Pharmacological action Tegretol XR:
Tegretol XR Antiepileptic drug (a derivative dibenzazepina), also has normotimicheskoe, antimaniakalnoe, antidiuretic (in patients with diabetes insipidus) and analgesic (in patients with neuralgia) effect. The mechanism of action related to the blockade of voltage Na +-channels, which leads to stabilization of the membrane of neurons, inhibition of production and reduction of discharges of neurons of synaptic impulses. Prevents re-formation of Na +-dependent action potentials in depolarized neurons. Reduces the release of excitatory amino acid glutamate neyromediatornoy increases the reduced seizure threshold and thus reduces the risk of epileptic seizure. Increases the conductivity for K +, modulates the voltage-Ca2 +-channels, which can also cause an anticonvulsant drug action. Corrects epileptic personality change and ultimately improves patient communication skills and promote their social rehabilitation. May be appointed as the main therapeutic drugs and in combination with other antiepileptic drugs. Effective with focal (partial) epileptic seizures (simple and complex), accompanied or not accompanied by secondary generalization, with generalized tonic-clonic epileptic seizures, as well as combinations of these types (usually not effective for small seizures – petit mal, myoclonic seizures and absansah) . In patients with epilepsy (particularly in children and adolescents) showed a positive effect on symptoms of anxiety and depression, as well as reducing irritability and aggressiveness. The effect on cognitive function and psychomotor performance depends on the dose and very variable. Start anticonvulsant effect varies from several hours to several days (sometimes up to 1 month due to autoinduktsii metabolism). In essential and secondary trigeminal neuralgia, in most cases, prevents the appearance of pain attacks. Effktiven to relieve neuropathic pain in tabes, post-traumatic paresthesia and postherpetic neuralgia. The weakening of the pain associated with trigeminal neuralgia was after 8-72 h. The alcohol withdrawal syndrome raises the threshold of convulsive readiness (which in this state is usually reduced), and reduces the severity of clinical manifestations of the syndrome (irritability, tremors, gait disturbances). In patients with diabetes insipidus leads to a rapid compensation of the water balance and reduces urine output and thirst. Antipsychotic (antimaniakalnoe), the action develops within 7-10 days, may be due to inhibition of metabolism of dopamine and norepinephrine. Prolonged dosage form maintains more stable concentrations of carbamazepine in the blood without the “peaks” and “failures” that reduces the incidence and severity of potential complications of therapy, to improve the effectiveness of therapy, even when using relatively low doses. Dr. important advantage is the possibility of prolonged form of reception 1-2 times a day.
Uses Tegretol XR:
Epilepsy (except absence seizures, myoclonic seizures, or sluggish) – partial seizures with complex symptomatology and simple, primary and secondary generalized forms of attacks with tonic-clonic seizures, mixed forms of seizures (monotherapy or in combination with other antiepileptic drugs). Idiopathic trigeminal neuralgia, trigeminal neuralgia in multiple sclerosis (typical and atypical), idiopathic neuralgia glossopharyngeal nerve. Acute mania (monotherapy and in combination with drugs of Li + and other antipsychotic drugs). Faznoprotekayuschie affective disorders (including bipolar) prevention of exacerbations, the weakening of clinical manifestations of an exacerbation. Alcohol withdrawal syndrome (anxiety, convulsions, hyperexcitability, sleep disorders). Diabetic neuropathy with pain. Diabetes insipidus of central origin. Polyuria and polydipsia neurohormonal nature. May also be used (evidence based on clinical experience, controlled studies have been conducted): – in psychotic disorders (in affective and schizoaffective disorders, psychosis, panic disorder, treatment-resistant schizophrenia, dysfunction of the limbic system) – the aggressive behavior of patients with organic brain damage, depression, chorea – with anxiety, dysphoria, somatization, tinnitus, senile dementia, Kluwer-Bucy syndrome (bilateral destruction of the amygdala), obsessive-compulsive disorders, benzodiazepine withdrawal, cocaine – in the genesis of neurogenic pain syndrome : in dorsal tabes, multiple sclerosis, acute idiopathic neuritis (Guillain-Barre syndrome), diabetic polyneuropathy, phantom limb pain, syndrome of “restless legs” syndrome (Ekboma), hemifacial spasm, post-traumatic neuropathy and neuralgia, postherpetic neuralgia – for prevention of migraine.
Contraindications Tegretol XR:
Hypersensitivity to carbamazepine or chemically similar drugs (eg tricyclic antidepressants) or any other component of the drug; disorders of bone marrow hematopoiesis (anemia, leukopenia), acute “intermittent” porphyria (including history), AV block, simultaneous inhibitors MAO.C caution. Decompensated heart failure, hyponatremia dilutions (ADH hypersecretion syndrome, hypopituitarism, hypothyroidism, adrenal insufficiency), advanced age, active alcoholism (increased CNS depression, increased metabolism of carbamazepine), inhibition of bone marrow hematopoiesis in patients receiving drugs (history), liver failure, chronic renal failure ; prostatic hyperplasia, increased intraocular pressure.
Side effects Tegretol XR:
In assessing the frequency of occurrence of various adverse reactions used the following grades: very often – 10% and more often, and often – 1-10%, sometimes – 0.1-1%, rare – 0.01-0.1% and very rarely – less 0.01%. Dose-dependent side-effects usually disappear within a few days, both spontaneously and after a temporary reduction in dose. The development of adverse reactions of the CNS may be due to relative overdose of the drug or significant fluctuations in the concentrations of the active substance in plasma. In such cases, monitor the concentration of drug in plasma. Central nervous system: very often – dizziness, ataxia, drowsiness, fatigue, and often – headache, paresis of accommodation, and sometimes – abnormal involuntary movements (eg tremor, “fluttering” tremor – asterixis, dystonia, tics); nystagmus rarely – orofacial dyskinesia , oculomotor disturbances, speech disorders (eg dysarthria), horeoatetoidnye disorders, peripheral neuritis, paresthesia, paresis of myasthenia gravis and symptoms. The role of carbamazepine as the drug that causes or promotes the development of neuroleptic malignant syndrome, especially when it is administered in conjunction with neuroleptics, remains unclear. On the part of psychiatric seldom – hallucinations (visual or auditory), depression, decreased appetite, anxiety, aggressive behavior, agitation, disorientation, very rarely – activation of psychosis. Allergic reactions: often – urticaria, and sometimes – erythroderma, rarely – lupus-like syndrome, skin itching, very rarely – erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), photosensitivity. Rarely – multiorgan delayed-type hypersensitivity reaction with fever, skin rashes, vasculitis (including erythema nodosum as a manifestation of cutaneous vasculitis), lymphadenopathy, symptoms resembling lymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly and altered liver function tests (these manifestations occur in various combinations). There may also be involved, and other organs (eg lungs, kidneys, pancreas, myocardium, colon). Very rarely – aseptic meningitis with myoclonus and peripheral eosinophilia, anaphylactoid reactions, angioedema, allergic pneumonitis or eosinophilic pneumonia. If you have any of the above allergic reactions the drug should be discontinued. On the part of hematopoiesis: very often – leukopenia and often – thrombocytopenia, eosinophilia, rarely – leukocytosis, lymphadenopathy, folic acid deficiency is very rare – agranulocytosis, aplastic anemia, erythrocytic aplasia true, megaloblastic anemia, acute “intermittent” porphyria, reticulocytosis, hemolytic anemia. From the digestive system: Very common – nausea, vomiting, and often – dry mouth, and sometimes – diarrhea or constipation, abdominal pain, very rarely – glossitis, stomatitis, pancreatitis. Of the liver: very often – increased activity of GGT (due to the induction of this enzyme in the liver), which is usually irrelevant and often – increased activity of alkaline phosphatase, and sometimes – increased activity of “liver” enzymes, rarely – hepatitis cholestatic, parenchymal (hepatocellular) or mixed type, jaundice is very rare – granulomatous hepatitis, hepatic failure. From the CCC: rarely – a violation of intracardiac conduction, decreased or increased blood pressure, very rarely – bradycardia, arrhythmias, AV block with fainting, collapse, worsening or development of heart failure, aggravation of coronary artery disease (including the appearance or increased frequency of angina attacks) thrombophlebitis, thromboembolic syndrome. From the Endocrine and Metabolic: often – edema, fluid retention, weight gain, hyponatremia (decrease in plasma osmolality due to an effect similar to the action of antidiuretic hormone, which in rare cases lead to hyponatremia dilutions, accompanied by lethargy, vomiting, headache, disorientation and neurological disorders), very rarely – hyperprolactinemia (may be accompanied by galactorrhea and gynecomastia) reducing the concentration of L-thyroxine (free T4, T4, T3) and increasing concentrations of TSH (usually not accompanied by clinical symptoms) disorders of calcium-phosphorus metabolism in bone tissue (reducing the concentration of Ca2 + and 25-OH-kolekaltsiferola in plasma): osteomalacia, high cholesterol (including HDL cholesterol) and hypertriglyceridemia. Genitourinary: very rare – interstitial nephritis, renal failure, renal dysfunction (eg albuminuria, haematuria, oliguria, increased urea / azotemia), urinary frequency, urinary retention, reduced potency. On the part of the musculoskeletal system: very rare – arthralgia, myalgia or cramps. From the senses: a very rare – taste disorders, cataract, conjunctivitis, hearing impairment, including tinnitus, hyperacusis, gipoakuziya, change the perception of pitch. Other: disorders of skin pigmentation, purpura, acne, increased sweating, alopecia. Reported on rare occasions, hirsutism, but the causal relationship of this complication with taking carbamazepine remains neyasnoy.Peredozirovka. Symptoms: usually reflect disorders of the CNS, cardiovascular and respiratory system. From the CNS and sensory organs – the oppression of central nervous system, disorientation, drowsiness, agitation, hallucinations, fainting, coma, visual disturbances (“fog” in front of the eyes), dysarthria, nystagmus, ataxia, dyskinesia, hyperreflexia (at first), hyporeflexia (later ), convulsions, psychomotor disturbances, myoclonus, hypothermia, mydriasis). From the CCC: tachycardia, decreased blood pressure, sometimes increase blood pressure, disorders of intraventricular conduction with the expansion of the complex QRS; cardiac arrest. On the part of the respiratory system: respiratory depression, pulmonary edema. Part of the digestive system: nausea and vomiting, delayed evacuation of food from the stomach, reducing the motility of the colon. The urinary system: urinary retention, oliguria or anuria, fluid retention, hyponatremia dilutions. Laboratory findings: leukocytosis or leukopenia, hyponatremia, metabolic acidosis, hyperglycemia and glycosuria, increase in muscle creatine kinase fraction. Treatment: no specific antidote. Treatment is based on the clinical condition of the patient, hospitalization is shown, determining the concentration of carbamazepine in plasma (for confirmation of poisoning with this drug and to assess the overdose), gastric lavage, activated charcoal appointment (late evacuation of gastric contents can result in delayed absorption of 2 and 3 days and re- symptoms of intoxication during the recovery period). Ineffective forced diuresis, hemodialysis and peritoneal dialysis (dialysis is shown with a combination of severe poisoning and kidney failure). Young children may need to exchange transfusion. Symptomatic supportive treatment in intensive care, monitoring of heart function, body temperature, corneal reflex, renal function and urinary bladder, correction of electrolyte disorders. By reducing blood pressure: the position with the lowered head end, plasma expanders, and inefficiency – in / dopamine or dobutamine, heart rhythm disturbances – Treatment is individually, with convulsions – the introduction of benzodiazepines (eg diazepam), with caution (because of the possible increase in depression breath) the introduction of other anticonvulsant drugs (eg phenobarbital). With the development of hyponatremia dilution (water intoxication) – to the introduction of fluids and a slow I / infusion 0.9% solution of NaCl (may help prevent the development of cerebral edema). We recommend holding hemosorption on coal sorbents.
Dosage and administration Tegretol XR:
Inside, outside of the meal along with a small amount of liquid. Retard tablets (whole or half tablet) should be swallowed whole without chewing, with a little liquid, 2 times a day. In some patients using retard tablets may be necessary to increase the dose. Epilepsy. In cases where this is possible, carbamazepine should be administered as a monotherapy. Treatment starts with the application of a small daily dose, which subsequently slowly increased until the optimum effect. Accession to carbamazepine antiepileptic therapy already under way should be gradual, with the dose of drugs used do not change or, if necessary, corrected. For adults the initial dose is 100-200 mg 1-2 times a day. Then slowly increase the dose to achieve optimal therapeutic effect (usually 400 mg 2-3 times per day, maximum – 1.6-2 g / d). Children from 4 years – the initial dose of 20-60 mg / day, gradually increasing to 20-60 mg a day. In children older than 4 years – the initial dose of 100 mg / day, increase the dose gradually every week by 100 mg. Maintenance dose: 10-20 mg / kg per day (in divided doses) for 4-5 years – 200-400 mg (1-2 doses), 6-10 years – 400-600 mg (2-3 doses ), for 11-15 years – 600-1000 mg (2-3 doses). When trigeminal neuralgia on the first day administered 200-400 mg / day, gradually increased by no more than 200 mg / day until the end of pain (an average of 400-800 mg / day) and then reduced to the minimum effective dose. The pain syndrome of neurogenic origin starting dose – 100 mg 2 times a day on the first day, then increase the dose by no more than 200 mg / day, if necessary, increasing it to 100 mg every 12 hours to reduce pain. Maintenance dose – 200-1200 mg / day in divided doses. In the treatment of elderly patients and patients with hypersensitivity initial dose – 100 mg 2 times a day. Alcohol withdrawal syndrome: high dose – 200 mg 3 times daily in severe cases in the first few days, the dose can be increased to 400 mg 3 times a day. Early treatment of severe withdrawal phenomena recommended in combination with a sedative-hypnotic drugs (klometiazol, chlordiazepoxide). Diabetes insipidus: the average dose for adults – 200 mg 2-3 times a day. In children, dosage should be reduced in accordance with the age and weight of the child. Diabetic neuropathy accompanied by pain: the average dose – 200 mg 2-4 times a day. For the prevention of recurrence of affective and schizoaffective psychoses – 600 mg / day in 3-4 doses. In acute manic states and affective (bipolar) disorders daily doses – 400-1600 mg. Average daily dose – 400-600 mg (2-3 doses). In acute manic state quickly increase the dose, if maintenance treatment of mood disorders – slowly (to improve endurance).
Cautions Tegretol XR:
Epilepsy monotherapy starting with the appointment of low-dose, making them individually to achieve the desired therapeutic effect. It is advisable to determine the plasma concentration to the optimal dose, particularly with combination therapy. When transferring a patient on carbamazepine should gradually reduce the dose previously assigned antiepileptic drug until its complete abolition. Sudden discontinuation of carbamazepine may cause epileptic seizures. If you want to cut short treatment, the patient should be transferred to other antiepileptic drugs under the cover shown in such cases, the drug (eg diazepam, administered intravenously or rectally, or phenytoin, administered in / in). Described several cases of vomiting, diarrhea and / or malnutrition, seizures and / or respiratory depression in newborns whose mothers took carbamazepine in conjunction with other antiepileptic drugs (possibly, these reactions are manifestations of the syndrome in the newborn “cancel”). Before the appointment of carbamazepine in the treatment process is necessary to study liver function, especially in patients with a history there is evidence of liver disease, as well as in elderly patients. In the case of strengthening the already existing liver dysfunction or active liver disease when the drug should be lifted immediately. Before treatment is necessary to conduct a study of the blood picture (including platelet count, reticulocyte count), the concentration of serum Fe, total urine analysis, urea concentration in blood, EEG, to determine the concentration of electrolytes in the blood serum (and periodically during treatment, as may develop hyponatremia). Subsequently, these indicators should be monitored during the first month of treatment weekly and then monthly. Carbamazepine should be withdrawn immediately if allergic reactions or symptoms, presumably indicating the development of Stevens-Johnson syndrome or Lyell’s syndrome. Mild skin reaction (macular or maculopapular isolated rash) usually disappear within a few days or weeks, even with continued treatment or after dose reduction of the drug (the patient at this time should be kept under close medical supervision). Carbamazepine has a weak anticholinergic activity, the appointment of patients with elevated intraocular pressure is needed to permanent control. Should take into account the ability to activate latent psychosis occurring, and in elderly patients – the possibility of confusion or excitement. To date, reported sporadic reports of violations of male fertility and / or disorders of spermatogenesis (the relationship of these disorders with receiving carbamazepine has not been established). Known reports of occurrence in women bleeding between menstrual periods when both were used oral contraceptives. Carbamazepine may affect the reliability of oral contraceptive drugs, so women of reproductive age in the period of treatment should be used for alternative methods of contraception. Carbamazepine should be used only under medical supervision. Necessary to inform patients about the early signs of toxicity inherent probable hematological disorders, as well as the symptoms of the skin and liver. The patient is informed of the need to consult a doctor immediately in case of occurrence of adverse reactions like fever, sore throat, rash, ulceration of the mucous membranes of the mouth, gratuitous appearance of “bruises” in the form of petechiae hemorrhage or purpura. In most cases, transient or persistent low platelet counts and / or white blood cells is not a harbinger of the beginning of aplastic anemia or agranulocytosis. However, before beginning treatment and periodically during treatment should be to conduct clinical blood tests, including platelet counts, and possibly reticulocytes and determine the concentration of Fe in blood serum. Neprogressiruyuschaya asymptomatic leukopenia does not require the cancellation, but treatment should be discontinued with the appearance of progressive leukopenia or leucopenia, accompanied by clinical symptoms of infectious disease. Before treatment is recommended to perform an eye examination, including fundus examination and slit lamp measurement if necessary intraocular pressure. In the case of appointment of the drug to patients with elevated intraocular pressure, continuous monitoring of this indicator. It is recommended to refuse the use of ethanol. The drug is a prolonged form can be taken once at night. The need to increase the dose during the transition to retard tablets are extremely rare. Although the relationship between the dose of carbamazepine, its concentration and clinical efficacy or tolerability is very small, however determine the regular concentration of carbamazepine may be useful in the following situations: when a sharp increase in seizure frequency, in order to verify whether the patient is taking medication properly, in pregnancy; when treating children or adolescents with suspected malabsorption of the drug, if you suspect the development of toxic reactions if the patient is taking multiple drugs. In women of reproductive age carbamazepine should preferably be used as monotherapy (using the lowest effective dose) – the frequency of congenital anomalies of infants born to women who underwent a combined anti-epileptic medication, higher than in those who received each of these drugs as monotherapy. In the event of pregnancy (when deciding on the appointment of carbamazepine during pregnancy) should carefully compare the expected benefits of therapy and its possible complications, especially in the first 3 months of pregnancy. It is known that children born to mothers with epilepsy are prone to violations of fetal development, including malformations. Carbamazepine, like all other antiepileptic drugs, can increase the risk of these disorders. There are isolated reports of cases of congenital diseases and malformations, including spina bifida (spina bifida). Patients should be given information about the possibility of increased risk of malformations and antenatal diagnosis of an opportunity to pass. Antiepileptic drugs increase folic acid deficiency, often observed during pregnancy, which may increase the incidence of congenital defects in children (before and during pregnancy should take extra folic acid). In order to prevent bleeding disorders in newborns women in the last weeks of pregnancy and newborns are encouraged to nominate vitamin K1. Carbamazepine passes into breast milk, you should compare the benefits and possible adverse effects of breast-feeding in conditions of continuing therapy. Mothers who take carbamazepine, can breastfeed, provided that the child will be placed under surveillance for the development of possible adverse reactions (such as severe drowsiness, and allergic skin reactions). During the period of treatment must be careful when driving and occupation of other potentially hazardous activities that require your full attention and psychomotor speed of reaction.
Interaction Tegretol XR:
Cytochrome CYP3A4 is the major enzyme providing the metabolism of carbamazepine. Simultaneous with the appointment of carbamazepine with CYP3A4 inhibitors may increase its concentration in plasma and cause adverse reactions. The combined use of inducers of CYP3A4 may lead to accelerated metabolism of carbamazepine, reduce the concentration of carbamazepine in plasma and a decrease in therapeutic effect, on the contrary, their removal may reduce the rate of metabolism of carbamazepine and lead to an increase in its concentration. Increase the concentration of carbamazepine in plasma, verapamil, diltiazem, felodipine, dextropropoxyphene, viloksazin, fluoxetine, fluvoxamine, cimetidine, acetazolamide, danazol, desipramine, nicotinamide (in adults only at high doses), macrolides (erythromycin, dzhozamitsin, clarithromycin, troleandomitsin); azoles (itraconazole, ketoconazole, fluconazole), terfenadine, loratadine, isoniazid, propoxyphene, grapefruit juice, protease inhibitors, viral used in the treatment of HIV infection (eg ritonavir) – requires adjustment of dosing regimen or monitoring the concentration of carbamazepine in plasma. Felbamate reduces the concentration of carbamazepine in plasma and increases the concentration of carbamazepine-10 ,11-epoxide, with the possible simultaneous decrease in the concentration of serum felbamate. Reduce the concentration of carbamazepine phenobarbital, phenytoin, primidone, metsuksimid, fensuksimid, theophylline, rifampicin, cisplatin, doxorubicin, perhaps: clonazepam, valpromid, valproic acid, oxcarbazepine, and herbal medicines containing St John’s wort (Hypericum perforatum). There are reports of possible displacement of carbamazepine by valproic acid and primidone in connection with plasma proteins and increased concentration of the pharmacologically active metabolite (carbamazepine-10 ,11-epoxide). Isotretinoin alters the bioavailability and / or clearance of carbamazepine and carbamazepine-10 ,11-epoxide (carbamazepine concentrations should be monitored in plasma). Carbamazepine may reduce plasma concentrations (to reduce or even completely reverse the effects) and require dosage adjustment following drugs: klobazama, clonazepam, ethosuximide, primidona, valproic acid, alprazolam, corticosteroids (prednisone, dexamethasone), cyclosporine, doxycycline, haloperidol, methadone, oral drugs that contain estrogen and / or progesterone (required selection of alternative methods of contraception), theophylline, oral anticoagulants (warfarin, fenprokumona, dikumarol), lamotrigine, topiramate, tricyclic antidepressants (imipramine, amitriptyline, nortriptyline, clomipramine), clozapine, felbamate, tiagabine, oxcarbazepine, protease inhibitors used in the treatment of HIV (indinavir, ritonavir, sakvinovira), BCCI (digidropiridonov group, such as felodipine), itraconazole, levothyroxine, midazolam, olazapina, praziquantel, risperidone, tramadol, tsiprazidona. It has been reported that in patients receiving carbamazepine levels of phenytoin in the plasma may either grow or decrease and the level of mefenitoina increase (in rare cases). Carbamazepine or combined with paracetamol increases the risk of toxic effects on the liver and reduces the therapeutic efficacy of (accelerated metabolism of paracetamol). Simultaneous with the appointment of carbamazepine with phenothiazine, pimozide, tioksantenami, molindonom, haloperidol, maprotiline, tricyclic antidepressants, and clozapine leads to increased inhibitory action on the central nervous system and weaken the anticonvulsant effect of carbamazepine. MAO inhibitors increase the risk of giperpiretichekih crises, hypertensive crises, convulsions, death (before prescribing carbamazepine MAO inhibitors should be discontinued at least 2 weeks or if the clinical situation allows, even for a longer period). Simultaneous with the appointment of diuretics (hydrochlorothiazide, furosemide) may lead to hyponatremia, accompanied by clinical manifestations. Attenuates the effects of nondepolarizing muscle relaxants (pancuronium). In the case of such a combination may need higher doses of muscle relaxants, and the need to carry out careful monitoring of patients, possibly because a more rapid end to their actions). Reduces the tolerance of ethanol. Accelerates the metabolism of indirect anticoagulants, hormonal contraceptive drugs, folic acid, praziquantel, may increase the elimination of thyroid hormones. Accelerates the metabolism of drugs for general anesthesia (enflurane, halothane, ftorotana) with an increased risk of hepatotoxic effects, enhances the formation of nephrotoxic metabolites of methoxyflurane. Enhances the hepatotoxic action of isoniazid. Myelotoxic drugs increase the expression gematotoksichnosti drug.
