Included as part of the PRECAUTIONS section.
Spread Of Localized Infection
Hyaluronidase should not be injected into or around an
infected or acutely inflamed area because of the danger of spreading a
Hyaluronidase should not be used to reduce the swelling
of bites or stings.
Hyaluronidase should not be applied directly to the
cornea. It is not for topical use.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Hyaluronidase is found in most tissues of the body.
Long-term animal studies have not been performed to assess the carcinogenic or
mutagenic potential of hyaluronidase.
Human studies on the effect of intravaginal hyaluronidase
in sterility due to oligospermia indicated that hyaluronidase may have aided
conception. Thus, it appears that hyaluronidase may not adversely affect
fertility in females. In addition, when recombinant human hyaluronidase was
administered to cynomolgus monkeys for 39 weeks at dose levels up to 220,000
U/kg, no evidence of toxicity to the male or female reproductive system was
found through periodic monitoring of in-life parameters, e.g., semen analyses,
hormone levels, menstrual cycles, and also from gross pathology, histopathology
and organ weight data.
Use In Specific Populations
Pregnancy Category C
In an embryo-fetal study, mice have been dosed daily by
subcutaneous injection with recombinant human hyaluronidase at dose levels up
to 2,200,000 U/kg. The study found no evidence of teratogenicity. Reduced fetal
weight and increased numbers of fetal resorptions were observed, with no
effects found at a daily dose of 360,000 U/kg, which represents several orders
of magnitude over the suggested human dose range of 50-300 U of HYLENEX
recombinant (0.8-5 U/kg in a 60 kg subject).
In a pre- and postnatal development study, mice have been
dosed daily by subcutaneous injection with recombinant human hyaluronidase at
dose levels up to 1,100,000 U/kg. The study found no adverse effects on sexual
maturation, learning and memory of offspring, or their ability to produce another
generation of offspring.
It is also not known whether HYLENEX recombinant can
cause fetal harm when administered to a pregnant woman. HYLENEX recombinant
should be given to a pregnant woman only if clearly needed.
Labor And Delivery
Administration of hyaluronidase during labor was reported
to cause no complications: no increase in blood loss or differences in cervical
trauma were observed.
It is not known whether hyaluronidase is excreted in
human milk. Because many drugs are excreted in human milk, caution should be
exercised when hyaluronidase is administered to a nursing woman.
Clinical hydration requirements for children can be
achieved through administration of subcutaneous fluids facilitated with HYLENEX
The dosage of subcutaneous fluids administered is
dependent upon the age, weight, and clinical condition of the patient as well
as laboratory determinations. The potential for chemical or physical
incompatibilities should be kept in mind [see DRUG INTERACTIONS].
The rate and volume of subcutaneous fluid administration
should not exceed those employed for intravenous infusion. For premature
infants or during the neonatal period, the daily dosage should not exceed 25
mL/kg of body weight, and the rate of administration should not be greater than
2 mL per minute.
During subcutaneous fluid administration, special care
must be taken in pediatric patients to avoid over hydration by controlling the
rate and total volume of the infusion [see DOSAGE AND ADMINISTRATION].
No overall differences in safety or effectiveness have
been observed between elderly and younger adult patients.