Carbamazepine oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of carbamazepine.
Drugs List
Therapeutic Indications
Uses
Epilepsy - grand mal
Epilepsy - partial seizures
Prophylaxis of manic-depressive illness unresponsive to lithium
Trigeminal neuralgia
Unlicensed Uses
Acute alcohol withdrawal
Diabetes insipidus
Diabetic neuropathy
Neuropathic pain
Dosage
Dose adjustment should always depend on the clinical response in the individual patient. Monitoring of plasma levels may be useful in certain conditions.
Modified release tablets are given in the same total daily dose as the standard preparations, usually in two divided doses only.
Adults
Epilepsy: generalised tonic-clonic and partial seizures
Initial dose: 100mg to 200mg once or twice daily, slowly increase, according to individual patient, until the best response is obtained.
Maintenance dose: 800mg to 1200mg daily, in divided doses. Dosage may be increased to 1600mg to 2000mg, if considered necessary.
Dose related adverse reactions may occur during initial therapy, these usually abate within a few days either spontaneously or after a transient dosage reduction.
In such cases monitoring of plasma levels and division of the daily dosage to smaller (i.e. 3 to 4) fractional doses is advised.
Trigeminal neuralgia
Initial dose: 100mg to 400mg a day, given in divided doses.
Dosage may be increased slowly until pain has stopped, maximum dose should not exceed 1600mg a day.
Once the pain is in remission, gradually reduce the dose to the lowest effective level.
Prophylaxis of manic-depressive psychosis unresponsive to lithium therapy
Initial dose: 100mg to 400mg daily, given in divided doses.
Maintenance dose: 400mg to 600mg. Dosage may be increased gradually based on individual patient response, until symptoms are controlled. Maximum dose should not exceed 1600mg a day.
Diabetic neuropathy (unlicensed)
Initial dose: 100mg once or twice daily.
Maintenance dose: 200mg three to four times a day. Increased gradually according to individual patient response. Maximum dose should not exceed 1600mg a day.
Treatment of alcohol withdrawal (unlicensed)
Initial dose: 800mg daily, given in divided doses.
Reduce dosage gradually to 200mg a day, over a period of 5 days.
Duration of treatment usually is 7 to 10 days.
Elderly
Epilepsy: generalised tonic-clonic and partial seizures
(See Dosage; Adult)
Trigeminal neuralgia
Initial dose: 100mg twice a day.
Dosage may be increased slowly until pain has stopped, maximum dose should not exceed 1200mg a day.
Once the pain is in remission, gradually reduce the dose to the lowest effective level.
Prophylaxis of manic depressive psychosis unresponsive to lithium therapy
(See Dosage; Adult)
Children
Epilepsy: generalised tonic-clonic and partial seizures
10mg/kg to 20mg/kg a day, given in divided doses.
Children aged 15 to 18 years
(See Dosage; Adult)
Children aged 10 to 15 years
600mg to 1000mg a day, given in divided doses
The dosage for prolonged release tablets varies between manufacturer and the following dosage is also suggested:
Initial dose: 200mg at night (or 100mg morning and night)
Maintenance dose: 100mg to 400mg in the morning and 400mg to 600mg at night.
Children aged 5 to 10 years
400mg to 600mg a day, given in divided doses
The dosage for prolonged release tablets varies between manufacturer and the following dosage is also suggested:
Initial dose: 200mg at night (or 100 mg morning and night)
Maintenance dose: 100mg to 200mg in the morning and 200mg to 400mg at night.
Children aged 1 to 5 years
Chewable tablets or oral solution should be used for this age group.
200mg to 400mg a day when appropriate.
Children under 1 year
The oral solution is suitable for this age group.
100mg to 200mg a day.
Partial and generalised tonic-clonic seizures, trigeminal neuralgia, and prophylaxis of bipolar disorder may be suitable
Children 12 years to 18 years
Initial dose: 100mg to 200mg once or twice daily.
Maintenance dose: 200mg to 400mg two to three times a day. Dosage may be increased slowly, if considered necessary. Maximum dose should not exceed 1800mg a day.
Children 1 month to 12 years
Initial dose: 5mg/kg at night or 2.5mg/kg twice a day. Dosage may be increased slowly, if considered necessary by 2.5mg/kg to 5mg/kg every 3 to 7 days.
Maintenance dose: 5mg/kg two to three times daily. Maximum dose should not exceed 20mg/kg a day.
Additional Dosage Information
Different preparations of carbamazepine vary in bioavailability; to avoid reduced effect or risk of breakthrough seizures or excessive side effects, it may be prudent to avoid changing the formulation.
A dose of the oral solution will result in higher plasma levels of carbamazepine than the same dose administered as tablets. When switching patients from tablets to liquid the same overall dose may be used but in smaller, more frequent doses. It is recommended to start with low doses of the liquid and to increase them slowly.
When transferring form standard release to prolonged release, the same total daily dose will be generally suitable. In a few patients, it may be necessary to increase the total daily dose, particularly when it is used with other antiepileptics.
If sudden withdrawal is required due to adverse reactions, the change to alternative medication should be under the cover of a suitable alternative such as intravenous or rectal diazepam or intravenous phenytoin.
Therapeutic Drug Monitoring
Refer to local therapeutic drug monitoring service for specific local carbamazepine guidelines.
Monitoring of plasma levels may be useful in certain conditions: dramatic increase in seizure frequency, verification of patient compliance, during pregnancy, when treating children or adolescents, possible absorption disorders and in suspected toxicity when more than one drug is being used.
Steady state plasma concentrations vary inter-individually, but are usually achieved within a period of 1 to 2 weeks. The recommended therapeutic plasma concentration range is between 4 to 12 micrograms per ml (17 to 50 micromoles per litre).
The bioavailability of carbamazepine in various oral formulations has been shown to be between 85 to 100%. The modified release preparation has a 15% lower bioavailability than standard preparations due mainly to the considerable reduction in peak plasma levels. To avoid reduced effect or risk of breakthrough seizures or excessive side effects, it may be prudent to avoid changing the formulation. Bioavailability is unaffected by food regardless of formulation.
Owing to enhanced carbamazepine elimination, children may require higher doses of carbamazepine (in mg/kg) than adults to maintain therapeutic concentrations.
Carbamazepine is 70 to 80% bound to serum protein.
Carbamazepine induces its own metabolism and the half life falls with repeated dosing. The elimination half-life of unchanged drug in the plasma averages 36 hours following a single dose. After repeated dosing (which leads to auto-induction of the hepatic enzymes) the half-life falls to approximately 16 to 24 hours. In patients receiving concomitant enzyme-inducing medications (phenobarbitone, phenytoin) the half life may be further reduced to 9 to 10 hours.
Contraindications
Neonates under 1 month
Within 2 weeks of discontinuing MAOIs
Atrioventricular block
History of myelosuppression
Porphyria
Precautions and Warnings
East Asian ancestry
Elderly
Females of childbearing potential
Thai and Han Chinese ancestry positive for HLA-B 1502
Breastfeeding
Cardiac impairment
Galactosaemia
Glaucoma
Glucose-galactose malabsorption syndrome
Haematological disorder
Hepatic impairment
Hereditary fructose intolerance
History of drug induced haematological reactions
Hypothyroidism
Lactose intolerance
Pregnancy
Renal impairment
Seizures
Urinary retention
Advise impaired alertness may affect ability to drive or operate machinery
Confirm HLA-B 1502 status in Han Chinese & Thai patients before initiating
Cross sensitivity can occur with other antiepileptics
Folic acid 5mg daily required pre-conception to end of 1st trimester
Increased risk of osteomalacia; consider vitamin D supplement
Not all available brands are licensed for all age groups
Not all formulations are suitable for use in children under 5 years
Prescribe by manufacturer's product to ensure seizure control maintenance
Oral liquid contains hydroxybenzoate: caution in hypersensitivity
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain lactose
Some formulations contain sunset yellow (E110); may cause allergic reaction
Blood counts should be performed before and periodically during treatment
Monitor hepatic function before treatment and regularly during treatment
Perform urine analysis before and periodically during treatment
Breastfeeding: Monitor infant for systemic effects of treating the mother
Monitor for signs of suicide ideation or behaviour
Monitor patients at risk of glaucoma for increases in intraocular pressure
Monitor plasma sodium in patients at risk of hyponatraemia
Monitor renal function
Monitor serum biochemistry regularly
Monitor thyroid function regularly
Plasma level monitoring may be useful: refer to local guidelines
Refer women considering pregnancy for specialist advice and monitoring
Advise patient to seek medical advice if severe skin reaction occurs
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Consult Dr.at once if rash, sore throat, mouth ulcers, bruising,fever occur
May cause activation of latent psychosis
May cause agitation and confusion in the elderly
May affect results of some laboratory tests
Avoid abrupt withdrawal
Discontinue if epilepsy is exacerbated
Discontinue if evidence of significant bone marrow depression
Discontinue if hypersensitivity reactions occur
Discontinue if severe skin reaction occurs
Discontinue if significant leucopenia occurs
Discontinue if significant/persistent hepatic function abnormalities occur
Adjust dose gradually in epilepsy
Begin therapy at low dosage
Bioavailability differs with preparations;caution on changing formulations
Reduce dose in elderly
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise patient grapefruit products may increase plasma level
May affect spermatogenesis
Female: Barrier or non-hormonal contraception advised during treatment
Female: Contraception required during and for 1 month after treatment
Female: Non-hormonal contraception or minimum 50mcg oestrogen advised
Neonate exposed in utero: Administer vitamin K at birth
Pregnancy: Administer vitamin K in the last few weeks of pregnancy
Advise patient of increased risk of falls
Advise patient/carers to report signs of suicide ideation or behaviour
Carbamazepine may reduce serum concentrations of thyroid hormones through enzyme induction requiring an increase in dose of thyroid replacement treatment in patients with hypothyroidism.
Some liver function tests in patients receiving carbamazepine may be found to be abnormal, particularly gamma glutamyl transferase. This is probably due to hepatic enzyme induction. Enzyme induction may also produce modest elevations in alkaline phosphatase. These enhancements of hepatic metabolising capacity are not an indication for the withdrawal of carbamazepine.
Severe dermatological reactions such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) have been rarely reported during treatment with carbamazepine. These reactions usually appear within the first few months of treatment. The HLA-B*1502 allele has been strongly associated with risk of developing SJS. If patient tests positive for this, allele carbamazepine treatment should not be initiated unless there is no other therapeutic option.
There are some data that suggest HLA-A*3101 is associated with an increased risk of carbamazepine induced cutaneous adverse drug reactions including SJS, TEN, Drug rash with eosinophilia (DRESS), or less severe acute generalised exanthematous pustulosis (AGEP) and maculopapular rash in people of European descent and the Japanese. There is insufficient data supporting a recommendation for HLA-A*3101 screening before starting carbamazepine treatment. If patients of European descent or Japanese origin are known to be positive for HLA-A*3101 allele, the use of carbamazepine may be considered if the benefits outweigh the risks.
Milder reactions (macular and maculopapular exanthema) may also occur and may dissipate upon dose reduction or continued treatment; these patients should be monitored closely for potential immediate withdrawal on worsening reaction.
Patients usually present with fever, rash, lymphadenopathy and other organ system involvement. Other possible symptoms include liver dysfunction, haematological, renal and pulmonary abnormalities, vasculitis and multi-organ failure. If signs or symptoms of hypersensitivity syndrome occur, the drug should be withdrawn immediately and expert advice sought.
Monitor serum sodium levels prior to initiating treatment, after 2 weeks and then every month for 3 months thereafter.
Pregnancy and Lactation
Pregnancy
Use carbamazepine with caution during pregnancy.
The manufacturer advises caution if carbamazepine is used during pregnancy. Available reports indicate a greater risk of teratogenic or developmental effects. Developmental disorders and malformations, including spina bifida, and also other congenital anomalies eg. craniofacial defects such as cleft lip/palate, cardiovascular malformations, hypospadias and anomalies involving various body systems, have been reported in association with the use of carbamazepine. Patients should be counselled regarding the possibility of an increased risk of malformations and given the opportunity of antenatal screening. During pregnancy, antiepileptic treatment should not be interrupted. Exposure to carbamazepine may cause vomiting, diarrhoea and decreased feeding to the neonate.
The minimum effective dose should be given and monitoring of plasma levels is recommended. Wherever possible, carbamazepine should be prescribed as monotherapy.
Lactation
Use carbamazepine with caution during breastfeeding.
The manufacturer advises caution if carbamazepine is used when breastfeeding. Carbamazepine is present in human breast milk (25-60% of the plasma concentrations), exposed infants should be monitored for possible adverse reactions. There have been some reports of cholestatic hepatitis in neonates exposed to carbamazepine during antenatal and or during breastfeeding.
Side Effects
Acne
Acute intermittent porphyria
Aggravation of coronary artery disease
Aggression
Agitation
Agranulocytosis
Allergic skin reactions
Anaphylactic reaction
Angioedema
Aplastic anaemia
Arrhythmias
Arthralgia
Aseptic meningitis
Atrioventricular block
Bradycardia
Changes of blood pressure
CNS disturbances
Confusion
Congestive cardiac failure
Decrease in plasma calcium
Decreased appetite
Delayed hypersensitivity reactions
Depression
Dyspnoea
Elevation of liver enzymes
Eosinophilia
Erythema multiforme
Erythema nodosum
Erythroderma
Exfoliative dermatitis
Fever
Fluid retention
Folic acid deficiency
Galactorrhoea
Gastro-intestinal symptoms
Glossitis
Gynaecomastia
Haemolytic anaemia
Hair loss
Hallucinations
Hearing disturbances
Hepatic failure
Hepatitis
Hepatosplenomegaly
Hirsutism
Hypersensitivity reactions
Hypogammaglobulinaemia
Hyponatraemia
Impaired renal function
Increase in plasma cholesterol
Increased intra-ocular pressure
Increased prolactin
Interference with spermatogenesis
Interstitial nephritis
Involuntary movement disorders
Jaundice
Leucocytosis
Leucopenia
Lymphadenopathy
Lymphoma-like disorder
Megaloblastic anaemia
Muscle weakness
Muscular cramps
Neuroleptic malignant syndrome
Osteomalacia
Pancreatitis
Paraesthesia
Paretic symptoms
Peripheral neuropathy
Photosensitivity
Pneumonia
Pneumonitis
Possible alteration of thyroid function tests
Proteinuria
Pruritus
Psychosis
Purpura
Red cell aplasia
Renal failure
Restlessness
Reticulocytosis
Sexual disturbances
Skin pigmentation changes
Speech disturbances
Stevens-Johnson syndrome
Stomatitis
Sweating
Syncope
Systemic lupus erythematosus
Taste disturbances
Thrombocytopenia
Thromboembolism
Thrombophlebitis
Toxic epidermal necrolysis
Urinary frequency
Urinary retention
Urticaria
Vanishing bile duct syndrome
Visual disturbances
Weight gain
Effects on Laboratory Tests
May result in false positive perphenazine concentrations in HPLC analysis due to interference.
Carbamazepine and the 10,11-epoxide metabolite may result in false positive tricyclic antidepressant concentration in fluorescence polarized immunoassay method.
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: November 2019
Reference Sources
Summary of Product Characteristics: Carbagen Tablets 100mg. Generics UK Ltd. Revised September 2018.
Summary of Product Characteristics: Carbagen Tablets 200mg. Generics UK Ltd. Revised September 2018.
Summary of Product Characteristics: Carbagen Tablets 400mg. Generics UK Ltd. Revised September 2018.
Summary of Product Characteristics: Carbagen Prolonged Release Tablets 200mg. Generics UK Ltd. Revised June 2016.
Summary of Product Characteristics: Carbagen Prolonged Release Tablets 400mg. Generics UK Ltd. Revised June 2016.
Summary of Product Characteristics: Carbamazepine Crescent tablets 100mg. Crescent Pharma Ltd. Revised April 2022.
Summary of Product Characteristics: Carbamazepine Crescent tablets 200mg. Crescent Pharma Ltd. Revised April 2022.
Summary of Product Characteristics: Carbamazepine Crescent tablets 400mg. Crescent Pharma Ltd. Revised April 2022.
Summary of Product Characteristics: Carbamazepine tablets 100mg. Medreich PLC. Revised February 2020.
Summary of Product Characteristics: Carbamazepine tablets 200mg. Medreich PLC. Revised February 2020.
Summary of Product Characteristics: Carbamazepine tablets 400mg. Medreich PLC. Revised February 2020.
Summary of Product Characteristics: Curatil prolonged release tablets 200mg. Tillomed Laboratories Ltd. Revised July 2020.
Summary of Product Characteristics: Tegretol 100mg, 200mg and 400mg Tablets. Novartis Pharmaceuticals UK Ltd. Revised December 2020
Summary of Product Characteristics: Tegretol 200mg and 400mg Prolonged Release Tablets. Novartis Pharmaceuticals UK Ltd. Revised December 2020.
Summary of Product Characteristics: Tegretol 100mg/5ml Liquid. Novartis Pharmaceuticals UK Ltd. Revised March 2019.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 13 March 2020
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