Carbamazepine Information
Carbamazepine ()
Carbamazepine ()
Carbamazepine ()
Carbamazepine () Description
Carbamazepine () USP, is an anticonvulsant and specific analgesic for trigeminal neuralgia, available for oral administration as chewable tablets of 100 mg and tablets of 100 mg, 200 mg, 300 mg, 400 mg. Its chemical name is -dibenz[]azepine-5-carboxamide, and its structural formula is
Carbamazepine () USP is a white to off-white powder, practically insoluble in water and soluble in alcohol and in acetone. Its molecular weight is 236.27.
Carbamazepine () tablets, USP, 100 mg, 200 mg, 300 mg and 400 mg contain the inactive ingredients: colloidal silicon dioxide, FD&C Red #40 aluminum lake, hypromellose, magnesium stearate, pregelatinized starch, corn starch, and sodium starch glycolate.
Carbamazepine () tablets, USP, (chewable) contain the inactive ingredients: artificial flavors, colloidal silicon dioxide, compressible sugar, corn starch, FD&C Red #40 aluminum lake, hydroxypropyl methyl cellulose, magnesium stearate, and sodium starch glycolate.
Carbamazepine () tablets, USP, 100 mg, 200 mg, 300 mg, 400 mg meet USP Dissolution Test 2 and Carbamazepine () Tablets USP (Chewable), 100 mg meet USP Dissolution Test 1.
Carbamazepine () Clinical Pharmacology
In controlled clinical trials, Carbamazepine () has been shown to be effective in the treatment of psychomotor and grand mal seizures, as well as trigeminal neuralgia.
Carbamazepine () has demonstrated anticonvulsant properties in rats and mice with electrically and chemically induced seizures. It appears to act by reducing polysynaptic responses and blocking the post-tetanic potentiation. Carbamazepine () greatly reduces or abolishes pain induced by stimulation of the infraorbital nerve in cats and rats. It depresses thalamic potential and bulbar and polysynaptic reflexes, including the linguomandibular reflex in cats. Carbamazepine () is chemically unrelated to other anticonvulsants or other drugs used to control the pain of trigeminal neuralgia. The mechanism of action remains unknown.
The principal metabolite of Carbamazepine () , Carbamazepine () -10,11-epoxide, has anticonvulsant activity as demonstrated in several animal models of seizures. Though clinical activity for the epoxide has been postulated, the significance of its activity with respect to the safety and efficacy of Carbamazepine () has not been established.
In clinical studies, Carbamazepine () suspension, conventional tablets, and extended-release tablets delivered equivalent amounts of drug to the systemic circulation. However, the suspension was absorbed somewhat faster, and the extended-release tablet slightly slower, than the conventional tablet. The bioavailability of the extended-release tablet was 89% compared to suspension. Following a b.i.d. dosage regimen, the suspension provides higher peak levels and lower trough levels than those obtained from the conventional tablet for the same dosage regimen. On the other hand, following a t.i.d. dosage regimen, Carbamazepine () suspension affords steady-state plasma levels comparable to Carbamazepine () tablets given b.i.d. when administered at the same total mg daily dose. Following a b.i.d. dosage regimen, Carbamazepine () -extended-release tablets afford steady-state plasma levels comparable to conventional Carbamazepine () tablets given q.i.d., when administered at the same total mg daily dose. Carbamazepine () in blood is 76% bound to plasma proteins. Plasma levels of Carbamazepine () are variable and may range from 0.5-25 µg/mL, with no apparent relationship to the daily intake of the drug. Usual adult therapeutic levels are between 4 and 12 µg/mL. In polytherapy, the concentration of Carbamazepine () and concomitant drugs may be increased or decreased during therapy, and drug effects may be altered (see Following chronic oral administration of suspension, plasma levels peak at approximately 1.5 hours compared to 4-5 hours after administration of conventional Carbamazepine () tablets, and 3-12 hours after administration of Carbamazepine () -extended-release tablets. The CSF/serum ratio is 0.22, similar to the 24% unbound Carbamazepine () in serum. Because Carbamazepine () induces its own metabolism, the half-life is also variable. Autoinduction is completed after 3-5 weeks of a fixed dosing regimen. Initial half-life values range from 25-65 hours, decreasing to 12-17 hours on repeated doses. Carbamazepine () is metabolized in the liver. Cytochrome P450 3A4 was identified as the major isoform responsible for the formation of Carbamazepine () -10,11-epoxide from Carbamazepine () . After oral administration of C-Carbamazepine () , 72% of the administered radioactivity was found in the urine and 28% in the feces. This urinary radioactivity was composed largely of hydroxylated and conjugated metabolites, with only 3% of unchanged Carbamazepine () .
The pharmacokinetic parameters of Carbamazepine () disposition are similar in children and in adults. However, there is a poor correlation between plasma concentrations of Carbamazepine () and Carbamazepine () dose in children. Carbamazepine () is more rapidly metabolized to Carbamazepine () -10,11-epoxide (a metabolite shown to be equipotent to Carbamazepine () as an anticonvulsant in animal screens) in the younger age groups than in adults. In children below the age of 15, there is an inverse relationship between CBZ-E/CBZ ratio and increasing age (in one report from 0.44 in children below the age of 1 year to 0.18 in children between 10-15 years of age).
The effects of race and gender on Carbamazepine () pharmacokinetics have not been systematically evaluated.
Carbamazepine () Indications And Usage
Carbamazepine () is indicated in the treatment of the pain associated with true trigeminal neuralgia.
Beneficial results have also been reported in glossopharyngeal neuralgia.
This drug is not a simple analgesic and should not be used for the relief of trivial aches or pains.
Carbamazepine () Contraindications
Carbamazepine () should not be used in patients with a history of previous bone marrow depression, hypersensitivity to the drug, or known sensitivity to any of the tricyclic compounds, such as amitriptyline, desipramine, imipramine, protriptyline, nortriptyline, etc. Likewise, on theoretical grounds its use with monoamine oxidase inhibitors is not recommended. Before administration of Carbamazepine () , MAO inhibitors should be discontinued for a minimum of 14 days, or longer if the clinical situation permits.
Coadministration of Carbamazepine () and nefazodone may result in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect. Coadministration of Carbamazepine () with nefazodone is contraindicated.
Carbamazepine () Warnings
Retrospective case-control studies have found that in patients of Chinese ancestry there is a strong association between the risk of developing SJS/TEN with Carbamazepine () treatment and the presence of an inherited variant of the HLA-B gene, HLA-B1502. The occurrence of higher rates of these reactions in countries with higher frequencies of this allele suggests that the risk may be increased in allele-positive individuals of any ethnicity.
Across Asian populations, notable variation exists in the prevalence of HLA-B1502. Greater than 15% of the population is reported positive in Hong Kong, Thailand, Malaysia, and parts of the Philippines, compared to about 10% in Taiwan and 4% in North China. South Asians, including Indians, appear to have intermediate prevalence of HLA-B1502, averaging 2 to 4%, but higher in some groups. HLA-B1502 is present in
HLA-B1502 is largely absent in individuals not of Asian origin (e.g., Caucasians, African-Americans, Hispanics, and Native Americans).
Over 90% of Carbamazepine () treated patients who will experience SJS/TEN have this reaction within the first few months of treatment. This information may be taken into consideration in determining the need for screening of genetically at-risk patients currently on Carbamazepine () .
The HLA-B1502 allele has not been found to predict risk of less severe adverse cutaneous reactions from Carbamazepine () , such as anticonvulsant hypersensitivity syndrome or nonserious rash (maculopapular eruption [MPE]).
Limited evidence suggests that HLA-B1502 may be a risk factor for the development of SJS/TEN in patients of Chinese ancestry taking other antiepileptic drugs associated with SJS/TEN. Consideration should be given to avoiding use of other drugs associated with SJS/TEN in HLA-B1502 positive patients, when alternative therapies are otherwise equally acceptable.
Application of HLA-B*1502 genotyping as a screening tool has important limitations and must never substitute for appropriate clinical vigilance and patient management. Many HLA-B1502-positive Asian patients treated with Carbamazepine () will not develop SJS/TEN, and these reactions can still occur infrequently in HLA-B1502-negative patients of any ethnicity. The role of other possible factors in the development of, and morbidity from, SJS/TEN, such as antiepileptic drug (AED) dose, compliance, concomitant medications, comorbidities, and the level of dermatologic monitoring have not been studied.
Antiepileptic drugs (AEDs), including Carbamazepine () , increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Table 1 shows absolute and relative risk by indication for all evaluated AEDs.
Table 1 Risk by Indication for Antiepileptic Drugs in the Pooled Analysis
The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing Carbamazepine () or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
Carbamazepine () has shown mild anticholinergic activity; therefore, patients with increased intraocular pressure should be closely observed during therapy.
Because of the relationship of the drug to other tricyclic compounds, the possibility of activation of a latent psychosis and, in elderly patients, of confusion or agitation should be borne in mind.
The use of Carbamazepine () should be avoided in patients with a history of hepatic porphyria (e.g., acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda). Acute attacks have been reported in such patients receiving Carbamazepine () therapy. Carbamazepine () administration has also been demonstrated to increase porphyrin precursors in rodents, a presumed mechanism for the induction of acute attacks of porphyria.
As with all antiepileptic drugs, Carbamazepine () should be withdrawn gradually to minimize the potential of increased seizure frequency.
Carbamazepine () can cause fetal harm when administered to a pregnant woman.
Epidemiological data suggest that there may be an association between the use of Carbamazepine () during pregnancy and congenital malformations, including spina bifida. There have also been reports that associate Carbamazepine () with developmental disorders and congenital anomalies (e.g., craniofacial defects, cardiovascular malformations, hypospadias and anomalies involving various body systems). Developmental delays based on neurobehavioral assessments have been reported. In treating or counseling women of childbearing potential, the prescribing physician will wish to weigh the benefits of therapy against the risks. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Retrospective case reviews suggest that, compared with monotherapy, there may be a higher prevalence of teratogenic effects associated with the use of anticonvulsants in combination therapy. Therefore, if therapy is to be continued, monotherapy may be preferable for pregnant women.
In humans, transplacental passage of Carbamazepine () is rapid (30-60 minutes), and the drug is accumulated in the fetal tissues, with higher levels found in liver and kidney than in brain and lung.
Carbamazepine () has been shown to have adverse effects in reproduction studies in rats when given orally in dosages 10-25 times the maximum human daily dosage (MHDD) of 1200 mg on a mg/kg basis or 1.5-4 times the MHDD on a mg/m basis. In rat teratology studies, 2 of 135 offspring showed kinked ribs at 250 mg/kg and 4 of 119 offspring at 650 mg/kg showed other anomalies (cleft palate, 1; talipes, 1; anophthalmos, 2). In reproduction studies in rats, nursing offspring demonstrated a lack of weight gain and an unkempt appearance at a maternal dosage level of 200 mg/kg.
Antiepileptic drugs should not be discontinued abruptly in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder are such that removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus.
Tests to detect defects using currently accepted procedures should be considered a part of routine prenatal care in childbearing women receiving Carbamazepine () .
There have been a few cases of neonatal seizures and/or respiratory depression associated with maternal Carbamazepine () and other concomitant anticonvulsant drug use. A few cases of neonatal vomiting, diarrhea, and/or decreased feeding have also been reported in association with maternal Carbamazepine () use. These symptoms may represent a neonatal withdrawal syndrome.
To provide information regarding the effects of in utero exposure to Carbamazepine () , physicians are advised to recommend that pregnant patients taking Carbamazepine () enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.
Carbamazepine () Precautions
Before initiating therapy, a detailed history and physical examination should be made.
Carbamazepine () should be used with caution in patients with a mixed seizure disorder that includes atypical absence seizures, since in these patients Carbamazepine () has been associated with increased frequency of generalized convulsions (see
Therapy should be prescribed only after critical benefit-to-risk appraisal in patients with a history of cardiac conduction disturbance, including second and third degree AV heart block; cardiac, hepatic, or renal damage; adverse hematologic or hypersensitivity reaction to other drugs, including reactions to other anticonvulsants; or interrupted courses of therapy with Carbamazepine () .
AV heart block, including second and third degree block, have been reported following Carbamazepine () treatment. This occurred generally, but not solely, in patients with underlying EKG abnormalities or risk factors for conduction disturbances.
Hepatic effects, ranging from slight elevations in liver enzymes to rare cases of hepatic failure have been reported (see and In some cases, hepatic effects may progress despite discontinuation of the drug.
Multiorgan hypersensitivity reactions occurring days to weeks or months after initiating treatment have been reported in rare cases (see and
Discontinuation of Carbamazepine () should be considered if any evidence of hypersensitivity develops.
Hypersensitivity reactions to Carbamazepine () have been reported in patients who previously experienced this reaction to anticonvulsants including phenytoin and phenobarbital. A history of hypersensitivity reactions should be obtained for a patient and the immediate family members. If positive, caution should be used in prescribing Carbamazepine () .
Patients should be made aware of the early toxic signs and symptoms of a potential hematologic problem, as well as dermatologic, hypersensitivity or hepatic reactions. These symptoms may include, but are not limited to, fever, sore throat, rash, ulcers in the mouth, easy bruising, lymphadenopathy and petechial or purpuric hemorrhage, and in the case of liver reactions, anorexia, nausea/vomiting, or jaundice. The patient should be advised that, because these signs and symptoms may signal a serious reaction, that they must report any occurrence immediately to a physician. In addition, the patient should be advised that these signs and symptoms should be reported even if mild or when occurring after extended use.
Patients, their caregivers, and families should be counseled that AEDs, including Carbamazepine () , may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
Carbamazepine () may interact with some drugs. Therefore, patients should be advised to report to their doctors the use of any other prescription or nonprescription medications or herbal products.
Caution should be exercised if alcohol is taken in combination with Carbamazepine () therapy, due to a possible additive sedative effect.
Since dizziness and drowsiness may occur, patients should be cautioned about the hazards of operating machinery or automobiles or engaging in other potentially dangerous tasks.
Patients should be encouraged to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see ).
For genetically at-risk patients (see high-resolution ‘is recommended. The test is positive if either one or two HLA-B*1502 alleles are detected and negative if no HLA-B*1502 alleles are detected.
Complete pretreatment blood counts, including platelets and possibly reticulocytes and serum iron, should be obtained as a baseline. If a patient in the course of treatment exhibits low or decreased white blood cell or platelet counts, the patient should be monitored closely. Discontinuation of the drug should be considered if any evidence of significant bone marrow depression develops.
Baseline and periodic evaluations of liver function, particularly in patients with a history of liver disease, must be performed during treatment with this drug since liver damage may occur (see and Carbamazepine () should be discontinued, based on clinical judgment, if indicated by newly occurring or worsening clinical or laboratory evidence of liver dysfunction or hepatic damage, or in the case of active liver disease.
Baseline and periodic eye examinations, including slit-lamp, funduscopy, and tonometry, are recommended since many phenothiazines and related drugs have been shown to cause eye changes.
Baseline and periodic complete urinalysis and BUN determinations are recommended for patients treated with this agent because of observed renal dysfunction.
Monitoring of blood levels (see has increased the efficacy and safety of anticonvulsants. This monitoring may be particularly useful in cases of dramatic increase in seizure frequency and for verification of compliance. In addition, measurement of drug serum levels may aid in determining the cause of toxicity when more than one medication is being used.
Thyroid function tests have been reported to show decreased values with Carbamazepine () administered alone.
Hyponatremia has been reported in association with Carbamazepine () use, either alone or in combination with other drugs.
Interference with some pregnancy tests has been reported.
CYP 3A4 inhibitors inhibit Carbamazepine () metabolism and can thus increase plasma Carbamazepine () levels. Drugs that have been shown, or would be expected, to increase plasma Carbamazepine () levels include:
cimetidine, danazol, diltiazem, macrolides, erythromycin, troleandomycin, clarithromycin, fluoxetine, fluvoxamine, nefazodone, loratadine, terfenadine, isoniazid, niacinamide, nicotinamide, propoxyphene, azoles (e.g., ketaconazole, itraconazole, fluconazole), acetazolamide, verapamil, grapefruit juice, protease inhibitors, valproate.
CYP 3A4 inducers can increase the rate of Carbamazepine () metabolism. Drugs that have been shown, or that would be expected, to decrease plasma Carbamazepine () levels include:
cisplatin, doxorubicin HCl, felbamate, rifampin, phenobarbital, phenytoin, primidone, methsuximide, theophylline.
When Carbamazepine () is given with drugs that can increase or decrease Carbamazepine () levels, close monitoring of Carbamazepine () levels is indicated and dosage adjustment may be required.
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†
Increased levels: clomipramine HCl, phenytoin, primidone
Carbamazepine () induces hepatic CYP activity. Carbamazepine () causes, or would be expected to cause, decreased levels of the following:
acetaminophen, alprazolam, dihydropyridine calcium channel blockers (e.g., felodipine), cyclosporine, corticosteroids (e.g., prednisolone, dexamethasone), clonazepam, clozapine, dicumarol, doxycycline, ethosuximide, haloperidol, itraconazole, lamotrigine, levothyroxine, methadone, methsuximide, midazolam, olanzapine, oral and other hormonal contraceptives, oxcarbazepine, phensuximide, phenytoin, praziquantel, protease inhibitors, risperidone, theophylline, tiagabine, topiramate, tramadol, tricyclic antidepressants (e.g., imipramine, amitriptyline, nortriptyline), valproate, warfarin, ziprasidone, zonisamide.
In concomitant use with Carbamazepine () , dosage adjustment of the above agents may be necessary.
Coadministration of Carbamazepine () with nefazodone results in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect. Coadministration of Carbamazepine () with nefazodone is contraindicated. (see
Concomitant administration of Carbamazepine () and lithium may increase the risk of neurotoxic side effects.
Alterations of thyroid function have been reported in combination therapy with other anticonvulsant medications.
Concomitant use of Carbamazepine () with hormonal contraceptive products (e.g., oral, and levonorgestrel subdermal implant contraceptives) may render the contraceptives less effective because the plasma concentrations of the hormones may be decreased. Breakthrough bleeding and unintended pregnancies have been reported. Alternative or back-up methods of contraception should be considered.
Carbamazepine () , when administered to Sprague-Dawley rats for two years in the diet at doses of 25, 75, and 250 mg/kg/day, resulted in a dose-related increase in the incidence of hepatocellular tumors in females and of benign interstitial cell adenomas in the testes of males.
Carbamazepine () must, therefore, be considered to be carcinogenic in Sprague-Dawley rats. Bacterial and mammalian mutagenicity studies using Carbamazepine () produced negative results. The significance of these findings relative to the use of Carbamazepine () in humans is, at present, unknown.
Carbamazepine () and its epoxide metabolite are transferred to breast milk. The ratio of the concentration in breast milk to that in maternal plasma is about 0.4 for Carbamazepine () and about 0.5 for the epoxide. The estimated doses given to the newborn during breast-feeding are in the range of 2-5 mg daily for Carbamazepine () and 1-2 mg daily for the epoxide.
Because of the potential for serious adverse reactions in nursing infants from Carbamazepine () , a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Substantial evidence of Carbamazepine () ’s effectiveness for use in the management of children with epilepsy (see ) is derived from clinical investigations performed in adults and from studies in several systems which support the conclusion that (1) the pathogenetic mechanisms underlying seizure propagation are essentially identical in adults and children, and (2) the mechanism of action of Carbamazepine () in treating seizures is essentially identical in adults and children.
Taken as a whole, this information supports a conclusion that the generally accepted therapeutic range of total Carbamazepine () in plasma (i.e., 4-12 mcg/mL) is the same in children and adults.
The evidence assembled was primarily obtained from short-term use of Carbamazepine () . The safety of Carbamazepine () in children has been systematically studied up to 6 months. No longer-term data from clinical trials is available.
Carbamazepine () Adverse Reactions
If adverse reactions are of such severity that the drug must be discontinued, the physician must be aware that abrupt discontinuation of any anticonvulsant drug in a responsive epileptic patient may lead to seizures or even status epilepticus with its life-threatening hazards.
The most severe adverse reactions have been observed in the hemopoietic system and skin (see the liver, and the cardiovascular system.
The most frequently observed adverse reactions, particularly during the initial phases of therapy, are dizziness, drowsiness, unsteadiness, nausea, and vomiting. To minimize the possibility of such reactions, therapy should be initiated at the low dosage recommended.
The following additional adverse reactions have been reported:
Some of these cardiovascular complications have resulted in fatalities. Myocardial infarction has been associated with other tricyclic compounds.
Testicular atrophy occurred in rats receiving Carbamazepine () orally from 4-52 weeks at dosage levels of 50-400 mg/kg/day. Additionally, rats receiving Carbamazepine () in the diet for 2 years at dosage levels of 25, 75, and 250 mg/kg/day had a dose-related incidence of testicular atrophy and aspermatogenesis. In dogs, it produced a brownish discoloration, presumably a metabolite, in the urinary bladder at dosage levels of 50 mg/kg and higher. Relevance of these findings to humans is unknown.
There have been reports of associated paralysis and other symptoms of cerebral arterial insufficiency, but the exact relationship of these reactions to the drug has not been established.
Isolated cases of neuroleptic malignant syndrome have been reported with concomitant use of psychotropic drugs.
Isolated cases of a lupus erythematosus-like syndrome have been reported. There have been occasional reports of elevated levels of cholesterol, HDL cholesterol, and triglycerides in patients taking anticonvulsants.
A case of aseptic meningitis, accompanied by myoclonus and peripheral eosinophilia, has been reported in a patient taking Carbamazepine () in combination with other medications. The patient was successfully dechallenged, and the meningitis reappeared upon rechallenge with Carbamazepine () .
Carbamazepine () Drug Abuse And Dependence
No evidence of abuse potential has been associated with Carbamazepine () , nor is there evidence of psychological or physical dependence in humans.
Carbamazepine () Overdosage
Lowest known lethal dose: adults, 3.2 g (a 24-year-old woman died of a cardiac arrest and a 24-year-old man died of pneumonia and hypoxic encephalopathy); children, 4 g (a 14-year-old girl died of a cardiac arrest), 1.6 g (a 3-year-old girl died of aspiration pneumonia).
Oral LD in animals (mg/kg): mice, 1100-3750; rats, 3850-4025; rabbits, 1500-2680; guinea pigs, 920.
The first signs and symptoms appear after 1-3 hours. Neuromuscular disturbances are the most prominent. Cardiovascular disorders are generally milder, and severe cardiac complications occur only when very high doses (> 60 g) have been ingested.
The prognosis in cases of severe poisoning is critically dependent upon prompt elimination of the drug, which may be achieved by inducing vomiting, irrigating the stomach, and by taking appropriate steps to diminish absorption. If these measures cannot be implemented without risk on the spot, the patient should be transferred at once to a hospital, while ensuring that vital functions are safeguarded. There is no specific antidote.
Gastric lavage. Even when more than 4 hours have elapsed following ingestion of the drug, the stomach should be repeatedly irrigated, especially if the patient has also consumed alcohol.
Dialysis is indicated only in severe poisoning associated with renal failure. Replacement transfusion is indicated in severe poisoning in small children.
Special periodic studies might be helpful as follows: (1) white cell and platelet antibodies, (2) Fe-ferrokinetic studies, (3) peripheral blood cell typing, (4) cytogenetic studies on marrow and peripheral blood, (5) bone marrow culture studies for colony-forming units, (6) hemoglobin electrophoresis for A and F hemoglobin, and (7) serum folic acid and B levels.
A fully developed aplastic anemia will require appropriate, intensive monitoring and therapy, for which specialized consultation should be sought.
Carbamazepine () Dosage And Administration (see Table Below)
Monitoring of blood levels has increased the efficacy and safety of anticonvulsants (see Dosage should be adjusted to the needs of the individual patient. A low initial daily dosage with a gradual increase is advised. As soon as adequate control is achieved, the dosage may be reduced very gradually to the minimum effective level. Medication should be taken with meals.
Conversion of patients from oral Carbamazepine () tablets to Carbamazepine () suspension: Patients should be converted by administering the same number of mg per day in smaller, more frequent doses (i.e., b.i.d. tablets to t.i.d. suspension).
Carbamazepine () How Supplied
Carbamazepine () Tablets USP (chewable), 100 mg are available in the following form: pink colored, circular, strawberry/vanilla flavored, flat beveled, uncoated tablets with "271" debossed on one side and scoreline on the other.
Bottle of 100 NDC 13668-271-01
Bottle of 500 NDC 13668-271-05
Bottle of 750 NDC 13668-271-49
Bottle of 1000 NDC 13668-271-10
Carbamazepine () Tablets USP, 100 mg are available in the following form: pink colored, capsule shaped, biconvex tablets with ‘539’ debossed on one side and plain on the other side.
Bottle of 100 NDC 13668-267-01
Bottle of 500 NDC 13668-267-05
Bottle of 1000 NDC 13668-267-10
Carbamazepine () Tablets USP, 200 mg are available in the following form: pink colored, capsule shaped, biconvex tablets with ‘268’ debossed on one side and scored on the other side.
Bottle of 30 NDC 13668-268-30
Bottle of 100 NDC 13668-268-01
Bottle of 500 NDC 13668-268-05
Bottle of 1000 NDC 13668-268-10
Bottle of 2500 NDC 13668-268-31
Carbamazepine () Tablets USP, 300 mg are available in the following form: pink colored, capsule shaped, biconvex tablets with ‘535’ debossed on one side and scored on the other side.
Bottle of 100 NDC 13668-269-01
Bottle of 500 NDC 13668-269-05
Bottle of 1000 NDC 13668-269-10
Carbamazepine () Tablets USP, 400 mg are available in the following form: pink colored, capsule shaped, biconvex tablets with ‘536’ debossed on one side and scored on the other side.
Bottle of 100 NDC 13668-270-01
Bottle of 500 NDC 13668-270-05
Bottle of 1000 NDC 13668-270-10
Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. Protect from light and moisture. Dispense in a tight, light-resistant container as defined in the USP.
Carbamazepine ()
Carbamazepine () Principal Display Panel
Carbamazepine ()
(Chewable)
Tablets, USP 100 mg
Carbamazepine () Principal Display Panel
NDC 13668-271-05 (Torrent)
Carbamazepine ()
Tablets, USP (Chewable)
100 mg
QTY 30
