Pharozepine
Pharozepine Uses, Dosage, Side Effects, Food Interaction and all others data.
The pharmacological activity of Pharozepine is primarily exerted through the metabolite derivative (the monohydroxy derivative, MHD) of Pharozepine. The mechanism of action of Pharozepine and MHD is thought to be mainly based on blockade of voltage-sensitive sodium channels, thus resulting in stabilization of hyper excited neural membranes, inhibition of repetitive neuronal firing and diminishment of propagation of synaptic impulses.
Pharozepine is an anticonvulsant drug that reduces the incidence of seizures in epilepsy by inhibiting abnormal electrical activity in the brain.
There have been rare reports of oxcarbazepine resulting in the development of hematologic abnormalities, including agranulocytosis and aplastic anemia. Patients should be undergo frequent laboratory testing and should be monitored closely for signs and symptoms of blood dyscrasias. Pharozepine has also been associated with the development of dermatologic reactions which can progress from a simple rash to potentially fatal reactions such as toxic epidermal necrolysis (TEN) or Stevens-Johnson Syndrome (SJS). Patients with the HLA-A3101 and/or HLA-B1502 alleles may be at higher risk of this reaction. Pharozepine should be discontinued at the first sign of a drug-induced skin reaction.
| Trade Name | Pharozepine |
| Availability | Prescription only |
| Generic | Oxcarbazepine |
| Oxcarbazepine Other Names | OCBZ, Oxcarbamazepine, Oxcarbazepina, Oxcarbazepine, Oxcarbazepinum |
| Related Drugs | gabapentin, clonazepam, lamotrigine, diazepam, pregabalin, Lyrica, topiramate, levetiracetam, Keppra, Topamax |
| Type | |
| Formula | C15H12N2O2 |
| Weight | Average: 252.268 Monoisotopic: 252.089877638 |
| Protein binding | The pharmacologically active metabolite of oxcarbazepine, MHD, is approximately 40% bound to plasma proteins, predominantly albumin. |
| Groups | Approved |
| Therapeutic Class | Adjunct anti-epileptic drugs |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Pharozepine is used for:
Adults: Monotherapy or adjunctive therapy in the treatment of partial seizures
Pediatrics:
- Monotherapy in the treatment of partial seizures in children 4-16 years
- Adjunctive therapy in the treatment of partial seizures in children 2–16 years
Pharozepine is also used to associated treatment for these conditions: Partial-Onset Seizures
How Pharozepine works
The exact mechanism through which oxcarbazepine and its active metaoblite, MHD, exert their anti-epileptic effects is unclear, but is thought to primarily involve the blockade of voltage-gated sodium channels. The opening and closing of sodium channels allows for the propagation of action potentials along neurons - in epilepsy, these action potentials can occur in excess of that required for normal function, and the repetitive and pathological firing of these action potentials leads to seizure activity. Both oxcarbazepine and MHD are thought to inhibit seizure activity by binding to the inactive state of voltage-gated sodium channels, thus prolonging the period in which the receptor is unavailable for action potential propagation. This helps to stabilize hyperexcited neuronal membranes, inhibit repetitive neuron firing, and prevent the spread of seizure activity within the CNS without affecting normal neuronal transmission.
Increased potassium conductance and modulation of voltage-activated calcium channels is also thought to play a role in the anti-seizure activity of oxcarbazepine. Inhibition of glutamatergic activity was thought to contribute to oxcarbazepine's activity, but this effect could not be replicated in vivo.
Dosage
Pharozepine dosage
Adults: initiate with a dose of 600 mg/day, given twice-a-day
- Adjunctive Therapy: Maximum increment of 600 mg/day at approximately weekly intervals. The recommended daily dose is 1200 mg/day
- Conversion to Monotherapy: withdrawal concomitant over 3 to 6 weeks;reach maximum dose of Pharozepine in 2 to 4 weeks with increments of 600 mg/day at weekly intervals to a recommended daily dose of 2400 mg/day
- Initiation of Monotherapy: Increments of 300 mg/day every third day to a dose of 1200 mg/day.
- Creatinine Clearance <30 mL/min: Initiate at one half the usual starting dose and increase slowly
Pediatrics: initiation with 8 to 10 mg/kg/day, given twice-a-day. For patients aged 2 to <4 years and under 20 kg, a starting dose of 16 to 20 mg/kg/day may be considered. Recommended daily dose is dependent upon patient weight.
- Adjunctive Patients (Aged 2–16 Years): For patients aged 4 to 16 years, target maintenance dose should be achieved over 2 weeks. For patients aged 2 to <4 years, maximum maintenance dose should be achieved over 2 to 4 weeks and should not to exceed 60 mg/kg/day
- Conversion to Monotherapy for Patients (Aged 4-16 Years): Maximum increment of 10 mg/kg/day at weekly intervals, concomitant antiepileptic drugs can be completely withdrawn over 3 to 6 weeks
- Initiation of Monotherapy for Patients (Aged 4–16 Years): Increments of 5 mg/kg/day every third day
Side Effects
The most commonly reported adverse reactions are somnolence, headache, dizziness, diplopia, nausea; vomiting and fatigue. Very rarely clinically significant hyponatraemia can develop during Oxazep use. Class I (immediate) hypersensitivity reactions including rash, pruritus, urticaria, angioedema and reports of anaphylaxis have been received.
Toxicity
The oral LD50 of oxcarbazepine in mammals is 1240 mg/kg and the oral TDLo in children has been reported to be 73 mg/kg. Isolated cases of oxcarbazepine overdose have been reported - patients who ingested up to 24,000mg recovered with symptomatic treatment. Symptoms may include respiratory and CNS depression, movement-related disorders (e.g. dyskinesia, ataxia), nausea/vomiting, hyponatremia, or QTc prolongation. There is no antidote for oxcarbazepine overdose - management should consist of supportive and symptomatic treatment, and consideration should be given to the use of gastric lavage or activated charcoal.
Precaution
Alcohol: Caution should be exercised if alcohol is taken in combination with Oxazep therapy, due to a possible additive sedative effect.
Withdrawal: As with all antiepileptic medicinal products, Oxazep should be withdrawn gradually to minimise the potential of increased seizure frequency.
Interaction
Pharozepine and its metabolite inhibit the enzyme CYP2C19 and therefore, interactions could arise when co-administering high doses of Oxazep with medicinal products that are metabolised by CYP2C19 (e.g. phenobarbital, phenytoin). Concurrent use of Oxazep with hormonal contraceptives may render few contraceptives ineffective (e.g. Ethinylestradiol and Levonorgestrel preparations). Co-administration of Oxazep lowers AUC of felodipine and Verapamil decreases bioavailability of MHD.
Food Interaction
- Avoid alcohol. Pharozepine has CNS depressant properties that may be potentiated by co-administration with alcohol.
- Take with or without food. Co-administration with food does not significantly affect absorption.
[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.
Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.
Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
Pharozepine Drug Interaction
Moderate: aripiprazole, diphenhydramine, duloxetine, clonazepam, lamotrigine, lurasidone, escitalopram, pregabalin, quetiapine, topiramate, cholecalciferol, alprazolam, sertraline, cetirizineUnknown: amphetamine / dextroamphetamine, omega-3 polyunsaturated fatty acids, levothyroxine, cyanocobalamin, ascorbic acid, lisdexamfetamine
Pharozepine Disease Interaction
Major: depression, liver disease, renal dysfunctionModerate: hyponatremia, suicidal tendency, arrhythmias, blood dyscrasias, thyroid dysfunction
Volume of Distribution
The apparent volume of distribution of oxcarbazepine is 49 L. The apparent volumes of distribution of (S)- and (R)-MHD were found to be 23.6 L and 31.7 L, respectively.
Elimination Route
Pharozepine is completely absorbed following oral administration. A single 600mg dose of oxcarbazepine resulted in an MHD Cmax of 34 μmol/L and a median Tmax of 4.5 hours. When administered twice daily, steady-state levels of MHD are attained within 2-3 days. The rate and extent of absorption of oxcarbazepine is not affected by food intake.
Half Life
The plasma half-life of oxcarbazepine is approximately 2 hours and the plasma half-life of MHD is approximately 9 hours.
Clearance
Plasma clearance of oxcarbazepine has been estimated to be approximately 84.9 L/h, whereas plasma clearance of its active metabolite, MHD, was estimated to be 2.0 L/h. Rapid metabolic clearance appears to be the main pathway for oxcarbazepine, while clearance of its metabolites occurs mainly via renal excretion.
Elimination Route
Following oral administration, more than 95% of the administered dose of oxcarbazepine is found in the urine. Of this, approximately 49% is MHD glucuronide metabolites, 27% is unchanged MHD, 3% is inactive DHD metabolites, 13% is conjugated oxcarbazepine, and less than 1% is unchanged parent drug. Fecal elimination accounts for only 4% of the administered dose.
Pregnancy & Breastfeeding use
Pregnancy: Data on a limited number of pregnancies indicate that Pharozepine may cause serious birth defects (e.g. cleft palate) when administered during pregnancy. In the newborn child. Bleeding disorders in the newborn caused by antiepileptic agents have been reported. As a precaution, vitamin K1 should be administered as a preventive measure in the last few weeks of pregnancy and to the newborn. Pharozepine and its active metabolite (MHD) cross the placenta. Neonatal and maternal plasma MHD concentrations were similar in one case.
Lactation: Pharozepine and its active metabolite (MHD) are excreted in human breast milk. Therefore, Oxazep should not be used during breast-feeding.
Contraindication
It is contraindicated to patients with hypersensitivity to the active substance or to any of the excipients.
Innovators Monograph
You find simplified version here Pharozepine
Pharozepine contains Oxcarbazepine see full prescribing information from innovator Pharozepine Monograph, Pharozepine MSDS, Pharozepine FDA label
FAQ
What is Pharozepine used for?
Pharozepine is a medication used to treat epilepsy and bipolar disorder. For epilepsy it is used for both focal seizures and generalized seizures. Pharozepine is an antiepileptic medication that works in the brain to prevent and control seizures. It is approved for the treatment of partial seizures. Pharozepine may also be helpful when prescribed “off-label” for nerve pain or as a mood stabilizer for bipolar disorder.
How safe is Pharozepine?
Pharozepine may rarely cause very serious skin reactions. Some people in certain ethnic groups are at greater risk. Your doctor may order a blood test to measure your risk before you start this medication. Pharozepine may cause life-threatening allergic skin reactions. These are called Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These may cause severe damage to your skin and internal organs. Your risk may be higher if you have Asian ancestry with a genetic risk factor.
How does Pharozepine work?
Pharozepine works by decreasing nerve impulses that cause seizures and pain.
What are the common side effects of Pharozepine?
Common side effects of Pharozepine are include:
- a change in vision.
- nystagmus, a condition with involuntary eye movements.
- drowsiness.
- dizziness.
- low energy.
- muscle tremors.
- headache.
- intense abdominal pain.
Is Pharozepine safe during pregnancy?
Pharozepine has not been well studied for use during pregnancy in humans.
Is Pharozepine safe during breastfeeding?
Pharozepine levels in breastmilk are low and it is not expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. A safety scoring system finds Pharozepine possible to use cautiously during breastfeeding.
Can I drink alcohol with Pharozepine?
Do not drink alcohol. Drinking alcohol can increase certain side effects, and may increase the risk of seizures.
Can I drive after taking Pharozepine?
Pharozepine may make you sleepy or impair your reaction times and affect your ability to drive or operate machinery. Do not drive or operate machinery if Pharozepine affects you in this way. Alcohol may make these effects worse.
When should be taken of Pharozepine?
The tablet and suspension are usually taken every 12 hours (twice a day) with or without food. The extended-release tablet is usually taken once a day on an empty stomach, 1 hour before or 2 hours after a meal.
How long does Pharozepine take to work?
A summary of studies in which Pharozepine was used adjunctively for partial seizures reported that 41% of adults who took Pharozepine had their seizures reduced in frequency by at least half.
How does Pharozepine make me feel?
Pharozepine can cause a decrease in the body's sodium level. Some signs of low sodium include nausea, tiredness, lack of energy, headache, confusion, or more frequent or more severe seizures.
How long does Pharozepine stay in my system?
The half-life of Pharozepine is 1 to 3.7 hours, while the half-life of licarbazepine is 8 to 10 hours.
What happens if I stop taking Pharozepine?
Do not stop taking Pharozepine without talking to your doctor, even if you experience side effects such as unusual changes in behavior or mood. If you suddenly stop taking Pharozepine, your seizures may get worse. Your doctor will probably decrease your dose gradually.
Does Pharozepine cause memory loss?
Pharozepine improved performance on a focused attention task and increased manual writing speed, and had no effect on long-term memory processes.
Does Pharozepine cause weight gain?
Risk of weight gain is high with lithium and valproate and low with carbamazepine, lamotrigine, and Pharozepine.
Can Pharozepine cause liver damage?
Pharozepine has been linked to rare instances of clinically apparent acute drug induced liver injury which resembles carbamazepine hepatotoxicity.
When should I stop taking Pharozepine ?
Do not stop Pharozepine suddenly, unless your doctor has told you to do so. It is best to discontinue Pharozepine slowly. Tell your doctor if you are pregnant, intending to become pregnant, or breastfeeding because Pharozepine may not be suitable for you.
Can I take Pharozepine long term?
To date, there are no known problems associated with long term use of Pharozepine. It is a safe and effective medication when used as directed.
Who should not take Pharozepine ?
You should not take Pharozepine if you have a history of bone marrow suppression, or if you are allergic to carbamazepine or to an antidepressant such as amitriptyline, desipramine, doxepin, imipramine, or nortriptyline. Do not use carbamazepine if you have taken an MAO inhibitor in the past 14 days.
Who should not take Pharozepine?
You should not take Pharozepine if you have a history of bone marrow suppression, or if you are allergic to Pharozepine or to an antidepressant such as amitriptyline, desipramine, doxepin, imipramine, or nortriptyline. Do not use Pharozepine if you have taken an MAO inhibitor in the past 14 days.
What happens if I miss 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.
What happens if I overdose?
Seek emergency medical attention. Overdose symptoms may include severe drowsiness, weak or shallow breathing, and loss of consciousness.
