Covid 19 - Important Information

Omnitrope (somatropin) injection, for subcutaneous use

 

Omnitrope pen

Figure 1: Omnitrope pen (Source: www.omnitrope.com)

Summary about Omnitrope

Growth hormone (GH) or somatotropin is a peptide produced by the somatotroph cells in the anterior pituitary gland. It binds to a transmembrane receptor and leads to the production of insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3), and the acid-labile subunit (ALS). This 3-peptide compound is brought to target cells, binds to IGF-I receptor, and stimulates metabolic functions. In infancy, childhood and adolescence GH is essential for normal linear growth.

Omnitrope (somatropin) injection is a laboratory-created recombinant version of human growth hormone (hGH). It was developed by Sandoz (Kundl, Austria) as the biosimilar medicinal product to the originator Genotropin® (Pfizer Limited, Sandwich, UK) and in 2006 was the first product to be approved by the European Medicines Agency (EMA) via the European biosimilar regulatory pathway.

Omnitrope is indicated for the treatment of paediatric patients with:

  • Growth failure due to growth hormone deficiency (GHD)
  • Prader-Willi Syndrome
  • Small for Gestational Age
  • Turner Syndrome, and
  • Idiopathic Short Stature.

Omnitropre is also indicated for the treatment of 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.

Omnitrope injections for subcutaneous use offer a liquid-formulation pen and a lyophilized powder.

 

lyophilized powder

Figure 1: lyophilized powder (Source: www.omnitrope.com)

Characteristics of Omnitrope convenient injection pens are:

  • Flexible dosing to fit your needs (5 mg and 10 mg)
  • Ready-to-use liquid cartridge eliminates the need to reconstitute or mix with a liquid
  • The liquid cartridge stays stable for 28 days after the first injection
  • Once a new cartridge is inserted, the Pen must be primed before use

 

 

Characteristics of Omnitrope reconstituted lyophilized powder are:

  • Each 5.8 mg vial of Omnitrope comes with a 1.14 mL vial of bacteriostatic water preserved with benzyl alcohol to mix in a solution before injecting
  • Three-week stability once reconstituted or mixed with liquid

Omnitrope 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.

 

Omnitrope (somatropin)

Active Ingredient

Somatropin

Administration Route

Subcutaneous

Alcohol Warning

No data about interaction

Available Strength

– OMNITROPE Cartridge 5 mg/1.5 mL is a prefilled sterile solution in a glass cartridge ready to be administered with the Omnitrope Pen 5

– OMNITROPE Cartridge 10 mg/1.5 mL is a prefilled sterile solution in a glass cartridge ready to be administered with the Omnitrope Pen 10

– OMNITROPE for injection 5.8 mg/vial is supplied with two vials, one containing somatropin as a powder and the other vial containing diluent

 

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:
The primary and most intensively studied action of somatropin is the stimulation of linear growth. This effect is demonstrated in children with GHD.

Skeletal Growth:
The measurable increase in bone length after administration of somatropin results from its effect on the cartilaginous growth areas of long bones. Studies in vitro have shown that the incorporation of sulfate into proteoglycans is not due to a direct effect of somatropin, but rather is mediated by the somatomedins or insulin-like growth factors (IGFs). The somatomedins, among them IGF-I, are polypeptide hormones which are synthesized in the liver, kidney, and various other tissues. IGF-I levels are low in the serum of hypopituitary dwarfs and hypophysectomized humans or animals, and increase after treatment with somatropin.

Cell Growth:
It has been shown that the total number of skeletal muscle cells is markedly decreased in children with short stature lacking endogenous GH compared with normal children, and that treatment with somatropin results in an increase in both the number and size of muscle cells.

Organ Growth:
Somatropin influences the size of internal organs, and it also increases red cell mass.

Protein Metabolism:
Linear growth is facilitated in part by increased cellular protein synthesis. This synthesis and growth are reflected by nitrogen retention which can be quantitated by observing the decline in urinary nitrogen excretion and blood urea nitrogen following the initiation of somatropin therapy.

Carbohydrate Metabolism:
Hypopituitary children sometimes experience fasting hypoglycemia that may be improved by treatment with somatropin. In healthy subjects, large doses of somatropin may impair glucose tolerance. Although the precise mechanism of the diabetogenic effect of somatropin is not known, it is attributed to blocking the action of insulin rather than blocking insulin secretion. Insulin levels in serum actually increase as somatropin levels increase. Administration of human growth hormone to normal adults and patients with growth hormone deficiency results in increases in mean serum fasting and postprandial insulin levels, although mean values remain in the normal range. In addition, mean fasting and postprandial glucose and hemoglobin A1c levels remain in the normal range.

Lipid Metabolism:
Somatropin stimulates intracellular lipolysis, and administration of somatropin leads to an increase in plasma free fatty acids and triglycerides. Untreated GHD is associated with increased body fat stores, including increased abdominal visceral and subcutaneous adipose tissue. Treatment of growth hormone deficient patients with somatropin results in a general reduction of fat stores, and decreased serum levels of low density lipoprotein (LDL) cholesterol.

Mineral Metabolism:
Administration of somatropin results in an increase in total body potassium and phosphorus and to a lesser extent sodium. This retention is thought to be the result of cell growth. Serum levels of phosphate increase in children with GHD after somatropin therapy due to metabolic activity associated with bone growth. Serum calcium levels are not altered. Although calcium excretion in the urine is increased, there is a simultaneous increase in calcium absorption from the intestine. Negative calcium balance, however, may occasionally occur during somatropin treatment.

Connective Tissue Metabolism:
Somatropin stimulates the synthesis of chondroitin sulfate and collagen, and increases the urinary excretion of hydroxyproline.

Pharmacokinetics

Absorption

Following a subcutaneous injection of single dose of 5 mg Omnitrope 5 mg/1.5 mL Cartridge or 5 mg Omnitrope 10 mg/1.5 mL Cartridge in healthy male and female adults, the peak concentration (Cmax) was 72-74 mcg/L. The time to reach Cmax (tmax) for Omnitrope was 4.0 hours.

The aqueous formulations of 5 mg/1.5 mL Omnitrope cartridge and 10 mg/mL Omnitrope cartridge are bioequivalent to the lyophilized 5.8 mg/vial Omnitrope formulation.

Metabolism

Somatropin is metabolized in both the liver and kidneys by proteolytic degradation. In renal cells, at least a portion of the breakdown products are returned to the systemic circulation.

Excretion

The mean terminal half-life of somatropin after subcutaneous administration of Omnitrope Cartridge in healthy adults is 2.5-2.8 hours. The mean clearance of subcutaneously administered Omnitrope Cartridge in healthy adults was about 0.14 L/hr·kg.

Specific Populations:

Pediatric: No pharmacokinetic studies of Omnitrope have been conducted in pediatric patients.

Gender: The effect of gender on pharmacokinetics of Omnitrope has not been evaluated in pediatric patients.

Race: No studies have been conducted with Omnitrope to assess pharmacokinetic differences among races.

Renal or hepatic impairment: No pharmacokinetic studies have been conducted with Omnitrope in patients with renal or hepatic impairment.

 

Cost

Approximate Retail Price

from  http://www.goodrx.com/Omnitrope

solution for injection:

  • 5 mg/1.5 mL (1 cartridge, 1.5 mL): $166.07
  • 10 mg/1.5 mL (4 cartridge, 1.5 mL): $5,632.39

lyophilisate for solution for injection:

  • 5.8 mg/vial (1 carton, 8 vials): $2,610.92

Dosage Form

Injection for subcutaneous use

Dose Schedule

Pediatric GHD: 0.16 to 0.24 mg/kg//week, divided into 6 – 7 daily injections.

Prader-Willi Syndrome: 0.24 mg/kg/week, divided into 6 – 7 daily injections.

Small for Gestational Age: Up to 0.48 mg/kg/week, divided into 6 – 7 daily injections.

Adult GHD: not more than 0.04 mg/kg/week (divided into daily injections) to be increased as tolerated to not more than 0.08 mg/kg/week); to be increased gradually every 1 – 2 months.

OMNITROPE Cartridges 5 mg/1.5 mL and 10 mg/1.5 mL must be used with the corresponding OMNITROPE® Pen 5 and Pen 10 delivery system, respectively.

Injection sites should always be rotated to avoid lipoatrophy.

Drug Class

H01AC – Somatropin and somatropin agonists

Drug Unit

mg/ml; mg/vial

Food Warning

No known interactions

Included In
Health Insurance Plan

Omnitrope 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 Omnitrope available.

Is Proprietary

Yes

Label Details

https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021426s028lbl.pdf

Legal Status

Legal.

Is not subject to the Controlled Substances Act.

Manufacturer

Sandoz GmbH

Maximum Intake

0.08 mg/kg per week as 7 equal daily injections

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.ema.europa.eu/en/documents/product-information/omnitrope-epar-product-information_en.pdf

Prescription Status

Prescription drug

Proprietary Name

Omnitrope

Related Drugs

Tesamorelin, Mecasermin rinfabate, Sermorelin, Mecasermin, Somatrem

RxCUI

644964

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.

Search

+