment with Isentress, appropriate precautions should be taken. In patients who had a genotype sensitivity( PGM)> 0, the highest drug efficacy was observed. Patients with PPV or phenotypic sensitivity( PFS) of 0 had a greater risk of developing resistance to raltegravir. Raltegravir should be used in combination with at least one active agent to increase efficacy and reduce the risk of developing resistance to raltegravir.

Patients with hepatic insufficiency. No data are available on the clinical efficacy and safety of the drug in patients with severe liver disease. Therefore, Isentress should be used with caution in patients with severe hepatic insufficiency. Patients with pre-documented hepatic insufficiency, including chronic hepatitis, had a greater incidence of side effects from the liver with combined antiretroviral therapy and required follow-up according to standard treatment practice. If liver disease worsens, these patients should decide whether to stop or discontinue therapy.

Patients with renal insufficiency. For patients with renal failure, no additional dose adjustment is required.

Immunodeficiency Syndrome. In HIV-infected patients with acute immunodeficiency in the administration of combination antiretroviral therapy( CART), an inflammatory response to symptomatic pathogens or residual opportunistic microorganisms may result, which leads to a severe clinical condition or worsening of symptoms. Typically, this reaction is observed during the first weeks or months after the start of MAP.For example: cytomegalovirus retinitis, general or focal mycobacterial infections, pneumonia caused by Pneumocystis jiroveci , etc. The development of such reactions may require additional diagnostic and therapeutic measures.

Use of Isentress in patients with viral hepatitis B and / or C. According to clinical studies, the safety profile of Isentress in patients with viral hepatitis B and / or C was comparable to the safety profile in patients who did not have viral hepatitis, despiteElevated parameters of ALT and AST.

Osteonecrosis .Cases of osteonecrosis in patients with progressive HIV infection and / or prolonged use of antiretroviral therapy are described. Patients should be warned about the need for urgent consultation with a doctor if they have experienced acute or prolonged pain in the joints, limited mobility of the joints or complication of movements.

Application for increased riskyomyopathy and arabdomyolysis .The likelihood of developing side effects such as myopathy, rhabdomyolysis, and increased serum creatine kinase concentration in Isentress therapy has not been determined, and caution should be given to prescribing to people at risk for myopathy and rhabdomyolysis, particularly for patients receiving drugs that can cause these side effects.

Caution should be used to administer Isentress simultaneously with the effective inducers of uridine diphosphate-glucuronosyltransferase( UDF-HT) 1A 1( i.e., rifampicin) becauseThey reduce the plasma concentration of raltegravir.

The drug Isentress contains lactose. Patients with rare hereditary diseases of galactose intolerance, lactase deficiency in lobes( Saami) or inadequate absorption of glucose-galactose use this drug.

Older patients. When choosing a dose, one should remember about the greater probability for the elderly person of such age-related features as decreased function of the liver, kidneys, heart, and also to take into account the accompanying pathology and concomitant drug therapy.

Application ofperiod of pregnancy and breastfeeding. There are no data on the safety of the drug in pregnant women. Isentress, like other antiretroviral drugs, is not recommended for use during pregnancy. There are no data on the penetration of raltegravir into the human breast milk. However, it has been established that raltegravir penetrates into the milk of animals. Therefore, breast-feeding during treatment with Isentress is not recommended. In addition, HIV-infected mothers are generally not recommended to breast-feed to avoid postnatal transmission of HIV to children.

Children .The safety and effectiveness of raltegravir under the age of 16 years has not been studied.

Ability to influence the speed of the response of the administration of vehicles or the operation of other mechanisms. Some side effects of the drug may affect the ability of the patient to drive vehicles and work with mechanisms. Therefore, it is recommended to refrain from driving or working with machinery during the period of application of the drug.

Who is contraindicated with Isentress?

  • Hypersensitivity to the drug.
  • Children under 16 years.

Side-Effects of Isentress

Hypersensitivity to the components of the drug.

Adverse reactions that were observed with a frequency ≥ 2%: diarrhea, nausea, headache, fever. Adverse reactions that occurred at a rate of & lt; 2% are classified by organ and system as often( ≥ 1/100, & lt; 1/10) and occasionally( ≥ 1/1000, <1/100).

  • On the part of the hematopoiesis system. Rare: anemia, including macrocytic anemia, neutropenia.
  • From the side of the cardiovascular system. Rarely: myocardial infarction, palpitations, ventricular extrasystoles.
  • From the nervous system. Rarely: vertigo, impaired vision, dizziness, headache, allodynia( sensation of pain when exposed to a non-motile stimulus), peripheral neuropathy, paresthesia, polyneuropathy, drowsiness.
  • From the digestive tract. Often: abdominal pain, diarrhea, constipation. Rarely: vomiting, discomfort and pain at the top of the abdomen, dyspepsia, flatulence, gastritis, glossitis, gastroesophageal reflux( heartburn), nausea, hepatitis, hepatomegaly( liver enlargement), hyperbilirubinemia, elevation of hepatic enzymes.
  • Common violations. Often: asthenia, fatigue. Rarely: chest discomfort, chills, fever, hot flashes, irritability.
  • From the immune system. Rarely: hypersensitivity to the drug, fever.
  • From the skin and subcutaneous tissues. Rarely: phlegmon, herpes simplex, acquired lipodystrophy, skin irritation, hyperhidrosis, acne dermatitis, erythema, subcutaneous tissue atrophy, night sweats, macular or maculopapular rash, xeroderma, pruritus.
  • From the side of metabolism. Rarely: diabetes mellitus, impaired fat metabolism, central obesity, dyslipidemia, facial atrophy, hyperlactacidemia, hyperlipidemia, hypertrophic glyceride, an increase in appetite, lipomatosis, a decrease or increase in body weight.
  • From the musculoskeletal system and connective tissue. Rarely: arthralgia, myalgia, pain in the extremities, back pain, muscle spasms, osteo-muscular pain, myositis, muscle atrophy.
  • On the part of the respiratory system. Rarely: nosebleeds.
  • From the urinary system. Rarely: toxic nephropathy, nephrotic syndrome, nocturia, pollakiuria, renal failure, chronic renal failure, impaired renal function, tubular necrosis.
  • From the side of the reproductive system. Rarely: erectile dysfunction and gynecomastia.
  • Mental disturbances. Rarely: depression, insomnia, unusual dreams, feelings of anxiety.
  • Effect on laboratory performance. Hyperglycemia, lactacidemia, hyperlipidemia, hypertroglyceridemia, increased levels of total bilirubin, AST, ALT, alkaline phosphatase and creatine phosphokinase.

Interaction of Isendress

Isentress does not affect the pharmacokinetic parameters of protease inhibitors, methadone, non-nucleoside reverse transcriptase inhibitors, opioid analgesics, statins, antifungal azoles, proton pump inhibitors, oral contraceptives, and drugs for the treatment of erectile dysfunction.

According to research, raltegravir is excreted from the body mainly by metabolism in the process of glucuronidization of UDF-HT 1A 1.Caution should be used to assign Isentress concomitantly with the effective inducers of uridine diphosphate-glucuronosyltransferase( UDF-HT) 1A 1, such as rifampicin, because they reduce the plasma concentration of raltegravir. The effect of other effective enzyme inducers, such as phenytoin, phenobarbital, involved in the metabolism of the drug on UDF-HT 1A 1, is not known. Other, less effective inducers( efavirenz, nevirapine, rifabutin, glucocorticoids, pioglitazone, St. John's wort) can be administered concomitantly with the recommended doses of Isentress. Simultaneous administration of the drug with effective inhibitors of UDP-HT 1A 1( eg, atazanavir) is accompanied by a slight increase in the plasma concentration of Isentress. According to clinical studies, combined therapy with two drugs was generally well tolerated by patients, there was no need for dose adjustment.

Overdose by Isentress

No specific symptoms of overdose were detected by Isentress. Raltegravir has a wide therapeutic range, and the likelihood of toxic manifestations in overdose is very low. In case of an overdose, standard supportive measures are recommended: removal of non-sucking drug from the gastrointestinal tract, symptomatic therapy, usual emergency care, monitoring of vital signs, including ECG, and the appointment of supportive therapy, if necessary. There is no data on the effectiveness of dialysis of Isentress.