‫רופא‬
‫בעלון ללרופא‬
‫בטיחות) בעלון‬
)‫מידע בטיחות‬
‫החמרה (( מידע‬
‫על החמרה‬
‫הודעה על‬
‫הודעה‬
___0010.1..____ ‫תאריך‬
____NutropinAQ____‫שם תכשיר באנגלית‬
__990..__‫מספר רישום‬
__Medison Pharma Ltd._‫שם בעל הרישום‬
‫השינויים בעלון מסומנים על רקע צהוב‬
‫ים‬/‫ים המבוקש‬/‫פרטים על השינוי‬
‫טקסט חדש‬
‫טקסט נוכחי‬
The adverse reactions reported in both adults
and children receiving Nutropin or NutropinAq
are listed in the table below, based on
experience from clinical trials all approved
indications (642 patients) and a post-marketing
surveillance survey. (National Cooperative
Growth Study [NCGS] in 35,344 patients).
Approximately 2.5% of patients from the NCGS
have experienced drug related adverse reactions,
with most of these adverse reactions being
reported in the “general disorders and
administration site conditions” system organ
class.
In addition, indication-specific adverse reactions
from the same clinical trials are listed in the text
below the table.
Within the system organ classes, adverse
reactions are listed under headings of frequency
using the following categories: very common (≥
1/10), common (≥ 1/100, < 1/10); uncommon (≥
1/1000, < 1/100); rare (≥ 1/10,000, < 1/1,000).
Within each frequency grouping, undesirable
effects are presented in order of decreasing
seriousness.
System
Organ
Class
Reactions
observed in
Pivotal and
Supportive
Clinical Trials (in
642 patients)
Postmarketing
Surveillance
(PMS) Reactions
Investigati
ons
Common: Drug
specific antibody
present
Rare: Blood
glucose increased,
weight increased
Cardiac
disorders
Blood and
lymphatic
system
disorders
Nervous
system
disorders
Uncommon:
Tachycardia
Uncommon:
Anaemia
Safety data from 9829 patients treated with
Nutropin or NutropinAq - derived from a postmarketing surveillance survey in the United States demonstrate that approximately 2% of patients have
been shown to experience drug-related adverse
reactions. Most of these adverse drug reactions
were reported in the “general disorders and
administration site conditions” system organ class.
The adverse reactions are listed in the table below,
based on experience from clinical trials and a postmarketing surveillance survey. Within the system
organ classes, adverse reactions are listed under
headings of frequency using the following
categories: very common (≥ 1/10), common (≥
1/100, < 1/10); uncommon (≥ 1/1000, < 1/100);
rare (≥ 1/10,000, < 1/1,000).
4.8
Neoplasms
benign, malignant and
unspecified (including
cysts and polyps)
Blood and lymphatic
system disorders
Immune
system
disorders
Endocrine disorders
Uncommon: neoplasm malignant,
neoplasm
Metabolism
and
nutrition disorders
Common:
glucose
tolerance
impaired
Uncommon:
hypoglycaemia,
hyperphosphatemia
Rare: diabetes mellitus
Uncommon: personality disorder
Psychiatric disorders
Common:
Headache,
hypertonia,
Nervous
disorders
system
Eye disorders
Uncommon:
Headache
Rare: Benign
‫פרק בעלון‬
Ear
and
labyrinth
disorders
Cardiac disorders
Undesirable
effects
Uncommon: anaemia
Common: antibody building
Common: hypothyroidism
Common: headache, hypertonia
Uncommon:
somnolence,
nystagmus
Rare: neuropathy, intracranial
pressure increased
Uncommon:
papilloedema,
diplopia
Uncommon: vertigo
Uncommon:
hypertension
tachycardia,
Uncommon: Carpal
tunnel syndrome,
somnolence,
nystagmus
Eye
disorders
Ear and
labyrinth
disorders
Respirator
y disorders
Gastrointe
stinal
disorders
Renal and
urinary
disorders
Skin and
subcutane
ous tissue
disorders
Musculosk
eletal and
connective
tissue
disorders
Uncommon:
Papilloedema,
diplopia
Uncommon:
Vertigo
Uncommon:
Abdominal pain,
vomiting, nausea,
flatulence
Uncommon:
Urinary
incontinence,
pollakiuria,
polyuria, urine
abnormality
Uncommon:
Exfoliative
dermatitis, skin
atrophy, skin
hypertrophy,
hirsutism,
lipodystrophy,
urticaria
Very common in
adults, common in
children:
Arthralgia, myalgia
Uncommon:
Muscle atrophy,
bone pain
Endocrine
disorders
Metabolis
m and
nutrition
disorders
Common:
Hypothyroidism
Common: Glucose
tolerance impaired
Uncommon:
Hypoglycaemia,
hyperphosphatemia
Neoplasms
benign,
malignant
and
unspecifie
d
(including
cysts and
polyps)
Vascular
disorders
General
disorders
and
administra
tion site
conditions
Uncommon:
Neoplasm
malignant,
neoplasm benign
Uncommon:
Hypertension
Very common in
adults, common in
children: Peripheral
oedema, oedema
Common:
Asthenia, injection
site reaction
Uncommon:
intracranial
hypertension,
intracranial
pressure
increased,
migraine, carpal
tunnel syndrome,
paraesthesia,
dizziness
Rare:
Papilloedema,
vision blurred
Rare: Tonsillar
hypertrophy
Rare: Abdominal
pain, diarrhoea,
nausea, vomiting
Gastrointestinal
disorders
Uncommon: vomiting, abdominal
pain, flatulence, nausea
Rare: diarrhoea
Skin and subcutaneous
tissue disorders
Uncommon: lipodystrophy, skin
atrophy, dermatitis exfoliative,
urticaria,
hirsutism,
skin
hypertrophy
Very common in adults, common
in children: arthralgia, myalgia
Uncommon: muscle atrophy, bone
pain, carpal tunnel syndrome
Musculoskeletal
and
connective
tissue
disorders
Renal
and
disorders
Reproductive
system
and breast disorders
General disorders and
administration
site
conditions
Rare: Generalised
pruritus,
urinary
Investigations
Uncommon: urinary incontinence,
haematuria,
polyuria,
urine
frequency/pollakiuria,
urine
abnormality
Uncommon: genital discharge
Very common in adults, common
in children: oedema, peripheral
oedema
Common: injection site reactions,
asthenia
Uncommon:
injection
site
atrophy,
injection
site
haemorrhage, injection site mass,
hypertrophy
Rare: renal function test abnormal
urticaria,rash
Uncommon:
Epiphysiolysis,
scoliosis
progression,
arthralgia
Rare: Bone
development
abnormal,
osteochondrosis,
muscular
weakness, pain in
extremity
Rare:
Hypothyroidism
Rare: Diabetes
mellitus,
hyperglycaemia,
hypoglycaemia,
glucose tolerance
impaired
Rare: Neoplasm
malignant
recurrence,
melanocytic
naevus
Rare:
Hypertension
Uncommon:
Peripheral
oedema, oedema,
injection site
reaction (irritation,
pain)
Rare: Asthenia,
As with all medicinal products, a small percentage
of patients may develop antibodies to the protein
somatropin. The binding capacity of growth
hormone antibodies was lower than 2 mg/l in
NutropinAq subjects tested, which has not been
associated with adversely affected growth rate.
Leukaemia has been reported in a small number of
growth hormone deficient patients treated with
growth hormone. A causal relationship to
somatropin therapy is unlikely.
Patients with endocrinological disorders are more
prone to develop an epiphysiolysis.
Indication-specific adverse drug reactions from
clinical trials
Paediatric patients:
Patients with growth failure due to inadequate
growth hormone secretion
Common: central nervous system neoplasm.
Patients with growth failure associated with Turner
syndrome
Common: menorrhagia.
Patients with growth failure associated with
chronic renal insufficiency
Common: renal failure, peritonitis, osteonecrosis,
blood creatinine increase.
Children with chronic renal insufficiency receiving
NutropinAq are more likely to develop intracranial
hypertension. The greatest risk is at the beginning
of treatment.
Adult patients:
Adults with growth hormone deficiency
Very common: paraesthesia.
Common: hyperglycaemia, hyperlipidaemia,
Reproducti
ve system
and breast
disorders
Psychiatric
disorders
Injection site
haemorrhage,
injection site
atrophy, injection
site mass,
hypertrophy
face oedema,
fatigue, irritability,
pain, pyrexia,
injection site
reaction
(haemorrhage,
haematoma,
atrophy, urticaria,
pruritus, swelling,
erythema)
Uncommon:
Uterine
haemorrhage,
genital discharge
Uncommon:
Personality
disorder
Rare:
Gynaecomastia
Rare: Abnormal
behaviour,
depression,
insomnia
As with all recombinant proteins, a small
percentage of patients may develop antibodies
to the protein somatropin. The binding capacity
of growth hormone antibodies was lower than 2
mg/l in NutropinAq subjects tested, which has
not been associated with adversely affected
growth rate.
Patients with endocrinological disorders are
more prone to develop an epiphysiolysis.
Indication-specific adverse drug reactions from
clinical trials
Paediatric patients:
Patients with growth failure due to inadequate
growth hormone secretion (n=236)
Common: central nervous system neoplasm. (2
patients experienced a recurrent
medulloblastoma, 1 patient experienced a
histiocytoma). See also section 4.4.
Patients with growth failure associated with
Turner syndrome (n=108)
Common: menorrhagia.
Patients with growth failure associated with
chronic renal insufficiency (n=171)
Common: renal failure, peritonitis,
osteonecrosis, blood creatinine increase.
Children with chronic renal insufficiency
receiving NutropinAq are more likely to
develop intracranial hypertension although
children with organic GHD and Turner
syndrome also have an increased incidence..
The greatest risk is at the beginning of
treatment.
Adult patients:
Adults with growth hormone deficiency (n=127)
Very common: paraesthesia.
Common: hyperglycaemia, hyperlipidaemia,
insomnia, synovial disorder, arthrosis, muscular
weakness, back pain, breast pain,
gynaecomastia.
insomnia, synovial disorder, arthrosis, muscular
weakness, back pain, breast pain, gynaecomastia.