Valproic Acid (Oral)

Valproic acid, known by the brand name Depakene or Depakote, is a commonly used, wide spectrum anti-seizure medicine which can be taken in conjunction with other medications to give patients effective relief from seizures and related side effects.

Overview

Valproic acid is a common medication with a broad spectrum of uses. It is primarily used as an anti-convulsant/anti-seizure medication, but can also be used for a variety of other treatments. When it comes to treating seizures of various types, Valproic acid is a common choice to help control the symptoms. It is effective in manipulating the chemicals in the body that are responsible for causing seizures. Depending on the situation, Valproic acid may be used in conjunction with other medications to tailor the effect to the patient.

Valproic acid is metabolized by the liver and is an 8 carbon, 2-chain fatty acid. It works in a similar fashion to conventional anticonvulsants.

Valproic acid is rapidly absorbed by the body when taken orally and is used as a broad spectrum anti-seizure drug that is most effective 1 to 4 hours after ingestion. Close monitoring of the patient is crucial in order for the treatment to be tailored properly to the individual, because the effects of the medication can vary widely from person to person.

It is important to note that Valproic acid has a very narrow therapeutic range, so dosing needs to be closely monitored in order for healthcare professionals to determine the optimal doses so the patient can get the greatest benefit. Side effects need to be closely monitored as well, in addition to keeping watch for an overdose. In order to determine if the patient is ingesting excessive amounts of the medication, a toxicology panel should regularly be performed.

In addition to treating a variety of seizures, Valproic acid is also used in the treatment of the manic phase of bipolar disorder. It can also be used to prevent migraine headaches. Valproic acid is normally taken orally in a variety of forms that range from capsules to a syrup form. When used to treat bipolar disorder, Valproic acid works as a mood stabilizer. For some individuals, it will be a more effective treatment than others. If the medication is found to help with the issue, then it will normally be prescribed in conjunction with an antidepressant. The main purpose of this practice is to help prevent the occurrence of mania. When the correct course of treatment is discovered, the medication will work to calm the brain.

Primarily, Valproic acid is used for the treatment of a wide range of issues which trigger seizures. Valproic acid is a broad spectrum anti-seizure medicine which is easily tailored to the needs of individual patients by using it in conjunction with other medications. In order to get an effective course of treatment in place, the medication dosages and effects on the patient need to be regularly monitored until the right combination is found. Monitoring not only consists of regular physical examinations, but also regular toxicology screening that allows healthcare providers and physicians to determine if the amount of the medication is near or in a toxic range, and can also show if the medication is in the therapeutic range.

Conditions treated

Type of medicine

  • Anti-seizure
  • Mood stabilizer

Side effects

In addition to the intended effect of Valproic acid, there are a variety of possible side effects associated with Valproic acid, ranging from mild to extreme. In terms of milder symptoms, some of the more common occurrences include:

  • Tarry black stool

While this can be alarming, it is not uncommon for users to experience this symptom. You are, however, advised to tell your doctor right away so they can make any changes to your medication regimen if necessary to prevent this side effect.

  • Bleeding gums

This is also a common and mild side effect. In most cases, the individual will adjust over the course of time, but if the bleeding becomes excessive, the health care provider or prescriber may choose to change the course of treatment to provide relief.

  • Swelling

Swelling is another common side effect of Valproic acid. If the swelling becomes excessive or seems to be unusually prevalent, you should immediately consult your doctor.

  • Blood in stool or urine

This common symptom should be immediately addressed by your doctor. They can either alter your treatment or change your treatment altogether. This may also be considered a more severe side effect in some cases.

  • Confusion

Many patients taking Valproic acid experience confusion initially as their body begins to adjust to the medication. Alert your medical care provider and monitor the situation. If the confusion becomes severe or persistent, you may need to have your course of treatment altered.

  • A persistent cough or hoarse throat

This is a common symptom that, in many cases, will go away over the course of time. If a cough becomes severe or causes you to have trouble breathing, it may be a sign of a more serious side effect. If this is the case, your healthcare professional should be alerted right away.

  • Crying

There can be significant mood swings that can cause crying when a person begins a treatment involving Valproic acid. Always keep your medical care provider informed about your moods so they can adjust the dose to be more beneficial.

In some cases, Valproic acid has been known to create the onset of dementia. This is yet another issue that should be monitored by a healthcare professional.

  • Vomiting

It has been observed that, in many cases, Valproic acid can cause vomiting with associated nausea. Keep your doctor informed of your condition.

  • Weight gain or loss

If you begin to experience either an unexpected weight gain or loss, it may be a side effect of using Valproic acid. Your doctor will want to keep track of your weight and other statistics on a regular basis to help them determine if you are getting the correct dose and if the medication is having the desired effect on the patient.

  • Weakness or tiredness

It is common for people taking Valproic acid to experience weakness or tiredness, especially during the first few weeks of their therapy. If the symptoms persist or become severe, your doctor may want to change your dose or change medications.

  • Bruising or bleeding

This side effect may indicate a more serious problem if it persists over the entire course of treatment. If the problem persists, the dose may require altering by your doctor. If the bleeding is severe, your doctor may choose to stop Valproic acid therapy.

Insomnia is a common side effect that may be aided by the use of a prescription. Ask your doctor what your options are if you experience insomnia over a prolonged period while taking Valproic acid.

  • Chest tightness

Some patients may experience chest tightness from time to time when they are taking this medication. If you experience severe chest tightness, however, you should immediately proceed to your emergency room to be assessed for a potentially life-threatening situation, especially if the chest tightness progresses to chest pain.

  • Sweating

Sweating, especially at night, is a common side effect. If you experience unusual sweating, or cold sweats in conjunction with chest tightness or a pain in the back or the arms, you should go to the emergency room immediately, because you could be experiencing a life-threatening emergency. If minor sweating persists over the course of treatment, you should inform your doctor, because your dose may need to be changed to eliminate this side effect.

Other common side effects of Valproic acid include trembling of the hands and feet, tingling sensations in the hands and feet, drowsiness, runny nose, mood changes that are rapid or unusual, rapid weight gain, emotional instability, small red spots on the skin's surface, problems with urination including pain, nervousness, nausea, depression, pain in the back or in the sides, discomfort, euphoria, dysphoria, trouble breathing and diarrhea.

Dosage

The dosage for an adult experiencing complex partial seizures:

The initial dose is 10 to 15 mg/kg orally per day. It should then increase by 5 to 10 mg/kg per week according to the individual case and overall clinical response by the patient.

The regular maintenance dose is 10 to 60 mg/kg per day. The maximum recommended dose of Valproic acid is 60 mg/kg per day.

Complex or simple absence seizures should be treated with the following dosage:

The initial dose should be 15 mg/kg taken orally. It should then be increased to 5 to 10 mg/kg weekly if deemed necessary and according to the patient's clinical response.

The regular maintenance dose is 10 to 60 mg/kg daily. The maximum recommended dose should not exceed 60 mg/kg per day.

Doses should be divided if the total daily dose exceeds 250 mg. A reduction of approximately 25% every two weeks can occur in the event of the conversion to monotherapy. It has been observed in most patients that the optimal dose to achieve the desired clinical response is under 60 mg/kg per day. Plasma levels are observed to determine whether or not the drug levels have achieved the therapeutic range during treatment. Safety indications for levels above 60 mg/kg per day are not currently available.

When a dose of Valproic acid is missed, it should immediately be taken, unless the next dose period is close. Do not double the dose if you miss your previous dose. It is important to not abruptly stop taking Valproic acid, due to the risk to the patient's life as a result of the precipitating status epilepticus with attendant hypoxia.

Interactions

  • Drug interactions

To date, it has been found that there are 766 drugs that interact with Valproic acid. There are a total of 22 major interactions, 689 moderate drug interactions, and 55 minor drug interactions. Always discuss all of the medications you take with your doctor before starting Valproic acid.

Some of the most common drugs that interact with Valproic acid include: Seroquel, Ativan, Cymbalta, Nexium, Lyrica, Zyprexa, Klonopin, Lamictal, Topamax, Valium, Zoloft, and Zyprexa.

  • Alcohol interaction

When taken with alcohol, Valproic acid can have magnified side effects on the nervous system. Some of the symptoms may include drowsiness, dizziness, and trouble concentrating. In addition, some individuals may suffer impaired judgment or thinking. It is advised to minimize alcohol consumption when taking Valproic acid in order to reduce your chances of severe side effects.

Do not attempt to operate a vehicle or other dangerous equipment when taking Valproic acid with alcohol. Alcohol consumption can cause unstable glucose levels and may trigger a serious or life-threatening medical event. Always ask your pharmacist or doctor about any questions or concerns you may have regarding alcohol and Valproic acid.

  • Mental health interaction

This particular medication has been known to increase an individual's depression in some instances. It can create a pattern of negative behaviors and suicidal thoughts. If any of these symptoms are suspected, they should be closely monitored for any emergency instances or worsening of the person's depression symptoms. Alert your doctor if you experience any unusual behaviors or sudden, unexpected changes in mood. Any caregiver or family member that notices these behaviors and symptoms should alert the attending physician or medical caregiver immediately.

Patients who suffer from hepatic dysfunction or hepatic disease may experience fatal hepatotoxicity. This risk is higher in children under the age of two years, especially if they are taking several anticonvulsants. This also applies to children with congenital metabolic disorders or severe seizure disorder. The risks decline after the patient becomes older.

Extreme caution should be used to treat patients with risk factors that can trigger valproate-related hepatotoxicity. Normally, the onset is observed during the first six months of the therapy and can exhibit itself with relatively benign symptoms. Some of the onset symptoms can include facial edema, lethargy, anorexia, vomiting, nausea, weakness, malaise, and loss of seizure control. It is important to note that there can be a fluctuation in serum levels that will level off over the course of treatment. A doctor should carefully monitor liver panels and concentrations to help prevent any adverse occurrences while undergoing treatment with Valproic acid.

  • Urea cycle disorders

Valproic acid should be avoided by individuals who have urea cycle disorder, or UCD, defined as hyperammonemic encephalopathy. This condition can sometimes be fatal in individuals who take Valproic acid. If the patient has a history of encephalopathy as a result of protein load, coma, pregnancy-related encephalopathy, mental retardation, or elevated levels of glutamine, plasma, or ammonia, Valproic acid should be avoided to prevent life-threatening complications.

This is also relevant for individuals who have a family history of unexplained infant deaths. In the event of the patient developing hyperammonemic encephalopathy while undergoing Valproic acid treatment, the medication should be immediately discontinued and an alternative course of treatment should be sought.

  • Suicidal tendency

There is an increased risk of suicidal thoughts and behaviors associated with the use of antiepileptic drugs or AEDs. Patients undergoing treatment with these types of drugs had experienced twice the risk of suicidal thoughts and behaviors in comparison to individuals not taking the medication who also experienced suicidal thoughts and behaviors previously. These figures include individuals in the age range of 5 years to 100 years. Before beginning a Valproic acid treatment, the risk of potential suicidal thoughts and behaviors should be assessed by a qualified mental health professional, especially if there has been any incidence of that behavior previously.

  • HIV/CMV

Studies have indicated that there may be a link to Valproic acid and an increase in the replication of CMV and HIV viruses when conditions were replicated in a lab. There is no concrete evidence to suggest that this is the case in patients who are undergoing Valproic acid treatment, but it is advisable for your doctor to monitor the progress of the virus for any unexpected changes or progression. Regular monitoring of the viral load is highly advised for patients with CMV or HIV.

Warnings

There are a number of issues to consider when taking Valproic acid. It can cause severe and even life-threatening liver damage to patients taking the medication during the first six months of their treatment program. This threat is significantly elevated for children under the age of two years, especially if their dose exceeds the recommended maximum pediatric amount. This medication can also alter the body's ability to convert ingested food into energy for the body to use for daily function. Before beginning a pediatric schedule, you should talk to your doctor about the risks associated with this medication.

It is important to discuss any inherited conditions related to the function of your liver, muscles, nerves, or the brain. In most cases, your doctor will avoid prescribing Valproic acid. If you begin to experience more frequent seizures or any of the following, vomiting, lack of appetite, dark urine, yellowing of the skin or eyes, swelling of the face, pain on the right side of your stomach, excessive tiredness, or weakness, you should alert your doctor immediately.

Valproic acid has also been known to cause a variety of serious birth defects. Most of these birth defects relate to the spinal cord and brain and result in significant decreased intelligence. Tell your doctor if you are planning on becoming pregnant, or if you are already pregnant. It is important for pregnant women to not take Valproic acid for migraines. Pregnant women should only take Valproic acid for the treatment of manic-depressive syndrome, bipolar disorder, or seizures.

There is also a significant risk to the pancreas when taking Valproic acid. The damage can occur at any time during the span of treatment with this medication. Some of the warning signs associated with pancreatic damage can include stomach pains that are ongoing and begin to spread to the back, loss of appetite, and vomiting with nausea.

Do not give Valproic acid to your child before seeking the advice of a physician. Read the patient information sheet that the doctor will provide when prescribing Valproic acid.

Storage

If stored at the appropriate temperature under regulated conditions, Valproic acid is stable for up to two years. When storing Valproic acid, make sure that it is stored in a tightly closed, preferably child resistant, container. It should also be stored away from heat and light. Prevent moisture from affecting the medication by avoiding storage in the bathroom.

Do not store your medication where it can be accessed by other individuals and children. If you should need to dispose of your medication, do not flush it down the toilet. If there is a take-back program in your area, this would be the preferred method of disposal.

Summary

Valproic acid is a versatile and widely used medication which is used to treat seizures, as well as bipolar disorder. The medication allows the brain to relax to prevent these conditions. It is commonly sold by the brand name Depakene or Depakote. It can even be used in some cases to treat migraine headaches.

It is important to have close medical supervision when taking Valproic acid because it has a very narrow therapeutic window. In order to adjust the dosage to most benefit the individual, the patient must undergo regular toxicology screening as well as physical evaluations. This medication is normally used in conjunction with an anti-depressant in order to prevent mania from occurring. It may also be prescribed in conjunction with other medications in order to achieve a marked improvement in the disorder. Although there are many potential side effects, the majority are mild; however, they should be monitored closely to avoid overdose or improper dosing.

Use caution when taking Valproic acid because it may cause a variety of side effects which can prove to be life-threatening within the first six months of therapy. If you are pregnant you should inform your doctor so they can tailor a treatment program to minimize any risk to the fetus. Valproic acid should be taken as directed, to avoid a possible overdose or increased likelihood of side effects. Always inform your medical care professional of any changes in other medications as well as any major dietary changes.

If an individual has a history of liver or pancreatic disease, or suicidal thoughts and behaviors, great care should be exercised when undergoing a course of treatment using Valproic acid. Always store medication away from heat, light, moisture, and children. If you miss a dose take it as soon as possible unless it is time for your next dose. Do not double your dose if you missed a dose previously. Always consult your doctor with any changes in your diet or medication.

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Last Reviewed:
December 23, 2017
Last Updated:
April 05, 2018
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