Valproate Sodium

Valproate Sodium is a medication used to treat certain types of seizure associated with epilepsy.

Overview

Valproate sodium is a useful medicine for the prevention of various partial seizures, generalized seizures, and absence seizures. It is typically administered intravenously although it can also be taken orally, with long and short-acting variations of the drug available.

The compound is manufactured from valproic acid, which is a branched, short-chain fatty acid which in itself is created from valeric acid. How the medicine works is currently unclear, although some proposed mechanisms include the theory that it can affect levels of GABA within the brain, as well as blocking certain voltage-gated sodium channels. Another hypothesis is that it inhibits histone deacetylases.

Valproate sodium was first created in 1881, although it would be almost a decade before it was used medically in 1962. It is currently included on the List of Essential Medicines issued by the World Health Organization (WHO), where it is regarded as a safe and effective medicine which is needed within a health system or service.

It is marketed under brand names including Epilim and Depakote among others, and it is also available as a generic medication, with wholesale costs sitting between 0.14 and 0.52 US Dollars per day. In the US, it generally retails at a cost of $0.90 per day.

As of 2017, the drug is approved in almost all developed countries across the world for preventing seizures, with a number of trials having tentatively taken place to test its efficacy in a number of different applications including mental health issues, chronic pain, and certain cancers.

Conditions treated

  • Epilepsy
  • Bipolar disorder
  • Schizophrenia
  • Dopamine dysregulation syndrome
  • Migraines
  • HIV/AIDS
  • Cancer

Type of medicine

  • Intravenous solution
  • Tablet

Side effects

Along with its required effects, Valproate Sodium may cause unwanted effects in certain individuals. The most commonly reported side effects include abdominal pain, drowsiness, nausea, vomiting, tremors, diarrhea, dizziness, asthenia, abnormal thinking, weight gain or weight loss, fever, depression, nystagmus, peripheral edema, bronchitis, tinnitus, pharyngitis, and constipation – however, there are further side effects, many of which are incredibly rare and only experienced by a small minority of users.

Other side effects include:

  • Black stools which are tar-like in consistency
  • Bleeding or sore gums
  • Bloating and swelling in the following areas: face, hands, arms, legs and feet
  • Blood present in stools or urine
  • Confusion
  • Crying
  • Coughing and hoarseness in the throat
  • Dementia
  • Delusional thinking
  • Depersonalization
  • Difficulty breathing
  • Dysphoria
  • Euphoric feelings
  • Chills and fevers
  • General malaise/feeling of discomfort
  • Pain in joints
  • Appetite loss
  • Pain in lower back/joints
  • Muscular aches or pains
  • Nervousness
  • Pain when urinating
  • Difficulty when urinating
  • Paranoia
  • Red spots on the skin
  • Emotional overreaction
  • Rapidly changing moods
  • Running nose
  • Twitchiness in legs, hands, arms and feet
  • Shivers
  • Sleepiness or excess drowsiness

Incredibly rare (less than 1 in 1000) side effects include:

  • Strange or abnormal dreams
  • An increase or decrease in body movement
  • Extreme anxiety
  • Nosebleeds
  • Cloudy urine
  • Blurred vision
  • A burning, crawling, itching or numb sensation, often described as “pins and needles”
  • Personality changes
  • An increase or decrease in walking pace
  • Balance problems
  • Changes in the rhythms or patterns of the heartbeat
  • Chest pains
  • Chills or cold feeling
  • Unsteadiness or clumsiness
  • Cold sweats
  • Dark urine
  • Degenerative joint disease
  • Discouragement
  • Faintness or light-headedness
  • A dry mouth
  • Increased muscle tone
  • Fast or irregular heartbeats at random intervals
  • Fear
  • Feeling warm or excessively hot
  • A feeling of sadness or emptiness
  • Flushing and redness of the skin
  • An increased urge to urinate
  • Indigestion and heartburn
  • Feeling irritable
  • Loss of appetite
  • Lack of coordination
  • Large blue or purple bruises or patches on the skin
  • Cramp in the legs
  • Smacking or puckering of lips
  • Loss of control of bladder
  • Loss of pleasure or interest in sex
  • Decreased energy or strength
  • Inflamed skin lesions
  • Muscular stiffness, tension or tightness
  • Menstrual bleeding occurring earlier or lasting longer than expected
  • Abdominal pain
  • Passing urine more frequently
  • Pounding noise in the ears
  • Puffy cheeks
  • Rapid tongue movements
  • Restlessness
  • Seeing or hearing things that aren’t there (hallucinations)
  • An unsteady walk
  • Slurring of speech
  • Excess sweating
  • Swelling of the joints
  • Fatigue
  • Difficulty concentrating
  • Difficulty speaking
  • Uncontrollable chewing movements
  • Vomiting of blood or material which resembles coffee grounds
  • Yellowing of the eyes or skin

Dosage

The level of Valproate Sodium varies dependent on the reason for its use and the age of the person taking it. The most common doses per treatment are as follows:

Epilepsy

Complex partial seizures in adults and children aged over 10

Typically, an adult will be prescribed a dose of either 10 or 15mg daily via tablet, or 10 to 15kg/mmol intravenously. This can be increased by a rate of 5-10mg/kg/mmol per week if required, dependent on the clinical response of the patient. As a maintenance dose, most patients will take between 10 to 60mg/kg/mmol daily. No more than 60mg/kg/mmol is advised by qualified health professionals.

Simple and complex absence seizures in adults and children aged over 10

Similarly to those suffering complex partial seizures, those experiencing absence seizures should begin by taking 15mg/kg/mmol per day, increasing by increments of 5 or 10 on a weekly basis until a satisfactory maintenance dose is found. Users should not exceed 60mg/kg/mmol in a single day.

Other Valproate Sodium dosage information for epilepsy patients

  • In rare instances, doses higher than 60mg/kg/mmol may be required. In these circumstances, the medication should be administered in divided doses throughout the day.
  • If a patient is switching to monotherapy, a reduction in anti-epilepsy drug (AED) dosage should commence by approximately 25 percent every fortnight. This reduction may begin at the start of monotherapy or can be delayed by up to two weeks if there are any concerns that seizures may occur in the event of a reduction. Duration and speed of AED withdrawal can be incredibly variable, and a qualified health professional should always be consulted before considering this.
  • The optimal response to Valproate Sodium is typically achieved with doses not exceeding 60mg/kg/mmol per day. Should this not be the case, blood plasma levels need to be taken in order to find out whether they are in the normal range. This is important, as there is no recommended safe use of this medicine in doses of around 60mg/kg per day.
  • In the event of missing a dose, this medication should be taken as soon as is feasible, unless it is nearly time for the next dose.
  • In the event of having skipped a dose, the patient should NOT double the following dose.
  • Vaproate Sodium use should not be stopped abruptly, as this can create a strong likelihood of precipitating status epilepticus along with attendant hypoxia which can threaten the life of the patient.

Notes on intravenous use

  • The intravenous formulation should be given as a one-hour infusion at a rate of no more than 20mg per minute – in the same frequency as oral Valproate Sodium. However, monitoring of plasma concentration and adjustments in dosage may be required.
  • Studies regarding the use of IV formulation of this medication for longer than a fortnight have not yet commenced.
  • Patients using the IV formulation should be switched to tablets as soon as is safe and clinically feasible.

Notes on dosage adjustments

When switching from an IV formulation to tablets for geriatric patients, the starting dose should be reduced and increased at slower intervals when compared to a healthy younger adult.

Dosage reductions should be considered when patients have decreased fluid or food intake, and in patients with excessive somnolence.

The likelihood of thrombocytopenia is increased significantly when total Valproate Sodium concentrations of 100mcg/mL in females or 135mcg/mL in males is administered.

Patients who have been stabilized using rufinamide prior to being prescribed valproate sodium should begin the medication with a lower dose before it is slowly increased to a dose which is clinically effective.

Bipolar disorder and mania dosage of valproate sodium

The standard dose of valproate sodium for those experiencing bipolar disorder is usually 750mg per day, taken orally, although this is often increased to anywhere between 1000mg and 2000mg per day.

Valproate sodium is available in controlled release form, which means that patients only need to take it once a day. Controlled release capsules should be swallowed whole with a glass of water, as opposed to being crushed or chewed.

The medication is also available in granule form, which can be sprinkled in cold food, taken within a drink, or poured directly into the mouth. If taken with a drink (a glass of water for example), another glass of water poured directly into the same glass should be consumed directly after. This is because some of the granules may stick to the side of the glass, resulting in less than the prescribed dose being administered.

In order for valproate sodium to be most effective in treating mental health issues, it needs to be taken on a daily basis. It typically only takes a few days for the medicine to start working, although some patients report having to take it for several months before feeling the true benefits of the drug. Most patients will remain on valproate sodium for at least six months in order to control symptoms of mania, although this should be discussed with a doctor in order for the drug to work best within the personal circumstances of the patient.

Interactions with Valproate Sodium

There are in excess of 750 drugs which are known to interact with Valproate Sodium. Before taking the medication, you should consult with a doctor to ensure any medicines you are currently taking do not interact with Valproate Sodium in a negative manner.

Major interactions

Using the following drugs with Valproate Sodium can cause one or more of the following side effects: dizziness, confusion, drowsiness, difficulty concentrating, liver problems, itching, skin rash, dark colored urine, abdominal pain, vomiting, respiratory distress, coma and even death:

  • Acetaminophen
  • Ammonul
  • Arava
  • Aspirin
  • Aubagio
  • Balacet
  • Buphenyl
  • Belbuca
  • Buprenorphine
  • Bunavail
  • Darvocet
  • Glycerol Phenylbutyrate
  • Juxtapid
  • Meropenem
  • Merrem
  • Propoxyphene
  • Subutex
  • Suboxone
  • Targetrin
  • Teriflunomide
  • Vabomere
  • Vorinostat
  • Xyrem
  • Wygesic
  • Zolinza

Moderate/minor interactions with Valproate Sodium

When taken in conjunction with Valproate Sodium, the following medications can cause mild discomfort or side effects including (but not limited to) impairment in judgment, slight differences in motor coordination and slightly decreased concentration levels. Although these may not seem like major disruptions, you should always consult your doctor before use and avoid operating any heavy machinery when using one or more of these medications with Valproate Sodium:

  • Over the counter cough relief
  • Over the counter allergy relief
  • Herbal sleep aids
  • Pseudoephedrine
  • Acetaminophen
  • Allopurinol
  • Codeine/Dihydrocodeine
  • Alprazolam
  • Anaflex
  • Alka-Seltzer
  • Oxycodone
  • Ibuprofen
  • Myolin
  • Norco
  • Oestrogel

Food and drink interactions with Valproate Sodium

Because alcohol affects the nervous system, it has the propensity to increase certain side effects of Valproate Sodium such as drowsiness, dizziness, and difficulty concentrating. Some patients might also experience impairment of judgment or clouded thinking. It is therefore advised that the use of alcohol should be severely restricted or even avoided during treatment with Valproate Sodium. If you have any concerns or questions regarding the simultaneous use of alcohol and Valproate Sodium, you should speak to your pharmacist or doctor.

Condition interactions with Valproate Sodium

Depression

It has been reported that certain antiepileptic medications like Valproate Sodium have a propensity to increase suicidal thoughts or depressive behaviors in patients. When starting treatment with the drug, patients with a history of depression should be monitored for the re-emergence or worsening of mood. Carers and family members should be on the lookout for symptoms of depression, and any drastic changes should be reported to a doctor or healthcare provider.

Liver disease

Patients with decreased hepatic function are at risk of serious hepatotoxicity when using Valproate Sodium. The risk is typically greater in young children (less than two years of age), with the onset likely to occur within the first 6 months of treatment. In these instances, symptoms which precede hepatotoxicity include general weakness, lethargy, vomiting and facial edema.

Warnings

Pregnancy

Pregnant women are advised that studies concerning Valproate Sodium on animals have revealed evidence of neural tube defects, skeletal changes, urogenital defects, cardiac problems, intrauterine growth retardation and brain changes in fetuses. Babies born to epileptic mothers who have used this medication during pregnancy are approximately four times more at risk of developing these conditions in the womb in comparison to mothers who used alternative anti-seizure monotherapies.

Other research has concluded that children who have been exposed to Valproate Sodium in the womb typically have lower IQ scores in comparison to those who have either been exposed to another anti-epileptic drug or no anti-epileptic drug whatsoever.

Hepatic failure in mothers and infants has also been reported when Valproate Sodium has been used during pregnancy.

Breastfeeding

Because there are low levels of valproic acid in breastmilk, no conclusive adverse to Valproate Sodium during breastfeeding have been reported. In theory, breastfed infants could be at risk to hepatotoxicity, however, so newborn babies should be monitored for signs of liver damage, including jaundice and unusual bruising.

Breastfeeding during Valproate Sodium use does not appear to have any adverse effect on infant development, growth, IQ rate or verbal ability.

Sodium Valproate storage

As a liquid prepared for IV use, Valproate Sodium should be stored at room temperature - between 20C and 25C (68F to 77F) - and out of direct sunlight. A medicinal storage cupboard should suffice, without the need to keep the medication in a refrigerator, except in particularly hot southern hemisphere climates.

The liquid is typically supplied in an amber-colored glass bottle with a polypropylene childproof cap, or tamper-evident polypropylene closure in 200mg or 300mg packs, ready for dilution.

It can also be stored in tablet or granule form in a cupboard at room temperature and out of direct sunlight.

Summary of Sodium Valproate

Sodium Valproate is an effective treatment for preventing various types of seizure, and its widespread use throughout the entire world since 1962 is testament to its efficacy. It is also useful in the treatment of various mental health disorders such as schizophrenia and bipolar (mania).

It is typically used in IV form to initially treat those experiencing simple and complex absence seizures, whereby the patient is gradually transferred onto the drug in tablet form.

For mood disorders, it is typically administered in higher, slow-release doses which need only be taken once a day.

In some countries, it is reported to be of minor benefit to those suffering from certain cancers as well as HIV/AIDS-related illnesses, although peer-reviewed studies have either proved inconclusive or have yet to have been published.

Before commencing treatment with Sodium Valproate, you should always consult a qualified doctor or health professional in order to ascertain whether it is the right medicine for you. Because it has certain major interactions, it can be potentially fatal to mix with other medicines; therefore, care and attention are advised before taking it. Pregnant women, in particular, should be aware of the potential issues caused when taking the medication and are advised to switch to another medicine for the duration of their pregnancy.

Resources
Last Reviewed:
December 23, 2017
Last Updated:
December 22, 2017
Content Source: