Microsoft word - r_enrollment form_print version_10829302 _2_
® ENROLLMENT FORM
TEV-TROPIN® [somatropin (rDNA origin) for injection]
Fax to: 1-877-838-8767
Hospital or Clinic/Contact Name/Phone and Ext. #:
Attach front and back copy of patient’s MEDICAL insurance card (enlarge if possible) OR COMPLETE the
Attach front and back copy of patient’s DRUG CARD
has no insurance
Attach front and back copy of (all) the patient’s
Healthcare professional must fill out information below.
Physician signature REQUIRED to order TEV-TROPIN
®, and Home-Based Injection Training.
® 5 mg vial with ancillary supplies:
30 day supply OR
90 day supply Refill: x ______
Preferred Specialty Pharmacy ________________________________________
® Injection Device
(supplies to include: syringe
days per week.
heads, vial adapters, Bact. NaCl practice vial).
5 mg TEV-TROPIN® vial with ______
30 day supply of 3cc Syringes w/needles for
Diluent and injection needles/syringes determined by fulfillment
: Administer prescribed dose as directed.
pharmacy unless otherwise indicated. B-D syringes recommended Dispense
: 90 day supply Refill
for proper fit for Inject-Ease
Preferred diluent syringe/needle ____________
TEV-TROPIN® sig when using Tjet
Preferred injection syringe/needle ___________
Dilute 5 mg TEV-TROPIN® vial with 1 mL/diluent.
® Device, inject _________
mg (must be
in even increments of 0.05 mg) _______days per
Check if Ordering Home-Based Training
(Skilled nurse visit X 1 first dose instruction on TEV-TROPIN® for patient.)
Injection Training will be/has been conducted by the physician’s office?
N Date: __________
Is this pediatric patient growth hormone deficient?
No If yes, Start Date and Product _________/_____________
Height:__________ Weight:__________kg IGF-1:__________ Date:__________
Please attach supporting documentation to assist in Prior Authorization
I hereby authorize Teva Pharmaceuticals USA to release the above information to the insurers identified above to assess coverage of human growth hormone products and related healthcare services, and to communicate those findings back to me. I have obtained consent from this patient to release this information. I understand that Teva Pharmaceuticals USA will keep this information confidential and will use it only for insurance assessment, for the insurance pre-authorization process, to arrange home nurse training, and to provide educational materials.
(Practitioner required license # ________________) X___________________________
TEV-TROPIN® and Tjet® are registered trademarks of Teva Pharmaceuticals USA. Growth Solutions®
is a registered service mark of Teva Pharmaceuticals USA. Inject-Ease® is a registered trademark of Palco Labs, Inc.
2010 Teva Pharmaceuticals USA 04/10 8293 10829302/100674
hormone deficiency after therapy with TEV-TROPIN® Prader-Willi syndrome who had one or more of the
[somatropin (rDNA origin) for injection]
or somatropin. Serum calcium concentrations are not following risk factors: severe obesity, history of upper
5 mg (15 IU)
significantly altered in patients treated with either airway obstructions or sleep apnea, or unidentified
respiratory infection. Male patients with one or
TEV-TROPIN® (somatropin, rDNA origin, for injection), F. Connective Tissue Metabolism
more of these factors may be at greater risk than
a polypeptide of recombinant DNA origin, has 191
Somatropin stimulates the synthesis of chondroitin females. Patients with Prader-Willi syndrome should
amino acid residues and a molecular weight of sulfate and collagen as well as the urinary excretion of be evaluated for signs of upper airway obstruction about 22,124 daltons. It has an amino acid sequence
and sleep apnea before initiation of treatment with
identical to that of human growth hormone of pituitary PHARMACOKINETICS
somatropin. If during treatment with somatropin,
origin. TEV-TROPIN® is synthesized in a strain of Following intravenous administration of 0.1 mg/kg patients show signs of upper airway obstruction Escherichia coli
modified by insertion of the human of TEV-TROPIN®, the elimination half-life was about (including onset of or increased snoring) and/or new growth hormone gene.
0.42 hours (approximately 25 minutes) and the mean onset sleep apnea, treatment should be interrupted.
TEV-TROPIN® is a sterile, white, lyophilized powder, plasma clearance (± SD) was 133 (± 16) mL/min in All patients with Prader-Willi syndrome treated with intended for subcutaneous administration, after healthy male volunteers.
somatropin should also have effective weight control
reconstitution with bacteriostatic 0.9% sodium In the same volunteers, after a subcutaneous injection and be monitored for signs of respiratory infection,
chloride injection, USP, (normal saline) (benzyl alcohol of 0.1 mg/kg TEV-TROPIN® to the forearm, the mean which should be diagnosed as early as possible and
preserved). The quantitative composition of the peak serum concentration (± SD) was 80 (± 50) treated aggressively (see CONTRAINDICATIONS
lyophilized drug per vial is:
ng/mL which occurred approximately 7 hours post- Unless patients with Prader-Willi syndrome also have
injection and the apparent elimination half-life was a diagnosis of growth hormone deficiency, TEV-
approximately 2.7 hours. Compared to intravenous TROPIN® is not indicated for the treatment of pediatric
administration, the extent of systemic availability from patients who have growth failure due to genetically
The diluent contains bacteriostatic 0.9% sodium chloride subcutaneous administration was approximately 70%. confirmed Prader-Willi syndrome.
injection, USP, (normal saline), 0.9% benzyl alcohol as INDICATION AND USAGE
Benzyl alcohol as a preservative in bacteriostatic
a preservative, and water for injection. A 5 mL vial of TEV-TROPIN® is indicated only for the treatment of normal saline, USP, has been associated with toxicity the diluent will be supplied with each dispensed vial of children who have growth failure due to an inadequate in newborns. When administering TEV-TROPIN® TEV-TROPIN®.
secretion of normal endogenous growth hormone.
to newborns, reconstitute with sterile normal saline
TEV-TROPIN® is a highly-purified preparation. CONTRAINDICATIONS
for injection, USP. WHEN RECONSTITUTING WITH
Reconstituted solutions have a pH in the range of 7.0 TEV-TROPIN® reconstituted with bacteriostatic 0.9% STERILE NORMAL SALINE, USE ONLY ONE DOSE PER to 9.0.
sodium chloride injection, USP (normal saline) (benzyl VIAL AND DISCARD THE UNUSED PORTION.
alcohol preserved) should not be administered to PRECAUTIONS
Clinical trials have demonstrated that TEV-TROPIN® patients with a known sensitivity to benzyl alcohol General
is equivalent in its therapeutic effectiveness and in (see WARNINGS
Therapy with TEV-TROPIN® should be directed by
its pharmacokinetic profile to those of human growth Somatropin should not be used for growth promotion physicians who are experienced in the diagnosis hormone of pituitary origin (somatropin). TEV-TROPIN® in pediatric patients with closed epiphyses.
and management of children with growth hormone
stimulates linear growth in children who lack adequate Somatropin is contraindicated in patients with active deficiency.
levels of endogenous growth hormone. Treatment of proliferative or severe non-proliferative diabetic Treatment with somatropin may decrease insulin growth hormone-deficient children with TEV-TROPIN® retinopathy.
sensitivity, particularly at higher doses in susceptible
produces increased growth rates and IGF-1 (Insulin- In general, somatropin is contraindicated in the patients. As a result, previously undiagnosed impaired Like Growth Factor/Somatomedin-C) concentrations presence of active malignancy. Any preexisting glucose tolerance and overt diabetes mellitus may be that are similar to those seen after therapy with human malignancy should be inactive and its treatment unmasked during somatropin treatment. Therefore, growth hormone of pituitary origin.
complete prior to instituting therapy with somatropin. glucose levels should be monitored periodically in
Both TEV-TROPIN® and somatropin have also been Somatropin should be discontinued if there is evidence all patients treated with somatropin, especially in shown to have other actions including:
of recurrent activity. Since growth hormone deficiency those with risk factors for diabetes mellitus, such as
may be an early sign of the presence of a pituitary obesity (including obese patients with Prader-Willi
Skeletal Growth. TEV-TROPIN® stimulates tumor (or, rarely, other brain tumors), the presence of syndrome), Turner syndrome, or a family history of skeletal growth in patients with growth hormone such tumors should be ruled out prior to initiation of diabetes mellitus. Patients with preexisting type 1 or deficiency. The measurable increase in body treatment. Somatropin should not be used in patients type 2 diabetes mellitus or impaired glucose tolerance length after administration of TEV-TROPIN® with any evidence of progression or recurrence of an should be monitored closely during somatropin results from its effect on the epiphyseal growth underlying intracranial tumor.
therapy. The doses of antihyperglycemic drugs (i.e.,
plates of long bones. Concentrations of IGF-1, Somatropin should not be used to treat patients insulin or oral agents) may require adjustment when which may play a role in skeletal growth, are with acute critical illness due to complications somatropin therapy is instituted in these patients.
low in the serum of growth hormone-deficient following open heart surgery, abdominal surgery Patients with preexisting tumors or growth hormone children but increase during treatment with TEV- or multiple accidental trauma, or those with acute deficiency secondary to an intracranial lesion should TROPIN®. Mean serum alkaline phosphatase respiratory failure. Two placebo-controlled clinical be examined routinely for progression or recurrence of concentrations are increased.
trials in non-growth hormone deficient adult patients the underlying disease process. In pediatric patients,
2. Cell Growth. It has been shown that there are (n = 522) with these conditions in intensive care units clinical literature has revealed no relationship between
fewer skeletal muscle cells in short statured revealed a significant increase in mortality (41.9% somatropin replacement therapy and central nervous
children who lack endogenous growth hormone vs. 19.3%) among somatropin-treated patients system (CNS) tumor recurrence or new extracranial
as compared with normal children. Treatment (doses 5.3 to 8 mg/day) compared to those receiving tumors. However, in childhood cancer survivors,
with somatropin results in an increase in both placebo (see WARNINGS
an increased risk of a second neoplasm has been
the number and size of muscle cells.
Somatropin is contraindicated in patients with Prader- reported in patients treated with somatropin after
3. Organ Growth. Somatropin influences the size Willi syndrome who are severely obese or have their first neoplasm. Intracranial tumors, in particular
of internal organs and it also increases red cell severe respiratory impairment (see WARNINGS
). meningiomas, in patients treated with radiation to the
Unless patients with Prader-Willi syndrome also have head for their first neoplasm, were the most common
a diagnosis of growth hormone deficiency, TEV- of these second neoplasms. In adults, it is unknown
Linear growth is facilitated, in part, by increased TROPIN® is not indicated for the treatment of pediatric whether there is any relationship between somatropin cellular protein synthesis. Nitrogen retention, patients who have growth failure due to genetically replacement therapy and CNS tumor recurrence.
as demonstrated by decreased urinary nitrogen confirmed Prader-Willi syndrome.
Intracranial hypertension (IH) with papilledema, visual
excretion and serum urea nitrogen, results from WARNINGS
changes, headache, nausea, and/or vomiting has been
for information on reported in a small number of patients treated with
increased mortality in patients with acute critical somatropin products. Symptoms usually occurred
Children with hypopituitarism sometimes experience illnesses due to complications following open heart within the first eight (8) weeks after the initiation
fasting hypoglycemia that is improved by treatment surgery, abdominal surgery or multiple accidental of somatropin therapy. In all reported cases, IH-with somatropin. Large doses of somatropin may trauma, or those with acute respiratory failure. The associated signs and symptoms rapidly resolved after impair glucose tolerance.
safety of continuing somatropin treatment in patients cessation of therapy or a reduction of the somatropin
receiving replacement doses for approved indications dose. Funduscopic examination should be performed
Administration of somatropin to growth hormone- who concurrently develop these illnesses has not routinely before initiating treatment with somatropin to
deficient patients mobilizes lipid, reduces body fat been established. Therefore, the potential benefit of exclude preexisting papilledema, and periodically during stores, and increases plasma fatty acids.
treatment continuation with somatropin in patients the course of somatropin therapy. If papilledema is
having acute critical illnesses should be weighed observed by funduscopy during somatropin treatment,
Sodium, potassium, and phosphorous are conserved against the potential risk.
treatment should be stopped. If somatropin-induced
by somatropin. Serum concentrations of inorganic There have been reports of fatalities after initiating IH is diagnosed, treatment with somatropin can be phosphates increased in patients with growth therapy with somatropin in pediatric patients with restarted at a lower dose after IH-associated signs
and symptoms have resolved. Patients with Turner hypoadrenalism may require an increase in their hormone therapy, or other associated treatments such
syndrome, chronic renal insufficiency, and Prader-Willi maintenance or stress doses; this may be especially as radiation therapy for intracranial tumors.
syndrome may be at increased risk for the development true for patients treated with cortisone acetate and OVERDOSAGE
prednisone since conversion of these drugs to their The recommended dosage of up to 0.1 mg/kg
In patients with hypopituitarism (multiple hormone biologically active metabolites is dependent on the (0.3 IU/kg) of body weight 3 times per week should deficiencies), standard hormonal replacement therapy activity of the 11ßHSD-1 enzyme.
not be exceeded. Acute overdose could cause initial
should be monitored closely when somatropin therapy Excessive glucocorticoid therapy may attenuate the hypoglycemia and subsequent hyperglycemia. Repeated is administered.
growth promoting effects of somatropin in children. use of doses in excess of those recommended could
Undiagnosed/untreated hypothyroidism may prevent Therefore, glucocorticoid replacement therapy should result in signs and symptoms of gigantism and/or an optimal response to somatropin, in particular, the be carefully adjusted in children with concomitant acromegaly consistent with the known effects of excess growth response in children. Patients with Turner GH and glucocorticoid deficiency to avoid both human growth hormone.
syndrome have an inherently increased risk of hypoadrenalism and an inhibitory effect on growth.
DOSAGE AND ADMINISTRATION
developing autoimmune thyroid disease and primary Limited published data indicate that somatropin A dosage of up to 0.1 mg/kg (0.3 IU/kg) of body weight hypothyroidism. In patients with growth hormone treatment increases cytochrome P450 (CP450) administered 3 times per week by subcutaneous deficiency, central (secondary) hypothyroidism may mediated antipyrine clearance in man. These data injection is recommended. The dosage schedule first become evident or worsen during somatropin suggest that somatropin administration may alter the for TEV-TROPIN® should be individualized for each treatment. Therefore, patients treated with somatropin clearance of compounds known to be metabolized patient. Subcutaneous injection of greater than 1 mL should have periodic thyroid function tests and thyroid by CP450 liver enzymes (e.g., corticosteroids, of reconstituted solution is not recommended.
hormone replacement therapy should be initiated or sex steroids, anticonvulsants, cyclosporine). After the dose has been determined, each vial of appropriately adjusted when indicated.
Careful monitoring is advisable when somatropin TEV-TROPIN® should be reconstituted with 1 to 5 mL
Patients should be monitored carefully for any is administered in combination with other drugs of bacteriostatic 0.9% sodium chloride for injection, malignant transformation of skin lesions.
known to be metabolized by CP450 liver enzymes. USP (benzyl alcohol preserved).* The stream of normal
When somatropin is administered subcutaneously However, formal drug interaction studies have not saline should be aimed against the side of the vial to at the same site over a long period of time, tissue been conducted.
prevent foaming. Swirl the vial with a GENTLE rotary
atrophy may result. This can be avoided by rotating In patients with diabetes mellitus requiring drug therapy, motion until the contents are completely dissolved the injection site.
the dose of insulin and/or oral agent may require and the solution is clear. DO NOT SHAKE. Since
As with any protein, local or systemic allergic reactions adjustment when somatropin therapy is initiated (see TEV-TROPIN® is a protein, shaking or vigorous mixing
may occur. Parents/patients should be informed that PRECAUTIONS
will cause the solution to be cloudy. If the resulting
such reactions are possible and that prompt medical Carcinogenesis, Mutagenesis, Impairment of
solution is cloudy or contains particulate matter, the
attention should be sought if allergic reactions occur.
Pediatric Patients (see PRECAUTIONS, General)
Carcinogenesis, mutagenesis and reproduction studies *
Benzyl alcohol as a preservative in bacteriostatic
Slipped capital femoral epiphysis may occur more have not been conducted with TEV-TROPIN®.
normal saline, USP, has been associated with toxicity
frequently in patients with endocrine disorders Pregnancy
in newborns. When administering TEV-TROPIN® to
(including pediatric growth hormone deficiency and Pregnancy Category C
newborns, reconstitute with sterile normal saline for
Turner syndrome) or in patients undergoing rapid Animal reproduction studies have not been conducted
growth. Any pediatric patient with the onset of a limp with TEV-TROPIN®. It is not known whether TEV- Occasionally, after refrigeration, some cloudiness or complaints of hip or knee pain during somatropin TROPIN® can cause fetal harm when administered to may occur. This is not unusual for proteins like therapy should be carefully evaluated.
a pregnant woman or can affect reproduction capacity. TEV-TROPIN® growth hormone. Allow the product to
Progression of scoliosis can occur in patients who TEV-TROPIN® should be given to a pregnant woman warm to room temperature. If cloudiness persists or experience rapid growth. Because somatropin only if clearly needed.
particulate matter is noted, the contents MUST NOT
increases growth rate, patients with a history of Nursing Mothers
scoliosis who are treated with somatropin should There have been no studies conducted with TEV- Before and after injection, the septum of the vial should be monitored for progression of scoliosis. However, TROPIN® in nursing mothers. It is not known whether be wiped with rubbing alcohol or an alcoholic antiseptic somatropin has not been shown to increase the this drug is excreted in human milk. Because many solution to prevent contamination of the contents by occurrence of scoliosis. Skeletal abnormalities drugs are excreted in human milk, caution should be repeated needle insertions. It is recommended that including scoliosis are commonly seen in untreated exercised when TEV-TROPIN® is administered to a TEV-TROPIN® be administered using sterile disposable Turner syndrome patients. Scoliosis is also commonly nursing woman.
syringes and needles. The syringes should be of small
seen in untreated patients with Prader-Willi syndrome. Geriatric Use
enough volume that the prescribed dose can be drawn
Physicians should be alert to these abnormalities, The safety and effectiveness of TEV-TROPIN® in from the vial with reasonable accuracy.
which may manifest during somatropin therapy.
patients aged 65 and over has not been evaluated STABILITY AND STORAGE
Information for Patients
in clinical studies. Elderly patients may be more Before Reconstitution – Vials of TEV-TROPIN® are
Patients being treated with TEV-TROPIN® (and/or sensitive to the action of somatropin, and therefore stable when refrigerated at 36° to 46°F (2° to 8°C). their parents) should be informed about the potential may be more prone to develop adverse reactions. Expiration dates are stated on the labels.
benefits and risks associated with TEV-TROPIN® A lower starting dose and smaller dose increments After Reconstitution – Vials of TEV-TROPIN® are treatment. This information is intended to better should be considered for older patients.
stable for up to 14 days when reconstituted with
educate patients (and caregivers); it is not a disclosure ADVERSE REACTIONS
bacteriostatic 0.9% sodium chloride (normal saline),
of all possible adverse or intended effects.
Utilizing a double-antibody immunoassay, no USP, and stored in a refrigerator at 36° to 46°F (2° to
Patients and caregivers who will administer TEV- antibodies to growth hormone could be detected in 8°C). Do not freeze the reconstituted solution.
TROPIN® should receive appropriate training and a group of 164 naïve and previously treated clinical HOW SUPPLIED
instruction on the proper use of TEV-TROPIN® from trial patients after treatment with TEV-TROPIN® for TEV-TROPIN® (somatropin, rDNA origin, for injection)
the physician or other suitably qualified health care up to 40 months. However, utilizing the less specific is supplied as 5 mg (15 IU) of lyophilized, sterile
professional. A puncture-resistant container for the polyethelene glycol (PEG) precipitation immunoassay, somatropin per vial, in a box containing one vial of TEV-
disposal of used syringes and needles should be 27 of the 164 patient group were tested after treatment TROPIN® (5 mg per vial) and one vial of diluent [5 mL of
strongly recommended. Patients and/or parents with TEV-TROPIN® for 4 to 6 months and antibodies to bacteriostatic 0.9% sodium chloride for injection, USP
should be thoroughly instructed in the importance growth hormone were detected in two patients (7.4%). (benzyl alcohol preserved)].
of proper disposal, and cautioned against any reuse The binding capacity of the antibodies from the two
of needles and syringes. This information is intended antibody positive patients was not determined.
to aid in the safe and effective administration of the None of the patients with anti-GH antibodies in the
BIO-TECHNOLOGY GENERAL (ISRAEL) LTD.
clinical studies experienced decreased linear growth
response to TEV-TROPIN® or any other associated
Serum levels of inorganic phosphorus, alkaline adverse event. Growth hormone antibody binding
phosphatase, parathyroid hormone (PTH) and IGF-1 capacities below 2 mg/L have not been associated
may increase during somatropin therapy.
with growth attenuation. In some cases, when binding
capacity exceeds 2 mg/L, growth attenuation has been
dehydrogenase type 1 (11ßHSD-1) in adipose/hepatic In studies of growth hormone-deficient children, tissue and may significantly impact the metabolism of headaches occurred infrequently. Injection site cortisol and cortisone. As a consequence, in patients reactions (e.g., pain, bruise) occurred in 8 of the 164 treated with somatropin, previously undiagnosed treated patients.
central (secondary) hypoadrenalism may be unmasked Leukemia has been reported in a small number of requiring glucocorticoid replacement therapy. patients treated with other growth hormone products. In addition, patients treated with glucocorticoid It is uncertain whether this risk is related to the replacement therapy for previously diagnosed pathology of growth hormone deficiency itself, growth
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