卡馬西平
卡馬西平(English: Carbamazepine) 是一種抗癲癇藥，主要用於治療癲癇和神經性痛楚。 卡馬西平與苯妥英鈉和丙戊酸鹽一起用於局部性和全身性癲癇發作。 對於失神或肌陣攣性癲癇發作無效。 它也能用於精神分裂，並作為對鋰無反應性的躁鬱症的二線治療藥物。
藥名
| Generic Name 藥名 | HA Code 藥物代碼 | Classification藥物分類 |
|---|---|---|
| Carbamazepine suspension 100mg/5ml | CARB49 | P1S1S3 |
| Carbamazepine tablet 200mg | CARB02 | P1S1S3 |
| Carbamazepine CR tablet 200mg | CARB51 | P1S1S3 |
藥理
抗癲癇藥 它是鈉通道阻滯劑。 它與鈉通道結合併抑制重複性神經元放電。
劑量
| 癲癇症 | 口服：最初每日 1-2次，每次100 – 200 mg，然後逐漸增加，每週增加200 mg，至通常的維持劑量0.8 – 1.2 g，分次服用； 有需要時每天最多2g。
直腸栓劑：可用於暫時無法口服治療的患者（短期，最多7天）； 125mg的栓劑大約相當於100mg的片劑，但最終調整應始終取決於臨床反應。 最高 每天1mg，分4劑。 老人：減少初始劑量。 兒童：每日的通常劑量可以根據年齡如下：
根據年齡，建議的最大每日劑量如下：
|
|---|---|
| 三叉神經痛 | 口服：最初每日1-2次，每次100mg，根據反應逐漸增加； 通常劑量每日3-4次，每次200mg。 |
| 雙相障礙 | 口服：最初每日400mg，分劑量服用，直至症狀得到控制； 通常範圍每日400-600mg； 最高 每日1.6g |
| 戒酒治療 | 口服：最初每日800mg，分劑量服用，5天內逐漸減少至每日200mg； 常規治療時間7-10天。 |
| 糖尿病性神經病變 | 口服：最初每日1-2次，每次100mg，根據反應逐漸增加； 通常劑量每日3-4次，每次200mg。 |
最佳血漿濃度為4-12 mg / L（20-50 micromol / L)
副作用
常見的副作用包括：
- 嗜睡，頭暈和頭痛
- 腸胃不適，例如噁心和嘔吐
- 運動協調障礙
- 低鈉血症和抗利尿激素分泌失调综合征(SIADH)的風險增加
- 血液異常（如白血球減少或血小板數量減少）
嚴重的副作用可能包括：
- 皮疹，剝脫性皮炎，表皮壞死，史蒂文斯-約翰遜綜合症(SJS)和全身性紅斑狼瘡(SLE)
- 骨髓功能下降
- 自殺念頭
- 心律異常
- 模糊或重影，眼球震顫
- 男性不育
- 骨質疏鬆症
- 男性乳房發育症
- 溢乳
藥動力學
| 生物利用度 | 卡馬西平易從腸胃吸收， 與血漿蛋白結合的比例大約70-80％。 |
|---|---|
| 代謝 | 卡馬西平被細胞色素P450同工酶CYP2C8，CYP3A4代謝。 |
| 消除半衰期 | 消除半衰期為70小時，但老年人可能增加至100小時 |
| 排泄 | 卡馬西平的代謝物大部份經尿液排泄，另有一部份經糞便排泄。 |
藥物管理資訊
監控
- 留意血液，肝臟或皮膚疾病的跡象。 如果出現發燒，皮疹，潰瘍或瘀傷等症狀，請立即就醫。
- 應定期稱量患有心力衰竭的患者，以檢測其水腫的跡象。
- 患有心臟傳導障礙的患者應予以仔細監測。
- 低鈉血症（監測有風險的患者的血漿鈉濃度）。
藥物相互影響
少數藥物通過細胞色素P450同工酶CYP3A4抑制卡馬西平的代謝，導致血漿濃度升高，増加中毒的風險。 相反，誘導同工酶CYP3A4的藥物可能會增加卡馬西平的代謝，從而導致血漿濃度降低，導致降低治療效果。 卡馬西平本身是一種肝酶誘導劑，並誘導其自身的代謝。
| 藥物 | 同服效果 |
|---|---|
| 抗酸劑（含鎂和鋁） | 抗酸劑可減少腸道中加巴噴丁的吸收。 建議在任何此類抗酸藥後至少2小時服用加巴噴丁。 |
| 嗎啡 | 嗎啡可降低加巴噴丁的清除率； 接受這兩種藥物治療的患者應監測中樞神經系統抑制的跡象，並相應減少劑量。 |
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 |
| 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 |
Increased 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) |
Caution
- avoid in patients with cardiac disease
- Genotype test for HLA-B*1502 allele in Han Chinese of Thai origin (avoid Carbamazepine unless no alternative – risk of Stevens-Johnson syndrome in presence of HLA-B*1502 allele);
- may exacerbate absence and myoclonic seizures
- consider vitamin D supplement for immobilized patients or who have inadequate sun exposure or dietary intake of calcium
- susceptibility to glaucoma
- cross-sensitivity reported with oxcarbazepine and with phenytoin
Contraindications
- AV conduction abnormalities
- History of bone-marrow depression
- Acute porphyria
Hepatic impairment Metabolism impaired in advanced liver disease.
Renal impairment Use with caution
Pregnancy Women of child-bearing potential should discuss with a specialist the impact of both epilepsy, and its treatment, on the outcome of pregnancy. There is an increased risk of teratogenicity associated with the use of antiepileptic drug (especially if used during the first trimester)
Breast-feeding Use during breast feeding is not recommended.
Warning:
- This medicine may make you sleepy. If this happens, do not drive or use tools or machines
- Do not stop taking this medicine unless your doctor tells you to stop
FAQ
How should I take the tablet?
Donepezil tablet and orodispersible tablet should be taken orally at bedtime, or as directed by the doctor. The orodispersible tablet should be placed on the tongue and allowed to disperse before swallowing with or without water. Both formulations can be taken with or without food.
What should I avoid while taking?
Avoid abruptly discontinue the medication.
What happen if I overdose?
Contact your primary care doctor. If emergency situation, call 999
What happen if I miss a dose?
Take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.
