Optison Warnings, Precautions, Pregnancy, Nursing, Abuse - Perflutren

Optison Warnings, Precautions, Pregnancy, Nursing, Abuse - Perflutren

WARNINGS

Cardiac Shunts: The safety of OPTISON in patients with right-to-left, bidirectional or transient right-to-left cardiac shunts has not been studied. In these patients, microspheres can bypass filtering by the lung and directly enter the arterial circulation. Extreme caution should be exercised when considering the administration of OPTISON to patients with congenital heart defects.

The potential toxicity of microspheres in patients with small pulmonary vascular beds or with small cross-sectional vascular surface area has not been studied. OPTISON should be administered with caution to patients with severe emphysema, pulmonary vasculitis or a history of pulmonary emboli. This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral disease. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral disease or CJD have ever been identified for albumin.

OPTISON should be administered with caution to patients with confirmed or suspected severe liver disease or respiratory distress syndrome. The safety of microspheres in patients on mechanical ventilation has not been studied.

Whenever protein-containing materials such as OPTISON are used in humans, hypersensitivity reactions may occur. In clinical studies of OPTISON, one patient had acute nausea, flushing, dizziness, tachycardia and fever that required treatment with antihistamines. Epinephrine, antihistamines, and corticosteroids should be available for immediate treatment of the patient’s symptoms.

Diagnostic echocardiography procedures that involve the use of OPTISON should be carried out under the direction of a licensed practitioner having a thorough knowledge of the procedure and the safe use of the product.

Immunologic tests of serum immunoglobulins, cytokines, and complement were monitored in a 3 week study of 20 healthy volunteers and 30 patients who received OPTISON or a 1% albumin control. Clinically relevant changes in the measured parameters were not noted. In another study 5 subjects received a skin test with OPTISON one year after receiving OPTISON. One subject had a positive skin test and was not given a repeat dose of OPTISON.

INFORMATION FOR PATIENTS

Patients receiving OPTISON:

1. Inform your physician or health care provider if you may be pregnant or are nursing an infant.

2. Inform your physician if you ever have had allergic or hypersensitivity reaction to blood, blood products, or albumin.

3. Inform your physician or health care provider if you have a congenital heart defect.

Animal studies were not carried out to determine the carcinogenic potential of OPTISON.

The result of the following genotoxicity studies with OPTISON were negative: 1) Salmonella/ Escherichia coli reverse mutation assay, 2) in vitro mammalian chromosome aberration assay using Chinese hamster ovary cells (CHO) with and without metabolic activation, 3) CHO/HGPRT forward mutation assay, and 4) in vivo mammalian micronucleus assay.

OPTISON administered intravenously to rats during organogenesis at doses of 0.25, 5.0 and 10.0 mL/kg/day was fetotoxic at 0.25 and 5.0 mL/kg (approximately 0.2 and 5 times the recommended maximum human dose, respectively, based on body surface area). Fetotoxicity was characterized by an increased incidence of reversible delayed pelvic ossification, the incidence of which was not related to dose. Signs of maternal toxicity at 5 mL/kg included respiratory and motor signs. Maternal death occurred at 10 mL/kg. A no observable adverse effect level (NOAEL) for fetotoxicity was not determined. Teratogenic effects were not observed at doses up to 10 mL/kg/day. The NOAEL for maternal toxicity was 0.25 mL/kg.

OPTISON administered intravenously to rabbits during organogenesis at doses of 0.25, 2.5 and 5.0 mL/kg/day was embryofetal toxic at 2.5 and 5.0 mL/kg (approximately 5 and 10 times the recommended maximum human dose, respectively, based on body surface area). Embryofetal toxicity was characterized by a decrease in fetal body weight and an increase in embryofetal death. Teratogenic effects (cleft palates and dilation of the lateral ventricles of the brain associated with skull abnormalities and compression deformities) were observed at 2.5 mL/kg but not 5 mL/kg. Neither the incidence nor the severity of embryofetal toxicity and teratogenicity exhibited a dose-dependent relationship. Maternal toxicity (significant suppression of body weight gain, abnormal stool) was observed at 2.5 and 5.0 mL/kg with the greatest effect observed at 2.5 mL/kg. The NOAEL for embryofetal and maternal toxicity was 0.25 mL/kg (approximately 0.5 times the recommended maximum human dose).

Adequate or well-controlled studies were not conducted in pregnant women. OPTISON should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk caution should be exercised when OPTISON is administered to a nursing woman.

Safety and efficacy have not been established in pediatric patients, or in patients with congenital heart disease. (See Warnings).