Accretropin

This section provides information on the proper use of a number of products that contain somatropin, e-coli derived. It may not be specific to Accretropin. Please read with care.

This medicine is given as a shot under your skin. Somatropin may sometimes be given at home to patients who do not need to be in the hospital. If you are using this medicine at home, your doctor will teach you how to prepare and inject the medicine. Be sure that you understand exactly how the medicine is prepared and injected.

This medicine comes with a patient information insert. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions.

There are many different forms (eg, vial, cartridge, injection device) available for this medicine. Read all instructions carefully to be sure you know how to use your device.

Each time you get your medicine, check to be sure you have received the proper device. Talk to your pharmacist if you have questions about the device that you were given.

You will be shown the body areas where this shot can be given. Use a different body area each time you give yourself a shot. Keep track of where you give each shot to make sure you rotate body areas. This will help prevent skin problems from the injections.

Use a new needle, unopened vial, or syringe each time you inject your medicine.

You might not use all of the medicine in each vial (glass container) or prefilled syringe. Use each vial or syringe only one time. Do not save an open vial or syringe. If the medicine in the vial or syringe has changed color, or if you see particles in it, do not use it.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form:
  • For all indications:
    • Adults—Dose is usually based on body weight (depending on the brand of somatropin you are using) and dose must be determined by your doctor. Your doctor will adjust your dose as needed.
    • Children—Dose is based on body weight and must be determined by your doctor. Your doctor will adjust your child's dose as needed.

Missed Dose

This medicine needs to be given on a fixed schedule. If you miss a dose or forget to use your medicine, call your doctor or pharmacist for instructions.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store this medicine in the refrigerator, away from direct light. Do not freeze or shake.

Throw away used needles in a hard, closed container that the needles cannot poke through. Keep this container away from children and pets.

If you will be taking this medicine for a long time, it is very important that your doctor check you at regular visits for any problems or unwanted effects that may be caused by this medicine.

This medicine may cause a serious allergic reaction that requires immediate medical attention. Tell your doctor right away if you have a rash, itching, swelling of the face, tongue, or throat, trouble breathing, or chest pain after you receive the medicine.

This medicine may cause a dislocation in the hip bone, especially in patients with growth hormone deficiency or Turner syndrome. Check with your doctor right away if you or your child has a limp or pain in the hip or knee.

This medicine may affect blood sugar levels. Check with your doctor if you notice a change in the results of your blood or urine sugar tests or if you have any questions.

This medicine may cause an increased pressure in the head. Check with your doctor immediately if headache, nausea, vomiting, blurred vision, or any other change in vision occurs during treatment. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

This medicine may cause fluid retention (extra water in the body). Tell your doctor if you have burning, numbness, pain, or tingling in all fingers except the smallest finger, swelling of the hands and feet, or pain, swelling, or stiffness of the muscles. Your doctor may adjust your dose to reduce these side effects.

Pancreatitis has occurred rarely in some patients receiving somatropin. Tell your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

Using this medicine may increase your risk of getting cancer. Talk to your doctor if you have concerns about this risk.

Before you have any medical tests, tell the medical doctor in charge that you are using this certain brand of somatropin (Humatrope®). The results of some tests may be affected by this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

As with all protein pharmaceuticals, some patients may develop antibodies to the protein. Over 3 years of Accretropin™ (somatropin injection) therapy, no patient with growth hormone deficiency or Turner syndrome developed anti-GH antibodies with binding capacities greater than 0.67 mg/L, which is below the threshold at which attenuation of growth velocity has been observed. Anti-GH antibody titers peaked by 6-12 months and remained stable or declined subsequently. Anti-E.coli antibody titers increased slightly during Accretropin™ (somatropin injection) treatment. No growth attenuation was noted in any patient who developed anti-hGH or anti-E. coli antibodies.

Pediatric Growth Hormone-Deficient Patients

In the clinical study conducted in children with GHD injection site reactions were the most frequent treatment-related adverse event reported in 50% of patients (includes the following descriptions: bruising, erythema, hemorrhage, edema, pain, pruritis, rash, swelling). Other treatment-related adverse events (as assessed by the investigators) with a frequency ≥ 3% were nausea, headache, fatigue, and scoliosis. One patient with pre- existing type-1 diabetes required adjustment of the insulin dose under observation. See also growth hormone associated adverse events under PRECAUTIONS and WARNINGS.

Turner Syndrome Patients

In the clinical study conducted in pediatric patients with Turner Syndrome the only treatment-related adverse event (as assessed by the investigators) that occurred in ≥ 3% of patients was injection site reaction which occurred in 32% of patients (includes the following descriptions: erythema, edema, pain, pruritis). See also growth hormone associated adverse events under PRECAUTIONS and WARNINGS.

Accretropin is a form of human growth hormone.

Accretropin is used to treat growth failure in children who lack natural growth hormone. Accretropin is also used for the treatment of short stature associated with Turner Syndrome in children.

Applies to somatropin: injectable kit, injectable powder for injection, subcutaneous kit, subcutaneous powder for injection, subcutaneous solution

General

The most common adverse events were glucose intolerance, fluid retention, injection site reactions, and unmasking of latent central hypothyroidism.[Ref]

Other

Very common (10% or more): Otitis media (up to 86.4%), surgical procedure (44.6%), peripheral edema (45.4%), edema (25%), flu syndrome (22.9%), ear disorders (17.6%), peripheral swelling (17.5%), leg edema (15%), pain in extremities (19.3%), pain (13.5%), headache (11.4%)
Common (1% to 10%): Hematoma, fatigue, flu-like symptoms, asthenia, fatigue, generalized edema
Uncommon (0.1% to 1%): Weakness
Frequency not reported: Sudden death, pyrexia, ear infection, influenza-like illness, otitis externa,
Postmarketing reports: Increased blood alkaline phosphatase level[Ref]

Endocrine

Very common (10% or more): IGF-1 scores above 2 standard deviations (38%), hypothyroidism (16%)
Common (1% to 10%): Hypothyroidism
Uncommon (0.1% to 1%): Central precocious puberty
Frequency not reported: Unmasking of latent central hypothyroidism
Postmarketing reports: Decrease in serum thyroxin levels[Ref]

Musculoskeletal

Scoliosis was reported as an adverse event in 5 out of 21 children with Noonan Syndrome who were followed for 11 years.[Ref]

Very common (10% or more): Arthralgia (37.1%), myalgia (30.4%), scoliosis (23.8%), skeletal pain (11%), back pain (10.9%), arthrosis (10.7%)
Common (1% to 10%): Musculoskeletal stiffness, stiffness of extremities, joint stiffness, joint swelling, joint disorder, leg pain, hip pain, progression of preexisting scoliosis,
Uncommon (0.1% to 1%): Localized muscle pain, jaw prominence, slipped capital femoral epiphysis
Frequency not reported: fracture, joint pain, growth attenuation, interference with growth response, excessive growth of hands or feet, exacerbation of preexisting scoliosis, disproportionate growth of the lower jaw, fracture
Postmarketing reports: Legg-Calvé-Perthes disease[Ref]

Metabolic

Very common (10% or more): Impaired fasting glucose (22%), elevated HbA1c (14%), blood glucose increased (13.8%)
Common (1% to 10%): Hyperglycemia, hyperlipidemia, glucose tolerance abnormal, fluid retention, hypertriglyceridemia, overt type II diabetes mellitus
Uncommon (0.1% to 1%): Diabetes mellitus, abnormalities of carbohydrate metabolism (glucose intolerance and high serum HbA1c)
Frequency not reported: Glucose intolerance including impaired glucose tolerance/impaired fasting glucose, increased appetite, transient episodes of fasting blood sugars between 100 and 126 mg/dL, transient episodes of fasting blood sugars exceeding 126 mg/dL, increased fasting blood glucose levels, increases in insulin levels, insulin resistance
Postmarketing reports: Exacerbation of preexisting diabetes mellitus, diabetic ketoacidosis, diabetic coma[Ref]

Nervous system

Intracranial hypertension with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in a small number of patients.[Ref]

Very common (10% or more): Paresthesia (17.3%), hypoesthesia (15%)
Common (1% to 10%): Hypesthesia, fatigue, carpal tunnel syndrome, Tinel's sign
Uncommon (0.1% to 1%): Benign intracranial hypertension, motor problem, seizure[Ref]

Gastrointestinal

Very common (10% or more): Pharyngitis (14.3%),
Common (1% to 10%): Nausea, gastroenteritis, gastritis
Frequency not reported: Abdominal pain, increased appetite
Postmarketing reports: Pancreatitis[Ref]

Hepatic

Very common (10% or more): AST increased (12.5%)
Common (1% to 10%): ALT increased[Ref]

Hematologic

Very common (10% or more): Eosinophilia (12%)[Ref]

Ocular

Very common (10% or more): Periorbital edema
Frequency not reported: Diabetic retinopathy[Ref]

Respiratory

Very common (10% or more): Upper respiratory infection (15.9%), rhinitis (13.5%)
Common (1% to 10%): Bronchitis, cough increased, laryngitis, respiratory disorder, dyspnea, sleep apnea
Frequency not reported: Influenza, tonsillitis, nasopharyngitis, sinusitis, bronchitis[Ref]

Immunologic

Very common (10% or more): Anti-rhGH antibodies (24%), infection (non-viral) (13%)
Frequency not reported: Antibody formation, anti-periplasmic Escherichia coli peptides (PECP) antibodies[Ref]

An IgG antibody has been identified. No antibodies to the IgE class have been detected. Growth hormone antibody binding capacities less than 2 mg/L have not led to growth attenuation. Testing for antibodies should be carried out in any patient failing to respond to treatment.

Primate studies have failed to reveal evidence of histopathological changes due to immune complex formation.[Ref]

Local

Common (1% to 10%): Injection site pain
Frequency not reported: Injection site reactions/rashes, lipoatrophy, nodules, rash, inflammation, pigmentation, bleeding[Ref]

Hypersensitivity

Common (1% to 10%): Hypersensitivity to solvent (m-cresol/glycerol)
Rare (less than 0.1%): Generalized hypersensitivity reactions
Postmarketing reports: Hypersensitivity[Ref]

Cardiovascular

Common (1% to 10%): Hypertension
Frequency not reported: Cardiac disorders[Ref]

Dermatologic

Common (1% to 10%): Increased sweating, excessive number of cutaneous nevi, acne
Uncommon (0.1% to 1%): Pruritus
Rare (less than 0.1%): Rash
Frequency not reported: Hair loss, progression of pigmented nevi, eczema[Ref]

Genitourinary

Common (1% to 10%): Gynecomastia, breast-related adverse reactions (e.g. nipple pain,
gynecomastia, breast pain/mass/tenderness/swelling/edema/hypertrophy)
Frequency not reported: Urinary tract infection[Ref]

Psychiatric

Common (1% to 10%): Insomnia
Frequency not reported: Aggressiveness, altered mood[Ref]

Renal

Uncommon (0.1% to 1%): Glucosuria
Frequency not reported: Hematuria[Ref]

Oncologic

Very rare (less than 0.01%): Leukemia
Frequency not reported: Intracranial tumors including meningiomas, melanocytic nevus[Ref]

Some side effects of Accretropin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Weight Based Regimen:
Initial dose: Not more than 0.004 mg/kg subcutaneously once a day (or a total of 0.04 mg/kg per week in divided doses).
Maximum dose: 0.016 mg/kg once a day (0.08 mg/kg per week in divided doses)

Non-Weight Based Regimen:
Approximately 0.2 mg subcutaneously once a day (range: 0.15 to 0.3 mg once a day)

Comments:
-The weekly dose should be divided over 6 or 7 days of subcutaneous injections.
-May increase dose (weight or non-weight based) at 4 to 8 week intervals, by increments of approximately 0.1 to 0.2 mg per day (not more than 0.004 mg/kg per day), based on clinical response and serum IGF-I concentrations.
-The dose should be decreased as necessary on the basis of adverse events and/or serum IGF-I concentrations above the age- and gender-specific normal range.
-Maintenance dosages vary considerably from person to person, and between male and female patients.
-Obese individuals are more likely to manifest adverse effects when treated with a weight-based regimen. -To reach the defined treatment goal, estrogen-replete women may need higher doses than men.

Uses: Replacement of endogenous growth hormone (GH) in adults with growth hormone deficiency (GHD) who meet either of the following two criteria:
-Adult Onset (AO): Patients who have GHD, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or
-Childhood Onset (CO): Patients who were GH deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes. Reevaluate patients treated for childhood GHD whose epiphyses are closed before continuing therapy at the reduced dose level recommended for adults.
-Confirmation of the diagnosis of adult GHD in both groups involves an appropriate growth hormone provocative test with two exceptions: (1) patients with multiple other pituitary hormone deficiencies due to organic disease; and (2) patients with congenital/genetic growth hormone deficiency.

Small for Gestational Age (SGA):
Up to 0.067 mg/kg subcutaneously daily

Short stature homeobox-containing gene (SHOX) deficiency:
0.05 mg/kg subcutaneously once a day (0.35 mg/kg per week in divided doses)

Comments:
-The weekly dose should be divided over 6 or 7 days of subcutaneous injections.
-SGA: Generally, a dose of up to 0.48 mg/kg body weight per week is recommended.
-SGA: Recent literature recommends initial treatment with larger doses (e.g., 0.067 mg/kg once a day), especially in very short children (HSDS of lower than -3), and/or older/pubertal children.
-SGA: In younger children (approximately less than 4 years, who respond the best in general) with less severe short stature (baseline HSDS values between -2 and -3), consider initiating treatment at a lower dose (0.033 mg/kg/day), and titrating the dose as needed over time.
-Individualize dosage and administration schedule based on the growth response.
-Serum insulin-like growth factor I (IGF-I) levels may be useful during dose titration.
-Response to therapy in pediatric patients tends to decrease with time, however, failure to increase height velocity, particularly during the first year of treatment, should prompt close assessment of compliance and evaluation of other causes of poor growth, such as hypothyroidism, under-nutrition, advanced bone age, and antibodies to recombinant human growth hormone.
-Treatment for short stature should be discontinued when the epiphyses are fused.

Uses:
-Treatment of pediatric patients with short stature born small for gestational age (SGA) with no catch-up growth by age 2 to 4 years.
-Treatment of short stature or growth failure in children with short stature homeobox-containing gene (SHOX) deficiency.

The dosage in children with chronic renal disease must be adjusted according to the individual response to therapy.

Administration advice:
-Alternate injection sites.

General:
-Therapy should be supervised by specialists experienced in the diagnosis and management of growth hormone (GH) deficiency.

Substance Name

Somatropin

CAS Registry Number

12629-01-5

Drug Class

Galactogogues

Human Growth Hormone