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how long does keppra stay in your system? how about the generic

Hi. I had a grand mal seizure on 9/11/2012. My brain cancer is/was in my left frontal lobe which is responsible for speech as well as other functions. My seizures always start the same: stuck on a thought, start to try and talk, gibberish and non nonsensical sounds come out of my mouth until I pass out. This time I was able to crawl out of the bathroom and wrote down on a piece paper for my wife to call 911.

When I saw my doctor, he said that I did not have enough of levetiracetam (generic keppra) in my system. He said that the half life was eight hours - i had no idea.

The last time I had a levetiracetam level check, it registered at 18 where the range is 12 - 46. THis time, the level was 3 within a range of 5.0 - 63.0.

Different labs have different ranges which I understand. But how does one get
to the upper ranges without having built a store in the body? Is it the kidneys that store it or the liver or does it just float around in the blood stream?

Confused and looking for another opinion. Thank you

Comments

Re: how long does keppra stay in your system?

Hi BrDietrich,

When I get my usual "aura" warning (off and on instances for about 30 minutes prior, if I stay awake) of impending about monthly seizure clusters that now usually lead to a secondarily
generalized tonic-clonic, I take an extra strong dose (at least 2000mg to 3000mg) of regular Keppra as soon as possible after the initial warnings.
Oral Keppra tablets reach peak plasma levels fast enough for me to have prevented my tonic-clonics for
about 3-and-a-half years now. I slowly reduce my every 6 to 12 hour doses back down to a residual dose level in a few days
(maintaining a once a day residual dose level (presently 250 mg at night) seems to prevent and/or reduce many side-effects of isolated maximum doses versus
no doses during the near monthly cycle). I haven't had any luck with any AEDs controlling my partial seizures, so I try
to prevent the tonic-clonics with minimal side-effects and minimal AED expense (and limited quanties of Keppra).

After a second initial slow first continual titration up to maximum doses for a few months, the at first initial side-effects of a then too rapid dose
increase, before the routine of now minimal residual dose levels, haven't re-occurred for me.

Regular Keppra is fast enough, with a short enough half-life, that with the most recent dosage in about 8 hours, the dosage will be verified by
most blood tests. Impaired renal functioning will typically result in a higher reading, and too rapid, or expelled, digestive passage, will
typically result in a lower reading. (My last full tonic-clonic happened when I couldn't keep the Keppra swallowed long enough, while,
especially with extended release levetiracetam, other patients reported passing excessive fragments).

After dosage considerations, I believe the amount of levetiractam still in the digestive system and a person's renal functioning is most controlling
of the person's plasma levels versus expected levels over a time period.

From "Pharmacokinetic profile of levetiracetam: toward ideal characteristics" by Patsalos (Pharmacol Ther. 2000 Feb;85(2):77-85):
"Sixty-six percent of an administered levetiracetam dose is eliminated unchanged in urine; 24% is metabolized to an inactive metabolite that is detectable in blood and is also excreted in urine. Total body clearance of levetiracetam is decreased in patients with renal impairment, and doses should be modified according to creatinine clearance values. Levetiracetam is not appreciably protein-bound, nor does it affect the protein binding of other drugs. Thus, because of its minimal protein binding and lack of hepatic metabolism, the risk of drug interactions is very low. "
http://www.ncbi.nlm.nih.gov/pubmed/10722121

My experiences with generics have been bad, as inert ingredients have unexpected effects, and generics have much wider ranges for fluctuation in amounts/purity of active ingredients.

Tadzio

P.S.: my computer keeps crashing while I'm editing, so here's an unedited batch of closely to distant related levetiracetam info/graphs, etc.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2000749/?tool=pmcentrez

http://www.ncbi.nlm.nih.gov/pubmed/10722121

http://www.google.com/search?q=Measurement+of+Levetiracetam+in+Serum+or+...

http://www.google.com/imgres?q=Measurement+of+Levetiracetam+in+Serum+or+...

http://www.nature.com/pr/journal/v72/n1/full/pr201251a.html

http://www.google.com/imgres?q=Measurement+of+Levetiracetam+in+Serum+or+...

http://www.google.com/imgres?q=Measurement+of+Levetiracetam+in+Serum+or+...

http://avmajournals.avma.org/doi/abs/10.2460/ajvr.71.3.337

Re: how long does keppra stay in your system?

Thanks for the information Tadzio. 

 In looking at your links, and doing some research, I found that the Mayo clinic defines the trough or the time immediatelly before your second dosing, for 3000 a day, to be: 12 to 46 mcg/mL.  My last test in February of this year measured my level at 17 (performed by the Mayo Clinic).  The test performed in the ER was 2.9 within LabCorp's range of 5-63.  Why the difference in ranges?  Is there not a common agreement of what the theraputic dose is for Keppra?  If you look at the difference beteen the two labs' low ranges, it is close to 42%.  Why the discrepancy? 

thank you    

Re: how long does keppra stay in your system?

Hi BrDietrich,

My last test was in April of this year (2012), with a Keppra (Levetiractam) level of 18 µg/mL. The test was listed as performed at ARUP Laboratory, Salt Lake City, Utah, and it listed their Reference Range as 5 to 30 µg/mL, with the added "interpretive information" note, of:
"The proposed therapeutic range for seizure control is 5-30 µg/mL. Pharmacokinetics of levetiracetam are affected by renal function. The relationship between serum concentration and toxicity is not known."

My blood was drawn at 09:05 AM, about 8 hours after a midnight/early-morning dose totaling 1000 mg of Keppra in tablets at 01:00 AM. The previous dosage was 1500 mg 25 hours earlier than the 01:00 AM dose (I was reducing Keppra intake back to residual levels after a day of clusters a couple days earlier, and the test matched mid-range for ARUP's Reference Range). Other blood tests the same day required fasting, so I hadn't any food or further liquids after taking the 01:00 AM Keppra dose, and the walk to the clinic's blood lab was 1.2 miles, so, also, the reading was probably increased somewhat by the exercise and initial Stage III chronic kidney disease, with my being 59 years old.

While all the medical groups can't establish a valid "proposed therapeutic/reference range" for levetiracetam levels in mutual agreement, epilepsy's rather subjective response seems the more objective. Wading through the various numbers involving "69 epileptic patients treated with 500 to 3000 mg/d of levetiracetam [with ranging] from 1.1 to 33.5 [µg/mL],":

"Good?" Responders had levetiracetam plasma concentrations of 4.6 to 21 µg/mL (with a mean of 12.9 µg/mL), but,
The Non--Responders had levetiracetam plasma concentrations of 1.1 to 20.9 µg/mL (with a mean of 9.5 µg/mL).

"Nevertheless, the levetiracetam plasma concentration could be used to help clinicians detect severe intoxication or to verify compliance by repeating the measurement in patients." http://www.ncbi.nlm.nih.gov/pubmed/17898647

A Medical Group's checking for mandatory satisfaction of such fickle "compliance" ranges seems like something somewhat removed from considering any self-evaluation of therapeutic benefits of a medical regimen, and more like a Catch-22 corporate medical group's attempt at hierarchy economics. With views of "Therapeutic drug monitoring: not needed", slightly older therapeutic ranges (2005) included "6-20 mg/L (35-120 µmol/L)" http://www.ncbi.nlm.nih.gov/books/NBK2597/#ch14.s68

Previously, a clinic continued to demand the economics from generic versions of Dilantin in stopping my grand mal seizures, but the wide variances of different batches of generics often resulted in ambulance trips to ER over about a two year period after emergency surgery by a neurosurgeon, when the clinic finally stopped blaming me for "non-compliance" and filed an "e-TAR" authorizing brand name Dilantin to save sub-contractors money on ambulance trips. Dilantin and osteoporosis with the economics of Boniva versus clinic denial of their own tests were then the next elements of a Catch-22 with the pharmacy therapeutics involving epilepsy.

References to the presently most recognized "reference range" of 12-46 mg/L is given in the footnotes to "From evaluation of 470 patients in a specialty epilepsy clinic, a reference range of 12–46 mg/L has been proposed [47]...Other than to evaluate potential toxicity or to assess compliance, the value of TDM for levetiracetam is mostly in adjusting dosage for renal insufficiency [120]."
in "Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications" by Matthew D. Krasowski, at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904466/
(All the newer measurement techniques are looking for a use too???:
"Multiple analytical methodologies have been reported for the measurement of levetiracetam in plasma/serum including HPLC [112, 113], GC [114, 115], GC/MS [116], LC/MS/MS [117], microemulsion electrokinetic chromatography [118] and capillary electrophoresis [119]."
[47. Leppik, I.E.; Rarick, J.O.; Walczak, T.S.; Tran, T.A.; White, J.R.; Gumnit, R.J. Effective levetiracetam doses and serum concentrations: Age effects. Epilepsia 2002, 43, 240.] currently (September 24, 2012) at, when not "locked":
Epilepsia, Volume 43, Issue Supplement s7, page 240:
http://onlinelibrary.wiley.com/doi/10.1046/j.1528-1157.43.s7.1.x/pdf (3.1 MB file size)
with the "Conclusions: The mean dose of LEV in this population was ~2,500 mg/day, but the range was large. Although females received lower daily doses, their doses were higher than males on a mg/kg basis. The apparent clearance was greatest in persons younger than 18 years and lowest in in those older than 65 (~26% greater). It appears the concentrations of 29 µg/ml with 1 SD of 17.2 are associated with the highest doses attained in a clinical setting, and thus a range of 12–46 µg/ml could be considered effective for most persons with epilepsy. (Supported by MINCEP Epilepsy Care.)"

"MINCEP,12 the epilepsy care research group, proposed a reference range of 12---46 mg/l (70---270 µmol/l) for levetiracetam. The lower limit of this interval was validated by Lancelin et al.13 [13 http://www.ncbi.nlm.nih.gov/pubmed/17898647 again] in a study of 69 patients carried out in 2007."
"Pharmacokinetic Monitoring of Antiepileptic Drugs" by A. Aldaz, et al. (Farm Hosp. 2011;xxx(xx):xxx---xxx), page 3 at: http://www.elsevier.es/sites/default/files/elsevier/eop/S2173-5085(11)00028-1.pdf

I tend to like many of sentences from Emilio Perucca in "The Treatment of Epilepsy", Simon D. Shorvon (Editor), Emilio Perucca (Editor), Jerome Engel Jr. (Editor), (2009):
http://books.google.com/books?id=rFFzFzZJtasC&pg=PA559&lpg=PA559&dq=leve...
and,
http://books.google.com/books?id=rFFzFzZJtasC&pg=PA559&lpg=PA559&dq=leve...
page 133 (and page 121), therapeutic range versus reference range...page 121: "The primary objective of treatment aims for complete seizure control, .... but, this, however, should not be achieved at all costs." "The situation should never arise where a patient is made to suffer more from the adverse effects of treatment than from the symptoms of the disease [4]." [4]: "Overtreatment In Epilepsy" (below) "Assessing the most disabling seizure types can require assistance from an external observer, but the patient's perceptions are more important." page 137: "Physicians must always remember that the priority aim of therapy is to treat a patient and not a laboratory value."

http://adisonline.com/cnsdrugs/Abstract/2005/19110/Overtreatment_in_Epil...
http://www.youtube.com/watch?v=Ax6xr2B5W-I

(Amazon-dot-com often has a preview of some of the pages with a search in the book for key word phrases for more pages).
(The same Emilio Perucca now President Elect of the ILAE???
http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(12)70196-5/fulltext#article_upsell ).

Tadzio

Re: how long does keppra stay in your system?

Hi Tadzio.  A wealth of information.  Thank you. 

I see the quote in the 2007 pubmed article which you copied above that says:  "Responders had levetiracetam plasma concentrations of 4.6 to 21 µg/mL (with a mean of 12.9 µg/mL), but,  The Non--Responders had levetiracetam plasma concentrations of 1.1 to 20.9 µg/mL (with a mean of 9.5 µg/mL)...." 

 I am a brain tumor patient with a resected AAIII in my left frontal lobe.  Is there a difference between epilepsy and brain tumor seizures and hence could I be considered inthe group of "non-responding" patients?  And why would the non-responsive low range be different with the respondive range yet the mid and high ranges between the two groups be basically the same?.  Or is this your point.  You agree that the doctors cannot really come to an agreement on what the theraputic ranges should be and then what is the difference between responsive and non-responding patients?    

 thanks for taking the time to answer my questions.  I really appreciate it. 

Re: how long does keppra stay in your system?

Hi BrDietrich,

I lost the chain of reasonnings used in the book I got mainly for the newer references involving TSC non-cancerous tumors ("tubers") versus cancerous tumors and inhibitors (mTOR inhibitors for both?), so I'm confused in the same area with the sub-section on "Cerebral tumor" overlapping with the other sections mentioning tumors.

The sub-section has 5 chapters (pages 433-466) that I don't know of which one might be the most relevant (if any). The amazon-dot-com search "look inside" lists 5 page entries for "levetiracetam" within this sub-section 3.9 of "The Causes of Epilepsy: Common and Uncommon Causes in Adults and Children" edited by Shorvon, Andermann, & Guerrini (2011), (I was fortunate to buy my copy for only $25.00 a few months ago).

Books-dot-google has some of the pages for preview at times also:
page 438 maybe:
http://books.google.com/books?id=BUs-AYMBbC0C&printsec=frontcover&dq=The...

page 465:
http://books.google.com/books?id=BUs-AYMBbC0C&printsec=frontcover&dq=The...

I haven't searched these chapter's numerous interesting sounding titled references with my computer still often crashing.

Tadzio