qanastek/EMEA-V3 huggingface dataset:
Caution is advised in case of combination with CYP3A4 substrates having a narrow therapeutic margin i. e. immunosuppressive agents (cyclosporine, tacrolimus, sirolimus) as well as CYP3A4- metabolised cytotoxics, i. e. cyclophosphamide, etoposide, finasteride, ifosfamide, tamoxifen, vinca- alcaloids.
L- attenzjoni hi rakkomandata f’ każ li jingħata ma ’ substrati ta ’ CYP3A4 li jkollhom marġni terapewtika dejqa, i. e. sustanzi immunosuppressivi (cyclosporine, tacrolimus, sirolimus) kif ukoll ċitotossi metabolati minn CYP3A4, i. e. cyclophosphamide, etoposide, finasteride, ifosfamide, tamoxifen, vinca- alcaloids.
A population analysis of plasma bexarotene concentrations in patients with CTCL indicated that concomitant administration of gemfibrozil resulted in substantial increases in plasma concentrations of bexarotene.
Analiżi tal- popolazzjoni tal- konċentrazzjonijiet fil- plażma ta ’ bexarotene f’ pazjenti bis- CTCL indikat li l- għoti fl- istess ħin ta ’ gemfibrozil irriżulta f’ żidiet sostanzjali tal- konċentrazzjonijiet fil- plażma ta ’ bexarotene.
The mechanism of this interaction is unknown.
Il- mekkaniżmu ta ’ din l- interazzjoni mhuwiex magħruf.
Under similar conditions, bexarotene concentrations were not affected by concomitant administration of atorvastatin or levothyroxine.
Taħt kundizzjonijiet simili, il - konċentrazzjonijiet ta ’ bexarotene ma kinux affettwati mill- għoti fl- istess ħin ta ’ atorvastatin jew levothyroxine.
Concomitant administration of gemfibrozil with bexarotene is not recommended.
L- għoti fl- istess ħin ta ’ gemfibrozil flimkien ma ’ bexarotene mhuwiex rakkomandat.
Effects of bexarotene on other substances: there are indications that bexarotene may induce CYP3A4.
L- effetti ta ’ bexarotene fuq sustanzi oħrajn: hemm indikazzjonijiet li bexarotene jista ’ jirriżulta f’ induzzjoni ta ’ CYP3A4.
Therefore, repeated administration of bexarotene may result in an auto-induction of its own metabolism and, particularly at dose levels greater than 300 mg/ m2/ day, may increase the rate of metabolism and reduce plasma concentrations of other substances metabolised by cytochrome P450 3A4, such as tamoxifen.
Għalhekk, l- għoti ripetut ta ’ bexarotene jista ’ jirriżulta f’ awto- induzzjoni tal- metaboliżmu tiegħu stess u, partikularment, f’ livelli tad- doża li jkunu ta ’ aktar minn 300 mg/ m2/ kuljum, jista ’ jżid ir- rata tal- metaboliżmu u jnaqqas il- konċentrazzjonijiet fil- plażma ta ’ sustanzi oħrajn li jkunu metabolat minn ċitokrom P450 3A4, bħal tamoxifen.
For example bexarotene may reduce the efficacy of oral contraceptives (see sections 4.4 and 4.6).
Pereżempju, bexarotene jista ’ jnaqqas l- effikaċja tal- kontraċettivi orali (ara sezzjonijiet 4. 4 u 4. 6).
Laboratory test interactions:
Interazzjonijiet tat- testijiet tal- laboratorju:
CA125 assay values in patients with ovarian cancer may be accentuated with bexarotene therapy.
Il- valuri ta ’ l- assaġġ CA125 f’ pazjenti b’ kanċer ta ’ l- ovarji jistgħu jiżdiedu bit- terapija b’ bexarotene.
Food interactions: in all clinical trials, patients were instructed to take Targretin capsules with or immediately following a meal.
Interazzjonijiet ma ’ l- ikel: fil- provi kliniċi kollha, il- pazjenti ngħataw parir biex jieħdu l- kapsuli Targretin kapsuli ma ’ l- ikel, jew immedjatament wara l- ikel.
In one clinical study, plasma bexarotene AUC and Cmax values were substantially higher following the administration of a fat-containing meal versus those following the administration of a glucose solution.
Fi studju kliniku wieħed, il- valuri ta ’ l - AUC u tas- Cmax ta ’ bexarotene fil- plażma kienu ogħla b’ mod sostanzjali wara l- għoti ta ’ ikla li kien fiha x- xaħam meta mqabbla mal- valuri wara l- għoti ta ’ soluzzjoni tal- glucose.
Because safety and efficacy data from clinical trials are based upon administration with food, it is recommended that Targretin capsules be administered with food.
Billi l- informazzjoni dwar is- sigurtà u l- effikaċja mill- provi kliniċi hi bbażata fuq l- għoti ma ’ l- ikel, hu rakkomandat li l - kapsuli Targretin jittieħdu ma ’ l- ikel.
On the basis of the oxidative metabolism of bexarotene by cytochrome P450 3A4, grapefruit juice may theoretically lead to an increase in plasma bexarotene concentrations.
Fuq il- bażi tal- metaboliżmu li jossida ta ’ bexarotene minn ċitokrom P450 3A4, il- meraq tal- grejpfrut teoretikament jista ’ jwassal għal żieda fil- konċentrazzjonijiet ta ’ bexarotene fil- plażma.
Pregnancy: there are no adequate data from the use of bexarotene in pregnant women.
Tqala: m’ hemmx informazzjoni biżżejjed mill- użu ta ’ bexarotene f’ nisa tqal.
Studies in animals have shown reproductive toxicity.
Studji fuq l- annimali wrew tossicità riproduttiva.
Based on the comparison of animal and patient exposures to bexarotene, a margin of safety for human teratogenicity has not been demonstrated (see section 5.3).
Fuq bażi tal- paragun ta ’ espożizzjonijiet ta ’ bexarotene fuq l- annimali u fuq il- pazjenti, ma ntweriex marġni ta ’ sigurtà għat- teratoġeniċità fil- bniedem (ara sezzjoni 5. 3).
Bexarotene is contraindicated in pregnancy (see section 4.3).
Bexarotene hu kontra- indikat waqt it- tqala (ara sezzjoni 4. 3).
If this medicinal product is used inadvertently during pregnancy, or if the patient becomes pregnant while taking this medicinal product, the patient should be informed of the potential hazard to the foetus.
5 Jekk dan il- prodott mediċinali jintuża bi żball matul it- tqala, jew jekk il- pazjenta toħroġ tqila meta tkun qed tieħu dan il- prodott mediċinali, il- pazjenta għandha tkun infurmata dwar il- periklu potenzjali lill- fetu.
Women of childbearing potential must use adequate birth-control measures when bexarotene is used.
Nisa li jista ’ jkollhom it- tfal għandhom jużaw miżuri kontraċettivi adegwati meta jużaw bexarotene.
A negative, sensitive, pregnancy test (e. g. serum beta-human chorionic gonadotropin, beta-HCG) should be obtained within one week prior to bexarotene therapy.
Test tat- tqala negattiv, sensittiv, (eż. serum beta- human chorionic gonadotropin, beta- HCG) għandu jinkiseb fi żmien ġimgħa qabel ma tinbeda t- terapija b’ bexarotene.
Effective contraception must be used from the time of the negative pregnancy test through the initiation of therapy, during therapy and for at least one month following discontinuation of therapy.
Għandha tintuża kontraċezzjoni effettiva minn meta jsir magħruf li t- test tat- tqala hu negattiv sal- bidu tat- terapija, matul it- terapija, u għall mill- anqas xahar wara t- twaqqif tat- terapija.
Whenever contraception is required, it is recommended that two reliable forms of contraception be used simultaneously.
Fejn il- kontraċezzjoni tkun meħtieġa, hu rakkomandat li żewġ forom affidabbli ta ’ kontraċezzjoni jintużaw flimkien.
Bexarotene can potentially induce metabolic enzymes and thereby theoretically reduce the efficacy of oestroprogestative contraceptives (see section 4.5).
Bexarotene jista ’ potenzjalment jikkaġuna enzimi metaboliċi, u għalhekk, teoretikament, inaqqas l- effikaċja tal - kontraċettivi oestroprogestative (ara sezzjoni 4. 5).
Male patients with sexual partners who are pregnant, possibly pregnant, or may
Għaldaqstant, jekk il- kura b’ bexarotene hi intenzjonata għal mara li jista ’ jkollha t- tfal, metodu kontraċettiv affidabbli u mhux ormonali hu rakkomandat ukoll.
5 potentially become pregnant must use condoms during sexual intercourse while taking bexarotene and for at least one month after the last dose.
Pazjenti rġiel b’ sieħba sesswali li huma tqal, possibbilment tqal, jew li potenzjalment jistgħu joħorġu tqal, għandhom jużaw il- kondoms waqt il- kopulazzjoni sesswali meta jkunu qed jieħdu bexarotene, u għal mill- anqas xahar wara l- aħħar doża.
Lactation: it is not known whether bexarotene is excreted in human milk.
Mhux magħruf jekk bexarotene jitneħħiex fil- ħalib tal- bniedem.
Bexarotene should not be used in breast-feeding mothers.
Bexarotene m’ għandux jintuża fuq ommijiet li jkunu qed ireddgħu.
However, dizziness and visual difficulties have been reported in patients taking Targretin.
Madankollu, l- isturdament u diffikultajiet fil- vista kienu rrappurtati f’ pazjenti li kienu qed jieħdu Targretin.
Patients who experience dizziness or visual difficulties during therapy must not drive or operate machinery.
Pazjenti li jkollhom sturdament jew diffikultajiet fil- vista matul it- terapija, m’ għandhomx isuqu jew iħaddmu xi makkinarju.
The safety of bexarotene has been examined in clinical studies of 193 patients with CTCL who received bexarotene for up to 118 weeks and in 420 non-CTCL cancer patients in other studies.
Is- sigurtà ta ’ bexarotene kien eżaminata fi studji kliniċi fuq 193 pazjent li kellhom CTCL li rċivew bexarotene sa 118- il ġimgħa, u f’ 420 pazjent li ma kellhomx kanċer tas- CTCL fi studji oħrajn.
In 109 patients with CTCL treated at the recommended initial dose of 300 mg/ m2/ day, the most commonly reported adverse reactions to Targretin were hyperlipaemia ((primarily elevated triglycerides) 74%), hypothyroidism (29%), hypercholesterolaemia (28%), headache (27%), leucopenia (20%), pruritus (20%), asthenia (19%), rash (16%), exfoliative dermatitis (15%), and pain (12%).
F’ 109 pazjent bis- CTCL li kienu kkurati fid- doża rakkomandata tal- bidu ta ’ 300 mg/ m2/ kuljum, l- aktar reazzjonijiet avversi għal Targretin li kienu rrappurtati b’ mod komuni kienu iperlipemija ((primarjament livell għoli ta ’ triglycerides) 74%), ipotirojdiżmu (29%), iperkolesterolemija (28%), uġigħ ta ’ ras (27%), lewkopenja (20%), ħakk (20%), astenja (19%), raxx (16%), dermatite bil- qxur (15%), u uġigħ (12%).
The following Targretin-related adverse reactions were reported during clinical studies in patients with CTCL (N=109) treated at the recommended initial dose of 300 mg/ m2/ day.
Dawn ir- reazzjonijiet avversi li ġejjin, marbuta ma ’ Tagretin, kienu rrappurtati matul studji kliniċi f’ pazjenti bis- CTCL (N=109) li kienu kkurati fid- doża rakkomandata tal- bidu ta ’ 300 mg/ m2/ kuljum.
The frequencies of adverse reactions are classified as very common (> 1/ 10), common (> 1/ 100 ,< 1/10), uncommon (> 1/ 1,000 ,< 1/100), rare (> 1/ 10,000, < 1/ 1,000), and very rare (< 1/ 10,000).
Il- frekwenzi tar- reazzjonijiet avversi huma kklassifikati bħala komuni ħafna (> 1/ 10), komuni (> 1/ 100, < 1/ 10), mhux komuni (> 1/ 1, 000, < 1/ 100), rari (> 1/ 10, 000, < 1/ 1, 000), u rari ħafna (< 1/ 10, 000).
Blood and lymphatic system disorders Very common:
Disturbi tad- demm u tas- sistema limfatika Komuni ħafna:
Leucopenia Lymphoma Like Reaction, Lymphadenopathy, Hypochromic Anaemia1,2,3, Blood Dyscrasia, Purpura, Coagulation Disorder, Coagulation Time Increased2,3, Anaemia1, Thrombocytopenia3, Thrombocythemia, Eosinophilia1, Leukocytosis2, Lymphocytosis
Diskrasija tad- Demm, Purpura, Disturbi tal- Koagulazzjoni, Żieda fil- Ħin tal - Koagulazzjoni2, 3, Anemija1, Tromboċitopenja3, Tromboċitemija, Eosinofilja1, Lewkoċitosi2, Limfoċitosi
Endocrine disorders
Disturbi fis- sistema Komuni ħafna:
Very common:
endokrinarja Ipotirojdiżmu
Common:
6 Komuni:
Hypothyroidism Thyroid Disorder Hyperthyroidism
Disturbi tat- Tirojde Ipertirojdiżmu
Gout, Bilirubinemia1,3, BUN Increased1, High Density Lipoprotein Decreased
Iperlipemija, Iperkolesterolemija Żieda fil- Piż, Żieda fis- SGOT, Żieda fis- SGPT, Żieda fil- Lactic Dehydrogenase, Żieda fil- Krejatinina, Ipoproteinemija, Gotta, Bilirubinemija1, 3, Żieda fil- BUN1, Tnaqqis fil- Lipoproteina b’ Densità Għolja
Nervous system disorders Common:
Komuni:
Dizziness, Hypesthesia, Insomnia Ataxia, Neuropathy, Vertigo, Hyperaesthesia, Depression1,2,3, Agitation
Sturdament, Ipestesija, Nuqqas ta ’ Rqad Atassja, Newropatija, Sturdament, Iperestesija, Dipressjoni1, 2, 3, Aġitazzjoni
Dry Eyes, Eye Disorder Cataract Specified1,2,3, Amblyopia3, Visual Field Defect, Corneal Lesion, Abnormal Vision1,2,3, Blepharitis, Conjunctivitis3
Għajnejn Xotti, Disturbi fl- Għajnejn Katarretti Speċifikati1, 2, 3, Amblijopija3, Difett fil- Kamp Viżiv, Leżjoni tal - Kornea, Vista Anormali1, 2, 3, Blefarite, Konġuntivite3
6 Ear and labyrinth disorders Common:
Disturbi fil- widnejn Komuni:
Deafness Ear disorder
u fis- sistema labirintika Tittarrax Disturbi tal- Widnejn
Cardiac disorders
Disturbi fil- qalb Mhux komuni:
Uncommon:
Takikardija
Tachycardia
Disturbi vaskulari
Peripheral Oedema Haemorrhage, Hypertension, Oedema3, Vasodilatation1,2,3, Varicose Vein
Edema Periferali Emorraġija, Pressjoni tad- Demm Għolja, Edema3, Vażodilatazzjoni1, 2, 3, Vini Varikużi
Vomiting, Diarrhoea1,3, Nausea3, Anorexia1, Liver Function Tests Abnormal, Cheilitis2, Dry Mouth2,3, Constipation, Flatulence,
Disturbi gastro- intestinali Rimettar, Dijarea1, 3, Nawseja3, Anoreksja1, Testijiet tal- Funzjoni tal- Kliewi Komuni: b’ Riżultat Anormali, Cheilitis2, Ħalq Xott2, 3, Stitikezza, Gass, Pankreatite1, 3, Insuffiċjenza Epatika, Disturbi Gastrointestinali1 Mhux komuni:
Serous Drainage1, Herpes Simplex, Pustular Rash, Skin Discoloration3 Hair Disorder1, Nail Disorder1,3
Dermatite bil- Qxur, Ħakk, Raxx Ulċera fil- Ġilda, Alopeċja1, Ipertrofija tal- Ġilda, Għoqod fil- Ġilda, Akne, Għaraq, Ġilda Xotta2, 3, Disturbi fil- Ġilda Ħruġ ta ’ Likwidu Qisu Serum1, Herpes Simplex, Raxx bil- Ponot, Tibdil fil - Kulur tal- Ġilda3 Disturbi fix- Xagħar1, Disturbi fid- Dwiefer1, 3
Musculoskeletal and Common:
Disturbi muskolu- skeltrali u tal- connective tissue Komuni:
connective tissue disorders Bone Pain, Arthralgia, Myalgia Myasthaenia1
Uġigħ fl- Għadam, Artralġja, Mijalġja Mijastenja1
Renal and urinary disorders Uncommon:
Disturbi fil- kliewi u fis- sistema urinarja Albuminuria1, 3, Funzjoni Anormali tal- Kliewi Mhux komuni:
General Disorders and administration site conditions Very common:
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Komuni ħafna:
Pain, Headache, Asthaenia Allergic Reaction, Infection, Chills1, Abdominal Pain, Hormone Level Altered1 Neoplasm, Fever1,2,3, Cellulitis, Infection Parasitic, Mucous Membrane Disorder3, Back Pain1,2,3, Lab Test Abnormal
Uġigħ, Uġigħ ta ’ ras, Astenja Reazzjoni Allerġika, Infezzjoni, Tertir ta ’ Bard1, Uġigħ ta ’ Żaqq, Livelli Mibdula ta ’ l- Ormoni1 Neoplażma, Deni1, 2, 3, Ċellulite, Infezzjoni Parassitika, Disturbi fil- Membrana Mukuża3, Uġigħ fid- Dahar1, 2, 3, Test tal- Laboratorju Anormali 7
1: adverse reactions noted with increased frequency when bexarotene was administered at a dose > 300mg/ m2/ day.
1: reazzjonijiet avversi osservati flimkien ma ’ żieda fil- frekwenza meta bexarotene ingħata f’ doża ta ’ > 300mg/ m2/ kuljum.
2: adverse reactions noted with increased frequency when bexarotene was administered at a dose of 300 mg/ m2/ day in non-CTCL cancer patients.
2: reazzjonijiet avversi osservati flimkien ma ’ żieda fil- frekwenza meta bexarotene ingħata f’ doża ta ’ 300 mg/ m2/ kuljum f’ pazjenti li m’ għandhomx kanċer tas- CTCL.
3: adverse reactions noted with increased frequency when bexarotene was administered at a dose of > 300 mg/ m2/ day (compared to administration to CTCL patients at 300 mg/ m2/ day) in non-CTCL cancer patients.
3: reazzjonijiet avversi osservati flimkien ma ’ żieda fil- frekwenza meta bexarotene ingħata f’ doża ta ’ > 300 mg/ m2/ kuljum (meta mqabbel ma ’ l- għoti lil pazjenti bis- CTCL f’ doża ta ’ 300 mg/ m2/ kuljum) f’ pazjenti li m’ għandhomx kanċer tas- CTCL.
Additional adverse reactions observed when used outside of the recommended dose and indication (i. e. used in CTCL at an initial dose > 300mg/ m2/ day or in non-CTCL cancer indications):
Reazzjonijiet avversi addizzjonali osservati meta l- mediċina tintuża ’ il barra mid- doża rakkomandata u l- indikazzjoni (i. e. tintuża fis- CTCL f’ doża tal- bidu ta ’ > 300mg/ m2/ kuljum jew f’ indikazzjonijiet ta ’ kanċer li mhux tas- CTCL):
Newly observed adverse reactions: ecchymosis, petechia, abnormal white blood cells, thromboplastin decreased, abnormal erythrocytes, dehydration, increased gonadotrophic luteinizing hormone, weight loss, increased alkaline phosphatase, increased creatinine phosphokinase, lipase increased, hypercalcaemia, migraine, peripheral neuritis, paraesthesia, hypertonia, confusion, anxiety, emotional lability, somnolence, decreased libido, nervousness, night blindness, nystagmus, lacrimation disorder, tinnitus, taste perversion, chest pain, arrhythmia, peripheral vascular disorder, generalized oedema, haemoptysis, dyspnoea, increased cough, sinusitis, pharyngitis, dysphagia, mouth ulceration, oral
Reazzjonijiet avversi ġodda li kienu osservati: ekkimożi, tbenġil, ċelluli bojod tad- demm anormali, tnaqqis fit- thromboplastin, eritroċiti anormali, deidrazzjoni, żieda fl- ormon gonadotrofiku luteinizing, telf ta ’ piż, żieda fl- alkaline phosphatase, żieda fil- krejatinina phosphokinase, żieda fil- lipase, iperkalċemija, emigranja, nevrite periferali, parestesija, ipertonija, konfużjoni, ansjetà, nuqqas ta ’ stabbilità emozzjonali, ngħas, tnaqqis fil- libido, nervożità, ma tibqax tara bil- lejl, nystagmus, disturbi fil- lakrimazzjoni, żanżin fil- widnejn, tibdil fit- togħma, uġigħ fis- sider, arritmija, disturbi vaskulari periferali, edema ġeneralizzata, emoptisi, qtugħ ta ’ nifs, żieda fis- sogħla, sinusite, farinġite, disfaġja, ulċerazzjoni tal- ħalq, moniliasi orali, stomatite, dispepsja, għatx, ippurgar anormali, titfewwaq, raxx vesikobulluż, raxx makulopapulari, bugħawwieġ fir- riġlejn, ematurja, sindrome ta ’ l- influwenza, uġigħ pelviku, u riħa tal- ġisem.
Single observations of the following were also reported: bone marrow depression, decreased prothrombin, decreased gonadotrophic luteinizing hormone, increased amylase, hyponatraemia, hypokalaemia, hyperuricaemia, hypocholesterolaemia, hypolipaemia, hypomagnesaemia, abnormal gait, stupor, circumoral paraesthesia, abnormal thinking, eye pain, hypovolaemia, subdural haematoma, congestive heart failure, palpitation, epistaxis, vascular anomaly, vascular disorder, pallor, pneumonia, respiratory disorder, lung disorder, pleural disorder, cholecystitis, liver damage, jaundice, cholestatic jaundice, melaena, vomiting, laryngismus, tenesmus, rhinitis, increased appetite, gingivitis, herpes zoster, psoriasis, furunculosis, contact dermatitis, seborrhoea, lichenoid dermatitis, arthritis, joint disorder, urinary retention, impaired urination, polyuria, nocturia, impotence, urine abnormality, breast enlargement, carcinoma, photosensitivity reaction, face oedema, malaise, viral infection, enlarged abdomen.
Osservazzjonijiet waħidhom ta ’ dawn li ġejjin kienu rrappurtati wkoll: nuqqas fil- funzjoni tal - mudullun, tnaqqis fil- prothrombin, tnaqqis fl- ormon gonadotrofiku luteinizing, żieda fl- amylase, iponatremija, ipokalemija, iperurikemija, ipokolesterolemija, ipolipemija, ipomanjesemija, timxi b’ mod anormali, sturdament, parestesija ċirkumorali, ħsibijiet anormali, uġigħ fl- għajnejn, ipovolemija, ematoma subdurali, insuffiċjenza konġestiva tal- qalb, palpitazzjoni, tinfaraġ, anomalija vaskulari, disturbi vaskulari, sfurija, pnewmonja, disturbi respiratorji, disturbi tal- pulmun, disturbi tal - plewra, koleċistite, ħsara fil- fwied, suffejra, suffejra kolestatika, melaena, rimettar, larinġiżmu, tenesmus, rinite, żieda fl- aptit, ġinġivite, herpes zoster, psorjasi, furunkolosi, dermatite tal- kuntatt, seborrea, dermatite lichenoid, artrite, disturbi tal- ġogi, żamma ta ’ l- awrina, indeboliment meta tagħmel l- awrina, tagħmel ammont eċċessiv ta ’ awrina, notturnja, impotenza, anormalità fl- awrina, tkabbir tas - sider, karċinoma, reazzjoni tas- sensittività għad- dawl, edema tal- wiċċ, telqa, infezzjoni virali, tkabbir fid- daqs taż- żaqq.
The majority of adverse reactions were noted at a higher incidence at doses greater than 300 mg/ m2/ day.
Il- maġġoranza tar- reazzjonijiet avversi kienu osservati f’ inċidenza ogħla f’ dożi akbar minn 300 mg/ m2/ kuljum.
Generally, these resolved without sequelae on dose reduction or withdrawal of treatment.
Ġeneralment, dawn fiequ mingħajr ma kien hemm l- ebda kundizzjonijiet jew mard b’ konsegwenza ta ’ dan, malli tnaqqset id- doża jew twaqqfet il- kura.
However, among a total of 810 patients, including those without malignancy, treated with bexarotene, there were three serious adverse reactions with fatal outcome (acute pancreatitis, subdural haematoma and liver failure).
Madankollu, fost total ta ’ 810 pazjenti, li jinkludi dawk mingħajr malinn, li kienu kkurati b’ bexarotene, kien hemm tliet reazzjonijiet avversi serji b’ riżultat fatali (pankreatite akuta, ematoma subdurali u insuffiċjenza tal- fwied).
Of these, liver failure, subsequently determined to be not related to bexarotene, was the only one to occur in a CTCL patient.
Minn dawn, l- insuffiċjenza tal- fwied, li sussegwentement kien stabbilit li ma kinitx marbuta ma ’ bexarotene, kienet l- unika waħda li seħħet f’ pazjent li kellu CTCL.
Hypothyroidism generally occurs 4-8 weeks after commencement of therapy.
L- ipotirojdiżmu ġeneralment iseħħ 4- 8 ġimgħat wara l- bidu tat- terapija.
It may be asymptomatic and responds to treatment with thyroxine and resolves upon withdrawal of treatment.
Dan jista ’ jkun asintomatiku u jirrispondi għall- kura b’ thyroxine u jfieq malli titwaqqaf il- kura.
Bexarotene has a different adverse reaction profile to other oral, non-retinoid X receptor (RXR) - selective retinoids.
Bexarotene għandu profil differenti għar- reazzjonijiet avversi għal retinojdi selettivi non- retinoid X receptor (RXR) orali oħrajn.
Owing to its primarily RXR-binding activity, bexarotene is less likely to cause mucocutaneous, nail, and hair toxicities; arthralgia; and myalgia; which are frequently reported with retinoic acid receptor (RAR) -binding agents.
Minħabba l- attività primarja tiegħu tat- twaħħil ma ’ RXR, bexarotene hu inqas probabbli li jikkawża tossiċitajiet fil- ġilda u fil- membrani mukużi, fid- dwiefer u fix- xagħar; artralġja; u mijalġja; li huma b’ mod frekwenti rrappurtati ma ’ sustanzi li jeħlu tar- retinoic acid receptor (RAR).
4.9 Overdose
8 4. 9 Doża eċċessiva
No clinical experience with an overdose of Targretin has been reported.
L- ebda esperjenza klinika b’ doża eċċessiva ta ’ Targretin ma kienet irrappurtata.
Any overdose should be treated with supportive care for the signs and symptoms exhibited by the patient.
Kwalunkwe doża eċċessiva għandha tkun ikkurata b’ kura ta ’ appoġġ għas- sinjali u s- sintomi li jintwerew mill- pazjent.
Doses up to 1000 mg/ m2/ day of bexarotene have been administered in clinical studies with no acute toxic effects.
Dożi ta ’ bexarotene sa 1000 mg/ m2/ kuljum ingħataw fi studji kliniċi mingħajr l- ebda effetti tossiċi akuti.
Single doses of 1500 mg/ kg (9000 mg/ m2) and 720 mg/ kg (14,400 mg/ m2) were tolerated without significant toxicity in rats and dogs, respectively.
Dożi waħidhom ta ’ 1500 mg/ kg (9000 mg/ m2) u ta ’ 720 mg/ kg (14, 400 mg/ m2) kienu ttollerati mingħajr tossiċità sinifikanti fil- firien u l- klieb, rispettivament.
Pharmacotherapeutic Group: other antineoplastic agents, ATC code:
Kategorija farmakoterapewtika: sustanzi antineoplastiċi oħrajn, Kodiċi ATC:
Bexarotene is a synthetic compound that exerts its biological action through selective binding and activation of the three RXRs: α, β, and γ.
Bexarotene hu kompost sintetiku li jeżercita l- azzjoni bijoloġika tiegħu permezz ta ’ twaħħil selettiv u l- attivazzjoni tal- tliet RXRs: α, β, u γ.
Once activated, these receptors function as transcription factors that regulate processes such as cellular differentiation and proliferation, apoptosis, and insulin sensitisation.
Ġaladarba attivati, dawn ir- riċetturi jiffunzjonaw bħala l- fatturi tat- traskrizzjoni li jirregolaw proċessi bħad- differenzazzjoni u l- proliferazzjoni ċellulari, l- apoptosi, u s- sensibilizzazzjoni ta ’ l- insulina.
The ability of the RXRs to form heterodimers with various receptor partners that are important in cellular function and in physiology indicates that the biological activities of bexarotene are more diverse than those of compounds that activate the RARs.
Il- ħila tal- RXRs li jiffurmaw heterodimers ma ’ l- imsieħba varji tar - riċetturi li huma importanti fil- funzjoni ċellulari u fil- fiżjoloġija tindika li l- attivitajiet bijoloġiċi ta ’ bexarotene huma aktar diversi milli minn dawk tal- komposti li jattivaw l- RARs.
In vitro, bexarotene inhibits the growth of tumour cell lines of haematopoietic and squamous cell origin.
In vitro, bexarotene jinibixxi t- tkabbir ta ’ razza ta ’ ċelluli tat- tumur, ta ’ oriġini ematopojetika u taċ- ċelluli skwamużi.
In vivo, bexarotene causes tumour regression in some animal models and prevents tumour induction in others.
In vivo, bexarotene jikkawża rigressjoni tat- tumur f’ xi mudelli ta ’ l- annimali, u jevita l- induzzjoni tat - tumur f’ oħrajn.
However, the exact mechanism of action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) is unknown.
Madankollu, il- mekkaniżmu eżatt ta ’ l- azzjoni ta ’ bexarotene fil- kura ta ’ cutaneous T - cell lymphoma (CTCL) mhuwiex magħruf.
8 Bexarotene capsules were evaluated in clinical trials of 193 patients with CTCL of whom 93 had advanced stage disease refractory to prior systemic therapy.
Il- kapsuli bexarotene kienu evalwati fi provi kliniċi fuq 193 pazjent li kellhom CTCL, li minnhom 93 kellhom il- marda li kienet fi stadju avvanzat u li kienet refrattarja għal terapija sistemika li saret qabel.
Among the 61 patients treated at an initial dose of 300 mg/ m2/ day, the overall response rate, according to a global assessment by the physician, was 51% (31/ 61) with a clinical complete response rate of 3%.
Fost il- 61 pazjent li kienu kkurati b’ doża tal- bidu ta ’ 300 mg/ m2/ kuljum, ir- rata tar- rispons totali, skond evalwazzjoni globali mit- tabib, kienet ta ’ 51% (31/ 61) b’ rata ta ’ rispons sħiħ kliniku ta ’ 3%.
Responses were also determined by a composite score of five clinical signs (surface area, erythema, plaque elevation, scaling and hypo/ hyperpigmentation) which also considered all extracutaneous CTCL manifestations.
Ir - risponsi kienu stabbiliti wkoll minn punteġġ kompost ta ’ ħames sinjali kliniċi (superfiċje tal- wiċċ, eritema, elevazzjoni tal- plakka, qoxra u ipo/ iperpigmentazzjoni) li kkunsidraw ukoll il - manifestazzjonijiet kollha tas- CTCL ’ il barra mill- ġilda.
The overall response rate according to this composite assessment was 31% (19/ 61) with a clinical complete response rate of 7% (4/ 61).
Ir- rata totali tar- rispons skond din l - evalwazzjoni komposta kienet ta ’ 31% (19/ 61) flimkien ma ’ rata ta ’ rispons sħiħ kliniku ta ’ 7% (4/ 61).
Absorption/ dose proportionality: pharmacokinetics were linear up to a dose of 650 mg/ m2.
Il- farmakokinetiċi kienu lineari sa doża ta ’ 650 mg/ m2.
Terminal elimination half-life values were generally between one and three hours.
Il - valuri tal- half- life ta ’ l- eliminazzjoni terminali kienu ġeneralment bejn siegħa u tliet sigħat.
Following repeat once daily dose administration at dose levels ≥ 230 mg/ m2, Cmax and AUC in some patients were less than respective single dose values.
Wara l - għoti ta ’ dożi ripetuti darba kuljum f’ livelli tad- doża ta ’ ≥ 230 mg/ m2, is- Cmax u l- AUC f’ xi pazjenti kienu anqas mill- valuri rispettivi għal doża waħda.
No evidence of prolonged accumulation was observed.
Ma kienet osservata l- ebda evidenza ta ’ akkumulazzjoni fit- tul.
At the recommended initial daily-dose level (300 mg/ m2), single-dose and repeated daily-dose bexarotene pharmacokinetic parameters were similar.
Fil- livell tad- doża rakkomandata tal- bidu ta ’ kuljum (300 mg/ m2), il- parametri farmakokinetiċi ta ’ dożi waħidhom u ta ’ dożi ripetuti ta ’ kuljum ta ’ bexarotene kienu simili.
Protein binding/ distribution: bexarotene is highly bound (> 99%) to plasma proteins.
Bexarotene jeħel ħafna (> 99%) mal- proteini tal- plażma.
The uptake of bexarotene by organs or tissues has not been evaluated.
It- teħid ta ’ bexarotene minn organi jew tessuti ma kienx evalwat.
Metabolism: bexarotene metabolites in plasma include 6- and 7-hydroxy-bexarotene and 6- and 7-oxo- bexarotene.
Il- metaboliti ta ’ bexarotene fil- plażma jinkludu 6 - u 7- hydroxy- bexarotene u 6 - u 7- oxo - bexarotene.
In vitro studies suggest glucuronidation as a metabolic pathway, and that cytochrome P450 3A4 is the major cytochrome P450 isozyme responsible for formation of the oxidative metabolites.
In vitro, l- istudji jissuġġerixxu l- glukoronidazzjoni bħala l- passaġġ metaboliku, u li ċitokrom P450 3A4 hu ċ- ċitokrom maġġuri ta ’ l- isożima P450 responsabbli għall- formazzjoni tal - metaboliti li jossidaw.
Based on the in vitro binding and the retinoid receptor activation profile of the metabolites, and on the relative amounts of individual metabolites in plasma, the metabolites have little impact on the pharmacological profile of retinoid receptor activation by bexarotene.
Ibbażat fuq it- twaħħil in vitro u l- profil ta ’ l- attivazzjoni tar- riċettur retinojdi tal- metaboliti, u fuq l- ammonti relattivi tal- metaboliti individwali fil- plażma, il- metaboliti għandhom impatt żgħir fuq il- profil farmakoloġiku ta ’ l- attivazzjoni tar- riċettur retinojdi minn bexarotene.
Excretion: neither bexarotene nor its metabolites are excreted in urine in any appreciable amounts.
La bexarotene u lanqas il- metaboliti tiegħu ma jitneħħew fl- awrina f’ xi ammonti apprezzabbli.
The estimated renal clearance of bexarotene is less than 1 ml/ minute.
It- tneħħija stmata renali ta ’ bexarotene hi anqas minn 1 ml/ minuta.
Renal excretion is not a significant elimination pathway for bexarotene.
It- tneħħija renali mhijiex passaġġ sinifikanti ta ’ l- eliminazzjoni għal bexarotene.
Carcinogenesis, mutagenesis, impairment of fertility: bexarotene is not genotoxic.
Karċinoġenesi, mutaġenesi, indeboliment tal- fertilità: bexarotene mhuwiex ġenotossiku.
Carcinogenicity studies have not been conducted.
Ma sarux studji dwar il- karċinoġeneċità.
Fertility studies have not been conducted; however, in sexually immature male dogs, reversible aspermatogenesis (28-day study) and testicular degeneration (91-day study) were seen.
Ma sarux studji dwar il- fertilità; madankollu, fi klieb irġiel li kienu sesswalment immaturi, kienu osservati l- aspermatoġenesi riversibbli (fi studju li dam 28 jum) u deġenerazzjoni (fi studju li dam 91 jum).
When bexarotene was administered for six months to sexually mature dogs, no testicular effects were seen.
Meta bexarotene ingħata għal sitt xhur lil klieb li kienu sesswalment maturi, ma kienu osservati l- ebda effetti testikulari.
Effects on fertility cannot be excluded.
L- effetti fuq fertilità ma jistgħux ikunu esklużi.
Bexarotene, in common with the majority of retinoids, was teratogenic and embryotoxic in an animal test species at systemic exposures that are achievable clinically in humans.
Bexarotene, bħal fil- każ tal- maġġoranza tar- retinojdi, kien teratoġeniku u embrijotossiku fi speċi ta ’ annimali li kienu ttestjati f’ espożizzjonijiet sistemiċi li jistgħu jintlaħqu klinikament fil- bnedmin.
Irreversible cataracts involving the posterior area of the lens occurred in rats and dogs treated with bexarotene at systemic exposures that are achievable clinically in humans.
Katarretti irriversibbli li kienu jinvolvu n- naħa ta ’ wara żona tal- lenti, seħħew fil- firien u fil- klieb li kienu kkurati b’ bexarotene f’ espożizzjonijiet sistemiċi li jistgħu jintlaħqu klinikament fil- bnedmin.
The aetiology of this finding is unknown.
L- etjoloġija ta ’ din is- sejba mhijiex magħrufa.
An adverse effect of long-term bexarotene treatment on cataract formation in humans has not been excluded.
Effett avvers tal - kura fit- tul ta ’ bexarotene fuq il- formazzjoni tal- katarretti fil- bnedmin ma kinitx eskluża.
Capsule content: macrogol polysorbate povidone butylated hydroxyanisole
Kontenut tal- kapsula: macrogol polysorbate povidone butylated hydroxyanisole
9 Capsule shell: gelatin sorbitol special-glycerin blend (glycerin, sorbitol, sorbitol anhydrides (1,4-sorbitan), mannitol and water) titanium dioxide (E171) printing ink (SDA 35A alcohol (ethanol & ethyl acetate), propylene glycol (E1520), iron oxide black (E172), polyvinyl acetate phthalate, purified water, isopropyl alcohol, macrogol 400, ammonium hydroxide 28%)
Qoxra tal- kapsula: gelatin sorbitol special- glycerin blend (glycerin, sorbitol, sorbitol anhydrides (1, 4- sorbitan), mannitol u ilma) titanium dioxide (E171) linka ta ’ l- istampar (SDA 35A alcohol (ethanol u ethyl acetate), propylene glycol (E1520), iron oxide black (E172), polyvinyl acetate phthalate, purified water, isopropyl alcohol, macrogol 400, ammonium hydroxide 28%)
High-density polyethylene bottles with child-resistant closures containing 100 capsules.
Fliexken tal- polyethylene b’ densità għolja b’ għatjien reżistenti għat- tfal, li fihom 100 kapsula.
European Knowledge Centre Mosquito Way Hatfield Hertfordshire AL10 9SN United Kingdom
European Knowledge Centre Mosquito Way Hatfield Hertfordshire AL10 9SN Ir- Renju Unit
29 March 2001.
29 ta ’ Marzu, 2001.
29 March 2006.
29 ta ’ Marzu, 2006.
• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON THE MARKETING AUTHORISATION HOLDER
DETENTUR TA ’ L- AWTORIZZAZZJONI TAL - MANIFATTURA RESPONSABBLI GĦALL- ĦRUĠ TAL - LOTT
Medicinal product subject to restricted medical prescription (See Annex I:
KUNDIZZJONIJIET TA ’ L- AWTORIZZAZZJONI GĦAT - TQEGĦID FIS- SUQ
12 ANNEX III
12 A DETENTUR TA ’ L- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- ĦRUĠ TAL- LOTT
LABELLING AND PACKAGE LEAFLET
Sommarju tal- Karatteristiċi tal - Prodott, sezzjoni 4. 2).
14 PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING
TIKKETTA
OUTER CARTON TEXT AND BOTTLE LABEL TEXT
KLIEM FUQ IL- KARTUNA TA ’ BARRA U FUQ IT- TIKKETTA TAL- FLIXKUN
Targretin 75 mg soft capsules Bexarotene
Targretin 75 mg kapsuli rotob Bexarotene
One capsule contains 75 mg of bexarotene.
Kapsula waħda fiha 75 mg ta ’ bexarotene.
Each capsule also contains macrogol, polysorbate, povidone and butylated hydroxyanisole and the colourant titanium dioxide (E171), and other ingredients.
Kull kapsula fiha wkoll macrogol, polysorbate, povidone u butylated hydroxyanisole u l- kolorant titanium dioxide (E171), u ingredjenti oħrajn.
100 soft capsules
100 kapsula iebsin
To be swallowed whole.
Il- kapsuli jinbelgħu sħaħ.
Do not store above 30°C.
Taħżinx f’ temperatura ’ l fuq minn °30C.
Mosquito Way Hatfield Hertfordshire AL10 9SN United Kingdom
Mosquito Way Hatfield Hertfordshire AL10 9SN Ir- Renju Unit
PACKAGE LEAFLET
INFORMAZZJONI BIL- BRAILLE
TARGRETIN 75 mg soft capsules Bexarotene
TARGRETIN 75 mg kapsuli rotob Bexarotene
Read all of this leaflet carefully before you start taking this medicine.
Aqra SEW dan il- fuljett kollu qabel tibda tieħu din il- mediċina..
What Targretin is and what it is used for 2.
X’ inhu Targretin u għalxiex jintuża 2.
Before you take Targretin 3.
Qabel ma tuża Targretin 3.
How to take Targretin 4.
Kif għandek tuża Targretin 4.
How to store Targretin 6.
Kif taħżen Targretin 6.
WHAT TARGRETIN IS AND WHAT IT IS USED FOR
X’ INHU TARGRETIN U GĦALXIEX JINTUŻA
The active substance in Targretin, bexarotene, belongs to a group of medicines known as retinoids, which are related to vitamin A.
Is- sustanza attiva f’ Targretin, bexarotene, tappartjeni għall- grupp ta ’ mediċini magħrufin bħala retinojdi, li huma relatati ma ’ vitamina A.
Targretin capsules are used by patients with advanced stage cutaneous T-cell lymphoma (CTCL) whose disease has not responded to other therapies.
Il- kapsuli Targretin jintużaw minn pazjenti li għandhom limfoma taċ- ċelluli T fil- ġilda (cutaneous T- cell lymphoma - CTCL)) fi stadju avvanzat, u li l- marda tagħhom ma tkunx irrispondiet għal terapiji oħrajn.
CTCL is a condition in which certain cells of the body’ s lymph system called T-lymphocytes become cancerous and affect the skin.
Is- CTCL hi kundizzjoni li fiha ċerti ċelluli tas - sistema tal- limfi tal- ġisem imsejħa T- limfoċiti, isiru kanċerużi u jaffettwaw il- ġilda.
BEFORE YOU TAKE TARGRETIN
QABEL MA ’ TUŻA TARGRETIN
Do not take Targretin
Tieħux Targretin
- if you know that you are allergic (hypersensitive) to bexarotene or to any of the other
- jekk taf li int allerġiku/ a (tbati minn sensittività eċċessiva) għal bexarotene jew għal xi sustanzi
ingredients.
mhux attivi.
- if you are pregnant or breast feeding or if you can become pregnant and are not using effective
- jekk inti tqila jew qed tredda ’, jew jekk tista ’ toħroġ tqila u m’ intix tuża miżuri effettivi ta ’
birth control measures.
kontraċezzjoni.
- if you have a history of pancreatitis, have uncontrolled lipid (blood fats) elevations (high blood
- jekk għandek storja ta ’ pankreatite, jekk għandek livelli għoljin ta ’ lipidi (xaħmijiet fid- demm)
cholesterol or high blood triglycerides), have a condition known as hypervitaminosis A, have uncontrolled thyroid disease, have insufficient liver function or have an ongoing systemic infection.
mhux ikkontrollati (kolesterol għoli fid- demm jew triglycerides għoljin fid- demm), jekk għandek kundizzjoni magħrufa bħala ipervitaminosi A, jekk għandek mard mhux ikkontrollat fit- tirojde, jekk għandek insuffiċjenza fil- funzjoni tal- fwied jew jekk għandek infezzjoni sistemika.
Take special care with Targretin
Oqgħod attent ħafna b’ Targretin
- if you have a known hypersensitivity to retinoids (related to vitamin A), suffer from liver
- jekk għandek sensittività eċċessiva magħrufa għar- retinojdi (marbuta ma ’ vitamina A), jekk tbati
disease, have high blood lipids or take medicines which may cause high blood lipids, have uncontrolled diabetes mellitus (sugar diabetes), have had gall bladder or biliary tract disease, or consume excessive amounts of alcohol.
mill- mard fil- fwied, jekk għandek livelli għoljin ta ’ lipidi fid- demm, jew jekk jew tieħu mediċini li jistgħu jikkawżaw livelli għoljin ta ’ lipidi fid- demm, jekk għandek dijabete mellitus (dijabete taz- zokkor) mhux ikkontrollata, jekk kellek mard fil- marrara jew fl- apparat biljari, jew jekk tikkonsma ammonti eċċessivi ta ’ alkoħol.
If any of these apply, you should inform your doctor.
Jekk xi waħda minn dawn tapplika għalik, għandek tinforma lit- tabib tiegħek.
Your fasting blood lipid determinations may have to be performed before therapy is initiated and at weekly intervals afterwards, and then monthly while taking this medicine.
Il- livelli tal- lipidi fid- demm tiegħek fl- istat sajjem, jista ’ jkollhom bżonn jitkejlu qabel ma tibda l - kura, u f’ intervalli ta ’ kull ġimgħa wara li tibda t- terapija, u mbagħad kull xahar waqt li tkun qed tieħu din il- mediċina.
Blood tests to evaluate the function of your liver and thyroid gland and to monitor your red blood cell and white blood cell counts will be obtained before therapy is started and will be monitored during therapy.
19 It- testijiet tad- demm biex issir evalwazzjoni tal- funzjoni tal- fwied u tal- glandola tat- tirojde tiegħek, u biex jiġi mmonitorat l- għadd taċ- ċelluli tad- demm ħomor u bojod, ser isiru qabel ma tibda t- terapija, u ser ikunu mmonitorati matul it- terapija.
18 Periodic eye exams may be needed if you experience visual difficulties while taking this medicine.
Eżamijiet perjodiċi ta ’ l- għajnejn jistgħu jkunu meħtieġa jekk ikollok problemi fil- vista waqt li tkun qed tieħu din il- mediċina.
Minimise exposure to sunlight as much as possible and avoid exposure to sun lamps.
Naqqas kemm jista ’ jkun l- espożizzjoni għad- dawl tax- xemx, u evita li tesponi ruħek għal- lampi li jintużaw sabiex wieħed jismar.
Do not take more than 15,000 International Units of vitamin A supplements per day during treatment.
Tiħux aktar minn 15, 000 Unitajiet Internazzjonali ta ’ supplimenti ta ’ vitamina A kuljum matul il- kura.
Targretin capsules should not be used in children or adolescents.
Il- kapsuli ta ’ Targretin m’ għandhomx jintużaw fit- tfal jew fl- adolexxenti.
Taking other medicines Before starting treatment, make sure your doctor knows if you are taking medicines (including those not prescribed by your doctor), such as ketoconazole and itraconazole (used against fungal infections), erythromycin, clarithromycin and rifampicin (used against bacterial infections), phenytoin and phenobarbital (used against seizures), gemfibrozil (used to reduce high levels of fats in the blood such as triglycerides and cholesterol), vitamin A supplements, protease inhibitors (used against viral infections), tamoxifen (used against some forms of cancer) or dexamethasone (used for inflammatory conditions).
Meta tuża mediċini oħra Qabel tibda l- kura, aċċerta ruħek li t- tabib tiegħek ikun jaf jekk qed tieħu mediċini (li jinkludi dawk li t- tabib tiegħek ma takx riċetta għalihom), bħal ketoconazole u itraconazole (jintużaw kontra l - infezzjonijiet fungali), erythromycin, clarithromycin u rifampicin (jintużaw kontra l- infezzjonijiet batterjali), phenytoin u phenobarbital (jintużaw kontra l- puplesiji), gemfibrozil (jintuża biex inaqqas livelli għolja ta ’ xaħmijiet fid- demm, bħal triglycerides u kolesterol), supplimenti tal- vitamina A, inibituri tal- protease (jintużaw kontra infezzjonijiet virali), tamoxifen (jintuża kontra xi forom ta ’ kanċer) jew dexamethasone (jintuża għal kundizzjonijiet infjammatorji).
This is important as using more than one medicine at the same time can strengthen or weaken the effect of the medicines.
Dan huwa importanti, għax li tuża aktar minn mediċina waħda fl- istess ħin jista ’ jsaħħaħ jew idgħajjef l- effett tal- mediċini.
Taking Targretin with food and drink Targretin should be taken with food.
Meta tieħu Targretin ma ’ l- ikel u max- xorb Targretin għandux jittieħed ma ’ l- ikel.
If you regularly consume grapefruit or grapefruit juice, please consult your doctor as these have the potential to alter your body’ s response to Targretin therapy.
Jekk inti regolarment tiekol il- grejpfrut jew tixrob il- meraq tal - grejpfrut, jekk jogħġbok kellem lit- tabib tiegħek, għax dawn jistgħu jibdlu r- rispons ta ’ ġismek għat - terapija ta ’ Targretin.
Pregnancy and breast-feeding Targretin may be harmful to a developing foetus.
Tqala u treddigħ Targretin jista ’ jkun ta ’ ħsara għal fetu li jkun qed jiżviluppa.
DO NOT use Targretin if you are pregnant or breast-feeding.
TUŻAX Targretin jekk inti tqila jew qed tredda ’.
If you are pregnant, thinking of becoming pregnant, or breast-feeding, ask your doctor for more information.
Jekk inti tqila, jew qed taħseb biex toħroġ tqila, jew qed tredda ’, staqsi it- tabib tiegħek għal aktar informazzjoni.
If you are capable of becoming pregnant, you must have a pregnancy test within one week before you start therapy, confirming you are not pregnant.
Jekk inti tista ’ toħroġ tqila, għandu jsirlek test tat- tqala fi żmien ġimgħa qabel ma tibda t- terapija, biex tikkonferma li m’ intix tqila.
You must use effective contraception (birth control) continuously starting one month before beginning therapy until one month after you stop taking Targretin.
Għandek tuża kontraċezzjoni effettiva l- ħin kollu, li tibda xahar qabel il - bidu tat- terapija, sa xahar wara li tieqaf tieħu Targretin.
It is recommended that two reliable forms of contraception be used together.
Hu rakkomandat li żewġ forom affidabbli ta ’ kontraċezzjoni jintużaw flimkien.
If you are taking a hormonal contraceptive (for example, birth control pills), you should discuss this with your doctor.
Jekk qed tieħu kontraċettiv ormonali (pereżempju pilloli tal - kontraċezzjoni), għandek tiddiskuti dan mat- tabib tiegħek.
If you are male and your partner is pregnant or capable of becoming pregnant, you must use condoms during sexual intercourse while taking bexarotene and for at least one month after the last dose.
Jekk inti raġel u s- sieħba tiegħek hi tqila, jew tista ’ toħroġ tqila, għandek tuża l- kondoms waqt il - kopulazzjoni sesswali, waqt li tkunu qed tieħu bexarotene, u għal mill- anqas xahar wara l- aħħar doża.
Driving and using machines It is not known whether Targretin has an effect on your ability to drive a car or operate machinery.
Sewqan u tħaddim ta ’ magni Mhux maghruf jekk Targretin għandux effett fuq il- ħila tiegħek biex issuq jew tħaddem magni.
If you experience dizziness or problems with your vision during therapy, do not drive or operate machinery.
Jekk ikollok sturdament jew problemi tal- vista waqt it- terapija, m’ għandekx issuq jew tħaddem xi makkinarju.
Important information about some of the ingredients of Targretin Butylated hydroxyanisole, an ingredient in Targretin, may cause irritation to the mucous membranes, therefore the capsules must be swallowed intact and not chewed.
Tagħrif importanti dwar xi wħud mis- sustanzi ta ’ Targretin Butylated hydroxyanisole, sustanza f’ Targretin, tista ’ tikkawża irritazzjoni lill- membrani mukużi; għalhekk il- kapsuli jridu jinbelgħu intatti, u m’ għandekx tomgħodhom.
HOW TO TAKE TARGRETIN
KIF GĦANDEK TUŻA TARGRETIN
Always take Targretin exactly as your doctor has told you.
Dejjem għandek tieħu Targretin skond il- parir tat- tabib.
The doctor will prescribe a suitable dose for you, which is generally 4 to 10 capsules to be taken once daily.
Ħu n- numru ta ’ kapsuli li
Take your prescribed number of capsules at the same time each day with a meal.
20 għalihom ingħatajt riċetta fl- istess ħin kuljum ma ’ l- ikel.
The capsules can be taken immediately before, during or immediately after the course of the meal, if preferred.
Il- kapsuli jistgħu jittieħdu immedjatament qabel, matul jew immedjatament wara l- ikel, jekk tkun tixtieq.
The capsules should be swallowed whole and not chewed.
Il- kapsuli għandhom jinbelgħu sħaħ u m’ għandekx tomgħodhom.
19 How long you should take Targretin Do not stop taking your medication until your doctor advises you to do so.
Għal kemm għandek tieħu Targretin Tiqafx tieħu l- mediċina tiegħek sakemm it- tabib tiegħek jagħtik parir biex tagħmel hekk.
Although some patients have improvement within the first several weeks, most patients require several months or more of treatment to improve.
Għalkemm xi pazjenti raw titjib fil- kundizzjoni tagħhom fi żmien l- ewwel diversi ġimgħat, il- biċċa l- kbira tal - pazjenti jeħtieġu diversi xhur jew aktar ta ’ kura biex jinnutaw titjib.
If you take more Targretin than you should If you have taken more than the prescribed dose of Targretin, you must contact your doctor.
Jekk tieħu aktar Targretin milli suppost Jekk tieħu aktar mid- doża ta ’ Targretin li għaliha ngħatajt riċetta, għandek tikkuntattja lit- tabib tiegħek.
If you forget to take Targretin If you forget to take one dose, take your daily dose with your next meal on the same day, then take your usual dose as normal, the following day.
Jekk tinsa tieħu Targretin Jekk tinsa tieħu doża waħda, ħu d- doża tiegħek ta ’ kuljum ma ’ l- ikla li jmiss fl- istess jum, imbagħad ħu d- doża normali bħas- soltu l- għada.
Do not take a double dose in one day to make up for a missed dose the previous day.
M’ għandekx tieħu doża doppja f’ jum wieħed biex tpatti għal doża li tkun insejt tieħu fil- jum ta ’ qabel.
Like all medicines, Targretin can cause side effects, although not everybody gets them.
Bħal kull mediċina oħra, Targretin jista ’ jkollu effetti sekondarji, għalkemm ma jidhrux fuq kulħadd.
Tell your doctor as soon as possible if you feel any deterioration in your condition while you are taking Targretin.
Għid it- tabib tiegħek kemm jista ’ jkun malajr jekk tħoss kwalunkwe deterjorament fil- kundizzjoni tiegħek waqt li tkun qed tieħu Targretin.
Sometimes it is necessary to adjust the dose or interrupt treatment.
Xi kultant ikun meħtieġ li taġġusta d- doża jew li twaqqaf il - kura.
Your doctor will advise you on what to do.
It- tabib tiegħek ser jagħtik parir dwar x’ għandek tagħmel.
The following side effects were reported in patients with CTCL who were treated with the recommended initial dose of capsules.
L- effetti sekondarji li ġejjin kienu rrappurtati f’ pazjenti li kellhom is- CTCL li kienu kkurati bid- doża rakkomandata tal- bidu tal- kapsuli.
Low white blood cell count.
Komuni ħafna (li jistgħu jseħħu f’ aktar minn 1 minn kull 10 pazjenti kkurati) Għadd baxx taċ- ċelluli tad- demm bojod.
Lowering of thyroid hormones level.
Tnaqqis fil- livell ta ’ l- ormoni tat- tirojde.
Elevation of blood fats (triglycerides and cholesterol).
Żieda fix- xaħmijiet fid- demm (triglycerides u kolesterol).
Skin reactions (Itching, redness, irritation, peeling).
Reazzjonijiet tal- ġilda (Ħakk, ħmura, irritazzjoni, ġilda li titqaxxar).
Headache, fatigue, pain.
Uġigħ ta ’ ras, għeja kbira, uġigħ.
Common (can occur in less than 1 in 10 but in more than 1 in 100 patients treated):
Komuni (jistgħu jseħħu f’ anqas minn 1 minn kull 10 pazjenti, iżda f’ aktar minn 1 minn kull 100 pazjent ikkurat):
Low red blood cell count, enlarged lymph nodes, worsening of lymphoma.
Għadd baxx ta ’ ċelluli tad- demm ħomor, tkabbir fl- għoqod tal- limfa, limfoma li tmur għall- agħar.