Indications, Safety, and Warnings
INTENDED USE/INDICATIONS FOR USE
Embozene Microspheres are intended for the embolization of arteriovenous malformations and hypervascular tumors, including uterine fibroids (UFE) and hepatoma, and for embolization of prostatic arteries (PAE) for symptomatic benign prostatic hyperplasia (BPH).
The device is not intended for neurovascular use.
MAGNETIC RESONANCE IMAGING
Embozene Microspheres are MR safe.
Embolization procedures shall not be performed if:
- Patient is unable to tolerate vascular occlusion procedures.
- Vascular anatomy precludes correct catheter placement or embolic injection.
- Presence or likely onset of vasospasm.
- Presence of a blood coagulation disorder that would prohibit arterial punctures.
- Presence of severe atheromatous disease that would preclude correct catheter placement.
- Presence of patent extra-to-intra-cranial anastomoses or shunts from the arterial to the venous circulation.
- Presence of collateral vessel pathways which could potentially endanger non-targeted tissue during an embolization procedure.
- Presence of any vasculature where Embozene Microspheres could pass directly into the central nervous system, central circulatory system or other non-target territories.
- Patient has high-flow arteriovenous shunt with diameter greater than the selected Embozene Microspheres.
- Patient is pregnant.
- Patient has known allergies to barium sulfate, 3-aminopropyltrialkoxysilane, polyphosphazene or IV radiopaque contrast agent
CONTRADICTIONS SPECIFIC TO UFE
In addition to the general emobolization contraindications, uterine fibroid embolization procedures shall not be performed if:
- Presence of suspected or active pelvic inflammatory disease.
- Presence of malignancy of the pelvic region.
- Presence of endometrial neoplasia or hyperplasia.
- Presence of submucosal fibroids with more than 50% growth into the uterine cavity.
- Presence of pedunculated serosal fibroid as the dominant fibroid(s).
- Presence of fibroids with significant collateral feeding by vessels other than the uterine arteries.
CONTRAINDICATIONS SPECIFIC TO PAE
In addition to the general embolization contraindications, Prostatic Artery Embolization (PAE) procedures for benign prostatic hyperplasia shall not be performed if:
- Evidence of prostatic cancer or bladder cancer.
- Urethral stricture.
- Prostate size (less than) 40 grams.
- Active prostatitis.
- Interest in the preservation of fertility.
- Patients with renal impairment.
- Peak urinary flow rate (greater than) 12 ml/sec.
- Large bladder diverticulas or stones.
- Neurogenic bladder.
- Detrusor failure.
- Vascular embolization is a high risk procedure. The procedure should be performed by specialized physicians trained in vascular embolization procedures.
- Care must be taken to choose larger sized Embozene Microspheres when embolizing arteriovenous malformations with large shunts to avoid passage of the microspheres into the venous and subsequently to the pulmonary circulation.
- Extreme caution should be used for any procedures above the neck, and risk benefit assessment should be performed to avoid non-target embolization complications.
- Risks of radiation from angiography and fluoroscopy used to visualize the blood vessels during embolization, which may include a radiation burn and risks to future fertility.
- Do not use Embozene Microspheres in conjunction with embolization devices based on organic solvents such as ethyl alcohol or dimethyl sulfoxide (DMSO) at the same embolization site.
- Do not use ionic contrast agent with this product. Ionic contrast agents could alter the microsphere characteristics resulting in microsphere deformation and procedure failure.
- Do not use heparinized saline as this could lead to microsphere agglomeration. Agglomeration may impede microsphere delivery through the catheter or result in non-target embolization.
- Should catheter obstruction occur, remove the catheter from the patient. Do not use forceful injection, guidewires or other instruments to dislodge the blockage.
WARNINGS SPECIFIC TO UFE
- Do not use microspheres smaller than 500 μm.
- The diagnosis of uterine sarcoma could be delayed by taking a nonsurgical approach (such as UFE) to treating fibroids. It is important to pay close attention to warning signs for sarcoma (e.g., rapid tumor growth, postmenopausal with new uterine enlargement, MRI findings) and to conduct a more thorough work-up of such patients prior to recommending UFE. Recurrent or continued tumor growth following UFE should be considered a potential warning sign for sarcoma and surgery should be considered.
WARNINGS SPECIFIC TO UFE AND PREGNANCY
There is no long-term data on the effects of UFE on the ability to become pregnant and carry a fetus to term, and on the development of the fetus. This procedure should only be performed on women who do not intend future pregnancy. Women who become pregnant following UFE may be at increased risk for the following:
- Postpartum hemorrhage
- Preterm delivery
- Caesarean delivery
- Abnormal placentation
- Devascularization of the uterine myometrium resulting from UFE may increase the risk of uterine rupture of women who subsequently become pregnant following UFE.
WARNINGS SPECIFIC TO PAE
- An appropriate urological work-up should be performed on all patients (e.g., urological history and appropriate testing, such as Prostate-Specific Antigen test and, when appropriate, biopsy to rule out carcinoma).
- The effect of prostatic embolization on male fertility has not been determined. Therefore, this procedure should only be performed on men who are willing to accept the risk of future infertility.
- Three-dimensional planning imaging (e.g., magnetic resonance angiography [MRA], computed tomographic angiography [CTA] should be performed prior to embolization on patients who have had any previous invasive treatment to the prostate (e.g., surgery, ablation, etc.) or pelvic irradiation.
To maintain safety, the following precautions shall be considered:
- Safety and effectiveness of Embozene Microspheres in the treatment of uterine fibroids has not been established
- Safety and effectiveness of Embozene Microspheres for hepatic and renal embolization uses has not been established.
- The physician should carefully select the size and quantity of Embozene Microspheres according to the lesion to be treated based on the physician’s education and training and currently available scientific evidence.
- Physicians must decide the most appropriate time to stop the infusion of Embozene Microspheres. Typically the artery will accept fewer Embozene Microspheres as the treatment progresses. Proximal slowing or termination of flow may indicate that the vessel or the target area is occluded by Embozene Microspheres. Careful fluoroscopic monitoring is required.
- Microparticle embolization must be performed slowly. The injection speed and manner must be controlled. Excessive injection rate may result in retrograde flow in the vessel leading to embolization of other non-target healthy tissue or organs
- The color of the Embozene Microspheres may be visible through the skin if injected into superficial arteries.
- If arteriovenous anastomoses, branch vessels which lead away from the targeted embolization area, or emergent vessels not evident prior to embolization are present, it can lead to non-targeted embolization and cause severe complications for the patient.
- Microspheres smaller than 100 μm can migrate to distal anastomotic feeders and embolize circulation to distal tissue. For this reason, smaller microspheres have a greater likelihood of causing unwanted ischemic injury. This should be considered prior to starting the embolization procedure.
- Ischemia of tissue adjacent to the targeted area may result from post-embolization swelling. Therefore, special care
should be taken to avoid such ischemia of non-tolerant, non-targeted tissue such as the nervous system.
- Consider upsizing Embozene Microspheres if angiographic appearance of embolization does not quickly appear
during injection of the microspheres.
- If there are any symptoms of unwanted embolization during injection, consider stopping the procedure to evaluate
the possibility of shunting. Such symptoms may include changes in patient vital signs, such as hypoxia or central
nervous system changes.
INTERACTIONS WITH PHARMACEUTICALS
There are no known chemical interactions between Embozene Microspheres and pharmaceuticals.
Potential adverse events associated with the use of Embozene Microspheres include, but may not be limited to:
- Allergic reaction
- Capillary bed saturation and tissue damage
- Cerebrovascular accident (CVA)
- Complications related to catheterization (e.g., hematoma at the site of entry, clot formation at the tip of the microcatheter and subsequent dislodgement, vasospasm, nerve injury, vessel trauma [e.g., dissection, perforation, rupture])
- Foreign body reactions (e.g., pain, rash, fever, inflammation)
- Incomplete occlusion of vascular beds or territories may give rise to the possibility of post-procedural hemorrhage,
- Development of alternative vascular pathways, recanalization, or recurrence of symptoms
- Ischemia at an undesirable location
- Ischemic infarction
- Neurological deficits including cranial nerve palsies
- Post-embolization syndrome
- Pulmonary embolization
- undesirable reflux, passage/migration or placement of Embozene™ Microspheres, resulting in non-target embolization
- Vessel or lesion rupture
Potential adverse events specific to UFE:
- Infection of the pelvic region
- Premature ovarian failure (i.e., menopause)
- Temporary or permanent stopping of menstrual bleeding
- Tissue passage, fibroid sloughing, or fibroid expulsion post-UFE
- Uterine rupture
- Uterine/Ovarian necrosis
- Vaginal discharge
- Worsening of fibroid-related symptoms or the onset of new symptoms
Potential adverse events specific to PAE:
- Acute urinary retention
- Bladder ischemia or necrosis requiring surgical intervention
- Rectal Bleeding
- Rectal or lower colonic strictures
- Sexual dysfunction or impaired fertility
- Urethral or anal burning sensation
- Urethral stricture
- Urinary incontinence
- Urinary symptoms (e.g. dysuria, urgency, frequency)