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Valproate is a mood stabilizer which can treat and prevent the
symptoms of bipolar disorder. It is particularly good at reducing manic
symptoms, and is also a good choice when mood swings happen frequently or
when manic and depressed symptoms occur close together. Like other mood
stabilizers, valproate was originally developed
to treat epilepsy.
Valproate is also approved for the prevention of migraines and
can reduce impulsivity and aggression (such as in Intermittent Explosive
Disorder). Although this medicine
can be very helpful, there are a few problems with valproate
you need to be aware of:
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Rare but serious medical side effects: liver failure, pancreatitis
and thrombocytopenia (a drop in blood platelets causing inability to clot
blood).
·
Pregnancy:
fetal defect have been caused by taking valproate
while pregnant, especially in the first trimester.
·
Blood levels:
the blood level of valproate will need to be
monitored while you take it.
There is
more information on these effects below.
How does it work?
Valproate helps stabilize nerve cell firing.
What types are available and how is it taken?
Valproate should be taken one to three times a day. It is often better tolerated when taken
food. This medicine is dosed by following the blood level, which should be
50-125 in bipolar disorder (see next section). If you miss a dose, ask
yourself if you are closer to the dose you missed or to your next
dose. If you are closer to your next
dose, just wait and take it then, otherwise it’s ok to take the dose
you missed.
There are several kinds of depakote available:
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Name
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Strengths
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Description
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Approximate price
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Divalproex sodium or Valproic acid (Depakote)
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Generic Tablets: 250mg. Liquid 50mg/ml.
Brand: 125, 250, 500mg, Liquid (25mg/ml).
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Original version.
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Generic: 30 of 250mg: $14. 150ml liquid: $18.
Brand: 60 of: 125mg ($37), 250mg ($67), 500mg ($110).
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Valproate ER (Depakote ER)
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Tablets: 250 and 500mg.
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Extended-release valproate;
taken once or twice a day with or without food. Dose should be 10-20%
higher than regular valproate. Do not crush or chew these tablets.
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30 tabs of: 250mg ($38), 500mg ($57).
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Depakote sprinkles
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Sprinkles: 125mg
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Can be sprinkled on food.
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60 of 125mg: $37.
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More about blood levels
Valproate levels need to be checked a few times in the
beginning to determine your dose. The best time to have your level checked
is 12 hours after your last dose or just before your next dose. If you take
it all at night, have it checked in the morning. If you take valproate in the morning, go to the lab before your
morning dose and then take that dose after your blood is drawn.
Once your dose is established,
your level should remain steady and can be checked every 6 months. We will
also monitor for changes in your liver or platelets when checking the
level. Because other medications can interact with valproate,
we may need to check levels again if your start new medicines.
How long will I need to take it for?
After your
symptoms have resolved, valproate continues to
work to prevent future episodes of bipolar disorder. Going without it can
lead to more bipolar episodes, and after too many episodes your brain can
get in a habit (called “kindling”) of mood swings that is
harder to treat. Therefore, it is
best to take valproate regularly as long as side
effects are not a problem. If it is ever stopped, it should be done slowly
to prevent a sudden return of symptoms.
What side effects can I expect?
Common side effects (many of these are worse at
higher doses):
Nausea (10-30%), vomiting (5-20%),
indigestion (5%), diarrhea (5%), stomach pain (5-15%), headache (10%),
fatigue (5-20%), tremor (10-20%), sensory changes (10%), dizziness (5%),
double vision (5%), blurred vision (5%), hair loss (5%), weight gain
(5-10%), poor concentration or changes in thinking (5%), menstrual
abnormalities.
Valproate may increase
bleeding and should not be taken with aspirin.
Rare but serious side effects:
·
Liver failure:
this is a rare side effect of valproate. If it
occurs, it is most likely during the first 6 months. It is also it is more common in children
and those with neurologic problems such as mental
retardation and severe epilepsy. To
reduce this risk, we will monitor your liver enzymes while taking valproate.
Rarely, valproate will impact only the
liver’s ability to detoxify ammonia, causing symptoms of lethargy and
confusion.
·
Pancreatitis: rare cases of severe pancreatitis
have been reported (rate approximately 1 in 1,000).
·
Thrombocytopenia (drops in platelet count): very rarely, valproate can
cause seriously impair the bloods ability to clot.
·
Polycystic Ovarian Disease: although valproate has been
rarely associated with this condition in women, it is not yet clear that it
causes it. The symptoms include
irregular or no menstrual periods, facial and other hair growth, acne,
changes in body shape and obesity.
Warning: the following may be
early signs that you are having a serious side effect to valproate; notify me or go to your emergency room if
these occur:
Flu-like
feelings, extreme fatigue, confusion, loss of consciousness, yellowing of
the skin or eyes, swelling of the face, vomiting, no appetite, belly pain,
increased or unusual bleeding.
An allergic
reaction is possible with any medication.
Symptoms include the following; stop the medication and call me if
these occur:
Pounding heartbeat; swelling of the face, throat, tongue, lips, eyes,
hands, feet, ankles, or lower legs; hoarseness; difficulty swallowing or
breathing; hives; rash.
Overdose
The
following are signs that your valproate level is
too high:
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Extreme fatigue,
slowing or failure of the heart, changes in consciousness or coma.
A high
level can be dangerous. If you think your level is too high, do the
following:
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Stop valproate, call your doctor or go to the emergency room.
Precautions
Since valproate may cause
drowsiness or discoordination, Make sure you
know how you react to it before you drive, use machines, or do anything
else that could be dangerous if you are not alert, well-coordinated, or
able to see well.
Pregnancy: Valproate
is a category-D drug and should not be taken during pregnancy. Valproate is
known to cause problems in pregnancy, such as neurotube
defects (a failure of the spinal chord to close), especially if taken during
the first trimester. Women of
childbearing age should take folic acid (0.5-1mg per day) to reduce the
risk of these defects in the event of unexpected pregnancy while on depakote. Valproate does not
affect pregnancies after it is stopped and it is not known to affect the
male reproductive system.
Breast-feeding:
Valproate comes out in breast milk.
Talk to your doctor if you plan to breast-feed while taking it.
Children: Valproate
has not been adequately studied in children under age 10.
Older adults: Valproate
may produce more side effects, especially fatigue, in people after age 65,
so lower dosages may be needed.
Medical problems that can worsen with valproate:
- HIV:
there is a small risk that valproate can
increase the replication of the virus.
- Thyroid
disease: there are rare reports
of valproate altering thyroid levels.
Drug Interactions
Valproate can lower
levels of:
Oxcarbazepine (Trileptal, by 18%), amitriptyline
(Elavil), nortriptyline, calcium-channel blockers
(verapamil, femlodipine;
by 30%).
Valproate can raise
levels of:
Diazepam (Valium), lamotrigine (also increase risk of lamotrigine-induced
rashes), ethosuximide, phenobarbital,
phenytoin, tolbutamide,
warfarin (Coumadin), zidovudine.
Drugs that
can lower valproate levels:
Phenytoin, carbamazepine (by 20%), phenobarbital, meropenem, rifampin
Drugs that
can raise valproate levels:
Aspirin (valproate
also can increase the risk of bleeding with aspirin), felbamate
(by 30-50%)
Drugs that
my increase the risk of liver problems with valproate:
High-dose or long-term acetaminophen (Tylenol), disulfiram
(Antabuse), naltrexone (Trexan),
certain seizure medications, plicamycin
(Mithracin).
Other drugs that
may interact with valproate:
Acetaminophen (Tylenol: long term or high-dose use may increase risk of
liver problems), amiodarone (Cordarone), anabolic
steroids (nandrolone, Anabolin,
oxandrolone, Anavar, oxymetholone, Anadrol, stanozolol, Winstrol),
androgens (male hormones), anticoagulants (aspirin, heparin, coumadin), carmustine
(BiCNU), dantrolene (Dantrium), daunorubicin (Cerubidine) or,
estrogens (female hormones), etretinate
(Tegison), gold salts (medicine for arthritis), mercaptopurine
(Purinethol), methotrexate (Mexate),
methyldopa (Aldomet), phenothiazines
(acetophenazine, Tindal, chlorpromazine, Thorazine, fluphenazine, Prolixin, mesoridazine Serentil, perphenazine, Trilafon, prochlorperazine, Compazine, promazine, Sparine, promethazine, Phenergan, thioridazine, Mellaril, trifluoperazine, Stelazine, triflupromazine, Vesprin, trimeprazine), Temaril, carbenicillin by
injection (Geopen), dipyridamole
(Persantine), pentoxifylline (Trental), sulfinpyrazone (Anturane), ticarcillin (Ticar), mefloquine.
Alcohol and Street Drugs
Although these do not interact directly with valproate,
they may worsen the side effects or worsen the symptoms of bipolar
disorder.
Storage
- Keep
out of the reach of children.
- Store
away from heat and direct light.
- Do
not store in the bathroom, near the kitchen sink, or in other damp
places. Heat or moisture may cause the medicine to break down.
- Do
not keep outdated medicine or medicine no longer needed. Be sure that
any discarded medicine is out of the reach of children.
Updated 9/18/4 by Chris Aiken,
M.D.
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