The safety profile of Isentress® is based on the results of general safety data obtained from clinical trials involving patients who had previously received antiretroviral therapy (ARVT) and patients who had not previously received ARVT.
In a combined analysis of the results of clinical trials of antiretroviral therapy in adult patients previously treated with ARVT, the frequency of discontinuation due to adverse reactions was 3.9% in the Isentress® group and optimized complementary therapy (ODT), and 4.6% in group of patients taking placebo and ODT. The frequency of withdrawal of therapy due to adverse reactions in adult patients who had not previously received ARV was 5.0% in the group of patients taking Isentress ® concurrently with emtricitabine and tenofovir, and 10.0% in the group of patients taking concomitantly efavirenz, emtricitabine and tenofovir.
The following are data on adverse events observed in clinical trials with varying degrees of likelihood associated with Isentress® or a combination of it with another ARVT. 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,herpes infection, herpes zoster, influenza, lymph node abscess, molluscum contagiosum, nasopharyngitis, upper respiratory tract infection.
Benign, malignant and unspecified neoplasms (including cysts and polyps)
Infrequent: papillomatosis of the skin.
On the part of the blood and lymphatic system
Infrequent: anemia, iron deficiency anemia, tenderness of lymph nodes, lymphadenopathy, neutropenia, thrombocytopenia1.
From the immune system
Infrequent: immune reconstitution syndrome, hypersensitivity to the drug, and hypersensitivity.
From the side of metabolism and nutrition
Frequent: decreased appetite.
Infrequent: cachexia, diabetes mellitus, dyslipidemia, hypercholesterolemia, hyperglycemia, hyperlipidemia, hyperphagia, increased appetite, polydipsia, impaired fat metabolism.
Disorders of the psyche
Frequent: unusual dreams, insomnia, nightmares, impaired behavior2, depression.
Infrequent: psychic disorders, suicidal attempts, feelings of anxiety, confusion, depressed mood, major depressive disorder, mid-sleeplessness, mood changes, panic attacks, sleep disturbances,suicidal ideas1, suicidal behavior1 (especially in patients with psychiatric illness in the history).
From the nervous system
Frequent: dizziness, headache, psychomotor hyperreactivity.
Infrequent: amnesia, carpal tunnel syndrome, cognitive disorders, attention disorders, postural dizziness, dysgeusia, hypersomnia, hypoesthesia, lethargy, memory disorder, migraine, peripheral neuropathy, paresthesia, drowsiness, tension headache, tremor, decreased sleep quality.
From the side of the organ of vision
Infrequent: decreased visual acuity.
From the side of the hearing organ and labyrinthine disorders
Frequent: Vertigo.
Infrequent: noise in ears.
From the heart
Infrequent: heart palpitations, sinus bradycardia, ventricular extrasystole.
From the side of the vessels
Infrequent: "tides" of blood to the skin of the face with a feeling of heat, hypertension.
On the part of the respiratory system, the organs of the thorax and the mediastinum
Infrequent: dysphonia, nosebleeds, nasal congestion.
From the gastrointestinal tract
Frequent: a feeling of raspiraniya in the abdomen, abdominal pain, diarrhea, flatulence, nausea, vomiting, indigestion.
Infrequent: gastritis, abdominal discomfort, pain in the upper abdomen, soreness in the abdomen, discomfort in the anus, constipation, dry mouth, discomfort in the epigastric region, erosive duodenitis, belching, gastroesophageal reflux, gingivitis, glossitis, tenderness when swallowing, acute pancreatitis, peptic ulcer, rectal bleeding.
From the liver and biliary tract
Infrequent: hepatitis, steatosis of the liver, alcoholic hepatitis, hepatic insufficiency1.
From the skin and subcutaneous tissues
Frequent: skin rash.
Infrequent: acne, alopecia, acne, dry skin, erythema, lipoatrophy of the face, hyperhidrosis, lipoatrophy, acquired lipodystrophy, lipohydrophy, night sweats, prurigo, itching (local and generalized), macular rash, maculopapular rash, itching rash, hives, xeroderma, others skin lesions, Stevens-Johnson syndrome1, a drug rash with eosinophilia and systemic symptoms1.
From the musculoskeletal and connective tissue
Infrequent: arthralgia, arthritis, back pain, side pain, musculoskeletal pain, myalgia, neck pain, osteopenia,pain in the extremities, osteoporosis, polyarthritis, tendonitis, myopathy, rhabdomyolysis1.
From the side of the kidneys and urinary tract
Infrequent: renal failure, nephritis, nephrolithiasis, nocturia, kidney cyst, renal dysfunction, tubulointerstitial nephritis.
From the genitals and breast
Infrequent: erectile dysfunction, gynecomastia, the symptoms of menopause.
General disorders and disorders at the site of administration
Frequent: asthenia, weakness, fever.
Infrequent: discomfort in the chest, chills, swelling of the face, increased fat tissue, anxiety, malaise, submandibular growth, peripheral edema, pain.
Laboratory and instrumental data
Frequent: an increase in plasma activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT), lipase and amylase of the pancreas, an increase in the concentration of triglycerides and the number of atypical lymphocytes.
Infrequent: decrease in the absolute number of plasma neutrophils; increased activity in plasma of alkaline phosphatase, amylase, creatine phosphokinase, decrease in albumin concentration; an increase in the concentration of bilirubin, cholesterol, creatinine, glucose (including those determined on an empty stomach),urea nitrogen, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol; increase the importance of the international normalized relationship; decrease in the number of platelets and leukocytes in the blood; the presence of glucose in the urine, the presence of erythrocytes in the urine; an increase in the circumference of the waist; increase or decrease in body weight.
Trauma, intoxication and complications of manipulation
Infrequent: unintentional overdose.
1 Undesirable phenomena without the presence of a cause-and-effect relationship with the use of Isentress®, which were observed during the post-registration period of observation and were not observed during clinical trials.
2 In one child of the child age, adverse drug reactions associated with taking the drug were observed: psychomotor hyperreactivity of the 3rd degree and behavioral disorder; also this patient had insomnia.
In clinical trials, patients who had previously received and previously did not receive ARVs had malignant tumors when using the combination of Isentress ® with other antiretroviral drugs.The characteristics and frequency of malignant neoplasms corresponded to those for patients with severe immunodeficiency. The risk of developing malignant neoplasms in clinical trials was the same both in the groups of patients taking Isentress® and in the groups of patients taking the comparator drugs.
In patients taking Isentress ®, an increase in activity of creatine phosphokinase 2-4 was observed. There have been cases of myopathy and rhabdomyolysis. Patients with myopathy or rhabdomyolysis in the history, and also having other risk factors (including concomitant therapy), the drug should be administered with caution.
Osteonecrosis has been reported, especially in patients with recognized risk factors, late HIV disease, or long-term exposure to combined ARV. The frequency of its development is unknown.
In clinical trials in patients previously treated with ARVT, skin rashes, regardless of etiology, were more common with Isentress® concomitantly with darunavir than with the use of these drugs alone.However, the incidence of skin rash associated with taking medications was comparable in all three treatment groups. Skin rash was mild and moderate
severity and did not affect the continuation of ARV. In patients who had not previously taken ARVT with Isentress® in combination with emtricitabine and tenofovir, the development of rash was less common than with efavirenz in combination with emtricitabine and tenofovir.
Patients with co-infection with hepatitis B and / or hepatitis C
In general, the safety profile of Isentress® in patients who had previously received or who did not receive ARVT co-infected with chronic (but not acute) active hepatitis B and / or hepatitis C was similar to the safety profile in patients without co-infection with hepatitis B and / or hepatitis C, although the incidence of abnormal ALT and ACT activity was sometimes higher in groups with co-infection with hepatitis B and / or hepatitis C.
Children
According to the results of clinical studies on the use of raltegravir in the recommended doses in combination with other antiretroviral drugs in HIV-1 infected children and adolescents 2 to 18 years, it was found that the frequency, type and severity of adverse reactions associated with taking the drug were comparable to those in adult patients.
In one patient, the following adverse drug reactions were observed: psychomotor hyperactivity of grade 3, behavioral disorders and insomnia. Another patient experienced a serious adverse reaction of the 2nd degree - an allergic rash.
Another patient had an increase in ACT 4 degree activity and grade 3 ALT, which was regarded as serious.