Octafluoropropane

Octafluoropropane, a diagnostic drug that is intended to be used for contrast enhancement during the indicated echocardiographic procedures, is comprised of lipid-coated microspheres filled with octafluoropropane(OFP) gas. When exposed to ultrasound waves, the microspheres resonate and "echo" strong signals back to the ultrasound machine. The difference in density between the gas-filled bubbles and the blood around them creates an increased level of contrast visible in the resulting ultrasound image. During echocardiography, activated Octafluoropropane enhances images of the inner edges or borders of the heart, producing an improved image that may enable physicians to better diagnose patients.

Octafluoropropane is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricle and to improve the delineation of the left ventricular endocardial borders.

DOSAGE AND ADMINISTRATION

Recommended Dosage

• The recommended dose of Octafluoropropane is 0.5 mL injected into a peripheral vein.
• If the contrast enhancement is inadequate after the dose of 0.5 mL, additional doses in increments of 0.5 mL may be repeated for further contrast enhancement as needed.
• The maximum total dose should not exceed 5mL in any 10 minute period.
• The maximum total dose should not exceed 8.7 mL in any one patient study.

Preparation Instructions

• Do not use if the container has been damaged, the protective seal and/or rubber cap have been entered, or the upper white layer is absent (may indicate the microspheres have been damaged and may result in poor or no echo contrast).
• Invert the Octafluoropropane vial and gently rotate to resuspend the microspheres. This process will allow the product to come to room temperature before use.
• Inspect the vial for complete resuspension. Do not use if the solution appears to be clear rather than opaque and milky-white.
• Vent the Octafluoropropane vial with a sterile vent spike or with a sterile 18 gauge needle before withdrawing the Octafluoropropane suspension into the injection syringe.
• Do not inject air into the vial.
• Use the product within one minute of suspension. If one minute is exceeded, resuspend by inverting and gently rotating the microsoheres in the syringe. Failure to adequately resuspend Octafluoropropane may cause inadequate delivery of the microspheres, and may result in inadequate contrast.

Administration Instructions

• Inspect visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not inject if the solution is not opaque, milky-white, and absent particulate matter.
• Inject through a 20-gauge or larger angiocatheter into a peripheral vein at a rate not exceeding 1 mL per second. Suggested methods of administration include: a short extension tubing, heparin lock, or intravenous line, all with a 3-way stopcock.
• Administer intravenously; do not administer Octafluoropropane by intra-arterial injection.
• Do not aspirate blood back into the Octafluoropropane containing syringe before administration; this may promote the formation of a blood clot within the syringe.
• For short extension tubing or heparin lock: fill one syringe with 0.9% Sodium Chloride Injection, USP, and FLUSH the line for patency before and after the injection of Octafluoropropane.
• For a continuous intravenous line: open an intravenous line with 0.9% Sodium Chloride Injection, USP (or 5% Dextrose Injection, USP) at a slow infusion rate to maintain vascular patency. Flush the line immediately after injection of Octafluoropropane
• Do not use the single-patient use vial for more than one patient. Discard unused product.

Octafluoropropane lipid microsphere preparation is an ultrasound contrast agent. Ultrasound contrast agents are used to help provide a clear picture during ultrasound. Ultrasound is a special kind of diagnostic procedure. It uses high-frequency sound waves to create images or “pictures” of certain areas inside the body. The sound waves produced by the ultrasound equipment can be reflected (bounced off) by different parts of the body, like for example, the heart. As the sound waves return they are electronically converted into images on a television screen. Unlike x-rays, ultrasound does not involve ionizing radiation.

The Octafluoropropane lipid microspheres preparation contains very small gas-filled lipid microspheres that reflect the sound waves and help create a better picture. The lipid microsphere preparation is given by injection into a vein before ultrasound to help diagnose problems of the heart.

Octafluoropropane lipid microsphere is to be given only by or under the direct supervision of a doctor with specialized training in ultrasound procedures.

Octafluoropropane® IS INTENDED FOR ADMINISTRATION ONLY AFTER ACTIVATION IN THE VIALMIX® APPARATUS. Before injection, this product must be activated and prepared according to the instructions outlined below. The Vialmix® apparatus should be ordered from Bristol-Myers Squibb Medical Imaging, 331 Treble Cove Road, North Billerica, MA 01862. For customer orders call 1-800-299-3431.

Octafluoropropane® may be injected by either an intravenous bolus or infusion.

Bolus: The recommended dose for activated Octafluoropropane® is 10 microliters (µL)/kg of the activated product by intravenous bolus injection within 30-60 seconds, followed by a 10 mL saline flush. If necessary, a second 10 microliters (µL)/kg dose followed by a second 10 mL saline flush may be administered 30 minutes after the first injection to prolong contrast enhancement.

Infusion: The recommended dose for activated Octafluoropropane® is via an IV infusion of 1.3 mL added to 50 mL of preservative-free saline. The rate of infusion should be initiated at 4.0 mL/minute, but titrated as necessary to achieve optimal image enhancement, not to exceed 10 mL/minute.

The maximum dose is either two bolus doses or one single intravenous infusion. The safety of bolus and infusion dosing in combination or in sequence, has not been studied.

Imaging: After baseline non-contrast echocardiography is completed, the mechanical index for the ultrasound device should be set at 0.8 or below. Then inject activated Octafluoropropane® (as described above) and begin ultrasound imaging immediately. The activated Octafluoropropane® echocardiogram images should be evaluated in combination with the non-contrast echocardiogram images.

Octafluoropropane® ACTIVATION, PREPARATION AND HANDLING INSTRUCTIONS:

1. Allow the vial to warm to room temperature before starting the activation procedure.
2. Activate Octafluoropropane® by shaking the vial for 45 seconds using a Vialmix®.

   Note: illustrations of this procedure are contained in the Vialmix® Users Guide.

   WARNING: DO NOT USE THIS DRUG UNLESS IT HAS COMPLETED A FULL 45 SECOND ACTIVATION CYCLE IN THE VIALMIX®. Octafluoropropane® WILL NOT BE PROPERLY ACTIVATED UNLESS THE FULL 45 SECOND ACTIVATION CYCLE IS COMPLETED. DO NOT REACTIVATE the vial if Vialmix® did not complete a full 45 second cycle. DO NOT REACTIVATE a successfully activated Octafluoropropane® vial. DO NOT USE a Vialmix® that is not functioning properly. Refer to the "VIALMIX® User's Guide" for the "VIALMIX® CALIBRATION AND REPLACEMENT PROCEDURES" to ensure that a properly functioning Vialmix® is used.

3. Immediately after activation in the Vialmix®, activated Octafluoropropane® appears as a milky white suspension and may be used immediately after activation. If the product is not used within 5 minutes of Vialmix® activation, the microspheres should be resuspended by 10 seconds of hand agitation by inverting the vial before the product is withdrawn in a syringe. The activated Octafluoropropane® may be used for up to 12 hours from the time of Vialmix®, but only after the microspheres are resuspended by hand agitation. Store the activated Octafluoropropane® at room temperature in the original product vial.

4. Invert the vial and withdraw the activated milky white suspension using the Intellipin™ (Dispensing Pin) or 18 to 20 gauge syringe needle. Withdraw the material from the middle of the liquid in the inverted vial. DO NOT INJECT AIR INTO THE Octafluoropropane® VIAL.

5. Use the product immediately after its withdrawal from the vial; do not allow the product to stand in the syringe.

FOR SINGLE USE ONLY: Octafluoropropane® does not contain bacterial preservative. Bacterial contamination with the risk of post-administration septicemia can occur following the puncture of the elastomeric septum. It is essential to follow directions for activation of Octafluoropropane® carefully and to adhere to strict aseptic procedures during preparation.

See also:
What is the most important information I should know about Octafluoropropane?

Do not administer Octafluoropropane® to patients with known or suspected:

• Right-to-left, bi-directional, or transient right-to-left cardiac shunts,
• Worsening or clinically unstable congestive heart failure,
• Acute myocardial infarction or acute coronary syndromes,
• Serious ventricular arrhythmias or high risk for arrhythmias due to prolongation of the QT interval,
• Respiratory failure, as manifest by signs or symptoms of carbon dioxide retention or hypoxemia,
• Severe emphysema, pulmonary emboli or other conditions that cause pulmonary hypertension due to compromised pulmonary arterial vasculature,
• Hypersensitivity to Octafluoropropane.

Do not administer Octafluoropropane® by intra-arterial injection.

Use Octafluoropropane (protein-type a microspheres) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Octafluoropropane (protein-type a microspheres) will be given as an injection at your doctor's office, hospital, or clinic.
• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Octafluoropropane (protein-type a microspheres), contact your doctor right away.

Ask your health care provider any questions you may have about how to use Octafluoropropane (protein-type a microspheres).

Use: Labeled Indications

Cardiovascular imaging: Opacification of the left ventricular chamber and improvement of delineation of the left ventricular endocardial border in patients with suboptimal echocardiograms

Off Label Uses

Focal liver lesion evaluation

Data from several observational studies support the use of Octafluoropropane lipid microspheres in the evaluation of focal liver lesions. Additional trials may be necessary to further define the role of Octafluoropropane lipid microspheres in this setting.

The World Federation for Ultrasound in Medicine and Biology guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver provides general advice on the use of ultrasound contrast agents (eg, Octafluoropropane lipid microspheres) when evaluating focal liver lesions.

See also:
What other drugs will affect Octafluoropropane?

Drug-drug interactions for activated Octafluoropropane® have not been studied.

See also:
What are the possible side effects of Octafluoropropane?

Clinical Trials Experience

Octafluoropropane was administered in clinical studies in 279 patients. Of these patients there were 192 (68.8%) men and 87 (31.2%) women. The racial demographics were 199 (71.3%) Caucasian, 52 (18.6%) Black, 24 (8.6%) Hispanic, and 4 (1.4%) other racial or ethnic groups.

In these patients, 47 (16.8%) reported at least one adverse event. Of these one event was serious and required treatment with antihistamines for hypersensitivity manifestations of dizziness, nausea, flushing and temperature elevation. Deaths were not reported during the clinical studies.

Of the reported adverse reactions following the use of Octafluoropropane the most frequently reported were headache (5.4%), nausea and/or vomiting (4.3%), warm sensation or flushing (3.6%), and dizziness (2.5%). The most common adverse events observed in clinical studies of Octafluoropropane are given in Table 4.

Adverse events reported in < 0.5% of subjects who received Octafluoropropane included: arthralgia, back pain, body or muscle aches, induration, urticaria, dry mouth, eosinophilia, palpitations, paresthesia, photophobia, premature ventricular contraction, pruritus, rash, irritableness, hypersensitivity, tinnitus, tremor, visual blurring, wheezing, oxygen saturation decline due to coughing, discoloration at the Heplock site, and burning sensation in the eyes.

Overall the reported adverse events with Octafluoropropane were similar in type and frequency to those reported in the 199 patients who received ALBUNEX®.

In the clinical dose ranging studies of 40 normal volunteers, doses higher than those recommended in the DOSAGE AND ADMINISTRATION section tended to be associated with an increased frequency of reported adverse events.

Postmarketing Experience

In a prospective, post-marketing safety surveillance study of Octafluoropropane used in routine clinical practice, a total of 1039 subjects received Octafluoropropane. Of these patients, 648 (62.4%) were male and 391 (37.6%) were female with average age of 59.9 years (min, max: 20, 97). The racial distributions were 864 (83.2%) White, 141 (13.6%) Black, 18 (1.7%) Asian, and 16 (1.5%) other racial or ethnic groups. Overall, 175 patients (16.8%) reported at least one adverse event. No serious adverse reactions, including deaths, were reported in this study, suggesting that these reactions are unlikely to occur at a rate of more than 0.3% when Octafluoropropane is used according to recommendations.

The following adverse reactions have been identified during the postmarketing use of Octafluoropropane. Because these 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.

Cardiac arrests and other serious but non-fatal adverse reactions were uncommonly reported. Most of these uncommon reactions included cardiopulmonary symptoms and signs such as cardiac arrest, hypotension, supraventricular and ventricular arrhythmias, respiratory distress or decreased oxygenation. Reports also identified neurologic reactions (loss of consciousness or convulsions) as well as anaphylactoid reactions.