Carbamazepine, History, Uses, Side Effects, Dosage, and 28 Popular brands in Pakistan

Introduction

Carbamazepine is a medication primarily used to treat epilepsy, bipolar disorder, and trigeminal neuralgia. It belongs to a class of drugs known as anticonvulsants or anti-seizure medications. It works by reducing the spread of seizure activity in the brain and restoring the normal balance of nerve activity.

History

Carbamazepine was first synthesized by Swiss chemist Walter Schindler in 1953. It was developed as a treatment for trigeminal neuralgia, a condition characterized by facial pain. In the early 1960s, carbamazepine’s anticonvulsant properties were observed in animal experiments and later in human clinical studies.

Approval and Launch

Carbamazepine was approved as an antiepileptic drug in Great Britain and Switzerland in 1963. It is now used to treat various conditions, including epilepsy, neuropathic pain, and certain mental disorders. It is available in different formulations, including tablets, extended-release tablets, and syrup, and is marketed under various brands.

Impact and Legacy

Carbamazepine has had a profound impact and legacy in the medical field, revolutionizing the treatment of epilepsy and trigeminal neuralgia with its effectiveness in reducing seizures and pain. Widely used for over 50 years, it remains a first-line treatment for partial seizures and trigeminal neuralgia and has also shown efficacy in treating bipolar disorder and other conditions. A pioneering development of anticonvulsant medications, it has improved the quality of life for millions of people worldwide.

Pharmacology

Carbamazepine is a sodium channel blocker, reducing neuronal excitability and preventing seizure activity. It also increases serotonin and dopamine levels, contributing to its mood-stabilizing effects.

Chemistry

Carbamazepine is a derivative of Iminostilbene, with a chemical structure that allows it to interact with sodium channels and neurotransmitter systems.

Formulations

Carbamazepine is available in various formulations, including tablets, capsules, and oral suspensions.

Mechanism of Action

Carbamazepine’s mechanism of action involves:

• Blockade of voltage-gated sodium channels: Carbamazepine binds to the alpha subunit of voltage-gated sodium channels, reducing the influx of sodium ions and thereby reducing the excitability of neurons.
• Stabilization of inactive sodium channels: It also stabilizes the inactive state of sodium channels, further reducing neuronal excitability.
• Inhibition of voltage-gated calcium channels: It blocks voltage-gated calcium channels, reducing the influx of calcium ions and further reducing neuronal excitability.
• Modulation of neurotransmitters: Carbamazepine also modulate the release and uptake of neurotransmitters such as serotonin, dopamine, and GABA, contributing to its therapeutic effects.
• Anticonvulsant effects: The combined effects on sodium and calcium channels reduce the excitability of neurons, making it more difficult for seizures to occur.
• Pain relief: Carbamazepine’s effects on sodium channels and neurotransmitter modulation may also contribute to its analgesic properties, particularly in the treatment of neuropathic pain.

Carbamazepine class

Carbamazepine is a medication that belongs to several classes, including anticonvulsants, antiepileptics, mood stabilizers, and sodium channel blockers. It is primarily used to treat epilepsy, trigeminal neuralgia, bipolar disorder, and neuropathic pain.

Carbamazepine Uses

Carbamazepine is a medication with various uses in the field of medicine. Here are some of its primary uses:

Treatment of Epilepsy and Seizures

Carbamazepine is commonly used as a first-line treatment for partial seizures, generalized seizures, and mixed seizure disorders. It helps to reduce the frequency and severity of seizures by stabilizing the electrical activity in the brain. It is also used to treat trigeminal neuralgia, a condition that causes facial pain. Additionally, it also prescribed off-label to treat other conditions such as bipolar disorder, neuropathic pain, and migraines.

Neuropathic pain

Carbamazepine is used to relieve nerve pain, also known as neuropathic pain, which is caused by damage or dysfunction of nerves. This type of pain can be severe and debilitating, and is often described as burning, shooting, or stabbing. It works by blocking the sodium channels in the nerve cells, which helps to reduce the abnormal electrical activity that causes the pain.

It is commonly used to treat conditions such as trigeminal neuralgia, diabetic neuropathy, and postherpetic neuralgia (shingles). By reducing nerve pain, carbamazepine can help improve quality of life, sleep, and daily functioning.

Management of Bipolar Disorder

It is also used to treat bipolar disorder, specifically for acute mania and mixed episodes, and as a maintenance therapy to prevent recurrences of mania or depression. It helps to stabilize mood and reduce symptoms such as irritability, agitation, and aggression.

Carbamazepine Use in Pregnancy

Carbamazepine, a medication used to treat epilepsy, bipolar disorder, and nerve pain, can be used during pregnancy, but with caution and close monitoring. It’s essential to weigh the benefits against the potential risks.

FDA Pregnancy Category

Category D: There is positive evidence of human fetal risk, but the benefits may outweigh the risks in certain situations.

Risks;

• Congenital anomalies (e.g., spina bifida, heart defects)
• Developmental delays
• Neonatal seizures
• Withdrawal symptoms in the newborn

Precautions:

• Use the lowest effective dose
• Monitor blood levels regularly
• Adjust dosages as needed
• Consider alternative medications
• Close monitoring by a healthcare provider

Carbamazepine Side Effects

Carbamazepine is a medication used to treat seizures, nerve pain, and bipolar disorder. While effective, it can cause several side effects, including:

Common Side Effects

• Dizziness or drowsiness
• Nausea or vomiting
• Blurred vision
• Headache
• Fatigue
• Dry mouth
• Increased appetite
• Weight gain

Serious Side Effects

• Allergic reactions (rash, itching, swelling)
• Blood disorders (easy bruising, bleeding)
• Liver damage (yellowing of skin or eyes)
• Kidney problems (painful urination, decreased urine output)
• Seizure worsening
• Suicidal thoughts or behavior
• Severe skin reactions (Stevens-Johnson syndrome)

Rare Side Effects

• Hallucinations or confusion
• Muscle weakness or cramps
• Tremors or shaking
• Changes in heart rate or blood pressure
• Increased risk of osteoporosis

Carbamazepine for Depression

Carbamazepine is an anticonvulsant medication that has been used off-label for the treatment of depression, particularly in cases where other treatments have been ineffective. It is thought to work by:

• Stabilizing neuronal membranes
• Inhibiting sodium channels
• Enhancing neurotransmitter activity (e.g., serotonin, dopamine)

Benefits for Depression

• Effective in treatment-resistant depression
• Rapid antidepressant effects in some cases
• May have mood-stabilizing properties

How it’s Used

• Typically started at a low dose (100-200 mg/day) and gradually increased
• Target dose range: 400-1200 mg/day
• Often used in combination with other antidepressants or mood stabilizers

Important Considerations

• Carbamazepine is not a first-line treatment for depression
• It has a narrow therapeutic index, requiring close monitoring of blood levels and side effects
• Regular blood tests are necessary to assess liver function

Carbamazepine Dosage

Carbamazepine is a medication used to treat epilepsy, nerve pain, and bipolar disorder. The dosage varies depending on the condition being treated, patient age, and individual response. Always consult a healthcare professional for specific guidance.

Epilepsy

• Initial dose: 200-400 mg per day (divided into 2-4 doses)
• Maintenance dose: 800-1,200 mg per day (divided into 2-4 doses)
• Maximum dose: 1,600 mg per day

Nerve Pain (Trigeminal Neuralgia)

• Initial dose: 100-200 mg per day (divided into 2 doses)
• Maintenance dose: 600-800 mg per day (divided into 2-3 doses)
• Maximum dose: 1,200 mg per day

Bipolar Disorder

• Initial dose: 200-400 mg per day (divided into 2 doses)
• Maintenance dose: 400-600 mg per day (divided into 2 doses)
• Maximum dose: 1,200 mg per day

Dosage Adjustments:

• Titrate dose upward every 3-7 days as needed and tolerated
• Reduce dose if side effects occur
• Monitor blood levels to ensure therapeutic range (4-12 μg/mL)

Pediatric Dosage:

• Children under 6 years: 10-20 mg/kg per day (divided into 2-3 doses)
• Children 6-12 years: 10-30 mg/kg per day (divided into 2-3 doses)

Carbamazepine Interactions

Carbamazepine, a widely used anticonvulsant and mood stabilizer, interacts with numerous medications, which can lead to adverse effects, reduced efficacy, or increased toxicity. Here are some significant interactions to consider:

Antiepileptic Drugs (AEDs)

1. Valproic Acid: Carbamazepine may decrease valproic acid levels, potentially reducing its efficacy. Conversely, valproic acid can increase carbamazepine levels, leading to toxicity. Monitoring of serum levels and clinical response is essential when co-administering these drugs.
2. Phenytoin: Co-administration of carbamazepine and phenytoin can result in decreased serum levels of both drugs due to mutual induction of hepatic enzymes. Dosage adjustments may be necessary to maintain therapeutic concentrations.
3. Lamotrigine: It can increase the metabolism of lamotrigine, leading to reduced lamotrigine levels. Dose adjustment of lamotrigine may be required to prevent loss of efficacy.
4. Topiramate: It also decrease topiramate levels, while topiramate may increase carbamazepine concentrations. Monitoring and dosage adjustments may be necessary when these drugs are co-administered.

Psychotropic Medications

1. Selective Serotonin Reuptake Inhibitors (SSRIs): It reduce the serum levels of SSRIs such as fluoxetine and sertraline, potentially diminishing their antidepressant effects. Close monitoring and dosage adjustments may be necessary.
2. Tricyclic Antidepressants (TCAs): Concurrent use of carbamazepine and TCAs may lead to decreased TCA levels due to enzyme induction by this medicine. Monitoring for reduced efficacy or adverse effects of TCAs is recommended.
3. Antipsychotics: Carbamazepine reduce the plasma concentrations of certain antipsychotics, including haloperidol and clozapine, through enzyme induction. Close monitoring for therapeutic response and adverse effects is essential.

Cardiovascular Medications

1. Warfarin: It decrease the efficacy of warfarin by inducing its metabolism, potentially leading to reduced anticoagulant effects. Monitoring of prothrombin time/international normalized ratio (PT/INR) is necessary, with adjustments in warfarin dosage as needed.
2. Calcium Channel Blockers: Concurrent use of carbamazepine and calcium channel blockers such as verapamil and diltiazem may lead to reduced plasma levels of calcium channel blockers, necessitating dose adjustments and monitoring for therapeutic efficacy.

Hormonal Contraceptives

1. Oral Contraceptives: Carbamazepine decrease the efficacy of hormonal contraceptives by inducing their metabolism, potentially leading to contraceptive failure. Alternative or additional contraceptive methods should be considered in women of childbearing potential receiving carbamazepine therapy.

Other Medications:

1. Anticoagulants: It reduce the efficacy of certain anticoagulants, including rivaroxaban and apixaban, through enzyme induction. Monitoring of coagulation parameters and adjustment of anticoagulant dosage may be necessary.
2. HIV Protease Inhibitors: Carbamazepine decrease the plasma levels of HIV protease inhibitors, potentially reducing their efficacy in HIV management. Close monitoring of viral load and adjustment of antiretroviral therapy may be warranted.

Precautions and Warnings

Carbamazepine, like any medication, has certain precautions and warnings that should be considered. Here are some important points to keep in mind:

Warnings

• Serious Dermatologic Reactions: Carbamazepine can cause severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Monitor patients for skin reactions and discontinue use if symptoms occur.
• Aplastic Anemia and Agranulocytosis: It also cause blood disorders, including aplastic anemia and agranulocytosis. Monitor blood cell counts and discontinue use if abnormalities occur.
• Suicidal Behavior and Ideation: Antiepileptic drugs, including carbamazepine, may increase the risk of suicidal thoughts and behavior. Monitor patients for changes in behavior and mood.
• Cognitive Impairment: It can cause cognitive impairment, including memory loss, confusion, and difficulty with concentration. Monitor patients for cognitive changes.

Precautions

• Pregnancy and Lactation: Carbamazepine cause fetal harm and is excreted in breast milk. Use during pregnancy and lactation requires careful consideration of benefits and risks.
• Hepatic Impairment: Carbamazepine can cause liver damage. Monitor liver function tests and adjust dosages or discontinue use if liver impairment occurs.
• Renal Impairment: It also cause renal impairment. Monitor renal function tests and adjust dosages or discontinue use if renal impairment occurs.
• Cardiovascular Disease: It can cause cardiovascular complications, including heart failure and arrhythmias. Monitor patients with cardiovascular disease.
• Hyponatremia: Carbamazepine can cause hyponatremia. Monitor serum sodium levels and adjust dosages or discontinue use if hyponatremia occurs.
• Drug Interactions: It interacts with numerous medications, including anticonvulsants, antidepressants, antibiotics, and muscle relaxants. Monitor patients for drug interactions and adjust dosages or discontinue use as needed.
• Allergic Reactions: It also cause allergic reactions, including anaphylaxis and angioedema. Monitor patients for signs of allergic reactions.

Special Populations

• Pediatric Patients: Carbamazepine cause developmental delays and cognitive impairment in pediatric patients. Monitor pediatric patients for developmental and cognitive changes.
• Geriatric Patients: It cause cognitive impairment, sedation, and confusion in geriatric patients. Monitor geriatric patients for cognitive and sedative effects.

Monitoring:

• Blood Cell Counts: Monitor blood cell counts regularly to detect potential blood disorders.
• Liver Function Tests: Monitor liver function tests regularly to detect potential liver damage.
• Renal Function Tests: Monitor renal function tests regularly to detect potential renal impairment.
• Serum Sodium Levels: Monitor serum sodium levels regularly to detect potential hyponatremia.

By understanding these precautions and warnings, healthcare professionals can provide safe and effective treatment with carbamazepine.

Carbamazepine brands names in Pakistan

In Pakistan, Carbamazepine is available under various brand names. Here are some common brands of Carbamazepine formulations that are found in the Pakistani market:

• Epitab-XR (Werrick Pharmaceuticals)
• Karbaton (Mass Pharma)
• Leptic (Bio Labs)
• Lexopine : It is Manufactured by Highnoon Laboratories
• Seizunil suspension: (Platinum Pharmaceuticals)
• Mezapine (Valor Pharmaceuticals)
• Mezicarb (Medera Pharmaceuticals)
• Mezine (Bloom Pharmaceuticals)
• Sadmic (Zeb Laboratories)
• Seizunil tablet 200mg: (Platinum Pharmaceuticals)
• Tabtol (Umair Associates)
• Tegral : It is Manufactured by Novartis Pharma
• Tegram (Mediate Pharmaceuticals)
• Teril tablets 200mg : It is manufactured by Martin Dow Pharma
• Alcrabane (Alson Pharmaceuticals)
• Azapin (Silver Oak Corporation)
• Carbacid (Candid Pharmaceuticals)
• Carbanil (Dosaco Laboratories)
• Carbapine (CSH Pharmaceuticals)
• Carbazine (S. Ejazuddin & Company)
• Cazap (Usawa Pharmaceuticals)
• Convul (Siza International)
• Epicar (Adamjee Pharmaceuticals)
• Epigral (Medicraft Pharmaceuticals)
• Epilepsin (Macter International)
• Epilex (Bryon Pharmaceuticals)
• Episiez (Medicaids Pakistan)
• Episol (Star Laboratories)