Description:   Healon®5 is a sterile, non-pyrogenic, transparent viscoelastic preparation of a highly purified, noninflammatory, high molecular weight (average molecular weight 4 million) of sodium hyaluronate. Healon5 contains 23 mg/mL of sodium hyaluronate 5000, dissolved in repeating disaccharide units of N-acetylglucosamine and sodium glucuronate linked by glycosidic bonds.

Sodium hyaluronate is a physiological substance that is widely distributed in the extracellular matrix of connective tissues in both animals and man. For example, it is present in the vitreous and aqueous humor of the eye, the synovial fluid, the skin, and the umbilical cord. Sodium hyaluronates derived from various human or animal tissues do not differ chemically.

The fraction of sodium hyaluronate in Healon5 is reported to be nonantigenic 1,3 and does not cause inflammatory 2 or foreign body reactions.

The graph below represents the flow curve (shear viscosity versus shear rate).

The viscosity of Healon5 at rest (at zero shear rate) is about 7 million mPas, a viscosity higher than Healon and HealonGV. At high shear rates, such as during injection, the viscosity of Healon5 decreases dramatically due to high pseudoplasticity, facilitating injection through a 25G cannula.

images/46/37003051.jpg

Indications:   Healon5 is intended for use in anterior segment ophthalmic surgical procedures of the human eye. Healon5 is designed to create and maintain a deep anterior chamber which facilitates manipulation inside the eye with reduced trauma to the corneal endothelium and other ocular tissues. 4 Healon5 also can be used to efficiently separate and control ocular tissues.

Healon5 is not designed to have any pharmacological effect.

Contraindications:   There are no known contraindications to the use of Healon5 when used as recommended.

Precautions:   Precautions normally considered during ophthalmic surgical procedures should be taken.

Special care should be taken to ensure complete removal of Healon5 from the entire eye including behind the lens and the chamber angles. Complete removal of Healon5 is important to avoid intraocular pressure peaks postoperatively. Due to the greater viscosity and higher concentration of sodium hyaluronate in Healon5, the rise in the postoperative intraocular pressure may be higher with Healon5 than if the same volume of other sodiumhyaluronate viscoelastic products, with lower zero shear viscosity, is left in the anterior segment of the eye.

Pre-existing glaucoma, other causes of compromised outflow, higher preoperative intraocular pressure and complications in surgical procedures also may lead to increased intraocular pressure; consequently, extra care should be taken in patients with these conditions. Prophylactic pressure-lowering treatment should always be considered and especially in cases where Healon5 has to be left in the eye for clinical reasons.

Both the Rock'n Roll technique and the "Behind the Lens" or the Two Compartment Technique (TCT) were evaluated during the clinical trial. The table below reflects IOPs >/=30 mm Hg at 5 hours postoperatively in association with removal technique.

Table 1. Patients with IOP >/=30 mm Hg at 5 Hour Visit
by Removal Technique
 
  Healon5
N=187
Healon
N=172
Rock'n Roll
>/=30 7 6
Behind-the-Lens (TCT)
>/=30 3 1
Combination of 1 and 2
>/=30 11 9
Other
>/=30 0 2

As a result of clinical experience, the following removal technique (TCT) is recommended to ensure efficient removal of Healon5:

Use a standard I/A tip, 0.3 mm, with effectual flow of 20-25 ml/min and vacuum of 250-300 mmHg with a potential maximum setting at 500 mmHg. When using a machine with a peristaltic pump, use the upper limits of the suggested settings. When using a Venturi pump use the lower limits of the suggested settings. Bottle height should be 60-70 cm above eye level.

  1. Start the removal directly after the IOL implantation, while the anterior chamber is still filled with Healon5 and before the IOL has been centered. Go behind the IOL optic without engaging the flow of the I/A tip (port up) and then start flow. Remove Healon5 from the capsular bag first and ensure that the lens has adequately centered. During removal of Healon5 from the capsular bag, the continuous flow of irrigation fluid keeps the bag inflated and reduces the risk of aspirating the capsular bag. While maintaining continuous flow remove the tip from behind the optic and place it on top of the optic.
  2. Continue the removal by circling the I/A tip at the iris plane, or on the optic surface, then make an additional sweep in the anterior chamber paying particular attention to the angles.

An alternative technique to remove Healon5 is to create maximum turbulene to makeHealon®5 fracture into large pieces. This can be accomplished by using the Rock'n Roll technique (described below) with standard I/A tip, 0.3 mm, with high settings; flow rates should be 25-30 ml/min and vacuum 350-500 mmHg, depending on the type of pump. If a peristaltic pump is used, the vacuum should be set towards the higher limit.

If a venturi pump is used, the vacuum should be set towards the lower limit. Bottle height should be 60-70 cm above eye level. Today's phaco machines often use linear control. The suggested machine settings can only be achieved if the surgeon operates the phaco machine with fully depressed foot pedal.

  1. Start by circling the hand piece in the anterior segment at iris plane.
  2. Gently rest the I/A piece on the anterior surface of the optic. Press on the IOL optic on one side and rotate the I/A hand piece directing the flow into the bag. Direct the hand piece port towards the equator of the capsular bag and stay in this position for a few seconds and then repeat on the other side of the IOL optic until Healon5 is completely removed. Finally, sweep the anterior chamber including the angles and repeat step 2 if necessary.

Healon5 is a highly purified fraction extracted from avian tissues which may contain minute amounts of protein. The potential risks associated with the injection of biological material should be considered.

Express a small amount of Healon5 from the syringe prior to use and carefully examine it during use to avoid injecting minute rubber particles which may be released when the syringe diaphragm is punctured.

Sodium hyaluronate solution may appear cloudy or form precipitates when it is injected. In-vitro studies have shown incompatibility, resulting in opalescence, between sodiumhyaluronate and solutions containing cationic components, e.g., detergents and benzalkonium chloride.

Reprocessed cannulas should not be used.

Do not use if the blister package has been damaged.

Do not resterilize.

Healon5 is for single use.

Adverse Events:   Increased intraocular pressure has been reported after use of sodium hyaluronate solutions.

Increased intraocular pressure is likely to occur if Healon5 is not removed as completely as possible. Clinical judgment concerning the use of this product should be considered in cases where thorough removal may not be possible. The precautions noted above should be taken to manage any increased postoperative intraocular pressure and to reduce the likelihood of occurrence of related postoperative complications such as optic neuropathy, pupillary atonia and dilation, and iris atrophy.

Rarely, postoperative inflammatory reactions (iritis, hypopyon, endophthalmitis) following the use of sodium hyaluronate, as well as incidents of corneal edema and corneal decompensation, have been reported. Their relationship to sodium hyaluronate has not been established.

CLINICAL TRIALS 5,6

A clinical trial of Healon5 was initiated on August 23 rd , 1999. A total of 359 patients were included. 187 patients with a mean age of 74.1 years were randomized into the Healon5 group and 172 into the Healon group with a mean age of 73.2 years.

The intraocular pressure (IOP) was assessed at 5 hours after surgery, since the expected IOP peak time period is 4-6 hours after surgery. The IOP was measured also at 24 hours and 7 days. No anti-glaucoma medication was permitted until after the 5-hour IOP assessment.

Eleven percent of the Healon5 patients and 10% of the Healon patients experienced IOP spikes >/=30 mmHg at 5 hours postoperatively.

Table 2. Number of patients in IOP categories per visits.
All randomized qualified patients.
 
  Visit
 
  Pre-
surgery
OP + 5
hours
OP + 24
hours
OP + 7
days
  Group
IOP   
  Healon5 N=187
0-19 164 87 117 162
20-29 23 75 61 23
30-39 0 16 7 1
40-49 0 5 0 0
50-59 0 0 1 0
60-69 0 0 1 0
  Healon N=172
0-19 161 92 122 154
20-29 11 62 43 17
30-39 0 13 7 0
40-49 0 3 0 0
50-59 0 1 0 0
60-69 0 1 0 0

There was no difference seen between the two groups with regard to the mean IOP at 5 hours after surgery and no difference in mean change. The increase was of the same magnitude in both groups. At 7 days postoperatively, the mean IOP was at pre-operative levels in both study groups.

Table 3. IOP (mmHg) during the study. All randomized qualified patients.
      Visit
      Pre-
surgery
OP +
5 hours
OP +
24 hours
OP +
7 days
Group      
Healon5
N=187
IOP MEAN 15.8 21.2 18.5 15.3
STD 2.9 7.2 6.1 3.7
MIN 10 9 8 6
MAX 23 46 60 30
N 187 183 187 186
Change
IOP from
preop
MEAN 0.0 5.3 2.7 -0.5
STD 0.0 6.7 6.2 3.6
MIN 0 -7 -9 -9
MAX 0 29 47 12
N 187 183 187 186
             Cont.
Healon
N=172
IOP MEAN 15.6 20.8 17.9 15.2
STD 2.7 7.7 4.7 3.1
MIN 8 8 7 8
MAX 24 65 37 26
N 172 172 172 171
Change
IOP from
preop
MEAN 0.0 5.2 2.3 -0.4
STD 0.0 7.2 4.9 2.9
MIN 0 -8 -10 -9
MAX 0 46 22 10
N 172 172 172 171

The specified complications were similar for both groups. All of the complications are commonly seen after cataract surgery. Blurred vision, scratchy sensation, foreign body sensation, itching, burning, tenderness, coreal oedema, represented most of the complications recorded in both groups.

Table 4. Number of patients with complications related to surgery.
All randomized qualified patients.
  Visit and group
  Op + 5 hours Op + 24 hours Op + 7 days
Complications
related to
surgery
Healon5
N=183
Healon
N=172
Healon5
N=187
Healon
N=172
Healon5
N=186
Healon
N=171
Missing 0 0 0 0 1 * 0
No 166 150 176 153 179 152
Yes 17 22 11 19 6 19
* For patient 341 complications related to surgery at visit 5 had not been recorded.

Iritis was equally distributed between the two groups.

Table 5. Number of patients with iritis. All randomized qualified patients.
 
Visit and group
 
Op + 24 hours Op + 7 days
 
Healon5
N=187
Healon
N=172
Healon5
N=187
Healon
N=172
 
Not assessed
0 0 1 * 0
None
107 95 121 109
Slight
54 49 63 60
Moderate
26 27 1 2
Severe
0 1 0 0
* For patient 114 iritis was not assessed at visit 5, 7 ± 2 days after surgery.

Two Healon5 events were scored as possibly device related by the investigators.

Table 6. Adverse Events. Number of patients in whom a medical event occurred
at least once. All randomized qualified patients.
      Group   
      Healon5 N=187 Healon N=172 Total
Body
system
Preferred term N % N % N %
Vision CONJUNCTIVAL HAEMORRHAGE 2 1.1 1 0.6 3 0.8
CORNEAL OPACITY 0 0 1 0.6 1 0.3
EYE INFECTION 0 0 1 0.6 1 0.3
EYE PAIN 0 0 1 0.6 1 0.3
INCREASED INTRAOCULAR PRESSURE 4 2.1 4 2.3 8 2.2

The difference in percent change in endothelial cell counts between the Healon5 and Healon has been investigated in another clinical study. The endothelial cell count evaluation included 81 patients in the Healon5 group and 78 in the Healon group. The mean age in the Healon5 group was 69.9 years and in the Healon group 68.9 years.

No difference was observed between the treatment groups with regard to the change from pre-operative values to the values determined at 3 months after surgery. The percentage cell loss in the Healon5 group was 9.4 and in the Healon group 11.2%.

Table 7 Endothelial cell counts, changes and percentage change in endothelial cell counts
from pre-surgery at 3 months.
 
  Visit
 
N Visit 1
(Pre-op)
Visit 7
(Op + 3 months)
Healon5
Endothelial cell counts
81 2548 ± 292 2314 ± 380
Change from pre-surgery
    -243 ± 283
Percentage changes from Pre-surgery
    -9.45 ± 10.67
Healon 
Endothelial cell counts
78 2454 ± 321 2193 ± 407
Change from pre-surgery
    -276 ± 295
Percentage changes from Pre-surgery
    -11.20 ± 11.50

How Supplied:   Healon5 is sterile, non-pyrogenic, viscoelastic preparation supplied in disposable 0.6 mL glass syringe. Each mL of Healon5 contains:

23 mg              sodium hyaluronate 5000

8.5 mg             sodium chloride

0.28 mg           disodium hydrogen phosphate dihydrate

0.04 mg           sodium dihydrogen phosphate monohydrate

q.s.                  water for injection

Healon5 syringes are terminally steam sterilized and aseptically packaged.

A sterile single-use, 25 gauge cannula is included with each syringe.

Preparation and Storage

Refrigerated Healon5 should be held at room temperature for approximately 30 minutes before use. Store between 2° to 8°C (35°-47°F). Protect from freezing and exposure to light.

Definition of symbols on syringe label and blister label.

images/46/37003052.jpg

= Exp. date:

images/46/37003053.jpg

= Lot No.:

images/46/37003054.jpg

= For single use only.

images/46/37003055.jpg

= Method of sterilization using steam or dry heat.

References

  1. Richter, W., Ryde, M. & Zetterström, O.
    Nonimmunogenicity of a purified sodium hyaluronate preparation in man.
    Int Arch Appl Immun 59:45-48 (1979)
  2. Balazs, E.A.: Ultrapure hyaluronic acid and the use thereof.
    U.S. patent 4,141,973 (1979)
  3. Richter, W.: Non-immunogenicity of purified hyaluronic acid preparations tested by passive cutaneous anaphylaxis.
    Int Arch All 47 (1974) p 211-217.
  4. Pharmacia & Upjohn
    Anterior chamber depth maintenance capacity of sodium hyaluronate 5000,23 mg/mL, during phacoemulsification in pig cadaver eyes. Data on file.
  5. Holst A, Osterling L. An open, randomized, parallel group, phase III study of Healon5 compared to Healon during cataract surgery with a 7 day follow up period.
    Pharmacia & Upjohn Report c0025536
  6. Lundberg K, Osterling L. A double-blind, randomized, parallel group study evaluating the safety of a new viscoelastic agent UPG-96 (Healon5), compared to Healon in the phacoemulsification with intraocular lens implantation.
    Pharmacia & Upjohn Report c0002131

Rx only

Caution: Federal (US) law restricts this device to sale by or on the order of a physician.

Manufactured by:

Pharmacia & Upjohn AB

SWEDEN

Manufactured for:

Pharmacia & Upjohn Company

Kalamazoo, MI 49001 USA

Revised: June 2000

Patent Pending PCT SE98/00 401

Healon5 is a trademark of Pharmacia & Upjohn AB.

All rights reserved.



Copyright© 2002 Medical Economics