1 Package leaflet: Infrmatin fr the patient Orxine 25 micrgram tablets Orxine 50 micrgram tablets Orxine 75 micrgram tablets Orxine 100 micrgram tablets Orxine 125 micrgram tablets Orxine 150 micrgram tablets Orxine 175 micrgram tablets Orxine 200 micrgram tablets levthyrxine sdium Read all f this leaflet carefully befre yu start taking this medicine because it cntains imprtant infrmatin fr yu. -Keep this leaflet. Yu may need t read it again. -If yu have any further questins, ask yur dctr r pharmacist. -This medicine has been prescribed fr yu nly. D nt pass it n t thers. It may harm them, even if their signs f illness are the same as yurs. - If yu get any side effects, talk t yur dctr r pharmacist. This includes any pssible side effects nt listed in this leaflet. See sectin 4. What is in this leaflet? This leaflet answers sme cmmn questins abut Orxine tablets. It des nt cntain all f the available infrmatin. It des nt take the place f talking t yur dctr r pharmacist. All medicines have risks and benefits. Yur dctr has weighed the expected benefits f yu taking Orxine against the risks this medicine culd have fr yu. 1. What Orxine is and what it is used fr 2. What yu need t knw befre yu take Orxine 3. Hw t take Orxine 4. Pssible side effects 5. Hw t stre Orxine 6. Cntents f the pack and ther infrmatin 1. What Orxine is and what it is used fr Levthyrxine sdium is a synthetic thyrid hrmne that chemically identical t thyrxine prduced by the thyrid gland. The aim f treatment with Orxine is t replace missing thyrid hrmne and/r t relieve stress n the thyrid gland. Orxine is used: t replace the missing thyrid hrmne in all frms f underactive thyrid functin (hypthyridism) r after the remval f the thytid gland, t prevent the return f new gitres after gitre surgery in patients with nrmal thyrid functin, t treat nn malignant gitre (benign struma) in patients with nrmal thyrid functin. Orxine 25 micrgrams
2 as add n therapy in the antithyrid treatment f an veractive thyrid, after nrmal metablic status has been reached. fr malignant thyrid tumurs, particularly after surgery t suppress new tumur grwth and as a supplement fr missing thyrid hrmne. Orxine 50 micrgrams as add n therapy in the antithyrid treatment f an veractive thyrid, after nrmal metablic status has been reached, fr malignant thyrid tumurs, particularly after surgery t suppress new tumur grwth and as a supplement fr missing thyrid hrmne. Orxine 75 micrgrams as add n therapy in the antithyrid treatment f an veractive thyrid, after nrmal metablic status has been reached, fr malignant thyrid tumurs, particularly after surgery t suppress new tumur grwth and as a supplement fr missing thyrid hrmne. Orxine 100 micrgrams as add n therapy in the antithyrid treatment f an veractive thyrid, after nrmal metablic status has been reached, fr malignant thyrid tumurs, particularly after surgery t suppress new tumur grwth and as a supplement fr missing thyrid hrmne, in the thyrid suppressin test. Orxine 125 micrgrams fr malignant thyrid tumurs, particularly after surgery t suppress new tumur grwth and as a supplement fr missing thyrid hrmne, Orxine 150 micrgrams fr malignant thyrid tumurs, particularly after surgery t suppress new tumur grwth and as a supplement fr missing thyrid hrmne, in the thyrid suppressin test. Orxine 175 micrgrams fr malignant thyrid tumurs, particularly after surgery t suppress new tumur grwth and as a supplement fr missing thyrid hrmne, Orxine 200 micrgrams fr malignant thyrid tumurs, particularly after surgery t suppress new tumur grwth and as a supplement fr missing thyrid hrmne, in the thyrid suppressin test. 2. What yu need t knw befre yu take Orxine Tell yur dctr if yu are allergic t any fds r medicines. D nt take Orxine: if yu are allergic t levthyrxine sdium r any f the ther ingredients (listed in sectin 6), if yu have any f the fllwing disrders r cnditins: an untreated veractive thyrid, if yu have untreated thyrtxicsis (high levels f thyrid hrmnes in the bld),
3 untreated adrenal crtex deficiency (a cnditin where the adrenal glands d nt make enugh hrmnes), untreated pituitary deficiency (a cnditin where the pituitary gland des nt make enugh hrmnes), recent heart attack, acute inflammatin f the heart muscle (mycarditis), acute inflammatin f all layers f the heart wall (pancarditis). Befre the start f treatment with Orxine, the fllwing disrders r cnditins must be ruled ut r treated: crnary heart disease, chest pain with tight chestedness (angina pectris), high bld pressure (hypertensin), pituitary and/r adrenal crtex deficiency (cnditins where the pituitary/ adrenal glands d nt prduce enugh hrmnes), areas in the thyrid that prduce uncntrlled amunts f thyrid hrmne (thyrid autnmy). Warnings and precautins Yu must nt take Orxine t achieve weight lss. If yur thyrid hrmne bld levels are within the nrmal range, additinal intake f thyrid hrmnes will nt cause weight lss. Such additinal intake may cause serius r even life threatening side effects, particularly in cmbinatin with certain weight lss prducts. Tell yur dctr if yu are taking weight lss drugs, such as Orlistat. Yur dctr shuld measure the values f thyrid hrmnes fur t six weeks after switching ver frm anther levthyrxine prduct t this prduct. Special care shuld be taken t maintain thyrid balance if yu: -Are pregnant r are planning t becme pregnant; -If yu have, an underactive thyrid since birth r acquired during childhd; -If yu are underging suppressive therapy fr previus thyrid cancer, especially if yu are frail r elderly; -If yu have central underactive thyrid (due t a disrder f ne f yur glands that prduce hrmnes); -If yu have any heart symptms, r diabetes Talk t yur dctr r pharmacist befre taking Orxine: if yu have crnary heart disease, weak heart muscle, heart rhythm disrders with a rapid heartbeat, chrnic underactive thyrid functin, r if yu have suffered a heart attack. Particular care is required fr milder signs f veractive thyrid functin caused by taking Levthyrxine sdium, s as t avid very high hrmne levels in the bld. In these cases, mre frequent checks n thyrid levels shuld be made (see Hw t take Orxine ). if yu have an underactive thyrid caused by a disease f the pituitary gland. Checks must be made t find ut whether yu als have adrenal crtex deficiency (a prblem with a gland that
4 releases hrmnes). This cnditin must be treated (with sterids) befre intrducing Levthyrxine sdium. if yu have uncntrlled prductin f thyrid hrmnes. Further tests are recmmended befre the start f treatment t check the hrmne system is wrking well. if yu have gne thrugh the menpause. Yur thyrid functin shuld be checked mre frequently t avid increased bld levels f levthyrxine, which can cause steprsis (brittle bnes). if yu have diabetes, as the dsage f yur diabetic treatment may need t be altered. if yu have epilepsy (fits). Fits have been rarely reprted when starting the treatment with levthyrxine. if yu have a cnditin called myxedema (skin and subcutaneus tissue swelling), as the dsage f Levthyrxine sdium may need t be reduced. if yu have any cnditins that affect hw yur gut absbs nutrients frm fd (e.g. celiac disease, lactse intlerance), as this may need t be treated t ensure that yur Levthyrxine sdium treatment wrks well. If yu are being treated with certain bld Levthyrxine sdium"). anti-cltting agents, (see Other medicines and In the elderly, the dse shuld be carefully and individually tailred, e.g. fr thse with heart prblems, and they shuld be mnitred by their dctr. Children If yur child is receiving Levthyrxine sdium, partial lss f hair may ccur during the first few mnths f taking this medicine, but this is usually shrt-term and hair usually grws back. Other medicines and Orxine Tell yur dctr r pharmacist if yu are taking, have recently taken, r might take any ther medicines. If yu are abut t have a test with idinated cntrast media yu shuld tell yur dctr that yu are taking Orxine. The fllwing medicines may affect the way Orxine wrks: medicines t treat diabetes (e.g. insulin, metfrmin) anticagulants such as warfarin, dicumarl (used t thin the bld) amidarne (used t treat sme heart cnditins) aspirin medicines cntaining estrgen (e.g. used fr hrmne replacement therapy r ral cntraceptives) antidepressants (e.g. sertraline and tricyclic antidepressants such as amitriptyline, imipramine) chlrquine and prguanil (medicines used in malaria and rheumatic diseases) 5-fluuracil, imatinib and sunitinib (used fr the treatment f cancer) medicines t cntrl yur heart rate such as digxin medicines that stimulate the sympathetic nervus system such as adrenaline carbamazepine, phenytin r barbiturates (medicines t treat epilepsy r seizures) fursemide (used t treat high bld pressure r edema)
5 rifampicin (used t treat serius infectins) ritnavir (used t cntrl HIV and chrnic hepatitis C virus) prpylthiuracil (used t treat veractive thyrid) medicines used fr treating abnrmal heart rhythms (beta receptr blckers such as prpranll) gluccrticids (such as crtisne, hydrcrtisne, prednisne, and dexamethasne) lithium (used t treat depressin and ther md disrders) idide (used t prtect the thyrid gland frm radiatin) ral cntrast agents (taken befre certain scans t make parts f the bdy shw up better n the scan) statins such as simvastatin and lvastatin (used t treat high chlesterl) methadne (used t treat drug addictin) weight lss medicatins (e.g. rlistat) Levthyrxine sdium shuld be taken at least 4 hurs befre taking the fllwing medicines. chlestyramine, clestipl r clfibrate (used t reduce chlesterl levels in the bld) sdium plystyrene sulphnic acid (used t treat kidney disease) rlistat (weight lss medicatin) Orxine shuld be taken at least 2 hurs befre taking the fllwing medicines: calcium, magnesium, aluminium r irn supplements medicines t treat stmach ulcers such as sucralfate, antacids medicines used t treat an excess f acid in the stmach (prtn pump inhibitrs such as meprazle, esmeprazle) Levthyrxine sdium with fd r drink: Sya cntaining prducts and fds that are high in fibre may affect the absrptin f Levthyrxine sdium. Yur dctr may need t adjust the dse f Levthyrxine as a result. Pregnancy, breast-feeding and fertility If yu are pregnant r breast-feeding, think yu may be pregnant r are planning t have a baby, ask yur dctr r pharmacist fr advice befre taking this medicine. Cnsistent treatment with thyrid hrmnes is particularly imprtant during pregnancy and breastfeeding and must therefre be cntinued under the supervisin f the treating dctr. The need fr levthyrxine may increase during pregnancy due t increased bld levels f estrgen (female sex hrmne). Thyrid functin shuld therefre be mnitred bth during and after pregnancy and the thyrid hrmne dse adjusted as apprpriate. Even during high dse levthyrxine therapy, the amunt f thyrid hrmne passing int breast milk during lactatin is very lw and therefre harmless. Driving and using machines Orxine shuld nt interfere with yur ability t drive r use machinery.
6 3. Hw t take Orxine Always take this medicine exactly as yur dctr r pharmacist has tld yu. Check with yur dctr r pharmacist if yu are nt sure. The individual daily dse shuld be determined by yur dctr by means f labratry diagnstic tests and clinical examinatins. If any residual thyrid functin remains, a lwer dse f thyrid hrmne may be sufficient. In elderly patients, patients with crnary heart disease and patients with severe r chrnic underactive thyrid functin, particular cautin is required when starting treatment with thyrid hrmnes. This means that a lwer starting dse must be selected, which is then increased slwly and at lnger intervals, with frequent thyrid hrmne mnitring. Experience has shwn that a lwer dse is als sufficient in patients with a lw bdy weight and in patients with large gitres. Dsage Fr individual treatment, tablets are available with graduated levels ranging frm 25-200 micrgrams f Orxine, which means that nly ne tablet daily needs t be taken in mst cases. Fr the treatment f underactive thyrid functin, adults initially take 25-50 micrgrams f Orxine daily. If instructed by the dctr, this dse can be increased by 25-50 micrgrams f Orxine at tw t fur week intervals, up t a daily dse f 100-200 micrgrams f Orxine. T prevent the frmatin f new gitres after gitre remval and fr the treatment f benign gitres, 75-200 micrgrams f Orxine are taken daily (up t 2 Orxine 100 micrgram tablets). Use in infants and children Fr newbrns and infants with inbrn thyrid hrmne deficiency, where it is particularly imprtant t start treatment as sn as pssible, in rder t achieve nrmal mental and physical develpment, the initial recmmended dsage is 10 t 15 micrgrams per kg per day fr the first 3 mnths. Thereafter, the dse wuld be adjusted individually accrding t the clinical findings and thyrid hrmne and TSH values measured in bld. Children with acquired hypthyridism start n 12.5-50 micrgrams f Orxine daily. The dse shuld be increased gradually every 2 t 4 weeks accrding t the clinical findings thyrid functin test values until the full replacement dse is reached. As well as ther values, the dsage in lng term treatment will depend n the age and bdy weight f the individual child. During the first 6 mnths f life, measurement f the levthyrxine bld level is mre reliable as a cntrl than measurement f TSH bld levels (thyrid stimulating hrmne). In individual cases, it may take up t tw years fr the TSH level t nrmalise, despite adequate administratin f levthyrxine. Methd f administratin The ttal daily dse is taken in the mrning n an empty stmach, at least half an hur befre breakfast, as the active substance is better absrbed n an empty stmach than befre r after a meal. The tablets are swallwed whle withut chewing, with a glass f water. Infants are given the ttal daily dse at least half an hur befre their first meal f the day. Fr this, the tablet is allwed t disslve in sme water (10-15 ml) and the resulting fine dispersin (nte: t be freshly prepared fr each dse) is administered with sme mre liquid (5-10 ml). Duratin f administratin Yu shuld take this medicine fr as lng as yur dctr tells yu. If yu have an underactive thyrid gland r have had thyrid surgery fr a malignant tumur f the thyrid, yu will usually take Orxine fr life.
7 Fr benign gitre and fr preventin f recurrent gitre grwth, yu must take Orxine fr anything between several mnths r years t the rest f yur life. In supprtive therapy fr the treatment f an veractive thyrid, yu must take Orxine as lng as yu take a thyrestatic medicine. Fr the treatment f benign gitre with nrmal thyrid functin, a treatment perid f 6 mnths t 2 years is necessary. If the treatment with Orxine has nt prduced the desired result within this perid, ther treatment ptins shuld be cnsidered. D nt remve the canister (xygen absrber) frm the bttle. After pening the cntainer the tablets shuld be used within 2 mnths. If yu take mre Orxine than yu shuld In the event f an verdse, cnsult yur dctr r pharmacist immediately. If neither is available, seek immediate help at the nearest hspital r pisn cntrl centre. If yu are an epileptic, seizures may ccur if the dse f levthyrxine is increased rapidly. Symptms f an veractive thyrid (such as agitatin, feeling cnfused, feeling irritable, anxius r nervus, hyperactivity, feeling tired r emtinal, headache, sweating, dilated pupils, rapid r irregular heartbeats, rapid breathing, fever, lse stls r seizures) may ccur in the event f an verdse (see Pssible side effects ). Excessive levthyrxine use may cause a decrease in the density f the bnes, particularly in wmen wh have gne thrugh the menpause. If yu frget t take Orxine If yu miss a dse, take the usual dse when yur next dse is due. D nt take a duble dse t make up fr frgtten individual dses. If yu are unsure, please seek advice frm yur dctr r pharmacist. If yu stp taking Orxine Fr yur treatment t be successful, yu must take Orxine regularly at the dsage prescribed by yur dctr. On n accunt shuld yu change, suspend r stp the prescribed treatment withut talking t yur dctr. If yu have any further questins n the use f this medicine, ask yur dctr r pharmacist. 4. Pssible Side Effects Like all medicines, this medicine can cause side effects, althugh nt everybdy gets them. All medicines can cause allergic reactins althugh serius allergic reactins are rare. Any sudden wheeziness, difficulty in breathing, swelling f the eyelids, face r lips, rash r itching (especially affecting yur whle bdy) shuld be reprted t a dctr immediately. If the dsage strength is nt tlerated, r in the case f an verdse, symptms similar t having an veractive thyrid may ccur, particularly if the dse is increased t quickly at the start f treatment. The belw reactins have been bserved (frequency nt knwn): Headache, flushing, excessive sweating, Lss f weight, Tremr (shaking), restlessness, excitability
8 Seizures Difficulty sleeping, Rapid heartbeat (tachycardia) r angina (chest pain with tight chestedness), Irregular heartbeats, palpitatins (thumping heart beats) High bld pressure (hypertensin), heart failure, heart attack Shrtness f breath (dyspnea) Increased appetite, feeling sick (nausea), being sick (vmiting), lse stls (diarrhea), stmach cramps Muscle weakness and muscle cramps Fever In wmen changes in yur menstrual cycle (perid) A decrease in the density f yur bnes, particularly in wmen wh have gne thrugh the menpause and are taking high dses fr lng perids Overactive thyrid (hyperthyridism) Yu shuld check with yur dctr if any f the abve effects ccur. The effects usually g away when the dse has been changed. Additinal side effects in children Increased brain pressure (especially in children) may als be bserved (rare: may affect up t 1 in 1,000 peple) as atypical symptms. In children, verdsing with levthyrxine may cause early fusin f the skull bnes and a premature halt in the child s grwth. Mild hair lss has als been seen in children this is usually shrt-term. Heat intlerance is als seen in children. In the case f hypersensitivity t levthyrxine sdium r any f the ther ingredients f Orxine, allergic reactins f the skin and respiratry tract regin may ccur. Measures t treat an verdse Tell yur dctr if side effects ccur. He/she will decide whether the daily dse shuld be reduced r whether yu shuld stp taking yur tablets fr a few days. As sn as the side effect has disappeared, treatment can be started again. Reprting f side effects If yu get any side effects, talk t yur dctr, pharmacist r nurse. This includes any pssible side effects nt listed in this leaflet. Yu can als reprt side effects directly via HPRA Pharmacvigilance, Earlsfrt Terrace, IRL -Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie. By reprting side effects yu can help prvide mre infrmatin n the safety f this medicine. 5. Hw t stre Orxine KEEP THIS MEDICINE OUT OF THE SIGHT AND REACH OF CHILDREN. D nt use this medicine after the expiry date which is stated n the bx and bttle. The expiry date refers t the last day f that mnth. After pening f the HDPE cntainer the tablets shuld be used within 2 mnths.
9 Fr Orxine 25 and 125 micrgrams tablets: Stre belw 25 C Fr Orxine 50 and 100 micrgrams tablets: Stre belw 30 C Fr Orxine 75 and 150-200 micrgrams tablets: This medicinal prduct des nt require any special strage cnditins. D nt thrw away any medicines via wastewater r husehld waste. Ask yur pharmacist hw t thrw away medicines yu n lnger use. These measures will help prtect the envirnment. 6. Cntents f the pack and ther infrmatin What Orxine cntains The active substance is levthyrxine sdium. Each tablet f Orxine 25 micrgram cntains 27.8 micrgram f levthyrxine sdium pentahydrate equivalent t 25 micrgram f levthyrxine sdium. Each tablet f Orxine 50 micrgram cntains 55.6 micrgram f levthyrxine sdium pentahydrate equivalent t 50 micrgram f levthyrxine sdium. Each tablet f Orxine 75 micrgram cntains 83.4 micrgram f levthyrxine sdium pentahydrate equivalent t 75 micrgram f levthyrxine sdium. Each tablet f Orxine 100 micrgram cntains 111.3 micrgram f levthyrxine sdium pentahydrate equivalent t 100 micrgram f levthyrxine sdium. Each tablet f Orxine 125 micrgram cntains 139.1 micrgram f levthyrxine sdium pentahydrate equivalent t 125 micrgram f levthyrxine sdium. Each tablet f Orxine 150 micrgram cntains 166.9 micrgram f levthyrxine sdium pentahydrate equivalent t 150 micrgram f levthyrxine sdium. Each tablet f Orxine 175 micrgram cntains 194.7 micrgram f levthyrxine sdium pentahydrate equivalent t 175 micrgram f levthyrxine sdium. Each tablet f Orxine 200 micrgram cntains 222.5 micrgram f levthyrxine sdium pentahydrate equivalent t 200 micrgram f levthyrxine sdium. The ther ingredients are: Micrcrystalline cellulse PH101 (E460) Pregelatinised maize starch Talc (E553b) Cllidal anhydrus silica (E551) Magnesium stearate (E470b) What Orxine lks like and cntents f the pack
10 Orxine tablets are packed in high density plyethylene (HDPE) bttles, clsed with white plyprpylene (PP) screw caps with fil heat inductin seals, and with a 1.0 g white plyprpylene canister cntaining xygen absrber in packs f 28, 50, 60, 84, 90, 100, 112. Nt all pack sizes may be marketed. Orxine 25 micrgram tablets are rund, 6.5mm in diameter, white clured, flat, bevelled tablets debssed with 25 n the ne side and a breakline n the ther side. The tablet can be divided int equal dses. Orxine 50 micrgram tablets are rund, 6.5mm in diameter, white clured, flat, bevelled tablets debssed with 50 n the ne side and L01 n the ther side. Orxine 75 micrgram tablets are rund, 6.5mm in diameter, white clured, flat, bevelled tablets debssed with 75 n the ne side and L02 n the ther side. Orxine 100 micrgram tablets are rund, 6.5mm in diameter, white clured, flat, bevelled tablets debssed with 100 n the ne side and L10 n the ther side. Orxine 125 micrgram tablets are rund, 6.5mm in diameter, white clured, flat, bevelled tablets debssed with 125 n the ne side and L12 n the ther side. Orxine 150 micrgram tablets are rund, 6.5mm in diameter, white clured, flat, bevelled tablets debssed with 150 n the ne side and L17 n the ther side. Orxine 175 micrgram tablets are rund, 6.5mm in diameter, white clured, flat, bevelled tablets debssed with 175 n the ne side and L20 n the ther side. Orxine 200 micrgram tablets are rund, 6.5mm in diameter, white clured, flat, bevelled tablets debssed with 200 n the ne side and L21 n the ther side. Marketing Authrisatin Hlder and Manufacturer Aspen Pharma Trading Limited, 3016 Lake Drive, Citywest Business Campus, Dublin 24, Ireland +353 1 6 308 400 Manufacturer Aspen Bad Oldesle GmbH Industriestraße 32-36 D-23843 Bad Oldesle Germany This medicinal prduct is authrised in the Member States f the EEA under the fllwing names: Austria Belgium Czech Republic Denmark Finland Orxine 25/50/75/88/100/112/125/137/150/175/200 mikrgramm tabletten Thevier 25/50/75/88/100/112/125/137/150/175/200 mcg tabletten Orxine 100 mikrgramů Orxine Orxine
11 France Germany Ireland Italy Luxemburg Nrway Pland Prtugal Slvenia Spain Sweden The Netherlands Orxine Orxine Orxine Orxine 25/50/75/88/100/112/125/137/150/175/200 µg cmpresse Thevier Orxine Orxine Orxine Nvtirx 25/50/100/150/200 mikrgramv tablete Thevier 25/50/75/100/125/150/175/200 micrgrams cmprimids Orxine Thevier 25/50/75/88/100/112/125/137/150/175/200 micrgram tabletten This leaflet was last revised in May 2018.