|Systematic (IUPAC) name|
|Metabolism||Enzymatic hydrolysis of acetamide group|
|Half-life||6 - 8 hr|
|Mol. mass||170.209 g/mol|
|(what is this?)|
Levetiracetam has been approved in the European Union as a monotherapy treatment for epilepsy in the case of partial seizures, or as an adjunctive therapy for partial, myoclonic and tonic-clonic seizures. It is also used in veterinary medicine for similar purposes.
Levetiracetam has potential benefits for other psychiatric and neurologic conditions such as Tourette syndrome, autism, bipolar disorder and anxiety disorder, as well as Alzheimer's disease. However, its most serious adverse effects are behavioral, and its benefit-risk ratio in these conditions is not well understood.
- Psychiatric reactions
- Suicidal Behavior and Ideation
- Somnolence and Fatigue
- Dermatologic Reactions
- Coordination Difficulties
- Hematologic Abnormalities
Suicidal Ideation: Antiepileptic drugs (AEDs), including KEPPRA XR, increases the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Studies have shown almost a doubling of risk of suicidal ideation from 0.2% to 0.4% for those taking the medication compared to placebo. Symptoms have been reported within 1 week of starting the medication with improvement following discontinuation. A study published in 2005 suggests that the addition of pyridoxine (vitamin B6) may curtail some of the psychiatric symptoms.
Somnolence: A study found somnolence as a reported symptom in 7.8% of patients taking Keppra XR compared to 2.5% in the placebo group. Patients should be monitored for exhibiting effects of somnolence before driving and operating machinery.
Serious Dermatological Reactions: Although rare, Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with levetiracetam. Recommendations are to discontinue Keppra upon signs of unexplained rash. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered. The incidence of SJS following exposure to anti-epileptics such as Levetiracetam is about 1 in 3,000
Measured Hematologic Abnormalities: One study of patients receiving Keppra IR showed decreased RBC, decreased mean hematocrit and mean hemoglobin compared to placebo. None of the patients however, experienced any symptoms related to the decreased blood counts and the medications were continued.
A meta-analysis done in 2008 Journal of Neuropyschiatry Disease and Treatment compared three studies conducted in 2000 analyzing the safety of therapeutic doses of levetiracetam for patients suffering partial seizures in an attempt to better quantify the most common side effects. They found the following incidence for 769 patients:
No significant pharmacokinetic interactions were observed between levetiracetam or its major metabolite and concomitant medications. The pharmacokinetic profile of Keppra is not influenced by phenytoin, phenobarbital, primidone, carbamazepine, valproic acid, lamotrigine, gabapentin, digoxin, oral contraceptives ethinylestradiol, and warfarin.
The highest human dose observed in the clinical development was 6000 mg / day or Keppra IR, double the highest recommended dose. No major adverse events were reported except for drowsiness in development trials. Cases of somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with immediate-release KEPPRA overdoses in postmarketing use.
There are no absolute Contraindications to starting a Keppra regimen unless previous hypersensitivity reaction to levetiracetam or metabolites
Keppra is a Pregnancy Category C drug, meaning that animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite the risks.
Pregnancy: Keppra is a Pregnancy Category C Drug
Studies in female pregnant rats have shown minor fetal skeletal abnormalities when given maximum recommended human doses of Keppra orally throughout pregnancy and lactation.
A study in the Journal Neurology retrospectively looked at 671 human pregnancies with known maternal exposure to Keppra and found that the rate of Major Congenital Malformations (MCM) was not significantly higher when Keppra was used as a monotherapy. However, the majority of the patients were also exposed to other anti-epileptic drugs as a combination therapy and found increases in Major Congential Malformations when combined with valproate and carbamazepine. The paper concluded that the data suggests Keppra monotherapy to be a suitable regimen if anti-epileptic medication is needed during pregnancy.
Keppra is renally cleared and the incidence of impaired renal function is higher in this age group. Studies were conducted to look for increased adverse effects in the elderly population as compared to younger patients. One such study published in Epilepsy Research showed no significant increase in incidence of adverse symptoms experience by young and elderly patients with CNS disorders.
Measurement in bodily fluids
There are only a few papers published reporting therapeutic drug monitoring methods of levetiracetam. Three of them employed HPLC with UV-detection, and two methods were using GC with NPD-detection. Microemulsion electrokinetic chromatography with UV-detection was utilized in one method. Two methods facilitating chiral separation of the S- and R- enantiomer of levetiracetam, one utilizing GC–MS and the other HPLC–UV, were published. These methods were designed to investigate in dogs the pharmacokinetic and pharmacodynamic properties of the two enantiomers separately. For routine therapeutic drug monitoring in men, these methods were not appropriate. In all but one of the methods, sample preparation with SPE or liquid–liquid extraction is necessary. Pucci et al. evaluated the feasibility of protein precipitation as the only sample preparation step in comparison to SPE. They concluded, that protein precipitation is a suitable and fast sample preparation for measuring routine patient samples. Mecarelli et al. studied the concentration of levetiracetam in both serum and saliva of patients with epilepsy.
Mechanism of action
The exact mechanism by which levetiracetam acts to treat epilepsy is unknown. However, the drug binds to a synaptic vesicle glycoprotein, SV2A, and inhibits presynaptic calcium channels  reducing neurotransmitter release and acting as a neuromodulator. This is believed to impede impulse conduction across synapses.
- Ready-to-administer bags of sodium chloride injection, at concentrations of 500 mg/100 mL, 1000 mg/100 mL and 1500 mg/100 mL
- 250 mg tablets
- 500 mg tablets
- 750 mg tablets
- 1000 mg tablets
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