Somatropin

For Adult Growth Hormone Deficiency (AGHD), dosing is highly individualized and is not typically based on body weight, but rather on clinical response and serum IGF-1 levels.

• Starting Dose: Usually 0.15 mg to 0.30 mg per day, administered subcutaneously.
• Maintenance Dose: The dose is gradually increased (titrated) by your doctor every 4–8 weeks based on side effects and IGF-1 levels. Most adults require less than 1.0 mg per day.
• HIV-Associated Wasting: The typical dose is 0.1 mg/kg daily (up to 6 mg) at bedtime.
• Short Bowel Syndrome: The typical dose is 0.1 mg/kg daily (up to 8 mg) for a duration of 4 weeks.

In children, dosing is almost always based on body weight or body surface area and varies significantly by the condition being treated.

• Growth Hormone Deficiency: Typically 0.16 to 0.24 mg/kg of body weight per week, divided into daily subcutaneous injections.
• Turner Syndrome: Usually higher doses, up to 0.375 mg/kg per week.
• Prader-Willi Syndrome: Typically 0.24 mg/kg per week.
• Idiopathic Short Stature: Up to 0.30 to 0.47 mg/kg per week.

Renal Impairment

No specific dosage adjustment is generally required for patients with renal impairment, though growth response may be decreased in children with chronic kidney disease. Monitoring for fluid retention is essential.

Hepatic Impairment

No specific dosage adjustment is required for patients with liver disease, but the production of IGF-1 (which occurs in the liver) may be impaired, potentially requiring higher doses to achieve clinical effects.

Elderly Patients

Patients over age 65 are often more sensitive to the effects of somatropin and are more likely to experience side effects like fluid retention and joint pain. Healthcare providers typically start with lower doses (e.g., 0.1 mg/day) and titrate more slowly.

• Route: Somatropin must be injected subcutaneously (under the skin). Common sites include the thighs, abdomen, or upper arms.
• Site Rotation: It is critical to rotate injection sites daily to prevent lipoatrophy (loss of fat under the skin) or localized tissue hardening.
• Timing: Injections are usually given in the evening to mimic the body's natural nocturnal surge of growth hormone.
• Preparation: If using a powder form, do not shake the vial during reconstitution; gently swirl to avoid denaturing the protein. The solution should be clear; do not use if it is cloudy or contains particles.
• Storage: Most somatropin products must be refrigerated (36°F to 46°F or 2°C to 8°C). Some pens can stay at room temperature for a limited time after the first use; check your specific brand's instructions.

If you miss a dose, take it as soon as you remember unless it is almost time for your next dose. Do not "double up" or take two doses at once to make up for a missed one. If you miss more than three doses in a row, contact your healthcare provider for guidance.

Acute overdose may lead to initial hypoglycemia (low blood sugar) followed by hyperglycemia (high blood sugar). Long-term overdose (chronic over-exposure) can lead to acromegaly, a condition characterized by the overgrowth of bones in the face, hands, and feet, as well as organ enlargement.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop treatment without medical guidance, as this can affect the success of the therapy.

These side effects occur frequently, especially when starting therapy or after a dose increase. They are often related to the drug's effect on fluid balance.

• Peripheral Edema: Swelling in the hands, feet, or ankles due to fluid retention. This usually feels like tightness in the skin or difficulty putting on shoes.
• Arthralgia: Joint pain, often affecting the knees, hips, or wrists. It typically resolves as the body adjusts to the medication.
• Myalgia: Muscle pain or stiffness, which may feel like the soreness after a workout.
• Injection Site Reactions: Redness, itching, or a small lump at the site of the injection. These are usually mild and temporary.
• Paresthesia: A sensation of tingling or "pins and needles," often in the hands or feet.

• Hypothyroidism: Somatropin can unmask or worsen a thyroid deficiency. Symptoms include fatigue, weight gain, and feeling cold.
• Hyperglycemia: Increased blood sugar levels. Patients may feel more thirsty than usual or need to urinate more frequently.
• Carpal Tunnel Syndrome: Numbness and tingling in the hand and wrist, caused by fluid pressing on the median nerve.
• Headache: Persistent headaches may occur and should be monitored.
• Gynecomastia: Temporary breast tissue enlargement in males.

• Intracranial Hypertension: Increased pressure inside the skull, causing severe headaches, nausea, and visual changes (papilledema).
• Slipped Capital Femoral Epiphysis (SCFE): A condition where the ball of the hip joint slips off the thigh bone. This is specific to growing children and presents as a limp or hip/knee pain.
• Pancreatitis: Inflammation of the pancreas, causing severe abdominal pain that radiates to the back.
• Progression of Scoliosis: In children with rapid growth, existing curvature of the spine may worsen.

> Warning: Stop taking Somatropin and call your doctor immediately if you experience any of these serious symptoms.

• Severe Allergic Reaction: Hives, difficulty breathing, or swelling of the face, lips, or throat (anaphylaxis).
• Vision Changes: Blurred vision, double vision, or sudden loss of vision, which may indicate intracranial hypertension.
• Severe Abdominal Pain: Especially if accompanied by nausea and vomiting, which may indicate pancreatitis.
• Hip or Knee Pain: In children, any new limp or joint pain must be evaluated immediately by an orthopedic specialist.
• Respiratory Distress: In patients with Prader-Willi syndrome, sudden onset of snoring or difficulty breathing may indicate a serious airway obstruction.

• Diabetes Mellitus: Chronic use of somatropin can lead to insulin resistance. In predisposed individuals, this may progress to Type 2 diabetes.
• Malignancy Risk: While somatropin does not appear to cause new cancers in healthy individuals, it can potentially stimulate the growth of existing tumors. Survivors of childhood cancers must be monitored closely for recurrence.
• Bone Deformities: Excessive use over many years can lead to acromegalic changes, such as a prominent jaw or enlarged hands.

There is no universal "Black Box Warning" for all somatropin products; however, specific brands carry contraindications for use in patients with Prader-Willi Syndrome who are severely obese or have severe respiratory impairment. There have been reports of sudden death in these patients when starting somatropin therapy, likely due to sleep apnea or airway obstruction.

Report any unusual symptoms to your healthcare provider. Monitoring through regular blood tests and physical exams is a standard part of somatropin therapy.

Somatropin is a potent hormone that affects almost every system in the body. It should only be prescribed by specialists, such as pediatric or adult endocrinologists. Patients must be monitored regularly to ensure the dose is effective and safe. It is vital to disclose your full medical history, including any history of cancer, diabetes, or kidney disease, before starting treatment.

While not a formal "Black Box" on all labels, the FDA issues a high-level warning regarding Prader-Willi Syndrome (PWS). Somatropin is contraindicated in pediatric patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. Sudden deaths have been reported in these specific populations. All PWS patients should be evaluated for sleep apnea before starting therapy and monitored for respiratory infections during treatment.

• Neoplasm (Tumor) Risk: Somatropin should not be used if there is any evidence of active malignancy (cancer). If a tumor was the cause of the growth hormone deficiency, it must be stable and inactive before starting somatropin. Patients should be monitored for any new skin growths or changes in moles.
• Glucose Tolerance: Somatropin can decrease insulin sensitivity. Patients with diabetes or pre-diabetes may require adjustments to their insulin or oral medications. Blood glucose should be monitored regularly.
• Intracranial Hypertension: This condition (increased brain pressure) usually occurs within the first few weeks of therapy. Symptoms include headache, nausea, and vomiting. An eye exam (fundoscopy) is recommended before starting and periodically during treatment.
• Fluid Retention: Edema and carpal tunnel syndrome are common in adults. These are usually dose-dependent and may require a dose reduction.
• Hypoadrenalism: Somatropin may reduce the levels of cortisol in the body. Patients receiving glucocorticoid replacement therapy may need an increase in their steroid dose.

To ensure safety, your doctor will require the following tests:

• IGF-1 Levels: Measured every 3 to 6 months to guide dosing.
• Thyroid Function: T4 and TSH levels to check for induced hypothyroidism.
• Hemoglobin A1c / Fasting Glucose: To monitor for the development of diabetes.
• Bone Age X-rays: In children, to monitor the closure of growth plates.
• Fundoscopic Exams: To check for swelling behind the eyes.

Somatropin generally does not affect the ability to drive or operate machinery. However, if you experience visual changes or severe headaches (symptoms of intracranial hypertension), you should avoid these activities until cleared by a doctor.

There is no direct contraindication between alcohol and somatropin. However, alcohol can affect blood sugar levels and growth hormone secretion. It is best to limit alcohol consumption to maintain the metabolic benefits of the medication.

In children, somatropin is typically discontinued once the epiphyses (growth plates) have closed or when a satisfactory height has been reached. In adults, therapy may be lifelong. Stopping somatropin suddenly does not typically cause a withdrawal syndrome, but the metabolic benefits (such as improved energy and body composition) will gradually disappear.

> Important: Discuss all your medical conditions and any family history of cancer with your healthcare provider before starting Somatropin.

• Active Malignancy Therapy: Somatropin should not be used concurrently with active chemotherapy or radiation for cancer, as growth hormone can potentially stimulate the growth of malignant cells.
• Acute Critical Illness Medications: Somatropin is contraindicated in patients with acute critical illness due to complications following open-heart surgery, abdominal surgery, or multiple accidental trauma. Clinical trials showed a significant increase in mortality in these settings.

• Glucocorticoids (e.g., Prednisone, Hydrocortisone): These medications can inhibit the growth-promoting effects of somatropin. Conversely, somatropin may affect the metabolism of cortisol. Patients on steroid replacement for adrenal insufficiency may need their steroid doses adjusted upward.
• Insulin and Oral Antidiabetics (e.g., Metformin, Glyburide): Somatropin may decrease insulin sensitivity, leading to higher blood sugar. Diabetic patients must monitor their glucose closely, as their diabetes medication doses may need to be increased.
• Oral Estrogen: Oral estrogens (but not transdermal patches) can interfere with the liver's production of IGF-1 in response to somatropin. Women on oral estrogen replacement may require significantly higher doses of somatropin to achieve the same effect.

• Cytochrome P450 Substrates: Somatropin may induce the CYP3A4 enzyme system. This can lower the blood levels of drugs metabolized by this enzyme, such as certain anticonvulsants (cyclosporine) and sex steroids. Monitoring of these drug levels is recommended when starting or stopping somatropin.
• Thyroid Hormones: Somatropin can increase the conversion of T4 to T3. Patients on levothyroxine may need dose adjustments based on thyroid function tests.

• High-Sugar Diets: Consuming excessive sugar can worsen the insulin resistance potentially caused by somatropin. A balanced, low-glycemic diet is often recommended.
• Fasting: Somatropin is most effective when the body is in a metabolic state conducive to growth. While food doesn't affect absorption of the injection, overall nutrition is vital for the drug to work in children.

• St. John's Wort: May potentially interact with the CYP450 enzyme system, complicating the metabolism of other drugs used alongside somatropin.
• Anabolic Steroids: Using somatropin with other performance-enhancing supplements can lead to dangerous levels of tissue growth and metabolic strain. This combination should only be used under strict medical supervision for specific conditions like HIV wasting.

• Serum Phosphorus, Alkaline Phosphatase, and Magnesium: Levels of these minerals and enzymes may increase during somatropin therapy as a result of increased metabolic activity and bone growth. These changes are usually clinically insignificant.
• IGF-1 and IGFBP-3: These are the primary markers used to monitor somatropin efficacy; their levels will rise significantly during treatment.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, as somatropin can alter how your body processes other substances.

Somatropin must NEVER be used in the following circumstances:

• Active Neoplasia (Cancer): Because growth hormone stimulates cell division, it could cause a tumor to grow more rapidly. Any active malignancy must be excluded before starting therapy.
• Closed Epiphyses: In children, once the growth plates in the bones have fused (closed), somatropin can no longer increase height. Using it after closure can cause bone deformities (acromegaly).
• Acute Critical Illness: Patients in intensive care following major surgery, trauma, or with acute respiratory failure have a significantly increased risk of death if treated with somatropin.
• Proliferative Diabetic Retinopathy: This is a severe form of eye disease caused by diabetes. Somatropin can worsen the abnormal blood vessel growth in the retina.
• Hypersensitivity: Any known allergy to somatropin or any of the ingredients in the injection (such as metacresol or benzyl alcohol used as preservatives).

These conditions require a careful risk-benefit analysis by a specialist:

• Prader-Willi Syndrome with Obesity: Due to the risk of sudden death from airway obstruction.
• Pre-existing Diabetes: Requires intensive monitoring of blood glucose and medication adjustments.
• Scoliosis: Rapid growth can worsen the curvature of the spine.
• History of Childhood Cancer: Requires frequent monitoring for recurrence of the original tumor.

Patients who are allergic to E. coli-derived products should be cautious, as many somatropin brands are produced using E. coli expression systems. Additionally, some liquid formulations contain benzyl alcohol; these should be avoided in newborns (due to "gasping syndrome") and used with caution in patients with known alcohol sensitivities.

> Important: Your healthcare provider will evaluate your complete medical history, including family history and previous lab results, before prescribing Somatropin.

Somatropin is generally classified as Pregnancy Category C (under the older FDA system). There are no adequate and well-controlled studies in pregnant women. Animal reproduction studies have not shown evidence of fetal harm, but human data is limited. Somatropin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is typically discontinued during pregnancy unless the mother has severe, symptomatic growth hormone deficiency.

It is not known whether somatropin is excreted in human milk. However, because somatropin is a large protein molecule, it is unlikely that significant amounts would be absorbed intact by the nursing infant's digestive system. Caution should be exercised, and the decision to breastfeed while taking somatropin should be made in consultation with a healthcare provider.

Somatropin is most commonly used in the pediatric population. It is approved for use in infants, children, and adolescents, depending on the specific condition.

• Monitoring: Children require regular monitoring of height, weight, and bone age (via X-ray) to ensure the treatment is working.
• Psychological Impact: Growth hormone therapy involves daily injections for many years, which can be a significant burden for children and families.
• Conditions NOT approved: Somatropin is not approved for children who are of normal height but wish to be taller for athletic or aesthetic reasons.

Clinical studies of somatropin did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently than younger subjects. However, elderly patients are known to be more prone to the side effects of somatropin, particularly fluid retention, joint pain, and impaired glucose tolerance. Dosing for geriatric patients should be conservative, starting at the lowest possible dose.

In children with chronic kidney disease (CKD), somatropin is used to treat growth failure. Treatment should be discontinued at the time of renal transplantation. In adults with renal failure, the clearance of somatropin is reduced, which may theoretically increase the risk of side effects, though specific dose adjustments are not standardized.

Patients with severe liver disease (Child-Pugh Class C) may have a reduced ability to produce IGF-1 in response to somatropin. This can lead to "growth hormone resistance," where higher doses are needed to achieve a clinical response. Close monitoring of serum IGF-1 levels is essential in these patients.

> Important: Special populations require individualized medical assessment and more frequent laboratory monitoring.

Somatropin is a potent metabolic hormone that acts by binding to the Growth Hormone Receptor (GHR), a member of the class I cytokine receptor family. Upon binding, the GHR undergoes dimerization, activating the intracellular signaling protein Janus kinase 2 (JAK2). This triggers the phosphorylation of STAT5 (Signal Transducers and Activators of Transcription) proteins, which then migrate to the nucleus to regulate gene expression. The most significant result of this pathway is the synthesis of Insulin-like Growth Factor-1 (IGF-1). IGF-1 then acts on its own receptors (IGF-1R) to stimulate systemic cell growth, particularly in skeletal muscle and bone.

• Linear Growth: In children, somatropin stimulates the growth of the epiphyseal plates of long bones.
• Protein Metabolism: It increases the transport of amino acids into cells and enhances protein synthesis while decreasing protein oxidation.
• Carbohydrate Metabolism: Somatropin acts as an insulin antagonist; it suppresses the ability of insulin to stimulate glucose uptake in peripheral tissues and enhances glucose synthesis in the liver (gluconeogenesis).
• Lipid Metabolism: It stimulates the mobilization of lipids from fat stores, increasing the concentration of free fatty acids in the blood.

| Parameter | Value |

|---|---|

| Bioavailability | 70% - 90% (Subcutaneous) |

| Protein Binding | Minimal (GH-binding proteins exist but are not traditional albumin binding) |

| Half-life | 2 - 5 hours (Subcutaneous) |

| Tmax | 3 - 6 hours |

| Metabolism | Hepatic and Renal (proteolysis) |

| Excretion | Renal <1% (unchanged) |

• Molecular Formula: C990H1529N263O299S7
• Molecular Weight: ~22,125 Daltons
• Structure: A single-chain polypeptide consisting of 191 amino acid residues with two internal disulfide bridges.
• Solubility: Soluble in water and physiological saline solutions.

Somatropin is classified as a Recombinant Human Growth Hormone [EPC]. It is a member of the somatotropin agonist class. Related medications include various brands of somatropin and long-acting (pegylated) growth hormones like lonapegsomatropin.