Saizen: Uses, Dosage & Side Effects

What Is Saizen and What Is It Used For?

Saizen contains the active substance somatropin, a recombinant human growth hormone (rHGH) produced using recombinant DNA technology in mammalian cells. Somatropin is a single-chain polypeptide consisting of 191 amino acids with a molecular weight of approximately 22,124 daltons. Its amino acid sequence and three-dimensional structure are identical to those of endogenous human growth hormone (hGH), which is naturally synthesized and secreted by the somatotropic cells of the anterior pituitary gland. This structural identity ensures that Saizen exerts the same biological effects as the body’s own growth hormone.

Growth hormone plays a central role in human physiology, particularly during childhood and adolescence when it is essential for normal linear growth. However, its importance extends far beyond growth promotion. Growth hormone regulates a wide range of metabolic processes throughout life, including protein synthesis, lipid metabolism, carbohydrate homeostasis, and bone mineral metabolism. It exerts its effects both directly, through binding to growth hormone receptors (GHR) on target cells, and indirectly, through stimulating the production of insulin-like growth factor 1 (IGF-1), primarily in the liver. The growth hormone–IGF-1 axis is the principal hormonal system driving skeletal growth and is also involved in the maintenance of normal body composition, cardiovascular function, and overall metabolic health in adults.

When somatropin binds to the growth hormone receptor on the surface of target cells, it activates the Janus kinase–signal transducer and activator of transcription (JAK-STAT) signaling pathway, which triggers a cascade of intracellular events leading to gene transcription. In the liver, this results in the synthesis and secretion of IGF-1 and its principal binding protein, IGFBP-3. IGF-1 then acts on growth plate chondrocytes in the long bones, stimulating their proliferation and differentiation, which drives longitudinal bone growth. In addition to its growth-promoting effects, somatropin enhances protein synthesis (anabolic effect), stimulates lipolysis (breakdown of fat), reduces visceral adiposity, improves lean body mass, increases bone mineral density, and modulates carbohydrate metabolism by reducing insulin sensitivity.

Saizen is approved for use in the following clinical indications:

• Growth hormone deficiency (GHD) in children: For children who have inadequate endogenous growth hormone secretion, leading to growth failure. Diagnosis is confirmed through provocative growth hormone stimulation tests, assessment of growth velocity, bone age determination, and measurement of IGF-1 and IGFBP-3 levels. Children with GHD typically present with short stature significantly below the expected range for their age and sex, delayed bone age, and reduced growth velocity.
• Turner syndrome: For growth failure in girls and women with Turner syndrome (45,X karyotype or variants), a chromosomal disorder characterized by short stature, gonadal dysgenesis, and various other features. Growth hormone therapy in Turner syndrome aims to increase adult height, with studies demonstrating an average height gain of 5–8 cm compared with untreated patients.
• Chronic renal insufficiency (CRI): For growth failure in children with chronic kidney disease who have impaired renal function (before kidney transplantation). Growth retardation is common in CRI due to multiple factors including metabolic acidosis, malnutrition, renal osteodystrophy, and resistance to growth hormone. Somatropin therapy can significantly improve growth velocity in these patients.
• Small for gestational age (SGA): For children born small for gestational age (birth weight and/or length below –2 standard deviations for gestational age) who have not achieved catch-up growth by age 4 years or later. Approximately 10–15% of SGA children fail to achieve spontaneous catch-up growth, and growth hormone therapy has been shown to significantly improve their final adult height.
• Growth hormone deficiency in adults: As replacement therapy in adults with confirmed GHD, whether of childhood onset (after re-evaluation following completion of growth) or adult onset (due to hypothalamic-pituitary disease, surgery, irradiation, or trauma). In adults, GHD is associated with reduced quality of life, increased visceral adiposity, decreased lean body mass, reduced bone mineral density, adverse lipid profiles, and increased cardiovascular risk. Growth hormone replacement therapy aims to normalize these metabolic abnormalities and improve well-being.

The efficacy of Saizen has been demonstrated in numerous clinical trials across all approved indications. In children with GHD, treatment with somatropin typically results in a marked increase in growth velocity during the first year of therapy (often doubling or tripling the pre-treatment growth rate), with continued improvement in subsequent years. Long-term studies have shown that growth hormone therapy can enable children with GHD to achieve a final adult height within the normal range for their genetic potential. In adults with GHD, randomized controlled trials have demonstrated improvements in body composition (reduction in fat mass and increase in lean body mass), bone mineral density, lipid profiles, exercise capacity, and patient-reported quality of life measures.

What Should You Know Before Taking Saizen?

Contraindications

Saizen must not be used in the following situations:

• Active malignancy (tumors): Growth hormone therapy is contraindicated in patients with active malignant disease. Any pre-existing tumor must be inactive and anti-tumor therapy must be completed before starting somatropin treatment. Saizen should be discontinued if there is evidence of tumor recurrence or new tumor growth.
• Closed epiphyses (for growth promotion): In pediatric patients, somatropin should not be used for growth promotion once the epiphyseal growth plates have fused (closed), as linear growth is no longer possible. Bone age assessment should be performed before initiating treatment.
• Acute critical illness: Treatment with somatropin is contraindicated in patients experiencing acute critical illness due to complications following open heart surgery, abdominal surgery, multiple accidental trauma, or acute respiratory failure. Studies have shown increased mortality in critically ill adult patients treated with high-dose growth hormone in intensive care settings.
• Active proliferative or severe non-proliferative diabetic retinopathy: Somatropin should not be initiated in patients with active proliferative or severe non-proliferative diabetic retinopathy due to the potential risk of worsening retinal disease.
• Hypersensitivity: Do not use Saizen if you are allergic to somatropin or any of the excipients in the formulation.

Warnings and Precautions

Before and during treatment with Saizen, the following precautions should be observed:

• Diabetes and glucose metabolism: Somatropin reduces insulin sensitivity and can cause hyperglycemia. Patients with pre-existing diabetes mellitus, impaired glucose tolerance, or risk factors for diabetes should have their blood glucose monitored regularly. Insulin doses or doses of oral hypoglycemic agents may need adjustment when somatropin therapy is initiated or the dose is changed. In previously non-diabetic patients, fasting glucose and HbA1c should be monitored periodically.
• Thyroid function: Growth hormone treatment can unmask previously undiagnosed central (secondary) hypothyroidism and may reduce T4 to T3 conversion, potentially lowering free T4 levels. Thyroid function should be tested before starting therapy and monitored regularly (every 6–12 months) during treatment. Untreated hypothyroidism can impair the response to somatropin therapy, so adequate thyroid hormone replacement is essential for optimal growth outcomes.
• Adrenal insufficiency: Patients receiving replacement therapy for adrenal insufficiency (e.g., with cortisol or hydrocortisone) may require an increase in their maintenance or stress doses following initiation of somatropin therapy, as growth hormone may reduce the conversion of cortisone to cortisol. Previously undiagnosed central adrenal insufficiency may be unmasked.
• Scoliosis: Scoliosis is known to progress more rapidly during periods of rapid growth. Since somatropin increases growth rate, patients with a history of scoliosis or risk factors for scoliosis should be monitored for progression during treatment. This is particularly relevant in patients with Turner syndrome, who have an increased prevalence of scoliosis.
• Slipped capital femoral epiphysis (SCFE): Children treated with growth hormone are at increased risk of developing slipped capital femoral epiphysis, particularly during rapid growth phases. Any child receiving somatropin who develops a limp, hip or knee pain, or reduced hip mobility should be evaluated promptly for SCFE.
• Intracranial lesions: In patients with growth hormone deficiency secondary to an intracranial lesion (e.g., pituitary tumor), regular imaging should be performed to monitor for tumor recurrence or progression.
• Injection site rotation: Injection sites should be rotated to prevent lipohypertrophy (local accumulation of fat) or lipoatrophy (local loss of fat tissue), which can impair drug absorption.
• Pancreatitis: Although rare, pancreatitis has been reported in children and adolescents receiving somatropin. Children who develop abdominal pain should be evaluated for pancreatitis.

Drug Interactions

Several classes of medications can interact with somatropin therapy. These interactions are primarily pharmacodynamic in nature, meaning they affect the clinical response to growth hormone rather than altering its blood levels. The following table summarizes the key drug interactions:

Pregnancy and Breastfeeding

There are no adequate and well-controlled studies of somatropin use in pregnant women. Animal reproduction studies have not demonstrated evidence of harm to the fetus, but animal studies are not always predictive of human response. As a precaution, Saizen should not be used during pregnancy unless clearly necessary, and the potential benefits must be weighed against the potential risks to the fetus. Women of childbearing potential should use effective contraception during treatment.

It is not known whether somatropin is excreted in human breast milk. Although large molecular weight proteins like somatropin are unlikely to be absorbed intact from the infant’s gastrointestinal tract, caution should be exercised when Saizen is administered to a breastfeeding woman. The decision to continue or discontinue breastfeeding or somatropin therapy should be made in consultation with the treating physician, considering the benefit of breastfeeding for the child and the benefit of therapy for the mother.

Driving and Operating Machinery

Saizen has no known effect on the ability to drive or operate machinery. Based on its pharmacological profile and known side effects, somatropin is not expected to impair these abilities. However, patients should be aware that transient side effects such as headache or visual disturbances (which may occur in the context of benign intracranial hypertension) could theoretically affect their ability to drive or use machines safely.

How Does Saizen Interact with Other Drugs?

Unlike many conventional small-molecule drugs, somatropin is a large protein hormone that is not metabolized by the cytochrome P450 (CYP) enzyme system in the liver. As a result, somatropin does not directly affect the metabolism of other drugs through traditional pharmacokinetic pathways. However, somatropin has significant pharmacodynamic interactions with several medication classes, meaning it can alter the clinical effects or requirements of concomitant therapies through its physiological actions on metabolism, hormonal axes, and tissue growth.

Understanding these interactions is critical for optimizing treatment outcomes and avoiding adverse effects, particularly in patients who require multiple concomitant medications, which is common in conditions such as Turner syndrome, chronic renal insufficiency, or adult GHD with multiple pituitary hormone deficiencies.

The interaction between corticosteroids and somatropin is of particular clinical importance in children. Glucocorticoids, even at replacement doses, can significantly attenuate the growth-promoting effects of somatropin. In patients requiring concomitant glucocorticoid replacement (such as those with multiple pituitary hormone deficiencies or adrenal insufficiency), the glucocorticoid dose should be carefully optimized to the minimum effective level. Hydrocortisone is generally preferred over longer-acting synthetic glucocorticoids (such as prednisolone or dexamethasone) for replacement therapy, as it allows more precise dose titration and has a shorter duration of action.

The interaction with oral estrogens is clinically relevant in adolescent and adult females, particularly those with Turner syndrome who require estrogen replacement for pubertal development and bone health. Oral estrogens exert a significant first-pass effect on the liver, increasing the production of growth hormone-binding protein (GHBP) and suppressing hepatic IGF-1 generation. This can reduce the efficacy of somatropin therapy by 30–50%. Transdermal estrogen delivery bypasses the hepatic first-pass effect and preserves the somatropin response, making it the preferred route of estrogen administration in women receiving growth hormone therapy.

What Is the Correct Dosage of Saizen?

Saizen should always be used exactly as prescribed by your doctor. The dosage is individualized based on the specific clinical indication, the patient’s body weight or body surface area, clinical response, and serum IGF-1 levels. Growth hormone therapy requires ongoing dose adjustments to optimize efficacy while minimizing the risk of adverse effects. Treatment is typically initiated and supervised by a specialist in endocrinology or pediatric endocrinology.

Saizen is administered as a subcutaneous injection once daily, preferably in the evening to mimic the body’s natural pulsatile secretion pattern of growth hormone, which peaks during sleep. The injection can be given in the thigh, abdomen, buttocks, or upper arm, and the injection site should be rotated regularly to prevent local tissue reactions such as lipohypertrophy.

Injection Devices

Saizen is available in pre-filled cartridges designed for use with compatible injection devices:

• easypod auto-injector: An electronic auto-injector that automatically injects the prescribed dose. The easypod features built-in adherence monitoring capabilities, recording the date, time, and dose of each injection. This data can be shared with the healthcare team via the easypod connect platform, enabling remote monitoring of treatment adherence and facilitating clinical decision-making. The device is particularly beneficial for pediatric patients and their families.
• aluetta pen: A reusable pen injector designed for manual dose selection and injection. The aluetta pen offers precise dose selection and a user-friendly design suitable for patients who prefer a manual injection device.

Before self-injecting for the first time, patients (or their caregivers) should receive thorough training from a healthcare professional on the correct use of the chosen injection device, proper injection technique, and safe sharps disposal.

Missed Dose

If you miss a dose of Saizen, administer it as soon as you remember, provided it is not close to the time of your next scheduled dose. Do not inject a double dose to compensate for a missed injection. Simply continue with your regular dosing schedule the following day. If you frequently forget doses, consider setting a daily alarm or using the easypod auto-injector, which provides dose reminders and adherence tracking. Consistent daily administration is important for achieving optimal treatment outcomes, as irregular dosing can reduce the overall growth response.

Overdose

Acute overdose of somatropin may initially lead to hypoglycemia (low blood sugar) followed by hyperglycemia (high blood sugar). Long-term overdosage could result in signs and symptoms consistent with the known effects of excess human growth hormone, including features of acromegaly (enlarged hands, feet, and facial features), fluid retention, and joint pain. If overdose is suspected, treatment should be discontinued temporarily and supportive care provided. There is no specific antidote for somatropin overdose. Contact your doctor or seek medical attention promptly if you believe you have administered too much Saizen.

What Are the Side Effects of Saizen?

Like all medicines, Saizen can cause side effects, although not everybody who takes it will experience them. The side effects of somatropin therapy are generally dose-dependent and can often be managed by dose reduction. Many side effects are more common in adults than in children, particularly those related to fluid retention. The safety profile of Saizen has been established through extensive clinical trials and decades of post-marketing surveillance.

It is important to distinguish between side effects that are expected and manageable (such as mild injection site reactions) and those that require prompt medical attention (such as symptoms of intracranial hypertension or signs of tumor recurrence). Patients and caregivers should be educated about warning signs that necessitate immediate consultation with their healthcare provider.

Injection site reactions are the most frequently reported side effects with Saizen. These typically include mild to moderate pain, redness, or swelling at the injection site and usually resolve within a few days. Rotating injection sites between the thigh, abdomen, buttocks, and upper arm can help minimize these reactions. If persistent lipohypertrophy (local fat accumulation) develops at an injection site, that site should be avoided as it can impair drug absorption.

Fluid retention-related side effects, including peripheral edema, joint stiffness, arthralgia, myalgia, and paresthesia, are more common in adults than in children and are typically dose-dependent. These effects are generally mild, reversible, and respond to dose reduction. They are more likely to occur at the start of treatment or after a dose increase, and they tend to diminish over time as the body adapts to therapy.

Carpal tunnel syndrome may develop in adult patients receiving somatropin, presenting as numbness, tingling, and pain in the hand and wrist. This is related to fluid retention and soft tissue swelling. The condition usually resolves with dose reduction or temporary treatment interruption. If symptoms persist, surgical release may be considered in severe cases.

Regarding the risk of malignancy, extensive epidemiological studies and post-marketing surveillance data spanning several decades have not established a causal link between growth hormone therapy and an increased overall cancer risk in patients without pre-existing risk factors. However, patients with a prior history of cancer should be monitored for recurrence. The safety surveillance of recombinant growth hormone therapy continues through registries and long-term follow-up studies.

How Should You Store Saizen?

Proper storage of Saizen is essential to maintain the potency, safety, and quality of the medication. As a protein-based biologic, somatropin is sensitive to temperature extremes, light, and physical agitation, all of which can compromise its molecular structure and reduce its therapeutic effectiveness.

Follow these storage guidelines carefully:

• Before first use: Store Saizen cartridges in the refrigerator at 2–8 °C (36–46 °F). Keep the cartridges in the outer packaging to protect from light. Do not freeze Saizen – freezing will damage the protein and render the medication ineffective. If a cartridge has been accidentally frozen, do not use it.
• After first use: Once a cartridge has been loaded into the injection device and the first dose has been administered, the cartridge should be stored in the refrigerator at 2–8 °C and used within 28 days. Keep the cartridge installed in the injection device and protect it from light. Do not use the cartridge beyond 28 days after the first injection, even if solution remains.
• Temporary room temperature storage: Saizen cartridges (both before and after first use) may be stored at temperatures up to 25 °C (77 °F) for a single period of no more than 7 days. After 7 days at room temperature, the cartridge must be discarded. Do not return a cartridge that has been stored at room temperature back to the refrigerator.
• Inspection before use: Before each injection, visually inspect the solution. It should be clear and colorless. Do not use the cartridge if the solution is cloudy, discolored, or contains particles. Do not use the cartridge if it appears damaged, has been frozen, or has passed its expiration date.
• Keep out of reach of children: Store Saizen and all injection equipment in a secure location inaccessible to children.
• Disposal: Used needles and empty cartridges should be placed in an approved sharps disposal container. Do not dispose of needles or cartridges in household waste. Ask your pharmacist about local disposal options for sharps containers.

When traveling with Saizen, use an insulated cooling bag with ice packs to maintain refrigerated temperatures. Avoid exposing the medication to direct sunlight, excessive heat, or freezing temperatures. Carry Saizen in your hand luggage when flying to avoid exposure to extreme temperatures in the cargo hold. Airport security x-ray screening does not affect the medication.

What Does Saizen Contain?

Understanding the composition of Saizen is important for patients with known allergies or sensitivities to pharmaceutical ingredients. Below is a detailed breakdown of the formulation.

Active Ingredient

The active substance is somatropin, a recombinant human growth hormone (rHGH). Somatropin is a 191-amino acid polypeptide with a molecular weight of approximately 22,124 daltons. It is produced using recombinant DNA technology and is structurally identical to the growth hormone naturally produced by the human pituitary gland.

• 6 mg cartridge: Contains 6 mg somatropin in 1.03 mL of solution (concentration: 5.83 mg/mL)
• 12 mg cartridge: Contains 12 mg somatropin in 1.50 mL of solution (concentration: 8 mg/mL)
• 20 mg cartridge: Contains 20 mg somatropin in 2.50 mL of solution (concentration: 8 mg/mL)

Inactive Ingredients (Excipients)

Appearance and Pack Sizes

Saizen solution for injection is supplied as a clear and colorless solution in glass cartridges designed for use with the easypod auto-injector or aluetta pen. The cartridges are available in three sizes: 6 mg (1.03 mL), 12 mg (1.50 mL), and 20 mg (2.50 mL). Each cartridge is intended for multiple-dose use and contains the preservative phenol to maintain sterility during the in-use period of up to 28 days. Not all cartridge sizes may be marketed in every country.

Marketing Authorization Holder and Manufacturer

Saizen is manufactured and marketed by Merck Serono (a division of Merck KGaA, Darmstadt, Germany). Merck Serono is a global leader in growth hormone therapy and has been producing somatropin products for clinical use since the late 1980s. Saizen is approved and available in numerous countries worldwide across Europe, Asia, Latin America, and other regions.