In studies on influenza treatment in adults / adolescent patients, the most frequent adverse reactions (HP) had nausea, vomiting and a headache. Most HP occurred on the first or second day of treatment and passed independently for 1-2 days. In studies on the prevention of influenza in adults and adolescents, the most frequent HP there was nausea, vomiting, headache and pain. Vomiting was most common in children. Described HP in most cases, did not require the withdrawal of the drug.
Treatment and prevention of influenza in adults and adolescents
Table 1 presents HP(≥1%) when taking the recommended dose of oseltamivir in studies on prevention and treatment of influenza in adults and adolescents (75 mg twice daily for 5 days for treatment and 75 mg once a day for up to 6 weeks for prophylaxis ), and whose frequency is at least 1% higher compared with placebo. The study on influenza treatment included adults / adolescents without concomitant pathology and patients at risk, i.e. patients with a high risk of developing complications of influenza (elderly and senile patients, patients with chronic heart or respiratory diseases).In general, the safety profile in patients at risk was consistent with that in adult / adolescent patients without concomitant pathology.
In studies on influenza prevention, the safety profile of patients receiving the recommended dose of the drug (75 mg once a day to 6 weeks) did not differ from that in studies on the treatment of influenza, despite the longer administration of the drug.
Table 1. Percentage of adults / adolescents with HP, occurring with a frequency> 1% in the group of oseltamivir in studies on the treatment and prevention of influenza infection (difference from placebo ≥1%)
| System-Organ Class Unwanted reaction | Treatment | Prevention | Frequency Category3 |
| Oseltamivir (75 mg 2 times / day) N=2647 | Placebo N = 1977 | Oseltamivir (75 mg once a day) N = 1945 | Placebo N = 1588 | |
| Disorders from the gastrointestinal tract |
| Nausea | 0% | 6% | 8% | 4% | Often |
| Vomiting | 8% | 3% | 2% | 1 % | often |
| Violations from the nervous systems |
| Headache | 2% | 1 % | 17% | 16% | Often |
| General disorders |
| Pain | <1 % | <1 % | 4% | 3% | often |
a The frequency category is only for the oseltamivir group. To estimate the frequency of HP, the following frequency categories are used: very often (≥1 / 10); often (≥1 / 100, <1/10).
The following are undesirable phenomena that occurred at a frequency of ≥1% in adults and adolescents who received oseltamivir as a therapy and prevention of influenza infection. These adverse events were either more frequently observed in patients receiving placebo, or the difference in frequency between oseltamivir and placebo groups was less than 1%.
Disorders from the gastrointestinal tract (oseltamivir versus placebo):
treatment - diarrhea (6% vs. 7%), abdominal pain (including pain in the upper abdomen, 2% vs. 3%);
prevention - diarrhea (3% versus 4%), pain in the upper abdomen (2% vs. 2%), dyspepsia (1% vs. 1%).
Infections and invasions (oseltamivir versus placebo):
treatment - bronchitis (3% vs. 4%), sinusitis (1% vs. 1%), herpes simplex (1% vs. 1%);
prevention - nasopharyngitis (4% vs. 4%), upper respiratory tract infection (3% vs. 3%), influenza infection (2% vs. 3%).
General disorders (oseltamivir versus placebo):
treatment - dizziness (including vertigo, 2% vs. 3%);
prevention - fatigue (7% vs. 7%), pyrexia (2% vs. 2%), flu-like disease (1% against 2%), dizziness (1% vs. 1%), pain in the extremities (1% against 1%).
Disturbances from the nervous system (oseltamivir versus placebo):
treatment - Insomnia (1% against 1%);
prevention - Insomnia (1% vs. 1%).
Disturbances from the respiratory system, chest and mediastinal organs (oseltamivir versus placebo):
treatment - coughing (2% vs. 2%), nasal congestion (1% vs. 1%);
prevention - Nasal congestion (7% versus 7%), angina (5% vs. 5%), cough (5% vs 6%), rhinorrhea (1% vs 1%).
Disturbances from musculoskeletal and connective tissue (oseltamivir versus placebo):
prevention - Back pain (2% vs. 3%), arthralgia (1% vs. 2%), myalgia (1% vs. 1%).
Violations of the genitals and mammary gland (oseltamivir versus placebo):
prevention - dysmenorrhea (3% vs. 3%).
Treatment and prevention of influenza infection in elderly and senile patients
The safety profile in 942 elderly and senile patients receiving oseltamivir or placebo, did not clinically differ from that in younger patients (up to 65 years of age).
Prevention of influenza infection in immunocompromised patients
In a 12-week study on influenza prevention involving 475 immunocompromised patients (including 18 children aged 1 to 12 years), in patients taking oseltamivir (n = 238), the safety profile was consistent with that described earlier in studies on influenza prevention.
Treatment and prevention of influenza infection in children without concomitant diseases aged 1-12 years and patients with bronchial asthma
In studies on the treatment of natural influenza infection in children aged 1 to 12 years HP when oseltamivir is used (n = 858), noted with a frequency> 1% and at least 1% more often compared with placebo (n = 622), was vomiting.
In children who received the recommended dose of the drug 1 time per day as postexposure prophylaxis at home, vomiting was most common (8% in the oseltamivir group versus 2% in the group not receiving preventive treatment). Oseltamivir well tolerated, the reported adverse events were consistent with those described earlier in the treatment of influenza in children. The following are undesirable events noted in children with a frequency of ≥1% in studies on influenza (n = 858) or with a frequency of ≥5% in studies on the prevention of influenza (n = 148). These adverse events were more frequently observed in the placebo group / absence of prophylaxis, differences between oseltamivir and placebo / absence of prophylaxis were less than 1%.
Disorders from the gastrointestinal tract (oseltamivir versus placebo):
treatment - diarrhea (9% vs 9%), nausea (4% vs. 4%), abdominal pain (including pain in the upper abdomen, 3% vs. 3%).
Infections and invasions (oseltamivir versus placebo):
treatment - otitis media (5% vs. 8%), bronchitis (2% vs. 3%), pneumonia (1% vs. 3%), sinusitis (1% vs. 2%).
Disturbances from the respiratory system, chest and mediastinal organs (oseltamivir versus placebo):
treatment - Asthma (including exacerbation, 3% vs. 4%), epistaxis (2% vs. 2%);
prevention - cough (12% vs. 26%), nasal congestion (11% vs. 20%).
Disturbances from the skin and subcutaneous tissues (oseltamivir versus placebo):
treatment - dermatitis (including allergic and atopic dermatitis, 1% vs. 2%).
Hearing disorders and labyrinthine disorders (oseltamivir versus placebo):
treatment - Pain in the ear (1% vs. 1%).
Disturbances on the part of the organ of sight (oseltamivir versus placebo):
treatment - conjunctivitis (including reddening of the eyes, discharge from the eye and pain in the eyes, 1% vs. <1%).
Additional adverse events noted during the treatment of influenza in children did not meet the criteria described above
Violations of the blood and lymphatic system (oseltamivir versus placebo):
treatment - lymphadenopathy (<1% against 1%).
Hearing disorders and labyrinthine disorders (oseltamivir versus placebo):
treatment - Damage to the tympanic membrane (<1% vs. 1%).
Postmarketing surveillance
The following are undesirable phenomena in the use of oseltamivir, which were observed during post-marketing surveillance. The frequency of these adverse events and / or the causal relationship with the use of the drug can not be established, since the true size of the population is not known due to the voluntary nature of the messages.
Disturbances from the skin and subcutaneous tissues: hypersensitivity reactions - dermatitis, skin rash, eczema, urticaria, multiforme exudative erythema, Stevens-Johnson syndrome and toxic epidermal necrolysis, allergy, anaphylactic and anaphylactoid reactions, Quincke's edema.
Disturbances from the liver and bile ducts: hepatitis, an increase in the activity of "hepatic" enzymes in patients with influenza-like symptoms who received oseltamivir; fulminant hepatitis (including fatal outcome), hepatic insufficiency, jaundice.
Disorders from the side of the neuropsychic sphere
Influenza infection can be associated with various neurological symptoms and behavioral changes, including symptoms such as hallucinations, delusions and abnormal behavior. In some cases, they can lead to death. Such phenomena can occur both against the background of the development of encephalopathy or encephalitis, and without the manifestation of these diseases.
In patients (mainly children and adolescents) who took oseltamivir with the aim of treating the flu, convulsions and delirions were recorded (including such symptoms as impairment of consciousness, disorientation in time and space, abnormal behavior, delirium, hallucinations, agitation, anxiety, nightmares). These cases were rarely accompanied by life-threatening acts. The role of oseltamivir in the development of these phenomena is unknown. Similar psychoneurological disorders were also noted in patients with influenza who did not receive oseltamivir.
Disorders from the gastrointestinal tract: gastrointestinal bleeding after taking oseltamivir (in particular, the connection between hemorrhagic colitis and the intake of oseltamivir can not be ruled out, since these events disappeared both after the patient recovered from the flu and after the drug was discontinued).
Disturbances on the part of the organ of sight: impaired vision.
Heart Disease: arrhythmia.