Zagretol
Zagretol Uses, Dosage, Side Effects, Food Interaction and all others data.
Zagretol depresses activity in the nucleus ventralis of the thalamus, reduces synaptic propagation of excitatory impulses or decreases summation of temporal stimulation leading to neural discharge by limiting influx of Na ions across cell membrane or other unknown mechanisms. It stimulates the release of antidiuretic hormone (ADH) and potentiates its action in promoting reabsorption of water.
General effects
Zagretol treats seizures and the symptoms of trigeminal neuralgia by inhibiting sodium channels. In bipolar 1 disorder, carbamazepine has been found to decrease mania symptoms in a clinically significant manner according to the Young Mania Rating Scale (YMRS). Zagretol has a narrow therapeutic index.
A note on genetic variation and carbamazepine use
Trade Name | Zagretol |
Availability | Prescription only |
Generic | Carbamazepine |
Carbamazepine Other Names | Carbamazepen, Carbamazepin, Carbamazepina, Carbamazépine, Carbamazepine, Carbamazepinum |
Related Drugs | Vraylar, gabapentin, fluoxetine, clonazepam, quetiapine, lamotrigine, Abilify, Prozac, pregabalin, Seroquel |
Type | |
Formula | C15H12N2O |
Weight | Average: 236.2686 Monoisotopic: 236.094963016 |
Protein binding | Carbamazepine is 75%-80% bound to plasma proteins. One pharmacokinetic study indicates that it is 72% bound to plasma proteins. |
Groups | Approved, Investigational |
Therapeutic Class | Primary anti-epileptic drugs |
Manufacturer | |
Available Country | Russia |
Last Updated: | September 19, 2023 at 7:00 am |
![Zagretol Zagretol](https://www.medicinesfaq.com/media/png/zagretol.png)
Uses
Zagretol is used for-
- partial and secondary generalized tonic-clonic seizures
- Primary generalized tonic-clonic seizures
- Trigeminal neuralgia
- Prophylaxis of bipolar disorder
Zagretol is also used to associated treatment for these conditions: Acute Mania, Alcohol Withdrawal Syndrome, Generalized Tonic Clonic Seizures, Mixed manic depressive episode, Pain, Partial Seizures With Secondary Generalization, Partial-Onset Seizures, Restless Legs Syndrome (RLS)
How Zagretol works
Zagretol's mechanism of action is not fully elucidated and is widely debated. One major hypothesis is that carbamazepine inhibits sodium channel firing, treating seizure activity. Animal research studies have demonstrated that carbamazepine exerts its effects by lowering polysynaptic nerve response and inhibiting post-tetanic potentiation. In both cats and rats, carbamazepine was shown to decrease pain caused by infraorbital nerve stimulation. A decrease in the action potential in the nucleus ventralis of the thalamus in the brain and inhibition of the lingual mandibular reflex were observed in other studies after carbamazepine use. Zagretol causes the above effects by binding to voltage-dependent sodium channels and preventing action potentials, which normally lead to stimulatory effects on nerves. In bipolar disorder, carbamazepine is thought to increase dopamine turnover and increase GABA transmission, treating manic and depressive symptoms.
A common issue that has arisen is resistance to this drug in up to 30% of epileptic patients, which may occur to altered metabolism in patients with variant genotypes. A potential therapeutic target to combat carbamazepine resistance has recently been identified as the EPHX1 gene promoter, potentially conferring resistance to carbamazepine through methylation.
Dosage
Zagretol dosage
Epilepsy:
- Adult: Initially, 100-200 mg once daily or bid, gradually increased by increments of up to 200 mg daily every wk. Maintenance: 0.8-1.2 gm daily in divided doses. Max: 2 gm daily.
- Child: 10-20 mg/kg daily in divided doses. Alternatively, <1 yr 100-200 mg daily. Max: 35 mg/kg daily; 1-5 yr 200-400 mg daily. Max: 35 mg/kg daily; >5-10 yr 400-600 mg daily. Max: 1 gm daily; >10-15 yr 0.6-1 gm daily. Max: 1 gm daily.
Prophylaxis of bipolar disorder:
- Adult: Initially, 400 mg daily in divided doses, increased gradually as necessary. Maintenance: 400-600 mg daily in divided doses. Max: 1.6 gm daily.
Trigeminal neuralgia:
- Adult: Initially, 100-200 mg bid, increased gradually as needed. Maintenance: 400-800 mg daily in divided doses. Max: 1.2 gm daily.
Side Effects
Common side effects are dizziness, drowsiness, ataxia, dry mouth, abdominal pain, nausea, vomiting, anorexia, leucopenia, proteinuria, bradycardia, heart failure and hypotension. Erythematous skin rash, aplastic anemia may also be observed.
The most severe adverse reactions have been observed in the hemopoietic system, the skin and the cardiovascular system.The most frequently observed adverse reactions, particularly during the initial phases of therapy, are dizziness, drowsiness, unsteadiness, nausea, and vomiting.This medicine may cause increased sensitivity to the sun. Exposure to the sun, sunlamps, or tanning booths should be avoided if the increased sensitivity is seen. A sunscreen or protective clothing may be helpful at outside for a prolonged period.
Toxicity
Toxicity information Oral LDLO (female): 1920 mg/kg/17W (intermittent); Oral LDLO (male): 54 mg/kg/9D (intermittent) Oral LD50 (rat): 1957 mg/kg
Overdose information
The initial signs of carbamazepine overdose occur 1-3 hours post ingestion. These signs and symptoms may vary in case of an overdose between carbamazepine and other drugs. Zagretol may cause various cardiovascular, neurological, respiratory, urinary symptoms as well as laboratory abnormalities including leukocytosis, reduced leucocytes, acetonuria, and glycosuria.
Neuromuscular symptoms may occur initially, followed by mild cardiac symptoms such as tachycardia, hypertension, or hypotension. Higher doses of carbamazepine may cause more severed cardiovascular effects. Restlessness, muscular twitching, tremor, dilated pupils, nystagmus, psychomotor disturbances, and other neurological symptoms may occur. Hyperreflexia in the initial stages of overdose may be followed by hyporeflexia. Nausea, vomiting, urinary retention, dizziness or drowsiness may also occur. In cases of overdose, contact the local poison control center. Ensure to provide supportive and symptomatic treatment, which may include monitoring and careful supervision by a medical professional. The possibility of overdose with multiple drugs must be considered in the case of carbamazepine overdose. Maintain an adequate airway, oxygen, in addition to ventilation. Vital signs should be monitored.
Precaution
Zagretol should be used with caution in cardiovascular disease, hepatic or renal disorders, changing treatment from Zagretol to another antiepileptic drug, haematological disorder, glaucoma etc.
Interaction
Galactorrhoea has been reported in few women on oral contraceptives within the first two months of Zagretol treatment Hepatic enzyme inducers such as Zagretol and Phenytoin may interact with Zagretol by increasing its metabolism. So an increase in dosage of Zagretol may be required.
Food Interaction
- Avoid alcohol. Ingesting alcohol may increase drowsiness and dizziness.
- Avoid grapefruit products.
- Exercise caution with St. John's Wort. This herb induces the CYP3A metabolism of carbamazepine and may reduce its serum concentration.
- Take with or without food.
[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine.
Use in combination may result in additive central nervous system depression and
In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%.
The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.
MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol.
Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.
Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.
Zagretol Drug Interaction
Major: quetiapine, quetiapineModerate: aripiprazole, aripiprazole, duloxetine, duloxetine, pregabalin, pregabalin, levothyroxine, levothyroxine, acetaminophen, acetaminophen, cholecalciferol, cholecalciferolUnknown: omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid
Volume of Distribution
The volume of distribution of carbamazepine was found to be 1.0 L/kg in one pharmacokinetic study. Another study indicates that the volume of distribution of carbamazepine ranges between 0.7 to 1.4 L/kg.. Zagretol crosses the placenta, and higher concentrations of this drug are found in the liver and kidney as opposed to lung and brain tissue. Zagretol crosses variably through the blood-brain barrier.
Elimination Route
The bioavailability of carbamazepine is in the range of 75-85% of an ingested dose. After one 200 mg oral extended-release dose of carbamazepine in a pharmacokinetic study, the Cmax carbamazepine was measured to be 1.9 ± 0.3 mcg/mL. The Tmax was 19 ± 7 hours. After several doses of 800 mg every 12 hours, the peak concentrations of carbamazepine were measured to be 11.0 ± 2.5 mcg/mL. The Tmax was reduced to 5.9 ± 1.8 hours. Extended-release carbamazepine demonstrated linear pharmacokinetics over a range of 200–800 mg.
Effect of food on absorption
A meal containing high-fat content increased the rate of absorption of one 400 mg dose but not the AUC of carbamazepine. The elimination half-life remained unchanged between fed and fasting state. The pharmacokinetics of an extended-release carbamazepine dose was demonstrated to be similar when administered in the fasted state or with food. Based on these findings, food intake is unlikely to exert significant effects on carbamazepine absorption.
Half Life
The mean elimination half-life of carbamazepine was 35 to 40 hours after one dose of carbamazepine extended-release formulations. The half-life ranged from 12-17 hours after several doses of carbamazepine. One pharmacokinetic study determined the elimination half-life of carbamazepine to range between 27 to 36.8 hours in healthy volunteers.
Clearance
In a pharmacokinetic study, the apparent oral clearance of carbamazepine was 25 ± 5 mL/min after one dose of carbamazepine and 80 ± 30 mL/min after several doses.
Elimination Route
After an oral dose of radiolabeled carbamazepine, 72% of the administered radioactive dose was detected in the urine and the remainder of the ingested dose was found in the feces. Zagretol is mainly excreted as hydroxylated and conjugated metabolites, and minimal amounts of unchanged drug.
Pregnancy & Breastfeeding use
Pregnancy category D. Zagretol and its epoxide metabolite are transferred to breast milk. Because of the potential serious side effects, decision should me made whether to discontinue nursing or discontinue the drug.
Contraindication
This medicine should not be used if anybody is allergic to one or any of its ingredients. It can not be used also in the following conditions:
- Problems with the electrical message pathways in the heart (atrioventricular block)
- History of decreased blood cell production by the bone marrow (bone marrow depression)
- Hereditary blood disorders called porphyrias
- Allergy to tricyclic antidepressants
- People who have taken a monoamine-oxidase inhibitor antidepressant (MAOI) in the last 14 days
Acute Overdose
Symptoms: Dizziness, ataxia, drowsiness, stupor, nausea, vomiting, opisthotonos, restlessness, agitation, disorientation, tremor, involuntary movements, adiadochokinesis, abnormal reflexes (hypoactive or hyperactive), mydriasis, nystagmus, flushing, cyanosis, urinary retention. Hypotension or HTN may develop. Coma may follow.
Management: Induce emesis or employ gastric lavage. General supportive treatment.
Storage Condition
Store at a cool & dry place, protected from light. Keep all medicines out of the reach of the children
Innovators Monograph
You find simplified version here Zagretol
Zagretol contains Carbamazepine see full prescribing information from innovator Zagretol Monograph, Zagretol MSDS, Zagretol FDA label
FAQ
What is Zagretol used for?
Zagretol is a medicine used to treat epilepsy. It can also be taken for nerve pain caused by diabetes or if you have a painful condition of the face called trigeminal neuralgia. Zagretol is occasionally used to treat bipolar disorder when other medicines have not worked. It is used as an adjunctive treatment in schizophrenia along with other medications and as a second-line agent in bipolar disorder.
How safe is Zagretol?
Zagretol is a safe and effective medication when used as directed. It is important to note that some of the side effects listed above (particularly changes in blood sodium, rash, and suicidal thoughts) may continue to occur or worsen if you continue taking the medication.
how does Zagretol work?
Zagretol works by stopping electrical signals from building up in the nerve cells in the brain.
What are the common side effects of Zagretol?
Common side effects of Zagretol are include feeling sleepy, dizziness, headaches and feeling or being sick.
Is Zagretol safe during pregnancy?
Zagretol increases the risk of neural tube defects. It does not increase the risk of other malformations. Zagretol is also not associated with an increased risk of developmental delay.
Is Zagretol safe during breastfeeding?
Zagretol are generally considered safe for use during breast feeding.
Can I drink alcohol with Zagretol?
You should avoid or limit the use of alcohol while being treated with Zagretol. Alcohol can increase the nervous system side effects of Zagretol such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment.
Can I drive after taking Zagretol?
Do not drink alcohol while you are taking Zagretol because this may increase the sedative effect of Zagretol.
When should be taken of Zagretol?
The regular tablet, chewable tablet, and suspension are usually taken two to four times a day with meals. The extended-release tablet Zagretol is usually taken twice a day with meals. The extended-release capsule is usually taken twice a day with or without meals.
How long does Zagretol take to work?
It can take 1 to 2 weeks for Zagretol to work properly.
How long does Zagretol stay in my system?
After single oral doses of Zagretol, the absorption is fairly complete and the elimination half-life is about 35 hours.
How often can I take Zagretol?
It's usual to take Zagretol between 1 and 4 times a day.
Can I take Zagretol for a long time?
Many people take Zagretol safely for many months or years. However, there are some side effects that can happen over a long time. Long-term treatment with Zagretol can cause osteoporosis and osteopenia.
Can I just stop taking Zagretol ?
Do not stop taking Zagretol suddenly, unless your doctor tells you to. You're unlikely to get any extra symptoms when you stop taking this medicine.
What happens when I stop taking Zagretol ?
If you suddenly stop taking Zagretol, you may experience a severe, long-lasting and possibly life-threatening seizure. Your doctor will probably decrease your dose gradually.
What should I do if I forget a dose?
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.
Who should not take Zagretol?
You should not take Zagretol if you have a history of bone marrow suppression, or if you are allergic to Zagretol or to an antidepressant such as amitriptyline, desipramine, doxepin, imipramine, or nortriptyline.
Can Zagretol make me high?
Zagretol is known to produce the side effect of euphoria. As such, it lends itself to being a drug of abuse, particularly in the adolescent population.
What happens if I take too much Zagretol ?
You take too much Zagretol and: feel sick or be sick (vomit) have breathing problems. feel dizzy or sleepy.
Can Zagretol affect my kidneys?
Zagretol can induce kidney water absorption by increasing aquaporin 2 expression.
Can Zagretol affects my liver?
Zagretol is an aromatic anticonvulsant that is widely used in therapy of epilepsy and trigeminal neuralgia and is a well established cause of clinically apparent liver injury which can be severe and even fatal.