Rapivab (Page 2 of 5)

3 DOSAGE FORMS AND STRENGTHS

Each vial of RAPIVAB injection contains 200 mg per 20 mL (10 mg per mL) as a clear, colorless solution [see How Supplied/Storage and Handling (16)].

4 CONTRAINDICATIONS

RAPIVAB is contraindicated in patients with known serious hypersensitivity or anaphylaxis to peramivir or any component of the product. Severe allergic reactions have included anaphylaxis, erythema multiforme, and Stevens-Johnson syndrome [see Warnings and Precautions (5.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Serious Skin/Hypersensitivity Reactions

Rare cases of serious skin reactions, including erythema multiforme, have been reported with RAPIVAB in clinical studies and in postmarketing experience. Cases of anaphylaxis and Stevens-Johnson syndrome have been reported in postmarketing experience with RAPIVAB. Discontinue RAPIVAB and institute appropriate treatment if anaphylaxis or a serious skin reaction occurs or is suspected. The use of RAPIVAB is contraindicated in patients with known serious hypersensitivity or anaphylaxis to RAPIVAB [see Contraindications (4), Adverse Reactions (6.2)].

5.2 Neuropsychiatric Events

Influenza can be associated with a variety of neurologic and behavioral symptoms that can include events such as hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur in uncomplicated influenza as well.

There have been postmarketing reports of delirium and abnormal behavior leading to injury in patients with influenza who were receiving neuraminidase inhibitors, including RAPIVAB. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made, but they appear to be uncommon. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of RAPIVAB to these events has not been established. Patients with influenza should be closely monitored for signs of abnormal behavior.

5.3 Risk of Bacterial Infections

There is no evidence for efficacy of RAPIVAB in any illness caused by agents other than influenza viruses. Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications during the course of influenza. RAPIVAB has not been shown to prevent such complications.

Prescribers should be alert to the potential for secondary bacterial infections and treat with antibiotics as appropriate.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in other sections of the labeling:

• Serious skin and hypersensitivity reactions [see Warnings and Precautions (5.1)]
• Neuropsychiatric events [see Warnings and Precautions (5.2)]

6.1 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.

Adverse Reactions in Adults (18 years of age and older)

In 5 randomized, double-blind, controlled trials, 1,399 subjects with acute uncomplicated influenza received a single dose of RAPIVAB, administered intravenously or intramuscularly, at doses up to 600 mg. Among the 664 subjects receiving RAPIVAB 600 mg (intravenous or intramuscular), the most commonly observed adverse reaction was diarrhea, occurring at a rate of 8% versus 7% in subjects receiving placebo. No subject receiving RAPIVAB 600 mg experienced a serious adverse event and <1% discontinued study because of an adverse reaction.

Clinically significant laboratory abnormalities (DAIDS Grades 2 to 4) listed in Table 4 occurred more frequently in subjects treated with RAPIVAB 600 mg (intravenous or intramuscular) than placebo. Only events occurring at ≥2% are included.

Table 4: Laboratory Abnormalities Occurring in ≥2% of Subjects Treated with RAPIVAB 600 mg

Laboratory Parameter Abnormalitya	RAPIVAB 600 mg	Placebo
a Frequencies based on treatment-emergent laboratory abnormalities.
Alanine Aminotransferase (>2.5 × ULN)	(n = 654) 3%	(n = 430) 2%
Serum Glucose (>160 mg/dL)	(n = 660) 5%	(n = 433) 3%
Creatine Phosphokinase (≥6.0 × ULN)	(n = 654) 4%	(n = 431) 2%
Neutrophils (<1.000 ×109 /L)	(n = 654) 8%	(n = 430) 6%

In a subset of subjects with serious influenza requiring hospitalization treated with RAPIVAB 600 mg as monotherapy (n = 101), the following adverse reactions were also reported more frequently with RAPIVAB as compared to placebo: constipation (4% versus 2%), insomnia (3% versus 0%), AST increased (3% versus 2%), and hypertension (2% versus 0%).

Adverse Reactions in Adolescent and Pediatric Subjects (6 months to 17 years of age)

Assessment of adverse reactions is based on a randomized, active-controlled study in which 130 adolescent and pediatric subjects ages 6 months to 17 years of age with acute uncomplicated influenza received open-label treatment with a single dose of RAPIVAB (n = 107), or 5 days of treatment with oseltamivir (n = 23) [see Use in Specific Populations (8.4), Clinical Studies (14.2)].

The safety profile of RAPIVAB in subjects 6 months to 17 years of age was generally similar to that observed in adults. The only adverse reaction reported in pediatric subjects treated with RAPIVAB (occurring in ≥2% of subjects) and not reported in adults was vomiting (3% versus 9% for oseltamivir). The only clinically significant laboratory abnormality (DAIDS Grade 2) occurring in ≥2% of pediatric subjects treated with RAPIVAB (and not previously reported in adults) was proteinuria by dipstick analysis (3% versus 0% for oseltamivir).

6.2 Postmarketing Experience

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

Dermatologic: Stevens-Johnson syndrome, exfoliative dermatitis, rash [see Warnings and Precautions (5.1)].

General Disorders and Administration Site Conditions: Anaphylactic/anaphylactoid reactions [see Warnings and Precautions (5.1)].

Psychiatric: Abnormal behavior, hallucination [see Warnings and Precautions (5.2)].

7 DRUG INTERACTIONS

This section describes clinically relevant drug interactions with RAPIVAB. Drug-drug interaction studies are described elsewhere in the labeling [see Clinical Pharmacology (12.3)].

7.1 Influenza Vaccines

Inactivated influenza vaccine can be administered at any time relative to use of RAPIVAB. For live attenuated influenza vaccine (LAIV), antiviral drugs may inhibit viral replication and thus may reduce vaccine efficacy. The concurrent use of RAPIVAB with LAIV intranasal has not been evaluated. Because of the potential for interference between these two products, avoid use of LAIV within 2 weeks before or 48 hours after administration of RAPIVAB unless medically indicated.