Pharmacological properties
Pharmacodynamics. As an anticonvulsant, Carbalex Retard is effective in focal (partial) seizures (simple and complex), accompanied or not accompanied by secondary generalization, in generalized tonic-clonic seizures, as well as in a combination of the above types of seizures.
In clinical studies, when using the drug Carbalex retard as monotherapy in patients with epilepsy (especially in children and adolescents), the psychotropic effect of the drug was noted, partly manifested by a positive effect on symptoms of anxiety and depression, as well as a decrease in irritability and aggressiveness. According to some studies, the effect of the drug Carbalex retard on cognitive function and psychomotor performance was dose-dependent and was either questionable or negative. In other studies, the positive effect of the drug on indicators characterizing attention, learning ability and memory was noted.
As a neurotropic agent, Carbalex retard is effective in some neurological diseases: it prevents pain attacks in idiopathic and secondary trigeminal neuralgia. In addition, Carbalex retard is used to relieve neurogenic pain in various conditions, including spinal cord tuberculosis, post-traumatic paresthesias of organs and bone marrow. In alcohol withdrawal syndrome, Carbalex retard increases the threshold of convulsive readiness (which is reduced in this condition) and reduces the severity of clinical manifestations of the syndrome, such as excitability, tremor, gait disturbance. In patients with diabetes insipidus of central genesis, Carbalex retard reduces diuresis and thirst.
It has been confirmed that as a psychotropic drug Carbalex retard is effective in disorders, namely: for the treatment of acute manic states, for the maintenance treatment of bipolar affective (manic-depressive) disorders (both monotherapy and in combination with neuroleptics, antidepressants or lithium preparations), for schizoaffective psychoses, manic psychoses, in which it is used in combination with neuroleptics, as well as for acute polymorphic schizophrenia (rapid cycling episodes). The mechanism of action of carbamazepine - the active substance of the drug Carbalex retard - has been partially elucidated. Carbamazepine stabilizes the membranes of overexcited nerve fibers, inhibits the occurrence of repeated neuronal discharges and reduces synaptic conduction of excitatory impulses. It has been established that the main mechanism of action of the drug is to prevent the re-formation of sodium-dependent action potentials in depolarized neurons by blocking sodium channels. The anticonvulsant effect of the drug is mainly due to a decrease in the release of glutamate and stabilization of neuronal membranes, while the antimanic effect may be due to inhibition of dopamine and noradrenaline metabolism.
Pharmacokinetics
Carbalex 300, 600 mg retard. After oral administration, carbamazepine is almost completely absorbed in the gastrointestinal tract. C max with a single dose is achieved after 12 hours. Binding to blood proteins is 70-80%. In the cerebrospinal fluid and saliva, a concentration is formed proportional to the proportion of the active substance not bound to proteins (20-30%). Penetrates into breast milk (25-60% of the level in blood plasma) and through the placental barrier. The volume of distribution is 0.8-1.9 l/kg. With a single dose, T ½ is 25-65 hours, with prolonged use - 8-29 hours (due to induction of metabolic enzymes). In patients using inducers of the monooxygenase system (phenytoin, phenobarbital), T ½ is 8-10 hours. Carbamazepine is metabolized in the liver and excreted mainly by the kidneys. The prolonged action of the tablets does not depend on food intake. If necessary, the tablets can be dissolved in a liquid (water, tea, orange juice, milk) without the risk of losing their effect. By inhibiting the activity of CYP450 IIIA4 enzymes in the stomach and liver, grapefruit juice significantly increases the bioavailability of carbamazepine.
The onset of anticonvulsant action varies from several hours to several days (sometimes up to 1 month).
Features of pharmacokinetics in certain groups of patients
Elderly patients: There is no evidence of altered pharmacokinetics of carbamazepine in the elderly (compared to young adults).
Patients with renal or hepatic impairment: There are no data on the pharmacokinetics of carbamazepine in patients with renal or hepatic impairment.
Indication
Epilepsy and complex/simple partial seizures (with/without loss of consciousness) with/without secondary generalization; generalized tonic-clonic seizures. mixed forms of seizures.
Carbalex retard can be used as monotherapy or as part of combination therapy.
Acute manic states and maintenance therapy of bipolar affective disorders to prevent exacerbations or reduce the clinical manifestations of exacerbations.
Alcohol withdrawal syndrome.
Idiopathic trigeminal neuralgia and trigeminal neuralgia in multiple sclerosis (typical and atypical). Idiopathic glossopharyngeal neuralgia.
Diabetic neuropathy with pain syndrome.
Diabetes insipidus of central genesis. Polyuria and polydipsia of neurohormonal nature.
Application
Epilepsy. Whenever possible, Carbalex retard should be administered as monotherapy.
Treatment should be started with a low daily dose, which should then be slowly increased until the optimal effect is achieved.
To select the optimal dose of the drug, it may be useful to determine the level of the active substance in the blood plasma.
When prescribing Carbalex retard in addition to current antiepileptic therapy, the dose should be gradually increased without changing the dose of the antiepileptic drug already used, or, if necessary, adjusting it.
Carbalex 300, 600 mg retard. The tablets can be divided into parts, they will not lose the effect of prolonged action, they can be dissolved in various drinks (in 1 glass of water, tea, orange juice or milk). Carbalex retard tablets cannot be used together with drinks containing grapefruit juice.
Children from 1 to 5 years: 150 mg 2 times a day (morning and evening).
Children from 6 to 10 years: 150-300 mg 2 times a day (15-20 mg/kg/day).
Adults and children over 10 years of age. Therapy should be started with a dose of 150 mg 2 times a day, gradually increasing the dose until the optimal effect is achieved. In general, the average therapeutic dose is 600 mg/day, which should be taken, as a rule, in the evening, if the doctor has prescribed 1 dose per day.
Some patients may require a dose of the drug reaching 1600 or even 2000 milligrams/day.
Acute manic states and maintenance therapy in bipolar affective disorders. Doses can be 300-1500 mg/day. Usually therapy should be carried out at a dose of 400-600 mg/day in 2-3 doses.
In the treatment of acute manic states, the dose should be increased rapidly, while gradual increases in small doses have the optimal effect and are recommended for the prevention of bipolar disorders.
Alcohol withdrawal syndrome. The average daily dose is 600 mg. In some cases, a dose of 1200 mg/day should be used during the first days of treatment.
In severe manifestations of alcohol withdrawal, treatment should be started with a combination of Carbalex retard with sedative-hypnotic drugs (e.g. clomethiazole, chlordiazepoxide), following the above dosage instructions. After the acute phase of the disease is over, treatment with Carbalex retard can be continued as monotherapy.
Trigeminal neuralgia. The initial dose is 300 mg/day. It should be gradually increased until the pain symptoms disappear. The average daily dose is 600 mg.
Diabetic neuropathy with pain syndrome. The average daily dose is 600 mg, which can be used once a day or divided into 2 doses of 300 mg - in the morning and evening.
Diabetes insipidus of central genesis. Polyuria and polydipsia of neurohormonal nature. The average dose is 300 mg 2-3 times a day. For children, the dose should be reduced according to the age and body weight of the child.
Contraindication
The drug should not be used:
with established hypersensitivity to carbamazepine or to chemically similar drugs (for example, tricyclic antidepressants) or to any component of the drug; with AV blockade; in patients with a history of bone marrow suppression; in patients with a history of hepatic porphyria (for example, acute intermittent porphyria, mixed porphyria, porphyria cutanea tarda); in acute liver failure; in combination with MAO inhibitors. children: Carbalex retard tablets - up to 1 year.
Side effects
Certain types of adverse reactions, for example from the central nervous system (dizziness, headache, ataxia, drowsiness, general weakness, diplopia), from the gastrointestinal tract (nausea, vomiting) or allergic skin reactions occur at the beginning of treatment with the drug Karabalex retard, when using too high an initial dose, when treating the elderly.
Dose-dependent adverse reactions usually resolve within a few days either spontaneously or after a temporary reduction in the dose of the drug. The development of adverse reactions from the central nervous system may be a consequence of a relative overdose of the drug or significant fluctuations in the concentrations of the active substance in the blood plasma. In such cases, it is recommended to monitor the level of the active substance in the blood plasma.
Nervous system: dizziness, ataxia, drowsiness, general weakness, headache, diplopia, accommodation disorders (e.g. blurred vision); abnormal involuntary movements (e.g. tremor, dystonia, tics), nystagmus; orofacial dyskinesia, visual disturbances, speech disorders (e.g. dysarthria or slurred speech), choreoathetosis, peripheral neuropathy, paresthesia, paresis, taste disturbances, neuroleptic malignant syndrome.
Psychiatric disorders: hallucinations (visual or auditory), depression, loss of appetite, restlessness, aggressiveness, agitation, confusion; activation of psychosis.
From the hematopoietic system: leukopenia; thrombocytopenia, eosinophilia; leukocytosis, lymphadenopathy, folic acid deficiency; agranulocytosis, aplastic anemia, pancytopenia, red cell aplasia, anemia, megaloblastic anemia, acute intermittent porphyria, mixed porphyria, porphyria cutanea tarda, reticulocytosis and possibly hemolytic anemia.
On the part of the hepatobiliary system: increased levels of gamma-glutamyltransferase (due to liver enzyme induction), usually of no clinical significance, increased levels of plasma ALP, increased levels of transaminases; hepatitis of cholestatic, parenchymal (hepatocellular) or mixed type, jaundice; granulomatous hepatitis, liver failure.
Gastrointestinal: nausea, vomiting, dry mouth; diarrhea or constipation, abdominal pain; glossitis, stomatitis, pancreatitis.
On the part of the immune system: multiorgan delayed-type hypersensitivity with fever, skin rashes, vasculitis, lymphadenopathy, signs resembling lymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly and altered liver function tests (these manifestations are noted in various combinations). There may be disorders from other organs (e.g. lungs, kidneys, pancreas, myocardium, intestines), aseptic meningitis with myoclonus and peripheral eosinophilia; anaphylactic reactions, angioedema.
Cardiac disorders: conduction disturbances, hypertension or hypotension; bradycardia, arrhythmias, AV block with syncope, circulatory collapse, congestive heart failure, exacerbation of coronary artery disease, thrombophlebitis, thromboembolism (e.g. pulmonary embolism).
On the part of the endocrine system: edema, fluid retention, weight gain, hyponatremia and decreased plasma osmolarity due to an effect similar to the action of antidiuretic hormone, which sometimes leads to dilutional hyponatremia, accompanied by lethargy, vomiting, headache, confusion and neurological disorders; increased prolactin levels in blood plasma, accompanied / not accompanied by such manifestations as galactorrhea, gynecomastia, changes in thyroid function: decreased levels of L-thyroxine (FT4, T4, T3) and thyroid-stimulating hormone, which, as a rule, is not accompanied by clinical manifestations; impaired bone metabolism (decreased levels of calcium and 25-OH-cholecalciferol in blood plasma), leading to osteomalacia / osteoporosis, in some cases - increased cholesterol concentrations, including HDL cholesterol and TG.
Renal and urinary disorders: interstitial nephritis, renal failure, renal dysfunction (albuminuria, hematuria, oliguria, increased urea level/azotemia), increased urination, urinary retention.
From the reproductive system: sexual dysfunction/impotence, impaired spermatogenesis (with a decrease in the number/motility of sperm).
From the organ of vision: lens opacity, conjunctivitis, increased intraocular pressure.
Hearing and labyrinth disorders: hearing disorders, such as tinnitus, increased auditory sensitivity, decreased auditory sensitivity, impaired pitch perception.
Musculoskeletal, connective tissue and bone disorders: arthralgia, myalgia, muscle spasms.
Respiratory system: pulmonary hypersensitivity reactions characterized by fever, dyspnea, pneumonitis, or pneumonia.
Abnormal laboratory test results: hypogammaglobulinemia.
Special instructions
Carbalex retard should be prescribed only under supervision and only after assessing the benefit/risk ratio and monitoring patients with cardiac, hepatic or renal disorders, adverse hematological reactions to other drugs in history, or patients with interrupted courses of therapy with the drug Carbalex retard. The drug is usually ineffective in minor seizures (petit mal, absence) and myoclonic seizures.
Hematological effects. The use of the drug is associated with the development of agranulocytosis and aplastic anemia, however, due to the extremely low incidence of these conditions, it is difficult to estimate a significant risk with the use of Carbalex retard. The overall risk for people not receiving therapy is 4.7 people / 1 million per year for the development of agranulocytosis and 2 people / 1 million per year for the development of aplastic anemia.
Periodically or frequently, a temporary or persistent decrease in the number of platelets or white blood cells is noted in connection with the use of the drug Carbalex retard. However, for most of these cases, their transience is confirmed and they do not indicate the development of aplastic anemia or agranulocytosis. Before the start of therapy and periodically during its conduct, a blood test should be performed, including determination of the number of platelets (as well as the number of reticulocytes and hemoglobin).
Patients should be informed about the early signs of toxicity and symptoms of possible haematological disorders, as well as symptoms of dermatological and hepatic reactions. The patient should be warned that in case of reactions such as fever, sore throat, skin rash, mouth ulcers, easy bruising, petechial haemorrhages or haemorrhagic purpura, they should seek medical advice immediately.
Serious dermatological reactions. Serious dermatological reactions, including toxic epidermal necrolysis (TEN or Lyell's syndrome), Stevens-Johnson syndrome (SJS), occur very rarely with Carbalex / Carbalex retard. Patients with serious dermatological reactions may require hospitalization, as these conditions can be life-threatening and fatal. Most cases of SJS / TEN occur during the first few months of treatment with Carbalex retard. If signs and symptoms suggestive of serious dermatological reactions (SJS, Lyell's syndrome / TEN) develop, Carbalex retard should be discontinued immediately and alternative therapy should be initiated.
Retrospective studies in Han Chinese patients have shown a strong correlation between carbamazepine-associated cutaneous reactions of SJS/TEN and the presence of the human leukocyte antigen (HLA) allele (HLA)-B*1502 in these patients. The high frequency of reports of SJS (rare rather than very rare) is characteristic of some Asian countries (e.g. Taiwan, Malaysia and the Philippines) where the HLA-B*1502 allele is prevalent in the population. The number of carriers of this allele in the Asian population is 15% in the Philippines, Thailand, Hong Kong and Malaysia, about 10% in Taiwan, almost 4% in Northern China, about 2 to 4% in South Asia (including India) and 1% in Japan and Korea. The prevalence of the (HLA) -B*1502 allele is insignificant among European, African peoples, among the indigenous population of America and the Latin American population.
Patients considered to be at genetic risk should be tested for the presence of the (HLA)-B*1502 allele before starting treatment with Carbalex retard. If the patient tests positive for the (HLA)-B*1502 allele, Carbalex retard should be avoided unless the benefits of treatment significantly outweigh the risks. The (HLA)-B*1502 allele may be a risk factor for the development of SCD/TEN in Chinese patients receiving other antiepileptic drugs that may be associated with the development of SCD/TEN. Therefore, the use of other drugs that may be associated with the development of SCD/TEN should be avoided in patients carrying the (HLA)-B*1502 allele if alternative therapies are available. Genetic screening of patients from ethnic groups with a low incidence of the (HLA)-B*+1502 allele is not generally recommended. Screening is not usually recommended in individuals already receiving Carbalex retard, as the risk of developing SCD/TEN is significantly limited to the first few months, regardless of the presence of the (HLA) -B*1502 allele in the patient's genes.
Genetic screening results should not replace appropriate clinical monitoring and treatment of the patient. Many Asian patients with the (HLA) -B * 1502 allele have been treated with Carbalex retard without developing SCD / TEN, and patients of any nationality who do not have the (HLA) -B * 1502 allele may develop SCD / TEN. The role of other possible factors in the development and incidence of SCD / TEN, such as the level of antiepileptic drug dosage, compliance, concomitant medications, the influence of other diseases and the level of monitoring of skin disorders, has not yet been studied.
Other dermatological reactions. Transient and non-life-threatening mild dermatological reactions, such as isolated macular or maculopapular exanthema, may occur. They usually resolve within a few days or weeks with either continued dosing or dose reduction. However, since early signs of more serious dermatological reactions may be difficult to distinguish from mild transient reactions, the patient should be monitored for prompt discontinuation of the drug if the reaction worsens with continued use.
The presence of the (HLA) -B*1502 allele in a patient is not a risk factor for developing less serious skin reactions to carbamazepine, such as anticonvulsant hypersensitivity syndrome or minor rashes (maculopapular rashes).
Hypersensitivity. Carbalex retard may provoke the development of hypersensitivity reactions, including multiple hypersensitivity reactions, localized in the skin, liver, hematopoietic organs and lymphatic system or other organs, collectively or separately, within the framework of a systemic reaction.
Patients with hypersensitivity reactions to carbamazepine should be informed that approximately 25-30% of such patients may also have hypersensitivity reactions to oxcarbazepine.
When using carbamazepine and phenytoin, cross-hypersensitivity may develop.
Seizures. Carbalex retard should be used with caution in patients with mixed seizures that include absences (typical/atypical). In such circumstances, the drug may provoke seizures. If seizures are provoked, the use of Carbalex retard should be discontinued immediately.
An increase in the frequency of attacks may occur when switching from oral to rectal forms of the drug.
Liver function. During the entire course of therapy with the drug, it is necessary to assess liver function at the initial stage and periodically monitor it, especially in patients with a history of liver disease and in the elderly. In case of exacerbation of liver function disorders or in patients with an active phase of liver disease, the drug should be discontinued immediately.
Renal function: It is recommended to assess renal function and determine the level of urea nitrogen at the beginning and periodically during the course of therapy.
Anticholinergic effects: Carbalex retard exhibits moderate anticholinergic activity. Therefore, patients with elevated intraocular pressure should be monitored during therapy.
Mental effects. It is necessary to remember about the possibility of activation of latent psychosis and in elderly patients - confusion or agitation.
Endocrine effects. There have been reports of breakthrough bleeding in women receiving Carbalex retard in combination with hormonal contraceptives. Since Carbalex retard may adversely affect the effectiveness of hormonal contraceptives, women of reproductive age should be advised to consider alternative forms of contraception while taking the drug. Due to the induction of liver enzymes, Carbalex retard may cause a decrease in the therapeutic effect of estrogen and/or progesterone preparations (i.e., interfere with effective contraception).
Monitoring of drug plasma levels. Although the correlation between dosage and carbamazepine plasma levels, as well as between carbamazepine plasma levels and clinical efficacy and tolerability, is uncertain, monitoring of drug plasma levels may be appropriate in the following cases: with a sudden increase in seizure frequency, to check patient compliance, during pregnancy, when treating children and adolescents, when suspected of impaired absorption, when suspected toxicity, when using 1 drug.
Dose reduction and drug withdrawal. Abrupt withdrawal of Carbalex retard may precipitate seizures. If abrupt withdrawal of the drug is necessary in patients with epilepsy, switching to a new antiepileptic drug should occur against the background of therapy with an appropriate drug (e.g., diazepam rectally or phenytoin intravenously).
Transferring a patient from taking tablets to taking retard tablets. Clinical experience shows that some patients may need to increase the dose of the drug when using retard tablets.
Given drug interactions and different pharmacokinetics of antiepileptic drugs, doses of Carbalex retard should be selected with caution in elderly patients.
Ability to influence the reaction rate when driving vehicles or operating machinery. Since the drug reduces the reaction rate, caution should be exercised when driving vehicles and operating machinery while using Carbalex retard.
Use during pregnancy and breastfeeding. Any medication during pregnancy, especially in the first trimester, can be dangerous. But if antiepileptic therapy is necessary, it should not be stopped during pregnancy - refusal of the drug carries a great threat to the mother and fetus.
The drug penetrates the placental barrier and into breast milk. To remove carbamazepine from the infant's body, breastfeeding should be gradually discontinued.
When breastfeeding, carbamazepine has a sedative effect on the infant's central nervous system, which may cause difficulties with sucking.
The following should be kept in mind:
The use of Carbalex retard in pregnant women with epilepsy requires special attention; if a woman receiving Carbalex retard becomes pregnant, plans to become pregnant, or during pregnancy there is a need to use Carbalex retard, the potential benefit of using the drug should be carefully weighed against the possible risk (especially in the first trimester of pregnancy); women of reproductive age should be prescribed Carbalex retard as monotherapy, if possible, since the frequency of congenital malformations in children of women who received combination therapy with antiepileptic drugs is higher than in women who used antiepileptic monotherapy; it is recommended to prescribe the drug in minimal effective doses and monitor the level of carbamazepine in the blood plasma; patients should be informed about the possibility of an increased risk of congenital malformations in the child and they should be provided with the opportunity for antenatal screening; During pregnancy, effective antiepileptic therapy should not be interrupted, as exacerbations of the disease can threaten the health of both the mother and the child.
Monitoring and prevention. It is known that folic acid deficiency may develop during pregnancy. Antiepileptic drugs may increase the level of folic acid deficiency. This type of deficiency may lead to an increased incidence of congenital malformations in children of women receiving antiepileptic therapy. Therefore, additional folic acid administration is recommended before and during pregnancy.
Newborns. In order to prevent blood clotting disorders in newborns, it is recommended to prescribe vitamin K 1 to the mother in the last weeks of pregnancy and to the newborn.
There have been several cases of convulsions and/or respiratory depression in newborns associated with maternal use of Carbalex retard and other anticonvulsants. There have been several cases of vomiting, diarrhea, and/or poor appetite in newborns associated with maternal use of Carbalex retard.
Breastfeeding. Carbamazepine passes into breast milk (25-60% of plasma concentration). The benefits of breastfeeding with the remote possibility of side effects in the newborn should be carefully weighed. Women receiving Carbalex retard can breastfeed provided that the child is observed for the development of possible side effects (e.g. excessive drowsiness, allergic reactions).
Children. Due to the rapid elimination of carbamazepine, children may require higher doses per kg of body weight than adults. Carbalex retard tablets can be taken by children from 1 year of age as prescribed and under the supervision of a doctor.
Carbalex retard should be used with caution only after a considered decision regarding the use and benefits outweigh the risks of complications and preferably as monotherapy.
Interactions
The effectiveness of drugs such as oral coagulants (coumarin derivatives), quinidine, hormonal contraceptives, some antibiotics (doxycycline), associated with the induction of liver enzymes, may decrease.
Grapefruit juice should be avoided, as it significantly increases the absorption of carbamazepine. Taking carbamazepine affects laboratory parameters of thyroid function (thyroid hormones).
Cytochrome P450 3A4 (CYP 3A4) is the main enzyme that catalyzes the formation of the active metabolite carbamazepine-10,11-epoxide. Concomitant use of CYP 3A4 inhibitors may lead to increased plasma concentrations of carbamazepine, which in turn may lead to the development of adverse reactions. Concomitant use of CYP 3A4 inducers may increase the metabolism of carbamazepine, resulting in a potential decrease in carbamazepine plasma concentrations and therapeutic effect. Similarly, discontinuation of a CYP 3A4 inducer may reduce the rate of carbamazepine metabolism, resulting in increased plasma levels of carbamazepine.
Carbamazepine is a potent inducer of CYP 3A4 and other phase I and phase II enzyme systems in the liver, and therefore may reduce plasma concentrations of other drugs that are predominantly metabolized by CYP 3A4 by inducing their metabolism.
Human microsomal epoxide hydrolase is the enzyme responsible for the formation of 10,11-transdiol derivatives from carbamazepine-10,11-epoxide. Concomitant administration of inhibitors of human microsomal epoxide hydrolase may lead to an increase in the plasma concentration of carbamazepine-10,11-epoxide.
Drugs that may increase carbamazepine plasma levels. Since an increase in carbamazepine plasma levels may lead to adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of Carbalex retard should be adjusted accordingly and/or its plasma levels monitored when used concomitantly with such drugs.
Analgesics, anti-inflammatory drugs: dextropropoxyphene, ibuprofen.
Androgens: danazol.
Antibiotics: macrolide antibiotics (e.g. erythromycin, oleandomycin, josamycin, clarithromycin).
Antidepressants: desipramine, fluoxetine, fluvoxamine, nefazodone, paroxetine, trazodone, viloxazine.
Antifungals: azoles (e.g. itraconazole, ketoconazole, fluconazole, voriconazole).
Antihistamines: loratadine, terfenadine.
Antipsychotic drugs: olanzapine.
Anti-tuberculosis drugs: isoniazid.
Antiviral drugs: protease inhibitors for HIV (e.g. ritonavir).
Carbonic anhydrase inhibitors: acetazolamide.
Cardiovascular drugs: diltiazem, verapamil.
Drugs for the treatment of gastrointestinal diseases: cimetidine, omeprazole.
Muscle relaxants: oxybutynin, dantrolene.
Antiplatelet drugs: ticlopidine.
Other ingredients: grapefruit juice, nicotinamide (in adults, only in high doses).
Drugs that may increase the level of the active metabolite carbamazepine-10,11-epoxide in blood plasma
Since increased levels of the active metabolite carbamazepine-10,11-epoxide in the blood plasma may cause the development of adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of Carbalex retard should be adjusted accordingly and/or the plasma levels of the drug monitored if Carbalex retard is taken concomitantly with the following drugs: loxapine, quetiapine, primidone, progabide, valproic acid, valnoctamide and valpromide.
Drugs that may reduce carbamazepine plasma levels
It may be necessary to adjust the dose of Carbalex retard when used simultaneously with such drugs.
Antiepileptic drugs: felbamate, methsuximide, oxcarbazepine, phenobarbital, phensuximide, phenytoin and fosphenytoin, primidone, and clonazepam (although data on this are conflicting).
Anticancer drugs: cisplatin or doxorubicin.
Anti-tuberculosis drugs: rifampicin.
Bronchodilators or anti-asthma drugs: theophylline, aminophylline.
Dermatological drugs: isotretinoin.
Interaction with other substances: herbal preparations containing St. John's wort (Hypericum perforatum).
Effect of Carbalex retard on the blood plasma levels of concomitantly administered drugs
Carbamazepine may reduce the plasma levels of some drugs and reduce or eliminate their effects. The dosage of the drugs listed below may need to be adjusted according to clinical requirements.
Analgesics, anti-inflammatory drugs: methadone, paracetamol, phenazone, tramadol.
Antibiotics: doxycycline.
Anticoagulants: oral anticoagulants (e.g. warfarin, phenprocoumon, dicumarol and acenocoumarol).
Antidepressants: bupropion, citalopram, nefazodone, trazodone, tricyclic antidepressants (e.g. imipramine, amitriptyline, nortriptyline, clomipramine). Carbalex retard is not recommended for use simultaneously with MAO inhibitors; before starting the drug, it is necessary to stop taking the MAO inhibitor (less than 2 weeks or earlier, if clinical circumstances allow).
Antiepileptic drugs: clobazam, clonazepam, ethosuximide, felbamate, lamotrigine, oxcarbazepine, primidone, tiagabine, topiramate, valproic acid, zonisamide. Both an increase in phenytoin plasma levels due to the action of carbamazepine and a decrease in it and isolated cases of an increase in mephenytoin plasma levels have been reported.
Antifungal drugs: itraconazole.
Anthelmintic drugs: praziquantel.
Anticancer drugs: imatinib.
Neuroleptic drugs: clozapine, haloperidol and bromperidol, olanzapine, quetiapine, risperidone, ziprasidone.
Antiviral drugs: protease inhibitors for the treatment of HIV (e.g. indinavir, ritonavir, saquinavir).
Anxiolytics: alprazolam, midazolam.
Bronchodilators or anti-asthma drugs: theophylline.
Contraceptive drugs: hormonal contraceptives (alternative methods of contraception should be considered).
Cardiovascular drugs: calcium channel blockers (dihydropyridine group), such as felodipine, digoxin.
Corticosteroids: corticosteroids (e.g. prednisolone, dexamethasone).
Immunosuppressants: cyclosporine, everolimus.
Thyroid medications: levothyroxine.
Interaction with other drugs: drugs containing estrogens and/or progesterone.
Drug combinations that require separate consideration
Concomitant use of carbamazepine and levetiracetam may lead to increased toxicity of carbamazepine.
Concomitant use of carbamazepine and isoniazid
