Omnitrope (somatropin)

No dosing information is available for this tab.

Somatropin is administered by subcutaneous injection. Subcutaneous injections should be made into the back of the upper arm, abdomen, buttock, or thigh with regular rotation of injection sites to avoid lipoatrophy.

Somatropin is commercially available in various dosage forms for subcutaneous administration including single-dose or multi-dose vial kits containing lyophilized powder and diluent vials, two-chamber cartridges containing lyophilized powder and diluent, and cartridge kits containing lyophilized powder and diluent in prefilled syringes; all powder formulations require reconstitution prior to administration, and some require product specific delivery devices.

Somatropin is also available as a solution for subcutaneous administration in ready-to-use prefilled pens, injection devices, or cartridges.

Prior to the first injection of somatropin, store preparations and diluent (if supplied) at 2-8degreesC in the original carton for protection from light and physical damage; exceptions include storing Serostim(R) at 15-30degreesC until the expiration date on the manufacturer's label and Genotropin Miniquick(R), which may be stored at or below 25degreesC for up to 3 months after dispensing. Avoid storage under conditions of extreme heat or cold, and do not shake or freeze the drug; protect from light.

Patients and/or their caregivers should be cautioned against sharing or reusing syringes, needles, and/or devices. Carefully instruct patients on the proper, safe disposal of needles, syringes, and unused drug. Patients should be supplied with a puncture-resistant container for the proper, safe disposal of such equipment after use.

No dosing information is available for this tab.

Somatropin is not known to be metabolized by cytochrome P-450 (CYP) isoenzymes or other drug metabolizing enzymes, however growth hormone can induce changes in CYP activity.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Agents Affecting Growth Hormone/Macimorelin

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Agents affecting growth hormone may impact the accuracy of the macimorelin diagnostic test.(1)

CLINICAL EFFECTS: Concurrent use of agents affecting growth hormone may impact the accuracy of the macimorelin diagnostic test.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of macimorelin states concurrent use with agents affecting growth hormone may impact the accuracy of the macimorelin diagnostic test. Discontinue growth hormone products at least 1 week before administering the macimorelin diagnostic test. Sufficient washout time of drugs affecting growth hormone release prior to administration of macimorelin is recommended.(1) Agents affecting growth hormone include: - Drugs that directly affect the pituitary secretion of growth hormone (e.g. somatostatin, insulin, glucocorticoids, cyclooxygenase inhibitors) - Drugs that may transiently elevate growth hormone concentrations (e.g. clonidine, levodopa, insulin) - Drugs that may blunt the growth hormone response (e.g. muscarinic antagonists, anti-thyroid medications, growth hormone products)

DISCUSSION: Concurrent use of agents affecting growth hormone may impact the accuracy of the macimorelin diagnostic test.(1)

Growth Hormone/Selected Retinoids (Systemic)

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Both systemic retinoids(1-8,11) and growth hormones(9-11) have been independently associated with medication-induced intracranial hypertension.

CLINICAL EFFECTS: The concurrent use of oral retinoids(1-8) with growth hormones(9-10) may increase the risk of intracranial hypertension (pseudotumor cerebri). Early signs of intracranial hypertension include papilledema (inflammation of the optic nerve), headache, nausea, vomiting, and visual disturbances such as blurred vision, double vision, and loss of vision.(12)

PREDISPOSING FACTORS: Women of childbearing age with high body mass may have a higher risk of developing intracranial hypertension.(8)

PATIENT MANAGEMENT: The US manufacturer of tretinoin advises avoiding concomitant use of other products that can cause intracranial hypertension.(1) Patients who present with symptoms of intracranial hypertension should be screened for papilledema. If papilledema is present, they should discontinue the drug and be referred to a neurologist for further treatment.(1-8)

DISCUSSION: Vitamin A derivatives and growth hormone have both been strongly associated with intracranial hypertension. A review of ocular side effects from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization, the Food and Drug Administration, and medical journals from 1979 to 2003 found 21 patients who developed intracranial hypertension while taking tretinoin, acitretin, or etretinate at prescribed doses. Symptom onset occurred at an average of 2-3 months after starting retinoid therapy and all except 3 cases resolved within a few months after discontinuing therapy.(8) In a systematic review of 580 reported cases of medication-induced intracranial hypertension between January 1900 and June 2019 found in MEDLINE, EMBASE, and Cochrane Review Databases, there were 259 verifiable cases of intracranial hypertension. Vitamin A derivatives were implicated in 84 cases, though 25 cases occurred with excessive vitamin A supplementation. Growth hormone was implicated in 24 cases, all of which occurred in pediatric patients and involved frequent or higher doses of growth hormone.(12)

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Growth Hormone/Oral Estrogens

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Growth hormone (somatropin or lonapegsomatropin-tcgd) binds to growth hormone receptors and stimulates Janus activating tyrosine kinases (JAK 1 and 2) and signal transducer activators of transcription (STAT1, STAT3, STAT5) to increase gene transcription and metabolism to produce and secrete insulin like growth factor-1 (IGF-1). IGF-1 promotes cell growth, proliferation, and survival. Estrogens block STAT phosphorylation and inhibit IGF-1 secretion and production.(1,2) Higher quantities of growth hormone are required to raise serum IGF-1 concentrations to the normal range.

CLINICAL EFFECTS: Oral estrogens may reduce the IGF-1 response to growth hormone (somatropin and lonapegsomatropin-tcgd).(1-9)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of somatropin states a larger dose of somatropin may be required to achieve the treatment goal.(3-9) The manufacturer of lonapegsomatropin-tcgd states adults of any age concurrently taking oral estrogen should increase the dose of lonapegsomatropin-tcgd to 2.1 mg once weekly.(3) The American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for growth hormone deficiency states that higher recombinant human growth hormone (rhGH) doses are advised in women on oral estrogen therapy and that switching women to transdermal estrogen patches may allow lower rhGH doses to be used for equivalent IGF-1 responses.(10)

DISCUSSION: A prospective study compared growth hormone replacement requirements in women with elevated estrogen (on oral estrogen), women without elevated estrogen (no estrogen therapy or on transdermal estrogen), and growth hormone treated adult hypopituitary males. Women on oral estrogen required 10.6 +/-0.7 mcg/kg/day or 867 +/- 45 mcg/day growth hormone, women not taking oral estrogen required 5.0 +/- 0.7 mcg/kg/day or 424 +/-57 mcg/day, and men required 4.1 +/- 0.6 mcg/kg/day or 376 +/-49 mcg/day.(1) A randomized cross-over study compared one month of treatment with ethinyl estradiol (20 mcg), conjugated equine estrogen (1.25 mg Premarin), and estradiol valerate (2 mg). All three formulations resulted in a significant reduction in IGF-1 levels compared to baseline.(11) A study compared IGF-1 concentrations in premenopausal women and postmenopausal women before and after 2 months of cyclical replacement therapy with either oral ethinyl estradiol (20 mcg daily) or transdermal 17 beta-estradiol (100 mcg patch applied twice weekly). Oral ethinyl estradiol significantly reduced circulating IGF-1 (0.70 +/- 0.09 to 0.47 +/- 0.04 units/mL, P < 0.02) levels. Transdermal 17-beta estradiol increased IGF-1 levels (0.86 +/- 0.15 to 1.10 +/- 0.14 units/mL, P < 0.005).(12) In a clinical trial, somapacitan administered once weekly was compared to somatropin once daily injections in patients with and without oral estrogen replacement therapy. Patients with oral estrogen therapy were administered 2 mg/wk compared to 1 mg/wk for patients without estrogen replacement therapy. Observed doses after titration for somapacitan and somatropin were highest for females on oral estrogen.(13) An open-label, randomized crossover study in growth hormone deficient women compared oral estrogen with transdermal estrogen treatment while on growth hormone. Women received incremental doses of growth hormone (0.5, 1.0, 2.0 units/day for 1 week; increased to next dose each week) for 8 weeks and estradiol valerate (2 mg/day) or transdermal estrogen patches (Estraderm-TTS 100 mcg). IGF-1 levels were significantly reduced during oral estrogen treatment and rose dose-dependently during growth hormone administration by a lower magnitude compared with transdermal treatment (change in IGF-1: 109 +/-43% vs. 135 +/-41%).(14)

*Acute critical illness after open heart surgery, abdominal surgery, or multiple accidental trauma, or acute respiratory failure.

*Hypersensitivity to somatropin or any of the excipients.

*Active malignancy.

*Active proliferative or severe non-proliferative diabetic retinopathy.

*Pediatric patients with closed epiphyses.

*Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea or have severe respiratory impairment, due to the risk of sudden death.

• Acute respiratory failure
• Diabetic retinopathy
• Major traumatic injury
• Morbid obesity
• Sleep apnea

• Adrenocortical insufficiency
• Idiopathic intracranial hypertension
• Malignancy
• Pancreatitis
• Slipped capital epiphyses
• Snoring
• Untreated hypothyroidism

• Carpal tunnel syndrome
• Diabetes mellitus
• Edema
• Hypertension
• Progression of nevus
• Scoliosis

Common adverse reactions reported in adult and pediatric patients receiving somatropin include upper respiratory infection, fever, pharyngitis, headache, injection site reactions (such as pain, numbness, redness, and swelling), rashes, lipoatrophy, otitis media, edema, flatulence, abdominal pain, arthralgia, carpal tunnel syndrome, paresthesia, myalgia, peripheral edema, flu syndrome, and impaired glucose tolerance.

Less Frequent

• Dyspnea
• Hypertension
• Hypothyroidism
• Increased alanine transaminase
• Increased aspartate transaminase

Rare or Very Rare

• Acute pancreatitis
• Adrenocortical insufficiency
• Anaphylaxis
• Angioedema
• Diabetic retinopathy
• Fracture
• Gastroenteritis
• Hyperglycemia
• Hyperparathyroidism
• Intracranial hypertension
• Leukemia
• Neoplasm
• Papilledema
• Pituitary insufficiency
• Retinal disorder
• Sleep apnea
• Slipped capital epiphyses

More Frequent

• Acute abdominal pain
• Arthralgia
• Carpal tunnel syndrome
• Edema
• Headache disorder
• Hematoma
• Injection site sequelae
• Lipodystrophy
• Muscle rigidity
• Myalgia
• Peripheral edema

Less Frequent

• Acne vulgaris
• Back pain
• Hypoesthesia
• Nausea
• Paresthesia
• Skin atrophy
• Upper respiratory infection
• Vomiting

Rare or Very Rare

• Abnormal glucose tolerance
• Acute bacterial otitis media
• Alopecia
• Body fluid retention
• Fatigue
• Fever
• Gynecomastia
• Hematuria
• Increased appetite
• Mood changes
• Pharyngitis
• Progression of nevus
• Skin rash
• Tonsillitis
• Type 2 diabetes mellitus
• Urinary tract infection

No enhanced messaging available.

Safety and efficacy of somatropin for the management of children with growth failure due to inadequate secretion of endogenous growth hormone are supported by 3 open-label, multicenter trials conducted over a duration of 2 years (2 trials) and 8 years (1 trial).

Safety and efficacy of somatropin for the management of children with short stature associated with Turner syndrome are supported by one long-term, randomized, dose-response study and 3 long-term, open-label, multicenter studies with concurrent or historical controls.

Safety and efficacy of somatropin for the management of children with idiopathic short stature are supported by one dose-response study, one placebo-controlled study, and 3 randomized studies.

Safety and efficacy of somatropin for the management of children with short stature or growth failure in SHOX deficiency are supported by a single randomized, controlled, 2-year, 3-arm, open-label study in 52 patients.

Safety and efficacy of somatropin for the management of short stature in children born small for gestational age with no catch-up growth by 2 to 4 years of age are supported by 4 clinical studies. One study was a randomized, double-blind, 2-arm study and another was a randomized study of prepubertal, non-GHD, Japanese pediatric patients.

Safety and efficacy of somatropin for the management of short stature associated with Noonan syndrome are supported by a prospective, open-label, randomized, parallel group, 2-year study in 21 pediatric patients.

Safety and efficacy of somatropin for the management of growth failure due to Prader-Willi syndrome are supported by 2 randomized, open label, controlled clinical trials. Sudden death after somatropin initiation has been reported in pediatric patients with Prader-Willi syndrome who had at least one of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection.

Safety and efficacy of somatropin in pediatric patients with HIV have not been established. Treatment appeared to be well tolerated and consistent with safety observations of adults treated with somatropin for HIV-associated wasting in 2 small studies of 11 children with HIV-associated failure to thrive who received somatropin 0.04 mg/kg per day for 26 weeks or somatropin 0.07 mg/kg per day for 4 weeks.

Risks of growth hormone therapy specific to pediatric patients include risk of sudden death in pediatric patients with Prader-Willi syndrome, increased risk of second neoplasm in pediatric cancer survivors treated with radiation to the brain and/or head, intracranial hypertension, slipped capital femoral epiphysis, progression of preexisting scoliosis, and pancreatitis.

Benzyl alcohol may be a component of somatropin products or the diluent used for reconstitution. Benzyl alcohol has been associated with serious adverse events and death; ''gasping syndrome,'' (characterized by CNS depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with dosages >99 mg/kg per day in neonates and low-birth weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. The combined daily metabolic load of benzyl alcohol from all sources should be considered. To decrease benzyl alcohol exposure in high-risk patients, consult the preparation-specific labeling to find a benzyl alcohol-free product or alternative diluents.

Available data with somatropin use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes or any impact on reproductive capacity.

The American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) and Endocrine Society guidelines state that due to insufficient evidence of safety or efficacy, routine use of somatropin for conception or continued use during pregnancy in women with GHD is not recommended.

Benzyl alcohol is rapidly metabolized in pregnancy; therefore, exposure to the fetus is unlikely. Intravenously administered drugs containing benzyl alcohol have caused adverse reactions in premature neonates and low birth weight infants. To avoid fetal exposure to benzyl alcohol in women continuing somatropin during pregnancy, consult the preparation-specific labeling to find a benzyl alcohol-free product or alternative diluents.

Animal reproduction studies were conducted with various somatropin preparations at doses in excess of normal human doses (e.g., 1 mg/kg per day, 3.3 mg/kg per day), resulting in growth hormone blood levels in excess of human therapeutic levels (e.g., 19 and 24 times higher, respectively), and administered at different time frames corresponding to the periods of organogenesis or gametogenesis. No adverse effects were observed on gestation, morphogenesis, parturition, lactation, postnatal development, or reproductive capacity of the offspring.

There is no information regarding the presence of somatropin in human milk; limited data indicate that exogenous somatropin does not increase normal breastmilk concentrations of growth hormone, and no adverse effects on the breastfed infant have been reported with somatropin.

Consider the benefits of breast-feeding and the importance of somatropin to the woman along with the potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Benzyl alcohol is rapidly metabolized in lactating women; therefore, exposure in the breast-fed infant is unlikely. Intravenously administered drugs containing benzyl alcohol have caused adverse reactions in premature neonates and low birth weight infants.

To avoid infant exposure to benzyl alcohol from women continuing somatropin while breast-feeding, consult the preparation-specific labeling to find a benzyl alcohol-free product or alternative diluents.

Elderly patients may be more sensitive to somatropin and may be more prone to develop adverse reactions; lower initial doses and smaller dose adjustment increments are recommended.

Experience in patients >=65 years of age is insufficient to determine whether they respond differently to somatropin than younger patients.

Elderly patients may be more sensitive to somatropin, may be more prone to develop adverse reactions, and lower initial doses with smaller dosage adjustment increments are recommended.