Prescription Drug Information: Saizen (Page 4 of 5)

12.3 Pharmacokinetics

Absorption — The absolute bioavailability of somatropin after subcutaneous administration ranges between 70 to 90%.

Distribution — The steady-state volume of distribution (mean ±SD) of somatropin following intravenous administration in healthy volunteers was estimated to be 12.0 ± 1.08 L.

Metabolism — The metabolic fate of somatropin involves classical protein catabolism in both the liver and kidneys. In renal cells, at least a portion of the breakdown products is returned to the systemic circulation. The mean half-life of intravenous somatropin in normal males is around 0.6 hours, whereas subcutaneously and intramuscularly administered somatropin has a half-life of around 2 hours. The longer half-life observed after subcutaneous or intramuscular administration is due to slow absorption from the injection site.

Excretion — The clearance (mean ±SD) of intravenously administered somatropin in six normal male volunteers was 14.6 ± 2.8 L/hr.

Specific Populations

Pediatric — The pharmacokinetics of somatropin is similar in children and adults. However, no pharmacokinetic studies of SAIZEN have been conducted in pediatric patients.

Gender — No gender studies have been performed in children for somatropin. In adults, the clearance of somatropin in both men and women tends to be similar. However, no studies have been conducted to evaluate the effect of gender on pharmacokinetics of SAIZEN .

Race — No studies have been conducted to determine the effect of race on the pharmacokinetics of SAIZEN.

Renal Impairment– Children and adults with chronic renal failure tend to have decreased somatropin clearance compared to those with normal renal function. However, no studies have been conducted to evaluate the effect of renal impairment on the pharmacokinetics of SAIZEN.

Hepatic Impairment — A reduction in somatropin clearance has been noted in patients with hepatic dysfunction as compared with normal controls.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies for carcinogenicity have not been performed with SAIZEN. There is no evidence from animal studies to date of SAIZEN-induced mutagenicity or impairment of fertility.

14 CLINICAL STUDIES

Adult Growth Hormone Deficiency (GHD)

A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in 115 adults with growth hormone deficiency comparing the effects of SAIZEN and placebo on body composition. Patients in the active treatment arm were treated with SAIZEN at an initial dose of 0.005 mg/kg/day for one month which was increased to 0.01 mg/kg/day if tolerated for the remaining five months of the study. The primary endpoint was the change from baseline in lean body mass measured by dual energy X-ray absorptiometry (DXA) after 6 months. Treatment with SAIZEN produced significant (p<0.001) increases from baseline in LBM compared to placebo (Table 2).

Table 2 – Lean Body Mass (kg) by DXA
SAIZEN (n=52) Placebo(n=51)
Baseline (mean) 47.7 54.0
Change from baseline at 6 months (mean) +1.9 -0.2
Treatment difference (mean)95% confidence intervalp-value 2.1(1.3, 2.9)<0.001

Sixty-seven (58%) of the 115 randomized patients were male. The adjusted mean treatment difference on the increase in lean body mass from baseline was significantly greater in males (2.9 kg) than females (0.8 kg).

Ninety-seven (84%) of the 115 randomized patients had adult onset GHD. The adjusted mean treatment differences on the increase in lean body mass from baseline were not significantly different in AO GHD (2.1 kg) compared with childhood onset GHD (1.0 kg) patients. However, there were relatively few patients with childhood onset GHD (n=18) on which to base the comparison.

Analysis of the treatment difference on the change from baseline in total fat mass (by DXA) revealed a significant decrease (p<0.001) in the SAIZEN-treated group compared to the placebo group. SAIZEN also produced beneficial effects on several bone turnover markers including bone specific alkaline phosphatase, C-terminal propeptide, osteocalcin, urine deoxypyridinoline and iPTH.

One hundred and eleven patients were enrolled in an open label follow up study and treated with SAIZEN for an additional 6-30 months. During this period, the beneficial effects on lean body mass and total fat mass achieved during the initial six months of treatment were maintained.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

SAIZEN can be administered using (1) a standard sterile disposable syringe and needle, (2) a compatible SAIZEN needle-free injection device or (3) a compatible SAIZEN needle injection device. For proper use, refer to the Instructions for Use provided with the administration device.

SAIZEN is a sterile, non pyrogenic, white, lyophilized powder supplied in packages containing:

1 vial of 5 mg SAIZEN and 1 vial of Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) NDC 44087-1005-2

1 vial of 8.8 mg SAIZEN and 1 vial of Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) NDC 44087-1088-1

1 saizenprep® cartridge of 8.8 mg SAIZEN and 1.51 mL Sterile Water for Injection 0.3% (w/v) metacresol as antimicrobial preservative NDC 44087-0016-1

16.2 Storage and Handling

Before Reconstitution — SAIZEN should be stored at room temperature (15°-30°C/59°-86°F). Expiration dates are stated on the labels.

After Reconstitution — SAIZEN 5 mg and 8.8 mg vials reconstituted with the Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) provided should be stored under refrigeration (2°–8°C/36°–46°F) for up to 14 days.

SAIZEN 8.8 mg saizenprep® cartridge reconstituted with the Sterile Water for Injection, 0.3% (w/v) metacresol provided should be stored under refrigeration (2°-8°C/36°-46°F) for up to 21 days.

Avoid freezing reconstituted vials or cartridges of SAIZEN.

17 PATIENT COUNSELING INFORMATION

Prior to self-administration of the product at home, ensure to train patients and caregivers how to prepare and administer the product correctly to help avoid wrong technique and dosing errors.

Patients being treated with SAIZEN (and/or their parents) should be informed about the potential benefits and risks associated with SAIZEN treatment. This information is intended to better educate patients (and caregivers); it is not a disclosure of all possible adverse or intended effects.

Patients and caregivers who will administer SAIZEN should receive appropriate training and instruction on the proper use of SAIZEN from the physician or other suitably qualified health care professional. A puncture-resistant container for the disposal of used syringes and needles should be strongly recommended. Patients and/or parents should be thoroughly instructed in the importance of proper disposal, and cautioned against any reuse of needles and syringes. This information is intended to aid in the safe and effective administration of the medication.

To reconstitute SAIZEN, inject the diluent into the vial of SAIZEN aiming the liquid against the glass vial wall. Swirl the vial with a GENTLE rotary motion until contents are dissolved completely. DO NOT SHAKE. Parenteral drug products should always be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. SAIZEN MUST NOT BE INJECTED if the solution is cloudy or contains particulate matter. Use it only if it is clear and colorless.

Never Share a SAIZEN Needle Between Patients

Counsel patients that they should never share a SAIZEN needle with another person, even if the needle is changed. Sharing of the pen between patients may pose a risk of transmission of infection.

For drug preparation instructions for saizenprep® cartridges, please refer to the Instructions for Use provided with saizenprep® reconstitution device.

Manufactured for: EMD Serono, Inc., Rockland, MA 02370 USA

Instructions for Use

saizenprep®

For use only with

Saizen ®
(somatropin) for injection 8.8 mg

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Important information

You must have received training before using saizenprep® (si-zin-prep).

Always follow all directions and training provided by your healthcare provider.

For children, use of the saizenprep® device must be supervised by an adult.

Contact our patient support services at 1-800-582-7989 for questions related to the device or Saizen® (somatropin) for injection.

What is in the box?

Tray
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Patient Information Leaflet
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saizenprep® Instructions for Use
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You will also need: sharps container, pen and alcohol wipes (not included)

Important information

What is saizenprep® ?

saizenprep® is a single use reconstitution (mixing) device used to mix SAIZEN.

How supplied

saizenprep® is supplied in a kit.

saizenprep® 8.8 mg contains: 8.8 mg vial and 1.51 mL cartridge.

Getting to know saizenprep®

saizenprep® Reconstitution DeviceDiluent Cartridge
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STEP 1

Check supplies

Note: Prepare a clean, hard, flat surface as a working area.

1.1 Box:
Confirm product is not expired
Open box
Carefully remove contents
1.2 Wash Hands:
Important
Wash Hands
Warning: Using the device with unclean hands may lead to contamination and possibly infection.
1.1

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1.2

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1.3 SAIZEN Vial:
Confirm vial label says SAIZEN
Confirm product is not expired
Confirm correct strength (e.g. 8.8 mg)
Confirm vial is not cracked and cap is not damaged
1.4 Diluent Cartridge:
Confirm cartridge label says Diluent for Saizen®
Confirm product is not expired
Confirm correct volume (e.g. 1.51 mL)
Confirm cartridge is not cracked
1.3 Vial

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1.4 Cartridge

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1.5 saizenprep® Packaging and Sterility Seal:
Confirm product is not expired
Confirm sterility seal is not damaged or loose
Confirm packaging is not cracked or damaged

Warning: Do not use if any items are damaged or expired. Call patient support services at 1-800-582-7989 for assistance.

1.5

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STEP 2

Prepare saizenprep®

SAIZEN Vial:

2.1
Remove blue protective flip off vial cap from vial and throw away (discard) in the trash.
2.2
Clean gray rubber at top of vial with alcohol wipe.
2.1

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2.2

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Diluent Cartridge:

2.3
Grasp arrow tab to peel outer label and tear off at perforation before discarding in the trash.
2.4
Clean rubber at top of cartridge with alcohol wipe.
2.3

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2.4

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saizenprep® Packaging:

2.5
Peel sterility seal from packaging and discard in the trash. Caution: Do not attempt to remove device from packaging.
2.5

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STEP 3

Attach saizenprep® to vial

3.1
Place saizenprep® on top of vial and push down firmly on packaging until it snaps in place. You will feel and hear a “click” confirming that it is fully inserted. Caution: Make sure that vial is fully inserted inside vial connector.
3.2
Pull off packaging with 1 hand while holding vial with the other hand. Discard packaging in the trash.
3.1

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3.2

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STEP 4

Attach cartridge

4.1
Hold the green cartridge holder with one hand. With the other hand unscrew the transfer unit and set aside for future use. Note: To enhance cartridge content visibility, line up clear cartridge label space with cartridge holder open slot.
4.2
Insert cartridge into cartridge holder opening with metal tip facing down. You will feel and hear a “click” confirming that it is fully inserted.
4.1

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4.2

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4.3
Screw transfer unit back onto cartridge holder. You will feel and hear a “click” confirming that it is attached correctly. Caution: Let the plunger rod rise by itself from the transfer unit during attachment step.
4.3

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STEP 5

Mix SAIZEN and Diluent in vial

Caution: To avoid foaming, always perform transfers slowly (minimum 10 sec).

5.1
Hold the device at a slight angle. Slowly push down on plunger rod to transfer all Diluent drop by drop to vial. You will feel some resistance. Release plunger rod after transfer is completed. Plunger rod will rise on its own once released. Warning: You may have to perform this step again if there is still Diluent visible in cartridge.
5.1

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5.2
Thoroughly mix SAIZEN and Diluent in vial by gently swirling device in circular motion.
Do not shake! Shaking will cause foaming.

Inspect vial:

IF THEN
Liquid in vial is clearProceed to Step 6
Liquid in vial is foamingAllow device to rest vertically until foam disappears (3-5 minutes)
Powder in vial is not completely dissolvedContinue to swirl gently until drug dissolves (less than 2 minutes)
Liquid in vial is cloudy or has particlesDo not use and call 1-800-582-7989
5.2

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STEP 6

Draw mixed SAIZEN into cartridge

Caution: Hold saizenprep® straight up — not at an angle when transferring SAIZEN.

6.1
Turn saizenprep® so vial is on top. Push up on plunger rod to remove all air from cartridge. You may feel some resistance.
6.2
Slowly pull plunger rod halfway down. You will start noticing mixed SAIZEN flowing into cartridge. Note: You may not have to pull as plunger rod may travel back on its own.
6.1

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6.2

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6.3
Push up on plunger rod again to remove any remaining air inside cartridge.
6.4
Slowly pull plunger rod downward until it stops. All liquid should now be in the cartridge. Note: It is ok to leave a small amount of air bubbles in the vial.
6.3

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6.4

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6.5
Hold the device so the top of the cartridge is at eye level and inspect for air bubbles inside the cartridge. The liquid should be at or above the cartridge shoulder line.
If the cartridge contains a large air bubble (see example pg 33) repeat steps 6.3 and 6.4.Note: If a large air bubble (liquid is below cartridge shoulder line) is not removed after 5 attempts call patient support services at 1-800-582-7989 for assistance.
6.5
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IF Liquid is at or above cartridge shoulder lineIF Liquid is below cartridge shoulder line
THEN Proceed to step 7THEN Repeat steps 6.3 and 6.4

STEP 7

Remove cartridge

7.1
Turn saizenprep® so vial is on bottom. Hold cartridge holder with one hand and unscrew transfer unit from cartridge holder with other hand. Discard transfer unit in the trash.
Caution: Make sure to hold the cartridge holder when removing the cartridge.

7.2
Remove cartridge from cartridge holder by pulling it straight up. Note: A small drop of SAIZEN may be visible inside cartridge holder opening.
7.1

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7.2

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7.3
Put the used cartridge holder with attached vial in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the cartridge holder with attached vial in your household trash.
If you do not have an FDA-cleared sharps container, you may use a household container that is: made of a heavy-duty plastic, can be closed with a tight-fitting lid, puncture-resistant lid, without sharps being able to come out, upright and stable during use, leak-resistant, and labeled to warn of hazardous waste inside.
When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: www.fda.gov/safesharpsdisposal
7.3

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STEP 8

Record date

8.1
Write today’s date (mixing date) in white box on cartridge inner label.
8.1

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STEP 9

SAIZEN storage and handling

9.1
Store SAIZEN in the refrigerator between 36°F to 46°F (2°C to 8°C) after mixing.
The cartridge will expire in 21 days after mixing (the date written on the cartridge).
SAIZEN vial, Diluent cartridge and mixed SAIZEN can be stored in the refrigerator near food or other medicine.
If you are traveling, keep SAIZEN away from light and use cool packs to maintain refrigerated temperature between 36°F to 46°F (2°C to 8°C). Warning: Do not freeze SAIZEN.
9.1

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For more information go to www.saizenus.com or call patient support services at 1-800-582-7989

Manufactured for: EMD Serono, Inc.
Rockland, MA 02370
Made in Italy

This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Approved: January 2017

EMD Serono, Inc.
is a subsidiary of Merck KGaA,
Darmstadt, Germany

20067247 MDT-535 US
MC-2724-2017

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