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Tamiflu Side Effects

Please note - some side effects for Tamiflu may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Tamiflu - for the Consumer

Tamiflu

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Tamiflu:

Diarrhea; nausea; stomach pain; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Tamiflu:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); abnormal behavior; confusion; hallucinations; mood or mental changes; reddened, blistered, peeling, or swollen skin; seizures; severe or persistent nausea, vomiting, or diarrhea; symptoms of infection (eg, fever, chills, persistent sore throat).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Tamiflu Suspension

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Tamiflu Suspension:

Diarrhea; nausea; stomach pain; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Tamiflu Suspension:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); abnormal behavior; confusion; hallucinations; mood or mental changes; reddened, blistered, peeling, or swollen skin; seizures; severe or persistent nausea, vomiting, or diarrhea; symptoms of infection (eg, fever, chills, persistent sore throat).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Tamiflu Side Effects - for the Professional

Tamiflu

The following serious adverse reactions are discussed below and elsewhere in the labeling:

The most common adverse reactions are nausea and vomiting.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Treatment Studies in Adult Subjects

A total of 1171 subjects who participated in adult controlled clinical trials for the treatment of influenza were treated with Tamiflu. The most frequently reported adverse events in these studies were nausea and vomiting. These events were generally of mild to moderate severity and usually occurred on the first 2 days of administration. Less than 1% of subjects discontinued prematurely from clinical trials due to nausea and vomiting.

Adverse events that occurred with an incidence of ≥1% in 1440 subjects taking placebo or Tamiflu 75 mg twice daily in adult treatment studies are shown in Table 6. This summary includes 945 healthy young adults and 495 "at risk" subjects (elderly patients and patients with chronic cardiac or respiratory disease). Those events reported numerically more frequently in subjects taking Tamiflu compared with placebo were nausea, vomiting, bronchitis, insomnia, and vertigo.

Prophylaxis Studies in Adult Subjects

A total of 4187 subjects (adolescents, healthy adults, and elderly) participated in prophylaxis studies, of whom 1790 received the recommended dose of 75 mg once daily for up to 6 weeks. Adverse events were qualitatively very similar to those seen in the treatment studies, despite a longer duration of dosing. Events reported more frequently in subjects receiving Tamiflu compared to subjects receiving placebo in prophylaxis studies, and more commonly than in treatment studies, were aches and pains, rhinorrhea, dyspepsia and upper respiratory tract infections. However, the difference in incidence between Tamiflu and placebo for these events was less than 1%. There were no clinically relevant differences in the safety profile of the 942 elderly subjects who received Tamiflu or placebo, compared with the younger population.

Table 6 Most Frequent Adverse Events in Studies in Naturally Acquired Influenza in Subjects 13 Years of Age and Older
Treatment Prophylaxis
Adverse Event* Placebo

N=716
Tamiflu
75 mg twice daily
N=724
Placebo/
No Prophylaxis
N=1688
Tamiflu
75 mg once daily
N=1790
*
Adverse events included are all events reported in the treatment studies with frequency ≥1% in the Tamiflu 75 mg twice daily group.
The majority of subjects received placebo; 254 subjects from a randomized, open-label postexposure prophylaxis study in households did not receive placebo or prophylaxis therapy.
Nausea (without vomiting) 40 (6%) 72 (10%) 56 (3%) 129 (7%)
Vomiting 21 (3%) 68 (9%) 16 (1%) 39 (2%)
Diarrhea 70 (10%) 48 (7%) 40 (2%) 50 (3%)
Bronchitis 15 (2%) 17 (2%) 22 (1%) 15 (1%)
Abdominal pain 16 (2%) 16 (2%) 25 (1%) 37 (2%)
Dizziness 25 (3%) 15 (2%) 21 (1%) 24 (1%)
Headache 14 (2%) 13 (2%) 306 (18%) 326 (18%)
Cough 12 (2%) 9 (1%) 119 (7%) 94 (5%)
Insomnia 6 (1%) 8 (1%) 15 (1%) 22 (1%)
Vertigo 4 (1%) 7 (1%) 4 (<1%) 4 (<1%)
Fatigue 7 (1%) 7 (1%) 163 (10%) 139 (8%)

Additional adverse events occurring in <1% of patients receiving Tamiflu for treatment included unstable angina, anemia, pseudomembranous colitis, humerus fracture, pneumonia, pyrexia, and peritonsillar abscess.

Treatment Studies in Pediatric Subjects

A total of 1032 pediatric subjects aged 1 to 12 years (including 698 otherwise healthy pediatric subjects aged 1 to 12 years and 334 asthmatic pediatric subjects aged 6 to 12 years) participated in controlled clinical trials of Tamiflu given for the treatment of influenza. A total of 515 pediatric subjects received treatment with Tamiflu for oral suspension.

Adverse events occurring in ≥1% of pediatric subjects receiving Tamiflu treatment are listed in Table 7. The most frequently reported adverse event was vomiting. Other events reported more frequently by pediatric subjects treated with Tamiflu included abdominal pain, epistaxis, ear disorder, and conjunctivitis. These events generally occurred once and resolved despite continued dosing resulting in discontinuation of drug in 8 out of 515 (2%) cases.

The adverse event profile in adolescents is similar to that described for adult subjects and pediatric subjects aged 1 to 12 years.

Prophylaxis Studies in Pediatric Subjects

Pediatric subjects aged 1 to 12 years participated in a postexposure prophylaxis study in households, both as index cases (n=134) and as contacts (n=222). Gastrointestinal events were the most frequent, particularly vomiting. In a separate 6-week, uncontrolled, pediatric seasonal prophylaxis study (n=49), the adverse events noted were consistent with those previously observed.

Table 7 Most Frequent Adverse Events Occurring in Children Aged 1 to 12 Years in Studies in Naturally Acquired Influenza
Treatment Trials* Household Prophylaxis Trial
Adverse Event Placebo

N=517
Tamiflu
2 mg/kg twice daily
N=515
No Prophylaxis§
N=87
Prophylaxis with Tamiflu
once daily§
N=99
*
Pooled data from trials of Tamiflu treatment of naturally acquired influenza.
A randomized, open-label study of household transmission in which household contacts received either prophylaxis or no prophylaxis but treatment if they became ill. Only contacts who received prophylaxis or who remained on no prophylaxis are included in this table.
Adverse events included in Table 7 are all events reported in the treatment studies with frequency ≥1% in the Tamiflu 75 mg twice daily group.
§
Unit dose = age-based dosing of 30 mg, 45 mg, or 60 mg
Vomiting 48 (9%) 77 (15%) 2 (2%) 10 (10%)
Diarrhea 55 (11%) 49 (10%) - 1 (1%)
Otitis media 58 (11%) 45 (9%) 2 (2%) 2 (2%)
Abdominal pain 20 (4%) 24 (5%) - 3 (3%)
Asthma (including aggravated) 19 (4%) 18 (3%) 1 (1%) 1 (1%)
Nausea 22 (4%) 17 (3%) 1 (1%) 4 (4%)
Epistaxis 13 (3%) 16 (3%) - 1 (1%)
Pneumonia 17 (3%) 10 (2%) 2 (2%) -
Ear disorder 6 (1%) 9 (2%) - -
Sinusitis 13 (3%) 9 (2%) - -
Bronchitis 11 (2%) 8 (2%) 2 (2%) -
Conjunctivitis 2 (<1%) 5 (1%) - -
Dermatitis 10 (2%) 5 (1%) - -
Lymphadenopathy 8 (2%) 5 (1%) - -
Tympanic membrane disorder 6 (1%) 5 (1%) - -

Prophylaxis Study in Immunocompromised Subjects

In a 12-week seasonal prophylaxis study in 475 immunocompromised subjects, including 18 pediatric subjects 1 to 12 years of age, the safety profile in the 238 subjects receiving Tamiflu was consistent with that previously observed in other Tamiflu prophylaxis clinical trials.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Tamiflu. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to Tamiflu exposure.

Body as a Whole: Swelling of the face or tongue, allergy, anaphylactic/anaphylactoid reactions, hypothermia

Dermatologic: Rash, dermatitis, urticaria, eczema, toxic epidermal necrolysis, Stevens-Johnson Syndrome, erythema multiforme [see Warnings and Precautions (5.1)]

Digestive: Hepatitis, liver function tests abnormal

Cardiac: Arrhythmia

Gastrointestinal disorders: Gastrointestinal bleeding, hemorrhagic colitis

Neurologic: Seizure

Metabolic: Aggravation of diabetes

Psychiatric: Abnormal behavior, delirium, including symptoms such as hallucinations, agitation, anxiety, altered level of consciousness, confusion, nightmares, delusions [see Warnings and Precautions (5.2)]

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Side Effects by Body System - for Healthcare Professionals

General

The most common side effects are nausea and vomiting.

The most common side effects reported in patients receiving oseltamivir during studies for the treatment of influenza were nausea, vomiting, bronchitis, insomnia, and vertigo. Nausea and vomiting were generally mild to moderate in severity and usually occurred on the first 2 days of treatment. Less than 1% of patients discontinued oseltamivir early due to nausea and vomiting.

Side effects in prophylaxis studies were similar to those in treatment studies. Side effects that occurred more frequently than in treatment studies were aches and pains, rhinorrhea, dyspepsia, and upper respiratory tract infections.

Gastrointestinal

Gastrointestinal side effects have been the most commonly reported and have included nausea (without vomiting; up to 10%), vomiting (up to 9%), diarrhea (up to 7%), abdominal pain (2%), and pseudomembranous colitis (less than 1%). Gastrointestinal bleeding and hemorrhagic colitis have been reported during postmarketing experience.

Respiratory

Respiratory side effects have included cough (up to 5%) and bronchitis (up to 2%). The incidences were similar or higher among placebo patients and may represent symptoms of underlying influenza infection. Pneumonia has been reported (less than 1%) and may also be a symptom of underlying disease. Nasopharyngitis, congestion, rhinitis, and dry, sore throat have also been reported.

Nervous system

Nervous system side effects have included headache (up to 18%), dizziness (up to 2%), insomnia (1%), and vertigo (up to 1%). The incidences were similar or higher among placebo patients and may represent symptoms of underlying influenza infection. Seizure has been reported during postmarketing experience.

Psychiatric

Psychiatric side effects have included abnormal behavior and delirium (including symptoms such as altered level of consciousness, confusion, delusions, hallucinations, agitation, anxiety, nightmares) during postmarketing experience.

Delirium and abnormal behavior leading to injury, with fatal outcomes in some cases, in influenza patients receiving oseltamivir have been reported during postmarketing experience (mostly in Japan). Although frequency is unknown, based on oseltamivir usage, these events appear to be uncommon. These events were primarily reported in pediatric patients and often had an abrupt onset and rapid resolution. Since influenza may be associated with a variety of neurologic and behavioral symptoms (including hallucinations, delirium, and abnormal behavior, with fatal outcomes in some cases) and may occur with encephalitis or encephalopathy but can occur without obvious severe disease, oseltamivir's contribution to these effects has not been established.

Other

Other side effects have included fatigue (up to 8%), humerus fracture (less than 1%), pyrexia (less than 1%), and peritonsillar abscess (less than 1%). Drowsiness and malaise have been reported; however, causality has not been established. Hypothermia has been reported during postmarketing experience.

Hematologic

Hematologic side effects have included anemia (less than 1%). Pancytopenia has been reported; however, causality has not been established.

Hypersensitivity

Hypersensitivity side effects have included allergy, anaphylactic/anaphylactoid reactions, and swelling of the face or tongue during postmarketing experience.

Dermatologic

Dermatologic side effects have included rash, dermatitis, urticaria, eczema, and serious skin reactions (including toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) during postmarketing experience.

Hepatic

Hepatic side effects have included hepatitis and abnormal liver function tests during postmarketing experience. Hepatic failure has been reported; however, causality has not been established.

Cardiovascular

Cardiovascular side effects have included unstable angina (less than 1%). Sudden cardiopulmonary arrest has been reported; however, causality has not been established. Arrhythmia has been reported during postmarketing experience.

Metabolic

Metabolic side effects have included aggravation of diabetes during postmarketing experience. Hyperglycemia has been reported; however, causality has not been established.

Immunologic

Immunologic side effects have included sepsis; however, causality has not been established.

Musculoskeletal

Musculoskeletal side effects have included arthralgia in at least one patient.

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