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Humatrope (Somatropin) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Growth Hormone-Deficient Pediatric Patients

As with all protein pharmaceuticals, a small percentage of patients may develop antibodies to the protein. During the first 6 months of Humatrope therapy in 314 naive patients, only 1.6% developed specific antibodies to Humatrope (binding capacity ≥0.02 mg/L). None had antibody concentrations which exceeded 2 mg/L. Throughout 8 years of this same study, two patients (0.6%) had binding capacity >2 mg/L. Neither patient demonstrated a decrease in growth velocity at or near the time of increased antibody production. It has been reported that growth attenuation from pituitary–derived growth hormone may occur when antibody concentrations are >1.5 mg/L.

In addition to an evaluation of compliance with the treatment program and of thyroid status, testing for antibodies to human growth hormone should be carried out in any patient who fails to respond to therapy.

In studies with growth hormone–deficient pediatric patients, injection site pain was reported infrequently. A mild and transient edema, which appeared in 2.5% of patients, was observed early during the course of treatment.

Leukemia has been reported in a small number of pediatric patients who have been treated with growth hormone, including growth hormone of pituitary origin as well as of recombinant DNA origin (somatrem and somatropin). The relationship, if any, between leukemia and growth hormone therapy is uncertain.

Patients with Turner Syndrome

In a randomized, concurrent controlled trial, there was a statistically significant increase in the occurrence of otitis media (43% vs. 26%), ear disorders (18% vs. 5%) and surgical procedures (45% vs. 27%) in patients receiving Humatrope compared with untreated control patients (Table 7). Other adverse events of special interest to Turner syndrome patients were not significantly different between treatment groups (Table 7). A similar increase in otitis media was observed in an 18–month placebo–controlled trial.

Table 7 Treatment–Emergent Events of Special Interest by Treatment Group in Turner Syndrome

Treatment Group

Adverse Event

Untreated 1

Humatrope 2

Significance 3

Total Number of Patients

62

74

Surgical procedure

17 (27.4%)

33 (44.6%)

p≤0.05

Otitis media

16 (25.8%)

32 (43.2%)

p≤0.05

Ear disorders

3 (4.8%)

13 (17.6%)

p≤0.05

Bone disorder

7 (11.3%)

6 (8.1%)

NS

Edema

   Conjunctival

1 (1.6%)

0

NS

   Non-specific

1 (1.6%)

2 (2.7%)

NS

   Facial

0

1 (1.4%)

NS

   Peripheral

1 (1.6%)

5 (6.8%)

NS

Hyperglycemia

0

0

NS

Hypothyroidism

5 (8.1%)

10 (13.5%)

NS

Increased nevi 4

2 (3.2%)

8 (10.8%)

NS

Lymphedema

0

0

NS

1 Open-label study.
2 Dose=0.3 mg/kg/wk.
3 NS=not significant.
4 Includes any nevi coded to the following preferred terms: melanosis, skin hypertrophy, or skin benign neoplasm.

Patients with Idiopathic Short Stature

In the placebo–controlled study, the adverse events associated with Humatrope therapy were similar to those observed in other pediatric populations treated with Humatrope (Table 8). Mean serum glucose level did not change during Humatrope treatment. Mean fasting serum insulin levels increased 10% in the Humatrope treatment group at the end of treatment relative to baseline values but remained within the normal reference range. For the same duration of treatment the mean fasting serum insulin levels decreased by 2% in the placebo group. The incidence of above–range values for glucose, insulin, and HbA1c were similar in the growth hormone and placebo–treated groups. No patient developed diabetes mellitus. Consistent with the known mechanism of growth hormone action, Humatrope–treated patients had greater mean increases, relative to baseline, in serum insulin–like growth factor–I (IGF–I) than placebo–treated patients at each study observation. However, there was no significant difference between the Humatrope and placebo treatment groups in the proportion of patients who had at least one serum IGF–I concentration more than 2.0 SD above the age– and gender–appropriate mean (Humatrope: 9 of 35 patients [26%]; placebo: 7 of 28 patients [25%]).

Table 8 Nonserious Clinically Significant Treatment–Emergent Adverse Events by Treatment Group in Idiopathic Short Stature

Treatment Group

Adverse Event

Humatrope

Placebo

Total Number of Patients

37

31

Scoliosis

7 (18.9%)

4 (12.9%)

Otitis media

6 (16.2%)

2 (6.5%)

Hyperlipidemia

3 (8.1%)

1 (3.2%)

Gynecomastia

2 (5.4%)

1 (3.2%)

Hypothyroidism

0

2 (6.5%)

Aching joints

0

1 (3.2%)

Hip pain

1 (2.7%)

0

Arthralgia

4 (10.8%)

1 (3.2%)

Arthrosis

4 (10.8%)

2 (6.5%)

Myalgia

9 (24.3%)

4 (12.9%)

Hypertension

1 (2.7%)

0

The adverse events observed in the dose–response study (239 patients treated for 2 years) did not indicate a pattern suggestive of a growth hormone dose effect. Among Humatrope dose groups, mean fasting blood glucose, mean glycosylated hemoglobin, and the incidence of elevated fasting blood glucose concentrations were similar. One patient developed abnormalities of carbohydrate metabolism (glucose intolerance and high serum HbA1c) on treatment.

Patients with SHOX Deficiency

Clinically significant” adverse events (adverse events previously observed in association with growth hormone treatment in general) were assessed prospectively during the 2-year randomized, open-label study; those observed are presented in Table 9. In both treatment groups, the mean fasting plasma glucose concentration at the end of the first year was similar to the baseline value and remained in the normal range. No patient developed diabetes mellitus or had an above normal value for fasting plasma glucose at the end of one-year of treatment. During the 2 year study period, the proportion of patients who had at least one IGF-I concentration greater than 2.0 SD above the age- and gender-appropriate mean was 10 of 27 [37.0%] for the Humatrope-treated group vs. 0 of 24 patients [0.0%] for the untreated group. The proportion of patients who had at least one IGFBP-3 concentration greater than 2.0 SD above the age and gender appropriate mean was 16 of 27 [59.3%] for the Humatrope treated group vs. 7 of 24 [29.2%] for the untreated group.

Table 9 Clinically Significant Treatment-Emergent Adverse Events 1 , 2 by Treatment Group and Patients with SHOX Deficiency

Adverse Event

Treatment Group

Untreated

Humatrope

 Total Number of Patients

25

27

 Patients with at least one event

2

5

 Arthralgia

2 (8.0%)

3 (11.1%)

 Gynecomastia 3

0 (0.0%)

1 (8.3%)

 Excessive number of cutaneous nevi

0 (0.0%)

2 (7.4%)

 Scoliosis

0 (0.0%)

1 (3.7%)

1 All events were non-serious.
2 Events are included only if reported for a greater number of Humatrope-treated than Untreated patients.
3 Percentage calculated for males only (1/12).

Adult Patients  — In clinical studies in which high doses of Humatrope were administered to healthy adult volunteers, the following events occurred infrequently: headache, localized muscle pain, weakness, mild hyperglycemia, and glucosuria.

In the first 6 months of controlled blinded trials during which patients received either Humatrope or placebo, adult–onset growth hormone–deficient adults who received Humatrope experienced a statistically significant increase in edema (Humatrope 17.3% vs. placebo 4.4%, p=0.043) and peripheral edema (11.5% vs. 0%, respectively, p=0.017). In patients with adult–onset growth hormone deficiency, edema, muscle pain, joint pain, and joint disorder were reported early in therapy and tended to be transient or responsive to dosage titration.

Two of 113 adult–onset patients developed carpal tunnel syndrome after beginning maintenance therapy without a low dose (0.00625 mg/kg/day) lead–in phase. Symptoms abated in these patients after dosage reduction.

All treatment–emergent adverse events with ≥5% overall incidence during 12 or 18 months of replacement therapy with Humatrope are shown in Table 10 (adult–onset patients) and in Table 11 (childhood–onset patients).

Adult patients treated with Humatrope who had been diagnosed with growth hormone deficiency in childhood reported side effects less frequently than those with adult–onset growth hormone deficiency.

Table 10 Treatment–Emergent Adverse Events with ≥5% Overall Incidence in Adult–Onset Growth Hormone–Deficient Patients Treated with Humatrope for 18 Months as Compared with 6–Month Placebo and 12–Month Humatrope Exposure 1

18 Months Exposure
[Placebo (6 Months)/GH (12 Months)]
(N=46)


18 Months GH Exposure
(N=52)

 Adverse Event

n

%

n

%

 Edema 2

7

15.2

11

21.2

 Arthralgia

7

15.2

9

17.3

 Paresthesia

6

13.0

9

17.3

 Myalgia

6

13.0

7

13.5

 Pain

6

13.0

7

13.5

 Rhinitis

5

10.9

7

13.5

 Peripheral edema 3

8

17.4

6

11.5

 Back pain

5

10.9

5

9.6

 Headache

5

10.9

4

7.7

 Hypertension

2

4.3

4

7.7

 Acne

0

0

3

5.8

 Joint disorder

1

2.2

3

5.8

 Surgical procedure

1

2.2

3

5.8

 Flu syndrome

3

6.5

2

3.9

1 Abbreviations: GH=Humatrope; N=number of patients receiving treatment in the period stated; n=number of patients reporting each treatment–emergent adverse event.
2 p=0.04 as compared to placebo (6 months).
3 p=0.02 as compared to placebo (6 months).

Table 11 Treatment–Emergent Adverse Events with ≥5% Overall Incidence in Childhood–Onset Growth Hormone–Deficient Patients Treated with Humatrope for 18 Months as Compared with 6–Month Placebo and 12–Month Humatrope Exposure 1

18 Months Exposure
[Placebo (6 Months)/GH (12 Months)]
(N=35)


18 Months GH Exposure
(N=32)

 Adverse Event

n

%

n

%

 Flu syndrome

8

22.9

5

15.6

 AST increased 2

2

5.7

4

12.5

 Headache

4

11.4

3

9.4

 Asthenia

1

2.9

2

6.3

 Cough increased

0

0

2

6.3

 Edema

3

8.6

2

6.3

 Hypesthesia

0

0

2

6.3

 Myalgia

2

5.7

2

6.3

 Pain

3

8.6

2

6.3

 Rhinitis

2

5.7

2

6.3

 ALT increased

2

5.7

2

6.3

 Respiratory disorder

2

5.7

1

3.1

 Gastritis

2

5.7

0

0

 Pharyngitis

5

14.3

1

3.1

1 Abbreviations: hGH=Humatrope; N=number of patients receiving treatment in the period stated; n=number of patients reporting each treatment–emergent adverse event; ALT=alanine amino transferase, formerly SGPT; AST=aspartate amino transferase, formerly SGOT.
2 p=0.03 as compared to placebo (6 months).

Other adverse drug events that have been reported in growth hormone–treated patients include the following:

  1. Metabolic: Infrequent, mild and transient peripheral or generalized edema.

  2. Musculoskeletal: Rare carpal tunnel syndrome.

  3. Skin: Rare increased growth of pre–existing nevi. Patients should be monitored carefully for malignant transformation.

  4. Endocrine: Rare gynecomastia. Rare pancreatitis.



REPORTS OF SUSPECTED HUMATROPE SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Humatrope. The information is not vetted and should not be considered as verified clinical evidence.

Possible Humatrope side effects / adverse reactions in 15 year old male

Reported by a physician from Japan on 2011-10-07

Patient: 15 year old male

Reactions: Retinal Detachment

Suspect drug(s):
Humatrope
    Dosage: unk
    Indication: Body Height Below Normal

Humatrope
    Dosage: 0.2 mg/kg, weekly (1/w)



Possible Humatrope side effects / adverse reactions in 15 year old male

Reported by a physician from Japan on 2011-10-12

Patient: 15 year old male

Reactions: Retinal Detachment

Suspect drug(s):
Humatrope
    Dosage: unk
    Indication: Body Height Below Normal

Humatrope
    Dosage: 0.2 mg/kg, weekly (1/w)



Possible Humatrope side effects / adverse reactions in 77 year old female

Reported by a consumer/non-health professional from United States on 2011-10-12

Patient: 77 year old female

Reactions: Vomiting, Diarrhoea, Anaemia, Incorrect Dose Administered, Joint Dislocation, Hypoaesthesia, Gastroenteritis Viral

Adverse event resulted in: hospitalization

Suspect drug(s):
Humatrope



See index of all Humatrope side effect reports >>

Drug label data at the top of this Page last updated: 2007-02-07

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