Forsteo

  • Name:

    Forsteo

  • Company:
    info
  • Active Ingredients:

    Teriparatide

  • Legal Category:

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

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 12/07/18

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Summary of Product Characteristics last updated on medicines.ie: 15/12/2017
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Eli Lilly and Company (Ireland) Limited

Eli Lilly and Company (Ireland) Limited

Company Products

Medicine NameActive Ingredients
Medicine Name ABASAGLAR 100 units/mL solution for injection in cartridge Active Ingredients Insulin glargine
Medicine Name ABASAGLAR 100 units/mL solution for injection in pre-filled pen Active Ingredients Insulin glargine
Medicine Name Adcirca Active Ingredients Tadalafil
Medicine Name Alimta Active Ingredients Pemetrexed disodium
Medicine Name Cialis 10mg Tablets Active Ingredients Tadalafil
Medicine Name Cialis 2.5mg Tablets Active Ingredients Tadalafil
Medicine Name Cialis 20mg Tablets Active Ingredients Tadalafil
Medicine Name Cialis 5mg Tablets Active Ingredients Tadalafil
Medicine Name Cymbalta Active Ingredients duloxetine hydrochloride
Medicine Name Cyramza 10 mg/ml concentrate for solution for infusion Active Ingredients Ramucirumab
Medicine Name Forsteo Active Ingredients Teriparatide
Medicine Name Humalog 100 units/ml Junior KwikPen, solution for injection in a pre-filled pen Active Ingredients Insulin lispro
Medicine Name Humalog 100 units/ml Kwikpen soluton for injection Active Ingredients Insulin lispro
Medicine Name Humalog 100 units/ml, solution for injection in cartridge (3ml) (insulin lispro) Active Ingredients Insulin lispro
Medicine Name Humalog 100 units/ml, solution for injection in vial Active Ingredients Insulin lispro
Medicine Name Humalog 200 Units/ml KwikPen, solution for injection in pre-filled pen Active Ingredients Insulin lispro
Medicine Name Humalog Mix25 100 units/ml Kwikpen suspension for injection Active Ingredients Insulin lispro
Medicine Name Humalog Mix25 100 units/ml suspension for injection in cartridge Active Ingredients Insulin lispro
Medicine Name Humalog Mix50 100 units/ml Kwikpen suspension for injection Active Ingredients Insulin lispro
Medicine Name Humalog Mix50 100 units/ml suspension for injection in cartridge Active Ingredients Insulin lispro
Medicine Name Humulin I (Isophane), 100IU/ml suspension for injection in cartridge Active Ingredients Insulin human
Medicine Name Humulin I (Isophane), 100IU/ml suspension for injection in vial Active Ingredients Human Insulin
Medicine Name Humulin I KwikPen 100 IU/ml suspension for injection Active Ingredients Human Insulin
Medicine Name Humulin M3 (Mixture 3), 100IU/ml suspension for injection in cartridge Active Ingredients Insulin human
Medicine Name Humulin M3 (Mixture 3), 100IU/ml suspension for injection in vial Active Ingredients Insulin human
1 - 0 of 41 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 7 September 2018 Ed-Ptnt

Reasons for updating

  • Add New Doc

Free text change information supplied by the pharmaceutical company

Upload to change category from 'HCP' to 'Patient'.

Updated on 12 July 2018 PIL

Reasons for updating

  • Change to section 2 - excipient warnings
  • Change to section 3 - how to take/use
  • Change to section 6 - date of revision

Updated on 15 December 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 15 December 2017 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
  • Improved presentation of SPC

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

Free text change information supplied by the pharmaceutical company

Changes

 

Added (underline) deleted (strikethrough)

 

Changed FORSTEO to Forsteo throughout in line with current readability expectations.

 

4.8       Undesirable effects

 

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Ireland: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517; website: www.hpra.ie; e-mail: medsafety@hpra.ie, or United Kingdom: Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. UK: www.mhra.gov.uk/yellowcard or Ireland: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, www.hpra.ie, medsafety@hpra.ie.

5.1       Pharmacodynamic properties

 

A 24-month, randomized, double-blind, comparator-controlled Phase 4 study included 1,360 postmenopausal women with established osteoporosis. 680 subjects were randomised to Forsteo and 680 subjects were randomised to oral risedronate 35 mg/week. At baseline, the women had a mean age of 72.1 years and a median of 2 prevalent vertebral fractures; 57.9% of patients had received previous bisphosphonate therapy and 18.8% took concomitant glucocorticoids during the study. 1,013 (74.5%) patients completed the 24-month follow-up. The mean (median) cumulative dose of glucocorticoid was 474.3 (66.2) mg in the teriparatide arm and 898.0 (100.0) mg in the risedronate arm. The mean (median) vitamin D intake for the teriparatide arm was 1433 IU/day (1400 IU/day) and for the risedronate arm was 1191 IU/day (900 IU/day). For those subjects who had baseline and follow-up spine radiographs, the incidence of new vertebral fractures was 28/516 (5.4%) in Forsteo- and 64/533 (12.0%) in risedronate-treated patients, relative risk (95% CI) = 0.44 (0.29-0.68), P<0.0001. The cumulative incidence of pooled clinical fractures (clinical vertebral and non vertebral fractures) was 4.8% in Forsteo and 9.8% in risedronate-treated patients, hazard ratio (95% CI) = 0.48 (0.32-0.74), P=0.0009.

10.       DATE OF REVISION OF THE TEXT

 

            01 January 201609 November 2017

 

 

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.

*FORSTEO (teriparatide) is a trademark of Eli Lilly and Company.        FS17MFS18M

Updated on 15 January 2016 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • 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

Changes

Added (bold), Deleted (strikethrough):

 

 

 

7.      MARKETING AUTHORISATION HOLDER
 Eli Lilly Nederland B.V., Grootslag 1‑5 NL‑3991 RA, HoutenPapendorpseweg 83, 3528 BJ Utrecht, The Netherlands

 

 

10.     DATE OF REVISION OF THE TEXT

 

25 April 201401 January 2016

Updated on 12 January 2016 PIL

Reasons for updating

  • New PIL for new product

Updated on 12 January 2016 PIL

Reasons for updating

  • Change to date of revision
  • Change to MA holder contact details

Updated on 30 May 2014 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 9 - Date of renewal of authorisation
  • 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

New text underlined, deleted text struck through

 

4.8          Undesirable effects

 

Summary of the safety profile

The most commonly reported adverse reactions in patients treated with FORSTEO are nausea, pain in limb, headache and dizziness.

 

Tabulated list of adverse reactions

Of patients in the teriparatide trials, 82.8 % of the FORSTEO patients and 84.5 % of the placebo patients reported at least 1 adverse event.

 

The adverse reactions associated with the use of teriparatide in osteoporosis clinical trials and post-marketing exposure are summarised in the table below. The following convention has been used for the classification of the adverse reactions: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1,000 to <1/100), rare (≥ 1/10,000 to <1/1,000), very rare (<1/10,000)

 

Blood and lymphatic system disorders

Common: Anaemia

Immune System Disorder

Rare: Anaphylaxis

Metabolism and nutrition disorders

Common: Hypercholesterolaemia

Uncommon: Hypercalcaemia greater than 2.76 mmol/L, hyperuricaemia

Rare: Hypercalcaemia greater than 3.25 mmol/L

…..

 

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via UK: www.mhra.gov.uk/yellowcard or Ireland: IMB Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, www.imb.ie, imbpharmacovigilance@imb.ie.

 

9.             DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Date of first authorisation:  10 June 2003

Date of the last renewal: 10 June 2008 2013

 

10.       DATE OF REVISION OF THE TEXT

 

13 February 2013 25 April 2014

Updated on 27 May 2014 PIL

Reasons for updating

  • Change to side-effects
  • Change to date of revision

Updated on 6 March 2014 PIL

Reasons for updating

  • Change to side-effects

Updated on 21 February 2013 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • 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 4.5 - Interaction with other medicinal products and other forms of interaction
  • 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 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.1 - List of excipients
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of renewal of authorisation
  • 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

No new safety information has been added, only format and template changes in all sections.

In Section 10, date of revision is updated.

Updated on 19 February 2013 PIL

Reasons for updating

  • Improved electronic presentation

Updated on 8 November 2011 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • 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

Internal change, reference to Forsteo 3ml pen removed. It was replaced by the 2.4ml pen, 2 years ago, and the 3 ml pen has been gradually phased out.

 

In Section 2, Qualitative and quantitative composition, the following text is deleted – ‘One pre-filled pen of 2.4 ml contains 600 micrograms of teriparatide (corresponding to 250 micrograms per ml). Or’

 

In Section 6.5, Nature and contents of container, the following text is deleted – ‘3ml solution in cartridge (siliconised Type I glass) with a plunger (halobutyl rubber), disc seal (polyisoprene/bromobutyl rubber laminate) and crimp cap (aluminium) assembled into a disposable pen. Or

Updated on 3 November 2011 PIL

Reasons for updating

  • Change due to harmonisation of PIL

Updated on 5 August 2011 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • 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

In Section 4.8 Undesirable effects, Nervous system disordersSyncope moved from ‘Not known’ to ‘Common’; Renal and Urinary disordersNephrolithiasis added to ‘Uncommon’; Renal failure/impairment moved from ‘Not known’ to ‘Rare’; Musculoskeletal and connective tissue disorders - Back cramp/pain moved from ‘Not known’ to ‘Uncommon’

In Section 10 Date of revision of the text, the date of revision is updated.

Updated on 5 August 2011 PIL

Reasons for updating

  • Change to side-effects

Updated on 10 June 2011 PIL

Reasons for updating

  • Change to further information section
  • Change to date of revision

Updated on 3 June 2011 SmPC

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • 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

4.6       Pregnancy and lactation

 

            Change to section 4.6 sub-section heading (QRD template change)

 

- to  4.6  Fertility, Ppregnancy and lactation.

               

5.1       Pharmacodynamic properties

 

Correction of table number & cross reference to table (table number) – from Table 4 to Table 1.

 

10.       DATE OF REVISION OF THE TEXT

 

New date (as previous date)

 

27 May 2011

Updated on 1 December 2010 SmPC

Reasons for updating

  • Correction of spelling/typing errors

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

Free text change information supplied by the pharmaceutical company

This SPC has been revised to remove the black triangle symbol (affecting UK SPC version only) – there are no other content changes.   Accordingly, the Lilly internal SPC code has been updated to FS11M only.

Updated on 16 June 2010 PIL

Reasons for updating

  • Change of manufacturer
  • Change to side-effects
  • Change to date of revision

Updated on 1 April 2010 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • 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

Changes

 

 

Added text: ‘in bold, over size’

 

4.             CLINICAL PARTICULARS

 

4.8          Undesirable effects

 

Of patients in the teriparatide trials, 82.8% of the FORSTEO patients and 84.5% of the placebo patients reported at least 1 adverse event.

 

The most commonly reported adverse reactions in patients treated with FORSTEO are nausea, pain in limb, headache and dizziness.

 

The undesirable reactions associated with the use of teriparatide in osteoporosis clinical trials and post-marketing exposure are summarised in the table below. The following convention has been used for the classification of the adverse reactions: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1,000 to <1/100), rare (≥ 1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

 

Investigations

Uncommon: Weight increased, Cardiac murmur, Alkaline phosphatase increase

Cardiac disorders

Common: Palpitations

Uncommon: Tachycardia

Blood and lymphatic system disorders

Common: Anaemia

Nervous system disorders

Common: Dizziness, Headache, Sciatica

Not known: Syncope

Ear and labyrinth disorders

Common: Vertigo

Respiratory, thoracic and mediastinal disorders

Common: Dyspnoea

Uncommon: Emphysema

Gastrointestinal disorders

Common: Nausea, Vomiting, Hiatus hernia, Gastro-oesophageal reflux disease

Uncommon: Haemorrhoids

Renal and urinary disorders

Uncommon: Urinary incontinence, Polyuria, Micturition urgency

Not known: Renal failure/impairment

Skin and subcutaneous tissue disorders

Common: Sweating increased

 

Musculoskeletal and connective tissue disorders

Very common: Pain in limb

Common: Muscle cramps

Uncommon: Myalgia, Arthralgia

Not known: Back cramp/pain*

Metabolism and nutrition disorders

Common: Hypercholesterolaemia

Uncommon: Hypercalcaemia greater than 2.76 mmol/L, Hyperuricaemia

Rare: Hypercalcaemia greater than 3.25 mmol/L

Vascular disorders

Common: Hypotension

General disorders and administration site conditions

Common: Fatigue, Chest pain, Asthenia, Mild and transient injection site events, including pain, swelling, erythema, localised bruising, pruritus and minor bleeding at injection site

Uncommon: Injection site erythema, Injection site reaction

Rare: Possible allergic events soon after injection: acute dyspnoea, oro/facial oedema, generalised urticaria, chest pain, oedema (mainly peripheral)

Psychiatric disorders

Common: Depression

* Serious cases of back cramp or pain have been reported within minutes of the injection.

 

In clinical trials the following reactions were reported at a ≥ 1% difference in frequency from placebo: vertigo, nausea, pain in limb, dizziness, depression, dyspnoea.

 

FORSTEO increases serum uric acid concentrations.  In clinical trials, 2.8% of FORSTEO patients had serum uric acid concentrations above the upper limit of normal compared with 0.7% of placebo patients.  However, the hyperuricaemia did not result in an increase in gout, arthralgia, or urolithiasis.

 

In a large clinical trial, antibodies that cross-reacted with teriparatide were detected in 2.8% of women receiving FORSTEO.  Generally, antibodies were first detected following 12 months of treatment and diminished after withdrawal of therapy.  There was no evidence of hypersensitivity reactions, allergic reactions, effects on serum calcium, or effects on BMD response.

 

 

 

 

10.          DATE OF REVISION OF THE TEXT

 

New date

 

18 March 2010

Updated on 8 October 2009 PIL

Reasons for updating

  • Change to side-effects
  • Change to further information section
  • Change to date of revision

Updated on 21 September 2009 SmPC

Reasons for updating

  • Change to section 4.3 - Contraindications
  • 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

4.             CLINICAL PARTICULARS

4.3          Contraindications

 

Added (bold) deleted (strikethrough):

 

·                Metabolic bone diseases (including hyperparathyroidism and Paget’s disease of the bone) other than primary osteoporosis or glucorticoid-induced osteoporosis (including hyperparathyroidism and Paget’s disease of the bone).

 

4.8          Undesirable effects

 

Added (bold):

 

The undesirable reactions associated with the use of teriparatide in osteoporosis clinical trials and post-marketing exposure are summarised in the table below.

 

Renal and urinary disorders

 

Added:

 

Not known: Renal failure/impairment

 

 

 

5.            PHARMACOLOGICAL PROPERTIES

 

5.1          Pharmacodynamic properties

 

 

Added (bold) deleted (strikethrough):

 

Pharmaco-therapeutic group: parathyroid hormones and analogues, ATC code: H05 AA023.

 

 

10.          DATE OF REVISION OF THE TEXT

 

New date

 

28 August 2009

Updated on 8 July 2009 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 6.5 - Nature and contents of container
  • 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

*Forsteo ‘new’ pen launch 2009 - SPC revised to create combined SPC for ‘old’ Forsteo pen and ‘new’ Forsteo pen. No other changes have been made.

 

 

 

2.             QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Added:

 

or

 

One pre-filled pen of 2.4 ml contains 600 micrograms of teriparatide (corresponding to 250 micrograms per ml).

 

 

 

6.             PHARMACEUTICAL PARTICULARS

 

6.5          Nature and contents of container

 

Added:

 

or

 

2.4 ml solution in cartridge (siliconised Type I glass) with a plunger (halobutyl rubber), disc seal (polyisoprene/bromobutyl rubber laminate)/aluminium assembled into a disposable pen.

 

 

 

10.          DATE OF REVISION OF THE TEXT

 

New date

 

25 February 2009

 

 

Updated on 2 July 2009 PIL

Reasons for updating

  • Addition of separate PILs covering individual presentations

Updated on 20 March 2009 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to date of revision
  • Change due to harmonisation of patient information leaflet

Updated on 10 March 2009 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.3 - Preclinical safety data
  • 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

4.              CLINICAL PARTICULARS

 

4.2           Posology and method of administration

 

Deleted (strikethrough) Added (bold):

 

The maximum total duration of treatment with FORSTEO should be 18 24 months (see section 4.4). The 18 24-month course of FORSTEO should not be repeated over a patients lifetime.

 

4.4       Special warnings and precautions for use

 

Deleted (strikethrough) Added (bold):

 

Studies in rats indicate an increased incidence of osteosarcoma with long-term administration of teriparatide (see section 5.3). Until further clinical data become available, the recommended treatment time of 18  24 months should not be exceeded.

 

 

 

5.         PHARMACOLOGICAL PROPERTIES

 

5.1           Pharmacodynamic properties

 

Deleted (strikethrough) Added (bold):

 

Postmenopausal women Postmenopausal osteoporosis:

 

 

Postmenopausal osteoporosis:

 

Added:

 

In an open-label study, 503 postmenopausal women with severe osteoporosis and a fragility fracture within the previous 3 years (83%) had received previous osteoporosis therapy) were treated with FORSTEO for up to 24 months. At 24 months, the mean increase from baseline in lumbar spine, total hip and femoral neck BMD was 10.5%, 2.6% and 3.9% respectively. The mean increase in BMD from 18 to 24 months was 1.4%, 1.2%, and 1.6% at the lumbar spine, total hip and femoral neck, respectively.

 

Glucocorticoid-induced osteoporosis:

 

Added (bold):

 

The efficacy of Forsteo in men and women (N=428) receiving sustained systemic glucocorticoid therapy (equivalent to 5 mg or greater of prednisone for at least 3 months) was demonstrated in the 18-month primary phase of a 36-month, randomised, double-blind, comparator-controlled study (alendronate 10 mg/day).

 

Sixty-nine percent of patients completed the 18-month primary phase.  At the 18-month endpoint, FORSTEO significantly increased lumbar spine BMD (7.2%) compared with alendronate (3.4%) (p<0.001). FORSTEO increased BMD at the total hip (3.6%) compared with alendronate (2.2%) (p<0.01), as well as at the femoral neck (3.7%) compared with alendronate (2.1%) (p<0.05).

Deleted:

 

A preliminary analysis of 336 spinal X-rays showed that 10 patients in the alendronate group (6.1%) had experienced a new vertebral fracture compared with 1 patient in the FORSTEO group (0.6%). In addition, 9 patients in the alendronate group (4.2%) had experienced a nonvertebral fracture compared with 12 patients in the FORSTEO group (5.6%).

 

Added:

 

In patients treated with teriparatide, lumbar spine, total hip and femoral neck BMD increased between 18 and 24 months by an additional 1.7%, 0.9%, and 0.4%, respectively.

 

At 36 months, analysis of spinal X-rays from 169 alendronate patients and 173 FORSTEO patients showed that 13 patients in the alendronate group (7.7%) had experienced a new vertebral fracture compared with 3 patients in the FORSTEO group (1.7%) (p=0.01). In addition, 15 of 214 patients in the alendronate group (7.0%) had experienced a nonvertebral fracture compared with 16 of 214 patients in the FORSTEO group (7.5%) (p=0.84).

 

Added (bold):

 

In premenopausal women, the increase in BMD from baseline to 18 month endpoint was significantly greater in the FORSTEO group compared with the alendronate group at the lumbar spine (4.2% versus −1.9%; p<0.001) and total hip (3.8% versus 0.9%; p=0.005).

 

5.3       Preclinical safety data

 

Added (bold):

 

Rats treated with near-life time daily injections had dose-dependent exaggerated bone formation and increased incidence of osteosarcoma most probably due to an epigenitic mechanism. Teriparatide did not increase the incidence of any other type of neoplasia in rats. Due to the differences in bone physiology in rats and humans, the clinical relevance of these findings is probably minor. No bone tumours were observed in ovariectomised monkeys treated for 18 months nor during a 3-year follow-up period after treatment cessation. In addition, no osteosarcomas have been observed in clinical trials or during the post treatment follow-up study.

 

 

 

10.          DATE OF REVISION OF THE TEXT

 

New date

 

25 February 2009

Updated on 10 June 2008 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.1 - List of excipients
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of renewal of authorisation
  • 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

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Added:

Each dose contains 20 micrograms of teriparatide.

Deleted:

Each dose contains 20 micrograms of teriparatide. The pre-filled pen is intended for 28 days of dosing.

Deleted (bold):

Teriparatide, rhPTH(1-34), (FORSTEO), produced in E. coli, using recombinant DNA technology, is identical to

the 34 N-terminal amino acid sequence of endogenous human parathyroid hormone.

4. CLINICAL PARTICULARS

4.2    Posology and method of administration

Changed whole paragraph:

Paediatric population and young adults with open epiphyses: There is no experience in paediatric patients (less

than 18 years). FORSTEO should not be used in paediatric patients (less than 18 years), or young adults with open

epiphyses.

4.8    Undesirable effects

Added (bold) deleted (strikethrough):

The most commonly reported adverse reactions in patients treated with FORSTEO are nausea, pain in limb,

headache and dizziness. Tables 1, 2 and 3 give an overview of all treatment emergent adverse events reactions

that were observed in the trial populations, irrespective of causal relationship. The following events reactions were

observed in clinical trials in 1382 patients.

Added:

The undesirable reactions associated with the use of teriparatide in osteoporosis clinical trials are summarised in

the table below. The following convention has been used for the classification of the adverse reactions: very

common (¡Ý 1/10), common (¡Ý 1/100 to <1/10), uncommon (¡Ý 1/1,000 to <1/100), rare (¡Ý 1/10,000 to <1/1,000)

very rare (<1/10,000), not known (cannot be estimated from the available data).

TABLE

* Serious cases of back cramp or pain have been reported within minutes of the injection.

In clinical trials the following reactions were reported at a ¡Ý 1% difference in frequency from placebo: vertigo,

nausea, pain in limb, dizziness, depression, dyspnoea.

Deleted:

The following table of adverse reactions is based on post-marketing spontaneous reports.

The following convention has been used for the classification of the adverse reactions: very common (¡Ý 1/10),

common (¡Ý 1/100 to <1/10), uncommon (¡Ý 1/1,000 to <1/100), rare (¡Ý 1/10,000 to <1/1,000) very rare

(<1/10,000), not known (cannot be estimated from the available data).

TABLE

4.9 Overdose

Overdose experience based on post-marketing spontaneous reports:

Changed to:

(up to 800 ¦Ìg)

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Deleted (strikethrough) Added (bold):

Pharmaco-therapeutic group: calcium homeostasis, ATC code: H05AA02 parathyroid hormones and

analogues, ATC code: H05 AA03.

5.3 Preclinical safety data

Changed to:

1000 ¦Ìg/kg and 100 ¦Ìg/kg

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Deleted (strikethrough):

Metacresol (preservative)

6.6 Special precautions for disposal

Changed (deleted strikethrough) to:

FORSTEO is supplied in a pre-filled pen and is intended for single patient use only. Each pen should be used by

only one patient. A new, sterile needle must be used for every injection.

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Added:

Date of last renewal 10 June 2008

10. DATE OF REVISION OF THE TEXT

New date

20 May 2008

Updated on 24 April 2008 PIL

Reasons for updating

  • Changes to therapeutic indications
  • Change to warnings or special precautions for use
  • Change to information about pregnancy or lactation
  • Change to further information section
  • Change to date of revision

Updated on 10 April 2008 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 4.6 - Pregnancy and lactation
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.3 - Preclinical safety data
  • 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

4.             CLINICAL PARTICULARS

 

4.1          Therapeutic indications

 

Added:

 

Treatment of osteoporosis associated with sustained systemic glucocorticoid therapy in women and men at increased risk for fracture (see section 5.1).

 

 

4.2          Posology and method of administration

 

Added (bold text):

 

The maximum total duration of treatment with FORSTEO should be 18 months (see section 4.4). The 18-month course of FORSTEO should not be repeated over a patient¡¯s lifetime.

 

 

4.3                Contraindications

 

Added (New Bullet):

 

¡¤                      Pregnancy and lactation (see section 4.4 and 4.6)

 

 

4.4          Special warnings and precautions for use

 

Added:

 

Experience in the younger adult population, including premenopausal women, is limited (see section 5.1).  Treatment should only be initiated if the benefit clearly outweighs risks in this population.

 

Women of childbearing potential should use effective methods of contraception during use of FORSTEO. If pregnancy occurs, FORSTEO should be discontinued.

 

 

4.6               Pregnancy and lactation

 

Deleted:

 

The potential risk for humans is unknown. Given the indication, FORSTEO should not be used during pregnancy or by breast-feeding women.

 

Added:

 

General recommendation

 

Studies in rabbits have shown reproductive toxicity (see section 5.3). The effect of teriparatide on human foetal development has not been studied. The potential risk for humans is unknown.

It is not known whether teriparatide is excreted in human milk.

 

FORSTEO is contraindicated for use during pregnancy or breast-feeding.

 

Women of childbearing potential / Contraception in females

 

Women of childbearing potential should use effective methods of contraception during use of FORSTEO.  If pregnancy occurs, FORSTEO should be discontinued.

 

Added (bold text):

 

 

System Organ Class

 

Adverse reactions

General Disorders and Administration Site Conditions

Rare: Possible allergic events soon after injection: acute dyspnoea, oro/facial oedema, generalized urticaria, chest pain, oedema (mainly peripheral).

Common: Mild and transient injection site events, including pain, swelling, erythema, localised bruising, pruritis and minor bleeding at injection site.

Metabolism and Nutrition Disorders

Uncommon: Hypercalcemia greater than 2.76 mmol/l (11mg/dl).

Rare: Hypercalcemia greater than 3.25 mmol/l (13mg/dl).

Musculoskeletal and Connective Tissue and Bone Disorders

Uncommon: myalgia, arthralgia,

Not known: Back cramp/pain*

 

Investigations

Uncommon: alkaline phosphatase increase

* Serious cases of back cramp or pain have been reported within minutes of the injection.

 

 

 

5.            PHARMACOLOGICAL PROPERTIES

 

5.1          Pharmacodynamic properties

 

Added:

Clinical efficacy

 

Risk Factors

 

Premenopausal women with glucocorticoid-induced osteoporosis should be considered at high risk for fracture if they have a prevalent fracture or a combination of risk factors that place them at high risk for fracture (e.g., low bone density [e.g., T score ¡Ü−2], sustained high dose glucocorticoid therapy [e.g., ¡Ý7.5 mg/day for at least 6 months], high underlying disease activity, low sex steroid levels).

Glucocorticoid-induced osteoporosis

 

The efficacy of Forsteo in men and women (N=428) receiving sustained systemic glucocorticoid therapy (equivalent to 5 mg or greater of prednisone for at least 3 months) was demonstrated in an 18-month, randomised, double-blind, comparator-controlled study (alendronate 10 mg/day). Twenty-eight percent of patients had one or more radiographic vertebral fractures at baseline. All patients were offered 1000 mg calcium per day and 800 IU vitamin D per day.

This study included postmenopausal women (N=277), premenopausal women (N=67), and men (N=83). At baseline, the postmenopausal women had a mean age of 61 years, mean lumbar spine BMD T score of −2.7, median prednisone equivalent dose of 7.5 mg/day, and 34% had one or more radiographic vertebral fractures; premenopausal women had a mean age of 37 years, mean lumbar spine BMD T score of −2.5, median prednisone equivalent dose of 10 mg/day, and 9% had one or more radiographic vertebral fractures; and men had a mean age of 57 years, mean lumbar spine BMD T score of −2.2, median prednisone equivalent dose of 10 mg/day, and 24% had one or more radiographic vertebral fractures.

 

Sixty-nine percent of patients completed the 18-month study.  At endpoint, FORSTEO significantly increased lumbar spine BMD (7.2%) compared with alendronate (3.4%) (p<0.001). FORSTEO increased BMD at the total hip (3.6%) compared with alendronate (2.2%) (p<0.01), as well as at the femoral neck (3.7%) compared with alendronate (2.1%) (p<0.05).

A preliminary analysis of 336 spinal X-rays showed that 10 patients in the alendronate group (6.1%) had experienced a new vertebral fracture compared with 1 patient in the FORSTEO group (0.6%). In addition, 9 patients in the alendronate group (4.2%) had experienced a nonvertebral fracture compared with 12 patients in the FORSTEO group (5.6%).

 

In premenopausal women, the increase in BMD from baseline to endpoint was significantly greater in the FORSTEO group compared with the alendronate group at the lumbar spine (4.2% versus −1.9%; p<0.001) and total hip (3.8% versus 0.9%; p=0.005).  However, no significant effect on fracture rates was demonstrated.

 

5.3          Preclinical safety data

 

Added (bold text):

 

Teriparatide was not genotoxic in a standard battery of tests. It produced no teratogenic effects in rats, mice or rabbits. There were no important effects observed in pregnant rats or mice administered teriparatide at daily doses of 30 to 1000 mcg/kg. However, foetal resorption and reduced litter size occurred in pregnant rabbits administered daily doses of 3 to 100 mcg/kg. The embryotoxicity observed in rabbits may be related to their much greater sensitivity to the effects of PTH on blood ionised calcium compared with rodents.

 

 

 

 

10.          DATE OF REVISION OF THE TEXT

 

New date

 

02 April 2008

Updated on 5 December 2007 PIL

Reasons for updating

  • Change to side-effects
  • Change to date of revision

Updated on 4 September 2007 PIL

Reasons for updating

  • Change to side-effects
  • Change to date of revision

Updated on 29 August 2007 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • 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

4.             CLINICAL PARTICULARS

 

4.8          Undesirable effects

 

Added ‘oedema (mainly peripheral)’ as a rare adverse reaction in the table listing post-marketing spontaneous reports.

 

 

 

10.          DATE OF REVISION OF THE TEXT

 

New date

 

21 August 2007

Updated on 20 August 2007 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to instructions about overdose
  • Change to storage instructions
  • Change to drug interactions
  • Change to side-effects
  • Change to information about drinking alcohol
  • Change to information about pregnancy or lactation
  • Change to information about driving or using machinery
  • Change to further information section
  • Change to date of revision

Updated on 2 July 2007 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • 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 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of renewal of authorisation
  • 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

2.             QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Added (new text in bold):

               

For a full list of excipients, see section 6.1.

 

 

 

4.             CLINICAL PARTICULARS

 

4.1          Therapeutic indications

 

Deletions in strikethrough text and added text in bold.

 

Treatment of established osteoporosis in postmenopausal women and in men at increased risk of fracture (see section 5.1).  In post menopausal women a significant reduction in the incidence of vertebral and non-vertebral fractures, but not hip fractures has been demonstrated.

 

4.2          Posology and method of administration

 

Deletions in strikethrough text and added text in bold.

 

Children:  Forsteo has not been studied in paediatric populations.  Forsteo should not be used in paediatric patients or young adults with open epiphyses. There is no experience in children.  Forsteo should not be used in paediatric patients or young adults with open epiphyses.

 

4.3          Contra-indications

 

Changed text shown in bold.

 

·         Hypersensitivity to the active substance or to any of the excipients.

 

4.8          Undesirable effects

 

Changed the way the frequency classification is expressed in all tables.

               

Changes to following statement shown in bold text.

 

The following convention has been used for the classification of the adverse reactions: very common (³1/10), common (³1/100 to<1/10), uncommon (³1/1,000 to <1/100), rare (³1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

 

 


 

5.             PHARMACOLOGICAL PROPERTIES

 

5.1          Pharmacodynamic properties

 

Added:

 

Independent risk factors, for example, low BMD, age, the existence of previous fracture, family history of hip fractures, high bone turnover and low body mass index should be considered in order to identify women and men at increased risk of osteoporotic fractures who could benefit from treatment.

 

Deletion shown in strikethrough text and added texts shown in bold.

 

Postmenopausal women: with established osteoporosis (T-score below -2.5 in the presence of one or more fragility fracture):

 

At baseline, ninety percent of the patients had one or more vertebral fractures and on average, vertebral BMD was 0.82 g/cm2 (equivalent to a T-score = -2.6).  All patients were offered 1000mg calcium per day and at least 400IU vitamin D per day.  Results from up to 24 months (median: 19 months) treatment with Forsteo demonstrate statistically significant fracture reduction (Table 4).  To prevent one or more new vertebral fractures, 11 women had to be treated for a median of 19 months.

 

Changes to table shown in bold text:

 

Table 4

Fracture Incidence in Postmenopausal Women

 

 

Placebo

n = 544

(%)

Forsteo

n = 541

(%)

Relative Risk

(95% CI)

vs Placebo

New vertebral fracture (³1)a

14.3

5.0 b

0.35

(0.22, 0.55)

Multiple vertebral fractures (³2)a

4.9

1.1 b

0.23

(0.09, 0.60)

Non-vertebral fragility fractures c

5.5%

2.6% c

0.47
(0.25, 0.87)

Major non-vertebral fragility fracturesc (hip, radius, humerus, ribs and pelvis)

3.9%

1.5% c

0.38
(0.17, 0.86)

Abbreviations:  n = number of patients randomly assigned to each treatment group;  CI = Confidence Interval.

 

 a The incidence of vertebral fractures was assessed in 448 placebo and 444 Forsteo patients who had baseline and follow-up spine radiographs.

 b P£0.001 compared with placebo

c P£0.025 compared with placebo

 

Added text in bold

 

Male osteoporosis:

 

437 patients (mean age 58.7 years) were enrolled in a clinical trial for men with hypogonadal (defined as low morning free testosterone or an elevated FSH or LH) or idiopathic osteoporosis.  . Baseline spinal and femoral neck bone mineral density mean T-scores were -2.2 and -2.1, respectively.  At baseline, 35% of patients had a vertebral fracture and 59% had a non-vertebral fracture.

 

 

 

6.             PHARMACEUTICAL PARTICULARS

 

6.4          Special precautions for storage

 

Changed storage instruction from ‘Store at 2ºC-8°C at all times.’ toStore in a refrigerator (2ºC-8°C) at all times.’.


 

6.6          Special precautions for disposal

 

Changed the title of 6.6 from ’Instructions for use and handling’ to the above and deleted the reference to Becton Dickson needles in this section.

 

Added:

 

Any unused product or waste material should be disposed of in accordance with local requirements.

 

 

 

9.             DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Added text in bold

 

Date of first authorisation: 10 June 2003

 

 

 

10.          DATE OF REVISION OF THE TEXT

 

New date

 

22 June 2007

Updated on 27 January 2006 SmPC

Reasons for updating

  • Change to section 4.3 - Contraindications
  • 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)

Updated on 19 December 2005 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to date of revision

Updated on 12 October 2004 PIL

Reasons for updating

  • New PIL for medicines.ie

Updated on 15 August 2003 SmPC

Reasons for updating

  • Improved electronic presentation

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

Updated on 30 June 2003 SmPC

Reasons for updating

  • New SPC for new product

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