Overview
11 DESCRIPTION Lonapegsomatropin-tcgd is a long-acting prodrug of a human growth hormone (somatropin) produced by recombinant DNA technology using E. coli . Lonapegsomatropin-tcgd consists of a parent drug, somatropin, that is conjugated to a methoxypolyethylene glycol carrier (4 × 10 kDa mPEG) via a proprietary TransCon Linker and has a molecular weight of 63 kDa (released somatropin is 22 kDa).
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action SKYTROFA is a pegylated human growth hormone (somatropin) for once-weekly subcutaneous injection [see Clinical Pharmacology (12.3) ] . Somatropin binds to the growth hormone (GH) receptor in the cell membrane of target cells resulting in intracellular signal transduction and a host of pharmacodynamic effects. Somatropin has direct tissue and metabolic effects, and indirect effects mediated by insulin-like growth factor-1 (IGF-1), including stimulation of chondrocyte differentiation and proliferation, stimulation of hepatic glucose output, protein synthesis and lipolysis. Somatropin stimulates skeletal growth in pediatric patients with growth hormone deficiency (GHD) as a result of effects on the growth plates (epiphyses) of long bones. 12.
Indications
- 1 INDICATIONS AND USAGE SKYTROFA (lonapegsomatropin-tcgd) is a human growth hormone indicated for the: Treatment of pediatric patients 1 year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone (GH). Replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD). SKYTROFA is a human growth hormone indicated for: Pediatric Patients: Treatment of pediatric patients 1 year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone (GH) ( 1 ).
Common Doses
- 0.24 mg
- 1.4 mg
- 2.1 mg
- 0.7 mg
Dosage
2 DOSAGE AND ADMINISTRATION SKYTROFA should be administered subcutaneously once weekly into the abdomen, buttock, or thigh with regular rotation of the injection sites ( 2.7 ). Pediatric Patients: Recommended dose is 0.24 mg/kg body weight once weekly ( 2.2 ). Adults: Recommended starting dose is based on age and concomitant use of oral estrogen. Titrate monthly until the desired clinical response and/or weekly average IGF-1 concentration are achieved ( 2.3 ). See Full Prescribing Information for instructions on preparation and administration of drug ( 2.5 , 2.6 , 2.7 ). 2.
Contraindications
- 4 CONTRAINDICATIONS SKYTROFA is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see Warnings and Precautions (5.1) ] . Hypersensitivity to somatropin or any of the excipients in SKYTROFA. Severe systemic hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported [see Warnings and Precautions (5.2) ]. Pediatric patients with closed epiphyses.
Side Effects
- 6 ADVERSE REACTIONS The following important adverse reactions are described elsewhere in the labeling: Increased mortality in patients with acute critical illness [see Warnings and Precautions (5.1) ] Severe hypersensitivity [see Warnings and Precautions (5.2) ] Increased risk of neoplasms [see Warnings and Precautions (5.3) ] Glucose intolerance and diabetes mellitus [see Warnings and Precautions (5.4) ] Intracranial hypertension [see Warnings and Precautions (5.5) ] Fluid retention [see Warnings and Precautions (5.6) ] Hypoadrenalism [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Table 4 includes a list of drugs with clinically important drug interactions when administered concomitantly with SKYTROFA and instructions for preventing or managing them. Table 4: Clinically Important Drug Interactions with SKYTROFA Replacement Glucocorticoid Treatment Clinical Impact: Microsomal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1) is required for conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue. Somatropin inhibits 11βHSD-1.