Carbamazepine
Carbamazepine(中文: 卡馬西平) is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. Carbamazepine appears to work as well as phenytoin and valproate for focal and generalized seizures. It is not effective for absence or myoclonic seizures. It is used in schizophrenia and as a second-line agent in the management of bipolar disorder unresponsive to lithium.
Drug Names
| Generic Name 藥名 | HA Code 藥物代碼 | Classification藥物分類 |
|---|---|---|
| Carbamazepine Suspension 100mg/5ml | CARB49 | P1S1S3 |
Mechanism of Action
Anticonvulsant medication. It is a sodium channel blocker. It binds to sodium channels and suppresses repetitive neuronal firing.
Dosage
| Epilepsy | Oral: initially 100 – 200 mg 1-2 times daily, increased slowly by increments of up 200 mg daily every week to an usual maintenance dose of 0.8 – 1.2 g daily in divided doses; up to 2 g daily may occasionally be necessary.
By rectum: for short-term use (Max. 7 days) when oral therapy temporarily not possible; 125-mg suppository approximately equivalent to 100-mg tablet, but final adjustment should always depend on clinical response. Max. 1 g daily in 4 divided doses. Elderly: reduce initial dose. Child: the usual daily dose may be given according to age as follows:
The maximum recommended daily dose, according to age, is as follows:
|
|---|---|
| Trigeminal neuralgia | Oral: initially 100 mg 1-2 times daily, increased gradually according to response; usual dose 200 mg 3-4 times daily, up to 1.6 g daily in some patients |
| Bipolar disorder | Oral: initially 400 mg daily in divided doses increasleed until symptoms controlled; usual range 400-600 mg daily; max. 1.6 g daily |
| Treatment of alcohol withdrawal | Oral: initially 800 mg daily in divided doses, reduced gradually over 5 days to 200 mg daily; usual treatment duration 7-10 days. |
| Diabetic neuropathy | Oral: initially 100 mg 1-2 times daily, increased gradually according to response; usual dose 200 mg 3-4 times daily, up to 1.6 g daily in some patients |
Note Plasma concentration for optimum response 4-12 mg/litre (20-50 micromol/litre)
Side Effects
Common side effects include:
- Drowsiness, dizziness and headaches
- Gastrointestinal disturbances, such as nausea and vomiting
- The loss of full control of bodily movements (motor coordination impairment)
- Increased risks of hyponatremia and SIADH
- Blood disorders (such as decreased white blood cell or platelet counts)
Serious side effects may include:
- Skin rashes, exfoliative dermatitis, epidermal necrolysis, Stevens-Johnson syndrome, and SLE
- Decreased bone marrow function
- Suicidal thoughts
- Abnormal heart rhythms
- Blurry or double vision, nystagmus
- Male infertility
- Osteoporosis
- Gynecomastia
- Galactorrhea
Pharmacokinetics
| Oral bioavailability | Carbamazepine is slowly but well absorbed after oral administration. It is about 70 to 80% bound to plasma proteins. |
|---|---|
| Onset of action | Its plasma half-life is about 30 hours when it is given as single dose, but it is a strong inducer of hepatic enzymes and the mean plasma half-life on repeated dosage is about 12 to 24 hours. |
| Metabolism | Metabolized in the liver by cytochrome P450 isoenzymes CYP3A4 and CYP2C8. |
| Elimination half-life | Excreted in the urine almost entirely in the form of its metabolites; some are also excreted in faeces. |
Drug Management
Monitoring
- Recognize signs of blood, liver, or skin toxicity. Seek immediate medical attention if symptoms such as fever, sore throat, rash, blistering, mouth ulcers, bruising or bleeding develop.
- Patients with heart failure should be weighed regularly to detect fluid retention.
- Patients with pre-existing cardiac conduction disorders should be carefully monitored.
- Hyponatremia (monitor plasma-sodium concentration in patients at risk).
Drug interaction
A few drugs inhibit its metabolism by the cytochrome P450 isoenzyme CYP3A4, resulting in raised plasma concentrations and associated toxicity. Conversely, drugs that induce CYP3a4 may increase the metabolism of carbamazepine, leading to reduced plasma concentrations and potentially a decrease in therapeutic effect. Carbamazepine is itself a hepatic enzyme inducer and induces its own metabolism.
| Drugs given with carbamazepine | Potential Effect |
| CYP3A4 inhibitors:
Cimetidine Clarithromycin erythromycin isoniazid |
Resulting in raised plasma-carbamazepine concentration and associated toxicity |
| CYP3A4 inducers:
Rifampicin Phenytoin |
May reduce plasma-carbamazepine concentration |
| Analgesic:
Tramadol |
Carbamazepine reduces effect of tramadol |
| Anticoagulants:
Apixaban, dabigatran, rivaroxaban, coumarins (warfarin) |
Carbamazepine possibly reduces their plasma concentration,
Advises avoid concomitant use and monitor signs of thrombosis |
| Antipsychotics:
aripiprazole clozapine Haloperidol Olanzapine Paliperidone Quetiapine risperidone |
Carbamazepine accelerates their metabolism and reduced their plasma concentration.
Avoid concomitant use or increase the dose |
| Anxiolytics:
Clonazepam midazolam |
Carbamazepine reduces their plasma concentration |
| Diuretics:
frusemide |
ncreased risk of hyponatraemia when carbamazepine given with diuretics |
| Oestrogens | Carbamazepine accelerates metabolism oestrogens, and reduced contraceptive effect |
| Theophylline | Carbamazepine accelerates metabolism of theophylline (reduced effect) |
| Thyroid hormones | Carbamazepine accelerates metabolism of thyroid hormones (may increase thyroxine dosage in hypothyroidism)
|
