FORSTEO, INN-teriparatide
Contents
1. HOLDERS RESPONSIBLE FOR BATCH RELEASE CONDITIONS OF THE MARKETING AUTHORISATION A MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDERS RESPONSIBLE FOR BATCH RELEASE Name and address of the manufacturer of the biological active substance Boehringer Ingelheim RCV GmbH amp Co KG Dr Boehringer Gasse 5 11 1121 Vienna Austria Name and address of the manufacturers responsible for batch release Lilly France S A S rue du colonel Lilly 67640 Fegersheim France The printed package leaflet of the medicinal product must state the name and address of the manufacturer responsible for the release of the concerned batch B CONDITIONS OF THE MARKETING AUTHORISATION e CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON THE MARKETING AUTHORISATION HOLDER Medicinal product subject to medical prescription CONDITIONS OR RESTRICTIONS WITH REGARDS THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT Not applicable e OTHER CONDITIONS Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance presented in Module 1 8 1 of the Marketing Authorisation is in place and functioning before and whilst the product is on the market The Marketing Authorisation Holder will submit PSURs annually Risk Management Plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan as agreed in the versi2. Subcutaneous use 2 METHOD OF ADMINISTRATION Read the package leaflet before use 3 EXPIRY DATE Exp MM YYYY 4 BATCH NUMBER Lot 5 CONTENTS BY WEIGHT BY VOLUME OR BY UNIT 2 4 ml 6 OTHER Store in a refrigerator B PACKAGE LEAFLET PACKAGE LEAFLET INFORMATION FOR THE USER FORSTEO 20 micrograms 80 microliters solution for injection in pre filled pen Teriparatide Read all of this leaflet carefully before you start using this medicine Keep this leaflet You may need to read it again If you have any further questions ask your doctor or pharmacist This medicine has been prescribed for you Do not pass it on to others It may harm them even if their symptoms are the same as yours If any of the side effects gets serious or if you notice any side effects not listed in this leaflet please tell your doctor or pharmacist In this leaflet 1 What FORSTEO is and what it is used for 2 Before you use FORSTEO 3 How to use FORSTEO 4 Possible side effects 5 How to store FORSTEO 6 Further information 1 WHAT FORSTEO IS AND WHAT IS USED FOR FORSTEO is used to make the bones stronger and to reduce the risk of fractures bone formation agent This product is used to treat osteoporosis Osteoporosis is a disease that causes your bones to become thin and fragile This disease is especially common in women after the menopause but it can also occur
3. 7 sland Icepharma hf Simi 354 540 80 00 Italia Eli Lilly Italia S p A Tel 39 055 42571 Phadisco Ltd Tq 357 22 715000 Latvija Eli Lilly Holdings Limited p rst vniec ba Latvija Tel 371 67364000 Lietuva Eli Lilly Holdings Limited atstovyb Tel 370 5 2649600 This leaflet was last approved on MM YYYY Rom nia Eli Lilly Rom nia S R L Tel 40 21 4023000 Slovenija Eli Lilly farmacevtska druZba d o o Tel 386 0 1 580 00 10 Slovensk republika Eli Lilly Slovakia s r o Tel 421 220 663 111 Suomi Finland Oy Lilly Finland Ab Puh Tel 358 0 9 85 45 250 Sverige Eli Lilly Sweden AB Tel 46 0 8 7378800 United Kingdom Eli Lilly and Company Limited Tel 44 0 1256 315000 Detailed information on this medicine is available on the European Medicines Agency web site http www ema europa eu 24 PEN USER MANUAL Forsteo FORSTEO 20 micrograms ug 80 microlitres solution for injection in pre filled pen Instructions for Use Before you use your new FORSTEO please read the section Instructions for Use completely Follow the directions carefully when using the FORSTEO Also read the package leaflet provided Do not share your pen or your needles as this may risk transmission of infectious agents Your FORSTEO contains 28 days of medication Forsteo Parts Yellow Shaft Black Injection button Red Stripe Blue Body Medicine C
4. ANNEXI SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT FORSTEO 20 micrograms 80 microliters solution for injection in pre filled pen 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each dose contains 20 micrograms of teriparatide One pre filled pen of 2 4 ml contains 600 micrograms of teriparatide corresponding to 250 micrograms per ml Teriparatide rhPTH 1 34 produced in E coli using recombinant DNA technology is identical to the 34 N terminal amino acid sequence of endogenous human parathyroid hormone For a full list of excipients see section 6 1 3 PHARMACEUTICAL FORM Solution for injection in a pre filled pen Colourless clear solution 4 CLINICAL PARTICULARS 4 4 Therapeutic indications Treatment of osteoporosis in postmenopausal women and in men at increased risk of fracture see section 5 1 In postmenopausal women a significant reduction in the incidence of vertebral and non vertebral fractures but not hip fractures has been demonstrated Treatment of osteoporosis associated with sustained systemic glucocorticoid therapy in women and men at increased risk for fracture see section 5 1 42 Posology and method of administration The recommended dose of FORSTEO is 20 micrograms administered once daily by subcutaneous injection in the thigh or abdomen Patients must be trained to use the proper injection techniques see section 6 6 A User Manual is also available to instruct patient
5. D was 0 82 g cm equivalent to a T score 2 6 All patients were offered 1000 mg calcium per day and at least 400 IU vitamin D per day Results from up to 24 months median 19 months treatment with FORSTEO demonstrate statistically significant fracture reduction Table 1 To prevent one or more new vertebral fractures 11 women had to be treated for a median of 19 months Table 1 Fracture Incidence in Postmenopausal Women Placebo FORSTEO Relative risk N 544 90 N 541 96 95 CI vs placebo 4 3 5 07 0 35 0 22 0 55 9 1 1 New vertebral fracture 21 Multiple vertebral 4 0 23 fractures 22 0 09 0 60 Non vertebral 5 5 2 6 0 47 fragility fractures 0 25 0 87 Major non vertebral 3 9 1 5 0 38 fragility fractures 0 17 0 86 hip radius humerus ribs and pelvis Abbreviations N number of patients randomly assigned to each treatment group CI Confidence Interval The incidence of vertebral fractures was assessed in 448 placebo and 444 Forsteo patients who had baseline and follow up spine radiographs px0 001 compared with placebo A significant reduction in the incidence of hip fractures has not been demonstrated lt 0 025 compared with placebo After 19 months median treatment bone mineral density BMD had increased in the lumbar spine and total hip respectively by 9 and 4 compared with placebo p 0 001 Post treatment management Following treatment with
6. FORSTEO 1262 postmenopausal women from the pivotal trial enrolled in a post treatment follow up study The primary objective of the study was to collect safety data of FORSTEO During this observational period other osteoporosis treatments were allowed and additional assessment of vertebral fractures was performed During a median of 18 months following discontinuation of FORSTEO there was a 4146 reduction p 0 004 compared with placebo in the number of patients with a minimum of one new vertebral fracture 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 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 All patients were offered 1000 mg calcium per day and at
7. ance of these findings is probably minor No bone tumours were observed in ovariectomised monkeys treated for 18 months or 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 Animal studies have shown that severely reduced hepatic blood flow decreases exposure of PTH to the principal cleavage system Kupffer cells and consequently clearance of PTH 1 84 6 PHARMACEUTICAL PARTICULARS 6 List of excipients Glacial acetic acid Sodium acetate anhydrous Mannitol Metacresol Hydrochloric acid Sodium hydroxide Water for injections Hydrochloric acid and or sodium hydroxide solution may be added to adjust pH 6 2 Incompatibilities In the absence of compatibility studies this medicinal product must not be mixed with other medicinal products 6 3 Shelf life 2 years Chemical physical and microbiological in use stability has been demonstrated for 28 days at 2 8 C Once opened the product may be stored for a maximum of 28 days at 2 C to 8 C Other in use storage times and conditions are the responsibility of the user 6 4 Special precautions for storage Store in a refrigerator 2 C 8 C at all times The pen should be returned to the refrigerator immediately after use Do not freeze Do not store the injection device with the needle attached 6 5 Nature and contents of container 2 4 ml solution in cart
8. and throw away 6 Point the needle down into an empty container Push in the black injection button until it stops Hold it in and count to 5 s l o w l y You may see a small stream or drop of fluid When you have finished the black injection button should be all the way in 7 Ifyou still see the yellow shaft showing please contact your healthcare professional 8 Putthe large needle cover on needle Unscrew the needle all the way by giving the needle cover 3 to 5 complete turns Pull off needle cover and throw away as directed by your healthcare professional Push the white cap back on and place FORSTEO in the refrigerator You can prevent this problem by always using a NEW needle for each injection and by pushing the black injection button all the way in and counting to 5 s l o w l y The FORSTEO is designed to inject the full dose every time it is used according to the directions in the section nstructions for Use The black injection button will be all the way in to show that the full dose has been injected from the FORSTEO 27 Remember to use a new needle every time you inject to be sure your FORSTEO will work properly Iseeanairbubblein gt A small air bubble will not affect your dose nor will it my FORSTEO harm you You can continue to take your dose as usual D I cannot get the e 1 Put the large needle cover on the needle needle off 2 Use the large needle cover to unsc
9. artridge White Cap Paper Tab Needle Large Needle Cover Needles not included Becton Dickinson and EN Company pen needles 29 to 7 TCE 31 gauge diameter 0 25 0 33 mm and 12 7 8 or 5 mm length can be used Ask your healthcare professional which needle gauge and length are best for you Small Needle Pictector Always wash your hands before every injection Prepare the injection site as directed by your healthcare professional 1 y gt p Pull off white cap 2 A i ie Attach new GPx aE ry A T needle j Pull off paper Push needle straight Screw on needle Pull off large tab onto medicine cartridge until firmly attached needle cover and save it 25 Gently hold a fold of skin from thigh or abdomen and insert needle straight into skin 3 Red Set stripe dose protecto 4 T p 3 i Pull out black Check to Pull off small injection make sure needle button until it stops red stripe protector and throw shows away If you cannot pull out the black injection button see Troubleshooting Problem E _ a os y Inject dose 97 df ex bun Push in black injection button until it stops Hold it in and count to 5 s l o w l y Then pull the needle from skin IMPORTANT After completing the injection Once the needle is removed from the skin check to make sure the black
10. blasts indirectly increasing the intestinal absorption of calcium and increasing the tubular re absorption of calcium and excretion of phosphate by the kidney Pharmacodynamic effects FORSTEO is a bone formation agent to treat osteoporosis The skeletal effects of FORSTEO depend upon the pattern of systemic exposure Once daily administration of FORSTEO increases apposition of new bone on trabecular and cortical bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity Clinical efficacy Risk Factors 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 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 lt 2 sustained high dose glucocorticoid therapy e g 27 5 mg day for at least 6 months high underlying disease activity low sex steroid levels Postmenopausal osteoporosis The pivotal study included 1637 postmenopausal women mean age 69 5 years At baseline ninety percent of the patients had one or more vertebral fractures and on average vertebral BM
11. ction under the skin subcutaneous injection in the thigh or abdomen To help you remember to take FORSTEO inject it at about the same time each day Inject FORSTEO each day for as long as your doctor prescribes it for you The total duration of treatment with FORSTEO should not exceed 24 months You should not receive more than one treatment course of 24 months over your lifetime FORSTEO can be injected at meal times Read the user manual booklet which is included in the carton for instructions on how to use the FORSTEO pen Injection needles are not included with the pen You can use Becton Dickinson and Company s insulin pen injection needles You should take your FORSTEO injection shortly after you take the pen out of the refrigerator as described in the user manual Put the pen back into the refrigerator immediately after you have used it Use a new injection needle for each injection and dispose of it after each use Never store your pen with the needle attached Your doctor may advise you to take FORSTEO with calcium and vitamin D Your doctor will tell you how much you should take each day If you use more FORSTEO than you should If by mistake you have used more FORSTEO than you should contact your doctor or pharmacist 20 The effects of overdose that might be expected include nausea vomiting dizziness and headache If you forget or cannot take FORSTEO at your usual time take it as soon as possible on that day Do no
12. ctures 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 lt 0 001 FORSTEO increased BMD at the total hip 3 6 compared with alendronate 2 2 p lt 0 01 as well as at the femoral neck 3 7 compared with alendronate 2 1 p lt 0 05 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 7 096 had experienced a nonvertebral fracture compared with 16 of 214 patients in the FORSTEO group 7 596 p 0 84 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 1 999 p lt 0 001 and total hip 3 8 versus 0 996 p 0 005 However no significant effect on fracture rates was demonstrated 5 2 Pharmacokinetic properties FORSTEO is eliminated through hepatic and extra hepatic clearance approximately 62 l hr in women and 94 in men The volu
13. erlands 22 Manufacturer Lilly France S A S Rue du Colonel Lilly F 67640 Fegersheim France For any information about this medicinal product please contact the local representative of the Marketing Authorisation Holder Belgi Belgique Belgien Eli Lilly Benelux S A T l Tel 32 0 2 548 84 84 TII 359 2 491 41 40 Cesk republika ELI LILLY CR s r o Tel 420 234 664 111 Danmark Eli Lilly Danmark A S TIf 45 45 26 60 00 Deutschland Lilly Deutschland GmbH Tel 49 0 6172 273 2222 Eesti Eli Lilly Holdings Limited Eesti filiaal Tel 3726817280 A E B E Tn 30 210 629 4600 Espana Elanco Valquimica S A Tel 34 91 623 1732 23 Luxembourg Luxemburg Eli Lilly Benelux S A T l Tel 32 0 2 548 84 84 Magyarorsz g Lilly Hung ria Kft Tel 4 36 1 328 5100 Malta Charles de Giorgio Ltd Tel 4 356 25600 500 Nederland Eli Lilly Nederland B V Tel 31 0 30 60 25 800 Norge Eli Lilly Norge A S TIf 47 22 88 18 00 sterreich Eli Lilly Ges m b H Tel 4 43 0 1 711 780 Polska Eli Lilly Polska Sp z o o Tel 48 0 22 440 33 00 Portugal Lilly Portugal Produtos Farmac uticos Lda Tel 351 21 4126600 France Lilly France SAS T l 33 0 1 55 49 34 34 Ireland Eli Lilly and Company Ireland Limited Tel 353 0 1 661 437
14. first few doses For the first doses inject FORSTEO where you can sit or lie down right away if you get dizzy The recommended treatment time of 24 months should not be exceeded Taking other medicines Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines including medicines obtained without a prescription because occasionally they may interact e g digoxin digitalis a medicine used to treat heart disease Using FORSTEO with food and drink Forsteo can be given with or without food Pregnancy and breast feeding Do not use FORSTEO if you are pregnant or breast feeding Women of child bearing potential should use effective methods of contraception during use of FORSTEO If pregnancy occurs FORSTEO should be discontinued Ask your doctor or pharmacist for advice before taking any medicine Driving and using machines Some patients may feel dizzy after injecting FORSTEO If you feel dizzy you should not drive or use machines until you feel better Important information about some of the ingredients of FORSTEO This medicinal product contains less than 1 mmol sodium 23 mg per dose This means that it is essentially sodium free 3 HOW TO USE FORSTEO Always use FORSTEO exactly as your doctor has told you to You should check with your doctor or pharmacist if you are not sure Never share your FORSTEO pen with others The recommended dose of FORSTEO is 20 micrograms given once daily by inje
15. ility pregnancy and lactation 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 4 7 Effects on ability to drive and use machines No studies on the effects on the ability to drive and use machines have been performed However transient orthostatic hypotension or dizziness was observed in some patients These patients should refrain from driving or the use of machines until symptoms have subsided 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 co
16. in men Osteoporosis is also common in patients receiving corticosteroids 2 BEFORE YOU USE FORSTEO Do not use FORSTEO if you are allergic hypersensitive to teriparatide or any of the other ingredients FORSTEO if you suffer from high calcium levels pre existing hypercalcaemia if you suffer from serious kidney problems if you have ever been diagnosed with bone cancer other cancers that have spread metastasised to your bones if you have certain bone diseases If you have a bone disease tell your doctor if you have unexplained high levels of alkaline phosphatase in your blood which means you might have Paget s disease If you are not sure ask your doctor if you have had radiation therapy involving your bones if you are pregnant or breast feeding FORSTEO should not be used in children less than 18 years or in growing adults Take special care with FORSTEO FORSTEO may cause an increase in the amount of calcium in your blood Tell your doctor if you have continuing nausea vomiting constipation low energy or muscle weakness These may be signs there is too much calcium in your blood FORSTEO may cause an increase in the amount of calcium in your urine You should tell your doctor if you suffer from kidney stones or have a history of kidney stones You should tell your doctor if you suffer from kidney problems moderate renal impairment Some patients get dizzy or get a fast heartbeat after the
17. injection button is all the way in If the yellow shaft does not show you have completed the injection steps correctly 5 Confirm dose You should NOT see any of the yellow shaft If you do and have already injected do not inject yourself a second time on the same day Instead you MUST reset FORSTEO see Troubleshooting Problem A 26 6 Large Remove e V Ae gt atm p Ae needle Put large needle cover on needle lt Unscrew the needle Pull off needle and Push white cap back all the way by throw away as directed on Place FORSTEO giving the large by your healthcare in the refrigerator needle cover3to 5 professional immediately after complete turns use um Forsteo FORSTEO 20 microgram ug 80 microlitres solution for injection in pre filled pen Problem A The yellow shaft is still showing after I push in the black injection button How do I reset my FORSTEO B How I tell if my FORSTEO works Troubleshooting Solution To reset the FORSTEO follow the steps below 1 If you have already injected DO NOT inject yourself a second time on the same day 2 Remove the needle 3 Attach a new needle pull off the large needle cover and save it 4 Pull out the black injection button until it stops Check to make sure the red stripe shows 5 Pull off the small needle protector
18. least 400 IU vitamin D day Lumbar spine BMD significantly increased by 3 months After 12 months BMD had increased in the lumbar spine and total hip by 5 and 1 respectively compared with placebo However no significant effect on fracture rates was demonstrated 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 the 18 month primary phase of a 36 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 fra
19. me of distribution is approximately 1 7 l kg The half life of FORSTEO is approximately 1 hour when administered subcutaneously which reflects the time required for absorption from the injection site No metabolism or excretion studies have been performed with FORSTEO but the peripheral metabolism of parathyroid hormone is believed to occur predominantly in liver and kidney Patient characteristics Geriatrics No differences in FORSTEO pharmacokinetics were detected with regard to age range 31 to 85 years Dosage adjustment based on age is not required 5 3 Preclinical safety data 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 ug kg However fetal resorption and reduced litter size occurred in pregnant rabbits administered daily doses of 3 to 100 ug 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 Rats treated with near life time daily injections had dose dependent exaggerated bone formation and increased incidence of osteosarcoma most probably due to an epigenetic 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 relev
20. micrograms and in repeated doses of up to 60 micrograms day for 6 weeks The effects of overdose that might be expected include delayed hypercalcaemia and risk of orthostatic hypotension Nausea vomiting dizziness and headache can also occur Overdose experience based on post marketing spontaneous reports In post marketing spontaneous reports there have been cases of medication error where the entire contents up to 800 ug of the teriparatide pen have been administered as a single dose Transient events reported have included nausea weakness lethargy and hypotension In some cases no adverse events occurred as a result of the overdose No fatalities associated with overdose have been reported Overdose management There is no specific antidote for FORSTEO Treatment of suspected overdose should include transitory discontinuation of FORSTEO monitoring of serum calcium and implementation of appropriate supportive measures such as hydration 5 PHARMACOLOGICAL PROPERTIES 5 1 Pharmacodynamic properties Pharmaco therapeutic group parathyroid hormones and analogues ATC code H05 AA02 Mechanism of action Endogenous 84 amino acid parathyroid hormone PTH is the primary regulator of calcium and phosphate metabolism in bone and kidney FORSTEO rhPTH 1 34 is the active fragment 1 34 of endogenous human parathyroid hormone Physiological actions of PTH include stimulation of bone formation by direct effects on bone forming cells osteo
21. mmon 2 1 10 common 2 1 100 to 1 10 uncommon 2 1 1 000 to 1 100 rare 1 10 000 to lt 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 Syncope Ear and labyrinth disorders Common Vertigo Respiratory thoracic and mediastinal disorders Common Dyspnoea Uncommon Emphysema Gastrointestinal disorders Common Nausea Vomiting Hiatus hernia Gastroesophageal reflux disease Uncommon Haemorrhoids Renal and urinary disorders Uncommon Urinary incontinence Polyuria Micturition urgency Nephrolithiasis Rare 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 Back cramp pain Metabolism and nutrition disorders Common Hypercholesterolaemia Uncommon Hypercalcemia greater than 2 76 mmol L Hyperuricemia Rare Hypercalcemia greater than 3 25 mmol L Vascular disorders Common Hypotension General disorders and administration site conditions Common Fatigue Chest pain Asthenia Mild and transient injectio
22. n site events including pain swelling erythema localised bruising pruritis 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 2 196 difference in frequency from phcebo 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 0 796 of placebo patients However the hyperuricemia 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 5 4 9 Overdose Signs and symptoms No cases of overdose were reported during clinical trials FORSTEO has been administered in single doses of up to 100
23. nt of the refrigerator to prevent freezing Do not use FORSTEO if it is or has been frozen Each pen should be properly disposed of after 28 days even if it is not completely empty FORSTEO contains a clear and colourless solution Do not use FORSTEO if solid particles appear or if the solution is cloudy or coloured Medicines should not be disposed of via wastewater or household waste Ask your pharmacist how to dispose of medicines no longer required These measures will help to protect the environment 6 FURTHER INFORMATION What FORSTEO contains The active substance is teriparatide Each millilitre of the solution for injection contains 250 micrograms of teriparatide The other ingredients are glacial acetic acid sodium acetate anhydrous mannitol metacresol 3 0 mg ml preservative and water for injections In addition hydrochloric acid and or sodium hydroxide solution may have been added to adjust the acidity What FORSTEO looks like and contents of the pack FORSTEO is a colourless and clear solution for injection under the skin subcutaneous use It is supplied in a cartridge contained in a pre filled disposable pen Each pen contains 2 4 ml of solution enough for 28 doses The pens are available in cartons containing one or three pens Not all pack sizes may be available Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder Eli Lilly Nederland B V Grootslag 1 5 NL 3991 RA Houten The Neth
24. ntinued treatment Caution should be exercised in patients with moderate renal impairment 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 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 24 months should not be exceeded 4 5 Interactions with other medicinal products and other forms of interaction FORSTEO has been evaluated in pharmacodynamic interaction studies with hydrochlorothiazide No clinically significant interactions were noted Co administration of raloxifene or hormone replacement therapy with FORSTEO did not alter the effects of FORSTEO on serum or urine calcium or on clinical adverse events In a study of 15 healthy subjects administered digoxin daily to steady state a single FORSTEO dose did not alter the cardiac effect of digoxin However sporadic case reports have suggested that hypercalcemia may predispose patients to digitalis toxicity Because FORSTEO transiently increases serum calcium FORSTEO should be used with caution in patients taking digitalis 4 6 Fert
25. on n 2 5 dated 17 January 2008 of the Risk Management Plan RMP presented in Module 1 8 2 of the Marketing Authorisation and any subsequent updates of the RMP agreed by the CHMP As per the CHMP Guideline on Risk Management Systems for medicinal products for human use the updated RMP should be submitted at the same time as the next Periodic Safety Update Report PSUR In addition an updated RMP should be submitted e When new information is received that may impact on the current Safety Specification Pharmacovigilance Plan or risk minimisation activities e Within 60 days of an important pharmacovigilance or risk minimisation milestone being reached e Atthe request of the European Medicines Agency ANNEX III LABELLING AND PACKAGE LEAFLET A LABELLING PARTICULARS TO APPEAR ON THE OUTER PACKAGING OUTER CARTON TEXT 1 NAME OF THE MEDICINAL PRODUCT FORSTEO 20 micrograms 80 microliters solution for injection in pre filled pen Teriparatide 2 STATEMENT OF ACTIVE SUBSTANCE S Each ml contains 250 micrograms of teriparatide 3 LIST OF EXCIPIENTS Glacial acetic acid sodium acetate anhydrous mannitol metacresol 3 0 mg ml preservative water for injections Hydrochloric acid solution and or sodium hydroxide solution as appropriate 4 PHARMACEUTICAL FORM AND CONTENTS Solution for injection 1 pen of 2 4 ml solution 3 pens of 2 4 ml solution each Each pen contains 28 d
26. or implant radiation therapy to the skeleton Patients with skeletal malignancies bone metastases should be excluded from treatment with teriparatide 4 4 Special warnings and precautions for use In normocalcemic patients slight and transient elevations of serum calcium concentrations have been observed following teriparatide injection Serum calcium concentrations reach a maximum between 4 and 6 hours and return to baseline by 16 to 24 hours after each dose of teriparatide Routine calcium monitoring during therapy is not required Therefore if any blood samples are taken from a patient this should be done at least 16 hours after the most recent FORSTEO injection FORSTEO may cause small increases in urinary calcium excretion but the incidence of hypercalciuria did not differ from that in the placebo treated patients in clinical trials FORSTEO has not been studied in patients with active urolithiasis FORSTEO should be used with caution in patients with active or recent urolithiasis because of the potential to exacerbate this condition In short term clinical studies with FORSTEO isolated episodes of transient orthostatic hypotension were observed Typically an event began within 4 hours of dosing and spontaneously resolved within a few minutes to a few hours When transient orthostatic hypotension occurred it happened within the first several doses was relieved by placing subjects in a reclining position and did not preclude co
27. oses of 20 micrograms per 80 microliters 5 METHOD AND ROUTE S OF ADMINISTRATION Subcutaneous use READ THE PACKAGE LEAFLET BEFORE USE 6 SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE REACH AND SIGHT OF CHILDREN Keep out of the reach and sight of children 7 OTHER SPECIAL WARNING S IF NECESSARY To open lift here and pull 8 EXPIRY DATE EXP MM YYYY The pen should be discarded 28 days after the first use Date of first use 9 SPECIAL STORAGE CONDITIONS Store in a refrigerator Do not freeze 10 SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS IF APPROPRIATE 11 NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER Eli Lilly Nederland B V Grootslag 1 5 NL 3991 RA Houten The Netherlands 12 MARKETING AUTHORISATION NUMBER S EU 1 03 247 001 Or EU 1 03 247 002 13 BATCH NUMBER Lot 14 GENERAL CLASSIFICATION FOR SUPPLY Medicinal product subject to medical prescription 15 INSTRUCTIONS ON USE 16 INFORMATION IN BRAILLE FORSTEO MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS LABEL TEXT 1 NAME OF THE MEDICINAL PRODUCT AND ROUTE S OF ADMINISTRATION FORSTEO 20 micrograms 80 microliters solution for injection in pre filled pen Teriparatide
28. pen needle Dispose of your FORSTEO and used needles as directed by your healthcare professional e Dispose of the device 28 days after first use Other Important Notes The FORSTEO contains 28 days of medication Do not transfer the medication into a syringe Write down your first injection date on a calendar Read and follow the instructions in the Information for the Patient leaflet for using 28 medication e Check the FORSTEO label to make sure you have the correct medication and that it has not expired Contact your healthcare professional if you notice any of the following The FORSTEO appears damaged The medication is NOT clear colourless and free of particles e Use a new needle for each injection During injection you may hear or more clicks this is a normal device operation e The FORSTEO is not recommended for use by the blind or visually impaired persons without the assistance of a person trained in the proper use of the device Keep the FORSTEO out of the reach and sight of children Manufactured by Lilly France F 67640 Fegersheim France for Hli Lilly and Company This user manual was last revised in MM YYYY 29
29. rew the needle 3 Unscrew the needle all the way by giving the large needle cover 3 to 5 complete turns 4 If you still cannot get the needle off ask someone to help you E What should I Change to a new FORSTEO to take your dose as cannot pull out the directed by your healthcare professional black injection button This indicates that you have now used all the medication that can be injected accurately even though you may still see some medication left in the medicine cartridge Cleaning and Storage Cleaning Your FORSTEO e Wipe the outside of the FORSTEO with a damp cloth Do not place the FORSTEO in water or wash or clean it with any liquid Storing Your FORSTEO e Refrigerate the FORSTEO immediately after every use Read and follow the instructions in the Information for the Patient leaflet on how to store medication e Do not store the FORSTEO with a needle attached as this may cause air bubbles to form in the medicine cartridge Store the FORSTEO with the white cap on Never store the FORSTEO in the freezer If the medication has been frozen throw the device away and use a new FORSTEO If the FORSTEO has been left out of the refrigerator do not throw the pen away Place the pen back in the refrigerator and contact your healthcare professional Disposal of Pen Needles and Device Disposal of Pen Needles and FORSTEO Device e Before disposing of the FORSTEO device be sure to remove the
30. ridge siliconised Type I glass with a plunger halobutyl rubber disc seal polyisoprene bromobutyl rubber laminate aluminium assembled into a disposable pen FORSTEO is available in pack sizes of 1 or 3 pens Each pen contains 28 doses of 20 micrograms per 80 microliters Not all pack sizes may be marketed 6 6 Special precautions for disposal FORSTEO is supplied in a pre filled pen Each pen should be used by only one patient new sterile needle must be used for every injection Each FORSTEO pack is provided with a user manual that fully describes the use of the pen No needles are supplied with the product The device can be used with insulin pen injection needles After each injection the FORSTEO pen should be returned to the refrigerator FORSTEO should not be used if the solution is cloudy coloured or contains particles Please also refer to the User Manual for instructions on how to use the pen Any unused product or waste material should be disposed of in accordance with local requirements 7 MARKETING AUTHORISATION HOLDER Eli Lilly Nederland B V Grootslag 1 5 NL 3991 RA Houten The Netherlands 8 MARKETING AUTHORISATION NUMBER S EU 1 03 247 001 002 9 DATE OF FIRST AUTHORISATION RENEWAL OF THE AUTHORISATION Date of first authorisation 10 June 2003 Date of last renewal 10 June 2008 10 DATE OF REVISION OF THE TEXT ANNEX II MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION
31. s on the correct use of the pen The maximum total duration of treatment with FORSTEO should be 24 months see section 4 4 The 24 month course of FORSTEO should not be repeated over a patient s lifetime Patients should receive supplemental Calcium and vitamin D supplements if dietary intake is inadequate Following cessation of FORSTEO therapy patients may be continued on other osteoporosis therapies Use in renal impairment FORSTEO should not be used in patients with severe renal impairment see 4 3 In patients with moderate renal impairment FORSTEO should be used with caution Use in hepatic impairment no data are available in patients with impaired hepatic function see section 5 3 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 Elderly patients Dosage adjustment based on age is not required see section 5 2 4 3 Contraindications Hypersensitivity to the active substance or to any of the excipients Pregnancy and lactation see section 4 4 and 4 6 Pre existing hypercalcemia Severe renal impairment Metabolic bone diseases including hyperparathyroidism and Paget s disease of the bone other than primary osteoporosis or glucorticoid induced osteoporosis Unexplained elevations of alkaline phosphatase Prior external beam
32. t take a double dose to make up for a forgotten dose Do not take more than one injection in the same day Do not try to make up for a missed dose If you have any further questions on the use of this product ask your doctor or pharmacist 4 POSSIBLE SIDE EFFECTS Like all medicines FORSTEO can cause side effects although not everybody gets them The most common side effects affects more than 1 user in 10 are e painin limb Common side effects 1 to 10 users in 100 are feeling sick headache dizziness increase in blood cholesterol levels depression neuralgic pain in the leg feeling faint irregular heart beats breathlessness increased sweating muscle cramps loss of energy tiredness chest pain low blood pressure heartburn painful or burning sensation just below the breast bone low haemoglobin or red blood cell count anaemia Uncommon side effects affects 1 to 10 users in 1000 are e increased heart rate shortness of breath haemorrhoids piles accidental loss or leakage of urine increased need to pass water weight increase kidney stones Other uncommon side effects reported include pain in the muscles and pain in the joints Some people may experience discomfort such as redness of the skin pain swelling itching bruising or minor bleeding around the area of the injection This should clear up in a few days or weeks Otherwise tell your doctor as soon as possible If you become dizz
33. y light headed after your injection you should sit or lie down until you feel better If you do not feel better you should call a doctor before you continue treatment Cases of fainting have been reported in association with teriparatide use 21 Some patients treated with FORSTEO have had an increase in their blood calcium level Rare side effects affects 1 to 10 users in 10 000 Some patients have experienced allergic reactions soon after injection consisting of breathlessness swelling of the face rash and chest pain Cases of reduced kidney function including renal failure have been reported in association with teriparatide use Other rare side effects include swelling mainly in the hands feet and legs Some patients have experienced severe back cramps or pain which led to hospitalisation FORSTEO may also cause an increase in an enzyme called alkaline phosphatase If any of the side effects gets serious or if you notice any side effects not listed in this leaflet please tell your doctor or pharmacist 5 HOW TO STORE FORSTEO Keep out of the reach and sight of children Do not use FORSTEO after the expiry date which is stated on the carton and pen FORSTEO should be stored in a refrigerator 2 C and 8 C at all times You can use FORSTEO for up to 28 days after the first injection as long as the pen is stored in a refrigerator 2 C to 8 C Do not freeze FORSTEO Avoid placing the pens close to the ice compartme
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