Kompozisyon:
Uygulama:
Tedavide kullanılır:
Oliinyk Elizabeth Ivanovna tarafından tıbbi olarak gözden geçirilmiştir, Eczane Son güncelleme: 06.04.2022
Dikkat! Sayfadaki bilgiler sadece sağlık profesyonelleri içindir! Bilgi kamu kaynaklarında toplanır ve anlamlı hatalar içerebilir! Dikkatli olun ve bu sayfadaki tüm bilgileri tekrar kontrol edin!
Aynı bileşenlere sahip en iyi 20 ilaç:
Tedavi sadece hastane veya uzman gözetimi altında başlatılmalı ve normal olarak izlenmelidir. Oral Trangorexe sadece diğer tedavilere cevap vermeyen şiddetli ritim bozukluklarının tedavisi veya başka bir tedavi kullanılamadığında endikedir.
Wolff-Parkinson-White sendromu ile ilişkili taşiaritmiler.
Diğer ilaçlar kullanılamadığında atriyal çarpıntı ve fibrilasyon.
Supraventriküler, nodal ve ventriküler taşikardi dahil olmak üzere paroksismal doğanın her türlü taşiaritmileri. ventriküler fibrilasyon; başka ilaçlar kullanılamadığında.
Tedavi sadece hastane veya uzman gözetimi altında başlatılmalı ve normal olarak izlenmelidir. Oral amiodaron sadece diğer tedavilere cevap vermeyen şiddetli ritim bozukluklarının tedavisi için veya başka tedaviler kullanılamadığında endikedir.
Wolff-Parkinson-White sendromu ile ilişkili taşiaritmi.
Diğer ilaçlar kullanılamadığında atriyal çarpıntı ve fibrilasyon.
Supraventriküler, nodal ve ventriküler taşikardi, ventriküler fibrilasyon: diğer ilaçlar kullanılamadığında dahil olmak üzere paroksismal doğanın her türlü taşiaritmileri.
Tabletler stabilizasyon ve uzun süreli tedavi için kullanılır.
Tedavi sadece hastane veya uzman gözetimi altında başlatılmalı ve normal olarak izlenmelidir. Oral Trangorex X sadece diğer tedavilere cevap vermeyen şiddetli ritim bozukluklarının tedavisi veya başka tedaviler kullanılamadığında endikedir.
Wolff-Parkinson-Beyaz Sendromu ile ilişkili taşiaritmiler.
Diğer ilaçlar kullanılamadığında atriyal çarpıntı ve fibrilasyon.
Supraventriküler, nodal ve ventriküler taşikardi, ventriküler fibrilasyon: diğer ilaçlar kullanılamadığında dahil olmak üzere paroksismal doğanın her türlü taşiaritmileri.
Yetişkinler:
Minimum etkili dozun kullanılması özellikle önemlidir. Her durumda hastanın yönetimi bireysel yanıt ve refah konusunda değerlendirilmelidir. Aşağıdaki dozaj alayı genellikle etkilidir:
İlk stabilizasyon:
Tedaviye günde üç kez 200 mg ile başlanmalıdır ve 1 hafta boyunca devam edilebilir.
Dozaj daha sonra bir hafta daha günde iki kez 200 mg'a düşürülmelidir.
Bakım:
İlk periyottan sonra dozaj günde 200 mg'a veya uygunsa daha azına düşürülmelidir.
Nadiren, hasta daha yüksek bir idame dozu gerektirebilir. Puanlanmış 100 mg tablet, aritminin kontrolünü korumak için gereken minimum dozu titre etmek için kullanılmalıdır. Bakım dozu, özellikle bunun günde 200 mg'ı aştığı durumlarda düzenli olarak gözden geçirilmelidir.
Genel düşünceler
İlk dozlama:
Hızlı bir şekilde yeterli doku seviyelerine ulaşmak için yüksek bir doza ihtiyaç vardır.
Bakım:
Bakım tedavisi sırasında çok yüksek bir doz, Trangorexe ve metabolitlerinin yüksek doku seviyeleri ile ilişkili olduğuna inanılan yan etkilere neden olabilir.
Trangorexe güçlü bir şekilde proteine bağlıdır ve ortalama plazma yarılanma ömrüne sahiptir (rapor edilen aralık 20 ila 100 gün). Doz ayarlamaları arasında yeni bir dağılım dengesinin sağlanması için yeterli zamana izin verilmesi gerektiği sonucuna varılır. Potansiyel olarak ölümcül aritmileri olan hastalarda uzun yarı ömür değerli bir korumadır, ara sıra dozların ihmal edilmesi genel terapötik etkiyi önemli ölçüde etkilemez. Minimum etkili dozajın kullanılması ve hastanın aşırı Trangorexe dozajının klinik özelliklerini tespit etmek için düzenli olarak izlenmesi özellikle önemlidir. Terapi daha sonra buna göre ayarlanabilir.
Dozaj azaltma / geri çekme
Doku seviyeleri düştükçe yan etkiler yavaşça kaybolur. İlaç çekilmesinin ardından, kalan dokuya bağlı Trangorexe hastayı bir aya kadar koruyabilir. Bununla birlikte, bu dönemde aritminin tekrarlama olasılığı dikkate alınmalıdır.
Pediyatrik popülasyon
Trangorexe'nin çocuklarda güvenliği ve etkinliği belirlenmemiştir.
<2.Yaşlılar:
Tüm hastalarda olduğu gibi, minimum etkili dozun kullanılması önemlidir. Bu hasta grubu için dozaj gereksinimlerinin farklı olduğuna dair bir kanıt olmasa da, çok yüksek bir doz kullanılırsa bradikardi ve iletim kusurlarına daha duyarlı olabilirler. Tiroid fonksiyonunun izlenmesine özellikle dikkat edilmelidir..
Trangorexe oral uygulama içindir.
Yetişkinler
Minimum etkili dozun kullanılması özellikle önemlidir. Her durumda hastanın yönetimi bireysel yanıt ve refah konusunda değerlendirilmelidir. Aşağıdaki dozaj rejimi genellikle etkilidir.
İlk stabilizasyon:
Tedaviye günde üç kez 200 mg ile başlanmalıdır ve 1 hafta boyunca devam edilebilir. Dozaj daha sonra bir hafta daha günde iki kez 200 mg'a düşürülmelidir.
Bakım
İlk periyottan sonra dozaj günde 200 mg'a veya uygunsa daha azına düşürülmelidir. Nadiren, hasta daha yüksek bir idame dozu gerektirebilir. Puanlanmış 100 mg tablet, aritminin kontrolünü korumak için gereken minimum dozu titre etmek için kullanılmalıdır. Bakım dozu, özellikle bunun günde 200 mg'ı aştığı durumlarda düzenli olarak gözden geçirilmelidir.
İntravenözden oral tedaviye geçiş:
Yeterli bir yanıt alınır alınmaz, oral tedavi olağan yükleme dozunda (günde üç kez 200 mg) eşzamanlı olarak başlatılmalıdır. İntravenöz amiodaron daha sonra aşamalı olarak kaldırılmalıdır.
Genel düşünceler
İlk dozlama
Hızlı bir şekilde yeterli doku seviyelerine ulaşmak için yüksek bir doza ihtiyaç vardır.
BAKIM
Bakım tedavisi sırasında çok yüksek bir doz, yüksek doku seviyeleri amiodaron ve metabolitleri ile ilişkili olduğuna inanılan yan etkilere neden olabilir.
Amiodaron güçlü bir şekilde proteine bağlıdır ve ortalama plazma yarılanma ömrü 50 gündür (rapor edilen aralık 20 ila 100 gün). Dozaj ayarlamaları arasında yeni bir dağılım dengesinin sağlanması için yeterli zamana izin verilmesi gerektiği sonucuna varılır. Minimum etkili dozajın kullanılması ve hastanın aşırı amiodaron dozajının klinik özelliklerini tespit etmek için düzenli olarak izlenmesi özellikle önemlidir. Terapi daha sonra buna göre ayarlanabilir.
Dozun azaltılması / geri çekilmesi
Doku seviyeleri düştükçe yan etkiler yavaşça kaybolur. İlaç çekilmesinin ardından, artık dokuya bağlı amiodaron hastayı bir aya kadar koruyabilir. Bununla birlikte, bu dönemde aritminin tekrarlama olasılığı dikkate alınmalıdır. Potansiyel olarak ölümcül aritmileri olan hastalarda, ara sıra dozların ihmal edilmesi genel terapötik etkiyi önemli ölçüde etkilemediğinden, uzun yarılanma ömrü değerli bir korumadır.
Pediyatrik popülasyon
<2.Yaşlı
Tüm hastalarda olduğu gibi, minimum etkili dozun kullanılması önemlidir.4 Özel uyarılar ve kullanım için özel önlemler.
Amiodaron oral uygulama içindir.
Yetişkinler
Minimum etkili dozun kullanılması özellikle önemlidir. Her durumda hastanın yönetimi bireysel yanıt ve refah konusunda değerlendirilmelidir. Aşağıdaki dozaj rejimi genellikle etkilidir.
İlk Stabilizasyon
Tedaviye günde üç kez 200 mg ile başlanmalıdır ve 1 hafta boyunca devam edilebilir. Dozaj daha sonra bir hafta daha günde iki kez 200 mg'a düşürülmelidir.
Bakım
İlk periyottan sonra dozaj günde 200 mg'a veya uygunsa daha azına düşürülmelidir. Nadiren, hasta daha yüksek bir idame dozu gerektirebilir. Puanlanmış 100 mg tablet, aritminin kontrolünü sürdürmek için gereken minimum dozu titre etmek için kullanılmalıdır. Bakım dozu, özellikle bunun günde 200 mg'ı aştığı durumlarda düzenli olarak gözden geçirilmelidir.
Genel Düşünceler
İlk dozlama
Hızlı bir şekilde yeterli doku seviyelerine ulaşmak için yüksek bir doza ihtiyaç vardır.
Bakım
Bakım tedavisi sırasında çok yüksek bir doz, yüksek doku seviyeleri amiodaron ve metabolitleri ile ilişkili olduğuna inanılan yan etkilere neden olabilir.
Amiodaron güçlü bir şekilde proteine bağlıdır ve ortalama plazma yarılanma ömrüne sahiptir (rapor edilen aralık 20-100 gün). Doz ayarlamaları arasında yeni bir dağılım dengesinin sağlanması için yeterli zamana izin verilmesi gerektiği sonucuna varılır. Potansiyel olarak ölümcül aritmileri olan hastalarda, ara sıra dozların ihmal edilmesi genel terapötik etkiyi önemli ölçüde etkilemediğinden, uzun yarılanma ömrü değerli bir korumadır. Aşırı amiodaron dozajının klinik özelliklerini tespit etmek için minimum etkili dozajın kullanılması ve hastanın düzenli olarak izlenmesi özellikle önemlidir. Terapi daha sonra buna göre ayarlanabilir.
Dozaj azaltma / geri çekme
Doku seviyeleri düştükçe yan etkiler yavaşça kaybolur. İlaç çekilmesinin ardından, artık dokuya bağlı amiodaron hastayı bir aya kadar koruyabilir. Bununla birlikte, bu dönemde aritminin tekrarlama olasılığı dikkate alınmalıdır.
Pediyatrik popülasyon
Çocuklarda amiodaronun güvenliği ve etkinliği belirlenmemiştir.
<2 ancak pozoloji hakkında herhangi bir öneri yapılamaz.Yaşlı
Tüm hastalarda olduğu gibi, minimum etkili dozun kullanılması önemlidir. Bu hasta grubu için dozaj gereksinimlerinin farklı olduğuna dair bir kanıt olmasa da, çok yüksek bir doz kullanılırsa bradikardi ve iletim kusurlarına daha duyarlı olabilirler. Tiroid fonksiyonunun izlenmesine özellikle dikkat edilmelidir.
Trangorex X 100 oral uygulama içindir.
Sinüs bradikardisi ve sino-atriyal kalp bloğu: Şiddetli iletim bozuklukları (yüksek dereceli AV bloğu, bifasiküler veya trifasiküler blok) veya sinüs düğümü hastalığı olan hastalarda, Trangorexe sadece kalp pili ile birlikte kullanılmalıdır.
Tiroid fonksiyon bozukluğu öyküsü kanıtı: Tüm hastalarda tedaviden önce tiroid fonksiyon testleri yapılmalıdır.
Trangorexe'nin Torsades de Pointes'i indükleyebilecek ilaçlarla kombinasyonu kontrendikedir.
Hamilelik - istisnai durumlar hariç
Emzirme .
Sinüs bradikardi ve sino-atriyal kalp bloğu. Şiddetli iletim bozuklukları (yüksek dereceli AV bloğu, bifasiküler veya trifasiküler blok) veya sinüs düğümü hastalığı olan hastalarda, amiodaron sadece kalp pili ile birlikte kullanılmalıdır.
Tiroid fonksiyon bozukluğunun kanıtı veya öyküsü. Tüm hastalarda tedaviden önce tiroid fonksiyon testleri yapılmalıdır.
İyot veya amiodarona (bir 100 mg tablet yaklaşık 37.5 mg iyot içerir) veya yardımcı maddelerden herhangi birine karşı bilinen aşırı duyarlılık.
Amiodaronun Torsades de Pointes'i indükleyebilecek ilaçlarla kombinasyonu kontrendikedir (see 4.5 Diğer tıbbi ürünler ile etkileşimler ve diğer etkileşim şekilleri).
Hamilelik - istisnai durumlar hariç
Emzirme .
Sinüs bradikardi ve sino-atriyal kalp bloğu. Şiddetli iletim bozuklukları (yüksek dereceli AV bloğu, bifasiküler veya trifasiküler blok) veya sinüs düğümü hastalığı olan hastalarda, Trangorex X sadece bir kalp pili ile birlikte kullanılmalıdır.
Tiroid fonksiyon bozukluğunun kanıtı veya öyküsü. Tedaviden önce tüm hastalarda tiroid fonksiyon testleri yapılmalıdır.
İyot veya amiodaron veya yardımcı maddelerden herhangi birine karşı bilinen aşırı duyarlılık. (100 mg'lık bir tablet yaklaşık 37.5 mg iyot içerir).
<).Hamilelik - istisnai durumlar hariç .
Emzirme .
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Trangorexe can cause serious adverse reactions affecting the eyes, heart, lung, liver, thyroid gland, skin and peripheral nervous system. Because these reactions may be delayed, patients on long-term treatment should be carefully supervised. As undesirable effects are usually dose-related, the minimum effective maintenance dose should be given.
Before surgery, the anaesthetist should be informed that the patient is taking Trangorexe .
Cardiac disorders :
Too high a dosage may lead to severe bradycardia and to conduction disturbances with the appearance of an idioventricular rhythm, particularly in elderly patients or during digitalis therapy. In these circumstances, Trangorexe treatment should be withdrawn. If necessary, beta-adrenostimulants or glucagon may be given. Because of the long half-life of Trangorexe, if bradycardia is severe and symptomatic the insertion of a pacemaker should be considered.
Oral Trangorexe is not contraindicated in patients with latent or manifest heart failure but caution should be exercised as, occasionally, existing heart failure may be worsened. In such cases, Trangorexe may be used with other appropriate therapies.
The pharmacological action of Trangorexe induces ECG changes: QT prolongation (related to prolonged repolarisation) with the possible development of U-waves and deformed T-waves; these changes do not reflect toxicity.
In the elderly, heart rate may decrease markedly.
Treatment should be discontinued in case of onset of 2nd or 3rd degree A-V block, sino-atrial block or bifascicular block.
Trangorexe has a low pro-arrhythmic effect. Onsets of new arrhythmias or worsening of treated arrhythmias, sometimes fatal, have been reported. It is important, but difficult, to differentiate a lack of efficacy of the drug from a proarrhythmic effect, whether or not this is associated with a worsening of the cardiac condition. Proarrhythmic effects generally occur in the context of drug interactions and/or electrolytic disorders. Despite QT interval prolongation, Trangorexe exhibits a low torsadogenic activity.
Before starting Trangorexe, it is recommended to perform an ECG and serum potassium measurement. Monitoring of ECG is recommended during treatment.
Trangorexe may increase the defibrillation threshold and/or pacing threshold in patients with an implantable cardioverter defibrillator or a pacemaker, which may adversely affect the efficacy of the device. Regular tests are recommended to ensure the proper function of the device after initiation of treatment or change in posology.
Severe Bradycardia :
Cases of severe, potentially life-threatening bradycardia and heart block have been observed when Trangorexe is used in combination with sofosbuvir in combination with another hepatitis C virus (HCV) direct acting antiviral (DAA), such as daclatasvir, simeprevir, or ledipasvir. Therefore, coadministration of these agents with Trangorexe is not recommended.
If concomitant use with Trangorexe cannot be avoided, it is recommended that patients are closely monitored when initiating sofosbuvir in combination with other DAAs. Patients who are identified as being at high risk of bradyarrhythmia should be continuously monitored for at least 48 hours in an appropriate clinical setting after initiation of the concomitant treatment with sofosbuvir.
Patients receiving these hepatitis C medicines with Trangorexe, with or without other medicines that lower heart rate, should be warned of the symptoms of bradycardia and heart block and should be advised to seek urgent medical advice if they experience them.
Endocrine disorders
Trangorexe may induce hypothyroidism or hyperthyroidism, particularly in patients with a personal history of thyroid disorders. Clinical and biological [including ultrasensitive TSH (usTSH)] monitoring should be performed prior to therapy in all patients. Monitoring should be carried out during treatment, at six-monthly intervals, and for several months following its discontinuation. This is particularly important in the elderly. In patients whose history indicates an increased risk of thyroid dysfunction, regular assessment is recommended. Serum usTSH level should be measured when thyroid dysfunction is suspected.
Trangorexe contains iodine and thus may interfere with radio-iodine uptake. However, thyroid function tests (free-T3, free-T4, usTSH) remain interpretable. Trangorexe inhibits peripheral conversion of levothyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (increase in serum free-T4, free-T3 being slightly decreased or even normal) in clinically euthyroid patients. There is no reason in such cases to discontinue Trangorexe treatment if there is no clinical or further biological (usTSH) evidence of thyroid disease.
Hypothyroidism
Hypothyroidism should be suspected if the following clinical signs occur: weight gain, cold intolerance, reduced activity, excessive bradycardia. The diagnosis is supported by an increase in serum usTSH and an exaggerated TSH response to TRH. T3 and T4 levels may be low. Euthyroidism is usually obtained within 3 months following the discontinuation of treatment. In life-threatening situations, Trangorexe therapy can be continued, in combination with levothyroxine. The dose of levothyroxine is adjusted according to TSH levels.
Hyperthyroidism
Hyperthyroidism may occur during Trangorexe treatment, or, up to several months after discontinuation. Clinical features, such as weight loss, asthenia, restlessness, increase in heart rate, onset of arrhythmia, angina, congestive heart failure should alert the physician. The diagnosis is supported by a decrease in serum usTSH level, an elevated T3 and a reduced TSH response to thyrotropin releasing hormone. Elevation of reverse T3 (rT3) may also be found.
In the case of hyperthyroidism, therapy should be withdrawn. Clinical recovery usually occurs within a few months, although severe cases, sometimes resulting in fatalities, have been reported. Clinical recovery precedes the normalisation of thyroid function tests.
Courses of anti-thyroid drugs have been used for the treatment of severe thyroid hyperactivity; large doses may be required initially. These may not always be effective and concomitant high dose corticosteroid therapy (e.g. 1mg/kg prednisolone) may be required for several weeks.
Eye disorders
If blurred or decreased vision occurs, complete ophthalmologic examination including fundoscopy should be promptly performed. Appearance of optic neuropathy and/or optic neuritis requires Trangorexe withdrawal due to the potential progression to blindness. Unless blurred or decreased vision occurs, opthamological examination is recommended annually.
Hepato-biliary disorders :
Trangorexe may be associated with a variety of hepatic effects, including cirrhosis, hepatitis, jaundice and hepatic failure. Some fatalities have been reported, mainly following long-term therapy, although rarely they have occurred soon after starting treatment particularly after Trangorexe intravenous. It is advisable to monitor liver function particularly transaminases before treatment and six monthly thereafter. Trangorexe dose should be reduced or the treatment discontinued if the transaminases increase exceeds three times the normal range.
At the beginning of therapy, elevation of serum transaminases which can be in isolation (1.5 to 3 times normal) may occur. These may return to normal with dose reduction, or sometimes spontaneously.
Isolated cases of acute liver disorders with elevated serum transaminases and/or jaundice may occur; in such cases treatment should be discontinued.
There have been reports of chronic liver disease. Alteration of laboratory tests which may be minimal (transaminases elevated 1.5 to 5 times normal) or clinical signs (possible hepatomegaly) during treatment for longer than 6 months should suggest this diagnosis. Routine monitoring of liver function tests is therefore advised. Abnormal clinical and laboratory test results usually regress upon cessation of treatment, but fatal cases have been reported. Histological findings may resemble pseudo-alcoholic hepatitis, but they can be variable and include cirrhosis.
Although there have been no literature reports on the potentiation of hepatic adverse effects of alcohol, patients should be advised to moderate their alcohol intake while taking Trangorexe tablets.
Nervous system disorders :
Trangorexe may induce peripheral sensorimotor neuropathy and/or myopathy. Both these conditions may be severe, although recovery usually occurs within several months after Trangorexe withdrawal, but may sometimes be incomplete.
Respiratory, thoracic and mediastinal disorders :
Onset of dyspnoea or non-productive cough may be related to pulmonary toxicity (hypersensitivity pneumonitis, alveolar/interstitial pneumonitis or fibrosis, pleuritis, bronchiolitis obliterans organising pneumonitis. Presenting features can include dyspnoea (which may be severe and unexplained by the current cardiac status), non-productive cough and deterioration in general health (fatigue, weight loss and fever). The onset is usually slow but may be rapidly progressive. Whilst the majority of cases have been reported with long term therapy, a few have occurred soon after starting treatment.
Patients should be carefully evaluated clinically and consideration given to chest X-rays before starting therapy. During treatment, if pulmonary toxicity is suspected, this should be repeated and associated with lung function testing including, where possible, measurement of transfer factor. Initial radiological changes may be difficult to distinguish from pulmonary venous congestion. Pulmonary toxicity has usually been reversible following early withdrawal of Trangorexe therapy, with or without corticosteroid therapy. Clinical symptoms often resolve within a few weeks followed by slower radiological and lung function improvement. Some patients can deteriorate despite discontinuing Trangorexe tablets.
Skin and subcutaneous tissue disorders
Patients should be instructed to avoid exposure to sun and to use protective measures during therapy as patients taking Trangorexe tablets can become unduly sensitive to sunlight, which may persist after several months of discontinuation of Trangorexe tablets. In most cases symptoms are limited to tingling, burning and erythema of sun-exposed skin but severe phototoxic reactions with blistering may be seen.
Severe bullous reactions:
Life-threatening or even fatal cutaneous reactions Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN). If symptoms or signs of SJS, TEN (e.g. progressive skin rash often with blisters or mucosal lesions) are present Trangorexe treatment should be discontinued immediately.
Drug interactions
Concomitant use of Trangorexe is not recommended with the following drugs: beta-blockers, heart rate lowering calcium channel inhibitors (verapamil, diltiazem), stimulant laxative agents which may cause hypokalaemia.
Increased plasma levels of flecainide have been reported with co-administration of Trangorexe. The flecainide dose should be reduced accordingly and the patient closely monitored.
.
Excipient warnings
This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Amiodarone can cause serious adverse reactions affecting the eyes, heart, lung, liver, thyroid gland, skin and peripheral nervous system. Because these reactions may be delayed, patients on long-term treatment should be carefully supervised. As undesirable effects are usually dose-related, the minimum effective maintenance dose should be given.
Before surgery, the anaesthetist should be informed that the patient is taking amiodarone .
Cardiac disorders :
Too high a dosage may lead to severe bradycardia and to conduction disturbances with the appearance of an idioventricular rhythm, particularly in elderly patients or during digitalis therapy. In these circumstances, amiodarone treatment should be withdrawn. If necessary beta-adrenostimulants or glucagon may be given. Because of the long half-life of amiodarone, if bradycardia is severe and symptomatic the insertion of a pacemaker should be considered.
Amiodarone Tablets may markedly reduce the heart rate of elderly patients.
Oral amiodarone is not contra-indicated in patients with latent or manifest heart failure but caution should be exercised as, occasionally, existing heart failure may be worsened. In such cases, amiodarone may be used with other appropriate therapies.
The pharmacological action of amiodarone induces ECG changes: QT prolongation (related to prolonged repolarisation) with the possible development of U-waves and deformed T-waves; these changes do not reflect toxicity.
Treatment should be discontinued in case of onset of 2nd or 3rd degree A-V block, sino-atrial block, or bifascicular block.
Amiodarone has a low pro-arrhythmic effect. Onsets of new arrhythmias or worsening of treated arrhythmias, sometimes fatal, have been reported. It is important, but difficult, to differentiate a lack of efficacy of the drug from a proarrhythmic effect, whether or not this is associated with a worsening of the cardiac condition. Proarrhythmic effects generally occur in the context of drug interactions and / or electrolytic disorders.
Before starting amiodarone, it is recommended to perform an ECG and serum potassium measurement. Monitoring of ECG is recommended during treatment.
Amiodarone may increase the defibrillation threshold and/or pacing threshold in patients with an implantable cardioverter defibrillator or a pacemaker, which may adversely affect the efficacy of the device. Regular tests are recommended to ensure the proper function of the device after initiation of treatment or change in posology.
Endocrine disorders
Amiodarone may induce hypothyroidism or hyperthyroidism, particularly in patients with a personal history of thyroid disorders. Clinical and biological [including ultrasensitive TSH (usTSH)] monitoring should be performed prior to therapy in all patients. Monitoring should be carried out during treatment, at six-monthly intervals, and for several months following its discontinuation. This is particularly important in the elderly. In patients whose history indicates an increased risk of thyroid dysfunction, regular assessment is recommended. Serum usTSH level should be measured when thyroid dysfunction is suspected.
Amiodarone contains iodine and thus may interfere with radio-iodine uptake. However, thyroid function tests (free-T3, free-T4, usTSH) remain interpretable. Amiodarone inhibits peripheral conversion of levothyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (increase in serum free-T4, free-T3 being slightly decreased or even normal) in clinically euthyroid patients. There is no reason in such cases to discontinue amiodarone treatment if there is no clinical or further biological (usTSH) evidence of thyroid disease.
Hypothyroidism
Hypothyroidism should be suspected if the following clinical signs occur: weight gain, cold intolerance, reduced activity, excessive bradycardia. The diagnosis is supported by an increase in serum usTSH and an exaggerated TSH response to TRH. T3 and T4 levels may be low. Euthyroidism is usually obtained within 3 months following the discontinuation of treatment. In life-threatening situations, amiodarone therapy can be continued, in combination with levothyroxine. The dose of levothyroxine is adjusted according to TSH levels.
Hyperthyroidism
Hyperthyroidism may occur during amiodarone treatment, or, up to several months after discontinuation. Clinical features, such as weight loss, asthenia, restlessness, increase in heart rate, onset of arrhythmia, angina, congestive heart failure should alert the physician. The diagnosis is supported by a decrease in serum usTSH level, an elevated T3 and a reduced TSH response to thyrotropin releasing hormone. Elevation of reverse T3 (rT3) may also be found.
In the case of hyperthyroidism, therapy should be withdrawn. Clinical recovery usually occurs within a few months, although severe cases, sometimes resulting in fatalities, have been reported. Clinical recovery precedes the normalisation of thyroid function tests.
Courses of anti-thyroid drugs have been used for the treatment of severe thyroid hyperactivity; large doses may be required initially. These may not always be effective and concomitant high dose corticosteroid therapy (e.g. 1mg/kg prednisolone) may be required for several weeks.
Eye disorders
If blurred or decreased vision occurs, complete ophthalmologic examination including fundoscopy should be promptly performed. Appearance of optic neuropathy and/or optic neuritis requires amiodarone withdrawal due to the potential progression to blindness. Unless blurred or decreased vision occurs, opthamological examination is recommended annually.
Hepato-biliary disorders :
Amiodarone may be associated with a variety of hepatic effects, including cirrhosis, hepatitis, jaundice and hepatic failure. Some fatalities have been reported, mainly following long-term therapy, although rarely they have occurred soon after starting treatment particularly after intravenous amiodarone. It is advisable to monitor liver function particularly transaminases before treatment and six monthly thereafter.
At the beginning of therapy, elevation of serum transaminases which can be in isolation (1.5 to 3 times normal) may occur. These may return to normal with dose reduction, or sometimes spontaneously.
Isolated cases of acute liver disorders with elevated serum transaminases and/or jaundice may occur; in such cases treatment should be discontinued.
There have been reports of chronic liver disease. Alteration of laboratory tests which may be minimal (transaminases elevated 1.5 to 5 times normal) or clinical signs (possible hepatomegaly) during treatment for longer than 6 months should suggest this diagnosis. Routine monitoring of liver function tests is therefore advised. Abnormal clinical and laboratory test results usually regress upon cessation of treatment, but fatal cases have been reported. Histological findings may resemble pseudo-alcoholic hepatitis, but they can be variable and include cirrhosis.
Although there have been no literature reports on the potentiation of hepatic adverse effects of alcohol, patients should be advised to moderate their alcohol intake while taking amiodarone.
Nervous system disorders :
Amiodarone may induce peripheral sensorimotor neuropathy and/or myopathy. Both these conditions may be severe, although recovery usually occurs within several months after amiodarone withdrawal, but may sometimes be incomplete.
Respiratory, thoracic and mediastinal disorders :
Onset of dyspnoea or non-productive cough may be related to pulmonary toxicity (hypersensitivity pneumonitis, alveolar/interstitial pneumonitis or fibrosis, pleuritis, bronchiolitis obliterans organising pneumonitis. Presenting features can include dyspnoea (which may be severe and unexplained by the current cardiac status), non-productive cough and deterioration in general health (fatigue, weight loss and fever). The onset is usually slow but may be rapidly progressive. Whilst the majority of cases have been reported with long term therapy, a few have occurred soon after starting treatment.
Skin and subcutaneous tissue disorders
Patients should be instructed to avoid exposure to sun and to use protective measures during therapy as patients taking amiodarone can become unduly sensitive to sunlight, which may persist after several months of discontinuation of amiodarone. In most cases symptoms are limited to tingling, burning and erythema of sun-exposed skin but severe phototoxic reactions with blistering may be seen.
Drug interactions
Concomitant use of amiodarone is not recommended with the following drugs: beta-blockers, heart rate lowering calcium channel inhibitors (verapamil, diltiazem), stimulant laxative agents which may cause hypokalaemia.
Increased plasma levels of flecainide have been reported with co-administration of amiodarone. The flecainide dose should be reduced accordingly and the patient closely monitored.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Amiodarone can cause serious adverse reactions affecting the eyes, heart, lung, liver, thyroid gland, skin and peripheral nervous system. Because these reactions may be delayed, patients on long-term treatment should be carefully supervised. As undesirable effects are usually dose-related, the minimum effective maintenance dose should be given.
Before surgery, the anaesthetist should be informed that the patient is taking amiodarone .
Cardiac disorders :
Too high a dosage may lead to severe bradycardia and to conduction disturbances with the appearance of an idioventricular rhythm, particularly in elderly patients or during digitalis therapy. In these circumstances, Trangorex X treatment should be withdrawn. If necessary beta-adrenostimulants or glucagon may be given. Because of the long half-life of amiodarone, if bradycardia is severe and symptomatic the insertion of a pacemaker should be considered.
Oral Trangorex X is not contra-indicated in patients with latent or manifest heart failure but caution should be exercised as, occasionally, existing heart failure may be worsened. In such cases, Trangorex X may be used with other appropriate therapies.
The pharmacological action of amiodarone induces ECG changes: QT prolongation (related to prolonged repolarisation) with the possible development of U-waves and deformed T-waves; these changes do not reflect toxicity.
In the elderly, heart rate may decrease markedly.
Treatment should be discontinued in case of onset of 2nd or 3rd degree A-V block, sino-atrial block, or bifascicular block.
Amiodarone has a low pro-arrhythmic effect. Onsets of new arrhythmias or worsening of treated arrhythmias, sometimes fatal, have been reported. It is important, but difficult, to differentiate a lack of efficacy of the drug from a proarrhythmic effect, whether or not this is associated with a worsening of the cardiac condition. Proarrhythmic effects generally occur in the context of QT prolonging factors such as drug interactions and/or electrolytic disorders. Despite QT interval prolongation, amiodarone exhibits a low torsadogenic activity.
Before starting amiodarone, it is recommended to perform an ECG and serum potassium measurement. Monitoring of ECG is recommended during treatment.
Amiodarone may increase the defibrillation threshold and/or pacing threshold in patients with an implantable cardioverter defibrillator or a pacemaker, which may adversely affect the efficacy of the device. Regular tests are recommended to ensure the proper function of the device after initiation of treatment or change in posology.
Severe Bradycardia :
Cases of severe, potentially life-threatening bradycardia and heart block have been observed when amiodarone is used in combination with sofosbuvir in combination with another hepatitis C virus (HCV) direct acting antiviral (DAA), such as daclatasvir, simeprevir, or ledipasvir. Therefore, coadministration of these agents with amiodarone is not recommended.
If concomitant use with amiodarone cannot be avoided, it is recommended that patients are closely monitored when initiating sofosbuvir in combination with other DAAs. Patients who are identified as being at high risk of bradyarrhythmia should be continuously monitored for at least 48 hours in an appropriate clinical setting after initiation of the concomitant treatment with sofosbuvir.
Patients receiving these hepatitis C medicines with amiodarone, with or without other medicines that lower heart rate, should be warned of the symptoms of bradycardia and heart block and should be advised to seek urgent medical advice if they experience them.
Endocrine disorders :
Amiodarone may induce hypothyroidism or hyperthyroidism, particularly in patients with a personal history of thyroid disorders. Clinical and biological [including ultrasensitive TSH (usTSH)] monitoring should be performed prior to therapy in all patients. Monitoring should be carried out during treatment, at six-monthly intervals, and for several months following its discontinuation. This is particularly important in the elderly. In patients whose history indicates an increased risk of thyroid dysfunction, regular assessment is recommended. Serum usTSH level should be measured when thyroid dysfunction is suspected.
Amiodarone contains iodine and thus may interfere with radio-iodine uptake. However, thyroid function tests (free-T3, free-T4, usTSH) remain interpretable. Amiodarone inhibits peripheral conversion of levothyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (increase in serum free-T4, free-T3 being slightly decreased or even normal) in clinically euthyroid patients. There is no reason in such cases to discontinue amiodarone treatment if there is no clinical or further biological (usTSH) evidence of thyroid disease.
Hypothyroidism:
Hypothyroidism should be suspected if the following clinical signs occur: weight gain, cold intolerance, reduced activity, excessive bradycardia. The diagnosis is supported by an increase in serum usTSH and an exaggerated TSH response to TRH. T3 and T4 levels may be low. Euthyroidism is usually obtained within 3 months following the discontinuation of treatment. In life-threatening situations, amiodarone therapy can be continued, in combination with levothyroxine. The dose of levothyroxine is adjusted according to TSH levels.
Hyperthyroidism:
Hyperthyroidism may occur during amiodarone treatment, or, up to several months after discontinuation. Clinical features, such as weight loss, asthenia, restlessness, increase in heart rate, onset of arrhythmia, angina, congestive heart failure should alert the physician. The diagnosis is supported by a decrease in serum usTSH level, an elevated T3 and a reduced TSH response to thyrotropin releasing hormone. Elevation of reverse T3 (rT3) may also be found.
In the case of hyperthyroidism, therapy should be withdrawn. Clinical recovery usually occurs within a few months, although severe cases, sometimes resulting in fatalities, have been reported. Clinical recovery precedes the normalisation of thyroid function tests.
Courses of anti-thyroid drugs have been used for the treatment of severe thyroid hyperactivity; large doses may be required initially. These may not always be effective and concomitant high dose corticosteroid therapy (e.g. 1 mg/kg prednisolone) may be required for several weeks.
Eye disorders :
If blurred or decreased vision occurs, complete ophthalmologic examination including fundoscopy should be promptly performed. Appearance of optic neuropathy and/or optic neuritis requires amiodarone withdrawal due to the potential progression to blindness. Unless blurred or decreased vision occurs, opthamological examination is recommended annually.
Hepato-biliary disorders :
Amiodarone may be associated with a variety of hepatic effects, including cirrhosis, hepatitis, jaundice and hepatic failure. Some fatalities have been reported, mainly following long-term therapy, although rarely they have occurred soon after starting treatment particularly after Trangorex X intravenous. It is advisable to monitor liver function particularly transaminases before treatment and six monthly thereafter. Amiodarone dose should be reduced or the treatment discontinued if the transaminases increase exceeds three times the normal range.
At the beginning of therapy, elevation of serum transaminases which can be in isolation (1.5 to 3 times normal) may occur. These may return to normal with dose reduction, or sometimes spontaneously.
Isolated cases of acute liver disorders with elevated serum transaminases and/or jaundice may occur; in such cases treatment should be discontinued.
There have been reports of chronic liver disease. Alteration of laboratory tests which may be minimal (transaminases elevated 1.5 to 5 times normal) or clinical signs (possible hepatomegaly) during treatment for longer than 6 months should suggest this diagnosis. Routine monitoring of liver function tests is therefore advised. Abnormal clinical and laboratory test results usually regress upon cessation of treatment, but fatal cases have been reported. Histological findings may resemble pseudo-alcoholic hepatitis, but they can be variable and include cirrhosis.
Although there have been no literature reports on the potentiation of hepatic adverse effects of alcohol, patients should be advised to moderate their alcohol intake while taking Trangorex X.
Nervous system disorders :
Amiodarone may induce peripheral sensorimotor neuropathy and/or myopathy. Both these conditions may be severe, although recovery usually occurs within several months after amiodarone withdrawal, but may sometimes be incomplete.
Respiratory, thoracic and mediastinal disorders :
Onset of dyspnoea or non-productive cough may be related to pulmonary toxicity (hypersensitivity pneumonitis, alveolar/interstitial pneumonitis or fibrosis, pleuritis, bronchiolitis obliterans organising pneumonitis. Presenting features can include dyspnoea (which may be severe and unexplained by the current cardiac status), non-productive cough and deterioration in general health (fatigue, weight loss and fever). The onset is usually slow but may be rapidly progressive. Whilst the majority of cases have been reported with long term therapy, a few have occurred soon after starting treatment.
Patients should be carefully evaluated clinically and consideration given to chest X-rays before starting therapy. During treatment, if pulmonary toxicity is suspected, this should be repeated and associated with lung function testing including, where possible, measurement of transfer factor. Initial radiological changes may be difficult to distinguish from pulmonary venous congestion. Pulmonary toxicity has usually been reversible following early withdrawal of amiodarone therapy, with or without corticosteroid therapy. Clinical symptoms often resolve within a few weeks followed by slower radiological and lung function improvement. Some patients can deteriorate despite discontinuing Trangorex X.
Skin and subcutaneous tissue disorders :
Patients should be instructed to avoid exposure to sun and to use protective measures during therapy as patients taking Trangorex X can become unduly sensitive to sunlight, which may persist after several months of discontinuation of Trangorex X. In most cases symptoms are limited to tingling, burning and erythema of sun-exposed skin but severe phototoxic reactions with blistering may be seen.
Severe bullous reactions:
Life-threatening or even fatal cutaneous reactions Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN). If symptoms or signs of SJS, TEN (e.g. progressive skin rash often with blisters or mucosal lesions) are present amiodarone treatment should be discontinued immediately.
Drug interactions :
Concomitant use of amiodarone is not recommended with the following drugs: beta-blockers, heart rate lowering calcium channel inhibitors (verapamil, diltiazem), stimulant laxative agents which may cause hypokalaemia.
Increased plasma levels of flecainide have been reported with co-administration of amiodarone. The flecainide dose should be reduced accordingly and the patient closely monitored.
Amiodaron kaynaklı göz bozukluklarının klinik semptomları olan hastalarda araç veya makine kullanma yeteneği bozulabilir.
The following adverse reactions are classified by system organ class and ranked under heading of frequency using the following convention: Very common (>1/10), Common (>1/100 to <1/10); Uncommon (>1/1,000 to <1/100), Rare (>1/10,000 to <1/1,000), Very rare (<1/10,000), not known (cannot be estimated from the available data).
Blood and lymphatic system disorders:
- Very rare:
- haemolytic anemia
- aplastic anaemia
- thrombocytopenia.
In patients taking Trangorexe there have been incidental findings of bone marrow granulomas. The clinical significance of this is unknown.
Cardiac disorders:
- Common: bradycardia, generally moderate and dose-related.
- Uncommon:
- onset or worsening of arrhythmia, sometimes followed by cardiac arrest
- conduction disturbances (sinoatrial block, AV block of various degrees)
- Very rare: marked bradycardia or sinus arrest in patients with sinus node dysfunction and/or in elderly patients.
- Not known: Torsade de pointes
Endocrine disorders :
- Common:
- hypothyroidism
- hyperthyroidism, sometimes fatal
- Very rare
- syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Eye disorders:
- Very common: corneal microdeposits usually limited to the area under the pupil, which are usually only discernable by slit-lamp examinations. They may be associated with colored halos in dazzling light or blurred vision. Corneal micro-deposits consist of complex lipid deposits and are reversible following discontinuation of treatment. The deposits are considered essentially benign and do not require discontinuation of Trangorexe.
- Very rare: optic neuropathy/neuritis that may progress to blindness.
Gastrointestinal disorders:
- Very common: benign gastrointestinal disorders (nausea, vomiting, dysgeusia) usually occurring with loading dosage and resolving with dose reduction.
- Common: Constipation
- Uncommon: Dry mouth
- Unknown: pancreatitis/acute pancreatitis
General Disorders:
- Not known: Granuloma, including bone marrow granuloma
Hepato-biliary disorders:.
- Very common: isolated increase in serum transaminases, which is usually moderate (1.5 to 3 times normal range), occurring at the beginning of therapy. It may return to normal with dose reduction or even spontaneously.
- Common: acute liver disorders with high serum transaminases and/or jaundice, including hepatic failure, which are sometimes fatal
- Very rare: chronic liver disease (pseudo alcoholic hepatitis, cirrhosis), sometimes fatal.
Immune system disorders:
Not known:
- Angioneurotic oedema (Quincke's Oedema)
- Anaphylactic shock/anaphylactoid reaction including shock
Investigations:
Very rare:
- increase in blood creatinine.
Metabolic and nutrition disorders
Not known:
- decreased appetite
Musculoskeletal and connective tissue disorders:
Not known:
- lupus like syndrome
Nervous system disorders:
- Common:
- extrapyramidal tremor, for which regression usually occurs after reduction of dose or withdrawal
- nightmares
- sleep disorders.
- Uncommon: peripheral sensorimotor neuropathy and/or myopathy, usually reversible on withdrawal of the drug.
- Very rare:
- cerebellar ataxia, for which regression usually occurs after reduction of dose or withdrawal
- benign intracranial hypertension (pseudo- tumor cerebri)
- headache
- vertigo.
Not known:
- parkinsonism
- parosmia
Psychiatric disorders:
Not known:
- confusional state/delirium
Reproductive system and breast disorders:
- Very rare:
- epididymo-orchitis
- impotence.
Respiratory, thoracic and mediastinal disorders:
- Common: pulmonary toxicity [hypersensitivity pneumonitis, alveolar/interstitial pneumonitis or fibrosis, pleuritis, bronchiolitis obliterans organising pneumonia (BOOP)], sometimes fatal.
- Very rare:
- bronchospasm in patients with severe respiratory failure and especially in asthmatic patients
- surgery (possible interaction with a high oxygen concentration).
Pulmonary haemorrhage (there have been some reports of pulmonary haemorrhage, although exact frequencies are not known)
Skin and subcutaneous tissue disorders:
- Very common: photosensitivity.
- Common:
- eczema,
- slate grey or bluish pigmentations of light-exposed skin, particularly the face, in case of prolonged treatment with high daily dosages; such pigmentations slowly disappear following treatment discontinuation
- Very rare:
- erythema during the course of radiotherapy
- skin rashes, usually non- specific
- exfoliative dermatitis
- alopecia.
- Unknown/ Not known:
- urticarial,
- severe skin reactions sometimes fatal including toxic epidermal necrolysis (TEN)/ Stevens- Johnson syndrome (SJS),
-bullous dermatitis, Drug reaction with eosinophilia and systematic symptoms (DRESS).
Vascular disorders:
- Very rare: vasculitis.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme.
Website: www.mhra.gov.uk/yellowcard.
The following adverse reactions are classified by system organ class and ranked under heading of frequency using the following convention: very common (> 10%), common (> 1% and < 10%); uncommon (> 0.1% and < 1%); rare (> 0.01% and < 0.1%), very rare (< 0.01%).
Blood and lymphatic system disorders:
- Very rare:
- haemolytic anemia
- aplastic anaemia
- thrombocytopenia.
In patients taking amiodarone there have been incidental findings of bone marrow granulomas. The clinical significance of this is unknown
Cardiac disorders:
- Common: bradycardia, generally moderate and dose-related.
- Uncommon:
- onset or worsening of arrhythmia, sometimes followed by cardiac arrest
- conduction disturbances (sinoatrial block, AV block of various degrees)
- Very rare: marked bradycardia or sinus arrest in patients with sinus node dysfunction and/or in elderly patients.
Endocrine disorders :
- Common:
- hypothyroidism
- hyperthyroidism, sometimes fatal
- Very rare
- syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Eye disorders:
- Very common: corneal microdeposits usually limited to the area under the pupil, which are usually only discernable by slit-lamp examinations. They may be associated with colored halos in dazzling light or blurred vision. Corneal micro-deposits consist of complex lipid deposits and are reversible following discontinuation of treatment. The deposits are considered essentially benign and do not require discontinuation of amiodarone.
- Very rare: optic neuropathy/neuritis that may progress to blindness.
Gastrointestinal disorders:
- Very common: benign gastrointestinal disorders (nausea, vomiting, dysgeusia) usually occurring with loading dosage and resolving with dose reduction.
Hepato-biliary disorders:.
- Very common: isolated increase in serum transaminases, which is usually moderate (1.5 to 3 times normal range), occurring at the beginning of therapy. It may return to normal with dose reduction or even spontaneously.
- Common: acute liver disorders with high serum transaminases and/or jaundice, including hepatic failure, which are sometimes fatal
- Very rare: chronic liver disease (pseudo alcoholic hepatitis, cirrhosis), sometimes fatal.
Immune system disorders:
Angioedema (there have been some reports of angioedema, although exact frequencies are not known)
Investigations:
- Very rare: increase in blood creatinine.
Nervous system disorders:
- Common:
- extrapyramidal tremor, for which regression usually occurs after reduction of dose or withdrawal
- nightmares
- sleep disorders.
- Uncommon: peripheral sensorimotor neuropathy and/or myopathy, usually reversible on withdrawal of the drug.
- Very rare:
- cerebellar ataxia, for which regression usually occurs after reduction of dose or withdrawal
- benign intracranial hypertension (pseudo- tumor cerebri)
- headache
- vertigo.
Reproductive system and breast disorders:
- Very rare:
- epididymo-orchitis
- impotence.
Respiratory, thoracic and mediastinal disorders:
- Common: pulmonary toxicity [hypersensitivity pneumonitis, alveolar/interstitial pneumonitis or fibrosis, pleuritis, bronchiolitis obliterans organising pneumonia (BOOP)], sometimes fatal.
- Very rare:
- bronchospasm in patients with severe respiratory failure and especially in asthmatic patients
- surgery (possible interaction with a high oxygen concentration).
Pulmonary haemorrhage (there have been some reports of pulmonary haemorrhage, although exact frequencies are not known)
Skin and subcutaneous tissue disorders:
- Very common: photosensitivity.
- Common: slate grey or bluish pigmentations of light-exposed skin, particularly the face, in case of prolonged treatment with high daily dosages; such pigmentations slowly disappear following treatment discontinuation.
- Very rare:
- erythema during the course of radiotherapy
- skin rashes, usually non- specific
- exfoliative dermatitis
- alopecia.
Vascular disorders:
- Very rare: vasculitis.
The following adverse reactions are classified by system organ class and ranked under heading of frequency using the following convention: very common (> 10%), common (> 1% and < 10%); uncommon (> 0.1% and < 1%); rare (> 0.01% and < 0.1%), very rare (< 0.01%), not known (cannot be estimated from the available data).
Blood and lymphatic system disorders:
Very rare:
- haemolytic anaemia
- aplastic anaemia
- thrombocytopenia.
In patients taking amiodarone there have been incidental findings of bone marrow granulomas. The clinical significance of this is unknown.
Cardiac disorders:
Common:
- bradycardia, generally moderate and dose-related.
Uncommon:
- onset or worsening of arrhythmia, sometimes followed by cardiac arrest
- conduction disturbances (sinoatrial block, AV block of various degrees)
Very rare:
- marked bradycardia or sinus arrest in patients with sinus node dysfunction and/or in elderly patients.
Not known:
- Torsade de pointes
Endocrine disorders :
Common:
- hypothyroidism
- hyperthyroidism, sometimes fatal
Very rare:
- syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Eye disorders:
Very common:
- corneal microdeposits usually limited to the area under the pupil, which are usually only discernable by slit-lamp examinations. They may be associated with colored halos in dazzling light or blurred vision. Corneal micro-deposits consist of complex lipid deposits and are reversible following discontinuation of treatment. The deposits are considered essentially benign and do not require discontinuation of amiodarone.
Very rare:
- optic neuropathy/neuritis that may progress to blindness.
Gastrointestinal disorders:
Very common:
- benign gastrointestinal disorders (nausea, vomiting, dysgeusia) usually occurring with loading dosage and resolving with dose reduction.
Common:
- constipation
Uncommon:
- dry mouth
Not known:
- pancreatitis/acute pancreatitis
General Disorders:
Not known:
- Granuloma, including bone marrow granuloma
Hepato-biliary disorders: :
Very common:
- isolated increase in serum transaminases, which is usually moderate (1.5 to 3 times normal range), occurring at the beginning of therapy. It may return to normal with dose reduction or even spontaneously.
Common:
- acute liver disorders with high serum transaminases and/or jaundice, including hepatic failure, which are sometimes fatal
Very rare:
- chronic liver disease (pseudo alcoholic hepatitis, cirrhosis), sometimes fatal.
Immune system disorders:
Not known:
- Angioneurotic oedema (Quincke's Oedema)
- Anaphylactic shock/anaphylactoid reaction including shock
Investigations:
Very rare:
- increase in blood creatinine.
Metabolism and nutrition disorders:
Not known:
- decreased appetite
Nervous system disorders:
Common:
- extrapyramidal tremor, for which regression usually occurs after reduction of dose or withdrawal
- nightmares
- sleep disorders.
Uncommon:
- peripheral sensorimotor neuropathy and/or myopathy, usually reversible on withdrawal of the drug.
Very rare:
- cerebellar ataxia, for which regression usually occurs after reduction of dose or withdrawal
- benign intracranial hypertension (pseudo- tumor cerebri)
- headache
- vertigo.
Not known:
- parkinsonism
- parosmia
Psychiatric disorders:
Not known:
- confusional state/delirium
Reproductive system and breast disorders:
Very rare:
- epididymo-orchitis
- impotence.
Respiratory, thoracic and mediastinal disorders:
Common:
- pulmonary toxicity [hypersensitivity pneumonitis, alveolar/interstitial pneumonitis or fibrosis, pleuritis, bronchiolitis obliterans organising pneumonia (BOOP)], sometimes fatal.
Very rare:
- bronchospasm in patients with severe respiratory failure and especially in asthmatic patients
- surgery (possible interaction with a high oxygen concentration).
Pulmonary haemorrhage (there have been some reports of pulmonary haemorrhage, although exact frequencies are not known)
Skin and subcutaneous tissue disorders:
Very common:
- photosensitivity.
Common:
- slate grey or bluish pigmentations of light-exposed skin, particularly the face, in case of prolonged treatment with high daily dosages; such pigmentations slowly disappear following treatment discontinuation.
- eczema
Very rare:
- erythema during the course of radiotherapy
- skin rashes, usually non- specific
- exfoliative dermatitis
- alopecia
Not known:
- urticaria
- severe skin reactions sometimes fatal including toxic epidermal necrolysis/Stevens-Johnson syndrome
- bullous dermatitis and drug reaction with eosinophilia and systematic symptoms
Vascular disorders:
Very rare:
- vasculitis.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Trangorexe ile akut doz aşımı hakkında çok az bilgi mevcuttur. Birkaç sinüs bradikardi, kalp bloğu, ventriküler taşikardi atakları, torsades de pointes, dolaşım yetmezliği ve hepatik yaralanma bildirilmiştir.
Doz aşımı tedavisi semptomatik olması durumunda, genel destekleyici önlemlere ek olarak emilimi azaltmak için mide lavajı kullanılabilir. Hasta izlenmeli ve bradikardi meydana gelirse beta-adrenostimülanlar veya glukagon verilebilir. Ventriküler taşikardi ataklarının kendiliğinden çözülmesi de meydana gelebilir. Trangorexe'nin farmakokinetiği nedeniyle, hastanın, özellikle kardiyak durumun yeterli ve uzun süreli gözetimi önerilir. Ne Trangorexe ne de metabolitleri diyaliz edilemez.
Oral amiodaron ile akut doz aşımı hakkında çok az bilgi mevcuttur. Birkaç sinüs bradikardi, kalp bloğu, ventriküler taşikardi atakları, torsades de pointes, dolaşım yetmezliği ve hepatik yaralanma bildirilmiştir.
Doz aşımı tedavisi semptomatik olması durumunda, genel destekleyici önlemlere ek olarak emilimi azaltmak için mide lavajı kullanılabilir. Hasta izlenmeli ve bradikardi meydana gelirse beta-adrenostimülanlar veya glukagon verilebilir. Ventriküler taşikardi ataklarının kendiliğinden çözülmesi de meydana gelebilir. Amiodaronun farmakokinetiği nedeniyle, hastanın, özellikle kardiyak durumun yeterli ve uzun süreli gözetimi önerilir. Ne amiodaron ne de metabolitleri diyaliz edilemez.
Oral amiodaron ile akut doz aşımı hakkında çok az bilgi mevcuttur. Birkaç sinüs bradikardi, kalp bloğu, ventriküler taşikardi atakları, torsades de pointes, dolaşım yetmezliği ve hepatik yaralanma bildirilmiştir.
Doz aşımı tedavisi semptomatik olması durumunda, genel destekleyici önlemlere ek olarak emilimi azaltmak için mide lavajı kullanılabilir. Hasta izlenmeli ve bradikardi meydana gelirse beta-adrenostimülanlar veya glukagon verilebilir. Ventriküler taşikardi ataklarının kendiliğinden çözülmesi de meydana gelebilir. Amiodaronun farmakokinetiği nedeniyle, hastanın, özellikle kardiyak durumun yeterli ve uzun süreli gözetimi önerilir. Ne amiodaron ne de metabolitleri diyaliz edilemez.
Farmakoterapötik grup: Trangorexe hidroklorür bir antiaritmiktir.
ATC Kodu: CO1B DOl
Pediyatrik popülasyon
Kontrollü pediatrik çalışma yapılmamıştır.
Yayınlanmış çalışmalarda, çeşitli aritmileri olan 1118 pediatrik hastada Trangorexe'nin güvenliği değerlendirilmiştir. Pediatrik klinik çalışmalarda aşağıdaki dozlar kullanılmıştır.
Oral
- Yükleme dozu: 7 ila 10 gün (veya 500 mg / m) için 10 ila 20 mg / kg / gün2metrekare başına ifade edilirse / gün)
- Bakım dozu: minimum etkili dozaj kullanılmalıdır; bireysel cevaba göre, 5 ila 10 mg / kg / gün (veya 250 mg / m) arasında değişebilir2metrekare başına ifade edilirse / gün)
İntravenöz
- Yükleme dozu: 20 dakika ila 2 saat boyunca 5 mg / kg vücut ağırlığı
- Bakım dozu: Birkaç saatten birkaç güne kadar 10 ila 15 mg / kg / gün
Gerekirse, oral tedavi olağan yükleme dozunda eşzamanlı olarak başlatılabilir.
Farmakoterapötik grup: Trangorex bir antiaritmiktir.
ATC Kodu: C01B D01
Pediyatrik popülasyon
Kontrollü pediatrik çalışma yapılmamıştır.
Yayınlanmış çalışmalarda, çeşitli aritmileri olan 1118 pediatrik hastada amiodaronun güvenliği değerlendirilmiştir. Pediatrik klinik çalışmalarda aşağıdaki dozlar kullanılmıştır.
Oral
- Yükleme dozu: 7 ila 10 gün (veya 500 mg / m) için 10 ila 20 mg / kg / gün2metrekare başına ifade edilirse / gün)
- Bakım dozu: minimum etkili dozaj kullanılmalıdır; bireysel cevaba göre, 5 ila 10 mg / kg / gün (veya 250 mg / m) arasında değişebilir2metrekare başına ifade edilirse / gün).
İntravenöz
- Yükleme dozu: 20 dakika ila 2 saat boyunca 5 mg / kg vücut ağırlığı,
- Bakım dozu: Birkaç saatten birkaç güne kadar 10 ila 15 mg / kg / gün
Gerekirse oral tedavi, normal yükleme dozunda eşzamanlı olarak başlatılabilir.
Amiodaron hidroklorür bir antiaritmiktir.
Kontrollü pediatrik çalışma yapılmamıştır.
Yayınlanmış çalışmalarda, çeşitli aritmileri olan 1118 pediatrik hastada amiodaronun güvenliği değerlendirilmiştir. Pediatrik klinik çalışmalarda aşağıdaki dozlar kullanılmıştır.
Oral
- Yükleme dozu: 7 ila 10 gün boyunca 10 ila 20 mg / kg / gün (veya metrekare başına ifade edilirse 500 mg / m² / gün).
- Bakım dozu: minimum etkili dozaj kullanılmalıdır; bireysel cevaba göre, 5 ila 10 mg / kg / gün (veya metrekare başına ifade edilirse 250 mg / m² / gün) arasında değişebilir.
İntravenöz
- Yükleme dozu: 20 dakika ila 2 saat boyunca 5 mg / kg vücut ağırlığı
- Bakım dozu: Birkaç saatten birkaç güne kadar 10 ila 15 mg / kg / gün
Gerekirse, oral tedavi olağan yükleme dozunda eşzamanlı olarak başlatılabilir.
Trangorexe güçlü bir şekilde proteine bağlıdır ve plazma yarılanma ömrü genellikle 50 gündür. Bununla birlikte, hastalar arası önemli farklılıklar olabilir; bireysel hastalarda 20 günden az bir yarılanma ömrü ve 100 günden fazla bir yarılanma ömrü bildirilmiştir. Mümkün olduğunca hızlı etkili doku seviyelerine ulaşmak için başlangıçta yüksek dozlarda Trangorexe, örneğin 600 mg / gün verilmelidir. İlacın uzun yarılanma ömrü nedeniyle, genellikle sadece 200 mg / gün veya daha az bir idame dozu gereklidir. Doz ayarlamaları arasında yeni bir dağılım dengesinin sağlanması için yeterli zaman tanınmalıdır.
Uzun yarılanma ömrü, nadiren dozların ihmal edilmesi Trangorexe tarafından sağlanan korumayı önemli ölçüde etkilemediğinden, ölümcül aritmileri olan hastalar için değerli bir korumadır.
Kontrollü pediatrik çalışma yapılmamıştır. Pediyatrik hastalarda mevcut sınırlı yayınlanmış verilerde yetişkinlere göre herhangi bir fark kaydedilmemiştir.
Trangorexe esas olarak CYP3A4 ve ayrıca CYP2C8 tarafından metabolize edilir. Trangorexe ve metaboliti desetilTrangorexe bir potansiyel sergiler in vitro CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 ve 2C8'i inhibe etmek. Trangorexe ve desetilTrangorexe ayrıca Pgp ve organik katyon taşıyıcısı (OCT2) gibi bazı taşıyıcıları inhibe etme potansiyeline sahiptir (Bir çalışma kreatin konsantrasyonunda% 1.1'lik bir artış (OCT 2 substratı) göstermektedir. İn vivo veriler CYP3A4, CYP2C9, CYP2D6 ve Pgp substratları üzerindeki Trangorexe etkileşimlerini açıklar.
Amiodaron güçlü bir şekilde proteine bağlıdır ve plazma yarılanma ömrü genellikle 50 gündür. Bununla birlikte, hastalar arası önemli farklılıklar olabilir; bireysel hastalarda 20 günden az bir yarılanma ömrü ve 100 günden fazla bir yarılanma ömrü bildirilmiştir. Etkili doku seviyelerine mümkün olduğunca hızlı ulaşmak için başlangıçta yüksek dozlarda amiodaron, örneğin 600 mg / gün verilmelidir. İlacın uzun yarı ömrü nedeniyle, genellikle sadece 200 mg / gün veya daha az bir idame dozu gereklidir. Doz ayarlamaları arasında yeni bir dağılım dengesinin sağlanması için yeterli zaman tanınmalıdır.
Uzun yarı ömür, nadiren dozların ihmal edilmesi amiodaronun sağladığı korumayı önemli ölçüde etkilemediğinden, potansiyel olarak ölümcül aritmileri olan hastalar için değerli bir korumadır.
Pediyatrik popülasyon
Kontrollü pediatrik çalışma yapılmamıştır. Pediyatrik hastalarda mevcut sınırlı yayınlanmış verilerde yetişkinlere göre herhangi bir fark kaydedilmemiştir.
Amiodaron güçlü bir şekilde proteine bağlıdır ve plazma yarılanma ömrü genellikle 50 gündür. Bununla birlikte, hastalar arası önemli farklılıklar olabilir; bireysel hastalarda 20 günden az bir yarılanma ömrü ve 100 günden fazla bir yarılanma ömrü bildirilmiştir. Etkili doku seviyelerine mümkün olduğunca hızlı ulaşmak için başlangıçta yüksek dozlarda Trangorex X, örneğin 600 mg / gün verilmelidir. İlacın uzun yarı ömrü nedeniyle, genellikle sadece 200 mg / gün veya daha az bir idame dozu gereklidir. Doz ayarlamaları arasında yeni bir dağılım dengesinin sağlanması için yeterli zaman tanınmalıdır.
Uzun yarılanma ömrü, nadiren dozların ihmal edilmesi Trangorex X tarafından sağlanan korumayı önemli ölçüde etkilemediğinden, potansiyel olarak ölümcül aritmileri olan hastalar için değerli bir korumadır
Kontrollü pediatrik çalışma yapılmamıştır. Pediyatrik hastalarda mevcut sınırlı yayınlanmış verilerde yetişkinlere göre herhangi bir fark kaydedilmemiştir.
Amiodaron esas olarak CYP3A4 ve ayrıca CYP2C8 tarafından metabolize edilir. Amiodaron ve metaboliti desetilamiodaron bir potansiyel sergiler in vitro CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 ve 2C8'i inhibe etmek. Amiodaron ve desetilamiodaron ayrıca P-gp ve organik katyon taşıyıcısı (OCT2) gibi bazı taşıyıcıları inhibe etme potansiyeline sahiptir (Bir çalışma kreatin konsantrasyonunda% 1.1'lik bir artış (OCT 2 substratı) göstermektedir. İn vivo veriler CYP3A4, CYP2C9, CYP2D6 ve P-gp substratları üzerindeki amiodaron etkileşimlerini açıklar.
Sıçanlarda yapılan 2 yıllık karsinojenisite çalışmasında Trangorexe, klinik olarak ilgili maruziyetlerde her iki cinsiyette tiroid foliküler tümörlerinde (adenomlar ve / veya karsinomlar) bir artışa neden oldu. Mutajenite bulguları negatif olduğundan, bu tip tümör indüksiyonu için genotoksik bir mekanizma yerine epigenik bir mekanizma önerilmektedir. Farede karsinomlar gözlenmedi, ancak doza bağlı tiroid foliküler hiperplazi görüldü. Sıçanlarda ve farelerde tiroid üzerindeki bu etkiler büyük olasılıkla Trangorexe'nin tiroid bezi hormonlarının sentezi ve / veya salınımı üzerindeki etkilerinden kaynaklanmaktadır. Bu bulguların insanla ilgisi düşüktür.
Sıçanlarda yapılan 2 yıllık karsinojenisite çalışmasında amiodaron, klinik olarak ilgili maruziyetlerde her iki cinsiyette tiroid foliküler tümörlerinde (adenomlar ve / veya karsinomlar) bir artışa neden oldu. Mutajenite bulguları negatif olduğundan, bu tip tümör indüksiyonu için genotoksik bir mekanizma yerine epigenik bir mekanizma önerilmektedir. Farede karsinomlar gözlenmedi, ancak doza bağlı tiroid foliküler hiperplazi görüldü. Sıçanlarda ve farelerde tiroid üzerindeki bu etkiler büyük olasılıkla amiodaronun tiroid bezi hormonlarının sentezi ve / veya salınımı üzerindeki etkilerinden kaynaklanmaktadır. Bu bulguların insanla ilgisi düşüktür.
Sıçanlarda yapılan 2 yıllık karsinojenisite çalışmasında amiodaron, klinik olarak ilgili maruziyetlerde her iki cinsiyette tiroid foliküler tümörlerinde (adenomlar ve / veya karsinomlar) bir artışa neden oldu. Mutajenite bulguları negatif olduğundan, bu tip tümör indüksiyonu için genotoksik bir mekanizma yerine epigenik bir mekanizma önerilmektedir. Farede karsinomlar gözlenmedi, ancak doza bağlı tiroid foliküler hiperplazi görüldü. Sıçanlarda ve farelerde tiroid üzerindeki bu etkiler büyük olasılıkla amiodaronun tiroid bezi hormonlarının sentezi ve / veya salınımı üzerindeki etkilerinden kaynaklanmaktadır. Bu bulguların insanla ilgisi düşüktür.
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