More than 2000 HIV-infected patients were taking emtricitabine as monotherapy or in combination with other antiretroviral drugs for 10 days to 200 weeks in clinical trials.
Since the conditions for conducting clinical trials vary widely, the frequency of observed side effects in a clinical trial of the drug can not be directly compared with the incidence of adverse reactions observed in clinical studies of another drug and may not correspond to the level of adverse events observed in practice. For a large number of the phenomena listed below, it is not known whether they are related to the effects of emtricitabine or other antiretroviral drugs, as well as to the action of a wide range of commonly prescribed drugs for the treatment of HIV infection, or the reported adverse reactions are the result of pathological processes underlying the disease .
The most frequent side effects (> 10%, regardless of severity) that were observed in patients receiving emtricitabine in combination with other antiretroviral drugs in 3 large-scale controlled clinical trials, were headache, diarrhea, nausea, fatigue, dizziness, depression, insomnia, abnormal dreams, rashes, abdominal pain, asthenia, cough and rhinitis.
Studies 301A and 303
The most frequent adverse reactions observed in patients who received emtricitabine in combination with other antiretroviral agents, included headache, diarrhea, nausea and rash, which were usually mild or moderate. About 1% of patients stopped taking the drug in connection with these adverse reactions. All adverse events were recorded at the same frequency in patients who received combination therapy with emtricitabine or other antiretroviral regimens, except for skin discoloration that was observed with a higher frequency in patients taking emtricitabine. Changes in skin color, manifested by hyperpigmentation of the palms and / or soles,was mild and asymptomatic. The mechanism of this phenomenon and its clinical significance are unknown.
Table 3. Adverse reactions observed in> or = 3% of patients in different treatment groups in studies 301A and 303
| | Study 303 | Study 301A |
| | Emtricitabine + zidovudine or stavudine + NNRTIs1 or IP2 (n = 294) | Lamivudine + zidovudine or stavudine + NNRTIs or IP (n = 146) | Emtricitabine + didanosine + efavirenz (n = 286) | Stavudine + didanosine + efavirenz (n = 285) |
| Organism as a whole: Fatigue | 16% | 10% | 12% | 17% |
| Headache | 13% | 6% | 22% | 25% |
| Disorders from the gastrointestinal tract tract: | |
| Diarrhea | 23% | 18% | 23% | 32% |
| Dyspepsia | 4% | 5% | 8% | 12% |
| Nausea | 18% | 12% | 13% | 23% |
| Vomiting | 9% | 7% | 9% | 12% |
| Abdominal pain | 8% | 11% | 14% | 17% |
| Disorders of the musculoskeletal system: | |
| Arthralgia | 3% | 4% | 5% | 6% |
| Myalgia | 4% | 4% | 6% | 3% |
| Disorders from the nervous system: | |
| Pathological dreams | 2% | <1% | 11% | 19% |
| Depressive disorders | 6% | 10% | 9% | 13% |
| Dizziness | 4% | 5% | 25% | 26% |
| Insomnia | 7% | 3% | 16% | 21% |
| Neuropathy / peripheral neuritis | 4% | 3% | 4% | 13% |
| Paresthesia | 5% | 7% | 6% | 12% |
| Disorders from the side respiratory organs: | |
| Coughing up | 14% | 11% | 14% | 8% |
| Rhinitis | 18% | 12% | 12% | 10% |
| Disturbances from the skin and subcutaneous tissue: | |
| Rash3 | 17% | 14% | 30% | 33% |
1 - non-nucleoside reverse transcriptase inhibitor
2 - protease inhibitor
3 - cases of rash included itching, maculopapular rash, hives, vesicle-bullous rash, pustular rash and allergic reactions.
Laboratory abnormalities in these studies were observed with the same frequency in patients who received emtricitabine, and in the comparison groups (Table 4).
Table 4. Significant deviations in laboratory indicators (grade 3 and 4), observed in> 1% of patients in different treatment groups of studies 301A and 303
| | Study 303 | Study 301A |
| | Emtricitabine + zidovudine or stavudine + NNRTI or PI (n = 294) | Lamivudine + zidovudine or stavudine + NNRTI or PI (n = 146) | Emtricitabine + didanosine + efavirenz (n = 286) | Stavudine + didanosine + efavirenz (n = 285) |
| |
| |
| | | | | |
| Laboratory abnormalities> or = 3 degrees of severity | 31% | 28% | 34% | 38% |
| ALT (> 5 VGN1) | 2% | 1% | 5% | 6% |
| ACT (> 5 VGN) | 3% | <1% | 6% | 9% |
| Bilirubin (> 2.5 VGN) | 1% | 2% | <1% | <1% |
| Creatine kinase (> 4 IUV) _ | 11% | 14% | 12% | 11% |
| Neutropenia (<750 / mm) | 5% | 3% | 5% | 7% |
| Pancreatic amylase (> 2 VGN) | 2% | 2% | <1% | 1% |
| Serum Amylase (> 2 VGN) | 2% | 2% | 5% | 10% |
| The serum glucose level (<40 or> 25 g / l) | 3% | 3% | 2% | 3% |
| Serum lipase (> 2 VGN) | <1% | <1% | 1% | 2% |
| Triglycerides (> 750 mg / dL) | 10% | 8% | 9% | 6% |
1 - VGN - the upper limit of the norm
Study 934
In the 934 study, 511 previously untreated antiretroviral drugs emtricitabine and tenofovir in combination with efavirenz (n = 257) or zidovudine / lamivudine in combination with efavirenz (n = 254). The side effects observed in this study are generally consistent with other patient studies,previously untreated with antiretroviral drugs or already receiving treatment (Table 5).
Table 5. Adverse Reactions1 2-4 degrees of severity, observed in> 5% of patients in
various study treatment groups 934 (0 to 144 weeks)
| | Emtricitabine + tenofovir + efavirenz2 (n = 257) | Zidovudine / lamivudine + efavirenz (n = 254) |
| Disorders from the gastrointestinal tract: Diarrhea | 9% | 5% |
| Nausea | 9% | 7% |
| Vomiting | 2% | 5% |
| On the part of the body as a whole - general adverse reactions: Fatigue | 9% | 8% |
| Infections and infestations: Sinusitis Upper respiratory infections ways Nasopharyngitis | 8% 8% 5% | 4% 5% 3% |
| Disorders from the nervous | | |
| system: | | |
| Headache | 6% | 5% |
| Dizziness | 8% | 7% |
| Mental disorders: | | |
| Depression | 9% | 7% |
| Insomnia | 5% | 7% |
| Disturbances from the skin and subcutaneous tissue: | | |
| Rash3 | 7% | 9% |
1 - The incidence of side effects is based on data from all treatment-related adverse events, regardless of the association with the study drug.
2 - during the period from 96 to 144 weeks of study, patients received a combined preparation in one tablet containing tenofovir disoproxil fumarate and emtricitabine, instead of these two drugs in separate dosage forms.
3 - a rash was observed exfoliative, generalized, spotted, macular, itchy and vesicular.
The significant laboratory abnormalities observed in this study are shown in Table 6.
Table 6. Significant laboratory abnormalities observed in> or = 1% of patients in different treatment groups of the study 934 (0 - 144 weeks)
| | Emtricitabine + tenofovir + efavirenz1 (n = 257) | Zidovudine / lamivudine + efavirenz (n = 254) |
| Laboratory abnormalities> or = 3 degrees of severity | 30% | 26% |
| Cholesterol (> 240 mg / dL) | 22% | 24% |
| Creatine kinase (males:> 990 U / l) (females:> 845 U / l) | 9% | 7% |
| Serum amylase (> 175 U / l) | 8% | 4% |
| Alkaline phosphatase (> 550 U / l) | 1% | 0% |
| ACT (male:> 180 U / l) (female:> 170 U / l) | 3% | 3% |
| ALT (male:> 215 U / l) (female:> 170 U / l) | 2% | 3% |
| Hemoglobin (<80 g / l) | 0% | 4% |
| Hyperglycemia (> 25 g / l) | 2% | 1% |
| Hematuria (> 75 erythrocytes in sight) | 3% | 2% |
| Glucosuria (> 3+) | <1% | 1% |
| Neutropenia (<750 / mm) | 3% | 5% |
| Triglycerides (> 750 mg / dL) | 4% | 2% |
1 - during the period from 96 to 144 weeks of study, patients received a combined preparation in one tablet containing tenofovir disoproxil fumarate and emtricitabine, instead of these two drugs in separate dosage forms.
Children
The evaluation of adverse reactions is based on an open, uncontrolled study 203 in which 116 HIV-1 infected children received emtricitabine within 48 weeks. In total, the profile of adverse reactions in children was comparable to that of adult patients. Hyperpigmentation was more common in children.To the additional undesirable phenomena registered at children, the anemia concerns.
In children who received emtricitabine therapy for 48 weeks, adverse events, regardless of the causative relationship, included the following: infection (44%), hyperpigmentation (32%), coughing (28%), vomiting (23%), otitis media (23%), rash (21%), rhinitis (20%), diarrhea (20%), fever (18%), pneumonia (15%), gastroenteritis (11%), abdominal pain (10%), anemia (7%). Changes in laboratory indicators of 3-4 degrees of severity that occurred during treatment were observed in 9% of children and included an increase in the level of amylase> 2 VGN (n = 4), neutropenia <750 / mm (n = 3), an increase in the level of ALT> 5 VGN (n = 2), creatine phosphokinase> 4 VGN (n = 2) and one case of increasing bilirubin (> 3 VGN), gamma glutamyltranspeptidase (> 10 VGN), lipase (> 2.5 UGN), a decrease in hemoglobin (<70 g / l), and a decrease in glucose level (<4 g / l).