Bulas Medicamentos Mepiadre | Page 2

Dosis máximas: 4,4 mg de clorhidrato de mepivacaína/kg (Cada Carpule de 1,8 ml contiene 36 mg de clorhidrato de mepivacaína y 0,018 mg de epinefrina) Peso (Kg) 10 20 30 40 50 60 70 80 90 100 N 0 Carpules MEPIADRE 1 2 3,5 4,5 6 7 8 8 8 8 Las dosis indicadas representan lo máximo sugerido para individuos sanos, normales; para pacientes debilitados o ancianos, deben ser menores. 7.Advertencias La seguridad y la eficacia de los anestésicos locales dependen de la dosificación recomendada, de la técnica correcta, de una anamnesia previa, de las precauciones adecuadas y de la rapidez y habilidad del profesional para intervenir en los casos de emergencia. Se debe usar la menor dosis que permita obtener una anestesia eficaz. La administración de dosis frecuentes de mepivacaína puede causar un acentuado aumento en los niveles plasmáticos debido a la absorción sistémica, al aumento de la cantidad del fármaco y sus metabolitos o a la lenta degradación metabólica. La tolerancia puede variar de acuerdo con el estado del paciente, ya que a pacientes debilitados, de edad avanzada, que padecen de enfermedades graves o a niños se les deben suministrar dosis reducidas, calculadas de acuerdo con la edad y las condiciones físicas. Se recomienda tomar cuidados especiales en el caso de administración frecuente a pacientes con graves trastornos hepáticos o renales, ya que su metabolismo está afectado. También se debe prestar atención especial al administrar anestésicos locales a pacientes con antecedentes de sensibilidad o alergia a los componentes de la fórmula. Pueden ocurrir serias arritmias cardíacas si se utilizan preparaciones que contienen vasoconstrictores en pacientes durante o después de la administración de halotano, tricloroetileno, ciclopropano o cloroformo. Existe un pequeño riesgo de que los vasoconstrictores causen isquemia o necrosis local en pacientes con enfermedades vasculares periféricas. Se debe tener en cuenta que el metabisulfito de potasio está presente en la fórmula, sustancia que puede causar reacciones alérgicas, incluyendo síntomas anafilácticos y que presentan riesgos fatales o episodios menos graves de asma en algunos individuos susceptibles. Esta sensibilidad al sulfito se observa con mayor frecuencia en individuos asmáticos que en no asmáticos. Antes del procedimiento se le debe advertir al paciente sobre la posibilidad de pérdida transitoria de la sensibilidad y de la función muscular después de las infiltraciones y bloqueos nerviosos. En pediatría o en pacientes con algún disturbio mental se debe advertir a los responsables de la observación del paciente a fin de evitar traumas labiales. 8. Uso en ancianos, niños y otros grupos de riesgo. En pacientes ancianos, cuyas funciones metabólicas, renales y hepáticas generalmente se encuentran debilitadas, se debe tener el cuidado de administrar la menor dosis necesaria y suficiente para proporcionar una anestesia específica y eficaz. En pacientes con disfunción hepática y/o disfunción renal y en pacientes asmáticos, MEPIADRE se debe administrar con cautela. Los pacientes con hipertensión arterial, enfermedades coronarias o cardiovasculares (principalmente si están relacionados con una secuela de fiebre reumática aguda) deben evitar el uso de anestésicos que contienen vasoconstrictores, como MEPIADRE . En pacientes con enfermedad vascular periférica existe un pequeño riesgo de isquemia o necrosis local causada por los vasoconstrictores. Todavía no se cuenta con estudios adecuados y bien controlados en mujeres embarazadas y además, los estudios sobre reproducción en animales no siempre consiguen predecir la respuesta en humanos. Todavía no se dispone de datos sobre la posible excreción de la mepivacaína a través de la leche humana y, como muchos fármacos se excretan por esa vía, se recomienda cuidado especial cuando se administra MEPIADRE a mujeres lactantes. El uso en niños menores de 10 años debe obedecer las recomendaciones del ítem Posología descrito anteriormente. Aún no se han determinado los datos de seguridad y eficacia correspondientes a los pacientes pediátricos menores de 3 años, por tal motivo se recomienda que no se les administre el producto. 9. Interacciones medicamentosas Segundo estudios de P. Henry e J. Van der Driesche, del Laboratorio de Farmacología del Centro Hospitalario de la Universidad de Rennes, el uso de anestésicos locales asociado al consumo de alcohol y de medicamentos tranquilizantes interfiere directamente en la eficiencia del anestésico ya sea aumentando o disminuyendo su tiempo de acción o afectando su potencia. MEPIADRE no se debe usar en pacientes que hagan uso de medicamentos que provocan alteraciones de la presión arterial como inhibidores de la monoaminooxidase (MAO), antidepresivos tricíclicos y fenotiacinas. Pueden ocurrir serias arritmias cardíacas si se emplean preparaciones con vasoconstrictores durante o después de la administración de halotano, tricloroetileno, ciclopropano o cloroformo. La administración simultánea de fármacos vasopresores y de drogas oxitócicas del tipo ergot puede causar hipertensión severa persistente o accidentes vasculares cerebrales. COMPOSITION: Each mL of the injectable solution of MEPIADRE contains: Mepivacaine Hydrochloride ... ................................. 20.0 mg Epinephrine ...............................................................10.0 µg Excipients e.f .......................................................... ...1.0 mL Excipients: Sodium Chloride, Potassium Metabisulfite, EDTA Disodium Salt and Water for Injection. Content: 50 cartridges. 10.Acciones adversas a medicamentos Los efectos colaterales son similares a los observados con otros anestésicos locales del tipo amida. Las acciones adversas, en general, están relacionadas con la dosificación y pueden resultar de altos niveles plasmáticos causados por dosis excesiva, absorción rápida o inyección intravascular accidental; también pueden ser el resultado de hipersensibilidad, idiosincrasia o tolerancia reducida por parte del paciente. Pueden ocurrir efectos sobre el sistema cardiovascular y el SNC. Las manifestaciones del SNC pueden ser de excitación o depresión, como fotofobia, nerviosismo, aprensión, euforia, confusión, mareos, somnolencia, zumbidos, visión borrosa, vómitos, sensación de calor, frío, hormigueo, temblores, pérdida de la conciencia, depresión y parada respiratoria. Las manifestaciones cardiovasculares normalmente son de depresión del sistema y caracterizadas por bradicardia, hipotensión y colapso cardiovascular, que pueden conducir a una parada cardíaca. Las señales y los síntomas de una función cardiovascular deprimida comúnmente pueden ser el resultado de una reacción vasovagal pero, eventualmente, pueden ser el resultado de un efecto directo de la droga. La somnolencia después de la administración de mepivacaína normalmente es la primera señal de que existe un alto nivel del fármaco en la sangre; puede ser consecuencia de la rápida absorción. Los tratamientos de auxilio para estas manifestaciones deben estar a la mano del profesional para el caso de que sea necesario actuar rápidamente. Se debe disponer para uso inmediato de equipos de reanimación, oxígeno u otras drogas para este tipo de emergencia. Prácticamente no se conocen casos de alergia a los anestésicos locales del tipo amida; a pesar de que sean factibles son extremamente raras las reacciones alérgicas documentadas y reproducibles. Las manifestaciones alérgicas suaves se caracterizan por lesiones cutáneas, urticaria, edema. Las reacciones anafilácticas son sumamente raras. Las manifestaciones neurológicas, por ejemplo deficiencia neurológica persistente, asociadas al uso de anestésicos locales pueden estar relacionadas a la técnica utilizada, la dosis total de anestésico administrada, la vía de administración y las condiciones físicas del paciente. 11. Sobredosis Las reacciones generalizadas del SNC o las reacciones cardiovasculares generalmente están relacionadas con altos niveles plasmáticos por causa de una inyección intravascular accidental o sobredosis. (Ver Advertencias y Acciones Adversas ). Las primeras señales y síntomas de la intoxicación por mepivacaína pueden incluir somnolencia, que puede causar pérdida de la conciencia y parada respiratoria. En estos casos se debe proceder de la siguiente manera: - Coloque al paciente en posición supina. Levántele las piernas con una inclinación de 30° a 45º sobre la horizontal. - Asegúrese de que haya pasaje de aire. Si la ventilación es inadecuada, ventile al paciente con oxígeno (si es posible). - Si el pulso está bajo (< 40) o no lo puede determinar, comience a hacerle un masaje cardíaco externo. - El tratamiento de auxilio de la deficiencia circulatoria puede necesitar la administración de líquidos por vía intravenosa (suero). 12.Almacenamiento El producto se debe conservar en su embalaje original al abrigo de la 0 luz. Se debe evitar el calor excesivo (temperatura superior a 40 C). El plazo de validez del producto es de 24 meses, contados a partir de la fecha de fabricación. VENTA BAJO PRESCRIPCIÓN MÉDICA PRODUCTO DE USO EXCLUSIVAMENTE PROFESIONAL MEPIADRE mepivacaine hydrochloride + epinephrine English Pharmaceutical form - Injectable solution Presentation - Box containing 5 blisters with 10 cartridges of 1.8 mLeach Exclusively for parenterally use by means of nerve blockade or infiltration injection FORADULTAND/OR PEDIATRIC USE THE USE BY CHILDREN UNDER 3 YEARS OLD IS NOT RECOMENDED. CHECK THE DOSAGE TABLE IN POSOLOGY. ASK YOUR PATIENT TO INFORM ABOUT THE OCCURRENCE OF ANY UNDESIRABLE REACTION AFTER THE USE OF MEPIADRE. ASK YOUR PATIENT ABOUT OTHER DRUGS THAT HE MIGHT BE USING. MEPIADRE SHOULD ONLY BE USED IN PREGNANT WOMEN AND IN NURSING MOTHERS WITH THE GUIDANCE OF THE HEALTH CARE PROFESSIONAL IN CHARGE. KEEP THE PRODUCT IN ITS ORIGINAL PACKAGE . PROTECT FROM LIGHT. AVOID EXCESSIVE HEAT 0 (TEMPERATURES ABOVE 40 C ). DO NOT USE THIS PRODUCT IF SHELF-LIFE HAD EXPIRED. BEFORE USE, OBSERVE THE PRODUCT´S ASPECT. PARTIALLY USED CARTRIDGES SHOULD NOT BE REUSED. EVERY DRUG SHOULD BE KEPT OUT OF THE REACH OF CHILDREN. TECHNICAL INFORMATION FOR THE HEALTH CARE PROFESSIONALS 1. Pharmacological characteristics Mepivacaine Hydrochloride Classification: Amide Chemical Formula: 1-methyl-2´,6´-pipecoloxilidide Hydrochloride. Potency: 2 (procaine = 1; lidocaine = 2). Toxicity: 1.5 to 2 (procaine = 1; lidocaine = 2). Absorption: The absorption of mepivacaine is complete following parenteral administration, its rate of absorption depending upon various factors, such as the site of injection and the presence or absence of a vasoconstrictor agent. Action Mechanism: Mepivacaine hydrochloride stabilizes the neuronal membrane by inhibiting the ionic flow that is necessary to the start and conduction of the impulses, causing a local anesthetic effect. Metabolism: Mepivacaine, because of its amide structure, is not detoxified by the circulating plasma esterases. The liver is the principal site of metabolism, which occurs through the action of microsomal fixed-function oxidases, with over 50 per cent of the administered dose being excreted into the bile as metabolites. Hydroxylation and N-demethylation play important roles in the metabolism of mepivacaine. Excretion: Mepivacaine hydrochloride is excre ted via the kidneys, with approximately 1 to 16% of anesthetic dose excreted unchanged. Most of the anaesthetic and its metabolites are eliminated within 30 hours. Epinephrine Other chemical names:Adrenaline It is a sympathomimetic amine, being chemically recognized as 3,4-dihydroxi (methylamino) methyl benzilic alcohol. It acts on both alpha and beta-adrenergic receptors, where beta effects predominate. It has been used in minimal concentrations which permit a prolonged anaesthetic effect, necessary for lengthy surgical interventions or where major bleeding occurs. 2. Efficacy Results Clinical trials have been evaluated and testified the capacity of the anesthetics to block the conduction in the axons of the peripheral nervous system (Friedman PM and others: Comparative study of the efficacy of four topical anesthetics , Dermatol Surg 25:12, 1999/ Buckley, J.A.; Ciancio, S.G.; Mc Mullen, J.A.: Efficacy of epinephrine concentration in local anesthesia during periodontal surgery , J. Periodontol 55:653-657, 1984/Covino BG: Clinical Pharmacology of local anesthetic agents . In Cousins MJ, Bridenbaugh PO, editors : Neural blockade in clinical anesthesia and nd management of pain , 2 ed, Philadelphia, 1988, JB Lippincott) and its efficacy in provide anesthesia when associated to several vasoconstrictor (Jacob, W.: Local anaesthesia and vasoconstrictive additional components , Newslett Int Fed Dent Anesthesiol Soc 2(1):3, 1989/Bennett, C.R.: Monheim's local anesthesia and pain control in dental practice , ed 7, St. Louis, 1983, Mosby-Year Book). 3. Indications The use of MEPIADRE is indicated for local anesthesia by nerve blockade or infiltration, for general procedures, multiple extractions, immediate prosthesis and endodontic procedures. MEPIADRE onset of action is rapid (30 to 2 minutes in the upper jaw and 1 to 4 minutes in the lower jaw). Pulpal anesthesia of aproximately 60 minutes´ duration and soft tissue anesthesia of 3 to 5 hours are to be expected. Epinephrine is included with the anaesthetic in order to achieve a deeper and more prolonged anesthesia, by localizing the solution at the site of the injection and intensifying and prolonging the anaesthetic effect and decreasing the rate at which the anaesthetic drug enters the systemic circulation. The presence of a vasoconstrictor also decreases surgical hemorrhage in the immediate area of injection. 4. Contraindications MEPIADRE is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type or to any other substance present in formula and in patients receiving drugs known to produce blood pressure alterations, as MAO inhibitors, tricyclic antidepressants and phenothiazines. Caution should be exercised when MEPIADRE is used in pregnant or nursing mothers or in asthmatic patients (See Warnings ). 5.Administration and storage conditions after opening cartridge This product is intended exclusively for professional use. The recommended specific techniques and procedures of local anesthesia in the oral cavity should be used. MEPIADRE should be kept in its original package, protected from light and excessive heat (temperatures above 40°C). Partially used cartridges should not be reused. It is recommended that chemical disinfection of the cartridge cap be accomplished by wiping it thoroughly with a pledget of cotton that has been moistened with 70% ethyl alcohol just prior to use. Immersion is not recommended. During administration, it is recommended to perform a slight aspiration in order to avoid the risks of an undesirable intravascular injection. If blood is aspirated, the needle must be repositioned until no return of blood can be elicited by aspiration. Note, however, that the absence of blood in the syringe does not assure that intravascular injection will be avoided and a double aspiration is always recommended. Local anaesthetic procedures should be used with caution when there is inflammation and/or sepsis in the region of the proposed injection. MEPIADRE should not be injected repeatedly at the same site because reduced blood flow and increased oxygen consumption in the affected tissues may cause tissue anoxia, delay healing, edema or necrosis at the injection site. 6. Dosage As occurs with all local anesthetics, dosages vary and depend on the area to be anesthetized, the vascularity of tissues, the number of nerve segments to be blocked, the individual tolerance and the technique of anesthesia. The least volume of injection that results in effective local anesthesia should be administered. The necessary dosage must be determined on an individual basis. The maximum dose recommended by Stanley F. Malamed in his th book “Manual of Local Anesthesia, 5 edition”, is 4.4 mg/kg, without exceeding 300 mg (the equivalent to 8 cartridges of MEPIADRE), for adults or children. The maximum dose recommended for children with less than 10 years, with normal lean body mass and normal body development, should be determined by the application of one of the standard pediatric drug formulas (e.g., Clark's rule). The maximum recommended dosage for epinephrine-sensitive patients, such as ASA III and ASA IV and clinically hyperthyroid patients, is 0.04 mg of epinephrine (2 cartridges of MEPIADRE ) per appointment. For routine work, 1 cartridge of MEPIADRE is usually enough. During administration, it is recommended to perform a slight aspiration in order to avoid the risks of intravenous injection. Maximum dose: 4.4 mg of mepivacaine hydrochloride/kg (Each 1.8 mL cartridge contains 36 mg of mepivacaine hydrochloride + 0.018 mg of epinephrine) Weight (Kg) 10 20 30 40 50 60 70 80 90 100 Number of Cartridges of MEPIADRE 1 2 3.5 4.5 6 7 8 8 8 8 Doses indicated are the maximum suggested for normal healthy individuals: they should be decreased for debilitated or elderly patients. 7. Warnings The safety and efficacy of local anesthetics depend on the recommended dosage, the correct technique, on a previously done anamnesis, on the adequate precautions and on the quickness and skill of the Professional in the intervention of emergency cases. The low est dose that results in effective anesthesia should be used. The frequent administration of the product may cause a rise in the plasmatic levels due to the slow metabolic degradation. The tolerance may vary according to the patient's state, children since weakened patients, with advanced age and serious disease patients must have reduced dosages administered, according to their age and physical conditions. Special care is recommended for frequent administration in patients with liver or kidney disturbances, since the metabolism in these patients will be compromised. Special attention should be taken in the administration of local anesthetics to patients with a history of sensitivity or allergy to the components of the formula. Serious cardiac arrhythmia may occur if preparations containing vasoconstrictors are used in patients during or after the administration of halotane, trichloroethylene, cyclopropane or chloroform. In patients with peripheral vascular disease, there is a little potential risk that vasoconstrictors cause ischemic injury or local necrosis. The presence of Sodium Metabisulfite in the formula must be taken into account when treating patients who are susceptible to asthma. This sensitivity to sulfite is more commonly observed in asthmatic individuals rather than in non-asthmatics. The patient must be previously informed of the possibility of temporary loss of sensitivity and muscle function, after infiltrations and nerve blocks. Parents should be advised, as well as people liable for patients with mental disturbance, to observe them, in order to avoid possible inadvertent trauma to the lips. 8. Use in elderly, children and other risk groups In elderly patients, in whom the metabolic, renal and hepatic functions are usually decreased, care must be taken in terms of administering the smallest necessary dose that is enough for providing a specific kind of anesthesia. Care should be taken in the use of MEPIADRE in patients with liver or kidney problems and in patients susceptible to asthma. Patients with hypertension, coronary or cardiovascular problems (particularly related to sequela of acute rheumatic fever), must avoid the use of anesthetics containing vasoconstrictors as MEPIADRE . In patients with peripheral vascular disease, there is a little potential risk that vasoconstrictors cause ischemic injury or local necrosis. There are no adequate and well-controlled studies in pregnant women and animal reproduction studies are not always predictive of human response. It is not known whether mepivacaine is excreted in human milk and, because many drugs are excreted this way, caution should be exercised when MEPIADRE is administered to nursing mothers. The use in children under 10 years old should follow the recommendations described previously in Dosage. Safety and effectiveness in pediatric patients below 4 years have not been established, therefore the use of this drug in these patients is not recommended. 9. Drug Interactions According to studies undertaken by P. Henry and J. Van der Driessche of the pharmacology laboratory of the Rennes University Hospital Center, the use of local anesthetic associated with the consumption of alcohol and/or tranquilizing medication directly interferes in the efficiency of the anesthetic, potentially increasing or decreasing its time of action and potency. MEPIADRE should not be used in patients in treatment with drugs known to affect blood pressure, as monoamine oxidase inhibitors, tricyclic antidepressants or phenothiazines. Serious cardiac arrhythmia may occur if preparations containing vasoconstrictors are used in patients during or after the administration of halotane, trichloroethylene, cyclopropane or chloroform. Concurrent administration of vasopressor drugs and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. 10.Adverse reactions Side effects following MEPIADRE administration are similar to those observed in other amide-based anesthetics. Adverse reactions are normally the result of high plasma levels caused by excessive dosage, rapid absorption or unintentional intravascular injection, or may result from hypersensitivity, idiosyncrasy, or reduced tolerance on the part of the patient. Effects involving cardiovascular and central nervous systems may occur. Reactions in the CNS are exciting and/or depressing and may be characterized by photo-phobia, irritability, apprehension, euphoria, confusion, dizziness, drowsiness, ringing in the ears, blurred vision, vomiting, burning sensation, cold or numbness, loss of consciousness, respiratory depression and arrest. Cardiovascular reactions are normally depressive and characterized by bradycardia, hypertension and cardiovascular collapse, which may lead to cardiac arrest. Signs and symptoms of a depressed cardiovascular system are commonly the result of a vasovagal reaction but may also be the result of a direct effect of the drug. Drowsiness following the administration of mepivacaine is usually an early sign of a high blood level of the drug and may occur as a consequence of rapid absorption. The health care professional should have support treatments for these reactions available within easy reach so as to effect a rapid response if, and when, necessary. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use. Allergy to amide local anesthetics is virtually nonexistent; true, documented and reproducible allergic reactions are extremely rare, though possible. Mild allergic reactions may include cutaneous lesions, itchiness and edema. Anaphylactic reactions are extremely rare. Neurological reactions, as persistent neurological deficiency, associated with the use of local anesthetics may be related to the technique used, the total dose of anesthetic administered, the route of administration and the patient's physical condition. 11. Overdose Generalized reactions in the central nervous system or cardiovascular reactions are generally related to high plasmatic levels due to accidental intravenous injection or overdose (See Warnings and Ad verse Reactions ). The first signs and symptoms of mepivacaine intoxication can include sleepiness, which can lead to the loss of conscience and respiratory arrest. In these cases the following procedures must be performed: - Place the patient in supine position. Elevate the legs 30° to 45° above the horizontal. - The airway must be assured. If ventilation is inadequate, ventilate the patient with oxygen, if possible. - If the pulse is low (< 40) or non determinable, begin external heart massage. - Support treatment for circulatory impairment can request the administration of parenteral solutions (serum). 12. Storage conditions This product should be kept in its original package and protected from 0 light. Excessive heat (temperatures above 40 C ) must be avoided. The expiry date of this product is equivalent to 24 months after manufacturing date. Fabricado e distribuído por/Fabricado y distribuido por/Manufactured and distributed by: Estrada do Guerenguê, 2059 Rio de Janeiro - RJ - Brasil CEP : 22713-002 CNPJ: 33112665/0001-46 Indústria Brasileira/ Industria Brasileña/ Made in Brazil SAC: 0800 602 68 80 Fax: 55-21-3342-4009 www.dfl.com.br - [email protected] Farmacêutico responsável Farmacéutico responsable/Pharmacist in charge: o Evaldo Rodrigues de Oliveira CRF - RJ N 2897 o ANVISA/MS N : 101770022 Número do lote, data de fabricação e prazo de validade: Vide cartucho. Número do lote, fecha de fabricación y validez (mes/año): Ver el cartucho. Lot #, manufacturing date and expire date: See product box. Rev. 04