ADVERSE REACTIONS
In
field studies, the following adverse reactions were
observed in approximately 1% of 280 dogs treated with
ProHeart® 6: vomiting, diarrhea,
listlessness, weight loss, seizures, injection site
pruritus, and elevated body temperature.
Post-Approval Experience: Although
not all adverse reactions are reported, the following
reactions are based on voluntary post-approval drug
experience reporting: anaphylaxis/toid reactions, depression/lethargy,
urticaria, head/facial edema. As with anahylactoid reactions
resulting from the use of other injectable products,
standard therapeutic intervention should be initiated
immediately. To report suspected adverse reactions or
to obtain technical assistance, call (800) 533-8536.
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ANIMAL SAFETY
General Safety:ProHeart®
6 has been safely administered to a wide variety of healthy
dogs six months of age and older, including a wide variety
of breeds, pregnant and lactating females, breeding males,
and ivermectin-sensitive collies. However, in clinical studies,
two geriatric dogs with a history of weight loss after the
initial ProHeart® 6 injection died within
a month of the second 6 month injection. A third dog who was
underweight for its age and breed and who had a history of
congenital problems experienced lethargy following the initial
injection of ProHeart® 6. The dog never
recovered and died 3 months later (see PRECAUTION).
ProHeart®
6 administered at 3 times the recommended dose in dogs with
patent heartworm infections and up to 5 times the recommended
dose in ivermectin-sensitive collies did not cause any adverse
reactions. ProHeart 6 administered at 3 times the recommended
dose did not adversely effect the reproductive performance
of male or female dogs. ProHeart 6 administered up to 5 times
the recommended dose in 7-8 month old puppies did not cause
any systemic adverse effects.In
well controlled clinical field studies, ProHeart 6 was safely
used in conjunction with a variety of veterinary products
including vaccines, anthelmintics, antiparasitics, antibiotics,
analgesics, steroids, non-steroidal anti-inflammatory drugs
(NSAIDs), anesthetics and flea control products.
Injection
Site Reactions: Injection site observations were
recorded during effectiveness and safety studies. In clinical
studies, ProHeart®
6 was administered at six-month intervals to client-owned
dogs under field conditions. There were no reports of injection
site reactions in these field studies and evaluations of the
injection sites revealed no abnormalities.
In a laboratory
safety study, ProHeart®
6 was administered at 1, 3 and 5 times the recommended dose
to 7-8 month old puppies. Injection sites were clipped to
facilitate observation. Slight swelling/edema at the injection
site was observed in some dogs from all treated groups. These
injection site reactions appeared as quickly as 8 hours post
injection and lasted up to 3 weeks. A three-year repeated
injection study was conducted to evaluate the safety of up
to 6 injections of ProHeart®
6 administered at the recommended dose (0.17 mg/kg) every
6 months.
Mild erythema
and localized deep subcuticular thickening were seen in dogs
that received four injections in the same area on the neck
and in one dog that received two injections in the same area
on the neck. Microscopic evaluation on the injection sites
from all dogs 6 months after the last injection consistently
showed mild granulomatous panniculitis with microvacuolation.
The only adverse reaction seen that was not related to the
injection site was weight loss in one dog.
Some dogs
treated with ProHeart®
6 in laboratory effectiveness studies developed transient,
localized inflammatory injection site reactions. These
injection site reactions were visible grossly for up to 3
weeks fter injection. Histologically, well-defined granulomas
were observed in some dogs at approximately 5 months after
injection.
CONSTITUTION PROCEDURES
The two-part
ProHeart®
6 product must be mixed at least 30 minutes prior to the intended
time of use.
Items needed
to constitute ProHeart®
6:
*Microspheres
(vial 1)
*Enclosed
vent needle (25G) Vehicle (vial 2)
*Sterile
20 mL syringe for transfer Transfer needle (18G or 20G)
Constitution of the 20 mL vial product.
1. Shake the microsphere vial to break up any aggregates prior
to constitution.
2. Using an 18G or 20G needle and sterile syringe withdraw
17.0 mL of the unique vehicle from the vial.
There is more vehicle supplied than the 17.0 mL required.
3. Insert the enclosed 25G vent needle into the microsphere
vial.
4. Slowly transfer the vehicle into the microsphere vial through
the stopper using the transfer needle and syringe.
5. Once the vehicle has been added, remove the vent and transfer
needles from the microsphere vial. Discard unused vehicle
and needles.
6. Shake the microsphere vial vigorously until a thoroughly
mixed suspension is produced.
7. Record the time and date of mixing on the microsphere vial.
8. Allow suspension to stand for at least 30 minutes to allow
large air bubbles to dissipate.
9. Before every use, gently swirl the mixture to achieve uniform
suspension. The microspheres and vehicle will gradually separate
on standing.
10. Use a 1 mL or 3 mL syringe and an 18G or 20G needle for
dosing. Dose promptly after drawing into dosing syringe. If
administration is delayed, gently roll the dosing syringe
prior to injection to maintain a uniform suspension and accurate
dosing.
11. Refrigerate the unused product. The constituted product
remains stable for 4 weeks in a refrigerator. Avoid direct
sunlight.
Storage Information: Store
the unconstituted product at or below 25° C (77° F).
do not expose to light for extended periods of time. After
constitution the product is stable for 4 weeks stored under
refrigeration at 2-8° C (36-46° F).
