Sogroya (somapacitan-beco)

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No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

Somapacitan is not known to be metabolized by cytochrome P-450 (CYP) isoenzymes or other drug metabolizing enzymes; however, GH 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 those with acute respiratory failure.

*Hypersensitivity to somatropin or any of the excipients; post-marketing systemic hypersensitivity reactions to somatropin have been reported.

*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 risk of sudden death.

• Diabetic retinopathy
• Morbid obesity
• Sleep apnea

• Child-pugh class B hepatic impairment
• Disease of liver
• Intracranial hypertension
• Malignancy
• Pancreatitis
• Papilledema
• Slipped capital epiphyses

• Adrenocortical insufficiency
• Diabetes mellitus
• Hyperglycemia
• Hypothyroidism
• Scoliosis

Adverse effects reported in >=2% of adult patients with GHD receiving somapacitan-beco include back pain, arthralgia, dyspepsia, sleep disorder, dizziness, tonsillitis, peripheral edema, vomiting, adrenal insufficiency, hypertension, increased blood creatine phosphokinase, weight increase, and anemia.

Adverse effects reported in >=5% of pediatric patients with GHD receiving somapacitan-beco include nasopharyngitis, headache, pyrexia, pain in extremity, and injection site reaction.

More Frequent

• Adrenocortical insufficiency
• Anemia
• Hypertension
• Influenza
• Upper respiratory infection

Less Frequent

• Pneumonia

Rare or Very Rare

• Avascular necrosis of bone
• Hyperglycemia
• Hyperparathyroidism
• Hypersensitivity drug reaction
• Intracranial hypertension
• Malignancy
• Pancreatitis
• Papilledema
• Progression of nevus
• Slipped capital epiphyses
• Type 2 diabetes mellitus

More Frequent

• Arthralgia
• Back pain
• Diarrhea
• Dizziness
• Dyspepsia
• Fever
• Headache disorder
• Increased creatine kinase level
• Infection of ear
• Injection site sequelae
• Pain in extremities
• Peripheral edema
• Pharyngitis
• Sleep disorder
• Tonsillitis
• Vomiting
• Weight gain

Less Frequent

• Lipodystrophy

Rare or Very Rare

• Body fluid retention
• Hyperphosphatemia
• Increased alkaline phosphatase
• Visual changes

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Safety and efficacy of somapacitan-beco have been established in pediatric patients >=2.5 years of age.

Safety and efficacy of somapacitan-beco for the treatment of growth failure due to inadequate secretion of endogenous GH have not been established in pediatric patients <2.5 years of age.

Risks of GH 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, slipped capital femoral epiphysis, progression of preexisting scoliosis, and pancreatitis.

There are no available data on somapacitan-beco use in pregnant patients; however, available somatropin data have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

The American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) and Endocrine Society (ES) 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.

There was no evidence of teratogenicity when pregnant rats or rabbits were administered subcutaneous somapacitan-beco during organogenesis at doses up to approximately 12 times the clinical dose.

There are no data on the presence of somapacitan-beco in human milk, effects on breastfed infants, or effects on human milk production.

Somapacitan-beco related material was secreted into the milk of lactating rats; the manufacturer states that when a substance is present in animal milk, it may be present in human milk.

Published data indicate that exogenous somatropin does not increase normal human milk GH concentrations and no adverse effects on breasted infants were reported.

Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for somatropin-beco and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

In patients >=65 years of age, the initial somapacitan-beco dosage is 1 mg once weekly and titration should occur in smaller dosage increments; the maximum recommended dosage is 8 mg once weekly.

A small proportion of patients >=65 (15.6%) and >=75 (0.9%) years of age received somapacitan-beco in clinical studies.

Patients >=65 years of age have higher exposure compared with younger subjects at the same dosage, may be more sensitive, and may be at increased risk for adverse effects.

Initiate somapacitan-beco therapy in geriatric patients with a dosage of 1 mg once weekly, and use smaller increments when increasing the dose.