Version May 2024
Growth hormone deficiency:
SubQ: Initial: 1.5 mg once weekly; may increase dose by 0.5 to 1.5 mg/week every 2 to 4 weeks based on clinical response and insulin-like growth factor 1 (IGF-1) levels; reduce dose if needed for adverse reactions or elevated IGF-1 levels. Maximum dose: 8 mg/week.
Duration of therapy: Consider discontinuing therapy if no apparent benefits are achieved after 12 to 18 months; therapy may be continued indefinitely if benefits are achieved (Ref).
Missed doses: Administer missed dose as soon as possible within 3 days; resume usual schedule thereafter. If >3 days have passed since the missed dose, skip dose and administer next dose on the next regular dosing day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; drug exposure increases with decreasing eGFR.
Mild impairment: No dosage adjustment is necessary.
Moderate impairment: Initial: 1 mg once weekly; adjust dose in smaller increments (maximum dose: 4 mg/week).
Severe impairment: Use is not recommended (has not been studied).
Malignancy: Discontinue therapy if evidence of tumor progression/recurrence of preexisting malignancy.
Papilledema: Discontinue therapy if papilledema occurs; if papilledema is a result of intracranial hypertension, may consider restarting at a lower dose once signs/symptoms of intracranial hypertension resolve.
Note: Avoid use, except as hormone replacement in patients with growth hormone deficiency due to an established etiology that is based on a rigorous diagnosis by evidence-based criteria (Ref).
SubQ: Initial: 1 mg once weekly; adjust dose in smaller increments.
(For additional information see "Somapacitan: Pediatric drug information")
Note: Somapacitan is available in multiple strengths of prefilled pens; use caution when prescribing and administering. Fundoscopic exam should be performed prior to initiation. Use actual body weight for dosing.
Growth hormone deficiency, treatment: Children ≥2.5 years and Adolescents: SUBQ: Initial dose: 0.16 mg/kg/dose once weekly; individualize and titrate dose based on patient response. If epiphyses are closed, reevaluate patient before continuing therapy.
Converting from daily growth hormone products: Begin therapy 1 day after last daily injection of other product.
Dosing adjustment for toxicity:
Malignancy: Discontinue therapy if evidence of tumor progression/recurrence of preexisting malignancy.
Papilledema: Discontinue therapy if papilledema occurs; if papilledema is a result of intracranial hypertension, may consider restarting at a lower dose once signs/symptoms of intracranial hypertension resolve.
There are no dosage adjustments provided in the manufacturer's labeling; drug exposure increases with decreasing eGFR.
Children ≥2.5 years and Adolescents:
Mild impairment: There are no dosage adjustments necessary.
Moderate to severe impairment: Use is not recommended (has not been studied).
Fluid retention may occur with growth hormone (GH) therapy; effects are generally transient and dose dependent. Manifestations of fluid retention may include peripheral edema, arthralgia, myalgia, and nerve compression syndromes (including carpal tunnel syndrome or paresthesias).
Mechanism: Dose-dependent; exact mechanism is unknown (Ref).
Onset: Varied; onset of symptoms consistent with fluid retention generally occur within 1 to 3 months of initiation or dose increase (Ref).
Risk factors:
• Patients being treated for adult-onset GH deficiency, especially those with an increased body mass index (Ref)
Treatment with growth hormone (GH) products, including somapacitan, may decrease insulin sensitivity. Previously undiagnosed impaired glucose tolerance or diabetes mellitus may be detected; new-onset type 2 diabetes mellitus and exacerbation of preexisting diabetes mellitus may occur.
Mechanism: Dose-dependent; related to the pharmacologic action. Somapacitan is a human GH analog which may antagonize the hepatic and peripheral effects of insulin on glucose metabolism (Ref).
Onset: Delayed; in one long-term observational trial of adults with GH deficiency receiving GH therapy, new diagnosis of type 2 diabetes occurred between 9 and 29 months of GH therapy (Ref).
Risk factors:
• Preexisting type 1 or 2 diabetes mellitus, prediabetes, risk factors for developing diabetes mellitus (eg, obesity, family history)
• Turner syndrome
Intracranial hypertension (IH) with headache, nausea, papilledema, visual changes, and/or vomiting has been reported in patients treated with growth hormone products (Ref); signs and symptoms of IH may rapidly resolve after discontinuation or reduction of dose.
Mechanism: Exact mechanism is unknown; may be dose related (Ref)
Onset: Delayed; according to the manufacturer, symptoms usually occur within the first 8 weeks of therapy. IH has also appeared after several years of therapy (Ref).
Risk factors:
• Preexisting IH (eg, preexisting papilledema)
• In general, idiopathic intracranial hypertension is most commonly reported in females of childbearing age and with a high body mass index (Ref)
• Chronic kidney insufficiency (Ref)
Growth hormone (GH) therapy may increase the risk of malignancy progression in patients with active malignancy. Malignant transformation or growth of preexisting nevi may also occur. An increased risk of second neoplasms, primarily meningiomas, has also been reported in pediatric patients who developed GH deficiency (GHD) after receiving radiation to the head/brain for first neoplasm. The use of GH therapy in GH-deficient patients without other risk factors for malignancy does not appear to increase the risk of developing malignancy (Ref).
Risk factors:
• Presence of preexisting malignancy, especially active malignancies or patients with malignancies who have not yet completed treatment.
Note: The American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) guidelines for the management of GH deficiency in adults suggest waiting ≥5 years after cancer remission before initiating low-dose recombinant human GH therapy due to the increased risk of secondary neoplasm (particularly adult survivors of childhood cancers); specific data on the effects of recombinant GH replacement and cancer risk are lacking (Ref).
• Presence of preexisting nevi
• Pediatric patients treated for GHD after radiation to head/brain for first neoplasm (risk for second neoplasm [eg, meningioma])
Pediatric patients receiving growth hormone (GH) therapy can develop slipped capital femoral epiphyses (SCFE) at an incidence rate higher than the general population (Ref).
Mechanism: Exact mechanism is unknown; recombinant GH may reduce resistance to shear stresses and contributes to the widening of the weakest zone of the epiphyseal plate enhancing weakness of the growth plate (Ref).
Onset: Varied; the median onset from the start of GH therapy ranges from 0.4 to 2.5 years (Ref) though there seems to be no correlation between the occurrence of SCFE and duration of GH therapy (Darendeliler 2007).
Risk factors:
• Rapid growth (Ref)
• Prior cancer diagnosis (Ref), including craniopharyngioma and cranial tumor (Ref)
• Total body irradiation (Ref) or radiation exposure to the spinal area (Ref)
• Trauma (Ref)
• Obesity (Ref)
• Turner syndrome (Ref)
• Panhypopituitarism (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults unless otherwise indicated.
>10%:
Endocrine & metabolic: Increased serum phosphate (18%)
Immunologic: Antibody development (children: 12%; no neutralizing antibodies were detected)
1% to 10%:
Cardiovascular: Hypertension (3%), peripheral edema (3%) (table 1)
|
Drug (Somapacitan) |
Placebo |
Number of Patients (Somapacitan) |
Number of Patients (Placebo) |
|---|---|---|---|
|
3% |
2% |
120 |
61 |
Endocrine & metabolic: Adrenocortical insufficiency (3%), weight gain (3%)
Gastrointestinal: Dyspepsia (5%), vomiting (3%)
Hematologic & oncologic: Anemia (3%)
Nervous system: Dizziness (4%), sleep disorder (4%)
Neuromuscular & skeletal: Arthralgia (7%) (table 2), back pain (10%), increased creatine phosphokinase in blood specimen (3% to 9%)
|
Drug (Somapacitan) |
Placebo |
Number of Patients (Somapacitan) |
Number of Patients (Placebo) |
|---|---|---|---|
|
7% |
2% |
120 |
61 |
Respiratory: Tonsillitis (3%)
Hypersensitivity to somapacitan or any component of the formulation; acute critical illness after open heart surgery, abdominal surgery, or multiple accidental trauma; acute respiratory failure; active malignancy; active proliferative or severe nonproliferative diabetic retinopathy; pediatric patients with closed epiphyses; Prader-Willi syndrome in pediatric patients who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment.
Concerns related to adverse effects:
• Pancreatitis: Has been rarely reported in pediatric patients receiving somatropin; incidence in children may be greater than adults. Consider pancreatitis diagnosis if abdominal pain occurs.
Disease-related concerns:
• Acute critical illness: Somapacitan is contraindicated in patients with acute critical illness due to potential complications following open heart or abdominal surgery, multiple accidental trauma, or acute respiratory failure; these concerns are based on studies that showed increased mortality in critically ill patients without growth hormone deficiency who were receiving supraphysiologic doses of growth hormone. Safety of continuing growth hormone products used at lower doses (eg, for replacement therapy) has not been established during critical illness.
• Hepatic impairment: Use is not recommended in patients with severe hepatic impairment; dosage adjustment is required in patients with moderate hepatic impairment.
• Hypoadrenalism: Patients who have or are at risk for pituitary hormone deficiency(ies) may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism with somapacitan therapy; patients with previously diagnosed hypoadrenalism may require increased dosages of glucocorticoids due to the effects of somapacitan.
• Hypothyroidism: Patients who have or are at risk for pituitary hormone deficiency(ies) may be at risk for reduced thyroid function (central hypothyroidism). Untreated/undiagnosed hypothyroidism may decrease response to therapy.
• Prader-Willi syndrome: Sudden death has been reported in pediatric patients with Prader-Willi syndrome following the use of somatropin. The reported fatalities occurred in patients with ≥1 risk factor, including severe obesity, history of upper airway obstruction or sleep apnea, respiratory impairment, or unidentified respiratory infection; male patients may be at greater risk. Use of somapacitan is not indicated for the treatment of pediatric patients who have growth failure due to Prader-Willi syndrome.
• Scoliosis: Progression of scoliosis may occur in pediatric patients experiencing rapid growth.
Special populations:
• Older adult: Patients ≥65 years of age may be more sensitive to the actions of somapacitan due to greater drug exposure than patients <65 years of age at the same dose level; lower starting doses and smaller dose increments are required.
• Pediatric: Failure to increase growth rate, particularly during the first year of therapy, indicates need for close assessment of compliance and evaluation for other causes of growth failure, such as hypothyroidism, undernutrition, advanced bone age, and antibodies to recombinant human growth hormone.
Dosage form specific issues:
• Multiple-dose injection pens: According to the Centers for Disease Control and Prevention, pen-shaped injection devices should never be used for more than 1 person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous:
Sogroya: Somapacitan-beco 5 mg/1.5 mL (1.5 mL); Somapacitan-beco 10 mg/1.5 mL (1.5 mL); Somapacitan-beco 15 mg/1.5 mL (1.5 mL) [contains phenol]
No
Solution Pen-injector (Sogroya Subcutaneous)
5 mg/1.5 mL (per mL): $1,116.52
10 mg/1.5 mL (per mL): $2,233.04
15 mg/1.5 mL (per mL): $3,349.56
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous:
Sogroya: Somapacitan-beco 5 mg/1.5 mL (1.5 mL); Somapacitan-beco 10 mg/1.5 mL (1.5 mL); Somapacitan-beco 15 mg/1.5 mL (1.5 mL) [contains phenol]
SUBQ: For SUBQ administration into the abdomen, buttocks, thigh, or upper arm. Rotate injection site weekly to avoid lipohypertrophy. Solution should be clear to slightly opalescent and colorless to slightly yellow; do not use if solution is cloudy or contains particles. Prime unused pen devices before injecting. Once injected, keep the needle in the skin for ~6 seconds after the dose dial has returned to 0 mg before removing the needle to ensure the full dose has been administered. Prefilled pen devices deliver doses from 0.025 to 2 mg in increments of 0.025 mg (5 mg/1.5 mL) or 0.05 to 4 mg in increments of 0.05 mg (10 mg/1.5 mL) or 0.1 to 8 mg in increments of 0.1 mg (15 mg/1.5 mL). Refer to manufacturer’s labeling for product-specific details.
Parenteral: SUBQ: For SUBQ administration only. Administer into the upper arm, thigh, abdomen, or buttocks. Administer on the same day each week; rotate injection site weekly. Solution should be clear to slightly opalescent and colorless to slightly yellow; do not use if solution is cloudy or contains particles. Prior to first use, each new pen must be primed; see manufacturer's labeling for specific priming procedure and additional administration instructions. Attach a new disposable needle to pen for each dose; set dial to appropriate dose, insert needle into clean skin, and activate device by holding the button down; continue to hold the button until the dose window reads "0." After the dose returns to "0," continue to hold the needle in the skin for ~6 seconds before removing the needle to ensure the full dose has been administered. Dispose of used needle. Doses delivered and increments vary with pen strength; verify correct pen is utilized.
5 mg/1.5 mL prefilled pen: Device delivers doses from 0.025 to 2 mg in 0.025 mg increments; prime pen with 0.025 mg.
10 mg/1.5 mL prefilled pen: Device delivers doses from 0.05 to 4 mg in 0.05 mg increments; prime pen with 0.05 mg.
15 mg/1.5 mL prefilled pen: Device delivers doses from 0.1 to 8 mg in 0.1 mg increments; prime pen with 0.1 mg.
Missed doses: Administer a missed dose as soon as possible if it is ≤3 days after the scheduled dose; resume usual schedule thereafter. If >3 days have passed since the missed dose, skip dose and administer next dose on the next regular dosing day.
Growth failure: Treatment of growth failure due to inadequate endogenous growth hormone secretion in pediatric patients ≥2.5 years of age.
Growth hormone deficiency: Replacement of endogenous growth hormone in adults with growth hormone deficiency.
Somapacitan may be confused with homatropine, Soma, somatropin, sumatriptan.
Beers Criteria: Growth hormone is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older except as hormone replacement in patients with growth hormone deficiency due to an established etiology that is based on a rigorous diagnosis by evidence-based criteria due to its minimal impact on body composition and its association with causing edema, arthralgia, carpal tunnel syndrome, gynecomastia, and impaired fasting glucose (Beers Criteria [AGS 2023]).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the therapeutic effect of Growth Hormone Analogs. Growth Hormone Analogs may decrease serum concentrations of the active metabolite(s) of Corticosteroids (Systemic). Risk C: Monitor therapy
Cortisone: May diminish the therapeutic effect of Growth Hormone Analogs. Growth Hormone Analogs may decrease serum concentrations of the active metabolite(s) of Cortisone. Risk C: Monitor therapy
Estrogen Derivatives: May diminish the therapeutic effect of Growth Hormone Analogs. Management: Initiate somapacitan at 2 mg once weekly in patients receiving oral estrogens. Monitor for reduced efficacy of growth hormone analogs; increased doses may be required. Risk D: Consider therapy modification
Macimorelin: Products that Affect Growth Hormone may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
PredniSONE: May diminish the therapeutic effect of Growth Hormone Analogs. Growth Hormone Analogs may decrease serum concentrations of the active metabolite(s) of PredniSONE. Risk C: Monitor therapy
Growth hormone replacement therapy may improve amenorrhea, dysmenorrhea, and fertility in females with growth hormone deficiency (information not specific to use of somapacitan) (Vila 2018).
During normal pregnancy, maternal production of endogenous growth hormone decreases as placental growth hormone production increases. Continued use of short-acting growth hormone replacement early in pregnancy in patients with growth hormone deficiency has not been associated with adverse pregnancy outcomes (information not specific to use of somapacitan) (Vila 2018).
It is not known if somapacitan is present in breast milk.
Maternal use of short-acting growth hormone has not been found to influence breast milk concentrations of endogenous growth hormone (information not specific to use of somapacitan). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Monitor clinical response, serum insulin-like growth factor 1 (IGF-1), and adverse reactions every 2 to 4 weeks during dose titration; check IGF-1 levels 3 to 4 days after the prior dose. Once at maintenance dose, monitor serum IGF-1, fasting glucose, HbA1c, BMI, waist circumference/waist to hip ratio, thyroid function (free T4), adrenal function, lipid profile, phosphorus, alkaline phosphatase, parathyroid hormone, BP, heart rate, clinical response, and adverse reactions every 6 to 12 months; fundoscopic examination to evaluate for papilledema (baseline and periodically during therapy); monitor scoliosis progression (in patients with history of scoliosis); monitor limp or hip or knee pain (evaluate for slipped capital femoral epiphyses); lipoatrophy at injection sites; monitor patients with preexisting tumors for recurrence or progression; monitor for malignant transformation of skin lesions; evaluate bone mineral density prior to therapy and dual-energy x-ray absorptiometry scan repeated every 1.5 to 3 years if initial bone scan is abnormal (AACE/ACE [Yuen 2019]; ES [Fleseriu 2016]; ES [Molitch 2011]; manufacturer’s labeling).
Somapacitan is a human growth hormone analog of recombinant DNA origin with a single substitution in the amino acid backbone to which an albumin-binding moiety has been attached. Somapacitan binds to a dimeric growth hormone receptor in the cell membrane of target cells resulting in multiple pharmacodynamic effects; some of these effects are primarily mediated by insulin-like growth factor 1 produced in the liver, while others are primarily a consequence of the direct effects of somapacitan.
Duration: ≥7 days (Rasmussen 2014; Rasmussen 2016).
Distribution: Vd:
Pediatric patients: 1.7 L.
Adults: ~14.6 L.
Protein binding: >99%.
Metabolism: Extensive; via proteolytic cleavage of the linker sequence between the peptide backbone and albumin binder sidechain.
Half-life elimination: ~2 to 3 days.
Time to peak: Single dose: 4 to 24 hours (dose dependent); steady state is achieved after 1 to 2 weeks of once weekly SubQ administration (Rasmussen 2014; Rasmussen 2016).
Excretion: Urine: ~81%; feces: ~13%.
Altered kidney function: Drug exposure increases with decreasing eGFR (AUC increased by 1.75-fold in severe renal impairment).
Hepatic function: Cmax was 3.52-fold higher in patients with moderate hepatic impairment compared to patients with normal hepatic function.
Older adult: Patients ≥65 years of age have greater drug exposure than patients <65 years of age at the same dose level.
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