Antiviral (HIV) medicine
ATX code: J05AX08
Raltegravir inhibits the catalytic activity of HIV integrase-an enzyme involved in HIV virus replication. Inhibition of pitegrase prevents covalent insertion (integration) of the HIV genome into the host cell genome in the early stages of infection.
The HIV genomes not incorporated into human DNA are incapable of inducing production of new viral particles, so suppression of the integration process prevents the spread of viral infection in the body.
The inhibitory ability of raltegravir against human phosphotransferases, including DNA polymerases α, β and γ, is insignificant.
At a plasma concentration of 31 ± 20 nmol/L, raltegravir provides 95% suppression of viral replication (95% inhibitory concentration, IC95) in human T cell cultures infected with an H9IIIB HIV-1 cell culture-adapted variant, compared to control virus-infected cell culture.
IK95 was achieved at concentrations ranging from 6 to 50 nmol/L in cultures of human mitogen-activated peripheral blood mononuclear cells. infected with various primary clinical strains of HIV-1, including strains of 5 non-B HIV-1 subtypes as well as strains resistant to HIV reverse transcriptase inhibitors and protease inhibitors.
In a single infection cycle assay, raltegravir suppressed infection caused by 23 strains of HIV representing non-B subtypes and 5 circulating recombinant forms, with IK50 at concentrations ranging from up to 12 nmol/L. Raltegravir also suppressed HIV-2 strain replication when tested on CEMx174 cells (IK95 = 6 nmol/L).
When raltegravir and nucleoside reverse transcriptase inhibitors (zidovudine, zalcitabine, stavudine, abacavir, tenofovir. didanosine and lamnvudine) were simultaneously introduced into cultures of human T cells infected with variant H9IIIB of HIV-1 virus.
. Non-nucleoside reverse transcriptase inhibitors (efavirenz, jevirapine and delavirdine), HIV protease inhibitors (indinavir, saquinavir, ritonavir, amnrenavir, loninavir, nelfinavir and atazanavir) or fusion inhibitor (enfuvirtide) showed additive to synergistic antiretroviral activity.
. HIV-1 nntegrase mutations that contribute to raltegravir-resistant strains of the virus (developed either in vitro or in patients taking raltegravir) Mainly include substitutions at positions 155 (N155 substitution for H), 148 (Q148 substitution for H, K or R) or 143 (Y143 substitution for C, H or R), combined with one or more additional mutations (e.g., L74M, E92Q, T97A, E138L/K, G140A/S. V151I, G163R, S230R).
The recombinant viruses with a single primary mutation (Q148H, K or R or N15511) were characterized by reduced replication ability and reduced sensitivity to raltegravir in vitro.
Secondary mutations of the virus further reduced sensitivity to raltegravir. sometimes compensating for the reduced replication ability of the virus. Mutations associated with the development of resistance to raltegravir can also lead to resistance to another integrase chain transfer inhibitor elvitegravir.
The substitution at position 143 reduces the sensitivity to raltegravir to a greater extent than the sensitivity to elvitegravir, while mutations in E92Q- greater resistance to elvitegravir than to raltegravir. Viruses with a mutation at position 148 in combination with one or more additional mutations causing resistance to raltegravir can also show clinically significant resistance to dolutegravir.
Impact on cardiac electrophysiologic activity or electrocardiogram scores
. In a placebo-controlled clinical study involving healthy volunteers, a single dose of 1,600 mg of raltegravir had no effect on QTc interval duration, even though the maximum plasma concentration (Cmax) of raltegravir was 4 times greater than that of a single dose of 400 mg raltegravir.
In adult patients
Raltegravir is rapidly absorbed after the drug is taken on an empty stomach; Cmax in plasma is determined after approximately 3 hours. The area under the curve “concentration-time” (AUC) and the value of Cmax of raltegravir increase in proportion to dose in the dose range from 100 mg to 1600 mg.
The Cmax values of raltegravir increase in proportion to dose in the dose range from 100 mg to 800 mg and increase to a somewhat lesser extent in the dose range from 100 mg to 1600 mg. With the twice-daily regimen, equilibrium is reached rapidly, within approximately 2 days of initiating treatment.
The AUC and Cmax values indicate in favor of no or minimal cumulation of the drug, the C12h value in favor of minor cumulation of the drug. In monotherapy regimen of 400 mg twice daily, the geometric mean for AUC0-12h was 14.3 μmol/L x h, the C12h value was 14 nmol/L.
The absolute bioavailability of raltegravir has not been established. Raltegravir can be taken regardless of the food regimen.
About 83% of raltegravir is bound to plasma proteins in the concentration range of 2 to 10 µmol/L. Raltegravir easily crossed the placental barrier in experimental studies in rats, but did not penetrate the blood-brain barrier to any appreciable degree.
In two clinical studies involving patients infected with HIV-1 who took raltegravir at a dose of 400 mg twice daily, raltegravir was rapidly detected in the cerebrospinal fluid. In the first study, the mean concentration of raltegravir in the cerebrospinal fluid was 5.8% (range 1 to 53.5%) of the corresponding plasma concentration.
In the second study, the mean concentration of raltegravir in the cerebrospinal fluid was 3% (range 1 to 61%) of the corresponding plasma concentration. The median values obtained were approximately 3-6 times lower than the concentrations of the free raltegravir fraction in plasma.
Metabolism and excretion
Studies using selective inhibitors of the uridine diphosphate-glucuronyltransferase (UDF-GT) enzyme isoform obtained by complementary DNA expression. showed that the UDF-GT1A1 isoform is the major enzyme involved in the formation of raltegravir-glucuronide. These data showed that the main pathway of raltegravir metabolism in humans is represented by the UDF-GT1A1-mediated glucuronidation process.
The duration of the terminal phase of the elimination half-life of raltegravir is approximately 9 hours, most of the AUC corresponds to the shorter a-phase apparent elimination half-life of raltegravir (is approximately 1 hour).
After oral administration of radioactively labeled raltegravir, approximately 51% of the administered dose was excreted through the intestine and 32% through the kidneys. Only raltegravir was detected in the feces, which was probably formed by hydrolysis of raltegravir-glucuronide excreted with the bile.
In the urine, raltegravir and raltegravir-glucuronide were detected at 9% and 23% of the dose taken, respectively. In plasma, the main circulating radioactive component was raltegravir (approximately 70% of total radioactivity), whereas raltegravir-glucuronide accounted for only 30%.
Pharmacokinesis in selected patient groups
Pass has no clinically significant effect on the pharmacokinetic parameters of raltegravir. There is no need to adjust the dose of the drug depending on the gender of the patient. Elderly patients
In studies in patients 18 years of age and older no significant effect of raltegravir pharmacokinetic parameters on patients’ age was found; therefore no dose adjustment of the drug according to age is required.
Adolescents and Children
Doses for adolescents and children over 6 years of age for the treatment of HIV-1 infection are recommended on the basis that the pharmacokinetic parameters of raltegravir are comparable to those of adult patients. The pharmacokinetics of raltegravir in children younger than 2 years have not been studied.
Patients of different racial and ethnic groups
Racial ethnicity had no clinically significant effect on the pharmacokinetic parameters of raltegravir. No dose adjustment is required.
Patients with different body mass index (BMI)
BMI had no clinically significant effect on the pharmacoknetic parameters of raltegravir in adult patients. There is no need to adjust the drug dose depending on the patient’s BMI.
Patients with hepatic impairment
Naltegravir is eliminated primarily by glucuronidation and hepatic excretion.
The pharmacokinetics of the drug have been studied in adult patients with moderate hepatic impairment and in a combined pharmacokinetic analysis. No clinically significant deviations of pharmacokinetic parameters were found in adult patients with moderate hepatic impairment compared to healthy volunteers.
Hence, correction of the drug dose in mild to moderate hepatic insufficiency is not required. The effect of severe hepatic impairment on the pharmacokinetic parameters of raltegravir has not been studied.
Patients with renal impairment
Relative clearance accounts for a small fraction of the elimination of raltegravir from the body. The pharmacokinetics of the drug have been studied in adult patients with severe renal impairment and in a complex pharmacokinetic analysis.
There were no clinically significant deviations of pharmacokinetic parameters in patients with severe renal failure compared to healthy volunteers. Thus, there is no need to adjust the drug dose in patients with severe renal failure.
Because the dialysis efficacy of raltegravir is unknown, it is not recommended to take the drug on the eve of a dialysis session.
Patients with UDF-GT1AI polymorphism
There is no evidence or any data suggesting that the presence of a polymorphism in the UDF-GT1A1 enzyme may have a clinically significant effect on the pharmacoknetic parameters of raltegravir.
In a comparative study involving 30 adult healthy volunteers with genetically determined reduced UDF-GT1A1 activity and 27 adult healthy volunteers with unchanged UDF-GT1A1 genotype, the ratio of the geometric mean AUC of raltegravir was 1.41 (90% confidence interval was 0.96; 2.09).
Treatment of HIV-1 infection in combination with other antiretroviral drugs in adults, adolescents and children from 6 years old and with a body weight of at least 25 kg, both previously received and not received antiretroviral therapy.
1 film-coated tablet contains:
The active ingredient: raltegravir potassium 434.4 mg (equivalent to 400 mg of raltegravir);
Auxiliary substances: microcrystalline cellulose 169.4 mg. lactose monohydrate 26.06 mg, calcium hydrophosphate 69.50 mg, hypromellose 2208 43.44 mg, poloxamer 407* 104.3 mg, sodium stsarylfumarate 8.688 mg, magnesium stearate 13.03 mg;
film coating: Opadray II pink dye (85F94224) 26.06 mg;
film coating composition: polyvinyl alcohol 44.75%, macrogol 22.0%, talc 21.415%, titanium dioxide 11.32%, iron oxide red dye 0.495%. iron oxide dye black 0.02%.
* contains 0.01% butylgndroxytoluene as an antioxidant.
How to take, the dosage
Ingestion. Tablets of the drug Isentress should not be chewed, crumbled or broken. The drug is used regardless of meals.
The treatment with Isentress should be done by a physician with sufficient experience in HIV therapy. Treatment with Isentress is carried out in combination with other antiretroviral drugs.
The recommended doses of Isentress for treatment of HIV-1 infection:
– for adults: 400 mg x 2 times daily;
– for children with a body weight of at least 25 kg: 400 mg x 2 times daily.
If pediatric patients have difficulty swallowing film-coated tablets, consider taking Isentress Chewable Tablets (see Instructions for Use for Isentress, Chewable Tablets).
Dose adjustment in elderly patients is not necessary.
Patients with impaired renal function
Dose adjustment in patients with impaired renal function is not required.
Patients with impaired liver function
Dose adjustment is not required in patients with mild to moderate hepatic impairment.
Patients should be informed that current antiretroviral drugs do not cure HIV infection or prevent transmission of HIV to others through blood or sexual contact. During treatment with Isentress, patients should continue to observe appropriate safety precautions.
Patients should also be informed that they may still develop infections or other conditions common among HIV-infected patients (opportunistic infections). During therapy with Isentress, it is very important to remain under medical supervision. Raltegravir has a relatively low genetic barrier to the development of resistance.
Therefore, raltegravir should be administered in combination with two other active antiretrovirals, if possible, to increase treatment efficacy and reduce the risk of developing resistance to the drug. It is important to explain to patients the need to read the instructions for use before starting therapy with Isentrsss and to reread them each time they get another prescription from their doctor.
Patients should be informed to tell their doctor if any unusual symptoms occur, or if any known symptom persists or worsens.
The immune reconstitution syndrome
. In the initial stages of combination ART, HIV-infected patients with severe immunodeficiency may develop what is known as immune reconstitution syndrome, which is an inflammatory response to asymptomatic ongoing or residual opportunistic infections (cytomegalovirus retinitis, Pneumocystis jiroveci pneumonia, disseminated or focal mycobacterial infections, etc.).).
This may contribute to a worsening of the clinical condition and exacerbation of existing symptoms. Usually this reaction can be observed in the first weeks or months after the start of combination therapy.
Any inflammatory symptoms should be evaluated and treatment prescribed if necessary. Autoimmune disorders such as Based’s disease have been described in the development of immune reconstitution syndrome. However, the development of such disorders may be seen many months after the start of treatment.
. Although the etiology of this complication is considered to be multifactorial (including corticosteroid therapy, alcohol use, severe immunodeficiency, high body mass index), cases of osteonecrosis have been described, particularly in the late stages of HIV infection and/or with long-term use of combination ART.
Patients who have symptoms such as joint pain, stiffness, or limited mobility should see a specialist right away.
Serious skin reactions and hypersensitivity reactions have been reported in patients who have had severe (potentially life-threatening) and fatal adverse skin reactions when taking Isentress in combination therapy with other drugs associated with these adverse reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
Hypersensitivity reactions have also been reported, which have manifested as a generalized rash, and sometimes organ dysfunction, including liver failure.
The use of Isentress and other drugs suspected of causing such reactions should be stopped immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions (including severe skin rash or rash Fever, general malaise, weakness, muscle or joint pain, blistering of the skin, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, but not limited to these).
In these cases, the clinical status, including hepatic aminotransferase activity, should be monitored and appropriate therapy initiated. Failure to discontinue therapy with Isentress or other drugs associated with these adverse reactions in a timely manner after the onset of a severe rash may lead to life-threatening reactions.
Myopathy and rhabdomyolysis
The development of myopathy and rhabdomyolysis has been reported. Caution should be exercised when prescribing the drug in patients with a history of myopathy and rhabdomyolysis or with any factors predisposing to their development, particularly in concomitant therapy with drugs that may cause these adverse reactions.
The safety and efficacy of Iseitress in patients with severe concomitant liver disease has not been established. Caution should be exercised when prescribing Isentrees in patients with severe hepatic impairment.
Patients with existing liver dysfunction, including chronic hepatitis, have an increased incidence of hepatic dysfunction on combination ART. and should be monitored according to standard practice. If such patients show signs of worsening liver disease, discontinuation or discontinuation of treatment should be considered.
Patients with chronic hepatitis B or C also receiving combination ART are at risk for severe and potentially fatal liver adverse events.
In patients who have previously received ARV therapy, skin rash is more common when using Isentress concomitantly with darunavprom than in patients using the drugs alone (see SIDE ACTIVITY).
Depression, including suicidal ideation and behavior, has been observed mainly in patients with a history of depression or psychiatric illness. Caution should be exercised when prescribing Isentress to patients with a history of depression or psychiatric illness.
Simultaneous use with other drugs
Powerful inducers of UDF-GT1AI
Caution should be exercised when prescribing Isentress concomitantly with other inducers of UDF-GT1A1, such as rifampicin. due to the decrease in plasma concentrations of raltegravir caused by them.
If combination therapy with rifampicin and Isentress is required, the dose of Isentress should be doubled in adult patients. There are no data to support dose adjustments when Isentress and rifampicin are used concomitantly in patients under 18 years of age (see section INTRODUCTION WITH OTHER MEDICINARY MEDICINATIONS).
The concomitant use of Isentress with antacids containing aluminum or magnesium leads to decreased plasma concentrations of raltegravir. Concomitant use of Isentress with antacids containing aluminum or magnesium is not recommended (see section INTRODUCTION WITH OTHER MEDICINATIONS).
Impact on the ability to drive vehicles and operate machinery
There have been no studies on the effect on the ability to drive vehicles and operate machinery. Taking into account that dizziness, weakness, somnolence and blurred vision may occur during treatment with Isentress which may influence the above mentioned abilities, special caution should be exercised while driving and operating machinery.
- High sensitivity to raltegravir and other drug components.
- Children under 6 years.
- Body weight up to 25 kg.
- Lactation period.
The drug contains lactose. Therefore, patients with rare hereditary lactose intolerance, lactase deficiency, or impaired glucose-galactose absorption should not take Isentress.
Myopathy and rhabdomyolysis (including a history), conditions and factors predisposing to their development.
Hepatic insufficiency is severe.
Concomitant use with strong inducers of UDF-GT1A1 (rifampicin).
Concomitant use of Isentress with antacids containing aluminum or magnesium.
Depression, including suppurative ideas and behavior, has been observed mainly in patients with a history of depression or psychiatric illness. Caution should be exercised when prescribing Isentress to patients with a history of depression or psychiatric illness.
Elderly age (because of limited information on the use of raltegravir in patients older than 65 years).
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.
The adverse events observed in clinical trials, with varying degrees of probability associated with Isentress® or its combination with another ART, are presented below. The adverse events are listed according to systemic organ classes and frequency classification: “frequent” (>1/100 and <1/10). “infrequent” (>1/1000 and <1/100).
Infectious and parasitic diseases
Infrequent: Hepital 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, thrombocytopenia .
Immune system disorders
Infrequent: immune reconstitution syndrome, hypersensitivity to the drug, hypersensitivity reactions.
Metabolism and nutrition disorders
Frequent: decreased appetite.
Infrequent: cachexia, diabetes mellitus, dyslipidemia, hypercholesterolemia, hyperglycemia, hyperlipidemia, hyperphagia, increased appetite, polydipsia, fat metabolism disorder.
Frequent: unusual dreams, insomnia, nightmares, behavior disorders, depression.
Infrequent: psychiatric disorders, suicide attempts, anxiety, confusion, depressed mood, major depressive disorder, midnight insomnia, mood changes, panic attacks, sleep disturbances, suicidal ideation1, suicidal behavior1 (especially in patients with a history of psychiatric illness).
Nervous system disorders
Frequent: dizziness, headache, psychomotor hyperresponsiveness2. Infrequent: amnesia, carpal tunnel syndrome, cognitive disorders, attention disorders, postural vertigo, dysgeusnia, hypersomnia. hyisthesia, lethargy, memory disorders, migraine, peripheral neuropathy, paresthesias, somnolence, tension headaches, tremor, decrease in sleep quality.
Visual organ disorders
Infrequent: decrease in visual acuity.
Hearing organ n labyrinth disorders
Frequent: vertigo. Infrequent: tinnitus.
Infrequent: palpitations, sinus bradycardia, ventricular extrasystoles.
Infrequent: “rushes” of blood 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 tract disorders
Prevalent: feeling of distention in the abdomen, abdominal pain, diarrhea, flatulence, nausea, vomiting, dyspepsia.
Infrequent: gastritis, feeling of abdominal discomfort, upper abdominal pain, abdominal pain, feeling of discomfort in the anus, constipation, dry mouth. Epigastric discomfort, 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 failure.
Skin and subcutaneous tissue disorders
Frequent: skin rash.
Infrequent: Acne, alopecia, acne, 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 syndrome, drug rash with eosinophilia and systemic symptoms (DRESS syndrome)1.
Musculoskeletal and connective tissue disorders
Infrequent: arthralgia, arthritis, back pain, side pain, musculoskeletal pain. myalgia, neck pain. osteopenia, pain in extremities, osteoporosis, polyarthritis. tendinitis, myopathy, rhabdomyolysis .
Renal and urinary tract disorders
Infrequent: renal failure, nephritis, nephrolithiasis, nycturia, renal cysts, renal dysfunction, tubulointerstitial nephritis.
Sr genital organs and the breast
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) activity. aspartate aminotransferase (ACT), pancreatic lipase and amylase, increased triglyceride concentration and atypical lymphocyte count.
Infrequent: decreased absolute plasma neutrophil count, increased plasma activity of alkaline phosphatase, amylase, creatine phosphokinase, decreased albumin concentration, increased concentration of bilirubin, cholesterol, creatinine, glucose (including determined on an empty stomach), urea nitrogen, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, increased international normalized ratio, decreased platelet and white blood cell count, presence of glucose in urine, presence of red blood cells in urine, increased waist circumference, increased or decreased body weight.
Injuries, intoxications and complications of manipulation
Infrequent: unintentional overdose.
Indesirable events with no causal relationship to the use of Issentress that were observed in the post-registration follow-up period and were not observed in clinical trials.
One pediatric patient had adverse reactions associated with the drug: Grade 3 psychomotor hyperresponsiveness and conduct disorder; the patient also had insomnia.
In clinical studies, there have been cases of malignancies in patients who have and have not previously received ARVs when combining Isentress with other antiretrovirals.
The characteristics and incidence of malignancies were consistent with those of patients with severe immunodeficiency. The risk of malignancies in the clinical trials was similar in both the patient groups taking Isentress* and the patient groups taking the comparison drugs.
In patients taking Isentress there was an increase in creatine phosphokinase activity of 2-4 degrees. 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 more frequently observed when Isentress was used concomitantly with darupavir than when the drugs were used alone. Nevertheless, the incidence of drug-related skin rash was comparable in all three treatment groups. The skin rashes were mild to moderate in severity and did not affect continuation of ART.
In patients who had not previously received ARV treatment with Isentress in combination with emtricitabine and tenofovir, the development of rash was less common than with treatment 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. In general, the safety profile of Isentress in patients both previously receiving and not receiving ART who were co-infected with chronic (but not acute) active hepatitis B and/or hepatitis C was similar to the safety profile 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.
In clinical trials of raltegravir at recommended doses in combination with other antiretrovirals and medications in HIV-1-infected children and adolescents aged 2 to 18 years, the frequency, type and severity of adverse reactions associated with taking the drug were found to be comparable to those in adult patients.
One patient had the following drug-related adverse reactions: Grade 3 psychomotor hyperactivity, conduct disorder, and insomnia. Another patient had a serious Grade 2 adverse reaction, an allergic rash.
Another patient had a grade 4 ACT and grade 3 ALT elevation that was considered serious.
No specific symptoms of Isentress overdose have been identified. Raltegravir was well tolerated in healthy volunteers in the regimen of 1600 mg x once daily and 800 mg x twice daily without any manifestation of toxicity.
A single dose of 1800 mg per day in phase II/III studies had no toxic effects. On the basis of the available data it can be concluded that raltegravir is well tolerated in doses up to 800 mg twice a day and also when administered together with drugs increasing its exposure by 50-70% (for example, genofovir and pazanavir).
Raltegravir has a wide therapeutic range, so the potential for toxic effects due to overdose is limited. In case of overdose, standard recommendations should be followed, such as removal of unabsorbed drug from the gastrointestinal tract, monitoring of vital signs, including ECG, prescription of symptomatic therapy.
There are no data on the effectiveness of dialysis in case of overdose with Isentress.
There have been no controlled studies of Isentress in pregnant women; therefore, Isentress is contraindicated for use during pregnancy.
There are no data on the uptake of raltegravir into human breast milk. However, raltegravir was found to enter the milk in rats: when administered in a daily dose of 600 mg/kg, the concentration of raltegravir in milk exceeded the plasma concentration by approximately 3 times.
Breastfeeding is not recommended for HIV-infected mothers to avoid postnatal HIV transmission to their children. If it is necessary to use the drug during lactation, it is recommended to stop breastfeeding.
2.5 years. Do not use after the expiration date printed on the package.
|Conditions of storage|
Temperature should not exceed 30°C. Store out of the reach of children.
R-Pharm AO, Russia
Buy Isentress, 400 mg 60 pcs with delivery to USA, UK, Europe and over 120 other countries.