Albumin, Microspheres (Human) (3215)
| Ingredients: |
Albumin, Microspheres (Human) |
| Indications: |
Echocardiography, adjunct |
| Pregnancy Category: |
B |
| FDA Approved: |
1994- 08- 01 |
| Classes: |
Plasma expanders |
| HCFA Jcodes: |
P9045, P9047 |
| Brand Names: |
Albumarc
-
US
;
Albumin-Alpine
-
US
;
Albuminar-25
-
US; Taiwan
;
Albuminar-5
-
US; Taiwan
;
Alburx
-
US
;
Albutein
-
US
;
Buminate
-
US
;
Plasbumin-20
-
US
;
Plasbumin-25
-
US
;
Plasbumin-5
-
US
;
|
| DEA schedules: |
(none)
|
DESCRIPTION
|
| |
Note: The trade name has been used throughout this monograph for clarity.
Albunex microspheres are produced by sonication of Albumin (Human), 5% Solution. The human albumin used to manufacture Albunex
is US Food and Drug Administration (FDA) licensed and is derived from plasma collected from donors who have been previously
screened and tested according to the methods specified by the FDA. The human albumin solution is held at 60°C for 10 hours.
The following stabilizers are added per gram of albumin: 0.08 millimole sodium acetyl tryptophanate, and 0.08 millimole sodium
caprylate.
The protein in the Albunex microspheres makes up approximately 1% (w/ w) of the total protein in the liquid, and the remaining
99% (w/ w) is unchanged 5% human albumin.
Albunex is a sterile, non- pyrogenic liquid. Prior to inversion it appears as a clear amber liquid with an upper white layer
containing the air- filled microspheres. Upon resuspension, the liquid is opaque (milky).
Parameters:
- pH: 6.4- 7.4
- Microsphere concentration: 3- 5 × 108/ ml
- Microsphere diameter (mean): 3.0- 5.0 μm
- Size distribution: 92.5% less than 10 μm
- Maximum diameter: 32 μm
- Volume per vial: 10 ml
- Single unit dose. Contains no preservatives.
Storage: Store Albunex in the refrigerator (2° to 8°C). Do not freeze .
|
CLINICAL PHARMACOLOGY
|
| |
No human pharmacokinetic studies have been performed with Albunex. For animal pharmacology refer to the animal data section.
|
INDICATIONS AND USAGE
|
| |
Albunex is intended as an aid for ultrasound contrast enhancement of ventricular chambers, and improves endocardial border
definition in patients with suboptimal echoes undergoing ventricular function and regional wall motion studies.
|
CONTRAINDICATIONS
|
| |
Albunex should not be administered to patients with known or suspected hypersensitivity to blood products.
|
WARNINGS
|
| |
The safety and effectiveness of Albunex have not been studied in children.
Inspect Albunex before resuspending:
- DO NOT USE if lower level of product is turbid or cloudy.
- DO NOT USE if white upper level of product is absent.
- DO NOT USE if the container has been damaged or protective seal and/ or rubber cap have been entered.
- DO NOT USE if after resuspending the Albunex, the product remains clear amber instead of changing to milky white.
- DO NOT INFUSE Albunex into a patient at rates faster than 1 ml/ sec.
Aspiration of blood back into the Albunex containing syringe prior to administration is not recommended as this may promote
the formation of clots.
|
PRECAUTIONS
|
| |
General
|
| |
Albunex should be administered with caution to patients with confirmed or suspected severe liver disease or adult respiratory
distress syndrome (ARDS). See Animal Toxicology section.
Diagnostic echocardiography procedures that involve the use of Albunex 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.
As in all non- contrast echocardiography studies, Albunex contrast echocardiography should be accompanied by ECG monitoring
to detect and document changes in cardiac cycles and wave patterns.
Hypersensitivity reactions should be anticipated whenever protein- containing materials such as Albunex are used in humans.
Epinephrine, antihistamines, and corticosteroids should be kept available for immediate treatment of the patient's symptoms.
Use an angiocatheter with a 20 Gauge or larger needle, and a three- way stopcock. The catheter should be inserted into as
large a vein as possible to avoid potential under- delivery of contrast agent to the heart chambers. Avoid the use of hand
or wrist veins.
Albunex administration should be followed immediately by flushing with normal saline for injection or dextrose (5%) in water.
It is advisable to maintain an open (TKO) intravenous line. The safety of other intravenous solutions has not been studied
when used with an intravenous Albunex injection.
Albunex may not enhance endocardial borders in echocardiographic views in which there is a poor acoustic window.
Albunex contains no bacteriostatic preservative and should not be used for more than one patient. Discard unused product.
|
Carcinogenesis, Mutagenesis, and Impairment of Fertility
|
| |
No long- term studies in animals have been performed to evaluate carcinogenesis, mutagenesis or impairment of fertility. An in vitro assay (Ames test) was negative for mutagenesis.
|
Pregnancy Category B
|
| |
Albunex may be given to a woman who may be pregnant only if the benefits to the patient outweigh the unknown risk to the fetus.
Animal reproduction studies have been performed in rats and in rabbits at doses up to 4 times the maximum cumulative dose
to humans and revealed no evidence of impaired fertility or harm to the fetus due to Albunex. There are, however, no adequate
and well- controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response,
Albunex should be given to a woman who may be pregnant only if the benefits to that patient outweigh the unknown risks to
the fetus.
|
Nursing Mothers
|
| |
It is not known whether Albunex is excreted in human milk. Because many administered substances are excreted in human milk,
caution should be exercised when Albunex is to be administered to nursing women.
|
Pediatric Use
|
| |
Safety and effectiveness have not been established in children.
|
|
ADVERSE REACTIONS
|
| |
Since Albunex is sterile when coming from the manufacturer, bacterial contamination with the risk of post- infusion septicemia
can only occur if the container has been damaged or following puncture of the rubber cap (see WARNINGS .)
Rare life- threatening and fatal anaphylactoid reactions have been associated with the administration of human albumin products.
Infusion of 5% human albumin has been associated with nausea, flushing, rash, headache, vomiting, chills and fever.
The reported adverse effects following the use of Albunex in human clinical studies of 370 subjects have been mild to moderate,
of short duration and have resolved without treatment. The most frequently reported adverse effect associated with the administration
of Albunex was transient altered taste (4.3%). Other reported adverse events were post- administration headache (1.9%), dizziness
(1.1%) and palpitations (1.1%). The remaining adverse events occurred in less than 1% of patients either coincidental to the
injection or within 24 hours following the study.
- Adverse effects greater than 1%: Transient altered taste, headache, dizziness, palpitations.
- Adverse effects less than 1%: Calming sensation, chest discomfort*, depression, diarrhea, diaphoresis, dyspnea, epigastric burning, flashing lights, flushing/
warmth, hand cramping, hematoma (mild), hypoglycemia, increased thirst, injection site tingling/ soreness, IV infiltration,
lightheadedness, low mid- back discomfort, malaise, fatigue, muscular/ body ache, nausea, numbness (hand/ finger), rash/ pruritus,
skin eruptions, tachycardia, transient blurred vision.
- *Reported in 2 patients with angina and reocclusion following PTCA.
Safe Medical Devices Act of 1990 (SMDA) Device User: As of November 28, 1991, device user facilities ( i.e., hospitals, nursing homes, ambulatory surgical facilities and outpatient treatment facilities) are required to report incidents "that reasonably suggest that a medical device has caused or contributed to a death of a patient, or serious injury or serious
illness of a patient".
Report only those deaths, serious injuries or serious illnesses which occur in your facility and for which it is probable that Albunex
may have caused or contributed to the event. Reports of deaths must be made to the Food and Drug Administration (FDA) and
to Mallinckrodt Medical, Inc. by telephone at 800- 696- 3636. Reports of serious injury and serious illness must be made to
Mallinckrodt Medical, Inc.
Please use Test Form Part I (Form FDA 3375- TEST), which is available from FDA.
Division of Surveillance Systems (HFZ- 533), Center for Devices and Radiological Health, Food and Drug Administration, 1350
Piccard Drive, Rockville, MD 20850 TEL: 301- 594- 2735
|
DOSAGE AND ADMINISTRATION
|
| |
- Special Handling Precautions
- Allow the vials to come to room temperature before use.
- Inspect all vials prior to injection.
- DO NOT USE if the bottom layer appears cloudy or turbid before resuspension.
- DO NOT USE if the white top layer is absent as this is indicative of destroyed microspheres and may result in poor or no echo
contrast.
- The Albunex vial must be inverted and gently rotated for approximately 3 minutes to completely resuspend the microspheres.
Failure to suspend the microspheres in this way may result in under- delivery of microspheres and inadequate contrast. If
after resuspension, Albunex appears clear amber instead of milky white, DO NOT USE.
- Albunex microspheres are FRAGILE. Never shake or drop the vial. To avoid destroying the microspheres, follow these precautions
after resuspension:
- ALWAYS VENT THE VIAL WITH A STERILE SPIKE OR STERILE NEEDLE BEFORE SLOWLY withdrawing Albunex suspension into the injection
syringe using a vent spike such as Burron Medical Inc.'s Mini- Spike Dispensing Pin (DP- 1000) or an 18 Gauge or larger gauge
needle.
- ALWAYS WITHDRAW OR INJECT Albunex no faster than 1 ml/ second.
- Albunex must be infused at a rate NOT TO EXCEED 1 ml/ second.
- The time from resuspension of the Albunex microspheres to injection must not exceed 1 minute.
|
Prior to administration, place a 20 G or larger angiocatheter needle in a large antecubital arm vein and attach a sterile
three- way stopcock. Avoid use of hand or wrist veins. Start intravenous infusion of normal saline for injection or dextrose
(5%) in water, at a "to keep open, or TKO" rate.
Left Heart Studies
|
| |
For left heart studies, the initial recommended dose is 0.08 ml/ kg. If left ventricular opacification is inadequate ( i.e., if moderate to full ventricular opacification is not visualized), a second dose up to 0.22 ml/ kg may be given. The total procedural dose should not exceed 0.30 ml/ kg. For equivalent Albunex doses in ml, see conversion chart.
Immediately after each injection, turn the stopcock to "wide open". The patient's infused arm may be raised until contrast appears in the left cardiac chambers.
At such time, the patient's arm may be lowered; return the infusion rate of the Normal Saline or D5W to "TKO".
|
Right Heart Studies
|
| |
For right heart studies, the initial recommended dose is 2.0 ml. If the right ventricular endocardial borders cannot be well visualized due to attenuation caused by the excessive backscatter
of the Albunex microspheres, continue to decrease the dose by 0.5 ml to a minimum of 0.5 ml or until endocardial border visualization
is optimized. The total procedural dose should not exceed 0.30 ml/ kg.
Immediately after each injection, turn the stopcock to "wide open" until contrast is seen in the patient's right cardiac chambers. Return the infusion rate
of the Normal Saline or D5W to "TKO". (See TABLE 1. )
|
| TABLE 1
Conversion Chart For Left Heart Echocardiography
|
| |
Recommended Dose |
| Patient Weight |
0.08 ml/ kg |
0.22 ml/ kg |
| 50 kg |
110 lb |
4.0 ml |
11.0 ml |
| 60 kg |
132 lb |
4.8 ml |
13.2 ml |
| 70 kg |
154 lb |
5.6 ml |
15.4 ml |
| 80 kg |
176 lb |
6.4 ml |
17.6 ml |
| 90 kg |
198 lb |
7.2 ml |
19.8 ml |
| 100 kg |
220 lb |
8.0 ml |
22.0 ml |
| 110 kg |
242 lb |
8.8 ml |
24.2 ml |
| 120 kg |
264 lb |
9.6 ml |
26.4 ml |
| 130 kg |
286 lb |
10.4 ml |
28.6 ml |
| 140 kg |
308 lb |
11.2 ml |
30.8 ml |
| 150 kg |
330 lb |
12.0 ml |
33.0 ml |
|
|
ANIMAL PHARMACOLOGY
|
| |
Biodistribution studies were performed in rats using radioiodinated Albunex microspheres. Albunex initially distributes in
the body following intravenous injection according to blood flow. The apparent mechanism for clearance of the Albunex microspheres
is from the blood into the Kupffer cells of the liver by phagocytosis. The plasma half- life (T½ ) of the radiolabeled microspheres was less than 1 minute. At 3 minutes post- injection, approximately 58% of the injected
dose was measured in the liver (maximum), 14% was in the blood, 3% was in the lungs and 6% in the spleen. Lung activity was
maximal at 10 minutes post- injection and did not exceed 5% of the injected dose in any of the rats tested. Blood radioactivity
was nearly all bound to protein (Albunex microspheres).
At 24 hours post- injection, 75% of radioactivity had been excreted as free iodide in the urine, and 1% cumulatively in the
feces. At 24 hours post- injection, 2% of the injected radioactivity was measured in blood and less than 1% remained in each
of the following organs: liver, spleen, kidney, and lung.
An acute intravenous limit study was performed in rats using up to 5 ml Albunex per kg body weight or 16 times the maximum
recommended cumulative dose to humans (0.3 ml/ kg) (MRCD). No signs of toxicity or abnormalities in gross anatomy or histopathology
were observed.
A subacute toxicity study in monkeys demonstrated that doses up to 2.8 times the maximum recommended cumulative dose to humans
administered 3 times per week for 3 weeks was not toxic in any way.
In pigs, intravenous Albunex caused pulmonary hypertension and systemic hypotension. Experimental evidence has revealed this
mechanism to be the phagocytosis of Albunex microspheres by pulmonary intravascular macrophages with subsequent release of
thromboxane A2, a vasoconstrictor hormone. This phenomenon is believed to be species- specific in that it has been confirmed
repeatedly in pigs using as little as one- tenth the recommended dose; thromboxane metabolite levels were found to be elevated
in blood in pigs but not in humans given intravenous Albunex compared to baseline levels; the adverse hemodynamic events in
pigs have been blocked using cyclooxygenase pathway inhibitors; and marginated monocytic phagocytic cells have not been observed
in normal human lung. 1, 2
The significance of this finding for humans is unknown. However, evidence of lung phagocytic activity has been found in patients
with severe liver disease undergoing liver/ spleen scans. 3- 5 Although similar events have not been observed in humans studied in clinical trials, caution is urged in patients with severe
liver disease or adult respiratory distress syndrome.
A safety study was performed in monkeys using doses up to 2.8 times the MRCD and did not produce any abnormal pulmonary hemodynamic
effects, i.e., Albunex did not increase mean pulmonary arterial pressure, pulmonary arterial systolic or diastolic pressure.
Studies conducted in humans and primates showed Albunex to be non- immunogenic.
|
References
|
| |
1. Gehr, P. et al. The normal lung: Ultrastructure and morphometric estimation of diffusion capacity. Respir Physiol. 32: 121- 140. 1978.
2. Zeltner T.B., et al. The postnatal development and growth of the human lung: I. Morphometry. Respir Physiol. 67: 247- 267, 1987.
3. Klingensmith, W.C. Ryerson, T.W. Lung uptake of Tc 99m sulfur colloid. J. Nucl, Med. 14: 201- 204, 1973.
4. Keyes, J.W., et al. An evaluation of lung uptake of colloid during liver imaging. J. Nucl. Med. 14: 687- 691. 1973.
5. Garty, I., et al. Tc 99m colloid lung uptake in rare case of toxoplasmosis with liver involvement. Clin Nucl Med. 9: 310- 313, 1984.
|
PRODUCT IDENTIFICATION
|
| |
None Available |
PRODUCT LISTING - EQUIVALENTS NOT AVAILABLE
|
| |
| solution - intravenous - 5% -
|
| 50.0 ml |
$18.13 |
Plasbumin- 5
Bayer Pharmaceutical Inc
|
00026068520 |
| 50.0 ml |
$24.75 |
Albuminar- 5
Aventis Behring LLC
|
00053767006 |
| 50.0 ml |
$31.25 |
Plasbumin- 5
Bayer Pharmaceutical Inc
|
00192068520 |
| 250.0 ml |
$61.88 |
Alburx
ZLB Bioplasma Inc
|
44206031025 |
| 250.0 ml |
$87.50 |
Plasbumin- 5
Bayer Pharmaceutical Inc
|
00192068525 |
| 250.0 ml |
$99.00 |
Albumin- Alpine
Alpine Biologics Inc
|
63546031025 |
| 250.0 ml |
$123.75 |
Albumarc
American National Red Cross
|
52769045025 |
| 250.0 ml |
$123.75 |
GENERIC
Baxter Healthcare/ Hyland Immuno
|
64193021825 |
| 250.0 ml |
$123.75 |
GENERIC
Baxter Healthcare Corporation
|
00944060326 |
| 250.0 ml |
$123.75 |
Albuminar- 5
Aventis Behring LLC
|
00053767031 |
| 250.0 ml |
$123.75 |
Albuminar- 5
Aventis Behring LLC
|
00053767001 |
| 250.0 ml |
$123.75 |
Albutein
Alpha Therapeutic Corporation
|
49669521101 |
| 250.0 ml |
$123.75 |
Plasbumin- 5
Bayer Pharmaceutical Inc
|
00026068525 |
| 250.0 ml x 12.0 |
$132.00 |
Buminate
Baxter Healthcare Corporation
|
00944049101 |
| 500.0 ml |
$123.75 |
GENERIC
Baxter Healthcare/ Hyland Immuno
|
64193021850 |
| 500.0 ml |
$123.75 |
Alburx
ZLB Bioplasma Inc
|
44206031050 |
| 500.0 ml |
$175.00 |
Plasbumin- 5
Bayer Pharmaceutical Inc
|
00192068527 |
| 500.0 ml |
$198.00 |
Albumin- Alpine
Alpine Biologics Inc
|
63546031050 |
| 500.0 ml |
$247.50 |
Albumarc
American National Red Cross
|
52769045050 |
| 500.0 ml |
$247.50 |
GENERIC
Baxter Healthcare Corporation
|
00944049202 |
| 500.0 ml |
$247.50 |
Albuminar- 5
Aventis Behring LLC
|
00053767002 |
| 500.0 ml |
$247.50 |
Albutein
Alpha Therapeutic Corporation
|
49669521102 |
| 500.0 ml |
$247.50 |
Buminate
Baxter Healthcare Corporation
|
00944049102 |
| 500.0 ml |
$247.50 |
Plasbumin- 5
Bayer Pharmaceutical Inc
|
00026068527 |
| 500.0 ml |
$1249.99 |
Albuminar- 5
Aventis Behring LLC
|
00053767032 |
| 1000.0 ml |
$360.00 |
Albuminar- 5
Aventis Behring LLC
|
00053767003 |
| solution - intravenous - 20% -
|
| 50.0 ml |
$58.21 |
Plasbumin- 20
Bayer Pharmaceutical Inc
|
00026069102 |
| 50.0 ml |
$58.21 |
Plasbumin- 20
Bayer Pharmaceutical Inc
|
00026069120 |
| solution - intravenous - 25% -
|
| 20.0 ml |
$36.00 |
Albutein
Alpha Therapeutic Corporation
|
49669521301 |
| 20.0 ml |
$47.52 |
Albuminar- 25
Aventis Behring LLC
|
00053768001 |
| 20.0 ml |
$49.50 |
GENERIC
Baxter Healthcare Corporation
|
64193022802 |
| 20.0 ml |
$74.25 |
Buminate
Baxter Healthcare Corporation
|
00944049001 |
| 20.0 ml |
$125.00 |
Plasbumin- 25
Bayer Pharmaceutical Inc
|
00026068416 |
| 50.0 ml |
$61.88 |
Alburx
ZLB Bioplasma Inc
|
44206025105 |
| 50.0 ml |
$87.50 |
Plasbumin- 25
Bayer Pharmaceutical Inc
|
00026068420 |
| 50.0 ml |
$99.00 |
Albumin- Alpine
Alpine Biologics Inc
|
63546025105 |
| 50.0 ml |
$123.75 |
Albumarc
American National Red Cross
|
52769045105 |
| 50.0 ml |
$123.75 |
GENERIC
American National Red Cross
|
52769025105 |
| 50.0 ml |
$123.75 |
Albuminar- 25
Aventis Behring LLC
|
00053768002 |
| 50.0 ml |
$123.75 |
Albuminar- 25
Aventis Behring LLC
|
00053768032 |
| 50.0 ml x 12.0 |
$123.75 |
Buminate
Baxter Healthcare Corporation
|
00944049002 |
| 50.0 ml |
$124.99 |
GENERIC
Aventis Behring LLC
|
14362011601 |
| 50.0 ml x 12.0 |
$702.47 |
Albutein
Alpha Therapeutic Corporation
|
49669521302 |
| 100.0 ml |
$74.41 |
Albuminar- 25
Aventis Behring LLC
|
00053768033 |
| 100.0 ml |
$123.75 |
Alburx
ZLB Bioplasma Inc
|
44206025110 |
| 100.0 ml |
$175.00 |
Plasbumin- 25
Bayer Pharmaceutical Inc
|
00026068471 |
| 100.0 ml |
$198.00 |
Albumin- Alpine
Alpine Biologics Inc
|
63546025110 |
| 100.0 ml |
$247.50 |
Albumarc
American National Red Cross
|
52769045110 |
| 100.0 ml |
$247.50 |
GENERIC
Baxter Healthcare Corporation
|
00944060470 |
| 100.0 ml |
$247.50 |
Albuminar- 25
Aventis Behring LLC
|
00053768003 |
| 100.0 ml |
$247.50 |
Albutein
Alpha Therapeutic Corporation
|
49669521303 |
| 100.0 ml |
$247.50 |
Buminate
Baxter Healthcare Corporation
|
00944049003 |
| 100.0 ml |
$247.80 |
GENERIC
American National Red Cross
|
52769025110 |
|
|