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Description
Composition Glimepiride 3 mg Auxiliary substances: lactose monohydrate - 136.95 mg, sodium carboxymethyl starch (type A) - 8 mg, povidone 25 000 - 1 mg, microcrystalline cellulose - 20 mg, magnesium stearate - 1 mg, iron dye yellow oxide (E172) - 0.05 mg. Pharmacological action: Oral hypoglycemic drug is a derivative of the third generation sulfonylurea. Glimepiride reduces the concentration of glucose in the blood, mainly due to the stimulation of the release of insulin from the pancreas cells. Its effect is mainly related to the improvement in the ability of the pancreas cells to respond to physiological stimulation with glucose. Compared to glibenclamide, glimepiride in low doses causes the release of a smaller amount of insulin when approximately the same decrease in blood glucose concentration is achieved. This fact argues in favor of the presence of extrapancreatic hypoglycemic effects in glimepiride (increased sensitivity of tissues to insulin and insulinomimetic effect). Insulin secretion. Like all other sulfonylurea derivatives, glimepiride regulates insulin secretion by interacting with ATP-sensitive potassium channels on the membranes of &. 946. -Cells. Unlike other sulfonylurea derivatives, glimepiride selectively binds to a protein with a molecular mass of 65 kilodalton, located in the membranes of pancreatic cells. This interaction of glimepiride with a protein that binds to it regulates the opening or closing of ATP-sensitive potassium channels. Glimepiride closes potassium channels. This causes depolarization of the & # 946. -Cell and leads to the opening of voltage-sensitive calcium channels and the entry of calcium into the cell. As a result, an increase in intracellular calcium concentration activates insulin secretion by exocytosis. Glimepiride is much faster and, accordingly, more often forms a bond and is released from the bond with the protein bound to it than glibenclamide. It is assumed that this property of the high rate of exchange of glimepiride with a protein binding to it causes its pronounced effect of sensitization of glucose to cells and their protection against desensitization and premature depletion.The effect of increasing the sensitivity of tissues to insulin. Glimepiride enhances the effects of insulin on glucose uptake by peripheral tissues. Insulinomimetic effect. Glimepiride has effects similar to those of insulin on the uptake of glucose by peripheral tissues and the release of glucose from the liver. Glucose uptake by peripheral tissues is carried out by its transport inside the muscle cells and adipocytes. Glimepiride directly increases the number of molecules transporting glucose in plasma membranes of muscle cells and adipocytes. An increase in the ingestion of glucose cells leads to the activation of glycosylphosphatidylinositol-specific phospholipase C. As a result, the intracellular calcium concentration decreases, causing a decrease in the activity of protein kinase A, which in turn leads to the stimulation of glucose metabolism. Glimepiride inhibits the release of glucose from the liver by increasing the concentration of fructose-2,6-bisphosphate, which inhibits gluconeogenesis. Effect on platelet aggregation. Glimepiride reduces platelet aggregation in vitro and in vivo. This effect appears to be associated with selective inhibition of COX, which is responsible for the formation of thromboxane A, an important endogenous platelet aggregation factor. Antiatherogenic action. Glimepiride contributes to the normalization of lipids, reduces the level of malondialdehyde in the blood, which leads to a significant decrease in lipid peroxidation. In animals, glimepiride leads to a significant decrease in the formation of atherosclerotic plaques. Reducing the severity of oxidative stress, which is constantly present in patients with type 2 diabetes. Glimepiride increases the level of endogenous.-Tocopherol, the activity of catalase, glutathione peroxidase and superoxide dismutase. Cardiovascular effects. Through the ATP-sensitive potassium channels, sulfonylurea derivatives also affect the cardiovascular system. Compared with traditional sulfonylurea derivatives, glimepiride has a significantly lower effect on the cardiovascular system, which can be explained by the specific nature of its interaction with the ATP-sensitive potassium channel that binds to it.In healthy volunteers, the minimum effective dose of glimepiride is 0.6 mg. The effect of glimepiride is dose-dependent and reproducible. The physiological response to physical activity (decrease in insulin secretion) while taking glimepiride persists. There are no significant differences in effect, depending on whether the drug was taken 30 minutes before a meal or just before a meal. In patients with diabetes mellitus, sufficient metabolic control can be achieved within 24 hours with a single dose of the drug. Moreover, in a clinical study, in 12 of 16 patients with renal insufficiency (CC 4–79 ml / min), sufficient metabolic control was also achieved. Combination therapy with metformin. In patients with insufficient metabolic control when using the maximum dose of glimepiride, combination therapy with glimepiride and metformin can be initiated. Two studies in combination therapy have shown an improvement in metabolic control compared with that in the treatment of each of these drugs separately. Combination therapy with insulin. In patients with insufficient metabolic control while taking glimepiride in maximum doses, simultaneous insulin therapy can be initiated. According to the results of two studies with the use of this combination, the same improvement in metabolic control is achieved as with the use of only one insulin. However, a lower dose of insulin is required in combination therapy.
Dosage and administration
Typically, the dose of the drug Amaryl. determined by the target concentration of glucose in the blood. The drug should be used in a minimum dose, sufficient to achieve the necessary metabolic control. During treatment with Amaryl. you must regularly determine the level of glucose in the blood. In addition, it is recommended to regularly monitor the level of glycated hemoglobin. Violation of the drug, for example, skipping the reception of the next dose should not be replenished by the subsequent administration of the drug at a higher dose. The physician should instruct the patient in advance about the actions that should be taken in case of errors in taking Amaryl. (in particular when skipping a regular dose or skipping a meal), or in situations where it is not possible to take the drug. Tablets drug Amaryl. should be taken whole without chewing, drinking plenty of liquid (about 1/2 cup).If necessary, the drug pills Amaryl. can be divided along risks into two equal parts. The initial dose of Amaryl. is 1 mg 1 time / day. If necessary, the daily dose can be gradually increased (at intervals of 1-2 weeks) under the regular control of blood glucose and in the following order: 1 mg-2 mg-3 mg-4 mg-6 mg (-8 mg) per day . In patients with well-controlled diabetes mellitus type 2 daily dose of the drug is usually 1-4 mg. A daily dose of more than 6 mg is more effective in only a small number of patients. The time of taking the drug Amaryl. and the distribution of doses throughout the day, the doctor determines, taking into account the lifestyle of the patient (meal time, amount of physical activity). The daily dose is prescribed in 1 reception, as a rule, immediately before a full breakfast or, if the daily dose was not taken, immediately before the first main meal. It is very important after taking the pills Amaryl. Do not skip meals. Since Improved metabolic control is associated with increased insulin sensitivity, and during treatment it is possible to reduce the need for glimepiride. In order to avoid the development of hypoglycemia, it is necessary to reduce the dose in a timely manner or stop taking Amaryl. Conditions in which dose adjustment of glimepiride may also be required: - weight loss. - lifestyle changes (change in diet, meal times, amount of physical activity). - the occurrence of other factors that lead to susceptibility to the development of hypoglycemia or hyperglycemia. Treatment with glimepiride is usually long-term. Transferring a patient from taking another oral hypoglycemic drug to taking Amaryl. There is no exact relationship between doses of the drug Amaryl. and other oral hypoglycemic drugs. When transferring from such drugs to Amaryl. The recommended initial daily dose of the latter is 1 mg (even if the patient is transferred to Amaryl. from the maximum dose of another oral hypoglycemic drug). Any dose increase should be carried out in stages, taking into account the reaction to glimepiride in accordance with the above recommendations.It is necessary to take into account the intensity and duration of the effect of the previous hypoglycemic agent. Interruption of treatment may be required to avoid an additive effect that increases the risk of hypoglycemia. Use in combination with metformin In patients with insufficiently controlled diabetes mellitus, when taking glimepiride or metformin at maximum daily doses, treatment can be initiated with a combination of these two drugs. In this case, earlier treatment with either glimepiride or metformin continues at the same doses, and the additional administration of metformin or glimepiride is started from a low dose, which is then titrated depending on the target level of metabolic control, up to the maximum daily dose. Combination therapy should be started under strict medical supervision. Use in combination with insulin Patients with insufficiently controlled diabetes mellitus while taking glimepiride in the maximum daily dose can be simultaneously assigned insulin. In this case, the last dose of glimepiride assigned to the patient remains unchanged. In this case, insulin treatment begins with low doses, which gradually increase under the control of the concentration of glucose in the blood. Combined treatment is carried out under careful medical supervision. Patients with impaired renal function may be more sensitive to the hypoglycemic effect of glimepiride. Data on the use of the drug Amaryl. in patients with renal failure are limited. Data on the use of the drug Amaryl. in patients with hepatic insufficiency are limited. Precautions During the period of treatment may worsen psoriasis. With pheochromocytoma, propranolol can be used only after taking an alpha blocker. After a long course of treatment, propranolol should be discontinued gradually, under the supervision of a physician. Against the background of treatment with propranolol, IV administration of verapamil, diltiazem should be avoided. A few days before anesthesia, you must stop taking propranolol or pick up a remedy for anesthesia with minimal negative inotropic effects. Influence on the ability to drive vehicles and control mechanisms In patients whose activities require increased attention, the question of the use of propranolol on an outpatient basis should be addressed only after evaluating the individual response of the patient.Side effect On the part of the metabolism: hypoglycemia is possible, which, as with the use of other sulfonylurea derivatives, can be prolonged. Symptoms of hypoglycemia - headache, hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, anxiety, aggressiveness, impaired concentration, alertness and reaction rate, depression, confusion, speech disorders, aphasia, visual disorders, tremor, paresis , sensory disturbances, dizziness, loss of self-control, delirium, cerebral seizures, drowsiness or loss of consciousness up to coma, shallow breathing, bradycardia. In addition, there may be manifestations of adrenergic counter-regulation in response to hypoglycemia, such as cold sticky sweat, anxiety, tachycardia, arterial hypertension, angina pectoris, palpitations, and heart rhythm disturbances. The clinical picture of severe hypoglycemia may resemble a stroke. Symptoms of hypoglycemia almost always disappear after its elimination. On the part of the organ of vision: transient visual disturbances due to a change in glucose concentration in the blood are possible (especially at the beginning of treatment). They are caused by a temporary change in the swelling of the lens, depending on the concentration of glucose in the blood, and thus the change in the index of refraction of the lens. On the part of the digestive system: rarely - nausea, vomiting, feeling of heaviness or fullness in the epigastrium, abdominal pain, diarrhea. in some cases, hepatitis, increased activity of liver enzymes and / or cholestasis and jaundice, which can progress to life-threatening liver failure, but may be reversed when the drug is withdrawn. From the hematopoietic system: rarely - thrombocytopenia. in some cases, leukopenia, hemolytic anemia, erythrocytopenia, granulocytopenia, agranulocytosis and pancytopenia. When postmarketing use of the drug was reported cases of severe thrombocytopenia with platelet count <10 000 / μl and thrombocytopenic purpura (frequency unknown). Allergic reactions: rarely - allergic and pseudo-allergic reactions, such as itching, urticaria, skin rash.Such reactions almost always have a mild form, but can turn into severe reactions with shortness of breath, a sharp decrease in blood pressure, which sometimes progresses to anaphylactic shock. in some cases, allergic vasculitis. Other: in some cases - hyponatremia, photosensitivity. If you experience symptoms of urticaria, you should immediately consult a doctor. Specific guidance In particular clinical stressful conditions, such as trauma, surgery, infections with febrile temperature, metabolic control may be worsened in patients with diabetes, therefore a temporary transfer to insulin therapy may be required to maintain adequate metabolic control. In the first weeks of treatment, there may be an increased risk of hypoglycemia, which requires particularly careful monitoring of the concentration of glucose in the blood. Factors contributing to the risk of hypoglycemia include: - The patient's unwillingness or inability (more often observed in elderly patients) to cooperate with a doctor. - malnutrition, irregular food intake or missed meals. - an imbalance between exercise and carbohydrate intake. - change in diet. - the use of alcohol, especially in combination with skipping meals. - Severe renal dysfunction. - severe liver dysfunction (in patients with severe liver dysfunction, an insulin therapy is indicated, at least until metabolic control is achieved). - overdose glimepirida. - some decompensated endocrine disorders that disturb carbohydrate metabolism or adrenergic counterregulation in response to hypoglycemia (for example, some dysfunction of the thyroid gland and the anterior pituitary, adrenal insufficiency). - simultaneous intake of certain drugs. - reception of glimepiride in the absence of indications for its reception. Treatment of sulfonylurea derivatives, which include glimepiride, can lead to the development of hemolytic anemia, therefore, in patients with glucose deficiency 6-phosphate dehydrogenase, special care should be taken when prescribing glimepiride, it is preferable to use hypoglycemic agents that are not sulfonylurea derivatives.In the case of the above risk factors for the development of hypoglycemia, as well as in case of intercurrent diseases during treatment or a change in the patient's lifestyle, a dose adjustment of glimepiride or the whole therapy may be required. Symptoms of hypoglycemia resulting from adrenergic counter-regulation of the body in response to hypoglycemia may be mild or absent with the gradual development of hypoglycemia, in elderly patients, patients with disorders of the autonomic nervous system or in patients receiving beta-adrenoblockers, clonidine, reserpine , guanethidine and other sympatholytic drugs. Hypoglycemia can be quickly eliminated by immediately taking fast-digesting carbohydrates (glucose or sucrose). As with the intake of other sulfonylurea derivatives, despite initial successful relief of hypoglycemia, hypoglycemia can resume. Therefore, patients should remain under constant surveillance. In severe hypoglycemia, immediate treatment and observation by a physician is required, and in some cases hospitalization of the patient. During treatment with glimepiride, regular monitoring of liver function and a picture of peripheral blood (especially the number of leukocytes and platelets) is required. Such side effects as severe hypoglycemia, serious changes in the blood picture, severe allergic reactions, liver failure can be life threatening, therefore, if such reactions develop, the patient should immediately inform the attending physician about them, stop taking the drug and not resume taking it without a doctor's recommendation . Use in pediatrics Data on the long-term efficacy and safety of the drug in children are not available. Influence on the ability to drive motor vehicles and control mechanisms At the beginning of treatment, after changing treatment or when taking glimepiride irregularly, there may be a decrease in attention concentration and psychomotor reactions caused by hypo- or hyperglycemia. This may adversely affect the ability to drive motor vehicles or to control various machines and mechanisms. Use during pregnancy and breastfeeding Amaryl. contraindicated in pregnancy.In the case of a planned pregnancy or pregnancy, a woman should be transferred to insulin therapy. It is established that glimepiride is excreted in breast milk. During lactation, you should transfer a woman to insulin or stop breastfeeding. Type: Medicine Quantity in packaging, pcs: 90 Shelf life: 36 months Scope of application: Endocrinology Active ingredient: Glimepiride (Glimepiride) Route of administration: Oral Vacation schedule: Prescription Release form: Prescription Storage conditions: In a dry place, In a protected from sun indoors, Keep away from children Maximum permissible storage temperature, ° C: 30 Pharmacological group: A10BB12 Glimepiride Minimum age: 18 yearsActive ingredients
Release form
Pills
Composition
Glimepiride 3 mg Auxiliary substances: lactose monohydrate - 136.95 mg, sodium carboxymethyl starch (type A) - 8 mg, povidone 25 000 - 1 mg, microcrystalline cellulose - 20 mg, magnesium stearate - 1 mg, iron dye yellow oxide (E172) - 0.05 mg.
Pharmacological effect
Oral hypoglycemic drug is a third generation sulfonylurea derivative. Glimepiride reduces the concentration of glucose in the blood, mainly due to the stimulation of the release of insulin from the pancreas cells. Its effect is mainly related to the improvement in the ability of the pancreas cells to respond to physiological stimulation with glucose. Compared to glibenclamide, glimepiride in low doses causes the release of a smaller amount of insulin when approximately the same decrease in blood glucose concentration is achieved. This fact argues in favor of the presence of extrapancreatic hypoglycemic effects in glimepiride (increased sensitivity of tissues to insulin and insulinomimetic effect). Insulin secretion. Like all other sulfonylurea derivatives, glimepiride regulates insulin secretion by interacting with ATP-sensitive potassium channels on the membranes of &. 946. -Cells. Unlike other sulfonylurea derivatives, glimepiride selectively binds to a protein with a molecular mass of 65 kilodalton, located in the membranes of pancreatic cells. This interaction of glimepiride with a protein that binds to it regulates the opening or closing of ATP-sensitive potassium channels. Glimepiride closes potassium channels. This causes depolarization of the & # 946. -Cell and leads to the opening of voltage-sensitive calcium channels and the entry of calcium into the cell.As a result, an increase in intracellular calcium concentration activates insulin secretion by exocytosis. Glimepiride is much faster and, accordingly, more often forms a bond and is released from the bond with the protein bound to it than glibenclamide. It is assumed that this property of the high rate of exchange of glimepiride with a protein binding to it causes its pronounced effect of sensitization of glucose to cells and their protection against desensitization and premature depletion. The effect of increasing the sensitivity of tissues to insulin. Glimepiride enhances the effects of insulin on glucose uptake by peripheral tissues. Insulinomimetic effect. Glimepiride has effects similar to those of insulin on the uptake of glucose by peripheral tissues and the release of glucose from the liver. Glucose uptake by peripheral tissues is carried out by its transport inside the muscle cells and adipocytes. Glimepiride directly increases the number of molecules transporting glucose in plasma membranes of muscle cells and adipocytes. An increase in the ingestion of glucose cells leads to the activation of glycosylphosphatidylinositol-specific phospholipase C. As a result, the intracellular calcium concentration decreases, causing a decrease in the activity of protein kinase A, which in turn leads to the stimulation of glucose metabolism. Glimepiride inhibits the release of glucose from the liver by increasing the concentration of fructose-2,6-bisphosphate, which inhibits gluconeogenesis. Effect on platelet aggregation. Glimepiride reduces platelet aggregation in vitro and in vivo. This effect appears to be associated with selective inhibition of COX, which is responsible for the formation of thromboxane A, an important endogenous platelet aggregation factor. Antiatherogenic action. Glimepiride contributes to the normalization of lipids, reduces the level of malondialdehyde in the blood, which leads to a significant decrease in lipid peroxidation. In animals, glimepiride leads to a significant decrease in the formation of atherosclerotic plaques. Reducing the severity of oxidative stress, which is constantly present in patients with type 2 diabetes. Glimepiride increases endogenous & # 945. -Tocopherol, catalase, glutathione peroxidase and superoxide dismutase activity.Cardiovascular effects. Through the ATP-sensitive potassium channels, sulfonylurea derivatives also affect the cardiovascular system. Compared with traditional sulfonylurea derivatives, glimepiride has a significantly lower effect on the cardiovascular system, which can be explained by the specific nature of its interaction with the ATP-sensitive potassium channel that binds to it. In healthy volunteers, the minimum effective dose of glimepiride is 0.6 mg. The effect of glimepiride is dose-dependent and reproducible. The physiological response to physical activity (decrease in insulin secretion) while taking glimepiride persists. There are no significant differences in effect, depending on whether the drug was taken 30 minutes before a meal or just before a meal. In patients with diabetes mellitus, sufficient metabolic control can be achieved within 24 hours with a single dose of the drug. Moreover, in a clinical study, in 12 of 16 patients with renal insufficiency (CC 4–79 ml / min), sufficient metabolic control was also achieved. Combination therapy with metformin. In patients with insufficient metabolic control when using the maximum dose of glimepiride, combination therapy with glimepiride and metformin can be initiated. Two studies in combination therapy have shown an improvement in metabolic control compared with that in the treatment of each of these drugs separately. Combination therapy with insulin. In patients with insufficient metabolic control while taking glimepiride in maximum doses, simultaneous insulin therapy can be initiated. According to the results of two studies with the use of this combination, the same improvement in metabolic control is achieved as with the use of only one insulin. However, a lower dose of insulin is required in combination therapy.
Indications
- diabetes mellitus type 2 (as monotherapy or as part of combination therapy with metformin or insulin).
Contraindications
- diabetes mellitus type 1. - diabetic ketoacidosis, diabetic precoma and coma. - severe violations of the liver (no clinical experience with the application). - severe renal dysfunction, incl.patients on hemodialysis (lack of clinical experience). - pregnancy. - lactation (breastfeeding). - children's age (lack of clinical experience). - rare inherited diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption. - hypersensitivity to the drug. - Hypersensitivity to other sulfonylurea derivatives and sulfa drugs (risk of hypersensitivity reactions). With caution should use the drug in the first weeks of treatment (increased risk of hypoglycemia). if there are risk factors for the development of hypoglycemia (may require a dose adjustment of glimepiride or the whole therapy). with intercurrent diseases during treatment or with a change in the lifestyle of patients (change in diet and meal times, increase or decrease in physical activity). in case of insufficiency of glucose-6-phosphate dehydrogenase. in violation of the absorption of food and medicines from the gastrointestinal tract (intestinal obstruction, intestinal paresis).
Use during pregnancy and lactation
Amaril. contraindicated in pregnancy. In the case of a planned pregnancy or pregnancy, a woman should be transferred to insulin therapy. It is established that glimepiride is excreted in breast milk. During lactation, you should transfer a woman to insulin or stop breastfeeding.
Dosage and administration
As a rule, the dose of the drug Amaryl. determined by the target concentration of glucose in the blood. The drug should be used in a minimum dose, sufficient to achieve the necessary metabolic control. During treatment with Amaryl. you must regularly determine the level of glucose in the blood. In addition, it is recommended to regularly monitor the level of glycated hemoglobin. Violation of the drug, for example, skipping the reception of the next dose should not be replenished by the subsequent administration of the drug at a higher dose. The physician should instruct the patient in advance about the actions that should be taken in case of errors in taking Amaryl. (in particular when skipping a regular dose or skipping a meal), or in situations where it is not possible to take the drug. Tablets drug Amaryl. should be taken whole without chewing, drinking plenty of liquid (about 1/2 cup).If necessary, the drug pills Amaryl. can be divided along risks into two equal parts. The initial dose of Amaryl. is 1 mg 1 time / day. If necessary, the daily dose can be gradually increased (at intervals of 1-2 weeks) under the regular control of blood glucose and in the following order: 1 mg-2 mg-3 mg-4 mg-6 mg (-8 mg) per day . In patients with well-controlled diabetes mellitus type 2 daily dose of the drug is usually 1-4 mg. A daily dose of more than 6 mg is more effective in only a small number of patients. The time of taking the drug Amaryl. and the distribution of doses throughout the day, the doctor determines, taking into account the lifestyle of the patient (meal time, amount of physical activity). The daily dose is prescribed in 1 reception, as a rule, immediately before a full breakfast or, if the daily dose was not taken, immediately before the first main meal. It is very important after taking the pills Amaryl. Do not skip meals. Since Improved metabolic control is associated with increased insulin sensitivity, and during treatment it is possible to reduce the need for glimepiride. In order to avoid the development of hypoglycemia, it is necessary to reduce the dose in a timely manner or stop taking Amaryl. Conditions in which dose adjustment of glimepiride may also be required: - weight loss. - lifestyle changes (change in diet, meal times, amount of physical activity). - the occurrence of other factors that lead to susceptibility to the development of hypoglycemia or hyperglycemia. Treatment with glimepiride is usually long-term. Transferring a patient from taking another oral hypoglycemic drug to taking Amaryl. There is no exact relationship between doses of the drug Amaryl. and other oral hypoglycemic drugs. When transferring from such drugs to Amaryl. The recommended initial daily dose of the latter is 1 mg (even if the patient is transferred to Amaryl. from the maximum dose of another oral hypoglycemic drug). Any dose increase should be carried out in stages, taking into account the reaction to glimepiride in accordance with the above recommendations.It is necessary to take into account the intensity and duration of the effect of the previous hypoglycemic agent. Interruption of treatment may be required to avoid an additive effect that increases the risk of hypoglycemia. Use in combination with metformin In patients with insufficiently controlled diabetes mellitus, when taking glimepiride or metformin at maximum daily doses, treatment can be initiated with a combination of these two drugs. In this case, earlier treatment with either glimepiride or metformin continues at the same doses, and the additional administration of metformin or glimepiride is started from a low dose, which is then titrated depending on the target level of metabolic control, up to the maximum daily dose. Combination therapy should be started under strict medical supervision. Use in combination with insulin Patients with insufficiently controlled diabetes mellitus while taking glimepiride in the maximum daily dose can be simultaneously assigned insulin. In this case, the last dose of glimepiride assigned to the patient remains unchanged. In this case, insulin treatment begins with low doses, which gradually increase under the control of the concentration of glucose in the blood. Combined treatment is carried out under careful medical supervision. Patients with impaired renal function may be more sensitive to the hypoglycemic effect of glimepiride. Data on the use of the drug Amaryl. in patients with renal failure are limited. Data on pr