Hormone Therapy for Women

Vagifem

(estradiol vaginal tablets) Fact Sheet

Product Description
Prescription Vagifem

(estradiol vaginal tablets) is used after menopause to treat

menopausal changes in and around the vagina

Dosage and Administration
Vagifem

is a small, white, round, film-coated, bi-convex vaginal tablet containing

10mcg or 25 mcg of estradiol.
Each vaginal tablet is 6mm in diameter and is administered in a disposable applicator
1 tablet daily for 2 weeks, followed by 1 tablet twice weekly (for example, Tuesday
and Friday)

Clinical benefits
A randomized, placebo-controlled 52-week multicenter trial, which found statistically
significant improvement with Vagifem 10 mcg versus placebo after 12 weeks
treatment in:
o The relief of most bothersome symptoms of atrophic vaginitis as identified by
patients, including vaginal dryness, vaginal and/or vulvar irritation/itching,
vaginal soreness, pain with urination, painful intercourse, and vaginal
bleeding associated with intercourse.
o The correction of important biologic markers, like vaginal pH and vaginal
maturation index, to levels seen in non-menopausal women.
One year of continuous treatment with Vagifem 10 mcg tablets was safe and well-
tolerated by patients.

Important Safety Information
Using estrogen-alone may increase your chance of getting cancer of the uterus
(womb)
Report any unusual vaginal bleeding right away while you are using Vagifem

.
Vaginal bleeding after menopause may be a warning sign of cancer of the uterus
(womb). Your healthcare provider should check unusual vaginal bleeding to find the
cause.
Do not use estrogen-alone to prevent heart disease, heart attacks, strokes or
dementia (decline of brain function)
Using estrogen-alone may increase your chances of getting strokes or blood clots
Using estrogen-alone may increase your chance of getting dementia, based on a
study of women age 65 years or older
Do not use estrogens with progestins to prevent heart disease, heart attack, or
dementia
Using estrogens with progestins may increase your chances of getting heart attacks,
strokes, breast cancer, or blood clots
Using estrogens with progestin may increase your chance of getting dementia, based
on a study of women 65 years and older
You and your healthcare provider should talk regularly about whether you still need
treatment with Vagifem

Do not start using Vagifem

if you currently have or have had certain cancers. Estrogens

may increase the chances of getting certain types of cancers, including cancer of the breast
or uterus. Also, do not start using Vagifem

if you have unusual vaginal bleeding, had a

stroke or heart attack, currently have or have had blood clots, currently have or have had
liver problems, have been diagnosed with a bleeding disorder, are allergic to Vagifem

or
any of its ingredients, or think you may be pregnant.

Vagifem

is only used in the vagina; however, the risks associated with oral estrogens
should be taken into account.

The most commonly reported side effects of Vagifem

included: headache, breast pain,

irregular vaginal bleeding or spotting, stomach/abdominal cramps, bloating, nausea and
vomiting, hair loss, fluid retention, and vaginal yeast infection.

Estrogens should be used at the lowest dose possible for your treatment only as long as
needed.
Please click here for Vagifem

Prescribing Information. Vagifem

is a prescription
medication.

Talk to your doctor to see if Vagifem

is right for you.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit
fda.gov/medwatch, or call 1-800-FDA-1088.

Novo Nordisk provides patient assistance for those who qualify. Please call 1-866-310-7549
to learn more about Novo Nordisk assistance programs.
###

http://www.myvagifem.com/

Hemophilia and Rare Bleeding Disorders
Tretten (Coagulation Factor XIII A-Subunit [Recombinant]) Fact Sheet
Product Description
Tretten is an injectable medicine used to prevent bleeding in adults and children
who have congenital Factor XIII (FXIII) A-subunit deficiency.
Tretten is not for use in patients with congenital Factor XIII B-subunit deficiency.

Dosage and Delivery
Treatment should be initiated under the supervision of a physician experienced in the
treatment of rare bleeding disorders.
The dose for routine prophylaxis for bleeding in patients with congenital factor XIII
(FXIII) A-subunit deficiency is 35 international units (IU) per kilogram body weight
once monthly to achieve a target trough level of FXIII activity at or above 10% using
a validated assay.
Consider dose adjustment if adequate coverage is not achieved with the
recommended 35 IU/kg dose.
Reconstitute only with sterile water for injection (provided with TRETTEN). The
product can be reconstituted using the vial adapter included or a needle.
Reconstitute using the following procedures:
1. Use aseptic technique.
2. Wash hands before starting.
3. Bring TRETTEN (white lyophilized powder) and sterile water for injection
(diluent) to room temperature, but not above 25C (77F).
4. Remove the plastic caps from the two vials.
5. Clean the rubber stoppers on the vials with sterile alcohol swabs and allow
them to dry before use.
6. Remove the protective paper from the vial adapter, but do not unscrew the
protective cap. Attach the vial adapter to the diluent vial, without taking the
vial adapter out of the protective cap. Once attached, remove the protective
cap from the vial adapter by lightly squeezing the protective cap with your
thumb and index finger as shown on the figure below.
7. Draw back the plunger of the sterile syringe and admit a volume of 3.2 mL air
into the syringe.
8. Screw the syringe onto the vial adapter on the diluent vial.
9. Inject the air from the syringe into the diluent vial until resistance is felt.
Then hold the syringe with the diluent vial upside down and withdraw 3.2 mL
water into the syringe.
10. Remove the empty diluent vial by tipping the syringe with the attached vial
adapter.
11. Attach the syringe with the vial adapter to the powder vial. Hold the syringe
slightly tilted with vial facing downwards. Push the plunger slowly to inject all
water (3.2 mL) into the powder vial. Do not inject the diluent directly on
the TRETTEN powder to avoid foaming.
12. Gently swirl the vial until all material is dissolved. Do not shake the vial.
The reconstituted TRETTEN is a clear and colorless solution. Use the
reconstituted TRETTEN immediately. If not, store the solution refrigerated
or at room temperature not to exceed 25C (77F) for up to three hours.
Discard after three hours.
NOTE:
o For larger dose that requires multiple vials of TRETTEN, reconstitute each
additional vial using the same procedure with a separate syringe.
o For smaller dose that requires less than the full volume in the vial,
reconstituted TRETTEN may be diluted with 0.9% sodium chloride to
facilitate measurement of small volumes. Discard remaining product.
o For home administration, any such changes should be communicated by the
pharmacist or healthcare provider to the patient or family.
Inspect the reconstituted TRETTEN visually for particulate matter and discoloration
prior to administration. Do not use if particulate matter or discoloration is observed.
Administer at a rate not exceeding 1-2 mL per minute.
Do not administer with other infusion solutions.
Do not administer as drip.

Clinical benefits
The phase 3 trial that included 41 patients showed that when compared with a
historic control group of individuals who did not receive routine FXIII infusions,
preventive treatment with monthly 35 IU/kg TRETTEN

injections significantly
decreased the number of treatment-requiring bleeding episodes.
The most common adverse reactions reported in the clinical trials (> or = 1 percent)
were headache, pain in the extremities, injection site pain, and D dimer increase.

Important Safety Information
Who should not use TRETTEN?
You should not use TRETTEN if you have ever had allergic (hypersensitivity)
reactions, including severe, whole body reaction (anaphylaxis) to TRETTEN or any
of the ingredients.

What should I tell my healthcare provider before TRETTEN is given?
Tell your healthcare provider about all of your medical conditions, including if you are
pregnant, think you may be pregnant or planning to become pregnant, are breast
feeding, or have a history of blood clots.
Tell your healthcare provider and pharmacist about all of the medicines you take,
including all prescription and non-prescription medicines such as over-the-counter
medicines, supplements, or herbal remedies.

What are the possible side effects of Tretten?
Call your healthcare provider or go to the emergency department right away if you
have any of the following symptoms after using Tretten:
o Signs of allergic reaction, including shortness of breath, rash, itching
(pruritus), redness of the skin (erythema), or fainting/dizziness.
o Signs of blood clot including pain, swelling, warmth,, redness, or a lump in
your legs or arms, chest pain, or sudden severe headache and/or loss of
consciousness or function.
o Unexpected bleeding.
Other possible side effects may include pain in your arms or legs, headache, and
pain at the injection site.
These are not all the possible side effects of Tretten. Tell your healthcare provider
about any side effects that bother you or that does not go away.
Please click here for Tretten Prescribing Information and Instructions for Use.
http://www.tretten-us.com/index.html