Genotropin (somatropin, rbe) Prescribing Information

Genotropin® (somatropin, rbe)

Abbreviated Prescribing Information

Genotropin 5.3 mg Pre-filled pen (GoQuick)
Genotropin 12 mg Pre-filled pen (GoQuick)
Genotropin 5.3 mg Two chamber cartridge
Genotropin 12 mg Two chamber cartridge
Genotropin MiniQuick 0.2 mg
Genotropin MiniQuick 0.4 mg
Genotropin MiniQuick 0.6 mg
Genotropin MiniQuick 0.8 mg
Genotropin MiniQuick 1 mg
Genotropin MiniQuick 1.2 mg
Genotropin MiniQuick 1.4 mg
Genotropin MiniQuick 1.6 mg
Genotropin MiniQuick 1.8 mg
Genotropin MiniQuick 2 mg

Please refer to the SmPC before prescribing Genotropin

Presentation

Genotropin Pre-filled Pen (GoQuick): Two-chamber cartridge sealed in a disposable multidose pre-filled pen GoQuick. The cartridges contain either 5.3 mg or 12 mg somatropin (rbe). Each cartridge also contains 0.3% metacresol as preservative.

The 5.3 mg pre-filled pen GoQuick is colour coded blue. The 12 mg pre-filled pen GoQuick is colour coded purple.

Genotropin Cartridge: Two-chamber cartridge for use in a re-useable injection device, Genotropin pen, or in a reconstitution device. The cartridges contain either 5.3 mg or 12 mg somatropin (rbe). Each cartridge also contains 0.3% metacresol as preservative.

The Genotropin Pens are colour coded, and must be used with the matching colour coded Genotropin two-chamber cartridge to give the correct dose. The Genotropin Pen 5.3 (blue) must be used with Genotropin 5.3 mg cartridge (blue). The Genotropin Pen 12 (purple) must be used with Genotropin 12 mg cartridge (purple).

Instruction on reconstitution plus use of devices is supplied separately as are the Pen and Genotropin Mixer devices and any necessary consumables.

Genotropin MiniQuick: Two compartment cartridge in single dose syringe containing powder and solvent for injection together with an injection needle.

Each device contains either 0.2 mg, 0.4 mg, 0.6 mg, 0.8 mg, 1 mg, 1.2 mg, 1.4 mg, 1.6 mg, 1.8 mg or 2 mg somatropin (rbe).

Indications

Children: Treatment of growth disturbance due to insufficient secretion of growth hormone (growth hormone deficiency, GHD) and growth disturbance associated with Turner Syndrome or chronic renal insufficiency or in short children born Small for Gestational Age (SGA) with a birth weight and/or length below –2SD, who failed to show catch-up growth by 4 years of age or later.

Prader-Willi syndrome (PWS), for improvement of growth and body composition. The diagnosis of PWS should be confirmed by appropriate genetic testing.

Adults: Replacement therapy in adults with pronounced GH deficiency.

Adult onset: Patients who have severe growth hormone deficiency associated with multiple hormone deficiencies as a result of known hypothalamic or pituitary pathology and who have at least one known deficiency of pituitary hormone not being prolactin.

Childhood Onset: Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.

Dosage and Administration

Dose should be personalised for each individual.  The subcutaneous injection site should be varied to prevent lipoatrophy.

Insufficient Secretion of GH in children: 0.025 - 0.035 mg/kg body weight per day or 0.7 - 1.0 mg/m² body surface area per day is recommended. Higher doses have been used.

Where childhood onset GHD persists into adolescence, treatment should be continued to achieve full somatic development (e.g. body composition, bone mass).

For monitoring, the attainment of a normal peak bone mass defined as a T score > –1 (i.e. standardized to average adult peak bone mass measured by dual energy X-ray absorptiometry taking into account sex and ethnicity) is one of the therapeutic objectives during the transition period.

Prader-Willi Syndrome:  0.035 mg/kg body weight per day or 1.0 mg/m2 body surface area per day.  Daily doses of 2.7 mg should not be exceeded.

Gonadal Dysgenesis (Turner Syndrome): 0.045 - 0.050 mg/kg body weight per day or 1.4 mg/m² body surface area per day is recommended.

CRI:  A dose of 0.045 - 0.050 mg/kg body weight per day (1.4 mg/m² body surface area per day) is recommended.  Higher doses can be needed if growth velocity is too low. Dose correction can be needed after 6 months treatment.

Short children born SGA:  0.035 mg/kg body weight per day (1 mg/m² body surface area per day) until final height is reached.

GH Deficient Adults: In patients who continue growth hormone therapy after childhood GHD, the recommended dose to restart is 0.2 – 0.5 mg per day. The dose should be gradually increased or decreased according to individual patient requirements as determined by the IGF-I concentration.

In patients with adult-onset GHD, start with low dose, 0.15 – 0.3 mg/day. The dose should be gradually increased as determined by the IGF-1 concentration. Clinical response and side effects may guide dose titration.

It is recognised that there are patients with GHD who do not normalize IGF-I levels despite a good clinical response, and thus do not require dose escalation.

The maintenance dose seldom exceeds 1.0 mg per day. Women may require higher doses than men, with men showing an increasing IGF-I sensitivity over time. This means that there is a risk that women, especially those on oral oestrogen replacement are under-treated while men are over-treated. The accuracy of the growth hormone dose should therefore be controlled every 6 months.

As normal physiological growth hormone production decreases with age, dose requirements are reduced. In patients above 60 years, therapy should start with a dose of 0.1 - 0.2 mg per day and should be slowly increased according to individual patient requirements. The minimum effective dose should be used. The maintenance dose in these patients seldom exceeds 0.5 mg per day.

Contra-indications

Hypersensitivity to the active substance or to any of the excipients. Somatropin must not be used when there is any evidence of activity of a tumour. Intracranial tumours must be inactive and antitumour therapy must be completed prior to starting growth hormone therapy. Treatment should be discontinued if there is evidence of tumour growth.  Genotropin should 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 should not be treated with Genotropin.

Special warnings and precautions

Diagnosis and therapy should be initiated and monitored by suitably qualified and experienced doctors. 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, a Genotropin presentation without metacresol should be used.

The maximum recommended daily dose should not be exceeded. Somatropin may reduce insulin sensitivity and in some patients induce diabetes mellitus. For patients with diabetes mellitus, the insulin dose may require adjustment after somatropin therapy is instituted. Patients with diabetes, glucose intolerance, or additional risk factors for diabetes should be monitored closely during somatropin therapy.

As thyroid function may be affected, monitoring of thyroid function should be conducted in all patients. In patients with hypopituitarism on standard replacement therapy, the potential effect of growth hormone treatment on thyroid function must be closely monitored.

Introduction of somatropin treatment may result in inhibition of 11βHSD-1 and reduced serum cortisol concentrations. In patients treated with somatropin, previously undiagnosed central (secondary) hypoadrenalism may be unmasked and glucocorticoid replacement may be required. In addition, patients treated with glucocorticoid replacement therapy for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses, following initiation of somatropin treatment. 

If a woman taking somatropin begins oral oestrogen therapy, the dose of somatropin may need to be increased to maintain the serum IGF-1 levels within the normal age-appropriate range. Conversely, if a woman on somatropin discontinues oral oestrogen therapy, the dose of somatropin may need to be reduced to avoid excess of growth hormone and/or side effects.

Signs of any relapse of malignant disease should be monitored. In childhood cancer survivors, an increased risk of a second neoplasm has been reported in patients treated with somatropin after their first neoplasm. Intracranial tumours, in particular meningiomas, in patients treated with radiation to the head for their first neoplasm, were the most common of these second neoplasms.

In patients with endocrine disorders, slipped epiphyses of the hip may occur more frequently than in the general population. Children limping during treatment with somatropin, should be examined clinically.

In case of severe or recurrent headache, visual problems, nausea and/or vomiting, a funduscopy for papilloedema is recommended as some rare cases of benign intracranial hypertension have been reported and if appropriate treatment should be discontinued.

Leukaemia has been reported in a small number of growth hormone deficiency patients, some of whom have been treated with somatropin. However, there is no evidence that leukaemia incidence is increased in growth hormone recipients without predisposition factors.

As with all somatropin containing products, a small percentage of patients may develop antibodies to Genotropin. The binding capacity of these antibodies is low and there is no effect on growth rate. Testing for antibodies to somatropin should be carried out in any patient with otherwise unexplained lack of response.

Experience in patients above 80 years is limited. Elderly patients may be more sensitive to the action of Genotropin, and therefore may be more prone to develop adverse reactions.

In acute, critically ill adult patients, GH may increase mortality these types of patients should not be treated with GENOTROPIN. As there is no information available on the safety of growth hormone substitution therapy in acutely critically ill patients, the benefits of continued treatment in this situation should be weighed against the potential risks involved.

Although rare, pancreatitis should be considered in somatropin-treated patients, especially children who develop abdominal pain.

In patients with Prader-Willi syndrome, treatment should always be in combination with a calorie-restricted diet. There have been reports of fatalities associated with the use of growth hormone in paediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity (those patients exceeding a weight/height of 200%), history of respiratory impairment or sleep apnoea, or unidentified respiratory infection. Patients with one or more of these factors may be at increased risk. Before initiation of treatment with somatropin in patients with Prader-Willi syndrome, signs for upper airway obstruction, sleep apnoea, or respiratory infections should be assessed. Patients should be monitored for signs of respiratory infections, which should be diagnosed as early as possible and treated aggressively. All patients with Prader-Willi syndrome should also have effective weight control before and during growth hormone treatment. Scoliosis is common in PWS and signs for scoliosis should be monitored. Experience of prolonged therapy in adults and patients with PWS is limited.

In short children born SGA other medical reasons or treatments that could explain growth disturbance should be ruled out before starting treatment. In SGA children it is recommended to measure the IGF-I level before start of treatment and twice a year thereafter. Not recommended to initiate treatment in SGA patients near onset of puberty. Some of the height gain obtained with treating short children born SGA with growth hormone may be lost if treatment is stopped before final height is reached.

In CRI, renal function should be below 50% of normal before institution of therapy and growth should be followed for a year preceding institution of therapy. Conservative treatment for renal insufficiency should have been established and be maintained during therapy. Discontinue GH after renal transplantation.

Interactions:

Concomitant treatment with glucocorticoids inhibits the growth-promoting effects of somatropin containing products. 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. 

The clearance of compounds metabolised by cytochrome P450 3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and ciclosporin) may be increased resulting in lower plasma levels of these compounds. The clinical significance of this is unknown.

Somatropin may reduce insulin sensitivity. For patients with diabetes mellitus, insulin dosage may need adjustment after somatropin therapy is instituted.

In patients with hypopituitarism on standard replacement therapy, the potential effect of growth hormone treatment on thyroid function must be closely monitored.

In women on oral oestrogen replacement, a higher dose of growth hormone may be required to achieve the treatment goal.

Pregnancy and Lactation:

Animal studies are insufficient with regard to effects on pregnancy, embryofoetal development, parturition or postnatal development. There are no clinical studies available on exposed pregnancies. Therefore, somatropin containing products are not recommended during pregnancy and in women of childbearing potential not using contraception.

There have been no clinical studies conducted with somatropin containing products in breast-feeding women. It is not known whether somatropin is excreted in human milk, but absorption of intact protein from the infant GI tract is unlikely. Therefore caution should be exercised when somatropin containing products are administered to breast-feeding women.

Overdosage:

Acute overdosage could lead initially to hypoglycaemia and subsequently to hyperglycaemia and long-term overdosage could result in signs and symptoms consistent with the known effects of human growth hormone excess.

Side Effects:

In adult patients, very common and common adverse effects such as oedema peripheral, musculosketal stiffness, carpal tunnel syndrome, paraesthesia, arthralgia and myalgia.

In children the following very common and common adverse events have been reported, injection site reaction (GHD, CRI and SGA), arthralgia (Turner Syndrome and PWS).

Children with PWS have also reported the following adverse events; paraesthesia, benign intracranial hypertension, myalgia and oedema peripheral. In general these effects are mild to moderate, arise within the first months of treatment and subside spontaneously or with dose reduction.

Formation of antibodies of low binding capacity in approximately 1% of patients.

Rare or very rare cases of leukaemia have been reported in GH deficient children treated with somatropin, but the incidence appears to be similar to that in children without GH deficiency.

Slipped capital femoral epiphysis and Legg-Calve-Perthes disease have been reported in children treated with GH. Slipped capital femoral epiphysis occurs more frequently in case of endocrine disorders and Legg-Calve-Perthes is more frequent in case of short stature.

In Prader-Willi Syndrome patients treated with somatropin rare cases of sudden death have been reported, although no causal link has been established.

Other adverse drug reactions may be considered somatropin class effects, such as possible hyperglycaemia caused by decreased insulin sensitivity, decreased free thyroxin level and benign intra-cranial hypertension.

For patients with diabetes, the insulin dose may require adjustment after somatropin therapy is instituted. Patients with diabetes, glucose intolerance, or additional risk factors for diabetes should be monitored closely during somatropin therapy.

Somatropin has been reported to reduce serum cortisol levels, possibly by affecting carrier proteins or by increased hepatic clearance. The clinical relevance of these findings may be limited. Corticosteroid replacement therapy should be optimised before initiation of Genotropin therapy.

Pharmaceutical Precautions

Keep Genotropin in the outer carton to protect from light. Before reconstitution, store in the refrigerator (2 – 8ºC).

Genotropin Miniquick: Before opening, the product may be taken out of the refrigerator, without being replaced, for a maximum period of 6 months at a temperature not above 25°C. The date when the medicinal product is taken out and the new expiry date should be written on the outer packaging. This new expiry date should never exceed the one initially mentioned on the outer carton.

If the medicinal product has not been used before the new expiry date, it should be disposed of. After reconstitution: Use immediately or within 24 hours if stored at 2°C – 8°C, Do not freeze.

Genotropin Cartridge: store in a refrigerator (2 – 8ºC) or f up to 1 month at or below 25ºC allowed. 

After reconstitution: Store in a refrigerator (2ºC – 8ºC), do not freeze.  Keep the two-chamber cartridge/pre-filled pen in the outer carton in order to protect from light. Use within 4 weeks 

Legal Category

CD (Sch 4, Part II), POM

Pack / Basic NHS Price/PL No

Genotropin 5.3 mg Pre-filled pen (GoQuick)     x 1    £92.15    00057/0987
Genotropin 12 mg Pre-filled pen (GoQuick)     x 1    £208.65    00057/0988
Genotropin 5.3 mg Two chamber cartridge     x 1    £92.15    00057/0987
Genotropin 12 mg Two chamber cartridge     x 1    £208.65    00057/0988
Genotropin MiniQuick 0.2 mg         x7    £24.35    00057/0989
Genotropin MiniQuick 0.4 mg         x7    £48.68    00057/0990
Genotropin MiniQuick 0.6 mg         x7    £73.03    00057/0991
Genotropin MiniQuick 0.8 mg         x7    £97.37    00057/0992
Genotropin MiniQuick 1.0 mg         x7    £121.71    00057/0993
Genotropin MiniQuick 1.2 mg         x7    £146.06    00057/0994
Genotropin MiniQuick 1.4 mg         x7    £170.39    00057/0995
Genotropin MiniQuick 1.6 mg         x7    £194.74    00057/0996
Genotropin MiniQuick 1.8 mg         x7    £219.08    00057/0997
Genotropin MiniQuick 2.0 mg         x7    £243.42    00057/0998

PL Holder

Pfizer Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK.

Further information is available on request from Medical Information Department at Pfizer Limited, Walton Oaks, Dorking Road, Tadworth, Surrey, KT20 7NS, UK.


Date of preparation:  03/2018
Company reference:  GN 33_0

 

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Pfizer Medical Information on 01304 616161

 

PP-GEN-GBR-0464. July 2018