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either been discontinued or is no longer marketed in New Zealand.
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professionals should continue to have access to this product information in the interim.
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Carbamazepine Tablets 200mg: 9mm, flat bevelled edge, white tablet, debossed G on one side and 
on the other.
Carbamazepine Tablets 400mg: 12.5mm, flat bevelled edge, white tablet, debossed G on one side and
on the other.
As an anti-epileptic agent its spectrum of activity embraces: partial seizures (simple and complex) with and without secondary generalisation; generalised tonic-clonic seizures (grand mal), as well as combinations of these types of epilepsy.
In clinical studies carbamazepine given as monotherapy to patients with epilepsy - in particular children and adolescents - has been reported to exert a psychotropic action, including a positive effect on symptoms of anxiety and depression, as well as a decrease in irritability and aggressiveness. As regards cognitive and psychomotor performance, in some studies equivocal or negative effects, depending also upon dosages administered, were reported. In other studies, a beneficial effect on attentiveness, cognitive performance/memory was observed.
As a neurotropic agent carbamazepine is clinically effective in a number of neurological disorders, e.g. it prevents paroxysmal attacks of pain in idiopathic trigeminal neuralgia; in alcohol-withdrawal syndrome it raises the lowered convulsion threshold and improves withdrawal symptoms (e.g. hyperexcitability, tremor, impaired gait); in diabetes insipidus centralis, carbamazepine reduces the urinary volume and relieves the feeling of thirst.
As a psychotropic agent carbamazepine proved to have clinical efficacy in affective disorders, i.e. as a treatment for acute mania as well as for the maintenance of manic-depressive (bipolar) disorders when given either as monotherapy or in combination with major neuroleptics, anti-depressants, or lithium.
The mechanism of action of carbamazepine, the active substance of carbamazepine, has only been partially elucidated. Carbamazepine stabilises hyperexcited nerve membranes, inhibits repetitive neuronal discharges, and reduces synaptic propagation of excitatory impulses. It is conceivable that prevention of repetitive firing of sodium-dependent action potentials in depolarized neurons via use- and voltage-dependent blockade of sodium channels may be its main mechanism of action.
Whereas reduction of glutamate release and stabilisation of neuronal membranes may account mainly for the anti-epileptic effects, the depressant effect on dopamine and noradrenaline turnover could be responsible for the antimanic properties of carbamazepine.
Carbamazepine is absorbed relatively slowly from the tablets. Conventional carbamazepine tablets yield mean peak plasma concentrations of the unchanged substance within 12 hours, following single oral doses. The absorption of carbamazepine is almost complete. With respect to the amount of active substance absorbed, there is no clinically relevant difference between the dosage forms. After a single oral dose of 400mg carbamazepine the mean peak concentration of unchanged carbamazepine (cbz) in the plasma is approximately 4.5μg/mL.
Ingestion of food has no significant influence on the rate and extent of absorption.
Steady-state plasma concentrations of carbamazepine are attained within about 1-2 weeks, depending individually upon auto-induction by carbamazepine and hetero-induction by other enzyme-inducing agents, as well as on pretreatment status, dosage, and duration of treatment. Carbamazepine is bound to serum proteins to the extent of 70-80%. The concentration of unchanged substance in cerebrospinal fluid and saliva reflects the non-protein bound portion in the plasma (20-30%). Concentrations in breast milk were found to be equivalent to 25-60% of the corresponding plasma levels. Carbamazepine crosses the placental barrier. Assuming complete absorption of carbamazepine, the apparent volume of distribution ranges from 0.8 to 1.9 L/kg.
The elimination half-life of unchanged carbamazepine averages approximately 36 hours following a single oral dose, whereas after repeated administration it averages only 16-24 hours (auto-induction of the hepatic monooxygenase system), depending on the duration of the medication. In patients receiving concomitant treatment with other liver-enzyme inducing agents (e.g. phenytoin, phenobarbitone), half-life values averaging 9-10 hours have been found.
The mean elimination half-life of 10,11-epoxide metabolite in the plasma is about 6 hours following single oral doses of the epoxide itself.
After administration of a single oral dose of 400mg carbamazepine, 72% is excreted in the urine and 28% in the faeces. In the urine, about 2% of the dose is recovered as unchanged medicine and about 1% as the pharmacologically active 10,11-epoxide metabolite. Carbamazepine is metabolised in the liver, where the epoxide pathway of biotransformation is the most important one, yielding the 10,11-trans-diol derivative and its glucuronide as the main metabolites. Cytochrome P4503A4 has been identified as the major isoform responsible for the formation of carbamazepine-10,11 epoxide from carbamazepine. 9-Hydroxy-methyl-10-carbamoyl acridan is a minor metabolite related to this pathway. After a single oral dose of carbamazepine about 30% appears in the urine as end-products of the epoxide pathway.
Other important biotransformation pathways for carbamazepine lead to various monohydroxylated compounds, as well as to the N-glucuronide of carbamazepine. The steady-state plasma concentrations of carbamazepine considered as "therapeutic range" vary considerably inter-individually: For the majority of patients a range between 4-12 μg/mL corresponding to 17-50 μmol/L has been reported. Concentrations of cbz-10,11-epoxide (pharmacologically active metabolite): about 30% of cbz levels.
Owing to enhanced carbamazepine elimination, children may require higher doses of carbamazepine (in mg/kg) than adults.
There is no indication of altered pharmacokinetics of carbamazepine in elderly patients as compared with young adults.
No data are available on the pharmacokinetics of carbamazepine in patients with impaired hepatic or renal function.
Epilepsy except absence seizures.
Partial seizures (with or without loss of consciousness) with or without secondary generalization:
Primary generalised epilepsy or secondarily generalised seizures with a tonic-clonic component. Mixed forms of these seizures.
Carbamazepine is suitable both for monotherapy and combination therapy.
Carbamazepine is usually not effective in absences (petit mal) and myoclonic seizures (see Warnings and Precautions).
Acute mania and maintenance treatment in manic-depressive (bipolar) disorders to prevent or attenuate recurrence.
Alcohol-withdrawal syndrome.
Idiopathic trigeminal neuralgia and trigeminal neuralgia due to multiple sclerosis (either typical or atypical. Idiopathic glossopharyngeal neuralgia.
Painful diabetic neuropathy.
Diabetes insipidus centralis.
Polyuria and polydipsia of neurohormonal origin.
The tablets may be taken during, after, or between meals with a little liquid, and possible remnants of the chewable tablets should be washed down with a little liquid. Due to drug interactions and different antiepileptic drug pharmacokinetics, the dosage of Carbamazepine should be selected with caution in elderly patients.
Wherever possible, carbamazepine should be prescribed as monotherapy.
Treatment should be initiated with a low daily dosage, to be slowly increased until an optimal effect is obtained. After obtaining adequate seizure control dosage may be reduced very gradually to the minimum effective level. Determination of plasma levels may help in establishing the optimum dosage (see Warnings and Precautions).
When carbamazepine is added to existing anticonvulsant therapy, this should be done gradually while maintaining, or if necessary adapting, the dosage of the other anticonvulsant(s) (see Interactions).
Adults:
Initially, 100-200mg once or twice daily; slowly raise the dosage until - generally at 400mg 2-3 times daily - an optimum response is obtained. In some patients 1600mg or even 2000mg daily may be appropriate. Refer to Table 1. In children aged 4 years or less, a starting dose of 20 to 60mg/day, increased by 20 to 60mg every second day, has been recommended. For children over the age of 4 years, therapy may begin with 100mg/day, increased at weekly intervals by 100mg.
Slowly raise the initial dosage of 200-400mg daily until freedom from pain is achieved (normally at 600-800mg daily). Then gradually reduce the dosage to the lowest possible maintenance level. In elderly patients an initial dose of 100mg twice daily is recommended.
Average dosage: 600mg daily. In severe cases it can be raised during the first few days (e.g. to 1200mg daily). At the start of treatment for severe withdrawal manifestations, carbamazepine should be given in combination with sedative-hypnotic medicines (e.g. clomethiazole, chlordiazepoxide). After the acute stage has abated, carbamazepine can be continued as monotherapy.
Average dosage for adults: 400-600mg daily. In children the dosage should be reduced proportionally to the child's age and body weight.
Average dosage: 400-800mg daily.
Dosage Range: about 400-1600mg daily, the usual dosage being 400-600mg daily given in 2-3 fractional dosed. When treating acute mania, the dosage should be increased rather quickly, whereas for maintenance of bipolar disorders small dosage increments are recommended in order to provide for optimal tolerability.
Known hypersensitivity to carbamazepine, any other component of the formulation or structurally related medicines (e.g. tricyclic antidepressants).
Table 1
| Children: 10-20 mg/kg body weight daily | |
|---|---|
| Up to 1 year of age | 100-200mg daily |
| 1-5 years of age | 200-400mg daily |
| 6-10 years of age | 400-600mg daily |
| 11-15 years of age | 600-1000mg daily |
| To be taken in several fractional doses | |
Patients with atrioventricular block, a history of previous bone marrow depression, or a history of acute intermittent
porphyria. On theoretical grounds (a structural relationship to tricyclic antidepressants) the use of carbamazepine is
not recommended in combination with monoamine-oxidase inhibitors (MAOIs); before administering carbamazepine, MAOIs
should be discontinued for a minimum of 2 weeks, or longer if the clinical situation permits.
Agranulocytosis and aplastic anaemia have been associated with carbamazepine; however, due to the very low incidence of these diseases, meaningful risk estimates for carbamazepine are difficult to obtain. The overall risk in the general untreated population has been estimated at 4.7 persons per million per year for agranulocytosis and 2.0 persons per million per year for aplastic anaemia.
Transient or persistent decreased platelet or white blood cell counts occur occasionally to frequently in association with the use of carbamazepine. However, in the vast majority of cases these effects prove transient and are unlikely to signal the onset of either aplastic anaemia or agranulocytosis. Nonetheless, complete pretreatment blood counts, including platelets and possibly reticulocytes and serum iron should be obtained as a baseline, and periodically thereafter.
If during treatment definitely low or decreased white blood cell or platelet counts are observed, the patient and the complete blood count should be monitored closely. Carbamazepine should be discontinued if any evidence of significant bone-marrow depression appears.
If signs and symptoms suggestive of severe skin reactions, e.g. Stevens-Johnson syndrome, Lyell's syndrome, appear, carbamazepine should be withdrawn at once.
Carbamazepine should be given only under medical supervision.
It should be used with caution in patients with a mixed seizure disorder which includes absences , either atypical or typical seizures. In case of exacerbation of seizures, carbamazepine should be discontinued.
Patients should be made aware of early toxic signs and symptoms of a potential haematological problem, as well as symptoms of dermatological or hepatic reactions. If reactions such as fever, sore throat, rash, ulcers in the mouth, easy bruising, petechial or purpuric haemorrhage appear, the patient should be advised to consult their physician immediately.
Carbamazepine should be prescribed only after a critical benefit-risk appraisal and under close monitoring in patients with a history of cardiac, hepatic, or renal damage, adverse haematological reactions to other medicines, or interrupted courses of therapy with carbamazepine.
Baseline and periodic evaluations of hepatic function, particularly in patients with a history of liver disease and in elderly patients, must be performed during treatment with carbamazepine. The medicine should be withdrawn immediately in cases of aggravated liver dysfunction or active liver disease.
Baseline and periodic complete urinalysis and BUN determinations are recommended.
Mild skin reactions, e.g. isolated macular or maculopapular exanthema, are mostly transient and not hazardous, and they usually disappear within a few days or weeks, either during the continued course of treatment or following a decrease in dosage; however, the patient should be kept under close surveillance (see above).
Carbamazepine has shown mild anticholinergic activity; patients with increased intra-ocular pressure should therefore be closely observed during therapy.
The possibility of activation of a latent psychosis and, in elderly patients, of confusion or agitation should be borne in mind.
Isolated reports of impaired male fertility and/or abnormal spermatogenesis are on file. A causal relationship has not been established.
Breakthrough bleeding has been reported in women taking oral contraceptives; the reliability of oral contraceptives may be adversely affected by carbamazepine.
Although correlations between dosage and plasma levels of carbamazepine, and between plasma levels and clinical efficacy or tolerability are rather tenuous, monitoring of the plasma levels may be useful in the following conditions: dramatic increase in seizure frequency/verification of patient compliance; during pregnancy; when treating children or adolescents; in suspected absorption disorders; in suspected toxicity when more than one medicine is being used (see Interactions).
Abrupt withdrawal of carbamazepine may precipitate seizures. If treatment with carbamazepine has to be withdrawn abruptly, the change-over to the new anti-epileptic compound should be made under cover of a suitable medicine (e.g. diazepam IV, rectal; or phenytoin IV).
Cross-hypersensitivity can occur between carbamazepine and oxcarbazepine (Trileptal® in approximately 25-30% of the patients.
Cross-hypersensitivity can occur between carbamazepine and phenytoin. 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, diarrhoea and/or decreased feeding have also been reported in association with maternal Carbamazepine use. These reactions may represent a neonatal withdrawal syndrome.
In rats treated with carbamazepine for 2 years, the incidence of tumours of the liver was found to be increased. The significance of these findings relative to the use of carbamazepine in humans is, at present, unknown. Bacterial and mammalian mutagenicity studies yielded negative results.
In animals (mice, rats, rabbits) oral administration of carbamazepine during organogenesis led to increased embryonic mortality at daily doses which caused maternal toxicity (above 200mg/kg body weight daily, i.e. 10-20 times the usual human dosage). In the rat there was also some indication of abortion at 300mg/kg body weight daily. Near-term rat foetuses showed growth retardation, again at maternally toxic doses. There was no evidence of teratogenic potential in the three animal species tested, but, in one study using mice, carbamazepine (40-240 mg/kg body weight daily, orally) caused defects (mainly dilation of cerebral ventricles) in 4.7% of exposed foetuses as compared with 1.3% in controls.
Pregnant women with epilepsy should be treated with special care.
In women of childbearing age carbamazepine should, wherever possible, be prescribed as monotherapy, because of the incidence of congenital abnormalities in the offspring of women treated with a combination of anti-epileptic medicines (e.g. valproic acid plus carbamazepine plus phenobarbitone and/or phenytoin) is greater than in those of mothers receiving the individual medicines as monotherapy.
Minimum effective doses should be given and monitoring of plasma levels is recommended.
If pregnancy occurs in women receiving carbamazepine, or if the problem of initiating treatment with carbamazepine arises during pregnancy, the medicine's potential benefits must be carefully weighed against its possible hazards, particularly in the first three months of pregnancy.
Offspring of epileptic mothers are known to be more prone to developmental disorders, including malformations. The possibility that carbamazepine, like all major anti-epileptic agents, increases this risk has been reported, although conclusive evidence from controlled studies with carbamazepine monotherapy is lacking. However, there are rare reports on developmental disorders and malformations including spina bifida and also other congenital anomalies, e.g. craniofacial defects, cardiovascular malformations, and anomalies involving various body systems, have been reported in association with carbamazepine.
Patients should be counselled regarding the possibility of an increased risk of malformations and given the opportunity of antenatal screening.
Folic acid deficiency is known to occur in pregnancy. Anti-epileptic agents have been reported to aggravate folic acid deficiency. This deficiency may contribute to the increased incidence of birth defects in the offspring of treated epileptic women. Folic acid supplementation has therefore been recommended before and during pregnancy.
Vitamin K1, to be given to the mother during the last weeks of pregnancy as well as to the newborn to prevent bleeding disorders in the offspring, has also been recommended.
Carbamazepine passes into the breast milk (about 25-60% of plasma concentrations). The benefits of breast-feeding should be weighed against the remote possibility of adverse effects occurring in the infant. Mothers taking carbamazepine may breast-feed their infants, provided the infant is observed for possible adverse reactions (e.g. excessive somnolence, allergic reactions.).
The patient's ability to react may be impaired by dizziness and drowsiness caused by carbamazepine, especially at the start of treatment or in connection with dose adjustments; patients should therefore exercise due caution when driving a vehicle or operating machinery.
Frequency of Adverse Effects:
Estimates from clinical trials and spontaneous ADR reports, classified in the following table.
| Classification | Frequency (%) |
|---|---|
| Very Common | > 10% |
| Common | > 1% to 10% |
| Uncommon | > 0.1% to <1% |
| Rare | < 0.01%-<0.1% |
| Very rare | <0.01% |
Particularly at the start of treatment with carbamazepine, or if the initial dosage is too high, or when treating
elderly patients, certain types of adverse reaction occur very commonly or commonly, e.g. CNS adverse reactions
(dizziness, headache, ataxia, drowsiness, fatigue, diplopia); gastrointestinal disturbances (nausea, vomiting), as well
as allergic skin reactions.
The dose-related adverse reactions usually abate within a few days, either spontaneously or after a transient dosage reduction. The occurrence of CNS adverse reactions may be a manifestation of relative overdosage or significant fluctuation in plasma levels. In such cases it is advisable to monitor the plasma levels and possibly to lower the daily dosage and/or divide it into 3-4 fractional doses.
Very Common: dizziness, ataxia, drowsiness, fatigue.
Common: headache, diplopia, accommodation disorders (e.g. blurred vision).
Uncommon: abnormal involuntary movements (e.g. tremor, asterixis, orofacial dyskinesia, choreoathetotic disorders, dystonia, tics), nystagmus.
Rare: oculomotor disturbances, speech disorders (e.g. dysarthria or slurred speech), peripheral neuritis, paraesthesia, muscle weakness, and paretic symptoms.
Rare: hallucinations (visual or acoustic), depression, loss of appetite, restlessness, aggressive behaviour, agitation, confusion.
Very rare: activation of psychosis.
Very Common: allergic skin reactions, urticaria, which may be severe.
Uncommon: exfoliative dermatitis and erythroderma.
Rare: systemic lupus erythematosus-like syndrome, pruritus.
Very rare: Stevens-Johnson syndrome ,toxic epidermal necrolysis, photosensitivity, erythema multiforme and nodosum, alterations in skin pigmentation, purpura, acne, sweating, hair loss. Isolated cases of hirsutism have been reported, but the causal relationship is not clear.
Very common: leucopenia.
Common: eosinophilia, thrombocytopenia.
Rare: leucocytosis, lymphadenopathy, folic acid deficiency.
Very Rare: agranulocytosis, aplastic anaemia, pure red cell aplasia, megaloblastic anaemia, acute intermittent porphyria, reticulocytosis, and possibly haemolytic anaemia.
Very Common: elevated gamma-GT (due to hepatic enzyme induction), usually not clinically relevant.
Uncommon: elevated alkaline phosphatase, rarely transaminases.
Rare: jaundice, hepatitis of cholestatic, parenchymal (hepatocellular), or mixed type jaundice.
Very rare: granulomatous hepatitis, hepatic failure.
Very Common: nausea, vomiting.
Common: dryness of the mouth.
Uncommon: diarrhoea or constipation.
Rare: abdominal pain.
Very Rare: glossitis, stomatitis.
Rare: a delayed multi-organ hypersensitivity disorder with fever, skin rashes, vasculitis, lymphadenopathy, disorders mimicking lymphoma, arthralgia, leucopenia, eosinophilia, hepato-splenomegaly and abnormal liver function tests, occurring in various combinations. Other organs may also be affected (e.g. lungs, kidneys, pancreas, myocardium).
Very Rare: asceptic meningitis, with myoclonus and peripheral eosinophilia; anaphylactic reaction, angioedema.
Treatment should be discontinued when such hypersensitivity reactions occur.
Rare: disturbances of cardiac conduction.
Very rare: bradycardia, arrhythmias, AV-block with syncope, collapse, congestive heart failure, hypertension or hypotension, aggravation of coronary artery disease, thrombophlebitis, thromboembolism.
Common: oedema, fluid retention, weight increase, hyponatraemia and reduced plasma osmolality due to an antidiuretic hormone (ADH)-like effect, leading in isolated cases to water intoxication accompanied by lethargy, vomiting, headache, mental confusion, neurological abnormalities.
Very Rare: increase in prolactin with or without clinical manifestations such as: gynaecomastia or galactorrhoea, abnormal thyroid function tests: decreased L-thyroxine (FT4, T4, T3) and increased TSH, usually without clinical manifestations, disturbances of bone metabolism (decrease in plasma calcium and 25-OH-cholecalciferol), leading in isolated cases to osteomalacia, elevated levels of cholesterol, including HDL cholesterol, and triglycerides.
Very rare: interstitial nephritis and renal failure, as well as signs of renal dysfunction (e.g. albuminuria, haematuria, oliguria and elevated BUN/azotaemia), urinary frequency, urinary retention, and sexual disturbances/impotence.
Very rare: taste disturbances, lens opacities, conjunctivitis, tinnitus, hyperacousia, hypoacusis, change in pitch perception.
Very rare: arthralgia, muscle pain or cramp.
Very rare: pulmonary hypersensitivity characterised by fever, dyspnoea, pneumonitis or pneumonia.
Cytochrome P4503A4 (CYP3A4) is the main enzyme catalyzing formation of carbamazepine-10,11 epoxide. Coadministration of inhibitors of CYP3A4 may result in increased plasma concentrations which could induce adverse reactions. Coadministration of CYP3A4 inducers might increase the rate of carbamazepine metabolism, thus leading to a potential decrease in carbamazepine serum level and potential decrease in the therapeutic effect. Similarly, discontinuation of a CYP3A4 inducer may decrease the rate of metabolism of carbamazepine, leading to an increase in carbamazepine plasma levels.
Isoniazid, verapamil, diltiazem, dextropropoxyphene, viloxazine, fluoxetine, fluvoxamine, possibly cimetidine, acetazolamide, danazol, possibly desipramine, nicotinamide (in adults, only in high dosage), nefazodone, macrolide antibiotics (e.g. erythromycin, troleandomycin, josamycin, clarithromycin), azoles (e.g. itraconazole, ketoconazole, fluconazole), terfenadine, loratadine, grapefruit juice, protease inhibitors for HIV treatment (e.g. ritonavir).
Since raised plasma carbamazepine levels may result in adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of Carbamazepine should be adjusted accordingly and/or the plasma levels monitored.
Phenobarbitone, phenytoin, primidone, progabide, or theophylline, methsuximide, phensuximide, rifampicin, cisplatin or doxorubicin and, although the data are partly contradictory, possibly also clonazepam, valproic acid or valpromide. Oxcarbazepine; herbal preparations containing St John's wort (Hypericum perforatum). On the other hand, valproic acid, valpromide and primidone have been reported to raise the plasma level of the pharmacologically active carbamazepine-10,11-epoxide metabolite. The dose of carbamazepine may consequently have to be adjusted.
Coadministration of felbamate might decrease the carbamazepine serum concentration associated with an increase in carbamazepine-epoxide concentration and might decrease the felbamate serum concentration.
Isotretinoin has been reported to alter the bioavailability and/or clearance of carbamazepine and carbamazepine-10,11-epoxide; plasma carbamazepine levels should be monitored.
Carbamazepine may lower the plasma level, or diminish, or even abolish the activity of certain drugs. The dosage of the following drugs may have to be adjusted to clinical requirements: clobazam, clonazepam, ethosuximide, primidone, valproic acid, alprazolam, corticosteroids, (e.g. prednisolone, dexamethasone); cyclosporin, digoxin, doxycycline, felodipine, haloperidol, imipramine, methadone, oral contraceptives (alternative contraceptive methods should be considered), theophylline, oral anticoagulants (warfarin, phenprocoumon, dicoumarol), felbamate, lamotrigine, zonisamide, tiagabine, topiramate, tricyclic antidepressants (e.g. imipramine, amitriptyline, nortriptyline, clomipramine), clozapine, oxcarbazepine; protease inhibitors for HIV treatment, e.g. indinavir, ritonavir, saquinavir; calcium channel blockers (dihydropyridine group), e.g., felodipine; itraconazole; levothyroxine; midazolam; olanzapine; products containing oestrogens and/or progesterones; praziquantel; risperidone; tramadol; ziprasidone.
Plasma phenytoin levels have been reported both to be raised and to be lowered by carbamazepine, and plasma mephenytoin levels have been reported in rare instances to increase.
Coadministration of carbamazepine and paracetamol may reduce the bioavailability of paracetamol/acetaminophen.
Concomitant use of carbamazepine and isoniazid has been reported to increase isoniazid-induced hepatotoxicity.
Combined use of carbamazepine and lithium or metoclopramide on the one hand, and carbamazepine and neuroleptics (haloperidol, thioridazine) on the other, may lead to increased neurological adverse reactions (with the latter combination even in the presence of 'therapeutic plasma levels').
Concomitant medication with carbamazepine and some diuretics (hydrochlorothiazide, furosemide) may lead to symptomatic hyponatraemia.
Carbamazepine may antagonize the effects of non-depolarizing muscle relaxants (e.g. pancuronium); their dosage may need to be raised, and patients should be monitored closely for more rapid recovery from neuromuscular blockade than expected.
Carbamazepine, like other psychoactive drugs, may reduce alcohol tolerance; it is therefore advisable for the patient to abstain from alcohol.
The presenting signs and symptoms of overdosage usually involve the central nervous, cardiovascular, and respiratory systems.
CNS depression; disorientation, somnolence, agitation, hallucination, coma; blurred vision, slurred speech, dysarthria, nystagmus, ataxia, dyskinesia, initially hyperreflexia, later hyporeflexia; convulsions, psychomotor disturbances, myoclonus, hypothermia.
Respiratory depression, pulmonary oedema.
Tachycardia, hypotension, at times hypertension, conduction disturbance with widening of QRS complex; syncope in association with cardiac arrest.
Vomiting, delayed gastric emptying, reduced bowel motility.
Retention of urine, oliguria or anuria; fluid retention, water intoxication due to an ADH-like effect of carbamazepine.
Hyponatraemia, possibly metabolic acidosis, possibly hyperglycaemia, increased muscle creatinine phosphokinase.
There is no specific antidote.
Management should initially be guided by the patient's clinical condition; admission to hospital. Measurement of the plasma level to confirm carbamazepine poisoning and to ascertain the size of the overdose.
Evacuation of the stomach, gastric lavage, and administration of activated charcoal. Supportive medical care in a intensive care unit with cardiac monitoring and careful correction of electrolyte imbalance.
Hypotension: Administer dopamine or dobutamine IV. Disturbances of cardiac rhythm: to be handled on an individual basis.
Convulsions: Administer a benzodiazepine (e.g. diazepam) or another anticonvulsant, e.g. phenobarbitone (with caution because of increase respiratory depression), or paraldehyde.
Hyponatraemia (water intoxication): Fluid restriction and slow and careful NaCl 0.9% infusion IV. These measures may be useful in preventing brain damage.
Charcoal haemoperfusion has been recommended. Forced diuresis, haemodialysis, and peritoneal dialysis have been reported to be not effective.
Relapse and aggravation of symptomatology on the 2nd and 3rd day after overdose, due to delayed absorption, should be anticipated.
Store below 25°C. Protect from moisture.
Prescription Medicine.
Tablets 200 mg: Bottles of 100's and 500's.
Tablets 400 mg: Bottles of 100's (not currently marketed)
Nil.
Pacific Pharmaceuticals Ltd
PO Box 11-183
Ellerslie
AUCKLAND
Telephone: 09-579-2792
25 January 2006