Somatrogon-Ghla - Indication, Dosage, Side Effects, Precautions, and Contraindications

Overview:

Somatrogon-ghla, a new form of human growth hormone, is used to treat children (aged three and above) with growth hormone deficiency, which can lead to short stature and delayed puberty. This drug was approved by the FDA (Food and Drug Administration) on June 28th, 2023. It is given as a weekly injection, instead of daily and helps replace the missing growth hormone in the body. However, it can cause side effects like injection site reactions, headaches, and stomach pain. It is important to watch for severe allergic reactions and other serious complications.

Drug Group:

Somatrogon is a special kind of long-acting recombinant human growth hormone that lasts for a long time in the body. Growth hormone is a natural substance made by the brain that helps kids grow taller and controls how the body uses energy when they become adults. Somatrogons are designed to last longer in the body compared to traditional growth hormone treatments. Somatrogon is given once a week instead of every day, making it easier for patients to stick to their treatment plan.

Available Doses and Dosage Forms:

Somatrogon-ghla is available in two strengths and is a clear or slightly light yellow solution.

• 24 mg (milligram)/1.2 mL (milliliter) (20 mg/mL) in a prefilled pen for single use. Each dose is delivered in 0.2 mg increments.

• 60 mg/1.2 mL (50 mg/mL) in a prefilled pen for single use. Each dose is delivered in 0.5 mg increments.

For Patients:

What Is Growth Hormone Deficiency?

Growth hormone deficiency (GHD), also called dwarfism or pituitary dwarfism, occurs when the body does not produce enough growth hormone. Children with GHD are shorter than usual but have normal body proportions.

What Are the Things to Inform the Doctor Before Taking the Somatrogon-ghla?

• Before deciding to take this medicine, the person and their doctor should consider the risks and benefits.

• Let the doctor know if the patient has any allergic reactions to this medicine or any other medications.

• Also, inform the doctors about any allergies they have to foods, dyes, preservatives, or animals.

• Studies have not revealed any particular issues if this medication is given to a child who is three years old or older, but it is not advised for younger children (under three years of age). There is no information about how this medicine affects older adults.

• If the patient is breastfeeding, talk to the doctor about the risks and benefits of taking this medicine.

How Is Somatrogon-ghla Administered?

• Somatrogon-ghla is a liquid solution that comes in a pre-filled injection pen. It is given by injecting it under the skin once a week, on the same day each week, at any time of day.

• The doctor or pharmacist will explain how to use it, so make sure to follow their instructions carefully.

• The first dose may be given at the doctor's office, but after that, the person or a caregiver can give the injections at home.

• Before each injection, check the expiration date on the pen and make sure the liquid is clear or slightly yellow.

• Do not use it if it is expired or if the liquid looks cloudy or has particles in it.

• A person can inject Somatrogon-ghla into the front of their thighs, buttocks, upper arms, or stomach (except around the belly button), but choose a different spot each time.

• Do not inject into tender, bruised, red, or hard areas or where a person has scars.

• Do not stop using Somatrogon-ghla without talking to the doctor first.

• After using the pen, dispose of the needles and pens in a special container to keep them safe.

• Ask the doctor or pharmacist for more information about how to use and dispose of the pens and needles.

What Are the Side Effects of Somatrogon-ghla?

• Higher risk of death in patients with severe critical illness.

• Severe allergic reactions.

• Increased chance of developing tumors.

• If blood sugar increases or decreases.

• Increased pressure inside the skull.

• Fluid retention in the body.

• Reduced function of the adrenal glands.

• Underactive thyroid gland.

• Slipping of the hip bone's growth plate.

• Worsening of existing spine curvature.

• Inflammation of the pancreas.

• Loss of fat tissue under the skin.

• Sudden death in children with Prader-Willi syndrome (a rare genetic disorder caused by particular gene mutations on chromosome 15 that cause weak muscles, feeding issues, and delayed development in neonates).

Dietary Considerations:

Unless the doctor recommends, continue with the normal diet.

Missed Dose:

If an individual misses a dose of Somatrogon-ghla, they should take it as soon as possible within three days. If it is been more than three days, skip the missed dose and take the next one as scheduled.

Overdose:

Taking too much growth hormone can cause low blood sugar at first, then high blood sugar later. It can also help the person to retain fluids. If an individual is taking too much of this medication for a long time, they might develop signs of gigantism, like growing too much. Some of the symptoms include enlarged hands and feet, lips, nose and tongue, excessive sweating, swelling of hands and feet, lower legs or ankles, and muscle or joint weakness.

Storage:

• Store Somatrogon-ghla pens in their original container in the refrigerator, away from light, but do not freeze them.

• If a pen has been frozen, throw it away. Keep track of the first usage of the pen and throw it away after 28 days, even if there is some medicine left.

• Keep all medicines out of reach of children, especially those that are not child-resistant.

• Lock safety caps and store medicines in a safe place that is out of sight and within reach of children.

• Do not flush medicine down the toilet. Instead, check if there is a medicine take-back program in the community.

For Doctors:

Indication:

• Somatropin injection is a medication used to replace the natural growth hormone in both adults and children with growth hormone deficiency.

• It is also prescribed to children with specific conditions affecting normal growth and development.

• In patients with HIV (human immunodeficiency virus), Somatropin injection is used to increase body weight and physical endurance in those with HIV-associated wasting syndrome.

• Another form of Somatropin injection is used to treat short bowel syndrome in adults who are receiving additional nutrition or fluids from intravenous (IV) therapy.

• Somatropin is a human growth hormone (hGH) analog that works by replacing the missing growth hormones in the body, potentially leading to increased growth, body weight, and improved absorption of nutrients and fluids from the intestines.

Dosing Considerations:

• The dosage of this medication varies depending on individual patients.

• It is important to follow the doctor's instructions or the dosage information on the label.

• The information provided here gives the average doses of the medication.

• Do not alter the dose unless instructed by the doctor.

• The dosage is determined based on the strength of the medication, the frequency of administration, and the duration of treatment, all of which are specific to the medical condition being treated.

• To treat growth failure due to growth hormone deficiency, it is dosed separately for children under three years and children over three years.

• For children aged three and older, the dose is calculated based on body weight and should be determined by the doctor. Typically, the dose is 0.66 milligrams per kilogram of body weight injected subcutaneously once weekly on the same day, at any time of the day.

• For children under three years of age, the appropriate use and dosage should be determined by the doctor.

Pharmacological Aspects of Somatrogon-ghla

• Pharmacodynamics: Somatrogon replicates the natural functions of endogenous growth hormone, including cell growth, metabolism, and development. Additionally, it has been demonstrated to elevate the levels of insulin-like growth factor (IGF-1) in the bloodstream.

• Mechanism of Action: Growth hormone plays a crucial role in regulating body growth and metabolism of carbohydrates, proteins, and lipids. Somatrogon is a hormone therapy designed to replenish deficient levels of growth hormone (GH). Similar to natural growth hormone, Somatrogon binds to the GH receptor, leading to the activation of JAK2 (Janus Kinase 2 gene) and subsequent phosphorylation of both JAK2 and GHR (growth hormone receptor). This activation recruits various signaling proteins and initiates multiple pathways responsible for growth and metabolism. One of these pathways is the STAT5b (signal transducer and activator of transcription) signaling pathway, which is essential for the effects of GH on body height.

• Pharmacokinetics: After subcutaneous administration of 0.66 mg/kg/week in pediatric patients with a growth hormone deficiency, Somatrogon reaches a maximum concentration (Cmax) of 690 ng/mL (nanogram per milliliter), with a time to reach maximum concentration (Tmax) of eight hours and an area under the concentration-time curve (AUC) of 21800 ng x h/mL (Planck’s constant per milliliter). Somatrogon exposure increases in proportion to the dose within the range of 0.25-0.66 mg/kg/week. Regarding distribution, the apparent central volume of distribution (Vc) is 0.812 L/kg, and the apparent peripheral volume of distribution (Vt) is 0.169 L/kg (liter per kilogram). Somatrogon does not accumulate after once-weekly administration. Somatrogon undergoes protein catabolism, leading to the reclamation of amino acids and their return to systemic circulation. The half-life of Somatrogon after subcutaneous administration of 0.66 mg/kg/week is approximately 28.3 hours, and it remains detectable in the circulation for about six days after the last dose. The clearance rate is 0.0336 L/h/kg (liters per hour per kilogram).

Toxicity:

There is no data available on the effects of subcutaneous doses of Somatrogon exceeding 0.66 mg/kg (milligram per kilogram) per week. However, based on similar growth hormone products, taking too much Somatrogon in a short period causes low blood sugar followed by high blood sugar levels. In the long term, excessive Somatrogon may lead to symptoms of gigantism or acromegaly due to excess growth hormone. Treatment for Somatrogon overdose involves general supportive measures.

Clinical Studies:

Due to the varying conditions in clinical trials, comparing adverse reaction rates between drugs or trials may not accurately reflect real-world rates. Safety data from a study of pediatric patients with growth hormone deficiency (GHD) showed that 109 patients received Somatrogon once weekly, while 115 received Somatropin once daily. The mean age was 7.7 years, with 71.9 % male and 28.1 % female patients. Adverse reactions occurring in ≥5 % of patients treated with Somatrogon or Somatropin included injection site reactions, nasopharyngitis, headache, pyrexia, anemia, vomiting, rash, cough, hypothyroidism, oropharyngeal pain and hypothyroidism. More Somatrogon-treated patients had elevated eosinophil levels compared to those receiving daily Somatropin (29 % vs 12 %) by the end of the 12-month study.

What Are the Contraindications of Somatrogon-ghla?

Somatrogon-ghla should not be used in certain conditions:

• Acute critical illness following procedures like open heart surgery, abdominal surgery, severe trauma, and acute respiratory failure poses a risk of increased mortality with Somatropin therapy.

• Hypersensitivity to Somatrogon-ghla or any components of Somatrogon-ghla is contraindicated.

• Patients with closed epiphyses should not receive Somatrogon-ghla.

• Active malignancy presents a risk of disease progression and is a contraindication to Somatrogon-ghla therapy.

• Patients with active proliferative or severe non-proliferative diabetic retinopathy should not receive Somatrogon-ghla.

• Prader-Willi syndrome patients who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment are at risk of sudden death with Somatrogon-ghla therapy.

Warnings and Precautions:

1. Increased Mortality: Somatrogon-ghla may increase the risk of death in patients with severe illnesses like heart surgery complications.

2. Severe Hypersensitivity: Rare allergic reactions, including anaphylaxis, may occur. Seek immediate medical help if allergic symptoms develop.

3. Increased Risk of Cancer: Patients with active cancer should avoid Somatrogon-ghla. Childhood cancer survivors treated with Somatrogon-ghla have a higher risk of developing another cancer.

4. Glucose Intolerance and Diabetes: Somatrogon-ghla may affect blood sugar levels, leading to new-onset diabetes or worsening control of pre-existing diabetes.

5. Intracranial Hypertension: Somatrogon-ghla may cause increased pressure in the brain, leading to symptoms like headaches and vision changes.

6. Fluid Retention: Some patients may experience fluid retention, causing swelling or nerve compression.

7. Hypoadrenalism: Somatrogon-ghla may lower cortisol levels in patients with pituitary hormone deficiencies.

8. Hypothyroidism: Patients should be monitored for thyroid hormone levels as Somatrogon-ghla therapy may worsen or reveal hypothyroidism.

9. Slipped Capital Femoral Epiphysis: Pediatric patients undergoing rapid growth with Somatrogon-ghla therapy may have an increased risk of hip joint problems.

10. Scoliosis Progression: Somatrogon-ghla can increase growth rate, potentially worsening pre-existing scoliosis in patients.

11. Pancreatitis: Cases of pancreatitis have been reported in patients receiving Somatrogon-ghla. Seek medical attention for severe abdominal pain.

12. Lipoatrophy: Long-term use of Somatrogon-ghla at the same injection site may result in fat loss. Rotate injection sites to prevent this.

13. Sudden Death in Prader-Willi Syndrome: Somatrogon-ghla is not recommended for pediatric patients with Prader-Willi syndrome due to the risk of sudden death, especially in those with obesity or respiratory issues.

14. Laboratory Tests: Some blood tests may show abnormal results during Somatrogon-ghla therapy. Regular monitoring is necessary.

Drug Interactions of Somatrogon-ghla:

The significant drug interactions observed with Somatrogon-ghla and guides for managing or preventing them:

1. Replacement Glucocorticoid Treatment: The impact of Somatrogon-ghla may inhibit the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1), which converts cortisone to cortisol, potentially leading to reduced serum cortisol levels. The intervention may be that patients receiving glucocorticoid replacement therapy for hypoadrenalism may need dose adjustments to avoid low cortisol levels.

2. Supraphysiologic Glucocorticoid Treatment: The Impact will be that high-dose glucocorticoid therapy may counteract the growth-promoting effects of NGENLA in pediatric patients. Intervention is that pediatric patients on glucocorticoid treatment should have their doses carefully adjusted to prevent growth inhibition and hypoadrenalism.

3. Cytochrome P450-Metabolized Drugs: The Impact of Somatrogon-ghla may affect the clearance of drugs metabolized by cytochrome P450 (CYP450) liver enzymes. Intervention by close monitoring is recommended when Somatrogon-ghla is used alongside medications metabolized by CYP450 liver enzymes.

4. Oral Estrogen: The impact of oral estrogen therapy may reduce the serum insulin-like growth factor 1 (IGF-1) response to Somatrogon-ghla. When a patient is on oral estrogen replacement treatment, Somatrogon-ghla dosages may need to be increased to have the desired effect.

5. Insulin and Other Antihyperglycemic Agents: The impact of Somatrogon-ghla treatment may decrease insulin sensitivity, especially at higher doses. To maintain appropriate glycemic control, patients with diabetes mellitus may require dose modifications for insulin and additional antihyperglycemic agents.

Specific Considerations:

1. Pregnancy: Animal studies showed no adverse effects on embryo-fetal development. The background risk of birth defects and miscarriage in the general population is two to four percent and 15-20 percent, respectively.

2. Lactation: Consider the benefits of breastfeeding along with the clinical need for Somatrogon-ghla.

3. Females and Males of Reproductive Potential: Somatrogon may interfere with hCG (human chorionic gonadotropin) pregnancy testing. Alternative methods are recommended for pregnancy determination.

4. Pediatric Use: Approved for treating growth hormone deficiency in children aged three years and older. Risks in pediatric patients include second neoplasm risk, slipped capital femoral epiphysis, scoliosis progression, pancreatitis, and sudden death in Prader-Willi Syndrome. Not indicated for genetically confirmed Prader-Willi syndrome.