INCRELEX

  • Name:

    INCRELEX

  • Company:
    info
  • Active Ingredients:

    Mecasermin

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 08/01/20

files-icon(Click to Download)
Summary of Product Characteristics last updated on medicines.ie: 8/1/2020
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. See section 4.8 for how to report adverse reactions.

Click on this link to Download PDF directly

Ipsen Pharmaceuticals Ltd

Ipsen Pharmaceuticals Ltd

Company Products

Medicine NameActive Ingredients
Medicine Name Cabometyx Tablets Active Ingredients Cabozantinib
Medicine Name Decapeptyl (triptorelin) 3-month Active Ingredients triptorelin pamoate
Medicine Name Decapeptyl (triptorelin) SR Active Ingredients triptorelin acetate
Medicine Name Decapeptyl 6 Month 22.5mg Active Ingredients triptorelin pamoate
Medicine Name Dysport Active Ingredients Clostridium botulinum type A toxin-haemagglutinin complex
Medicine Name INCRELEX Active Ingredients Mecasermin
Medicine Name Mucodyne 375mg Capsules- Discontinued Active Ingredients Carbocisteine
Medicine Name NutropinAq Active Ingredients Somatropin
Medicine Name Somatuline Autogel 60 mg, 90 mg and 120 mg solution for injection in a pre-filled syringe Active Ingredients Lanreotide acetate
Medicine Name Somatuline LA 30mg Active Ingredients Lanreotide acetate
Medicine Name Xermelo 250 mg film-coated tablets Active Ingredients Telotristat ethyl
1 - 0 of 11 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 1 July 2020 Ed-Ptnt

Reasons for updating

  • Add New Doc

Updated on 1 July 2020 Ed-HCP

Reasons for updating

  • Add New Doc

Updated on 1 July 2020 Ed-HCP

Reasons for updating

  • Add New Doc

Free text change information supplied by the pharmaceutical company

Update with respect to the information relating to an adverse event, neoplasia

Updated on 1 July 2020 Ed-HCP

Reasons for updating

  • Replace document

Free text change information supplied by the pharmaceutical company

Update with respect to the information relating to an adverse event, neoplasia

Updated on 1 July 2020 Ed-Ptnt

Reasons for updating

  • Add New Doc

Free text change information supplied by the pharmaceutical company

Update with respect to the information relating to an adverse event, neoplasia

Updated on 8 January 2020 PIL

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 3 - overdose, missed or forgotten doses
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

Update to add neoplasia AE

Updated on 8 January 2020 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Type II update to add neoplasia

Updated on 8 December 2019 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 6 - what the product contains
  • Change to other sources of information section

Free text change information supplied by the pharmaceutical company

Update to warning for pregnancy to include standard QRD template wording

Update for excipient warning to include sodium and to update wording for benzyl alcohol

Update to section 6 to reference updated excipient warnings in section 2

Updated on 8 December 2019 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.3 - Shelf life
  • Change to section 6.5 - Nature and contents of container

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Update to section 4.1 to include statement that physician can decide to carry out IGF-1 generation test

Update to section 4.2 to include text for posology for special populations

Update to section 4.6 to update section on breast-feeding

Rewording of section 4.7

Reformating of AEs for immune system disorders in reactions observed from post-marketing in section 4.8.

Inclusion of age range for paediatric patients in first paragraph under clinical efficacy and safety in section 5.1

Removal of statement regarding in-use storage being the responsibility of the user in section 6.3.

Removal of statement relating to appearance of the solution on removal from the fridge in section 6.5.

Updated on 1 August 2019 Ed-HCP

Reasons for updating

  • Add New Doc

Free text change information supplied by the pharmaceutical company

Version 5 of HCP dosing guide approved 16 April 2018.

Updated on 22 September 2017 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 22 September 2017 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 2: addition of product presentation
Section 4: addition of wording relating to the use of antibody testing for allergic reactions for patients treated with IGF-1

Updated on 21 September 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 21 September 2017 PIL

Reasons for updating

  • Change to section 6 - date of revision
  • Change to other sources of information section

Updated on 10 June 2015 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company



Update of section 4.4 of the SmPC to include information regarding the possible occurrence of avascular necrosis in relation to slipped capital femoral epiphysis.

Slipped capital femoral epiphysis (with the potential to lead to avascular necrosis) and progression of scoliosis can occur in patients who experience rapid growth. These conditions and other symptoms and signs known to be associated with GH treatment in general should be monitored during INCRELEX treatment. Any patient with the onset of a limp or complaint of hip or knee pain should be evaluated. 

Updated on 8 May 2015 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.8 (undesirable effects):

The following AEs can be removed from the SmPC:

Otorrhoea, Retching, Hypertrophy, Injection site fibrosis, Injection site discoloration, Spinal deformity, Dyspnoea,  Mouth  breathing,  Obstructive airway disorder, Adenotonsillectomy and Adenoidectomy, Lymphadenopathy, Atrial hypertrophy, Myopia, Visual acuity reduced, Dysphagia, Asthenia, Lethargy, Chest discomfort, Febrile infection (Pyrexia), Oral candidiasis, Otitis externa, Tonsillitis, Upper Respiratory Tract Infection, Pharyngitis, Increased alanine aminotransferase, Increased aspartate aminotransferase, Obesity, Hyperlipidaemia, Flank pain, Muscle cramp (PT Muscle spasms), Febrile convulsion, Loss of consciousness, Restless leg syndrome, Abnormal behaviour, Disorientation, Sleep terror, Hydronephrosis, Nephrolithiasis, Renal colic, Ovarian cyst, Abnormal respiration (Breath sounds abnormal), Nasal congestion, Nasal turbinate hypertrophy and Acrochordon.

Section 5.1 Pharmacodynamic properties
Further information added to: Clinical efficacy and safety

Section 10: date of Preparation updated 23 April 2015

Updated on 1 May 2015 PIL

Reasons for updating

  • Change to side-effects
  • Addition of manufacturer

Updated on 29 September 2014 SmPC

Reasons for updating

  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

There has been a slight change to the SPC which I recently sent you for Increlex.  The change is as follows:

Date of revision of text field has been updated to 15th July 2014.   

Updated on 23 September 2014 PIL

Reasons for updating

  • Addition of black triangle

Updated on 19 September 2014 SmPC

Reasons for updating

  • Addition of black triangle
  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 4.8- Healthcare professionals are asked to report any suspected adverse reactions.

Updated on 19 December 2012 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to MA holder contact details

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Ipsen's CCSI version 3, consisted of the addition of alopecia as a new AE to section 4.8 of the SmPC

Updated on 14 December 2012 PIL

Reasons for updating

  • Change to side-effects
  • Change to MA holder contact details

Updated on 27 January 2012 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

$0Major changes are required to sections      4.8$0$0$0$0$0Please note table in 5.1 need formatting  correctly, the content is correct but some rows are out of alignment and the table footnote text is not presented as such at present.$0$0Please also note section 10 requires updating.$0

Updated on 26 January 2012 PIL

Reasons for updating

  • Change due to user-testing of patient information
  • Correction of spelling/typing errors

Updated on 19 June 2011 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.8         Undesirable effects

 

An integrated safety database from clinical studies contains 76 subjects with severe Primary IGFD treated for a mean duration of 4.4 years and representing 321 subject-years.

 

Hypoglycaemia is the most frequently reported adverse drug reaction. The thirty-six subjects (47%) who had one or more episodes of hypoglycaemia included 4 subjects who had hypoglycaemic seizure on one or more occasion. Of the 36 subjects, 12 (33%) had a history of hypoglycaemia prior to beginning treatment. The frequency of hypoglycaemia was highest in the first month of treatment, and episodes were more frequent in younger children. Symptomatic hypoglycaemia was generally avoided when a meal or snack was consumed either shortly before or after the administration of INCRELEX.

 

Injection site hypertrophy occurred in 24 subjects (32%). This reaction was generally associated with lack of proper rotation of injections. When injections were properly dispersed, the condition resolved.

 

Tonsillar hypertrophy was noted in 12 (16%) subjects, particularly in the first 1 to 2 years of therapy with lesser tonsillar growth in subsequent years.

 

Snoring, generally beginning in the first year of treatment, was reported in 17 subjects (22%).

 

Hypoacusis was reported in 15 subjects (20%).

 

Intracranial hypertension occurred in three subjects (4%). In two subjects the events resolved without interruption of INCRELEX treatment. INCRELEX treatment was discontinued in the third subject and resumed later at a lower dose without recurrence. Fourteen subjects (18%) had headache considered related to study drug.

 

During clinical trials in other indications totalling approximately 300 patients,

reports of local and/or systemic hypersensitivity were received for 8% of patients. All

cases were mild or moderate in severity and none was serious.

 

As with all protein pharmaceuticals, some patients may develop antibodies to INCRELEX. Anti-IGF‑1 antibodies were observed in 11 of 23 children with severe Primary IGFD tested during the first year of therapy. No attenuation of growth was observed as a consequence of the development of antibodies.

 

Table 1 contains very common (≥ 1/10) and common (≥ 1/100 to < 1/10) adverse reactions for which there is at least a reasonable suspicion of a causal relationship to INCRELEX treatment which occurred in clinical trials. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Table 1:  Adverse Drug Reactions in Clinical Trials

System Organ Class

Adverse Reaction

Very Common

Common

Investigations

 

 

Cardiac murmur, abnormal tympanometry, abnormal echocardiogram, increased alanine aminotransferase*, increased aspartate aminotransferase*, increased weight

 

Cardiac Disorders

       

 

Cardiomegaly, ventricular hypertrophy, atrial hypertrophy*, tachycardia, tachycardia paroxysmal*, mitral valve incompetence*, tricuspid valve incompetence*

 

Congenital, Familial and Genetic Disorders

 

Congenital jaw malformation, pigmented naevus*

 

Blood and Lymphatic System Disorders

 

Thymus hypertrophy

 

Lymphadenopathy*

 

Nervous System Disorders

 

Headache

 

Convulsions, febrile convulsion*, benign intracranial hypertension, loss of consciousness*, sleep apnoea syndrome, dizziness, tremor*, restless leg syndrome*

 

Eye Disorders

 

 

Papilloedema, reduced visual acuity*, myopia*

 

Ear and Labyrinth Disorders

 

Hypoacusis

 

Otorrhoea, ear disorder*, middle ear disorder*, tympanic membrane disorder*, ear pain, ear congestion*, fluid in middle ear

 

Respiratory, Thoracic and Mediastinal Disorders

 

Tonsillar hypertrophy, snoring

 

Adenoidal hypertrophy, nasal turbinate hypertrophy*, dyspnoea*, nasal mucosal disorder*, obstructive airway disorder*, abnormal respiration*, nasal congestion, mouth breathing

 

Gastrointestinal Disorders

 

 

Vomiting, retching*, abdominal pain*, upper abdominal pain*, abdominal distension*, dysphagia*

 

Renal and Urinary Disorders

 

Nephrolithiasis*, hydronephrosis*, renal colic*

 

Skin and Subcutaneous Tissue Disorders

 

 

Skin hypertrophy, acrochordons*, abnormal hair texture*

 

Musculoskeletal and Connective Tissue Disorders

 

 

Arthralgia, pain in extremity, myalgia, scoliosis*, spinal deformity*, soft tissue disorder*, muscle cramp*, flank pain*, musculoskeletal stiffness*

 

Metabolism and Nutrition Disorders

Hypoglycaemia

Hypoglycaemic seizure, hyperglycaemia, hyperlipidaemia*, obesity*

 

Infections and Infestations

      

 

Febrile infection*, upper respiratory tract infection*, otitis media, otitis media serous, chronic otitis media serous *, otitis externa*, pharyngitis*, tonsillitis, ear infection, oral candidiasis*

 

Surgical and Medical Procedures

 

 

Adenotonsillectomy*, adenoidectomy, ear tube insertion

 

General Disorders and Administration Site Conditions

 

Injection site hypertrophy

 

Mucosal membrane hyperplasia, hypertrophy, injection site pain, injection site bruising, injection site fibrosis*, injection site reaction*, injection site swelling*, injection site induration*, injection site pigmentation changes*, mucosal oedema*, asthenia*, lethargy*, chest discomfort*

 

Reproductive System and Breast Disorders

 

 

Gynaecomastia, ovarian cyst*

Psychiatric Disorders

 

 

Depression*, sleep terror, nervousness, abnormal behaviour*, disorientation*

 

* = occurred in only 1 subject (1%)  

 

The following adverse reactions have been identified during post approval use of

INCRELEX:

-Systemic hypersensitivity: anaphylaxis, generalized urticaria, angioedema, dyspnoea.

-Local allergic reactions at the injection site: pruritus, urticaria.

 

In the post-marketing setting, the frequency of cases indicative of anaphylaxis was

estimated to be 0.3%. Symptoms included hives, angioedema, and dyspnoea, and

some patients required hospitalization. Upon re-administration, symptoms did not

re-occur in all patients.

Clinical efficacy

 

Five clinical studies (4 open-label and 1 double-blind, placebo-controlled) were conducted with INCRELEX. Subcutaneous doses of mecasermin, generally ranging from 60 to 120 mg/kg given twice daily (BID), were administered to 76 paediatric subjects with severe Primary IGFD. Patients were enrolled in the studies on the basis of extreme short stature, slow growth rates, low IGF‑1 serum concentrations, and normal GH secretion. Baseline characteristics for the patients evaluated in the primary and secondary efficacy analyses from the combined studies were (mean ± SD): chronological age (years): 6.8 ± 3.8; height (cm): 85.0 ± 15.3; height standard deviation score (SDS): -6.7 ± 1.8; height velocity (cm/yr): 2.8 ± 1.8; height velocity SDS: -3.3 ± 1.7; IGF‑1 (ng/ml): 21.9 ± 24.8; IGF1 SDS: ‑4.4 ± 2.0; and bone age (years): 3.9 ± 2.8. Sixty-two subjects had at least one year of treatment. Of these, 53 (85%) had Laron syndrome-like phenotype; 7 (11%) had GH gene deletion, and 1 (2%) had neutralizing antibodies to GH. Thirty-eight (61%) of the subjects were male; 49 (79%) were Caucasian. Fifty-six (90%) of the subjects were prepubertal at baseline.

 

Annual results for height velocity, height velocity SDS, and height SDS are shown in Table 2. Pre-treatment height velocity data were available for 59 subjects. The height velocities at a given year of treatment were compared by paired t-tests to the pre-treatment height velocities of the same subjects completing that treatment year.

 

Table 2:  Annual Height Results by Number of Years Treated with INCRELEX

 

Pre-Tx

Year 1

Year 2

Year 3

Year 4

Year 5

Year 6

Year 7

Year 8

Height Velocity (cm/yr)

 

 

 

 

 

 

 

 

 

N

59

59

54

48

39

21

20

16

14

Mean (SD)

2.8 (1.8)

8.0 (2.2)

5.8 (1.4)

5.5 (1.9)

4.7 (1.4)

4.7 (1.6)

4.8 (1.5)

4.6 (1.5)

4.5 (1.2)

Mean (SD) for change from pre-Tx

 

+5.2 (2.6)

+3.0 (2.3)

+2.6 (2.3)

+1.6 (2.1)

+1.5 (1.8)

+1.5 (1.7)

+1.0 (2.1)

+0.9 (2.4)

P-value for change from pre-Tx [1]

 

<0.0001

<0.0001

<0.0001

<0.0001

0.0015

0.0009

0.0897

0.2135

Height Velocity SDS

 

 

 

 

 

 

 

 

 

N

59

59

53

47

38

19

18

15

12

Mean (SD)

-3.3 (1.7)

1.9 (2.9)

-0.2 (1.6)

-0.3 (2.0)

-0.7 (1.9)

-0.6 (2.1)

-0.4 (1.4)

-0.4 (1.9)

-0.3 (1.8)

Mean (SD) for change from pre-Tx

P-value for change from pre-Tx [1]

 

+5.1 (3.1)

<0.0001

+3.2 (2.2)

<0.0001

+3.1  (2.4)

<0.0001

+2.5 (2.1)

<0.0001

+2.5 (2.2)

0.0001

+2.7 (1.7)

<0.0001

+2.5 (2.1)

0.0003

+2.8 (2.7)

0.0041

Height SDS

 

 

 

 

 

 

 

 

 

N

62

62

57

51

41

22

20

16

14

Mean (SD)

-6.7 (1.8)

-5.9 (1.7)

-5.6 (1.8)

-5.3 (1.8)

-5.3 (1.8)

-5.5 (1.8)

-5.4 (1.8)

-5.2 (2.0)

-5.2 (1.9)

Mean (SD) for change from pre-Tx

P-value for change from pre-Tx [1]

 

+0.8 (0.5)

<0.0001

+1.1 (0.8)

<0.0001

+1.4 (1.0)

<0.0001

+1.4 (1.1)

<0.0001

+1.4 (1.3)

<0.0001

+1.4 (1.2)

<0.0001

+1.4 (1.1)

0.0001

+1.6 (1.1)

<0.0001

Pre-Tx = Pre-treatment; SD = Standard Deviation; SDS = Standard Deviation Score

[1] P-values for comparison versus pre-Tx values were computed using paired t-tests.

 

Forty-seven subjects were included in an analysis of the effects of INCRELEX on bone age advancement.  The mean ± SD change in chronological age was 5.1 ± 3.0 years and the mean ± SD change in bone age was 5.8 ± 2.9 years.

 

Efficacy is dose dependent. For subjects receiving doses between 100 and 120 μg/kg BID, the mean first year height velocity was approximately 8.7 cm/yr.

 

 

Updated on 27 May 2010 PIL

Reasons for updating

  • Improved electronic presentation

Updated on 26 May 2010 PIL

Reasons for updating

  • New PIL for new product

Updated on 27 August 2008 SmPC

Reasons for updating

  • New SPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)