卡馬西平

Carbamazepine 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.

Pronunciation

Carbamazepine 200mg

Carbamazepine controlled-released 200mg (TEGRETOL CR 200mg)

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

1. 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:
	• Up to 1 year: 100 to 200 mg
	• 1 to 5 years: 200 to 400 mg
	• 5 to 10 years: 400 to 600 mg
	• 10 to 15 years: 0.6 to 1 g
	• Over 15 years: usual adult doses
	The maximum recommended daily dose, according to age, is as follows:
	• Up to 6 years: 35 mg/kg
	• 6 to 15 years: 1 g
	• Over 15 years: 1.2 g

2. 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

3. Bipolar disorder

Oral	initially 400 mg daily in divided doses increased until symptoms controlled; usual range 400-600 mg daily; max. 1.6 g daily

4. Treatment of alcohol withdrawal

Oral	initially 400 mg daily in divided doses increased until symptoms controlled; usual range 400-600 mg daily; max. 1.6 g daily

5. 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

• signs of blood, liver, or skin disorders. Seek immediate medical attention if symptoms such as fever, rash 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