PRESCRIBING INFORMATION

Ngenla®▼ (somatrogon)

Please refer to full Summary of Product Characteristics (SmPC) before prescribing Ngenla®. Presentation: Solution for injection in pre-filled pen containing 24 mg (20 mg/ml) or 60 mg (50 mg/ml) somatrogon in 1.2 mL solution. Indications: For the treatment of children and adolescents from 3 years of age with growth disturbance due to insufficient secretion of growth hormone. Dosage: Treatment should be initiated and monitored by physicians who are qualified and experienced in the diagnosis and management of paediatric patients with growth hormone deficiency (GHD). Posology: The recommended dose is 0.66 mg/kg body weight administered once weekly by subcutaneous injection. Each pre-filled pen is capable of setting and delivering the dose prescribed by the physician. Dose may be rounded up or down based on the physician’s expert knowledge of the individual patient needs. When doses higher than 30 mg are needed (i.e. bodyweight > 45 kg), two injections have to be administered. Starting dose for patients switching from daily growth hormone medicinal products: For patients switching from daily growth hormone medicinal products, the weekly therapy with somatrogon may be initiated at a dose of 0.66 mg/kg/week on the day following their last daily injection. Dose titration: Somatrogon dose may be adjusted as necessary, based on growth velocity, adverse reactions, body weight and serum insulin-like growth factor 1 (IGF-1) concentrations. When monitoring for IGF-1, samples should always be drawn 4 days after the prior dose. Dose adjustments should be targeted to achieve average IGF-1 standard deviation score (SDS) levels in the normal range, i.e. between -2 and +2 (preferably close to 0 SDS). In patients whose serum IGF-1 concentrations exceed the mean reference value for their age and sex by more than 2 SDS, the dose of somatrogon should be reduced by 15%. More than one dose reduction may be required in some patients. Treatment evaluation and discontinuation: Evaluation of efficacy and safety should be considered at approximately 6 to 12 month intervals and may be assessed by evaluating auxological parameters, biochemistry (IGF-1, hormones, glucose levels) and pubertal status. Routine monitoring of serum IGF-1 SDS levels throughout the course of treatment is recommended. More frequent evaluations should be considered during puberty. Treatment should be discontinued when there is evidence of closure of the epiphyseal growth plates. Treatment should also be discontinued in patients having achieved final height or near final height, i.e. an annualised height velocity < 2 cm/year or a bone age > 14 years in girls or > 16 years in boys. Missed dose: Patients should maintain their regular dosing day. If a dose is missed, somatrogon should be administered as soon as possible within 3 days after the missed dose, and then the usual once weekly dosing schedule should be resumed. If more than 3 days have passed, the missed dose should be skipped and the next dose should be administered on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule. Changing the dosing day: The day of weekly administration can be changed if necessary as long as the time between two doses is at least 3 days. After selecting a new dosing day, the once weekly dosing should be continued. Special populations: Elderly: The safety and efficacy of somatrogon in patients over the age of 65 years have not been established. No data are available. Renal impairment: Somatrogon has not been studied in patients with renal impairment. No dose recommendation can be made. Hepatic impairment: Somatrogon has not been studied in patients with hepatic impairment. No dose recommendation can be made. Paediatric population: The safety and efficacy of somatrogon in neonates, infants and children less than 3 years of age have not yet been established. No data are available. Method of administration: Somatrogon is administered by subcutaneous injection. Somatrogon is to be injected in the abdomen, thighs, buttocks or upper arms. The site of injection should be rotated at each administration. Injections to the upper arms and buttocks should be given by the caregiver. The patient and caregiver should receive training to ensure understanding of the administration procedure to support self-administration. If more than one injection is required to deliver a complete dose, each injection should be administered at a different injection site. Somatrogon is to be administered once weekly, on the same day each week, at any time of the day. See the SmPC and package leaflet for instructions on how to prepare the medicinal product before administration. 
Contra-indications: Hypersensitivity to somatrogon or to any of the excipients. Somatrogon must not be used when there is any evidence of activity of a tumour based on experience with daily growth hormone medicinal products. Intracranial tumours must be inactive and antitumour therapy must be completed prior to starting growth hormone (GH) therapy. Treatment should be discontinued if there is evidence of tumour growth. Somatrogon must not be used for growth promotion in children with closed epiphyses. Patients with acute critical illness suffering complications following open heart surgery, abdominal surgery, multiple accidental trauma, acute respiratory failure or similar conditions must not be treated with somatrogon (regarding patients undergoing substitution therapy, see the SmPC). Warnings and Precautions: Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Hypersensitivity: If a serious hypersensitivity reaction occurs, use of somatrogon should be immediately discontinued; patients should be treated promptly per standard of care and monitored until signs and symptoms resolve. Hypoadrenalism: Patients should be monitored for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism. Thyroid function impairment: Growth hormone increases the extrathyroidal conversion of T4 to T3 and may unmask incipient hypothyroidism. Patients with pre-existing hypothyroidism should be treated accordingly prior to the initiation of treatment with somatrogon as indicated based on clinical evaluation. As hypothyroidism interferes with the response to growth hormone therapy, patients should have their thyroid function tested regularly and should receive replacement therapy with thyroid hormone when indicated. Prader-Willi syndrome: Somatrogon has not been studied in patients with Prader-Willi syndrome. Somatrogon is not indicated for the long-term treatment of paediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome unless they also have a diagnosis of GHD. Glucose metabolism impairment: Additional monitoring should be considered in patients treated with somatrogon who have glucose intolerance, or additional risk factors for diabetes. In patients treated with somatrogon who have diabetes mellitus, hypoglycaemic medicinal products might require adjustment. Neoplasm: In patients with previous malignant disease, special attention should be given to signs and symptoms of relapse. Patients with pre-existing tumours or growth hormone deficiency secondary to an intracranial lesion should be examined routinely for progression or recurrence of the underlying disease process. Benign intracranial hypertension: Funduscopic examination is recommended at the initiation of treatment and as clinically warranted. In patients with clinical or funduscopic evidence of IH, somatrogon should be temporarily discontinued. At present there is insufficient evidence to give specific advice on the continuation of growth hormone treatment in patients with resolved IH. If treatment with somatrogon is restarted, monitoring for signs and symptoms of IH is necessary. Acute critical illness: In critically ill adult patients suffering complications following open heart surgery, abdominal surgery, multiple accidental trauma or acute respiratory failure mortality was higher in patients treated with 5.3 mg or 8 mg somatropin daily (i.e. 37.1 – 56 mg/week) compared to patients receiving placebo, 42% vs. 19%. Based on this information, these types of patients should not be treated with somatrogon. As there is no information available on the safety of growth hormone substitution therapy in acutely critically ill patients, the benefits of continued somatrogon treatment in this situation should be weighed against the potential risks involved. In all patients developing other or similar acute critical illness, the possible benefit of treatment with somatrogon must be weighed against the potential risk involved. Pancreatitis: Although rare in patients treated with growth hormone medicinal products, pancreatitis should be considered in somatrogon-treated patients who develop severe abdominal pain during treatment. Scoliosis: Because somatrogon increases growth rate, signs of development or progression of scoliosis should be monitored during treatment. Epiphyseal disorders: Epiphyseal disorders, including slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders or in patients undergoing rapid growth. Any paediatric patient with the onset of a limp or complaints of hip or knee pain during treatment should be carefully evaluated. Oral oestrogen therapy: Oral oestrogen influences the IGF-1 response to growth hormone. If a female patient taking somatrogon begins or discontinues oral oestrogen containing therapy, IGF-1 value should be monitored to determine if the dose of growth hormone should be adjusted to maintain the serum IGF-1 levels within the normal range. Excipients: Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium free.’ Metacresol: Myositis is a very rare adverse event that may be related to the preservative metacresol. In the case of myalgia or disproportionate pain at injection site, myositis should be considered and if confirmed, other growth hormone medicinal products without metacresol should be used. Drug Interactions: No interactions studies in paediatrics have been performed. Glucocorticoids: Concomitant treatment with glucocorticoids may inhibit the growth-promoting effects of somatrogon. Patients with adrenocorticotropic hormone (ACTH) deficiency should have their glucocorticoid replacement therapy carefully adjusted to avoid any inhibitory effect on growth. Therefore, patients treated with glucocorticoids should have their growth monitored carefully to assess the potential impact of glucocorticoid treatment on growth. Growth hormone decreases the conversion of cortisone to cortisol and may unmask previously undiscovered central hypoadrenalism or render low glucocorticoid replacement doses ineffective. Insulin and hypoglycaemic medicinal products: In patients with diabetes mellitus requiring medicinal product therapy, the dose of insulin and/or oral/injectable hypoglycaemic medicinal products may require adjustment when somatrogon therapy is initiated. Thyroid medicinal products: Treatment with daily growth hormone may unmask previously undiagnosed or subclinical central hypothyroidism. Thyroxine replacement therapy may need to be initiated or adjusted. Oral oestrogen therapy: In female patients on oral oestrogen-containing therapy, a higher dose of somatrogon may be required to achieve the treatment goal. Cytochrome P450 metabolised products: Drug-drug interaction studies have not been performed with somatrogon. Somatrogon has been shown to induce CYP3A4 mRNA expression in vitro. The clinical significance of this is unknown. The clearance of compounds metabolised by CYP3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and ciclosporin) may be increased and could result in lower exposure of these compounds. Fertility, pregnancy, and lactation: Pregnancy: There are no data from the use of somatrogon in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Ngenla is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding: It is unknown whether somatrogon/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from somatrogon therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility: The risk of infertility in females or males of reproductive potential has not been studied in humans. In a rat study, the fertility in males and females was not affected. Driving and operating machinery: Ngenla has no or negligible influence on the ability to drive and use machines. Side Effects: The commonly reported adverse reactions after treatment with somatrogon are injection site reactions (ISRs) (25.1%), headache (10.7%) and pyrexia (10.2%). Injection site reaction (ISR): In the phase 3 clinical study, reporting of ISRs was actively solicited during the course of the study. In the majority of cases, local ISRs tended to be transient, occurred mainly in the first 6 months of treatment and were mild in severity; ISRs had a mean onset on the day of the injection and a mean duration of < 1 day. Among them, injection site pain, erythema, pruritus, swelling, induration, bruising, hypertrophy, inflammation and warmth were reported in 43.1% of patients treated with somatrogon compared to 25.2% of patients administered daily injections of somatropin. In the long-term OLE of the clinical phase 3 study, local ISRs were similar in nature and severity, and reported early in subjects switching from somatropin to somatrogon treatment. ISRs were reported in 18.3% of patients originally treated with somatrogon in the main study and continuing treatment in the OLE portion of the study, and likewise, 37% were reported among patients originally treated with somatropin that were switched in the OLE portion of the study to treatment with somatrogon. Immunogenicity: In the pivotal safety and efficacy study, among 109 subjects treated with somatrogon, 84 (77.1%) tested positive for anti-drug antibodies (ADAs). There were no clinical or safety effects observed with the formation of antibodies. Refer to SmPC for further information on side effects. Special precaution for storage: Store in a refrigerator (2 °C to 8 °C). Do not freeze. Keep Ngenla in the outer carton in order to protect from light. Refer to SmPC for storage conditions after first use of the medicinal product. Legal Category: S1A. Package Quantities, Marketing Authorisation Numbers: Ngenla 24 mg solution for injection in pre-filled pen, 1 pre-filled pen EU/1/21/1617/001; Ngenla 60 mg solution for injection in pre-filled pen, 1 pre-filled pen, EU/1/21/1617/002. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. Date of revision: 11/2022. Ref: NL 2_0 IE.

For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or [email protected]. For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building, 9 Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 4676500

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Refer to section 4.8 of the SmPC for how to report adverse reactions.

Ngenla▼ Prescribing Information