What should I know when using Carbamazepine (Tegretol)?
Carbamazepine or Tegretol has been used for epilepsy treatment for half a century and is used for multiple other conditions as well. However, unlike some other anti-epileptic medication, Carbamazepine cannot be used in all patients and can in fact worsen some forms of epilepsy. Here are some important facts that you should know when using Carbamazepine.
In what types of epilepsy can we use Carbamazepine?
Carbamazepine is best used to treat focal epilepsy but can also be used in treating generalized seizures as well. However, it has a potential to worsen some cases of primary generalized epilepsy like Juvenile myoclonic epilepsy.
Is Carbamazepine safe to use in children?
Yes, although it is generally used for treating adults and children 6 years and older, it can be given to younger children as well.
Can Carbamazepine be used to treat conditions other than Epilepsy?
Yes, Carbamazepine is used as a mood stabilizer for bipolar disorder and helps a lot with trigeminal neuralgia.
How does Carbamazepine work?
Carbamazepine blocks the sodium channel so it is a sodium channel blocker, and it can also affect the L-Type calcium channel. By this, it reduces the spread of seizure activity in the brain and restores the normal balance of nerve activity.
Carbamazepine can also affect the turnover of dopamine and noradrenaline which can explain the antidepressant effect and its use in bipolar disorder. It also stimulates the release of antidiuretic hormone which might explain the risk of low sodium levels it can cause.
How to dose Carbamazepine?
Carbamazepine is available in tablets, extended release, chewable and suspensions. IV formulations are not widely available now.
In adults, we start with 100 mg twice a day for 1 week then increase to 200 mg twice a day for one week then increase to 300 mg twice a day afterwards and then reassess. Maximum dose is 1600 mg daily. In clinical practice some patients process the medicine faster so there could be cases going up to 2000 mg to 3000 mg daily.
In children, the dose depends on the weight, we start with 10 to 20 mg/kg/day orally in 2 or 3 divided doses, for example, if your child is 20 Kg then we give 10 mg x 20 Kg = 200 mg, so we give 100 mg twice a day. Then the dose is increased weekly with a maximum dose of 35 mg/kg/day.
Are there any tests that need to be done before starting Carbamazepine?
Yes. The investigations that should be before starting treatment are:
- Liver function tests.
- Kidney function tests.
- Serum electrolytes.
- Full blood count.
Are there any risks of starting Carbamazepine for specific Asian populations?
There is a high risk for skin rash and allergic reaction in those with HLA-B*1502 allele, which can be found in Hans Chinese and Vietnamese populations. Therefore, we need to do a genetic test for the above allele in these populations before starting treatment.
At what level should we keep the blood Carbamazepine level?
Serum levels will usually range between 4 to 12 mcg/mL. To keep the blood carbamazepine levels at this range, it is important to slowly titrate the medication till the desirable levels are reached. This can also prevent side effects from developing since the body will be able to adapt to the medicine and also improve the compliance.
What to do if Carbamazepine is not working for me?
There are many reasons why an anti-seizure medicine like Carbamazepine might not be working for you. In this case,
First, we need to confirm that the correct type of epilepsy is being treated since Carbamazepine can worsen generalized epilepsy and juvenile myoclonic epilepsy.
The most likely reason is noncompliance, since missing daily doses can place you at risk of having seizures. Therefore drug compliance has to be improved if unsatisfactory.
Enough time must be given for the medication to show a satisfactory response, which is around 3-6 months.
The dose that you are being treated with may not be adequate for you. Therefore the doses may need to be adjusted by your doctor. This can be guided by blood levels.
It is possible that you are among the 25% of people who have drug resistant epilepsy that does not respond well to medications and needs some type of surgical treatment. This will be decided by your neurologist.
What are the side effects of Carbamazepine I need to worry about?
The common side effects of Carbamazepine are:
- Nausea
- Vomiting
- Ataxia
- Dizziness
- Tinnitus
- Blurry vision
- Nystagmus
- Diarrhea
- Rash
- itching
- Fluid retention.
Carbamazepine affects the antidiuretic hormone so it can cause low sodium levels (Hyponatremia) which can cause
- Nausea and vomiting
- Headache, confusion
- Loss of energy
- Drowsiness and fatigue
- Restlessness and irritability
- Muscle weakness
- Spasms or cramps
If severe, can result in seizures and coma
Normal range for blood Sodium level is around 140 milliequivalent/liter (mEq/L), and hyponatremia is usually not a major issue unless it drops below 120. If the sodium levels drop and you are symptomatic, the treatment is fluid restriction, so drinking 1L/day can reduce the symptoms.
Carbamazepine can rarely affect the liver, bone marrow, kidney, pancreas, heart and the cardiac conduction leading to heart block and maybe heart failure.
What are the more serious adverse effects of Carbamazepine?
A rare but dangerous adverse effect of Carbamazepine for which a black box warning has been issued by American FDA is Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) which can be seen especially in Asians and people with the HLA-B*1502 allele.
The second FDA warning is for aplastic anemia and agranulocytosis which is a reduction in the blood cells counts.
How can we prevent these serious adverse effects?
Slow titration of the medication can help avoid these serious adverse effects.
Can Carbamazepine cause sexual dysfunction?
Yes, Carbamazepine can cause sexual dysfunction in men by causing low testosterone levels. However, this is rare adverse effect.
Can Carbamazepine affect contraceptive medication?
Yes, since Carbamazepine induces the liver enzymes it can interact with many other medications that are processed through the liver, thus making them less effective. Hence, it can make estrogen contraceptive pills less effective as well, therefore contraceptives must be planned accordingly.
Can my bones get affected due to Carbamazepine and if so, how can I prevent it?
Yes it can. In the long term Carbamazepine can cause bone loss and osteoporosis leading to broken bones. We can treat the bone loss by giving Vitamin D and calcium. You can also do daily exercise routines to further strengthen your bones.
Can I drive or drink alcohol with Carbamazepine?
No, you should avoid alcohol with Carbamazepine due to the adverse effects on the liver. Overall, alcohol is bad for epilepsy and better to be avoided altogether.
Carbamazepine is also a sedative, therefore initially after starting the medication, you should avoid driving until you get used to the sedative effects of the medication.
How to stop Carbamazepine if it is not working?
If Carbamazepine needs to be stopped, it should be taken off slowly over a period of weeks depending on treatment circumstances and other drugs you use. The decision to stop Carbamazepine should be taken by your doctor.
Is Carbamazepine safe in pregnancy and breastfeeding?
Carbamazepine can cross the placenta and cause birth defects in rare cases and hence can be considered as a teratogenic drug. It is considered to be less safe than Lamotrigine and Levetiracetam, which are the safest anti epileptics to use in pregnancy but is safer than Valproate and Topiramate, which have the highest teratogenic risk.
The average fetal malformation or birth defects risk (without medication) ranges between 1 and 3 percent in pregnancy. Considering all the different studies, malformation risk of Carbamazepine is 2.6% - 5.9%. So yes, if you have epilepsy, you can use Carbamazepine in pregnancy knowing the risk and benefits of seizure control. However, it is always recommended for all women of childbearing age to take folic acid daily even before pregnancy to protect the baby.
Carbamazepine is safe in breastfeeding. Therefore, it can be continued while breastfeeding. However, the mother should look out for excessive sleepiness in the baby.
In conclusion, Carbamazepine is an antiepileptic which is used in treating focal epilepsy in patient with good liver and kidney functions. It is also useful in treating epileptic patients with mood disorders like bipolar disorder, pain or neuropathy. Carbamazepine is best avoided in Asians with positive HLA-B*1502 allele and in patients with liver, kidney issues or those who are taking medications that interact with Carbamazepine.