Skytrofa

Drug overview for SKYTROFA (lonapegsomatropin-tcgd):

Generic name: lonapegsomatropin-tcgd (LOE-na-peg-SOE-ma-TROE-pin)
Drug class: Growth Hormone Modulators
Therapeutic class: Endocrine

Lonapegsomatropin-tcgd is a long-acting prodrug of human growth hormone (hGH, somatropin). Recombinant somatropin is conjugated to a methoxypolyethylene glycol (mPEG) carrier (4 x 10 kDa mPEG) via a TransCon(R) linker.

No enhanced Uses information available for this drug.

DRUG IMAGES

No Image Available

The following indications for SKYTROFA (lonapegsomatropin-tcgd) have been approved by the FDA:

Indications:
Pituitary dwarfism

Professional Synonyms:
GH deficiency dwarfism
Growth failure due to isolated growth hormone deficiency
Growth failure due to isolated somatotropin deficiency
Hypophysial dwarfism
Lorain-Levi dwarfism
Lorain-Levi infantilism
Lorain-Levi syndrome
Pituitary infantilism

The following drug interaction information is available for SKYTROFA (lonapegsomatropin-tcgd):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 1 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Selected Retinoids (Systemic)/Growth Hormone SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. 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)	ABSORICA, ABSORICA LD, ACCUTANE, ACITRETIN, AMNESTEEM, CLARAVIS, ISOTRETINOIN, RETINOIC ACID, TRETINOIN, TRETINOIN ACID, ZENATANE

Drug Interaction

Drug Names

Selected Retinoids (Systemic)/Growth Hormone

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

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)

ABSORICA, ABSORICA LD, ACCUTANE, ACITRETIN, AMNESTEEM, CLARAVIS, ISOTRETINOIN, RETINOIC ACID, TRETINOIN, TRETINOIN ACID, ZENATANE

There are 0 moderate interactions.

The following contraindication information is available for SKYTROFA (lonapegsomatropin-tcgd):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

*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; severe systemic hypersensitivity reactions (e.g., anaphylactic reactions, angioedema) have been reported. *Closed epiphyses.

*Active malignancy. *Active proliferative or severe non-proliferative diabetic retinopathy. *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.

There are 5 contraindications. Absolute contraindication.

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

There are 6 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Adrenocortical insufficiency
Idiopathic intracranial hypertension
Malignancy
Pancreatitis
Slipped capital epiphyses
Untreated hypothyroidism

There are 5 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Carpal tunnel syndrome
Diabetes mellitus
Edema
Progression of nevus
Scoliosis

The following adverse reaction information is available for SKYTROFA (lonapegsomatropin-tcgd):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse effects reported in >=5% of pediatric patients include viral infection, pyrexia, cough, nausea and vomiting, hemorrhage, diarrhea, abdominal pain, and arthralgia and arthritis.

There are 10 severe adverse reactions.

More Frequent	Less Frequent
Hemorrhage	None.

Rare/Very Rare
Adrenocortical insufficiency Anaphylaxis Angioedema Hypersensitivity drug reaction Hypothyroidism Intracranial hypertension Malignancy Pancreatitis Slipped capital epiphyses

There are 11 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Arthralgia Arthritis Cough Diarrhea Fever Nausea Viral infection Vomiting	Body fluid retention Hyperglycemia

Rare/Very Rare
None.

The following precautions are available for SKYTROFA (lonapegsomatropin-tcgd):

Pediatric
Pregnant
Lactation
Geriatric

The safety and efficacy of lonapegsomatropin-tcgd have been established in pediatric patients with GHD who are >=1 year of age and who weigh >=11.5 kg. The safety and efficacy is not established in pediatric patients <1 year of age. Lonapegsomatropin-tcgd is not indicated in pediatric patients with growth failure due to genetically confirmed Prader-Willi syndrome due to the association between somatropin use and reports of sudden death in those patients.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

There are no available data on lonapegsomatropin-tcgd 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 embryo-fetal or neonatal harm when pregnant rats were administered subcutaneous lonapegsomatropin-tcgd at doses up to 13-fold the clinical dose of 0.24

mg/kg per week. The manufacturer reports a similar lack of observed adverse effects when a structurally related pegylated somatropin prodrug (up to 13-fold the clinical dose of 0.24 mg/kg per week) was administered to female rats from implantation through weaning.

There are no data on the presence of lonapegsomatropin-tcgd in human milk, effects on infants fed human milk, or effects on human milk production. High molecular weight therapeutic proteins, including lonapegsomatropin-tcgd, are expected to have low passage into human milk and limited systemic exposure in infants fed human milk. Published data indicate that exogenous somatropin does not increase normal human milk GH concentrations.

No adverse effects on infants fed human milk have been reported with somatropin. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for lonapegsomatropin-tcgd and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

No specific studies have been performed.

Pituitary dwarfism
E23.0	Hypopituitarism