Componentes:
Método de ação:
Opção de tratamento:
Medicamente revisado por Fedorchenko Olga Valeryevna, Farmácia Última atualização em 16.03.2022
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20 principais medicamentos com os mesmos componentes:
2) Para o manejo e profilaxia da angina de peito (incluindo angina variante).
3) O tratamento e profilaxia da taquicardia supraventricular paroxística e a redução da taxa ventricular na fibrilação / vibração atrial. U-Sodin não deve ser utilizado para fibrilação / vibração atrial em pacientes com síndrome de Wolff-Parkinson-White.
Os comprimidos de CALAN são indicados para o tratamento do seguinte:
Angina
- Angina em repouso, incluindo:
- Angina vasospástica (variante de Prinzmetal)
- Angina instável (crescendo, pré-infarto)
- Angina estável crônica (angina associada ao esforço clássico)
Arritmias
- Em associação com o digital para o controle da taxa ventricular em repouso e durante o estresse em pacientes com vibração atrial crônica e / ou fibrilação atrial (ver AVISO: Trato de desvio acessório)
- Profilaxia da taquicardia supraventricular paroxística repetitiva
Hipertensão essencial
CALAN está indicado no tratamento da hipertensão, para baixar a pressão arterial. A redução da pressão arterial reduz o risco de eventos cardiovasculares fatais e não fatais, principalmente derrames e infartos do miocárdio. Esses benefícios foram observados em ensaios controlados de medicamentos anti-hipertensivos de uma ampla variedade de classes farmacológicas, incluindo este medicamento.
O controle da pressão alta deve fazer parte do gerenciamento abrangente dos riscos cardiovasculares, incluindo, conforme apropriado, controle de lipídios, controle do diabetes, terapia antitrombótica, cessação do tabagismo, exercício e ingestão limitada de sódio. Muitos pacientes precisarão de mais de um medicamento para atingir as metas de pressão arterial. Para aconselhamento específico sobre objetivos e gerenciamento, consulte diretrizes publicadas, como as do Comitê Nacional Conjunto de Prevenção, Detecção, Avaliação e Tratamento de Pressão Sanguínea (JNC) do Programa Nacional de Educação em Alta Pressão Sanguínea.
Inúmeros medicamentos anti-hipertensivos, de uma variedade de classes farmacológicas e com diferentes mecanismos de ação, foram mostrados em ensaios clínicos randomizados para reduzir a morbimortalidade cardiovascular, e pode-se concluir que é uma redução da pressão arterial, e não alguma outra propriedade farmacológica dos medicamentos, isso é amplamente responsável por esses benefícios. O maior e mais consistente benefício de resultado cardiovascular foi uma redução no risco de acidente vascular cerebral, mas reduções no infarto do miocárdio e mortalidade cardiovascular também foram observadas regularmente.
A pressão sistólica ou diastólica elevada causa risco cardiovascular aumentado, e o aumento absoluto do risco por mmHg é maior em pressões sanguíneas mais altas, de modo que mesmo reduções modestas da hipertensão grave podem proporcionar benefícios substanciais. A redução relativa do risco de redução da pressão arterial é semelhante em populações com risco absoluto variável, portanto, o benefício absoluto é maior em pacientes com maior risco, independentemente de sua hipertensão (por exemplo, pacientes com diabetes ou hiperlipidemia) e espera-se que esses pacientes se beneficiem de um tratamento mais agressivo para uma meta de pressão arterial mais baixa.
Alguns medicamentos anti-hipertensivos têm efeitos menores na pressão arterial (como monoterapia) em pacientes negros, e muitos medicamentos anti-hipertensivos têm indicações e efeitos adicionais aprovados (por exemplo,., em angina, insuficiência cardíaca ou doença renal diabética). Essas considerações podem orientar a seleção da terapia.
U-Sodin é indicado para o tratamento da hipertensão, para baixar a pressão arterial. A redução da pressão arterial reduz o risco de eventos cardiovasculares fatais e não fatais, principalmente derrames e infartos do miocárdio. Esses benefícios foram observados em ensaios controlados de medicamentos anti-hipertensivos de uma ampla variedade de classes farmacológicas, incluindo este medicamento.
O controle da pressão alta deve fazer parte do gerenciamento abrangente dos riscos cardiovasculares, incluindo, conforme apropriado, controle de lipídios, controle do diabetes, terapia antitrombótica, cessação do tabagismo, exercício e ingestão limitada de sódio. Muitos pacientes precisarão de mais de um medicamento para atingir as metas de pressão arterial. Para aconselhamento específico sobre objetivos e gestão, consulte as diretrizes publicadas, como as do Comitê Nacional Conjunto de Prevenção, Detecção, Avaliação e Tratamento de Pressão Sanguínea (JNC) do Programa Nacional de Educação para Pressão Sanguínea.
Inúmeros medicamentos anti-hipertensivos, de uma variedade de classes farmacológicas e com diferentes mecanismos de ação, foram mostrados em ensaios clínicos randomizados para reduzir a morbimortalidade cardiovascular, e pode-se concluir que é uma redução da pressão arterial, e não alguma outra propriedade farmacológica dos medicamentos, isso é amplamente responsável por esses benefícios. O maior e mais consistente benefício de resultado cardiovascular foi uma redução no risco de acidente vascular cerebral, mas reduções no infarto do miocárdio e mortalidade cardiovascular também foram observadas regularmente.
A pressão sistólica ou diastólica elevada causa risco cardiovascular aumentado, e o aumento absoluto do risco por mmHg é maior em pressões sanguíneas mais altas, de modo que mesmo reduções modestas da hipertensão grave podem proporcionar benefícios substanciais. A redução relativa do risco de redução da pressão arterial é semelhante em populações com risco absoluto variável, portanto, o benefício absoluto é maior em pacientes com maior risco, independentemente de sua hipertensão (por exemplo, pacientes com diabetes ou hiperlipidemia) e espera-se que esses pacientes se beneficiem de um tratamento mais agressivo para uma meta de pressão arterial mais baixa.
Alguns medicamentos anti-hipertensivos têm efeitos menores na pressão arterial (como monoterapia) em pacientes negros, e muitos medicamentos anti-hipertensivos têm indicações e efeitos adicionais aprovados (por exemplo,., em angina, insuficiência cardíaca ou doença renal diabética). Essas considerações podem orientar a seleção da terapia.
Os comprimidos de U-Sodin são indicados para o tratamento do seguinte:
Angina
- Angina em repouso, incluindo:
- Angina vasospástica (variante de Prinzmetal)
- Angina instável (crescendo, pré-infarto)
- Angina estável crônica (angina associada ao esforço clássico)
Arritmias
- Em associação com o digital para o controle da taxa ventricular em repouso e durante o estresse em pacientes com vibração atrial crônica e / ou fibrilação atrial (ver AVISO: Trato de desvio acessório)
- Profilaxia da taquicardia supraventricular paroxística repetitiva
Hipertensão essencial
U-Sodin é indicado para o tratamento da hipertensão, para baixar a pressão arterial. A redução da pressão arterial reduz o risco de eventos cardiovasculares fatais e não fatais, principalmente derrames e infartos do miocárdio. Esses benefícios foram observados em ensaios controlados de medicamentos anti-hipertensivos de uma ampla variedade de classes farmacológicas, incluindo este medicamento.
O controle da pressão alta deve fazer parte do gerenciamento abrangente dos riscos cardiovasculares, incluindo, conforme apropriado, controle de lipídios, controle do diabetes, terapia antitrombótica, cessação do tabagismo, exercício e ingestão limitada de sódio. Muitos pacientes precisarão de mais de um medicamento para atingir as metas de pressão arterial. Para aconselhamento específico sobre objetivos e gerenciamento, consulte diretrizes publicadas, como as do Comitê Nacional Conjunto de Prevenção, Detecção, Avaliação e Tratamento de Pressão Sanguínea (JNC) do Programa Nacional de Educação em Alta Pressão Sanguínea.
Inúmeros medicamentos anti-hipertensivos, de uma variedade de classes farmacológicas e com diferentes mecanismos de ação, foram mostrados em ensaios clínicos randomizados para reduzir a morbimortalidade cardiovascular, e pode-se concluir que é uma redução da pressão arterial, e não alguma outra propriedade farmacológica dos medicamentos, isso é amplamente responsável por esses benefícios. O maior e mais consistente benefício de resultado cardiovascular foi uma redução no risco de acidente vascular cerebral, mas reduções no infarto do miocárdio e mortalidade cardiovascular também foram observadas regularmente.
A pressão sistólica ou diastólica elevada causa risco cardiovascular aumentado, e o aumento absoluto do risco por mmHg é maior em pressões sanguíneas mais altas, de modo que mesmo reduções modestas da hipertensão grave podem proporcionar benefícios substanciais. A redução relativa do risco de redução da pressão arterial é semelhante em populações com risco absoluto variável, portanto, o benefício absoluto é maior em pacientes com maior risco, independentemente de sua hipertensão (por exemplo, pacientes com diabetes ou hiperlipidemia) e espera-se que esses pacientes se beneficiem de um tratamento mais agressivo para uma meta de pressão arterial mais baixa.
Alguns medicamentos anti-hipertensivos têm efeitos menores na pressão arterial (como monoterapia) em pacientes negros, e muitos medicamentos anti-hipertensivos têm indicações e efeitos adicionais aprovados (por exemplo,., em angina, insuficiência cardíaca ou doença renal diabética). Essas considerações podem orientar a seleção da terapia.
ISOPTIN SR (verapamil HCl) é indicado para o tratamento da hipertensão essencial.
Posologia
Adultos:
Angina : Recomenda-se 120mg três vezes ao dia. 80mg três vezes ao dia pode ser completamente satisfatório em alguns pacientes com angina de esforço. É improvável que menos de 120 mg três vezes ao dia seja eficaz na angina variante.
Taquicardias supraventriculares : 40-120mg três vezes ao dia, dependendo da gravidade da condição.
População pediátrica :
Foi observado um aumento paradoxal na taxa de arritmias em crianças. Portanto, o U-Sodin deve ser usado apenas sob supervisão de um especialista.
Até 2 anos: 20mg 2-3 vezes ao dia.
2 anos ou mais: 40-120mg 2-3 vezes ao dia, de acordo com a idade e a eficácia.
Idosos: A dose para adultos é recomendada, a menos que a função hepática ou renal esteja comprometida.
Método de administração
Para administração oral.
A dose de verapamil deve ser individualizada por titulação. A utilidade e segurança de dosagens superiores a 480 mg / dia não foram estabelecidas; portanto, esta dose diária não deve ser excedida. Como a meia-vida do verapamil aumenta durante a administração crônica, a resposta máxima pode ser adiada.
Angina
Os ensaios clínicos mostram que a dose habitual é de 80 mg a 120 mg três vezes ao dia. No entanto, 40 mg três vezes ao dia podem ser justificados em pacientes que podem ter uma resposta aumentada ao verapamil (por exemplo, diminuição da função hepática, idosos, etc.). A titulação para cima deve ser baseada na eficácia e segurança terapêuticas avaliadas aproximadamente oito horas após a administração. A dosagem pode ser aumentada diariamente (por exemplo, pacientes com angina instável) ou intervalos semanais até obter uma resposta clínica ideal.
Arritmias
A dosagem em pacientes digitalizados com fibrilação atrial crônica (ver PRECAUÇÕES) varia de 240 a 320 mg / dia em dividido (t.i.d. ou q.i.d.) doses. A dosagem para profilaxia do PSVT (pacientes não digitalizados) varia de 240 a 480 mg / dia em dividido (t.i.d. ou q.i.d.) doses. Em geral, os efeitos máximos para qualquer dose serão aparentes durante as primeiras 48 horas de terapia.
Hipertensão essencial
A dose deve ser individualizada por titulação. A dose inicial usual de monoterapia em ensaios clínicos foi de 80 mg três vezes ao dia (240 mg / dia). Dosagens diárias de 360 e 480 mg foram usadas, mas não há evidências de que doses além de 360 mg tenham efeito adicional. Deve-se considerar o início da titulação a 40 mg três vezes ao dia em pacientes que possam responder a doses mais baixas, como idosos ou pessoas de baixa estatura. Os efeitos anti-hipertensivos do CALAN são evidentes na primeira semana de terapia. A titulação para cima deve ser baseada na eficácia terapêutica, avaliada no final do intervalo de dosagem.
Hipertensão essencial
A dose de U-Sodin deve ser individualizada por titulação e o medicamento deve ser administrado com alimentos. Inicie a terapia com 180 mg de verapamil HCl de liberação sustentada, U-Sodin, administrado pela manhã. Doses iniciais mais baixas de 120 mg por dia podem ser justificadas em pacientes que podem ter uma resposta aumentada ao verapamil (por exemplo, idosos ou pessoas pequenas). A titulação para cima deve ser baseada na eficácia e segurança terapêuticas avaliadas semanalmente e aproximadamente 24 horas após a dose anterior. Os efeitos anti-hipertensivos do U-Sodin são evidentes na primeira semana de terapia.
Se não for obtida uma resposta adequada com 180 mg de CALAN SR, a dose pode ser titulada para cima da seguinte maneira :
- 240 mg todas as manhãs
- 180 mg por manhã mais
180 mg todas as noites; ou
240 mg por manhã mais
120 mg todas as noites - 240 mg a cada 12 horas.
Ao mudar de CALAN de liberação imediata para U-Sodin, a dose diária total em miligramas pode permanecer a mesma.
A dose de verapamil deve ser individualizada por titulação. A utilidade e segurança de dosagens superiores a 480 mg / dia não foram estabelecidas; portanto, esta dose diária não deve ser excedida. Como a meia-vida do verapamil aumenta durante a administração crônica, a resposta máxima pode ser adiada.
Angina
Os ensaios clínicos mostram que a dose habitual é de 80 mg a 120 mg três vezes ao dia. No entanto, 40 mg três vezes ao dia podem ser justificados em pacientes que podem ter uma resposta aumentada ao verapamil (por exemplo, diminuição da função hepática, idosos, etc.). A titulação para cima deve ser baseada na eficácia e segurança terapêuticas avaliadas aproximadamente oito horas após a administração. A dosagem pode ser aumentada diariamente (por exemplo, pacientes com angina instável) ou intervalos semanais até obter uma resposta clínica ideal.
Arritmias
A dosagem em pacientes digitalizados com fibrilação atrial crônica (ver PRECAUÇÕES) varia de 240 a 320 mg / dia em dividido (t.i.d. ou q.i.d.) doses. A dosagem para profilaxia do PSVT (pacientes não digitalizados) varia de 240 a 480 mg / dia em dividido (t.i.d. ou q.i.d.) doses. Em geral, os efeitos máximos para qualquer dose serão aparentes durante as primeiras 48 horas de terapia.
Hipertensão essencial
A dose deve ser individualizada por titulação. A dose inicial usual de monoterapia em ensaios clínicos foi de 80 mg três vezes ao dia (240 mg / dia). Dosagens diárias de 360 e 480 mg foram usadas, mas não há evidências de que doses além de 360 mg tenham efeito adicional. Deve-se considerar o início da titulação a 40 mg três vezes ao dia em pacientes que possam responder a doses mais baixas, como idosos ou pessoas de baixa estatura. Os efeitos anti-hipertensivos do U-Sodin são evidentes na primeira semana de terapia. A titulação para cima deve ser baseada na eficácia terapêutica, avaliada no final do intervalo de dosagem.
Hipertensão essencial
A dose de ISOPTIN SR deve ser individualizada por titulação e o medicamento deve ser administrado com alimentos. Inicie a terapia com 180 mg de verapamil HCl de liberação sustentada, ISOPTIN SR, administrado pela manhã. Doses iniciais mais baixas de 120 mg por dia podem ser justificadas em pacientes que podem ter uma resposta aumentada ao verapamil (por exemplo,., idosos ou pessoas pequenas etc.). A titulação para cima deve ser baseada na eficácia e segurança terapêuticas avaliadas semanalmente e aproximadamente 24 horas após a dose anterior. Os efeitos anti-hipertensivos do ISOPTIN SR são evidentes na primeira semana de terapia.
Se não for obtida uma resposta adequada com 180 mg de ISOPTIN SR, a dose pode ser titulada para cima da seguinte maneira :
- 240 mg todas as manhãs
- 180 mg por manhã mais 180 mg por noite ou 240 mg por manhã mais 120 mg por noite
- 240 mg a cada doze horas.
Ao mudar da liberação imediata ISOPTIN para ISOPTIN SR, a dose diária total em miligramas pode permanecer a mesma.
O verapamil HCl está contra-indicado em :
- Disfunção ventricular esquerda grave (ver AVISO)
- Hipotensão (pressão sistólica menor que 90 mmHg) ou choque cardiogênico
- Síndrome do seio doente (exceto em pacientes com um marcapasso ventricular artificial em funcionamento)
- Bloco AV de segundo ou terceiro grau (exceto em pacientes com um marcapasso ventricular artificial em funcionamento).
- Pacientes com vibração atrial ou fibrilação atrial e um trato de desvio acessório (por exemplo,., Síndromes Wolff-Parkinson-White, Lown-Ganong-Levine). (Vejo AVISO).
- Pacientes com hipersensibilidade conhecida ao cloridrato de verapamil.
U-Sodin may affect left ventricular contractility as a result of its mode of action. The effect is small and not normally important. However, cardiac failure may be aggravated or precipitated if it exists. In cases with poor ventricular function, U-Sodin should therefore only be administered after appropriate therapy for cardiac failure such as digitalis, etc.
U-Sodin may affect impulse conduction and should be administered with caution in patients with first degree atrioventricular block. The effects of U-Sodin and beta-blockers or other drugs may be additive both in respect of conduction and contraction, therefore care should be exercised when these are administered concurrently or closely together. This is especially true when either drug is administered intravenously.
Caution should be observed in the acute stage of myocardial infarction.
Patients with atrial fibrillation/flutter and an accessory pathway (eg Wolff-Parkinson-White syndrome) may rarely develop increased conduction across the anomalous pathway and ventricular tachycardia may be precipitated.
Since U-Sodin is extensively metabolised in the liver, careful dose titration of U-Sodin is required in patients with liver disease. The disposition of U-Sodin in patients with renal impairment has not been fully established and therefore careful patient monitoring is recommended. U-Sodin is not removed during dialysis.
WARNINGS
Heart Failure
Verapamil has a negative inotropic effect, which in most patients is compensated by its afterload reduction (decreased systemic vascular resistance) properties without a net impairment of ventricular performance. In clinical experience with 4,954 patients, 87 (1.8%) developed congestive heart failure or pulmonary edema. Verapamil should be avoided in patients with severe left ventricular dysfunction (eg, ejection fraction less than 30%) or moderate to severe symptoms of cardiac failure and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker (see DRUG INTERACTIONS). Patients with milder ventricular dysfunction should, if possible, be controlled with optimum doses of digitalis and/or diuretics before verapamil treatment. (Note interactions with digoxin under PRECAUTIONS)
Hypotension
Occasionally, the pharmacologic action of verapamil may produce a decrease in blood pressure below normal levels, which may result in dizziness or symptomatic hypotension. The incidence of hypotension observed in 4,954 patients enrolled in clinical trials was 2.5%. In hypertensive patients, decreases in blood pressure below normal are unusual. Tilt-table testing (60 degrees) was not able to induce orthostatic hypotension.
Elevated Liver Enzymes
Elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have been reported. Such elevations have sometimes been transient and may disappear even with continued verapamil treatment. Several cases of hepatocellular injury related to verapamil have been proven by rechallenge; half of these had clinical symptoms (malaise, fever, and/or right upper quadrant pain), in addition to elevation of SGOT, SGPT, and alkaline phosphatase. Periodic monitoring of liver function in patients receiving verapamil is therefore prudent.
Accessory Bypass Tract (Wolff-Parkinson-White Or Lown-Ganong-Levine)
Some patients with paroxysmal and/or chronic atrial fibrillation or atrial flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node, producing a very rapid ventricular response or ventricular fibrillation after receiving intravenous verapamil (or digitalis). Although a risk of this occurring with oral verapamil has not been established, such patients receiving oral verapamil may be at risk and its use in these patients is contraindicated (see CONTRAINDICATIONS). Treatment is usually DC-cardioversion. Cardioversion has been used safely and effectively after oral CALAN.
Atrioventricular Block
The effect of verapamil on AV conduction and the SA node may cause asymptomatic first-degree AV block and transient bradycardia, sometimes accompanied by nodal escape rhythms. PR-interval prolongation is correlated with verapamil plasma concentrations especially during the early titration phase of therapy. Higher degrees of AV block, however, were infrequently (0.8%) observed. Marked first-degree block or progressive development to second-or third-degree AV block requires a reduction in dosage or, in rare instances, discontinuation of verapamil HCl and institution of appropriate therapy, depending on the clinical situation.
Patients With Hypertrophic Cardiomyopathy (IHSS)
aIn 120 patients with hypertrophic cardiomyopathy (most of them refractory or intolerant to propranolol) who received therapy with verapamil at doses up to 720 mg/day, a variety of serious adverse effects were seen. Three patients died in pulmonary edema; all had severe left ventricular outflow obstruction and a past history of left ventricular dysfunction. Eight other patients had pulmonary edema and/or severe hypotension; abnormally high (greater than 20 mm Hg) pulmonary wedge pressure and a marked left ventricular outflow obstruction were present in most of these patients. Concomitant administration of quinidine (see PRECAUTIONS, DRUG INTERACTIONS) preceded the severe hypotension in 3 of the 8 patients (2 of whom developed pulmonary edema). Sinus bradycardia occurred in 11% of the patients, second-degree AV block in 4%, and sinus arrest in 2%. It must be appreciated that this group of patients had a serious disease with a high mortality rate. Most adverse effects responded well to dose reduction, and only rarely did verapamil use have to be discontinued.
PRECAUTIONS
General
Use In Patients With Impaired Hepatic Function
Since verapamil is highly metabolized by the liver, it should be administered cautiously to patients with impaired hepatic function. Severe liver dysfunction prolongs the elimination half-life of verapamil to about 14 to 16 hours; hence, approximately 30% of the dose given to patients with normal liver function should be administered to these patients. Careful monitoring for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects (see OVERDOSE) should be carried out.
Use In Patients With Attenuated (Decreased) Neuromuscular Transmission
It has been reported that verapamil decreases neuromuscular transmission in patients with Duchenne’s muscular dystrophy, prolongs recovery from the neuromuscular blocking agent vecuronium, and causes a worsening of myasthenia gravis. It may be necessary to decrease the dosage of verapamil when it is administered to patients with attenuated neuromuscular transmission.
Use In Patients With Impaired Renal Function
About 70% of an administered dose of verapamil is excreted as metabolites in the urine. Verapamil is not removed by hemodialysis. Until further data are available, verapamil should be administered cautiously to patients with impaired renal function. These patients should be carefully monitored for abnormal prolongation of the PR interval or other signs of overdosage (see OVERDOSE).
Carcinogenesis, Mutagenesis, Impairment Of Fertility
An 18-month toxicity study in rats, at a low multiple (6-fold) of the maximum recommended human dose, and not the maximum tolerated dose, did not suggest a tumorigenic potential. There was no evidence of a carcinogenic potential of verapamil administered in the diet of rats for two years at doses of 10, 35, and 120 mg/kg/day or approximately 1, 3.5, and 12 times, respectively, the maximum recommended human daily dose (480 mg/day or 9.6 mg/kg/day).
Verapamil was not mutagenic in the Ames test in 5 test strains at 3 mg per plate with or without metabolic activation.
Studies in female rats at daily dietary doses up to 5.5 times (55 mg/kg/day) the maximum recommended human dose did not show impaired fertility. Effects on male fertility have not been determined.
Pregnancy
Reproduction studies have been performed in rabbits and rats at oral doses up to 1.5 (15 mg/kg/day) and 6 (60 mg/kg/day) times the human oral daily dose, respectively, and have revealed no evidence of teratogenicity. In the rat, however, this multiple of the human dose was embryocidal and retarded fetal growth and development, probably because of adverse maternal effects reflected in reduced weight gains of the dams. This oral dose has also been shown to cause hypotension in rats. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery.
Labor And Delivery
It is not known whether the use of verapamil during labor or delivery has immediate or delayed adverse effects on the fetus, or whether it prolongs the duration of labor or increases the need for forceps delivery or other obstetric intervention. Such adverse experiences have not been reported in the literature, despite a long history of use of verapamil in Europe in the treatment of cardiac side effects of beta-adrenergic agonist agents used to treat premature labor.
Nursing Mothers
Verapamil is excreted in human milk. Because of the potential for adverse reactions in nursing infants from verapamil, nursing should be discontinued while verapamil is administered.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
WARNINGS
Heart Failure
Verapamil has a negative inotropic effect, which in most patients is compensated by its afterload reduction (decreased systemic vascular resistance) properties without a net impairment of ventricular performance. In clinical experience with 4,954 patients, 87 (1.8%) developed congestive heart failure or pulmonary edema. Verapamil should be avoided in patients with severe left ventricular dysfunction (eg, ejection fraction less than 30%) or moderate to severe symptoms of cardiac failure and in patients with any degree of ventricular dysfunction if they are receiving a betaadrenergic blocker (see PRECAUTIONS: DRUG INTERACTIONS). Patients with milder ventricular dysfunction should, if possible, be controlled with optimum doses of digitalis and/or diuretics before verapamil treatment. (Note interactions with digoxin under PRECAUTIONS)
Hypotension
Occasionally, the pharmacologic action of verapamil may produce a decrease in blood pressure below normal levels, which may result in dizziness or symptomatic hypotension. The incidence of hypotension observed in 4,954 patients enrolled in clinical trials was 2.5%. In hypertensive patients, decreases in blood pressure below normal are unusual. Tilt-table testing (60 degrees) was not able to induce orthostatic hypotension.
Elevated Liver Enzymes
Elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have been reported. Such elevations have sometimes been transient and may disappear even in the face of continued verapamil treatment. Several cases of hepatocellular injury related to verapamil have been proven by rechallenge; half of these had clinical symptoms (malaise, fever, and/or right upper quadrant pain) in addition to elevation of SGOT, SGPT, and alkaline phosphatase. Periodic monitoring of liver function in patients receiving verapamil is therefore prudent.
Accessory Bypass Tract (Wolff-Parkinson-White Or Lown-Ganong-Levine)
Some patients with paroxysmal and/or chronic atrial fibrillation or atrial flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node, producing a very rapid ventricular response or ventricular fibrillation after receiving intravenous verapamil (or digitalis). Although a risk of this occurring with oral verapamil has not been established, such patients receiving oral verapamil may be at risk and its use in these patients is contraindicated (see CONTRAINDICATIONS). Treatment is usually DC-cardioversion. Cardioversion has been used safely and effectively after oral CALAN.
Atrioventricular Block
The effect of verapamil on AV conduction and the SA node may cause asymptomatic first-degree AV block and transient bradycardia, sometimes accompanied by nodal escape rhythms. PR-interval prolongation is correlated with verapamil plasma concentrations, especially during the early titration phase of therapy. Higher degrees of AV block, however, were infrequently (0.8%) observed. Marked firstdegree block or progressive development to second- or third-degree AV block, requires a reduction in dosage or, in rare instances, discontinuation of verapamil HCl and institution of appropriate therapy, depending upon the clinical situation.
Patients With Hypertrophic Cardiomyopathy (IHSS)
In 120 patients with hypertrophic cardiomyopathy (most of them refractory or intolerant to propranolol) who received therapy with verapamil at doses up to 720 mg/day, a variety of serious adverse effects were seen. Three patients died in pulmonary edema; all had severe left ventricular outflow obstruction and a past history of left ventricular dysfunction. Eight other patients had pulmonary edema and/or severe hypotension; abnormally high (greater than 20 mm Hg) pulmonary wedge pressure and a marked left ventricular outflow obstruction were present in most of these patients. Concomitant administration of quinidine (see PRECAUTIONS: DRUG INTERACTIONS) preceded the severe hypotension in 3 of the 8 patients (2 of whom developed pulmonary edema). Sinus bradycardia occurred in 11% of the patients, second-degree AV block in 4%, and sinus arrest in 2%. It must be appreciated that this group of patients had a serious disease with a high mortality rate. Most adverse effects responded well to dose reduction, and only rarely did verapamil use have to be discontinued.
PRECAUTIONS
General
Use In Patients With Impaired Hepatic Function
Since verapamil is highly metabolized by the liver, it should be administered cautiously to patients with impaired hepatic function. Severe liver dysfunction prolongs the elimination half-life of immediate-release verapamil to about 14 to 16 hours; hence, approximately 30% of the dose given to patients with normal liver function should be administered to these patients. Careful monitoring for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects (see OVERDOSAGE) should be carried out.
Use In Patients With Attenuated (Decreased) Neuromuscular Transmission
It has been reported that verapamil decreases neuromuscular transmission in patients with Duchenne's muscular dystrophy, and that verapamil prolongs recovery from the neuromuscular blocking agent vecuronium. It may be necessary to decrease the dosage of verapamil when it is administered to patients with attenuated neuromuscular transmission.
Use In Patients With Impaired Renal Function
About 70% of an administered dose of verapamil is excreted as metabolites in the urine. Verapamil is not removed by hemodialysis. Until further data are available, verapamil should be administered cautiously to patients with impaired renal function. These patients should be carefully monitored for abnormal prolongation of the PR interval or other signs of overdosage (see OVERDOSAGE).
Carcinogenesis, Mutagenesis, Impairment Of Fertility
An 18-month toxicity study in rats, at a low multiple (6-fold) of the maximum recommended human dose, and not the maximum tolerated dose, did not suggest a tumorigenic potential. There was no evidence of a carcinogenic potential of verapamil administered in the diet of rats for two years at doses of 10, 35, and 120 mg/kg/day or approximately 1, 3.5, and 12 times, respectively, the maximum recommended human daily dose (480 mg/day or 9.6 mg/kg/day).
Verapamil was not mutagenic in the Ames test in 5 test strains at 3 mg per plate with or without metabolic activation.
Studies in female rats at daily dietary doses up to 5.5 times (55 mg/kg/day) the maximum recommended human dose did not show impaired fertility. Effects on male fertility have not been determined.
Pregnancy
Pregnancy Category C
Reproduction studies have been performed in rabbits and rats at oral doses up to 1.5 (15 mg/kg/day) and 6 (60 mg/kg/day) times the human oral daily dose, respectively, and have revealed no evidence of teratogenicity. In the rat, however, this multiple of the human dose was embryocidal and retarded fetal growth and development, probably because of adverse maternal effects reflected in reduced weight gains of the dams. This oral dose has also been shown to cause hypotension in rats. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery.
Labor And Delivery
It is not known whether the use of verapamil during labor or delivery has immediate or delayed adverse effects on the fetus, or whether it prolongs the duration of labor or increases the need for forceps delivery or other obstetric intervention. Such adverse experiences have not been reported in the literature, despite a long history of use of verapamil in Europe in the treatment of cardiac side effects of beta-adrenergic agonist agents used to treat premature labor.
Nursing Mothers
Verapamil is excreted in human milk. Because of the potential for adverse reactions in nursing infants from verapamil, nursing should be discontinued while verapamil is administered.
Pediatric Use
Safety and efficacy of U-Sodin in pediatric patients below the age of 18 years have not been established.
WARNINGS
Heart Failure
Verapamil has a negative inotropic effect, which in most patients is compensated by its afterload reduction (decreased systemic vascular resistance) properties without a net impairment of ventricular performance. In clinical experience with 4,954 patients, 87 (1.8%) developed congestive heart failure or pulmonary edema. Verapamil should be avoided in patients with severe left ventricular dysfunction (eg, ejection fraction less than 30%) or moderate to severe symptoms of cardiac failure and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker (see DRUG INTERACTIONS). Patients with milder ventricular dysfunction should, if possible, be controlled with optimum doses of digitalis and/or diuretics before verapamil treatment. (Note interactions with digoxin under PRECAUTIONS)
Hypotension
Occasionally, the pharmacologic action of verapamil may produce a decrease in blood pressure below normal levels, which may result in dizziness or symptomatic hypotension. The incidence of hypotension observed in 4,954 patients enrolled in clinical trials was 2.5%. In hypertensive patients, decreases in blood pressure below normal are unusual. Tilt-table testing (60 degrees) was not able to induce orthostatic hypotension.
Elevated Liver Enzymes
Accessory Bypass Tract (Wolff-Parkinson-White Or Lown-Ganong-Levine)
Some patients with paroxysmal and/or chronic atrial fibrillation or atrial flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node, producing a very rapid ventricular response or ventricular fibrillation after receiving intravenous verapamil (or digitalis). Although a risk of this occurring with oral verapamil has not been established, such patients receiving oral verapamil may be at risk and its use in these patients is contraindicated (see CONTRAINDICATIONS). Treatment is usually DC-cardioversion. Cardioversion has been used safely and effectively after oral U-Sodin.
Atrioventricular Block
The effect of verapamil on AV conduction and the SA node may cause asymptomatic first-degree AV block and transient bradycardia, sometimes accompanied by nodal escape rhythms. PR-interval prolongation is correlated with verapamil plasma concentrations especially during the early titration phase of therapy. Higher degrees of AV block, however, were infrequently (0.8%) observed. Marked first-degree block or progressive development to second-or third-degree AV block requires a reduction in dosage or, in rare instances, discontinuation of verapamil HCl and institution of appropriate therapy, depending on the clinical situation.
Patients With Hypertrophic Cardiomyopathy (IHSS)
aIn 120 patients with hypertrophic cardiomyopathy (most of them refractory or intolerant to propranolol) who received therapy with verapamil at doses up to 720 mg/day, a variety of serious adverse effects were seen. Three patients died in pulmonary edema; all had severe left ventricular outflow obstruction and a past history of left ventricular dysfunction. Eight other patients had pulmonary edema and/or severe hypotension; abnormally high (greater than 20 mm Hg) pulmonary wedge pressure and a marked left ventricular outflow obstruction were present in most of these patients. Concomitant administration of quinidine (see PRECAUTIONS, DRUG INTERACTIONS) preceded the severe hypotension in 3 of the 8 patients (2 of whom developed pulmonary edema). Sinus bradycardia occurred in 11% of the patients, second-degree AV block in 4%, and sinus arrest in 2%. It must be appreciated that this group of patients had a serious disease with a high mortality rate. Most adverse effects responded well to dose reduction, and only rarely did verapamil use have to be discontinued.
PRECAUTIONS
General
Use In Patients With Impaired Hepatic Function
Since verapamil is highly metabolized by the liver, it should be administered cautiously to patients with impaired hepatic function. Severe liver dysfunction prolongs the elimination half-life of verapamil to about 14 to 16 hours; hence, approximately 30% of the dose given to patients with normal liver function should be administered to these patients. Careful monitoring for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects (see OVERDOSE) should be carried out.
Use In Patients With Attenuated (Decreased) Neuromuscular Transmission
It has been reported that verapamil decreases neuromuscular transmission in patients with Duchenne’s muscular dystrophy, prolongs recovery from the neuromuscular blocking agent vecuronium, and causes a worsening of myasthenia gravis. It may be necessary to decrease the dosage of verapamil when it is administered to patients with attenuated neuromuscular transmission.
Use In Patients With Impaired Renal Function
About 70% of an administered dose of verapamil is excreted as metabolites in the urine. Verapamil is not removed by hemodialysis. Until further data are available, verapamil should be administered cautiously to patients with impaired renal function. These patients should be carefully monitored for abnormal prolongation of the PR interval or other signs of overdosage (see OVERDOSE).
Carcinogenesis, Mutagenesis, Impairment Of Fertility
An 18-month toxicity study in rats, at a low multiple (6-fold) of the maximum recommended human dose, and not the maximum tolerated dose, did not suggest a tumorigenic potential. There was no evidence of a carcinogenic potential of verapamil administered in the diet of rats for two years at doses of 10, 35, and 120 mg/kg/day or approximately 1, 3.5, and 12 times, respectively, the maximum recommended human daily dose (480 mg/day or 9.6 mg/kg/day).
Verapamil was not mutagenic in the Ames test in 5 test strains at 3 mg per plate with or without metabolic activation.
Studies in female rats at daily dietary doses up to 5.5 times (55 mg/kg/day) the maximum recommended human dose did not show impaired fertility. Effects on male fertility have not been determined.
Pregnancy
Reproduction studies have been performed in rabbits and rats at oral doses up to 1.5 (15 mg/kg/day) and 6 (60 mg/kg/day) times the human oral daily dose, respectively, and have revealed no evidence of teratogenicity. In the rat, however, this multiple of the human dose was embryocidal and retarded fetal growth and development, probably because of adverse maternal effects reflected in reduced weight gains of the dams. This oral dose has also been shown to cause hypotension in rats. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery.
Labor And Delivery
It is not known whether the use of verapamil during labor or delivery has immediate or delayed adverse effects on the fetus, or whether it prolongs the duration of labor or increases the need for forceps delivery or other obstetric intervention. Such adverse experiences have not been reported in the literature, despite a long history of use of verapamil in Europe in the treatment of cardiac side effects of beta-adrenergic agonist agents used to treat premature labor.
Nursing Mothers
Verapamil is excreted in human milk. Because of the potential for adverse reactions in nursing infants from verapamil, nursing should be discontinued while verapamil is administered.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
WARNINGS
Heart Failure
Verapamil has a negative inotropic effect which, in most patients, is compensated by its afterload reduction (decreased systemic vascular resistance) properties without a net impairment of ventricular performance. In clinical experience with 4,954 patients, 87 (1.8%) developed congestive heart failure or pulmonary edema. Verapamil should be avoided in patients with severe left ventricular dysfunction (e.g., ejection fraction less than 30%, or moderate to severe symptoms of cardiac failure) and in patients with any degree of ventricular dysfunction if they are receiving a beta adrenergic blocker (see DRUG INTERACTIONS). Patients with milder ventricular dysfunction should, if possible, be controlled with optimum doses of digitalis and/or diuretics before verapamil treatment (Note interactions with digoxin under: PRECAUTIONS).
Hypotension
Occasionally, the pharmacologic action of verapamil may produce a decrease in blood pressure below normal levels which may result in dizziness or symptomatic hypotension. The incidence of hypotension observed in 4,954 patients enrolled in clinical trials was 2.5%. In hypertensive patients, decreases in blood pressure below normal are unusual. Tilt table testing (60 degrees) was not able to induce orthostatic hypotension.
Elevated Liver Enzymes
Elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have been reported. Such elevations have sometimes been transient and may disappear even in the face of continued verapamil treatment. Several cases of hepatocellular injury related to verapamil have been proven by rechallenge; half of these had clinical symptoms (malaise, fever, and/or right upper quadrant pain) in addition to elevations of SGOT, SGPT and alkaline phosphatase. Periodic monitoring of liver function in patients receiving verapamil is therefore prudent.
Accessory Bypass Tract (Wolff-Parkinson-White or Lown-Ganong-Levine)
Some patients with paroxysmal and/or chronic atrial fibrillation or atrial flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node, producing a very rapid ventricular response or ventricular fibrillation after receiving intravenous verapamil (or digitalis). Although a risk of this occurring with oral verapamil has not been established, such patients receiving oral verapamil may be at risk and its use in these patients is contraindicated (see CONTRAINDICATIONS). Treatment is usually DC-cardioversion. Cardioversion has been used safely and effectively after oral ISOPTIN.
Atrioventricular Block
The effect of verapamil on AV conduction and the SA node may cause asymptomatic first-degree AV block and transient bradycardia, sometimes accompanied by nodal escape rhythms. PR interval prolongation is correlated with verapamil plasma concentrations, especially during the early titration phases of therapy. Higher degrees of AV block, however, were infrequently (0.8%) observed. Marked first-degree block or progressive development to second- or third-degree AV block requires a reduction in dosage or, in rare instances, discontinuation of verapamil HCI and institution of appropriate therapy depending upon the clinical situation.
Patients with Hypertrophic Cardiomyopathy (IHSS)
In 120 patients with hypertrophic cardiomyopathy (most of them refractory or intolerant to propranolol) who received therapy with verapamil at doses up to 720 mg/day, a variety of serious adverse effects were seen. Three patients died in pulmonary edema; all had severe left ventricular outflow obstruction and a past history of left ventricular dysfunction. Eight other patients had pulmonary edema and/or severe hypotension; abnormally high (greater than 20 mmHg) pulmonary wedge pressure and a marked left ventricular outflow obstruction were present in most of these patients. Concomitant administration of quinidine (see DRUG INTERACTIONS) preceded the severe hypotension in 3 of the 8 patients (2 of whom developed pulmonary edema). Sinus bradycardia occurred in 11% of the patients, second- degree AV block in 4% and sinus arrest in 2%. It must be appreciated that this group of patients had a serious disease with a high mortality rate. Most adverse effects responded well to dose reduction and only rarely did verapamil have to be discontinued.
PRECAUTIONS
General
Use in Patients with Impaired Hepatic Functions
Since verapamil is highly metabolized by the liver, it should be administered cautiously to patients with impaired hepatic function. Severe liver dysfunction prolongs the elimination half-life of immediate release verapamil to about 14 to 16 hours; hence, approximately 30% of the dose given to patients with normal liver function should be administered to these patients. Careful monitoring for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects (see OVERDOSAGE) should be carried out.
Use in Patients with Attenuated (Decreased) Neuromuscular Transmission
It has been reported that verapamil decreases neuromuscular transmission in patients with Duchenne's muscular dystrophy, prolongs recovery from the neuromuscular blocking agent vecuronium, and causes a worsening of myasthenia gravis. It may be necessary to decrease the dosage of verapamil when it is administered to patients with attenuated neuromuscular transmission.
Use in Patients with Impaired Renal Function
About 70% of an administered dose of verapamil is excreted as metabolites in the urine. Verapamil is not removed by hemodialysis. Until further data are available, verapamil should be administered cautiously to patients with impaired renal function. These patients should be carefully monitored for abnormal prolongation of the PR interval or other signs of overdosage (see OVERDOSAGE).
Carcinogenesis, Mutagenesis, Impairment of Fertility
An 18-month toxicity study in rats, at a low multiple (6 fold) of the maximum recommended human dose, and not the maximum tolerated dose, did not suggest a tumorigenic potential. There was no evidence of a carcinogenic potential of verapamil administered in the diet of rats for two years at doses of 10, 35, and 120 mg/kg per day or approximately 1x, 3.5x, and 12x, respectively, the maximum recommended human daily dose (480 mg per day or 9.6 mg/kg/day).
Verapamil was not mutagenic in the Ames test in 5 test strains at 3 mg per plate, with or without metabolic activation.
Studies in female rats at daily dietary doses up to 5.5 times (55 mg/kg/day) the maximum recommended human dose did not show impaired fertility. Effects on male fertility have not been determined.
Pregnancy
Pregnancy Category C. Reproduction studies have been performed in rabbits and rats at oral doses up to 1.5 (15 mg/kg/day) and 6 (60 mg/kg/day) times the human oral daily dose, respectively, and have revealed no evidence of teratogenicity. In the rat, however, this multiple of the human dose was embryocidal and retarded fetal growth and development, probably because of adverse maternal effects reflected in the reduced weight gains of the dams. This oral dose has also been shown to cause hypotension in rats. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery.
Labor and Delivery
It is not known whether the use of verapamil during labor or delivery has immediate or delayed adverse effects on the fetus, or whether it prolongs the duration of labor or increases the need for forceps delivery or other obstetric intervention. Such adverse experiences have not been reported in the literature, despite a long history of use of verapamil in Europe in the treatment of cardiac side effects of beta-adrenergic agonist agents used to treat premature labor.
Nursing Mothers
Verapamil is excreted in human milk. Because of the potential for adverse reactions in nursing infants from verapamil, nursing should be discontinued while verapamil is administered.
Pediatric Use
Safety and efficacy of ISOPTIN tablets in pediatric patients below the age of 18 years have not been established.
Dependendo da suscetibilidade individual, a capacidade do paciente de dirigir ou operar máquinas pode ser prejudicada devido a sentimentos de sonolência. Isso é particularmente verdadeiro nos estágios iniciais do tratamento ou ao mudar de outro medicamento. Foi demonstrado que o U-Sodin aumenta os níveis sanguíneos de álcool e diminui sua eliminação. Portanto, os efeitos do álcool podem ser exagerados.
Immune system disorders: allergic reactions (e.g. erythema, pruritus, urticaria) are very rarely seen.
Nervous system disorders: headaches occur rarely, dizziness, paraesthesia, tremor, extrapyramidal syndrome (e.g. parkinsonism), dystonia.
Ear and labyrinth disorders: vertigo, tinnitus.
Cardiac disorders: bradycardic arrhythmias such as sinus bradycardia, sinus arrest with asystole, 2nd and 3rd degree AV block, bradyarrhythmia in atrial fibrillation, palpitations, tachycardia, development or aggravation of heart failure, hypotension.
Vascular disorders: flushing, peripheral oedema.
Gastrointestinal disorders: nausea, vomiting, constipation is not uncommon, ileus and abdominal pain/discomfort. Gingival hyperplasia may very rarely occur when the drug is administered over prolonged periods. This is fully reversible when the drug is discontinued.
Skin and subcutaneous tissue disorders: alopecia, ankle oedema, Quincke's oedema, Steven-Johnson syndrome, erythema multiforme, erythromelalgia, purpura.
Musculoskeletal and connective tissue disorders: muscular weakness, myalgia and arthralgia.
Reproductive system and breast disorders: impotence (erectile dysfunction) has been rarely reported and isolated cases of galactorrhoea. Gynaecomastia was observed on very rare occasions in elderly male patients under longer term U-Sodin treatment which was fully reversible in all cases when the drug was discontinued.
General disorders and administration site conditions: fatigue.
Investigations: On very rare occasions, a reversible impairment of liver function characterised by an increase in transaminases and/or alkaline phosphatase, may occur during U-Sodin treatment and is most probably a hypersensitivity reaction.
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 the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard
Serious adverse reactions are uncommon when CALAN therapy is initiated with upward dose titration within the recommended single and total daily dose. See WARNINGS for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of verapamil) non-obstructive, paralytic ileus has been infrequently reported in association with the use of verapamil. The following reactions to orally administered verapamil occurred at rates greater than 1.0% or occurred at lower rates but appeared clearly drug-related in clinical trials in 4,954 patients:
Constipation | 7.3% | CHF, Pulmonary edema | 1.8% |
Dizziness | 3.3% | Dyspnea | 1.4% |
Nausea | 2.7% | Bradycardia (HR <50/min) | 1.4% |
Hypotension | 2.5% | AV block total (1°, 2°, 3°) | 1.2% |
Headache | 2.2% | 2° and 3° | 0.8% |
Edema | 1.9% | Rash | 1.2% |
Fatigue | 1.7% | Flushing | 0.6% |
Elevated liver enzymes (see WARNINGS) |
In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or flutter, ventricular rates below 50 at rest occurred in 15% of patients and asymptomatic hypotension occurred in 5% of patients.
The following reactions, reported in 1.0% or less of patients, occurred under conditions (open trials, marketing experience) where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship:
Cardiovascular: angina pectoris, atrioventricular dissociation, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope.
Digestive system: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia.
Hemic and lymphatic: ecchymosis or bruising.
Nervous system: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, paresthesia, psychotic symptoms, shakiness, somnolence, extrapyramidal symptoms.
Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, macules, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme.
Special senses: blurred vision, tinnitus.
Urogenital: gynecomastia, galactorrhea/hyperprolactinemia, increased urination, spotty menstruation, impotence.
Treatment Of Acute Cardiovascular Adverse Reactions
The frequency of cardiovascular adverse reactions that require therapy is rare; hence, experience with their treatment is limited. Whenever severe hypotension or complete AV block occurs following oral administration of verapamil, the appropriate emergency measures should be applied immediately; eg, intravenously administered norepinephrine bitartrate, atropine sulfate, isoproterenol HCl (all in the usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), alpha-adrenergic agents (phenylephrine HCl, metaraminol bitartrate, or methoxamine HCl) should be used to maintain blood pressure, and isoproterenol and norepinephrine should be avoided. If further support is necessary, dopamine HCl or dobutamine HCl may be administered. Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician.
Serious adverse reactions are uncommon when verapamil therapy is initiated with upward dose titration within the recommended single and total daily dose. See WARNINGS for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of verapamil) non-obstructive, paralytic ileus has been infrequently reported in association with the use of verapamil. The following reactions to orally administered verapamil occurred at rates greater than 1.0% or occurred at lower rates but appeared clearly drug-related in clinical trials in 4,954 patients:
Constipation | 7.3% |
Dizziness | 3.3% |
Nausea | 2.7% |
Hypotension | 2.5% |
Headache | 2.2% |
Edema | 1.9% |
CHF, Pulmonary edema | 1.8% |
Fatigue | 1.7% |
Dyspnea | 1.4% |
Bradycardia (HR < 50/min) | 1.4% |
AV block (total 1°, 2°, 3°) | 1.2% |
(2° and 3°) | 0.8% |
Rash | 1.2% |
Flushing | 0.6% |
Elevated liver enzymes (see WARNINGS) |
In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or flutter, ventricular rates below 50/min at rest occurred in 15% of patients and asymptomatic hypotension occurred in 5% of patients.
The following reactions, reported in 1% or less of patients, occurred under conditions (open trials, marketing experience) where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship:
Cardiovascular: angina pectoris, atrioventricular dissociation, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope.
Digestive system: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia.
Hemic and lymphatic: ecchymosis or bruising.
Nervous system: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, paresthesia, psychotic symptoms, shakiness, somnolence.
Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, macules, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme.
Special senses: blurred vision, tinnitus.
Urogenital: gynecomastia, galactorrhea/hyperprolactinemia, increased urination, spotty menstruation, impotence.
Treatment Of Acute Cardiovascular Adverse Reactions
The frequency of cardiovascular adverse reactions that require therapy is rare; hence, experience with their treatment is limited. Whenever severe hypotension or complete AV block occurs following oral administration of verapamil, the appropriate emergency measures should be applied immediately; eg, intravenously administered norepinephrine bitartrate, atropine sulfate, isoproterenol HCl (all in the usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), alpha-adrenergic agents (phenylephrine HCl, metaraminol bitartrate, or methoxamine HCl) should be used to maintain blood pressure, and isoproterenol and norepinephrine should be avoided. If further support is necessary, dopamine HCl or dobutamine HCl may be administered. Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician.
Serious adverse reactions are uncommon when U-Sodin therapy is initiated with upward dose titration within the recommended single and total daily dose. See WARNINGS for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of verapamil) non-obstructive, paralytic ileus has been infrequently reported in association with the use of verapamil. The following reactions to orally administered verapamil occurred at rates greater than 1.0% or occurred at lower rates but appeared clearly drug-related in clinical trials in 4,954 patients:
Constipation | 7.3% | CHF, Pulmonary edema | 1.8% |
Dizziness | 3.3% | Dyspnea | 1.4% |
Nausea | 2.7% | Bradycardia (HR <50/min) | 1.4% |
Hypotension | 2.5% | AV block total (1°, 2°, 3°) | 1.2% |
Headache | 2.2% | 2° and 3° | 0.8% |
Edema | 1.9% | Rash | 1.2% |
Fatigue | 1.7% | Flushing | 0.6% |
Elevated liver enzymes (see WARNINGS) |
In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or flutter, ventricular rates below 50 at rest occurred in 15% of patients and asymptomatic hypotension occurred in 5% of patients.
The following reactions, reported in 1.0% or less of patients, occurred under conditions (open trials, marketing experience) where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship:
Cardiovascular: angina pectoris, atrioventricular dissociation, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope.
Digestive system: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia.
Hemic and lymphatic: ecchymosis or bruising.
Nervous system: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, paresthesia, psychotic symptoms, shakiness, somnolence, extrapyramidal symptoms.
Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, macules, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme.
Special senses: blurred vision, tinnitus.
Urogenital: gynecomastia, galactorrhea/hyperprolactinemia, increased urination, spotty menstruation, impotence.
Treatment Of Acute Cardiovascular Adverse Reactions
The frequency of cardiovascular adverse reactions that require therapy is rare; hence, experience with their treatment is limited. Whenever severe hypotension or complete AV block occurs following oral administration of verapamil, the appropriate emergency measures should be applied immediately; eg, intravenously administered norepinephrine bitartrate, atropine sulfate, isoproterenol HCl (all in the usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), alpha-adrenergic agents (phenylephrine HCl, metaraminol bitartrate, or methoxamine HCl) should be used to maintain blood pressure, and isoproterenol and norepinephrine should be avoided. If further support is necessary, dopamine HCl or dobutamine HCl may be administered. Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician.
Serious adverse reactions are uncommon when verapamil therapy is initiated with upward dose titration within the recommended single and total daily dose. See WARNINGS for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of verapamil) non-obstructive, paralytic ileus has been infrequently reported in association with the use of verapamil. The following reactions to orally administered verapamil occurred at rates greater than 1.0% or occurred at lower rates but appeared clearly drug-related in clinical trials in 4,954 patients.
Constipation | 7.3% |
Fatigue | 1.7% |
Dizziness | 3.3% |
Dyspnea | 1.4% |
Nausea | 2.7% |
Bradycardia (HR < 50/min) | 1.4% |
Hypotension | 2.5% |
AV Block-total (1°,2°, 3°) | 1.2% |
Headache | 2.2% |
2 ° and 3° | 0.8% |
Edema | 1.9% |
Rash | 1.2% |
CHF/Pulmonary Edema | 1.8% |
Flushing | 0.6% |
Elevated Liver Enzymes
(see WARNINGS)
In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or atrial flutter, ventricular rates below 50/min at rest occurred in 15% of patients and asymptomatic hypotension occurred in 5% of patients.
The following reactions, reported in 1.0% or less of patients, occurred under conditions (open trials, marketing experience) where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship.
Cardiovascular: angina pectoris, atrioventricular dissociation, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope.
Digestive System: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia.
Hemic and Lymphatic: ecchymosis or bruising.
Nervous System: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, parasthesia, psychotic symptoms, shakiness, somnolence, extrapyramidal symptoms.
Skin: arthralgia and rash, exanthema, hair loss hyperkeratosis, maculae, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme.
Special Senses: blurred vision, tinnitus.
Urogenital: gynecomastia, impotence, galactorrhea/ hyperprolactinemia, increased urination, spotty menstruation.
Treatment of Acute Cardiovascular Adverse Reactions
The frequency of cardiovascular adverse reactions that require therapy is rare, hence, experience with their treatment is limited. Whenever severe hypotension or complete AV block occurs following oral administration of verapamil, the appropriate emergency measures should be applied immediately, e.g., intravenously administered isoproterenol HCl, norepinephrine bitartrate, atropine sulfate (all in the usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), alpha-adrenergic agents (phenylephrine HCl, metaraminol bitartrate or methoxamine HCl) should be used to maintain blood pressure, and isoproterenol and norepinephrine should be avoided. If further support is necessary, (dopamine HCl or dobutamine HCl) may be administered. Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician.
O curso dos sintomas na intoxicação por U-Sodin depende da quantidade tomada, do momento em que são tomadas medidas de desintoxicação e da contratilidade do miocárdio (relacionada à idade). Os principais sintomas são os seguintes: queda da pressão arterial (às vezes para valores não detectáveis) sintomas de choque, perda de consciência, Bloco AV de 1o e 2o grau (freqüentemente como fenômeno de Wenckebach com ou sem ritmos de escape) bloco AV total com dissociação AV total, ritmo de fuga, assim como, bradicardia até bloco AV de alto grau e, prisão sinusal, hiperglicemia, estupor e acidose metabólica. As fatalidades ocorreram como resultado de overdose.
As medidas terapêuticas a serem tomadas dependem do momento em que o U-Sodin foi tomado e do tipo e gravidade dos sintomas de intoxicação. Em intoxicações com grandes quantidades de preparações de liberação lenta, deve-se notar que a liberação do medicamento ativo e a absorção no intestino podem levar mais de 48 horas. O cloridrato de U-Sodin não pode ser removido por hemodiálise. Dependendo do tempo de ingestão, deve-se levar em consideração que pode haver alguns pedaços de comprimidos incompletamente dissolvidos ao longo de todo o comprimento do trato gastrointestinal, que funcionam como depósitos ativos de drogas.
Medidas gerais a serem tomadas: Lavagem gástrica com as precauções usuais, o mais tardar 12 horas após a ingestão, se nenhuma motilidade gastrointestinal (sons peristálticos) for detectável. Onde houver suspeita de intoxicação por uma preparação de liberação modificada, são indicadas medidas extensas de eliminação, como vômitos induzidos, remoção do conteúdo do estômago e intestino delgado sob endoscopia, lavagem intestinal, enemas laxantes e altos. As medidas usuais de ressuscitação intensiva se aplicam, como massagem cardíaca extratorácica, respiração, desfibrilação e / ou terapia com marcapasso.
Medidas específicas a serem tomadas: Eliminação de efeitos cardiodepressivos, hipotensão ou bradicardia. O antídoto específico é o cálcio, p. 10 20ml de uma solução de gluconato de cálcio a 10% administrada por via intravenosa (2,25 - 4,5 mmol), repetida se necessário ou administrada como uma infusão contínua de gotejamento (por exemplo,. 5 mmol / hora).
Também podem ser necessárias as seguintes medidas: No caso de bloqueio AV de 2o ou 3o grau, bradicardia sinusal, asistole - atropina, isoprenalina, orciprenalina ou terapia com marcapasso. Em caso de hipotensão - dopamina, dobutamina, noradrenalina (noradrenalina). Se houver sinais de falha miocárdica contínua - dopamina, dobutamina, se necessário, injeções repetidas de cálcio.
Trate todas as overdoses de verapamil como graves e mantenha a observação por pelo menos 48 horas (especialmente CALAN SR), de preferência sob atendimento hospitalar contínuo. Consequências farmacodinâmicas atrasadas podem ocorrer com a formulação de liberação sustentada. Sabe-se que o verapamil diminui o tempo de trânsito gastrointestinal.
O tratamento da superdosagem deve ser favorável. A estimulação beta-adrenérgica ou a administração parenteral de soluções de cálcio podem aumentar o fluxo de íons de cálcio através do canal lento e foram efetivamente usadas no tratamento de superdosagem deliberada com verapamil. Em alguns casos relatados, a overdose com bloqueadores dos canais de cálcio tem sido associada a hipotensão e bradicardia, inicialmente refratária à atropina, mas se tornando mais responsiva a esse tratamento quando os pacientes receberam grandes doses (próximo a 1 grama / hora por mais de 24 horas) de cloreto de cálcio. O verapamil não pode ser removido por hemodiálise. Reações hipotensivas clinicamente significativas ou bloqueio AV de alto grau devem ser tratadas com agentes vasopressores ou ritmo cardíaco, respectivamente. A asistole deve ser tratada pelas medidas usuais, incluindo a ressuscitação cardiopulmonar.
A sobredosagem com verapamil pode levar a hipotensão pronunciada, bradicardia e anormalidades no sistema de condução (por exemplo, ritmo juncional com dissociação AV e bloqueio AV de alto grau, incluindo asistole). Outros sintomas secundários à hipoperfusão (por exemplo, acidose metabólica, hiperglicemia, hipercalemia, disfunção renal e convulsões) podem ser evidentes.
Trate todas as overdoses de verapamil como graves e mantenha a observação por pelo menos 48 horas (especialmente U-Sodin), de preferência sob atendimento hospitalar contínuo. Consequências farmacodinâmicas atrasadas podem ocorrer com a formulação de liberação sustentada. Sabe-se que o verapamil diminui o tempo de trânsito gastrointestinal.
Em sobredosagem, ocasionalmente foram relatados que as cápsulas de U-Sodin formam concreções no estômago ou intestinos. Essas concreções não foram visíveis em radiografias simples do abdômen, e nenhum meio médico de esvaziamento gastrointestinal é de eficácia comprovada na remoção delas. A endoscopia pode ser razoavelmente considerada em casos de overdose maciça quando os sintomas são extraordinariamente prolongados.
O tratamento da superdosagem deve ser favorável. A estimulação beta-adrenérgica ou a administração parenteral de soluções de cálcio podem aumentar o fluxo de íons de cálcio através do canal lento e foram efetivamente usadas no tratamento de superdosagem deliberada com verapamil. O tratamento continuado com grandes doses de cálcio pode produzir uma resposta. Em alguns casos relatados, a overdose com bloqueadores dos canais de cálcio que inicialmente era refratária à atropina tornou-se mais responsiva a esse tratamento quando os pacientes receberam grandes doses (próximas a 1 g / h por mais de 24 horas) de cloreto de cálcio. O verapamil não pode ser removido por hemodiálise. Reações hipotensivas clinicamente significativas ou bloqueio AV de alto grau devem ser tratadas com agentes vasopressores ou ritmo cardíaco, respectivamente. A asistole deve ser tratada pelas medidas usuais, incluindo a ressuscitação cardiopulmonar.
Trate todas as overdoses de verapamil como graves e mantenha a observação por pelo menos 48 horas (especialmente U-Sodin SR), de preferência sob atendimento hospitalar contínuo. Consequências farmacodinâmicas atrasadas podem ocorrer com a formulação de liberação sustentada. Sabe-se que o verapamil diminui o tempo de trânsito gastrointestinal.
O tratamento da superdosagem deve ser favorável. A estimulação beta-adrenérgica ou a administração parenteral de soluções de cálcio podem aumentar o fluxo de íons de cálcio através do canal lento e foram efetivamente usadas no tratamento de superdosagem deliberada com verapamil. Em alguns casos relatados, a overdose com bloqueadores dos canais de cálcio tem sido associada a hipotensão e bradicardia, inicialmente refratária à atropina, mas se tornando mais responsiva a esse tratamento quando os pacientes receberam grandes doses (próximo a 1 grama / hora por mais de 24 horas) de cloreto de cálcio. O verapamil não pode ser removido por hemodiálise. Reações hipotensivas clinicamente significativas ou bloqueio AV de alto grau devem ser tratadas com agentes vasopressores ou ritmo cardíaco, respectivamente. A asistole deve ser tratada pelas medidas usuais, incluindo a ressuscitação cardiopulmonar.
A sobredosagem com verapamil pode levar a hipotensão pronunciada, bradicardia e anormalidades no sistema de condução (por exemplo,., ritmo juncional com dissociação AV e bloqueio AV de alto grau, incluindo asistole). Outros sintomas secundários à hipoperfusão (por exemplo,.acidose metabólica, hiperglicemia, hipercalemia, disfunção renal e convulsões) podem ser evidentes.
Trate todas as overdoses de verapamil como graves e mantenha a observação por pelo menos 48 horas [especialmente ISOPTIN® SR (cloridrato de verapamil)], de preferência sob cuidados hospitalares contínuos. Consequências farmacodinâmicas atrasadas podem ocorrer com a formulação de liberação sustentada. Sabe-se que o verapamil diminui o tempo de trânsito gastrointestinal.
Em sobredosagem, ocasionalmente foram relatados comprimidos de ISOPTIN SR para formar concreções no estômago ou intestinos. Essas concreções não foram visíveis em radiografias simples do abdômen, e nenhum meio médico de esvaziamento gastrointestinal é de eficácia comprovada na remoção delas. A endoscopia pode ser razoavelmente considerada em casos de overdose maciça quando os sintomas são extraordinariamente prolongados.
O tratamento da superdosagem deve ser favorável. A estimulação beta adrenérgica ou a administração parenteral de soluções de cálcio podem aumentar o fluxo de íons de cálcio através do canal lento e foram usadas efetivamente no tratamento de superdosagem deliberada com verapamil. O tratamento continuado com grandes doses de cálcio pode produzir uma resposta. Em alguns casos relatados, a overdose com bloqueadores dos canais de cálcio que inicialmente era refratária à atropina tornou-se mais responsiva a esse tratamento quando os pacientes receberam grandes doses (próximo a 1 grama / hora por mais de 24 horas) de cloreto de cálcio. O verapamil não pode ser removido por hemodiálise. Reações hipotensivas clinicamente significativas ou bloqueio AV de alto grau devem ser tratadas com agentes vasopressores ou ritmo cardíaco, respectivamente. A asistole deve ser tratada pelas medidas usuais, incluindo a ressuscitação cardiopulmonar.
Grupo farmacoterapêutico: bloqueadores seletivos dos canais de cálcio com efeitos cardíacos diretos, derivados da fenilalquilamina.
Código ATC: C08 DA01
O cloridrato de U-Sodin é um bloqueador dos canais de cálcio e é classificado como um agente antiarrítmico de classe IV.
Mecanismo de ação
A U-Sodin inibe a entrada de cálcio nas células musculares lisas das artérias sistêmica e coronariana e nas células do músculo cardíaco e no sistema de condução intracardíaca.
O U-Sodin reduz a resistência vascular periférica com pouca ou nenhuma taquicardia reflexa. Pensa-se que sua eficácia na redução da pressão arterial sistólica e diastólica aumentada seja devida principalmente a esse modo de ação.
A diminuição da resistência vascular sistêmica e coronariana e o efeito poupador no consumo intracelular de oxigênio parecem explicar as propriedades anti-anginais do produto.
Devido ao efeito no movimento do cálcio no sistema de condução intracardíaca, o U-Sodin reduz a automação, diminui a velocidade de condução e aumenta o período refratário.
Absorção
U-Sodin é aproximadamente 90% absorvido pelo trato gastrointestinal.
Distribuição
O U-Sodin atua dentro de 1-2 horas após administração oral com um pico de concentração plasmática após 1-2 horas. Há uma variação interindividual considerável nas concentrações plasmáticas. O U-Sodin está cerca de 90% ligado às proteínas plasmáticas.
Biotransformação
O U-Sodin está sujeito a um metabolismo de primeira passagem muito considerável no fígado e a biodisponibilidade é de apenas cerca de 20%. É extensamente metabolizado no fígado para pelo menos 12 metabólitos, dos quais nem U-Sodin demonstrou ter alguma atividade.
Eliminação
O U-Sodin exibe cinética de eliminação bi ou tri-fasica e é relatado ter uma meia-vida plasmática terminal de 2-8 horas após uma dose oral única. Após doses orais repetidas, isso aumenta para 4,5-12 horas. Cerca de 70% de uma dose é excretada pelos rins na forma de seus metabólitos, mas cerca de 16% também é excretado na bílis nas fezes. Menos de 4% é excretado inalterado.
Gravidez e aleitamento
U-Sodin atravessa a placenta e é excretado no leite materno.
Não aplicável.
Nenhum conhecido.
Não aplicável.
However, we will provide data for each active ingredient