Primidone 125mg Tablets
It is used to help control certain kinds of seizures.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Anticonvulsant
Pharmacologic Class
Barbiturate Anticonvulsant
Pregnancy Category
Category D
FDA Approved
Jan 1970
DEA Schedule
Not Controlled
Overview
What is this medicine?
Primidone is a medication used to help control certain types of seizures (epilepsy). It works by affecting brain activity to reduce the frequency and severity of seizures. It is converted in your body into another medicine called phenobarbital, which also helps with seizure control.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, take it exactly as directed by your doctor. Carefully read all the information provided with your prescription, and follow the instructions closely. Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry location, avoiding the bathroom. Keep all medications in a secure place, out of the reach of children and pets. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless specifically instructed to do so. Instead, consult with your pharmacist for guidance on the proper disposal method. You may also want to inquire about drug take-back programs available in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
To get the most benefit from your medication, take it exactly as directed by your doctor. Carefully read all the information provided with your prescription, and follow the instructions closely. Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry location, avoiding the bathroom. Keep all medications in a secure place, out of the reach of children and pets. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless specifically instructed to do so. Instead, consult with your pharmacist for guidance on the proper disposal method. You may also want to inquire about drug take-back programs available in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Take this medication exactly as prescribed by your doctor. Do not stop taking it suddenly, as this can cause seizures to worsen or occur more frequently.
- Avoid alcohol and other medications that can cause drowsiness (e.g., sedatives, tranquilizers, opioids) while taking primidone, as this can increase side effects like extreme drowsiness and breathing problems.
- Be cautious when driving or operating machinery until you know how this medication affects you, as it can cause dizziness, drowsiness, and unsteadiness.
- If you are a woman of childbearing potential, discuss effective birth control methods with your doctor, as primidone can reduce the effectiveness of oral contraceptives. Also, discuss the risks of primidone during pregnancy.
- Maintain good oral hygiene and regular dental check-ups.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
750-1500 mg/day in 2-4 divided doses
Dose Range:
125 - 2000 mg
Condition-Specific Dosing:
initial_titration:
Start with 125 mg once daily at bedtime for 3 days, then 125 mg twice daily for 3 days, then 125 mg three times daily for 3 days, then 125 mg four times daily for 3 days. Increase by 125-250 mg/day every 3-7 days until desired effect or maximum dose.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Initial: 50 mg/day at bedtime for 3 days, then 50 mg twice daily for 3 days, then 100 mg twice daily for 3 days. Maintenance: 10-25 mg/kg/day in 3-4 divided doses (typically 250-1000 mg/day).
Adolescent:
Initial: 125 mg/day at bedtime for 3 days, then 125 mg twice daily for 3 days, then 125 mg three times daily for 3 days, then 125 mg four times daily for 3 days. Increase by 125-250 mg/day every 3-7 days until desired effect or maximum dose (typically 750-1500 mg/day).
Dose Adjustments
Renal Impairment:
Mild:
Adjustment needed (monitor levels)
Moderate:
Reduce dose by 25-50% (monitor levels)
Severe:
Reduce dose by 50% or more (monitor levels closely)
Dialysis:
Primidone and its active metabolites are dialyzable; supplemental dose may be required post-dialysis. Monitor levels.
Hepatic Impairment:
Mild:
Adjustment needed (monitor levels)
Moderate:
Reduce dose by 25-50% (monitor levels)
Severe:
Reduce dose by 50% or more (monitor levels closely)
Pharmacology
Mechanism of Action
Primidone is an anticonvulsant that is metabolized in the liver to two active metabolites: phenobarbital and phenylethylmalonamide (PEMA). Phenobarbital is thought to exert its anticonvulsant effect by enhancing GABAergic neurotransmission, thereby increasing the seizure threshold and limiting the spread of seizure activity. PEMA also possesses anticonvulsant activity, though its exact mechanism is less understood. The combined action of primidone and its metabolites contributes to its broad-spectrum anticonvulsant properties.
Pharmacokinetics
Absorption:
Bioavailability:
High (approximately 90-100%)
Tmax:
Primidone: 3 hours; Phenobarbital (metabolite): 6-8 hours
FoodEffect:
Minimal effect on absorption, can be taken with or without food.
Distribution:
Vd:
0.6 L/kg
ProteinBinding:
Primidone: 20-25%; Phenobarbital: 40-60%
CnssPenetration:
Yes
Elimination:
HalfLife:
Primidone: 3-23 hours (average 10-12 hours); Phenobarbital: 53-118 hours
Clearance:
Not readily available as a single rate, varies by individual and renal/hepatic function.
ExcretionRoute:
Renal (primarily as metabolites)
Unchanged:
Approximately 15-25% of primidone is excreted unchanged in urine.
Pharmacodynamics
OnsetOfAction:
Slow (due to conversion to phenobarbital)
PeakEffect:
Delayed (due to phenobarbital accumulation)
DurationOfAction:
Long (due to long half-life of phenobarbital)
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Erectile dysfunction
Changes in vision
Inability to control eye movements
Fever, chills, or sore throat
Swollen lymph nodes
Shortness of breath
Balance problems
Difficulty walking
Like other medications used to treat seizures, this drug may increase the risk of suicidal thoughts or behaviors, particularly in individuals with a history of suicidal ideation. If you experience any new or worsening symptoms, such as:
Depression
Anxiety, restlessness, or irritability
Panic attacks
Mood or behavioral changes
contact your doctor immediately. If you have suicidal thoughts or attempt to harm yourself, seek emergency medical help right away.
Other Possible Side Effects
Most medications can cause side effects, but many people may not experience any or may only have mild symptoms. If you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical attention if they bother you or persist:
Dizziness, drowsiness, fatigue, or weakness
Nausea, vomiting, or upset stomach
Decreased appetite
This is not an exhaustive list of potential side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Erectile dysfunction
Changes in vision
Inability to control eye movements
Fever, chills, or sore throat
Swollen lymph nodes
Shortness of breath
Balance problems
Difficulty walking
Like other medications used to treat seizures, this drug may increase the risk of suicidal thoughts or behaviors, particularly in individuals with a history of suicidal ideation. If you experience any new or worsening symptoms, such as:
Depression
Anxiety, restlessness, or irritability
Panic attacks
Mood or behavioral changes
contact your doctor immediately. If you have suicidal thoughts or attempt to harm yourself, seek emergency medical help right away.
Other Possible Side Effects
Most medications can cause side effects, but many people may not experience any or may only have mild symptoms. If you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical attention if they bother you or persist:
Dizziness, drowsiness, fatigue, or weakness
Nausea, vomiting, or upset stomach
Decreased appetite
This is not an exhaustive list of potential side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe skin rash, especially if accompanied by fever, swollen glands, or facial swelling (could be a sign of a serious allergic reaction like Stevens-Johnson syndrome or DRESS syndrome).
- Unusual bleeding or bruising, pale skin, extreme tiredness, or frequent infections (could indicate blood problems).
- Yellowing of the skin or eyes (jaundice), dark urine, or persistent abdominal pain (could indicate liver problems).
- Increased seizure frequency or severity.
- Extreme drowsiness, confusion, or unsteadiness that significantly impacts daily activities.
- Thoughts of self-harm or suicide (report immediately).
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have porphyria, a rare genetic disorder that affects the production of heme, a vital molecule in the body.
This list is not exhaustive, and it is crucial to discuss all your medications, health conditions, and concerns with your doctor. Please provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or supplements you are using
Vitamins you are taking
Any health problems you have, including pre-existing conditions and medical history
Before starting, stopping, or changing the dose of any medication, including this one, consult with your doctor to ensure your safety. It is vital to verify that it is safe to take this medication with all your other medications and health conditions.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have porphyria, a rare genetic disorder that affects the production of heme, a vital molecule in the body.
This list is not exhaustive, and it is crucial to discuss all your medications, health conditions, and concerns with your doctor. Please provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or supplements you are using
Vitamins you are taking
Any health problems you have, including pre-existing conditions and medical history
Before starting, stopping, or changing the dose of any medication, including this one, consult with your doctor to ensure your safety. It is vital to verify that it is safe to take this medication with all your other medications and health conditions.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Until you understand how this medication affects you, avoid operating a vehicle or engaging in activities that require your full attention.
Do not abruptly discontinue this medication without consulting your doctor, as this may increase your risk of experiencing seizures. If you need to stop taking this medication, your doctor will instruct you on how to gradually taper off the dosage to minimize potential risks.
You may not notice the full effects of this medication for several weeks. As directed by your doctor, have your blood work checked and discuss the results with them.
Before consuming alcohol, using marijuana or other cannabis products, or taking prescription or over-the-counter medications that can impair your reactions, consult with your doctor.
If you experience changes in your seizure patterns or if they worsen after starting this medication, notify your doctor promptly.
When taking this medication, birth control pills and other hormone-based contraceptives may be less effective in preventing pregnancy. To minimize the risk of unplanned pregnancy, use an additional form of birth control, such as condoms, in conjunction with your primary method.
If you are pregnant or become pregnant while taking this medication, you should contact your doctor immediately, as it may pose a risk to the unborn baby.
If you are breastfeeding, inform your doctor, as you will need to discuss the potential risks to your baby and determine the best course of action.
Until you understand how this medication affects you, avoid operating a vehicle or engaging in activities that require your full attention.
Do not abruptly discontinue this medication without consulting your doctor, as this may increase your risk of experiencing seizures. If you need to stop taking this medication, your doctor will instruct you on how to gradually taper off the dosage to minimize potential risks.
You may not notice the full effects of this medication for several weeks. As directed by your doctor, have your blood work checked and discuss the results with them.
Before consuming alcohol, using marijuana or other cannabis products, or taking prescription or over-the-counter medications that can impair your reactions, consult with your doctor.
If you experience changes in your seizure patterns or if they worsen after starting this medication, notify your doctor promptly.
When taking this medication, birth control pills and other hormone-based contraceptives may be less effective in preventing pregnancy. To minimize the risk of unplanned pregnancy, use an additional form of birth control, such as condoms, in conjunction with your primary method.
If you are pregnant or become pregnant while taking this medication, you should contact your doctor immediately, as it may pose a risk to the unborn baby.
If you are breastfeeding, inform your doctor, as you will need to discuss the potential risks to your baby and determine the best course of action.
Overdose Information
Overdose Symptoms:
- Severe drowsiness or sedation
- Ataxia (loss of coordination)
- Nystagmus (involuntary eye movements)
- Slurred speech
- Respiratory depression (slow, shallow breathing)
- Hypotension (low blood pressure)
- Hypothermia
- Coma
- Renal failure (in severe cases)
What to Do:
Seek immediate medical attention. Call 911 or your local emergency number. For poison control, call 1-800-222-1222. Treatment may involve supportive care, activated charcoal, and in severe cases, hemodialysis to remove the drug and its metabolites.
Drug Interactions
Contraindicated Interactions
- Patients with acute intermittent porphyria
Major Interactions
- Alcohol and other CNS depressants (increased sedation, respiratory depression)
- Oral contraceptives (decreased efficacy of contraceptives due to enzyme induction)
- Warfarin (decreased anticoagulant effect due to enzyme induction)
- Corticosteroids (decreased corticosteroid effect)
- Doxycycline (decreased doxycycline levels)
- Valproic acid (increased phenobarbital levels, potential toxicity)
- Phenytoin (complex interaction, can increase or decrease primidone/phenobarbital levels)
- Lamotrigine (decreased lamotrigine levels)
- Topiramate (decreased topiramate levels)
- Tiagabine (decreased tiagabine levels)
- Zonisamide (decreased zonisamide levels)
- Felbamate (increased phenobarbital levels)
Moderate Interactions
- Tricyclic antidepressants (decreased antidepressant levels, increased CNS depression)
- Antipsychotics (increased CNS depression)
- Carbamazepine (complex interaction, can alter levels of both drugs)
- Clonazepam (increased CNS depression)
- Griseofulvin (decreased griseofulvin levels)
- Methadone (decreased methadone levels, risk of withdrawal)
- Quetiapine (decreased quetiapine levels)
- Rifampin (decreased primidone/phenobarbital levels)
Minor Interactions
- Folic acid (may increase seizure frequency in some patients, primidone can cause folate deficiency)
Monitoring
Baseline Monitoring
Complete Blood Count (CBC)
Rationale: To establish baseline hematologic parameters and monitor for potential blood dyscrasias (e.g., megaloblastic anemia, leukopenia, thrombocytopenia).
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs)
Rationale: To establish baseline hepatic function and monitor for potential hepatotoxicity.
Timing: Prior to initiation of therapy.
Renal Function Tests (BUN, Creatinine)
Rationale: To establish baseline renal function, as primidone and its metabolites are renally excreted.
Timing: Prior to initiation of therapy.
Primidone and Phenobarbital Plasma Levels
Rationale: To establish baseline levels and guide initial dosing, especially in complex cases or when switching from other AEDs. Therapeutic range for phenobarbital is typically 15-40 mcg/mL.
Timing: Prior to initiation or shortly after starting therapy.
Routine Monitoring
Complete Blood Count (CBC)
Frequency: Every 6-12 months, or more frequently if clinically indicated (e.g., signs of infection, bruising).
Target: Within normal limits
Action Threshold: Significant deviations (e.g., persistent leukopenia, thrombocytopenia, macrocytosis) warrant investigation and potential dose adjustment or discontinuation.
Liver Function Tests (LFTs)
Frequency: Every 6-12 months, or more frequently if clinically indicated (e.g., signs of hepatic dysfunction).
Target: Within normal limits
Action Threshold: Persistent elevation of liver enzymes (e.g., AST, ALT > 3x ULN) warrants investigation and potential dose adjustment or discontinuation.
Primidone and Phenobarbital Plasma Levels
Frequency: Periodically (e.g., every 6-12 months) once stable, or more frequently during dose titration, if seizures are not controlled, or if toxicity is suspected.
Target: Phenobarbital: 15-40 mcg/mL (therapeutic range for seizure control)
Action Threshold: Levels outside therapeutic range, or signs of toxicity/lack of efficacy, warrant dose adjustment.
Vitamin D and Calcium Levels
Frequency: Annually for long-term therapy.
Target: Within normal limits
Action Threshold: Deficiency may require supplementation.
Symptom Monitoring
- Drowsiness
- Sedation
- Ataxia (unsteadiness)
- Nystagmus (involuntary eye movements)
- Dizziness
- Nausea
- Vomiting
- Cognitive impairment (e.g., memory problems, confusion)
- Mood changes (e.g., irritability, depression)
- Skin rash (especially early in therapy, can indicate severe hypersensitivity reaction)
- Fever
- Sore throat
- Unusual bleeding or bruising
- Yellowing of skin or eyes (jaundice)
- Dark urine
- Abdominal pain
Special Patient Groups
Pregnancy
Primidone is classified as Pregnancy Category D, indicating positive evidence of human fetal risk. It is associated with an increased risk of congenital malformations, particularly cleft lip/palate and cardiac defects. Neonatal withdrawal symptoms and hemorrhagic disease of the newborn can also occur. Use during pregnancy should only be considered if the benefits outweigh the risks, and patients should be counseled on potential fetal harm. Folic acid supplementation (e.g., 4 mg/day) is recommended for women of childbearing potential and during pregnancy to reduce the risk of neural tube defects.
Trimester-Specific Risks:
First Trimester:
Increased risk of major congenital malformations, including oral clefts, cardiac defects, and neural tube defects.
Second Trimester:
Continued risk of fetal exposure and potential for developmental effects.
Third Trimester:
Risk of neonatal withdrawal syndrome (irritability, tremors, hypertonia, feeding difficulties) and hemorrhagic disease of the newborn (due to vitamin K deficiency, requiring prophylactic vitamin K administration to the infant at birth).
Lactation
Primidone and its active metabolite, phenobarbital, are excreted into breast milk. The American Academy of Pediatrics considers phenobarbital to be compatible with breastfeeding, but caution is advised. Monitor the infant for signs of sedation, poor feeding, excessive weight gain, or developmental delay.
Infant Risk:
L3 (Moderately safe; monitor infant for sedation, poor feeding, and developmental milestones).
Pediatric Use
Dosing must be carefully titrated based on age and weight, starting with low doses to minimize side effects. Children may be more susceptible to behavioral side effects (e.g., hyperactivity, irritability). Regular monitoring of drug levels and clinical response is essential.
Geriatric Use
Elderly patients may be more sensitive to the CNS depressant effects of primidone and its metabolites, such as sedation, dizziness, and ataxia, increasing the risk of falls. Lower initial doses and slower titration are recommended. Renal and hepatic function should be carefully assessed and monitored.
Clinical Information
Clinical Pearls
- Primidone is a prodrug that is primarily effective due to its conversion to phenobarbital and PEMA. Therefore, monitoring phenobarbital levels is crucial for therapeutic management.
- Slow titration is essential to minimize common dose-related side effects such as sedation, dizziness, and ataxia, especially during initiation of therapy.
- Patients should be warned about the potential for significant CNS depression, especially when combined with alcohol or other sedatives.
- Due to enzyme induction, primidone can reduce the effectiveness of many other medications, including oral contraceptives, warfarin, and certain antiretrovirals. Comprehensive medication review is necessary.
- Long-term use may lead to folate deficiency and osteomalacia; consider supplementation with folic acid and vitamin D/calcium.
Alternative Therapies
- Carbamazepine
- Phenytoin
- Valproic acid
- Lamotrigine
- Levetiracetam
- Topiramate
- Oxcarbazepine
- Zonisamide
- Gabapentin
- Pregabalin
Cost & Coverage
Average Cost:
$15 - $50 per 30 tablets (125mg)
Generic Available:
Yes
Insurance Coverage:
Tier 1 or Tier 2 (Generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, a patient fact sheet that provides crucial information. Please read this guide carefully and review it again whenever you receive a refill of this medication. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call the poison control center or seek emergency medical attention. Be prepared to provide detailed information about the overdose, including the substance taken, the amount, and the time it occurred.