OFIRMEV SIDE EFFECTS

SIDE EFFECTS

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

• Hepatic Injury
• Serious Skin Reactions
• Allergy and Hypersensitivity

Clinical Trial Experience

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

Adult Population

A total of 1020 adult patients have received OFIRMEV in clinical trials, including 37.3% (n=380) who received 5 or more doses, and 17.0% (n=173) who received more than 10 doses. Most patients were treated with OFIRMEV 1000 mg every 6 hours. A total of 13.1% (n=134) received OFIRMEV 650 mg every 4 hours.

All adverse reactions that occurred in adult patients treated with either OFIRMEV or placebo in repeated dose, placebo-controlled clinical trials at an incidence ≥ 3% and at a greater frequency than placebo are listed in Table 1. The most common adverse events in adult patients treated with OFIRMEV (incidence ≥ 5% and greater than placebo) were nausea, vomiting, headache, and insomnia.

Table 1. Treatment-Emergent Adverse Reactions Occurring in ≥ 3% of OFIRMEV-treated Adult Patients and at a greater frequency than Placebo in Placebo-Controlled, Repeated Dose Studies

Other Adverse Reactions Observed During Clinical Studies Of OFIRMEV In Adults

The following additional treatment-emergent adverse reactions were reported by adult subjects treated with OFIRMEV in all clinical trials (n=1020) that occurred with an incidence of at least 1% and at a frequency greater than placebo (n=525).

Blood and lymphatic system disorders: anemia

General disorders and administration site conditions: fatigue, infusion site pain, edema peripheral

Investigations: aspartate aminotransferase increased, breath sounds abnormal

Metabolism and nutrition disorders: hypokalemia

Musculoskeletal and connective tissue disorders: muscle spasms, trismus

Psychiatric disorders: anxiety

Respiratory, thoracic and mediastinal disorders: dyspnea

Vascular disorders: hypertension, hypotension

Pediatric Population

A total of 483 pediatric patients (72 neonates, 167 infants, 171 children, and 73 adolescents) have received OFIRMEV in active-controlled (n=250) and open-label clinical trials (n=225), including 43.9% (n=212) who received 5 or more doses and 31.2% (n=153) who received more than 10 doses. Pediatric patients received OFIRMEV doses up to 15 mg/kg on an every 4 hours, every 6 hours, or every 8 hours schedule. The maximum exposure was 7.7, 6.4, 6.8, and 7.1 days in neonates, infants, children, and adolescents, respectively.

The most common adverse events (incidence ≥ 5%) in pediatric patients treated with OFIRMEV were nausea, vomiting, constipation, and pruritus.

Other Adverse Reactions Observed During Clinical Studies Of OFIRMEV In Pediatrics

The following additional treatment-emergent adverse reactions were reported by pediatric subjects treated with OFIRMEV (n=483) that occurred with an incidence of at least 1%.

Blood and lymphatic system disorders: anemia

Gastrointestinal disorders: diarrhea

General disorders and administration site conditions: pyrexia, injection site pain

Metabolism and nutrition disorders: hypokalemia, hypomagnesemia, hypoalbuminemia, hypophosphatemia

Musculoskeletal and connective tissue disorders: muscle spasm

Nervous system disorders: headache

Psychiatric disorders: agitation

Renal and urinary disorders: oliguria

Respiratory, thoracic and mediastinal disorders: atelectasis, pleural effusion, pulmonary edema, stridor, wheezing

Vascular disorders: hypotension, hypertension