divalproex sodium
PrintTrade Name(s): Depakote; Divalproex Sodium | |
Group 2: Non-Antineoplastic Hazardous | AHFS Class: Anticonvulsants, Miscellaneous |
Activity | Gloves | Gown | Eye/Face | Mask | Notes/Instructions |
Dispensing prepackaged formulations |
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Counting/Repackaging tablets and capsules | Recommended if pregnant, breast feeding, or trying to conceive | If risk of dust inhalation |
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Repackaging oral liquids | If risk of spill or splash | If risk of inhalation |
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Formulation | Gloves | Gown | Eye/Face | Mask | Notes/Instructions |
Tablet or capsule - from unit dose package | or Recommended if pregnant, breast feeding, or trying to conceive. |
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Liquid - oral or feeding tube | or Recommended if pregnant, breast feeding, or trying to conceive. | Recommended if pregnant, breast feeding, or trying to conceive. | If potential for splash, vomit or spit up. |
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Reference: NIOSH 2016, USP <800>
Type of Instance | Gloves | Gown | Mask | Eye/Face | Notes/Instructions |
Receiving undamaged HD shipping container |
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Receiving damaged HD shipping container | If container must be opened | If container must be opened | If container must be opened |
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Spill Cleanup | Large volume | Large volume |
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Reference: USP <800>
Hazardous Pharmaceutical | Trace Chemo | Biohazardous and Sharps |
1. Non-returnable hazardous, chemo and EPA regulated drugs. (Patient specific prescriptions, partially used blister packs, containers with more than 3% medication remaining) 2. Empty bottles or packaging of P-Listed drugs. (Warfarin, nicotine, epinephrine, nitroglycerin, physostigmine) 3. PPE with visible contamination from hazardous drug. | 1. Waste contaminated through contact with chemotherapeutic agents. (Empty vials, IV bags, syringes and tubing) 2. PPE worn while handling hazardous drugs with NO visible contamination. (Gowns, gloves and masks) 3. Used CSTD devices. | 1. All sharps capable of cutting or piercing the skin. (Needles/syringes, broken ampules, lancets) 2. Items contaminated with blood or other potentially infectious materials. (Tubing, bags or dressings containing blood, contaminated waste from isolation patients) |
Dosage Form | Ship to Institution or Pharmacy | Ship to Locations Outside of ODOC |
Tablets and Capsules |
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Liquid, Topical, and Transdermal |
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PPE | Standards |
Shoe Covers |
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Gowns |
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Gloves |
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Face Shields |
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Goggles |
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N95 Masks |
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Removal and Disposal |
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Reference: USP <800>
- Harmful if swallowed.
- Causes skin irritation.
- Causes serious eye irritation.
- May damage fertility or the unborn child.
Reference: SDS - Cayman Chemical
Only met the NIOSH criteria as a developmental and/or reproductive hazard; Black box warning on embryo-fetal death or severe birth defects; Recommend effective contraception for females during therapy and for seven months after treatment; Present in semen; No sperm donation during and three months post-treatment
The exact mechanisms by which valproate exerts it's effects on epilepsy, migraine headaches, and bipolar disorder are unknown however several pathways exist which may contribute to the drug's action.
Valproate is known to inhibit succinic semialdehyde dehydrogenase.12 This inhibition results in an increase in succinic semialdehyde which acts as an inhibitor of GABA transaminase ultimately reducing GABA metabolism and increasing GABAergic neurotransmission. As GABA is an inhibitory neurotransmitter, this increase results in increased inhibitory activity.1 A possible secondary contributor to cortical inhibition is a direct suppression of voltage gated sodium channel activity and indirect suppression through effects on GABA.
It has also been suggested that valproate impacts the extracellular signal-related kinase pathway (ERK).1 These effects appear to be dependent on mitogen-activated protein kinase (MEK) and result in the phosphorylation of ERK1/2. This activation increases expression of several downstream targets including ELK-1 with subsequent increases in c-fos, growth cone-associated protein-43 which contributes to neural plasticity, B-cell lymphoma/leukaemia-2 which is an anti-apoptotic protein, and brain-derived neurotrophic factor (BDNF) which is also involved in neural plasticity and growth. Increased neurogenesis and neurite growth due to valproate are attributed to the effects of this pathway. An additional downstream effect of increased BDNF expression appears to be an increase in GABAA receptors which contribute further to increased GABAergic activity.13
Valproate exerts a non-competitive indirect inhibitory effect on myo-inosital-1-phophate synthetase.14This results in reduced de novo synthesis of inositol monophosphatase and subsequent inositol depletion. It is unknown how this contributed to valproate's effects on bipolar disorder but [lithium] is known to exert a similar inositol-depleting effect.15 Valproate exposure also appears to produce down-regulation of protein kinase C proteins (PKC)-α and -ε which are potentially related to bipolar disorder as PKC is unregulated in the frontal cortex of bipolar patients. This is further supported by a similar reduction in PKC with lithium.16 The inhibition of the PKC pathway may also be a contributor to migraine prophylaxis.17 Myristoylated alanine-rich C kinase substrate, a PKC substrate, is also downregulated by valproate and may contribute to changes in synaptic remodeling through effects on the cytoskeleton.18
Valproate also appears to impact fatty acid metabolism.1 Less incorporation of fatty acid substrates in sterols and glycerolipids is thought to impact membrane fluidity and result in increased action potential threshold potentially contributing to valproate's antiepileptic action.19 Valproate has been found to be a non-competitive direct inhibitor of brain microsomal long-chain fatty acyl-CoA synthetase.20 Inhibition of this enzyme decreases available arichidonyl-CoA, a substrate in the production of inflammatory prostaglandins. It is thought that this may be a mechanism behind valproate's efficacy in migraine prophylaxis as migraines are routinely treated with non-steroidal anti-inflammatory drugs which also inhibit prostaglandin production.
Finally, valproate acts as a direct histone deactylase (HDAC) inhibitor.22 Hyperacetylation of lysine residues on histones promoted DNA relaxation and allows for increased gene transcription. The scope of valproate's genomic effects is wide with 461 genes being up or down-regulated.21 The relation of these genomic effects to therapeutic value is not fully characterized however H3 and H4 hyperacetylation correlates with improvement of symptoms in bipolar patients.23 Histone hyperacetylation at the BDNF gene, increasing BDNF expression, post-seizure is known to occur and is thought to be a neuroprotective mechanism which valproate may strengthen or prolong.24 H3 hyperacetylation is associated with a reduction in glyceraldehyde-3-phosphate dehydrogenase, a pro-apoptotic enzyme, contributing further to valproate's neuroprotective effects.25Reference: Drug Bank