Saizen (somatropin) injection, for subcutaneous use
Summary about Saizen
Saizen (somatropin) is a human growth hormone produced by recombinant DNA technology. It is a type of treatment called growth hormone replacement therapy and is available by prescription only. The structure of the growth hormone used in treatment is identical to the growth hormone produced by the pituitary gland.
Saizen is used for growth hormone therapy to replace the hormone that the body fails to produce on its own. It works to stimulate skeletal growth, increase the number and size of skeletal muscle cells, influence the size and function of internal organs, and has important effects on metabolism.
Treatment may not only help a body grow in height, but will also play an important role in stimulating the liver and other tissues to secrete IGF-1, a protein which supports muscle growth and metabolic functions.
Saizen is indicated for the treatment of:
- Pediatric patients with growth failure due to growth hormone deficiency (GHD) and
- Adults with either adult onset or childhood onset GHD.
The goal of GH therapy in pediatric patients is to sustain normal linear growth and achieve a normal adult height. In addition to promoting linear growth, GH has favourable effects on muscle accretion and bone mineral density. GH stimulates osteoblast and osteoclast differentiation and promotes the accretion of bone mass. GH stimulates the proliferation of adipose precursor cells, restricts their differentiation into mature adipocytes, and limits deposition of fat in the abdominal visceral area. Consequently, children with growth hormone deficiency (GHD) demonstrate reduced linear growth, reduced lean body mass, increased body fat with disproportionate deposition of visceral and truncal fat, subnormal bone mineral density and lipid abnormalities. Untreated patients with adult onset GHD demonstrate all the pediatric consequences with the exception of a linear growth effect. Untreated adults with GHD have also decreased muscle strength, impaired cardiac function, and decreased quality of life.
Saizen is available in following forms:
- Saizen® lyophilized powder in vial: 5 mg and 8.8 mg
- Saizen® click.easy® reconstitution device: One vial Saizen® containing 8.8 mg somatropin and one cartridge diluent containing 1.51 ml 0.3% (w/v) metacresol in Sterile Water for Injection
Saizen is contrainidicated in following cases:
- Acute critical illness
- Children with Prader-Willi Syndrome who are severely obese or have severe respiratory impairment – reports of sudden death
- Active malignancy
- Hypersensitivity to somatropin or its excipients
- Active proliferative or severe non-proliferative diabetic retinopathy
- Children with closed epiphyses
- Known hypersensitivity to somatropin or excipients
- Diabetic retinopathy.
Saizen (somatropin) |
|
Active Ingredient |
Somatropin |
Administration Route |
Subcutaneous |
Alcohol Warning |
No data about interaction |
Available Strength |
· Saizen® lyophilized powder in vial: 5 mg and 8.8 mg · Saizen® click.easy® reconstitution device: One vial Saizen® containing 8.8 mg somatropin and one cartridge diluent containing 1.51 ml 0.3% (w/v) metacresol in Sterile Water for Injection |
Breastfeeding Warning |
Caution is recommended. Excretion into human milk is unknown.
Following subcutaneous administration of radiolabelled medication in animal studies, radioactivity was transferred to milk reaching four times the concentration found in maternal plasma. However, absorption of the intact protein in the gastrointestinal tract of the infant is considered extremely unlikely. |
Clinical Pharmacology |
Pharmacodynamics
Tissue Growth: Skeletal Growth: Cell Growth: Organ Growth: Protein Metabolism: Carbohydrate Metabolism: Lipid Metabolism: Mineral Metabolism: Connective Tissue Metabolism: 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. |
Cost |
Approximate Retail Price
from http://www.goodrx.com/Saizen lyophilisate for solution for injection:
lyophilisate for solution for injection:
|
Dosage Form |
Injection for subcutaneous use |
Dose Schedule |
Pediatric GHD: 0.18 mg/kg/week, divided into equal doses given either on 3 alternate days, 6 times per week or daily
Adult GHD: Either a non-weight based or a weight based dosing regimen may be followed, with doses adjusted based on treatment response and IGF-1 concentrations. Non-weight-based dosing: A starting dose of approximately 0.2 mg/day (range, 0.15-0.30 mg/day) may be used without consideration of body weight, and increased gradually every 1 to 2 months by increments of approximately 0.1 to 0.2 mg/day. Weight-based dosing: The recommended initial dose is not more than 0.005 mg/kg/day; the dose may be increased as tolerated to not more than 0.01 mg/kg/day after 4 weeks. |
Drug Class |
H01AC – Somatropin and somatropin agonists |
Drug Unit |
mg/ml |
Food Warning |
No known interactions |
Included In
|
Saizen sometimes is covered by health insurance if considered medically necessary, but some patients have had coverage denied. The Magic Foundation offers help making the case for coverage or appealing a denial, and outlines patients’ experiences getting approval. |
Interacting Drug |
Inhibitors of 11ß-Hydroxysteroid Dehydrogenase Type 1: May require the initiation of glucocorticoid replacement therapy. Patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance dosesGlucocorticoid Replacement Therapy: Should be carefully adjustedCytochrome P450-Metabolized Drugs: Monitor carefully if used with somatropinOral Estrogen: Larger doses of somatropin may be required in womenInsulin and/or Oral/Injectable Hypoglycemic Agents: May require adjustment |
Is Available Generically |
No. There is currently no therapeutically equivalent version of Saizen available. |
Is Proprietary |
Yes |
Label Details |
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019764s072lbl.pdf |
Legal Status |
Legal.
Is not subject to the Controlled Substances Act. |
Manufacturer |
EMD Serono, Inc. |
Maximum Intake |
0.0125 mg/kg/day |
Mechanism of Action |
Somatropin binds to the human growth hormone receptor (GHR). Upon binding, soatropin causes dimerization of GHR, activation of the GHR-associated JAK2 tyrosine kinase, and tyrosyl phosphorylation of both JAK2 and GHR. These events recruit and/or activate a variety of signaling molecules, including MAP kinases, insulin receptor substrates, phosphatidylinositol 3′ phosphate kinase, diacylglycerol, protein kinase C, intracellular calcium, and Stat transcription factors. These signaling molecules contribute to the GH-induced changes in enzymatic activity, transport function, and gene expression that ultimately culminate in changes in growth and metabolism. |
Non Proprietary Name |
Somatropin |
Overdosage |
Short-term overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia. Furthermore, overdose with somatropin is likely to cause fluid retention.
Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess growth hormone |
Pregnancy Category |
AU TGA pregnancy category B2: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. |
Pregnancy Warning |
Use is not recommended unless clearly needed.
Animal studies did not show any teratogenicity or adverse effects on gestation, morphogenesis, parturition, lactation, postnatal development, or reproductive capacity of the offspring; a slight increase in fetal death and increased body weight of pups, and reduced pregnancy rate, increased litter size, irregular estrus cycles, and decreased sperm motility in the parents were seen. There are no controlled data in human pregnancy. |
Prescribing Info |
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019764s072lbl.pdf |
Prescription Status |
Prescription drug |
Proprietary Name |
Saizen |
Related Drugs |
Tesamorelin, Mecasermin rinfabate, Sermorelin, Mecasermin, Somatrem |
RxCUI |
202830 |
Warning |
Acute Critical Illness: Potential benefit of treatment continuation should be weighed against the potential risk. Prader-Willi Syndrome in Children: Evaluate for signs of upper airway obstruction and sleep apnea before initiation of treatment for GHD. Discontinue treatment if these signs occur. Neoplasm: Monitor patients with preexisting tumors for progression or recurrence. Increased risk of a second neoplasm in childhood cancer survivors treated with somatropin – in particular meningiomas in patients treated with radiation to the head for their first neoplasm. Impaired Glucose Tolerance and Diabetes Mellitus: May be unmasked. Periodically monitor glucose levels in all patients. Doses of concurrent antihyperglycemic drugs in diabetics may require adjustment. Intracranial Hypertension: Exclude preexisting papilledema. May develop and is usually reversible after discontinuation or dose reduction. Hypersensitivity: Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention. Fluid Retention (i.e., edema, arthralgia, carpal tunnel syndrome – especially in adults): May occur frequently. Reduce dose as necessary. Hypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism. Hypothyroidism: May first become evident or worsen. Slipped Capital Femoral Epiphysis: May develop. Evaluate children with the onset of a limp or hip/knee pain. Progression of Preexisting Scoliosis: May develop. Pancreatitis: Consider pancreatitis in patients with persistent severe abdominal pain. |
Links:
https://www.saizenus.com/
https://www.drugs.com/mtm/saizen.html
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ab750de2-3eda-411a-924e-00c499eda39b
https://www.drugbank.ca/drugs/DB00052