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Ixiaro

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Ixiaro

Ixiaro

SIDE EFFECTS

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

Overall Adverse Events

The most common ( ≥ 10%) systemic adverse events observed in clinical trials with IXIARO (japanese encephalitis vaccine) were headache and myalgia. The most common ( ≥ 10%) local reactions after IXIARO (japanese encephalitis vaccine) administration were pain and tenderness.

In five clinical studies1, 2, 3, 4, 5 conducted in North America, Europe, Australia and New Zealand, a total of 3,558 adults aged 18 to 86 years received at least one dose of IXIARO (japanese encephalitis vaccine) (92% completed the 2 dose series) and were followed-up for safety for at least 6 months after the first dose. In this pooled dataset of subjects who received IXIARO (japanese encephalitis vaccine) , one death occurred in a subject with metastatic lung adenocarcinoma four months after completing the two-dose regimen. Approximately 1% of subjects who received IXIARO (japanese encephalitis vaccine) experienced a serious adverse event, including one case of multiple sclerosis. Approximately 1% of subjects who received IXIARO (japanese encephalitis vaccine) discontinued due to adverse events.

Clinical Trials Experience

Adverse Events in a Clinical Trial Comparing IXIARO (japanese encephalitis vaccine) to a Control

The safety of IXIARO (japanese encephalitis vaccine) was evaluated in a randomized, controlled, double-blind clinical trial in healthy male and female subjects1. IXIARO (japanese encephalitis vaccine) was compared to a control: Phosphate Buffered Saline containing 0.1% aluminum hydroxide [PBS + Al(OH)3]. A total of 2,675 subjects were randomized in a 3:1 ratio to receive either an intramuscular injection of IXIARO (japanese encephalitis vaccine) (0.5 mL) each on Day 0 and Day 28, or an intramuscular injection of PBS + Al(OH)3 (0.5 mL) each on Day 0 and Day 28. Analysis of safety was carried out using the safety population including 1,993 subjects receiving at least one dose of IXIARO (japanese encephalitis vaccine) and 657 subjects receiving at least one dose of PBS + Al(OH)3 (mean age: 33.8 years, range 18 to 86 years; 55.3% female; race: White: 91.7%, Asian: 1.8%, Black: 3.4%, Other: 3.0%). The IXIARO (japanese encephalitis vaccine) and control groups were similar with regard to demographics. Subjects recorded adverse events on a diary card for the first seven days after each vaccination. In addition, the study investigator took a medical history and performed a physical exam to evaluate for adverse events on the day of each vaccination and at a visit 4 weeks after the second vaccination.

Serious Adverse Events

No deaths occurred during this trial. Sixteen serious adverse events (SAE) were reported during the study period. Ten subjects (0.5%) who received IXIARO (japanese encephalitis vaccine) and 6 subjects (0.9%) who received PBS + Al(OH)3 experienced a SAE. The serious adverse events occurring in the IXIARO (japanese encephalitis vaccine) group were as follows: dermatomyositis, appendicitis, rectal hemorrhage, limb abscess (contralateral to the injected arm), chest pain, ovarian torsion, ruptured corpus luteal cyst, and three orthopedic injuries.

Systemic Adverse Events

Overall, the percentage of subjects who experienced at least one adverse event during the study period was 58.9% in the IXIARO (japanese encephalitis vaccine) group compared to 56.6% in the PBS + Al(OH)3 group. The severity of adverse events was as follows: mild in 33.7% of subjects receiving IXIARO (japanese encephalitis vaccine) compared to 34.1% of subjects receiving PBS + Al(OH)3, moderate in 20.1% of subjects receiving IXIARO (japanese encephalitis vaccine) compared to 17.4% of subjects receiving PBS + Al(OH)3, and severe in 5.1% of subjects receiving IXIARO (japanese encephalitis vaccine) compared to 5.2% of subjects receiving PBS + Al(OH)3. Severity was defined as follows: Mild, awareness of signs or symptoms, but easily tolerated; Moderate, discomfort enough to interfere with usual activity; and Severe, incapable of work or usual activity. Adverse events of any severity grade occurring with an incidence of ≥ 1% of subjects are shown in Table 1.

Table 1: Common Systemic Adverse Events* After IXIARO (japanese encephalitis vaccine) or Control [PBS + Al(OH)3], Safety Population

Adverse Event Incidence (% of subjects) in the First Vaccination Period
(Day 0 to Day 28)
Incidence (% of subjects) in the
Second Vaccination Period
(Day 28 to Day 56)
Incidence (% of subjects) in the Total Vaccination Period
(Day 0 to Day 56)
IXIARO
N‡=1993
PBS + Al(OH)3
N‡=657
IXIARO
N‡=1968
PBS + Al(OH)3
N‡=645
IXIARO
N‡=1993
PBS + Al(OH)3
N‡=657
Headache† 21.6 20.2 13.4 13.0 27.9 26.2
Myalgia† 13.3 12.9 5.6 5.3 15.6 15.5
Fatigue† 8.6 8.7 5.2 5.9 11.3 11.7
Influenza-like Illness† 8.2 8.5 5.8 4.3 12.3 11.7
Nausea† 4.7 5.3 2.6 3.7 6.6 7.5
Nasopharyngitis 2.3 1.8 2.6 2.3 4.7 4.0
Pyrexia† 1.9 2.1 1.5 1.7 3.2 3.0
Rhinitis 1.0 0.8 0.5 0.6 1.4 1.4
Upper Respiratory Tract Infection 0.9 0.9 0.8 0.9 1.7 2.0
Back Pain 0.8 0.9 0.6 0.2 1.3 1.1
Pharyngolaryngeal Pain 0.8 0.9 1.0 0.5 1.6 1.4
Rash† 0.8 0.9 0.7 0.8 1.3 1.5
Diarrhea 0.8 0.8 0.7 0.3 1.5 1.1
Cough 0.8 0.8 0.6 0.6 1.2 1.2
Vomiting† 0.6 0.8 0.8 0.9 1.4 1.7
*The adverse events in this table are those observed at an incidence of ≥ 1% in the IXIARO (japanese encephalitis vaccine) or PBS + Al(OH)3 groups.
† These symptoms were solicited in a subject diary card. Percentages include unsolicited events that occurred after the 7 day period covered by the diary card.
‡N=number of subjects in the safety population (subjects treated with at least one dose) who received the respective dose

Injection Site Reactions

Injection site reactions after IXIARO (japanese encephalitis vaccine) were compared to reactions after PBS + Al(OH)3. Symptoms were recorded into a subject diary for the first seven days after each injection, and the injection site was assessed by the investigator at each visit. Pain, tenderness, and pruritis severity was assessed subjectively as absent, mild, moderate or severe by the subject. The amount of erythema, induration and edema was measured by the subject and/or the investigator and rated as absent, mild ( ≤ 1cm), moderate ( > 1 to < 3cm), or severe ( ≥ 3cm). The severity of injection site reactions observed after either dose was as follows: mild in 41.6% of subjects receiving IXIARO (japanese encephalitis vaccine) compared to 44.2% of subjects receiving PBS + Al(OH)3, moderate in 9.5% of subjects receiving IXIARO (japanese encephalitis vaccine) compared to 7.7% of subjects receiving PBS + Al(OH)3, and severe in 3.2% of subjects receiving IXIARO (japanese encephalitis vaccine) compared to 3.1% of subjects receiving PBS + Al(OH)3. The frequency of injection site reactions of any severity grade is shown in Table 2.

Table 2: Injection Site Solicited Adverse Reactions* After IXIARO (japanese encephalitis vaccine) or Control [PBS + Al(OH)3], Subjects in the Safety Population With Evaluable Diary Cards

Adverse Reaction Incidence Post Dose 1
(% of subjects†)
Incidence Post Dose 2
(% of subjects†)
Incidence Post Dose 1 or Dose 2 (% of subjects†)
IXIARO
N‡=1963
PBS +Al(OH)3
N‡=645
IXIARO
N‡=1951
PBS +Al(OH)3
N‡=638
IXIARO
N‡=1963
PBS +Al(OH)3
N‡=645
Any Reaction 48.5 47.7 32.6 32.2 55.4 56.2
Pain 27.7 28.2 17.7 18.2 33.0 35.8
Tenderness 28.8 26.9 22.5 18.1 35.9 32.6
Erythema 6.8 5.4 4.6 4.1 9.6 7.4
Induration 4.8 5.3 4.0 3.0 7.5 7.4
Edema 2.4 3.3 2.3 1.6 4.2 4.6
Pruritis 2.6 3.3 1.6 1.9 3.8 4.5
* Injection site reactions were assessed for 7 days after each dose.
† Denominators used to calculate percentages are based on the number of evaluable diary card entries (defined as documented presence on any day [i.e., entry of “yes”] or absence on all days [i.e., entry of “no”]) for each individual symptom and observation period.
‡N=number of subjects who returned diary cards after each dose

Adverse Events in a Clinical Trial Comparing IXIARO (japanese encephalitis vaccine) to JE-VAX

The safety of IXIARO (japanese encephalitis vaccine) compared to another inactivated JE vaccine (JE-VAX) was evaluated in a randomized, double-blind clinical trial2.

No deaths occurred during this trial. One serious adverse event occurred in this trial in a subject with a history of myocardial infarction (MI) who experienced a MI three weeks after receiving the 2nd dose of IXIARO (japanese encephalitis vaccine) . The most common adverse events after immunization occurring in ≥ 1% of subjects were headache, myalgia, fatigue, influenza-like illness, nausea, nasopharyngitis, pyrexia, pharyngolaryngeal pain, cough, rash, diarrhea, sinusitis, upper respiratory tract infection, back pain, migraine, vomiting and influenza, which occurred with similar frequency in both treatment groups. Local injection site reactions solicited in diary cards were observed at a rate of 54% in the IXIARO (japanese encephalitis vaccine) group (N=428) compared to a rate of 69.1% in the JE-VAX group (N=435).

Safety in Concomitant Use with the Hepatitis A Vaccine, HAVRIX3

The safety of IXIARO (japanese encephalitis vaccine) when administered concomitantly with inactivated Hepatitis A Virus vaccine (HAVRIX) was evaluated in a controlled trial in which subjects were assigned randomly to one of three treatment groups: Group A (N=62) received IXIARO (japanese encephalitis vaccine) + HAVRIX; Group B (N=65) received IXIARO (japanese encephalitis vaccine) + control [PBS + Al(OH)3]; Group C (N=65) received HAVRIX + control [PBS + Al(OH)3]. One serious adverse event occurred in this trial in a subject with a history of alcoholism and seizure disorder who experienced a seizure three weeks after receiving the 2nd dose of IXIARO (japanese encephalitis vaccine) + control.

The percentage of subjects who experienced at least one adverse event was as follows: Group A: 38.7%; Group B: 41.5%; Group C: 47.7%. The most frequently reported injection site reaction on the day of the first vaccination in all three groups was injection site pain in 59.0% of subjects in Group A, in 48.4% of subjects in Group B and in 48.4% of subjects in Group C.

Read the Ixiaro (japanese encephalitis vaccine) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Use with HAVRIX

In one clinical trial3, IXIARO (japanese encephalitis vaccine) was administered concomitantly with HAVRIX (Hepatitis A Vaccine) [See ADVERSE REACTIONS and Clinical Studies]. In this trial, there was no evidence for interference with the immune response to IXIARO (japanese encephalitis vaccine) or to HAVRIX when HAVRIX was administered concomitantly with dose 1 of IXIARO [See Clinical Studies]. Data are not available on concomitant administration of IXIARO (japanese encephalitis vaccine) with other US-licensed vaccines.

When IXIARO (japanese encephalitis vaccine) is administered concomitantly with injectable vaccines, they should be given with separate syringes at different injection sites. IXIARO (japanese encephalitis vaccine) should not be mixed with any other vaccine in the same syringe or vial.

Use with Immunosuppressive Therapies

There are no data regarding the use of IXIARO (japanese encephalitis vaccine) concomitantly with immunosuppressive therapies, e.g., irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses) [See WARNING AND PRECAUTIONS].

REFERENCES

1. Clinical study referred to as NCT00605085 in the National Library of Medicine clinical trial database, also referred to as study IC51-302 in the Biologics License Application.

2. Clinical study referred to as NCT00604708 in the National Library of Medicine clinical trial database, also referred to as study IC51-301 in the Biologics License Application.

3. Clinical study referred to as NCT00596271 in the National Library of Medicine clinical trial database, also referred to as study IC51-308 in the Biologics License Application.

4. Clinical study referred to as NCT00595790 in the National Library of Medicine clinical trial database, also referred to as study IC51-304 in the Biologics License Application.

5. Clinical study referred to as NCT00594958 in the National Library of Medicine clinical trial database, also referred to as study IC51-309 in the Biologics License Application.

Last reviewed on RxList: 3/11/2010
This monograph has been modified to include the generic and brand name in many instances.

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