Keppra

Keppra - General Information

Keppra is an anticonvulsant medication used to treat epilepsy. Keppra may selectively prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity. Keppra binds to the synaptic vesicle protein SV2A, which is thought to be involved in the regulation of vesicle exocytosis. Although the molecular significance of levetiracetam binding to synaptic vesicle protein SV2A is not understood, levetiracetam and related analogs showed a rank order of affinity for SV2A which correlated with the potency of their antiseizure activity in audiogenic seizure-prone mice.

 

Pharmacology of Keppra

Not Available

 

Keppra for patients

KEPPRA® (pronounced KEPP-ruh)
(levetiracetam)
250 mg, 500 mg and 750 mg tablets and 100 mg/mL oral solution

Read the Patient Information that comes with KEPPRA® before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your condition or your treatment.

Before taking your medicine, make sure you have received the correct medicine. Compare the name above with the name on your bottle and the appearance of your medicine with the description of KEPPRA® provided below. Contact your pharmacist immediately if you believe a dispensing error may have occurred.

What is KEPPRA®?

KEPPRA® is a medicine that is used to treat partial seizures in adults and children 4 years of age and older with epilepsy. It is used with other seizure medicines to help control your seizures. KEPPRA® comes in tablets and in liquid.

250 mg KEPPRA® tablets are blue, oblong-shaped, scored, film-coated tablets marked with "ucb" and "250" on one side.

500 mg KEPPRA® tablets are yellow, oblong-shaped, scored, film-coated tablets marked with "ucb" and "500" on one side.

750 mg KEPPRA® tablets are orange, oblong-shaped, scored, film-coated tablets marked with "ucb" and "750" on one side.

KEPPRA® oral solution is a clear, colorless, grape-flavored liquid.

Who should not take KEPPRA®?

Do not take KEPPRA® if you are allergic to any of its ingredients. The active ingredient is levetiracetam. See the end of this leaflet for a list of all the ingredients in KEPPRA®.

Tell your healthcare provider:

• if you are pregnant or planning to become pregnant. If you use KEPPRA® while you are pregnant, ask your healthcare provider about being in the Keppra® Pregnancy Registry. You can join this registry by calling (888) 537-7734 (toll free). You may also join the North American Antiepileptic Drug Pregnancy Registry by calling (888) 233-2334 (toll free).

• if you are breast feeding. KEPPRA® can pass into your milk and may harm your baby. You should choose to either take KEPPRA® or breast feed, but not both.

• if you have kidney disease. You may need a lower dose of KEPPRA®.

• about all the medicines you take, including prescription, nonprescription, vitamins, and herbal supplements.

KEPPRA® has not been approved for children below 4 years of age.

How should I take KEPPRA®?

• Take KEPPRA® exactly as prescribed. KEPPRA® is usually taken twice a day. Once in the morning and once at night. Take KEPPRA® at the same times each day.

• Your healthcare provider may start you on a lower dose of KEPPRA® and increase it as your body gets used to the medicine.

• Take KEPPRA® with or without food. Swallow the tablets whole. Do not chew or crush tablets. Use the KEPPRA® oral solution if you cannot swallow tablets. Use a medicine dropper or medicine cup to measure KEPPRA® oral solution. Do not use a teaspoon. Ask your pharmacist for a medicine dropper or medicine cup to help you measure KEPPRA®.

• If your healthcare provider has given you KEPPRA® oral solution for your child, be sure to ask your pharmacist for a medicine syringe to help you measure the correct amount of KEPPRA® oral solution. Ask your pharmacist for instructions on how to properly use the medicine syringe or dosing device that has been provided to you.

• If you take too much KEPPRA® or overdose, call your local Poison Control Center or emergency room right away.

• Do not stop taking KEPPRA® or any other seizure medicine unless your healthcare provider told you to. Stopping a seizure medicine all at once can cause status epilepticus (seizures that will not stop), a very serious problem.

• Tell your healthcare provider if your seizures get worse or if you have any new types of seizures.

• Talk to your healthcare provider about what to do if you miss a dose.

What should I avoid while taking KEPPRA®?

Do not drive, operate complex machinery or participate in other hazardous activities until you know how KEPPRA® affects you. KEPPRA® may make you dizzy or sleepy.

What are the possible side effects of KEPPRA®?

Adults

KEPPRA® may cause the following serious problems in adults. Call your healthcare provider right away if you get any of the following symptoms:

• Extreme sleepiness, tiredness, and weakness.

• Problems with muscle coordination (problems walking and moving).

• Mood and behavior changes such as aggression, agitation, anger, anxiety, apathy, depression, hostility, and irritability. A few people may get psychotic symptoms such as hallucinations (seeing or hearing things that are really not there). A few people may get thoughts of suicide (thoughts of killing yourself).

The most common side effects with KEPPRA® in adults are:

• sleepiness

• weakness

• dizziness

• infection

These side effects could happen at any time but happen most often within the first four weeks of treatment except for infection.

Children

KEPPRA® may cause the following serious problems in children. Call your child's healthcare provider right away if they get any of the following symptoms:

• Extreme sleepiness, tiredness and weakness.

• Mood and behavior changes such as aggression, agitation, anger, anxiety, apathy, depression, hostility, and irritability.

The most common side effects with KEPPRA® in children are:

• sleepiness

• accidental injury

• hostility

• irritability

• weakness

These side effects could happen at any time.

These are not all the side effects of KEPPRA®. For more information, ask your healthcare provider or pharmacist. If you get any side effects that concern you, call your healthcare provider.

General information about KEPPRA®.

Medicines are sometimes prescribed for conditions other than those described in patient information leaflets. Do not use KEPPRA® for a condition for which it was not prescribed. Do not give your KEPPRA® to other people, even if they have the same symptoms that you have. It may harm them.

Store KEPPRA® at room temperature away from heat and light. Keep KEPPRA® and all medicines out of the reach of children.

This leaflet summarizes the most important information about KEPPRA®. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about KEPPRA® that is written for healthcare professionals. You can also get information about KEPPRA® at www.keppra.com.

What are the ingredients of KEPPRA®?

KEPPRA® tablets contain the labeled amount of levetiracetam. Inactive ingredients: colloidal silicon dioxide, corn starch, hydroxypropyl methylcellulose, magnesium stearate, polyethylene glycol 4000, povidone, talc, titanium dioxide and coloring agents.

The individual tablets contain the following coloring agents: 250 mg tablets: FD&C Blue No. 2, 500 mg tablets: yellow iron oxide, 750 mg tablets: FD&C Blue No. 2, FD&C Yellow No. 6 and red iron oxide.

KEPPRA® oral solution contains 100 mg of levetiracetam per mL. Inactive ingredients: ammonium glycyrrhizinate, citric acid monohydrate, glycerin, maltitol solution, methylparaben, potassium acesulfame, propylparaben, purified water, sodium citrate dihydrate and natural and artificial flavor.

KEPPRA® does not contain lactose or gluten. It does contain carbohydrates. The liquid is dye-free.

 

Keppra Interactions

in vitro data on metabolic interactions indicate that Keppra® is unlikely to produce, or be subject to, pharmacokinetic interactions. Levetiracetam and its major metabolite, at concentrations well above c_max levels achieved within the therapeutic dose range, are neither inhibitors of nor high affinity substrates for human liver cytochrome P450 isoforms, epoxide hydrolase or UDP-glucuronidation enzymes. In addition, levetiracetam does not affect the in vitro glucuronidation of valproic acid.

Levetiracetam circulates largely unbound (<10% bound) to plasma proteins; clinically significant interactions with other drugs through competition for protein binding sites are therefore unlikely.

Potential pharmacokinetic interactions were assessed in clinical pharmacokinetic studies (phenytoin, valproate, oral contraceptive, digoxin, warfarin, probenecid) and through pharmacokinetic screening in the placebo-controlled clinical studies in epilepsy patients.

Drug-Drug Interactions Between Keppra® And Other Antiepileptic Drugs (AEDs)

Phenytoin

Keppra® (3000 mg daily) had no effect on the pharmacokinetic disposition of phenytoin in patients with refractory epilepsy. Pharmacokinetics of levetiracetam were also not affected by phenytoin.

Valproate

Keppra® (1500 mg twice daily) did not alter the pharmacokinetics of valproate in healthy volunteers. Valproate 500 mg twice daily did not modify the rate or extent of levetiracetam absorption or its plasma clearance or urinary excretion. There also was no effect on exposure to and the excretion of the primary metabolite, ucb L057.

Potential drug interactions between Keppra® and other AEDs (carbamazepine, gabapentin, lamotrigine, phenobarbital, phenytoin, primidone and valproate) were also assessed by evaluating the serum concentrations of levetiracetam and these AEDs during placebo-controlled clinical studies. These data indicate that levetiracetam does not influence the plasma concentration of other AEDs and that these AEDs do not influence the pharmacokinetics of levetiracetam.

Effect of AEDs in Pediatric Patients

There was about a 22% increase of apparent total body clearance of levetiracetam when it was co-administered with enzyme-inducing AEDs. Dose adjustment is not recommended.Levetiracetam had no effect on plasma concentrations of carbamazepine, valproate, topiramate, or lamotrigine.

Other Drug Interactions

Oral Contraceptives

Keppra® (500 mg twice daily) did not influence the pharmacokinetics of an oral contraceptive containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel, or of the luteinizing hormone and progesterone levels, indicating that impairment of contraceptive efficacy is unlikely.

Coadministration of this oral contraceptive did not influence the pharmacokinetics of levetiracetam.

Digoxin

Keppra® (1000 mg twice daily) did not influence the pharmacokinetics and pharmacodynamics (ECG) of digoxin given as a 0.25 mg dose every day. Coadministration of digoxin did not influence the pharmacokinetics of levetiracetam.

Warfarin

Keppra® (1000 mg twice daily) did not influence the pharmacokinetics of R and S warfarin. Prothrombin time was not affected by levetiracetam. Coadministration of warfarin did not affect the pharmacokinetics of levetiracetam.

Probenecid

Probenecid, a renal tubular secretion blocking agent, administered at a dose of 500 mg four times a day, did not change the pharmacokinetics of levetiracetam 1000 mg twice daily. Cssmax of the metabolite, ucb L057, was approximately doubled in the presence of probenecid while the fraction of drug excreted unchanged in the urine remained the same. Renal clearance of ucb L057 in the presence of probenecid decreased 60%, probably related to competitive inhibition of tubular secretion of ucb L057. The effect of Keppra® on probenecid was not studied.

 

Keppra Contraindications

This product should not be administered to patients who have previously exhibited hypersensitivity to levetiracetam or any of the inactive ingredients in Keppra® tablets or oral solution.

 

Additional information about Keppra

Keppra Indication: Used as adjunctive therapy in the treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.
Mechanism Of Action: The precise mechanism(s) by which levetiracetam exerts its antiepileptic effect is unknown. The antiepileptic activity of levetiracetam was assessed in a number of animal models of epileptic seizures. Keppra did not inhibit single seizures induced by maximal stimulation with electrical current or different chemoconvulsants and showed only minimal activity in submaximal stimulation and in threshold tests. Protection was observed, however, against secondarily generalized activity from focal seizures induced by pilocarpine and kainic acid, two chemoconvulsants that induce seizures that mimic some features of human complex partial seizures with secondary generalization. Keppra also displayed inhibitory properties in the kindling model in rats, another model of human complex partial seizures, both during kindling development and in the fully kindled state. The predictive value of these animal models for specific types of human epilepsy is uncertain.
Drug Interactions: Carbamazepine This association may increases the risks of carbamazepine toxicity
Food Interactions: Take without regard to meals. Food does not affect bioavailabilty.
Generic Name: Levetiracetam
Synonyms: Levetiracetam [INN]; Levetiracetamum [INN-Latin]; Levitiracetam
Drug Category: Anticonvulsants; Nootropic Agents
Drug Type: Small Molecule; Approved; Investigational

Other Brand Names containing Levetiracetam: Keppra;
Absorption: Rapidly and almost completely absorbed after oral administration (99%). Peak plasma concentrations occurring in about an hour following oral administration in fasted subjects.
Toxicity (Overdose): Side effects include aggression, agitation, coma, drowsiness, reduced consciousness, slowed breathing
Protein Binding: Very low (<10%)
Biotransformation: The major metabolic pathway of levetiracetam (24% of dose) is an enzymatic hydrolysis of the acetamide group. No CYP450 metabolism detected.
Half Life: 6-8 hours
Dosage Forms of Keppra: Tablet Oral
Chemical IUPAC Name: (2R)-2-(2-oxopyrrolidin-1-yl)butanamide
Chemical Formula: C8H14N2O2
Levetiracetam on Wikipedia: https://en.wikipedia.org/wiki/Levetiracetam
Organisms Affected: Humans and other mammals