What happens if you take keppra and don’t need it?

Contents

Keppra

Generic Name: levetiracetam (LEE ve tye RA se tam)
Brand Names: Keppra, Keppra XR, Roweepra, Spritam

Medically reviewed by Philip Thornton, DipPharm Last updated on Jan 6, 2020.

  • Overview
  • Side Effects
  • Dosage
  • Professional
  • Tips
  • Interactions
  • More

What is Keppra?

Keppra (levetiracetam) is an anti-epileptic drug, also called an anticonvulsant.

Keppra is used to treat partial onset seizures in adults and children who are at least 1 month old.

Keppra is also used to treat tonic-clonic seizures in people who are at least 6 years old, and myoclonic seizures in people who are at least 12 years old.

Important Information

Do not stop using Keppra without first talking to your doctor, even if you feel fine. You may have increased seizures if you stop using this medicine suddenly. You may need to use less and less before you stop the medication completely.

Some people have thoughts about suicide when first taking this medicine. Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor.

Wear a medical alert tag or carry an ID card stating that you take Keppra. Any medical care provider who treats you should know that you take seizure medication.

Levetiracetam may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Do not start or stop taking Keppra during pregnancy without your doctor’s advice. Having a seizure during pregnancy could harm both the mother and the baby. Seizure control is very important during pregnancy and the benefits of preventing seizures may outweigh any risks posed by using this medicine.

Before taking this medicine

You should not use Keppra if you are allergic to levetiracetam.

Tell your doctor if you have ever had:

  • kidney disease (or if you are on dialysis);

  • depression or other mood problems;

  • mental illness or psychosis; or

  • suicidal thoughts or actions.

You may have thoughts about suicide while taking Keppra. Your doctor should check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Follow your doctor’s instructions about taking seizure medication if you are pregnant. Seizure control is very important during pregnancy, and having a seizure could harm both mother and baby. Your dose needs may be different during pregnancy. Do not start or stop taking this medicine without your doctor’s advice, and tell your doctor right away if you become pregnant.

If you are pregnant, your name may be listed on a pregnancy registry to track the effects of levetiracetam on the baby.

It may not be safe to breastfeed while using Keppra. Ask your doctor about any risk.

Do not give this medicine to a child without medical advice.

How should I take Keppra?

Take Keppra exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

Take the medicine at the same time each day, with or without food.

Levetiracetam doses are based on weight in children. Your child’s dose needs may change if the child gains or loses weight.

Your dose needs may change if you switch to a different brand, strength, or form of this medicine. Avoid medication errors by using only the form and strength your doctor prescribes.

Measure liquid medicine carefully. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).

Swallow the extended-release tablet whole and do not crush, chew, or break it.

You should not stop using Keppra suddenly, unless your doctor tells you to stop the medicine because of a serious side effect. Stopping suddenly may cause increased seizures. Follow your doctor’s instructions very carefully.

Use all seizure medications as directed and read all medication guides you receive. Do not change your dose or dosing schedule without your doctor’s advice.

In case of emergency, wear or carry medical identification to let others know you use seizure medication.

Your kidney function may need to be tested often.

Store at room temperature away from moisture, heat, and light.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

Get your prescription refilled before you run out of medicine completely.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include extreme drowsiness, agitation, aggression, shallow breathing, weakness, or fainting.

What should I avoid while taking Keppra?

Drinking alcohol with this medicine can cause side effects and may also increase the risk of seizures.

Avoid driving or hazardous activity until you know how this medicine will affect you. Dizziness or drowsiness can cause falls, accidents, or severe injuries.

Keppra side effects

Get emergency medical help if you have signs of an allergic reaction to Keppra (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, depression, anxiety, panic attacks, trouble sleeping, or if you feel agitated, hostile, irritable, hyperactive (mentally or physically), or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have:

  • unusual changes in mood or behavior (unusual risk-taking behavior, being irritable or talkative);

  • confusion, hallucinations, loss of balance or coordination;

  • extreme drowsiness, feeling very weak or tired;

  • problems with walking or movement;

  • the first sign of any skin rash, no matter how mild;

  • easy bruising, unusual bleeding; or

  • fever, chills, weakness, or other signs of infection.

Common Keppra side effects may include:

  • dizziness, drowsiness, tiredness;

  • weakness;

  • feeling aggressive or irritable;

  • loss of appetite;

  • stuffy nose; or

  • infection.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Keppra?

Other drugs may interact with levetiracetam, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Keppra only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2020 Cerner Multum, Inc. Version: 12.02.

Related questions

  • How long does it take to get Keppra out of your system?
  • What is the difference between Briviact and Keppra?

Medical Disclaimer

More about Keppra (levetiracetam)

  • Side Effects
  • During Pregnancy or Breastfeeding
  • Dosage Information
  • Patient Tips
  • Drug Images
  • Drug Interactions
  • Compare Alternatives
  • Support Group
  • Pricing & Coupons
  • En Español
  • 202 Reviews
  • Generic Availability
  • Drug class: pyrrolidine anticonvulsants
  • FDA Alerts (4)

Consumer resources

  • Keppra (Levetiracetam Injection)
  • Keppra (Levetiracetam Oral Solution)
  • Keppra (Levetiracetam Tablets)
  • Keppra (Advanced Reading)
  • Keppra Intravenous (Advanced Reading)

Other brands: Roweepra, Roweepra XR

Professional resources

  • Keppra (AHFS Monograph)
  • … +1 more

Other Formulations

  • Keppra XR

Related treatment guides

  • Seizures
  • Epilepsy

What should I discuss with my healthcare provider before taking levetiracetam?

You should not use levetiracetam if you are allergic to it.

Tell your doctor if you have ever had:

  • kidney disease (or if you are on dialysis);
  • depression or other mood problems;
  • mental illness or psychosis; or
  • suicidal thoughts or actions.

You may have thoughts about suicide while taking this medicine. Your doctor should check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Follow your doctor’s instructions about taking seizure medication if you are pregnant. Seizure control is very important during pregnancy, and having a seizure could harm both mother and baby. Do not start or stop taking this medicine without your doctor’s advice, and tell your doctor right away if you become pregnant.

If you are pregnant, your name may be listed on a pregnancy registry to track the effects of levetiracetam on the baby.

You should not breast-feed while you are using levetiracetam.

Do not give this medicine to a child without medical advice.

How should I take levetiracetam?

Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

Take the medicine at the same time each day, with or without food.

Levetiracetam doses are based on weight in children. Your child’s dose needs may change if the child gains or loses weight.

Your dose needs may change if you switch to a different brand, strength, or form of this medicine. Avoid medication errors by using only the form and strength your doctor prescribes.

Measure liquid medicine carefully. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).

Swallow the extended-release tablet whole and do not crush, chew, or break it.

To take the Spritam dissolvable tablet:

  • Remove a tablet from the package only when you are ready to take the medicine.
  • Use dry hands to remove the tablet and place it on your tongue. Then take a sip of liquid and hold it in your mouth.
  • Do not swallow the tablet whole. Allow it to dissolve in your mouth with the sip of liquid.
  • Swallow only after the tablet has completely dissolved, which should take less than 30 seconds.

Do not stop using levetiracetam suddenly, even if you feel fine. Stopping suddenly may cause increased seizures. Follow your doctor’s instructions about tapering your dose.

Use all seizure medications as directed and read all medication guides you receive. Do not change your dose or dosing schedule without your doctor’s advice.

In case of emergency, wear or carry medical identification to let others know you use seizure medication.

Your kidney function may need to be tested often.

Store at room temperature away from moisture, heat, and light.

Levetiracetam for preventing seizures

This leaflet is about the use of levetiracetam to prevent epileptic seizures. (Seizures may also be called convulsions or fits.)

This leaflet has been written specifically for parents and carers about the use of this medicine in children. The information may differ from that provided by the manufacturer. Please read this leaflet carefully. Keep it somewhere safe so that you can read it again.

Do not stop giving levetiracetam suddenly, as your child may have more seizures.

Name of drug

Levetiracetam
Brand names: Keppra ®, Keppra® XR

Why is it important for my child to take this medicine?

It is important that your child takes levetiracetam regularly so that they have fewer seizures.

What is levetiracetam available as?

  • Tablets: 250 mg, 500 mg, 750 mg, 1000 mg
  • Modified release tablets (Keppra XR): 500 mg, 750 mg
  • Liquid medicine: 500 mg in 5 mL

When should I give levetiracetam?

Levetiracetam is usually given twice each day, once in the morning and once in the evening. Ideally, these times are 10–12 hours apart, for example sometime between 7 and 8 am and between 7 and 8 pm.

Modified-release tablets

Your doctor may prescribe modified release tablets (Keppra XR). These are usually given once each day. This can be in the morning OR evening.

Give the medicine at about the same time(s) each day so that this becomes part of your child’s daily routine, which will help you to remember.

How much should I give?

Your doctor will work out the amount of levetiracetam (the dose) that is right for your child. The dose will be shown on the medicine label.

Your doctor will start your child on a low dose and then gradually increase it over a few days or weeks to help your child get used to the medicine. If you are not sure how much to give, check with your doctor or pharmacist.

It is important that you follow your doctor’s instructions about how much to give.

How should I give it?

Tablets should be swallowed whole with a glass of water, milk or juice. Your child should not chew the tablet.
You can crush the tablet and mix it with about 2 tablespoons of fruit juice or soft food such as yogurt, honey or jam. Make sure your child swallows it straight away, without chewing.

Liquid medicine: Measure out the right amount using an oral syringe or medicine spoon. You can get these from your pharmacist. Do not use a kitchen teaspoon as it will not give the right amount.
To hide the taste of the liquid medicine, you can add the dose into a glass of water, milk or fruit juice (preferably at room temperature. Your child should drink all the mixture straight away.

When should the medicine start working?

It may take a few weeks for levetiracetam to work properly, so your child may still have seizures during this time. This is because the amount of medicine has to be increased slowly. Continue to give the medicine in the way you have been told to by your doctor or epilepsy nurse.

Levetiracetam may not stop your child’s seizures completely. If you are worried about whether it is helping, contact your doctor but continue to give the medicine.

What if my child is sick (vomits)?

  • If your child is sick less than 30 minutes after having a dose of levetiracetam, give them the same dose again.
  • If your child is sick more than 30 minutes after having a dose of levetiracetam, you do not need to give them another dose. Wait until the next normal dose.

What if I forget to give it?

If you usually give it twice a day: If you remember up to 4 hours after you should have given a dose, give your child the missed dose. For example, if you usually give a dose at about 7 am, you can give the missed dose at any time up to 11 am. If you remember after that time, do not give the missed dose. Just give the next dose as usual.

Modified release tablets

If you usually give it once a day in the morning: Give the missed dose when you remember during the day, as long as this is at least 12 hours before the next dose is due.

If you usually give it once a day in the evening: If you remember before bedtime, give the missed dose. You do not need to wake up a sleeping child to give a missed dose. You can give the missed dose in the morning, as long as this is at least 12 hours before the evening dose is due.

Never give a double dose of levetiracetam.

What if I give too much?

You are unlikely to do harm if you give an extra dose of levetiracetam by mistake.
If you think you may have given your child too much levetiracetam, contact your doctor or NHS Direct (0845 4647 in England and Wales; 08454 24 24 24 in Scotland) or take your child to hospital.

Take the medicine container or packaging with you, even if it is empty. This will be useful to the doctor. Have the packaging with you if you telephone for advice.

Are there any possible side-effects?

We use medicines to make our children better, but sometimes they have other effects that we don’t want (side-effects).

Levetiracetam usually causes only mild side-effects or none at all. These should get better as your child’s body gets used to the medicine. If they are still a problem after 2 weeks or you are worried, contact your doctor, but continue to give levetiracetam.

  • Your child’s behaviour may change – they may be drowsy (sleepy), seem less alert than normal and may say they cannot think clearly or remember things. They may develop a tremor (shakiness), or their coordination may be affected (they may seem clumsy). They may also have changes in mood and may be aggressive or hyperactive (more active than usual and finding it hard to relax).
  • Your child may have a decreased appetite, feel sick (nausea) or be sick (vomit) or have stomach ache or diarrhoea (runny poo).
  • Your child may have a headache or feel dizzy.
  • They may develop a rash.

There may, sometimes, be other side-effects that are not listed above. If you notice anything unusual and are concerned, contact your doctor.

Can other medicines be given at the same time as levetiracetam?

  • You can give your child medicines that contain paracetamol or ibuprofen, unless your doctor has told you not to.
  • Check with your doctor or pharmacist before giving any other medicines to your child. This includes herbal or complementary medicines.

Epilepsy and pregnancy

  • Pregnancy presents a risk to both the mother with epilepsy and her unborn baby. If your daughter has sex, it is essential that she uses adequate contraception to prevent an unplanned pregnancy.
  • If your daughter thinks that she may be pregnant, it is important that she sees your family doctor as early as possible. Your daughter should keep taking her medication until she sees her doctor.

Levetiracetam and pregnancy

  • Doctors don’t yet know whether levetiracetam can harm an unborn baby.
  • The oral contraceptive pill can be used safely in women or girls who are taking levetiracetam.

General advice about medicines for seizures

Do not suddenly stop giving any of these medicines to your child, as they may have a seizure. If you are worried, contact your doctor but carry on giving the medicine to your child as usual.

If your child seems to have more seizures than usual, contact your doctor or epilepsy nurse.

  • If your doctor decides to stop a particular medicine, they will discuss this with you. You will usually reduce the dose bit by bit.

Do not change the dose of any drug without talking to your doctor first.

  • It is best that your child always has the same brand of each medicine, as there may be differences between brands. Keep a record of which medicines your child has.
  • Try to give medicines at about the same times every day, to help you remember.
  • Only give the medicine(s) to your child. Never give them to anyone else, even if their condition appears to be the same, as this could do harm.
  • If you think someone else may have taken the medicine by accident, contact your doctor straight away.
  • Make sure that you always have enough medicine. Order a new prescription at least 2 weeks before you will run out.
  • Make sure that the medicines you have at home have not reached the ‘best before’ or ‘use by’ date on the packaging. Give old medicines to your pharmacist to dispose of.

Where I should keep this medicine?

  • Keep the medicine in a cupboard, away from heat and direct sunlight. It does not need to be kept in the fridge.
  • Make sure that children cannot see or reach the medicine.
  • Keep the medicine in the container it came in.

Who to contact for more information

Your doctor, pharmacist or nurse will be able to give you more information about levetiracetam and other medicines used to treat epilepsy.

Keppra Side Effects

Generic Name: levetiracetam

Medically reviewed by Drugs.com. Last updated on Jan 14, 2019.

  • Overview
  • Side Effects
  • Dosage
  • Professional
  • Tips
  • Interactions
  • More

Note: This document contains side effect information about levetiracetam. Some of the dosage forms listed on this page may not apply to the brand name Keppra.

In Summary

Common side effects of Keppra include: infection, neurosis, drowsiness, asthenia, headache, nasopharyngitis, nervousness, abnormal behavior, aggressive behavior, agitation, anxiety, apathy, depersonalization, depression, fatigue, hostility, hyperkinetic muscle activity, personality disorder, emotional lability, irritability, laceration, and mood changes. Other side effects include: tonic clonic epilepsy, dizziness, vertigo, decreased neutrophils, depressed mood, neck pain, and pain. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to levetiracetam: oral solution, oral tablet, oral tablet for suspension, oral tablet extended release

Other dosage forms:

  • intravenous solution

Along with its needed effects, levetiracetam (the active ingredient contained in Keppra) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking levetiracetam:

More common

  • Aggressive or angry
  • anxiety
  • change in personality
  • chills
  • cough or hoarseness
  • crying
  • depersonalization
  • diarrhea
  • dry mouth
  • euphoria
  • fever
  • general feeling of discomfort or illness
  • headache
  • hyperventilation
  • irregular heartbeats
  • irritability
  • joint pain
  • loss of appetite
  • lower back or side pain
  • mental depression
  • muscle aches and pains
  • nausea
  • painful or difficult urination
  • paranoia
  • quick to react or overreact emotionally
  • rapidly changing moods
  • restlessness
  • shaking
  • shivering
  • shortness of breath
  • sleepiness or unusual drowsiness
  • sore throat
  • stuffy or runny nose
  • sweating
  • trouble sleeping
  • unusual tiredness or weakness
  • vomiting

Less common

  • Bloody nose
  • burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
  • clumsiness or unsteadiness
  • discouragement
  • dizziness or lightheadedness
  • double vision
  • earache
  • feeling of constant movement of self or surroundings
  • feeling sad or empty
  • increase in body movements
  • loss of bladder control
  • loss of memory
  • mood or mental changes
  • outburst of anger
  • pain or tenderness around the eyes and cheekbones
  • problems with memory
  • redness or swelling in the ear
  • seizures
  • sensation of spinning
  • shakiness and unsteady walk
  • shakiness in the legs, arms, hands, or feet
  • tightness of the chest
  • tiredness
  • trembling or shaking of the hands or feet
  • trouble concentrating
  • unsteadiness, trembling, or other problems with muscle control or coordination

Incidence not known

  • Attempts at killing oneself
  • being forgetful
  • bleeding gums
  • blistering, peeling, or loosening of the skin
  • bloating
  • blood in the urine or stools
  • bloody, black, or tarry stools
  • blurred vision
  • changes in vision
  • chest pain
  • constipation
  • dark urine
  • difficulty with moving
  • fast heartbeat
  • fever with or without chills
  • general feeling of tiredness or weakness
  • high fever
  • increase in body movements
  • indigestion
  • itching
  • light-colored stools
  • muscle pains or stiffness
  • painful or difficult urination
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • pale skin
  • pinpoint red spots on the skin
  • red skin lesions, often with a purple center
  • red, irritated eyes
  • sores, ulcers, or white spots on the lips or in the mouth
  • stomach pain, continuing
  • swollen glands
  • swollen joints
  • thoughts or attempts at killing oneself
  • trouble with balance
  • twitching, twisting, or uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
  • uncontrolled jerking or twisting movements of the hands, arms, or legs
  • uncontrolled movements of the lips, tongue, or cheeks
  • unexplained bleeding or bruising
  • unusual bleeding or bruising
  • upper right abdominal or stomach pain
  • weight loss
  • yellow eyes or skin

Some side effects of levetiracetam may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Loss of strength or energy
  • muscle pain or weakness
  • pain
  • tender, swollen glands in the neck
  • trouble swallowing
  • unusual weak feeling
  • voice changes

Less common

  • Body aches or pain
  • burning, dry, or itching eyes
  • change in the color of the skin
  • congestion
  • cough increased
  • rash
  • sneezing

Incidence not known

  • Hair loss or thinning of the hair
  • skin rash, encrusted, scaly, and oozing

For Healthcare Professionals

Applies to levetiracetam: intravenous solution, oral solution, oral tablet, oral tablet dispersible, oral tablet extended release

General

The more commonly reported adverse reactions in adults have included somnolence, asthenia, and dizziness; in children, fatigue, aggression, nasal congestion, decreased appetite, and irritability.

Nervous system

Very common (10% or more): Headache (14%), somnolence (14%)

Common (1% to 10%): Dizziness, ataxia, vertigo, paresthesia, coordination difficulties

Postmarketing reports: Choreoathetosis, dyskinesia

Psychiatric

Very Common (10% or more): Non-psychotic behavioral symptoms (up to 38%), psychotic symptoms (up to 17%)

Postmarketing reports: Panic attack

In studies, non-psychotic behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, hyperkinesias, irritability, nervousness, neurosis, and personality disorder) were reported in 13% of adults and 38% of pediatric patients aged 4 to 16 years compared to 6% and 19%, respectively in placebo patients. In patients less than 4 years old, irritability was reported in 12% compared to 0% in placebo patients. In adult patients, behavioral symptoms resulted in dose reduction or discontinuation 0.8% and 1.7% of patients, respectively. Dose reduction or discontinuation due to behavioral symptoms occurred in 11% of pediatric patients.

Hematologic

In adults, 3.2% of patients receiving this drug had at least 1 WBC of 2.8 x 10(9)/L or lower and 2.4% had at least 1 neutrophil count of 1 x 10(9)/L or lower compared to 1.8% and 1.4% of placebo patients, respectively. Of those with a low neutrophil count, only 1 patient did not have resolution with continued treatment. No patient discontinued therapy due to a low neutrophil count. In pediatric patients 4 to 16 years old, mean decreases in WBC and neutrophils were 0.4 x 10(9)/L and 0.3 x 10(9)/L, respectively, compared to small increases in placebo patients. Mean relative lymphocyte counts increased by 1.7% in patients receiving this drug (placebo=decrease of 4%).

Common (1% to 10%): Decreased white blood cell count (WBC), decreased neutrophil count, increased lymphocyte counts, higher eosinophil counts

Frequency not reported: Decreases in white blood cell, neutrophil, and red blood cell counts; decreased in hemoglobin and hematocrit; increases in eosinophil counts

Postmarketing reports: Pancytopenia (with bone marrow suppression reported in some cases), thrombocytopenia, agranulocytosis

Hypersensitivity

Postmarketing reports: Anaphylaxis

Dermatologic

Alopecia reported with this drug resolved with discontinuation of therapy in most cases.

Frequency not reported: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)

Postmarketing reports: Erythema multiforme, alopecia, angioedema

Other

Very common (10% or more): Asthenia (15%), fatigue (10%)

Common (1% to 10%): Pain, vertigo

Respiratory

Common (1% to 10%): Pharyngitis, rhinitis, increased cough, sinusitis

Gastrointestinal

Common (1% to 10%): Diarrhea, gastroenteritis, constipation

Uncommon (0.1% to 1%): Nausea

Postmarketing reports: Pancreatitis

Ocular

Common (1% to 10%): Diplopia

Hepatic

Postmarketing reports: Abnormal liver function tests, hepatic failure, hepatitis

Musculoskeletal

Common (1% to 10%): Neck pain

Postmarketing reports: Muscular weakness

Immunologic

Very common (10% or more): Infection (13%)

Common (1% to 10%): Influenza

Postmarketing reports: Drug reaction with eosinophilia and systemic symptoms (DRESS)

Metabolic

Common (1% to 10%): Anorexia

Postmarketing reports: Weight loss, hyponatremia

Cardiovascular

Very common (10% or more): Increased diastolic blood pressure (less than 4 years of age; 17%)

In a clinical trial in patients 1 month to less than 4 years, 17% of patients had a significantly elevated diastolic blood pressure (placebo=2%). No overall difference in mean diastolic blood pressure was observed in treated patients compared with placebo nor was this effect observed in trials with older pediatric patients or adults.

Renal

Postmarketing reports: Acute kidney injury

1. Cerner Multum, Inc. “UK Summary of Product Characteristics.” O 0

3. “Product Information. Keppra (levetiracetam)” UCB Pharma Inc, Smyrna, GA.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

  • How long does it take to get Keppra out of your system?
  • What is the difference between Briviact and Keppra?

Medical Disclaimer

  • During Pregnancy or Breastfeeding
  • Dosage Information
  • Patient Tips
  • Drug Images
  • Drug Interactions
  • Compare Alternatives
  • Support Group
  • Pricing & Coupons
  • En Español
  • 202 Reviews
  • Generic Availability
  • Drug class: pyrrolidine anticonvulsants
  • FDA Alerts (4)
  • Keppra
  • Keppra (Levetiracetam Injection)
  • Keppra (Levetiracetam Oral Solution)
  • Keppra (Levetiracetam Tablets)
  • Keppra (Advanced Reading)
  • Keppra Intravenous (Advanced Reading)

Other brands: Roweepra, Spritam, Roweepra XR

  • Keppra (AHFS Monograph)
  • … +1 more
  • Keppra XR
  • Seizures
  • Epilepsy

What is Keppra used for?

  • Partial seizures, with or without secondary generalised seizures in adults and children from one month of age with epilepsy. (Keppra can be used on its own to treat people aged 16 years and over with newly diagnosed epilepsy. In children aged one month and over it should be used as an additional medicine when other antiepileptic medicines have failed to fully control the seizures.)
  • Primary generalised tonic-clonic seizures in adults and adolescents from 12 years of age with generalised epilepsy with no known cause (in combination with other treatments).
  • Myoclonic seizures in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy (in combination with other treatments).

How does Keppra work?

Keppra contains the active ingredient levetiracetam, which is a medicine used to treat epilepsy. It works by stabilising electrical activity in the brain.

The brain and nerves are made up of many nerve cells that communicate with each other through electrical signals. These signals must be carefully regulated for the brain and nerves to function properly. When abnormally rapid and repetitive electrical signals are released in the brain, it becomes over-stimulated and normal function is disturbed. This results in fits or seizures.

It is not fully understood how levetiracetam works to control seizures, but its mechanism appears to be different from other antiepileptic medicines.

Levetiracetam may be used on its own, or as an additional treatment, if other antiepileptic medicines have failed to fully control the epileptic seizures.

The medicine can be given as a drip into a vein (intravenous infusion) when administration by mouth is not possible.

Important information about Keppra

  • This medicine may reduce your ability to drive or operate machinery safely. Do not drive or operate machinery until you know how this medicine affects you and you are sure it won’t affect your performance.
  • There may be a small increased risk of depression, suicidal thoughts and behaviour in people taking antiepileptic medicines such as levetiracetam for any condition. For this reason, it is very important to seek medical advice if you, or someone else taking this medicine, experience any changes in mood, distressing thoughts, or feelings about suicide or self-harm at any point while taking this medicine. For more information speak to your doctor or pharmacist.
  • If you have epilepsy it is important to take your medication regularly, as directed by your doctor, because missing doses can trigger seizures in some people. If you have trouble remembering to take your medicine you should ask your pharmacist for advice. You may find a pill reminder box helpful.
  • You should not stop taking this medicine suddenly unless your doctor tells you otherwise, as this may result in your seizures returning or getting worse. If it is decided that you should stop taking this medicine, it should be withdrawn gradually, according to the instructions given by your doctor.

Keppra should be used with caution in

  • Children and adolescents (although available data in children do not suggest an impact of this medicine on growth and puberty, long term effects on learning, intelligence, growth, hormone function, puberty and childbearing potential in children remain unknown).
  • Decreased kidney function.
  • Severely decreased liver function.
  • Keppra injection contains sodium, which should be taken into consideration in people on a low sodium diet.

Keppra should not be used in

  • This medicine is not recommended for children under one month of age, as there is insufficient information about its safety and effectiveness in this age group. Keppra tablets are not suitable for children under six months of age. Keppra intravenous infusion is not recommended for children under four years of age.
  • Keppra oral solution contains maltitol and is not suitable for patients with rare hereditary problems of fructose intolerance.

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

  • The safety of this medicine for use during pregnancy has not been established. The manufacturer states that it is not recommended for use in pregnancy unless considered essential by your doctor. It is very important for women with epilepsy to talk to the doctor responsible for their epilepsy treatment before becoming pregnant. Stopping antiepileptic treatment during pregnancy runs the risk of the mother having seizures, which can harm both the mother and the foetus. This risk may be higher than that from continuing the medication. It is important that all the risks and benefits of treatment are weighed up. Seek medical advice from your doctor.
  • This medicine passes into breast milk. Breastfeeding is not recommended while taking this medicine. Mothers who need to take this medicine should seek medical advice from their doctor.

Possible side effects of Keppra

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

Very common (affect more than 1 in 10 people)

  • Sleepiness.
  • Feeling weak or fatigued.

Common (affect between 1 in 10 and 1 in 100 people)

  • Dizziness or loss of balance.
  • Shaky movements and unsteady walk (ataxia).
  • Headache.
  • Problems with attention or memory.
  • Hyperactivity.
  • Shaking, usually of the hands (tremor).
  • Depression.
  • Unstable moods (emotional lability).
  • Difficulty sleeping (insomnia).
  • Nervousness, agitation.
  • Hostility, irritability, aggression.
  • Personality disorders.
  • Gut disturbances such as abdominal pain, diarrhoea, nausea, vomiting, indigestion.
  • Loss of appetite.
  • Double or blurred vision.
  • Rash or itching.

Unknown frequency

  • Disturbances in the normal numbers of blood cells in the blood.
  • Inflammation of the liver or pancreas.
  • Hair loss.
  • Pins and needles sensations.

The side effects listed above may not include all of the side effects reported by the medicine’s manufacturer. For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

If you think you have experienced a side effect from a medicine or vaccine you should check the patient information leaflet. This lists the known side effects and what to do if you get them. You can also get advice from your doctor, nurse or pharmacist. If they think it’s necessary they’ll report it for you.

You can also report side effects yourself using the yellow card website: www.mhra.gov.uk/yellowcard.

How can Keppra affect other medicines?

No significant interactions have so far been reported with this medicine. However, you should tell your doctor what other medicines you are taking before starting treatment with this medicine, and likewise, check with your doctor or pharmacist before taking any new medicines once you have started treatment. This includes medicines bought without a prescription and herbal medicines.

This medicine does not affect the contraceptive pill.

It is recommended that people who are taking any antiepileptic medicines should avoid taking the herbal remedy St John’s wort (Hypericum perforatum). This is because St John’s wort may affect the level of antiepileptic medicines in the blood and could increase the risk of seizures.

Other medicines containing the same active ingredient

There are currently no other medicines available in the UK that contain levetiracetam as the active ingredient.

Further reading

For background information about our medicine factsheets, including the references used to produce them, .

Last updated 31.01.2010

PMC

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General Information

Keppra is an antiepileptic drug to be used as an adjunctive therapy in adult patients with epilepsy for whom current therapies have not been effective in controlling partial seizures. Partial seizures, which are the most common type of seizures in adults, may be characterized by impaired consciousness, loss of awareness, involuntary motor behaviors, and other non-conscious, involuntary events. For physicians and patients, the attraction of Keppra is that it increases seizure control without adverse interaction with co-administered antiepileptic drugs.

Epilepsy is caused by excessive electrical activity in the brain. Those who suffer from the disorder (2.3 million in America alone) experience recurring seizures. Even with treatment, only about 50% of epilepsy patients have complete control of their seizures, and 600,000 patients do not respond at all to the previously available therapies.

Clinical Results

Three clinical studies compared 3 distinct dosages of Keppra (1000 mg/day, 2000 mg/day, or 3000 mg/day) with a placebo. All of the 1393 epilepsy patients who participated in the trials had continued to experience seizures during the baseline period despite their being treated with 1-2 antiepileptic drugs. Concomitant AED regimens were held constant during administration of Keppra. Effectiveness of the Keppra therapy was measured primarily by reduction in weekly partial seizure frequency for the entire treatment period.

Results of the trials indicated that Keppra significantly reduces the weekly seizure frequency over a placebo. Percent reduction ranged from 17.1% to 30.1% depending on the study number and the dose of Keppra in the treatment. In general, higher doses yielded greater reduction in number of seizures, although results varied over trials.

Another appealing result of the trials was the overall lack of negative interaction when taken in conjunction with other AEDs.

Side Effects

Although Keppra was well tolerated by participants, the following adverse events were reported during trials:

  • somnolence
  • asthenia (lack or loss of strength)
  • infection
  • dizziness

15% of patients receiving Keppra, compared to 11.6% of patients receiving the placebo treatment discontinued therapy or had the dose reduced as a result of an adverse effect.

Exercise caution when giving Keppra to patients with moderate and severe renal impairment and patients undergoing hemodialysis, since levetiracetam is substantially excreted by the kidney.

Mechanism of Action

Keppra is rapidly absorbed after oral administration and food does not affect the extent of bioavailability. Pharmacokinetics are linear and steady state is achieved after two days of multiple twice daily dosing. Keppra is not protein bound (<10 percent bound) and its metabolism is not liver cytochrome P450 dependent, with sixty-six percent (66 percent) of the dose renally excreted unchanged. Plasma half-life of the medication is approximately 6 to 8 hours but is increased in the elderly (due to age-related decrease in renal function) and in patients with renal impairment. Keppra is unlikely to produce, or be subject to, pharmacokinetic drug interactions. (From Doctor’s Guide to Medical and Other News)

Literature References

For more information about epilepsy, visit the official web site of the Epilepsy Foundation, a non-profit volunteer agency devoted to research, education, advocacy, and services in the community for people with epilepsy and their families:

To read more about UCB Pharma, Inc., the company that developed Keppra, visit the UCB web site:

Additional Information

This is what the Epilepsy Foundation says to do and not to do if you encounter a person having an epileptic seizure:

What To Do:

  • Look for medical identification.
  • Protect from nearby hazards.
  • Loosen ties or shirt collars.
  • Protect head from injury.
  • Turn on side to keep airway clear unless injury exists.
  • Reassure as consciousness returns.
  • If a single seizure lasted less than 5 minutes, ask if hospital evaluation wanted.
  • If there are multiple seizures, or if one seizure lasts longer than 5 minutes, call an ambulance.
  • If person is pregnant, injured, or diabetic, call for aid at once.

What Not To Do:

  • Don’t put any hard implement in the mouth.
  • Don’t try to hold tongue. It can’t be swallowed.
  • Don’t try to give liquids during or just after seizure,
  • Don’t use artificial respiration unless breathing is absent after muscle jerks subside, or unless water has been inhaled.
  • Don’t restrain.

CLINICAL PHARMACOLOGY

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. Levetiracetam 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. Levetiracetam 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.

In vitro and in vivo recordings of epileptiform activity from the hippocampus have shown that levetiracetam inhibits burst firing without affecting normal neuronal excitability, suggesting that levetiracetam may selectively prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity.

Levetiracetam at concentrations of up to 10 μM did not demonstrate binding affinity for a variety of known receptors, such as those associated with benzodiazepines, GABA (gamma-aminobutyric acid), glycine, NMDA (N-methyl-Daspartate), re-uptake sites, and second messenger systems. Furthermore, in vitro studies have failed to find an effect of levetiracetam on neuronal voltage-gated sodium or T-type calcium currents and levetiracetam does not appear to directly facilitate GABAergic neurotransmission. However, in vitro studies have demonstrated that levetiracetam opposes the activity of negative modulators of GABA- and glycine-gated currents and partially inhibits N-type calcium currents in neuronal cells.

A saturable and stereoselective neuronal binding site in rat brain tissue has been described for levetiracetam. Experimental data indicate that this binding site is the synaptic vesicle protein SV2A, thought to be involved in the regulation of vesicle exocytosis. Although the molecular significance of levetiracetam binding to 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. These findings suggest that the interaction of levetiracetam with the SV2A protein may contribute to the antiepileptic mechanism of action of the drug.

Pharmacodynamics

Effects On QTc Interval

The effect of KEPPRA on QTc prolongation was evaluated in a randomized, double-blind, positive-controlled (moxifloxacin 400 mg) and placebo-controlled crossover study of KEPPRA (1000 mg or 5000 mg) in 52 healthy subjects. The upper bound of the 90% confidence interval for the largest placebo-adjusted, baseline-corrected QTc was below 10 milliseconds. Therefore, there was no evidence of significant QTc prolongation in this study.

Pharmacokinetics

Absorption And Distribution

Absorption of levetiracetam is rapid, with peak plasma concentrations occurring in about an hour following oral administration in fasted subjects. The oral bioavailability of levetiracetam tablets is 100% and the tablets and oral solution are bioequivalent in rate and extent of absorption. Food does not affect the extent of absorption of levetiracetam but it decreases Cmax by 20% and delays Tmax by 1.5 hours. The pharmacokinetics of levetiracetam are linear over the dose range of 500-5000 mg. Steady state is achieved after 2 days of multiple twice-daily dosing. Levetiracetam and its major metabolite are less than 10% bound to plasma proteins; clinically significant interactions with other drugs through competition for protein binding sites are therefore unlikely.

Metabolism

Levetiracetam is not extensively metabolized in humans. The major metabolic pathway is the enzymatic hydrolysis of the acetamide group, which produces the carboxylic acid metabolite, ucb L057 (24% of dose) and is not dependent on any liver cytochrome P450 isoenzymes. The major metabolite is inactive in animal seizure models. Two minor metabolites were identified as the product of hydroxylation of the 2-oxo-pyrrolidine ring (2% of dose) and opening of the 2-oxo-pyrrolidine ring in position 5 (1% of dose). There is no enantiomeric interconversion of levetiracetam or its major metabolite.

Elimination

Levetiracetam plasma half-life in adults is 7 ± 1 hour and is unaffected by either dose or repeated administration. Levetiracetam is eliminated from the systemic circulation by renal excretion as unchanged drug which represents 66% of administered dose. The total body clearance is 0.96 mL/min/kg and the renal clearance is 0.6 mL/min/kg. The mechanism of excretion is glomerular filtration with subsequent partial tubular reabsorption. The metabolite ucb L057 is excreted by glomerular filtration and active tubular secretion with a renal clearance of 4 mL/min/kg. Levetiracetam elimination is correlated to creatinine clearance. Levetiracetam clearance is reduced in patients with renal impairment .

Specific Populations

Elderly

Pharmacokinetics of levetiracetam were evaluated in 16 elderly subjects (age 61-88 years) with creatinine clearance ranging from 30 to 74 mL/min. Following oral administration of twice-daily dosing for 10 days, total body clearance decreased by 38% and the half-life was 2.5 hours longer in the elderly compared to healthy adults. This is most likely due to the decrease in renal function in these subjects.

Pediatric Patients

Pharmacokinetics of levetiracetam were evaluated in 24 pediatric patients (age 6-12 years) after single dose (20 mg/kg). The body weight adjusted apparent clearance of levetiracetam was approximately 40% higher than in adults.

A repeat dose pharmacokinetic study was conducted in pediatric patients (age 4-12 years) at doses of 20 mg/kg/day, 40 mg/kg/day, and 60 mg/kg/day. The evaluation of the pharmacokinetic profile of levetiracetam and its metabolite (ucb L057) in 14 pediatric patients demonstrated rapid absorption of levetiracetam at all doses with a Tmax of about 1 hour and a t½ of 5 hours across the three dosing levels. The pharmacokinetics of levetiracetam in children was linear between 20 to 60 mg/kg/day. The potential interaction of levetiracetam with other AEDs was also evaluated in these patients. Levetiracetam had no significant effect on the plasma concentrations of carbamazepine, valproic acid, topiramate or lamotrigine. However, there was about a 22% increase of apparent clearance of levetiracetam when it was co-administered with an enzyme-inducing AED (e.g. carbamazepine).

Following single dose administration (20 mg/kg) of a 10% oral solution to children with epilepsy (1 month to < 4 years), levetiracetam was rapidly absorbed and peak plasma concentrations were observed approximately 1 hour after dosing. The pharmacokinetic results indicated that half-life was shorter (5.3 h) than for adults (7.2 h) and apparent clearance was faster (1.5 mL/min/kg) than for adults (0.96 mL/min/kg).

Population pharmacokinetic analysis showed that body weight was significantly correlated to the clearance of levetiracetam in pediatric patients; clearance increased with an increase in body weight.

Pregnancy

Levetiracetam levels may decrease during pregnancy.

Gender

Levetiracetam Cmax and AUC were 20% higher in women (N=11) compared to men (N=12). However, clearances adjusted for body weight were comparable.

Race

Formal pharmacokinetic studies of the effects of race have not been conducted. Cross-study comparisons involving Caucasians (N=12) and Asians (N=12), however, show that pharmacokinetics of levetiracetam were comparable between the two races. Because levetiracetam is primarily renally excreted and there are no important racial differences in creatinine clearance, pharmacokinetic differences due to race are not expected.

Renal Impairment

The disposition of levetiracetam was studied in adult subjects with varying degrees of renal function. Total body clearance of levetiracetam is reduced in patients with impaired renal function by 40% in the mild group (CLcr = 50-80 mL/min), 50% in the moderate group (CLcr = 30-50 mL/min) and 60% in the severe renal impairment group (CLcr <30 mL/min). Clearance of levetiracetam is correlated with creatinine clearance.

In anuric (end stage renal disease) patients, the total body clearance decreased 70% compared to normal subjects (CLcr >80 mL/min). Approximately 50% of the pool of levetiracetam in the body is removed during a standard 4- hour hemodialysis procedure .

Hepatic Impairment

In subjects with mild (Child-Pugh A) to moderate (Child-Pugh B) hepatic impairment, the pharmacokinetics of levetiracetam were unchanged. In patients with severe hepatic impairment (Child-Pugh C), total body clearance was 50% that of normal subjects, but decreased renal clearance accounted for most of the decrease. No dose adjustment is needed for patients with hepatic impairment.

Drug Interactions

In vitro data on metabolic interactions indicate that levetiracetam is unlikely to produce, or be subject to, pharmacokinetic interactions. Levetiracetam and its major metabolite, at concentrations well above Cmax 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.

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

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. Â There also was no effect on exposure to and the excretion of the primary metabolite, ucb L057.

Other Antiepileptic Drugs

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.

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. Css max 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.

Clinical Studies

Partial Onset Seizures

Effectiveness In Partial Onset Seizures In Adults With Epilepsy

The effectiveness of KEPPRA as adjunctive therapy (added to other antiepileptic drugs) in adults was established in three multicenter, randomized, double-blind, placebo-controlled clinical studies in patients who had refractory partial onset seizures with or without secondary generalization. The tablet formulation was used in all these studies. In these studies, 904 patients were randomized to placebo, 1000 mg, 2000 mg, or 3000 mg/day. Patients enrolled in Study 1 or Study 2 had refractory partial onset seizures for at least two years and had taken two or more classical AEDs. Patients enrolled in Study 3 had refractory partial onset seizures for at least 1 year and had taken one classical AED. At the time of the study, patients were taking a stable dose regimen of at least one and could take a maximum of two AEDs. During the baseline period, patients had to have experienced at least two partial onset seizures during each 4-week period.

Study 1

Study 1 was a double-blind, placebo-controlled, parallel-group study conducted at 41 sites in the United States comparing KEPPRA 1000 mg/day (N=97), KEPPRA 3000 mg/day (N=101), and placebo (N=95) given in equally divided doses twice daily. After a prospective baseline period of 12 weeks, patients were randomized to one of the three treatment groups described above. The 18-week treatment period consisted of a 6-week titration period, followed by a 12-week fixed dose evaluation period, during which concomitant AED regimens were held constant. The primary measure of effectiveness was a between group comparison of the percent reduction in weekly partial seizure frequency relative to placebo over the entire randomized treatment period (titration + evaluation period). Secondary outcome variables included the responder rate (incidence of patients with ≥ 50% reduction from baseline in partial onset seizure frequency). The results of the analysis of Study 1 are displayed in Table 10.

Table 10: Reduction in Mean Over Placebo in Weekly Frequency of Partial Onset Seizures in Study 1

The percentage of patients (y-axis) who achieved ≥ 50% reduction in weekly seizure rates from baseline in partial onset seizure frequency over the entire randomized treatment period (titration + evaluation period) within the three treatment groups (x-axis) is presented in Figure 1.

Figure 1: Responder Rate (≥ 50% Reduction from Baseline) in Study 1

Study 2

The first period of the study (Period A) was designed to be analyzed as a parallel-group study. After a prospective baseline period of up to 12 weeks, patients were randomized to one of the three treatment groups described above. The 16-week treatment period consisted of the 4-week titration period followed by a 12-week fixed dose evaluation period, during which concomitant AED regimens were held constant. The primary measure of effectiveness was a between group comparison of the percent reduction in weekly partial seizure frequency relative to placebo over the entire randomized treatment period (titration + evaluation period). Secondary outcome variables included the responder rate (incidence of patients with ≥ 50% reduction from baseline in partial onset seizure frequency). The results of the analysis of Period A are displayed in Table 11.

Table 11: Reduction in Mean Over Placebo in Weekly Frequency of Partial Onset Seizures in Study 2: Period A

The percentage of patients (y-axis) who achieved ≥ 50% reduction in weekly seizure rates from baseline in partial onset seizure frequency over the entire randomized treatment period (titration + evaluation period) within the three treatment groups (x-axis) is presented in Figure 2.

Figure 2: Responder Rate (≥ 50% Reduction from Baseline) in Study 2: Period A

The comparison of KEPPRA 2000 mg/day to KEPPRA 1000 mg/day for responder rate was statistically significant (P=0.02). Analysis of the trial as a cross-over yielded similar results.

Study 3

Study 3 was a double-blind, placebo-controlled, parallel-group study conducted at 47 centers in Europe comparing KEPPRA 3000 mg/day (N=180) and placebo (N=104) in patients with refractory partial onset seizures, with or without secondary generalization, receiving only one concomitant AED. Study drug was given in two divided doses. After a prospective baseline period of 12 weeks, patients were randomized to one of two treatment groups described above. The 16-week treatment period consisted of a 4-week titration period, followed by a 12-week fixed dose evaluation period, during which concomitant AED doses were held constant. The primary measure of effectiveness was a between group comparison of the percent reduction in weekly seizure frequency relative to placebo over the entire randomized treatment period (titration + evaluation period). Secondary outcome variables included the responder rate (incidence of patients with ≥ 50% reduction from baseline in partial onset seizure frequency). Table 12 displays the results of the analysis of Study 3.

Table 12: Reduction in Mean Over Placebo in Weekly Frequency of Partial Onset Seizures in Study 3

Placebo (N=104) KEPPRA 3000 mg/day (N=180)
Percent reduction in partial seizure frequency over placebo 23.0%*
*statistically significant versus placebo

The percentage of patients (y-axis) who achieved ≥ 50% reduction in weekly seizure rates from baseline in partial onset seizure frequency over the entire randomized treatment period (titration + evaluation period) within the two treatment groups (x-axis) is presented in Figure 3.

Figure 3: Responder Rate (≥ 50% Reduction from Baseline) in Study 3

Effectiveness In Partial Onset Seizures In Pediatric Patients 4 Years To 16 Years With Epilepsy

The effectiveness of KEPPRA as adjunctive therapy (added to other antiepileptic drugs) in pediatric patients was established in one multicenter, randomized double-blind, placebo-controlled study (Study 4), conducted at 60 sites in North America, in pediatric patients 4 to 16 years of age with partial seizures uncontrolled by standard antiepileptic drugs (AEDs). Eligible patients on a stable dose of 1-2 AEDs, who still experienced at least 4 partial onset seizures during the 4 weeks prior to screening, as well as at least 4 partial onset seizures in each of the two 4-week baseline periods, were randomized to receive either KEPPRA or placebo. The enrolled population included 198 patients (KEPPRA N=101, placebo N=97) with refractory partial onset seizures, whether or not secondarily generalized. The study consisted of an 8-week baseline period and 4-week titration period followed by a 10-week evaluation period. Dosing was initiated at a dose of 20 mg/kg/day in two divided doses. During the treatment period, KEPPRA doses were adjusted in 20 mg/kg/day increments, at 2-week intervals to the target dose of 60 mg/kg/day. The primary measure of effectiveness was a between group comparison of the percent reduction in weekly partial seizure frequency relative to placebo over the entire 14-week randomized treatment period (titration + evaluation period). Secondary outcome variables included the responder rate (incidence of patients with ≥ 50% reduction from baseline in partial onset seizure frequency per week). Table 13 displays the results of this study.

Table 13: Reduction in Mean Over Placebo in Weekly Frequency of Partial Onset Seizures in Study 4

Placebo
(N=97)
KEPPRA
(N=101)
Percent reduction in partial seizure frequency over placebo 26.8%*
*statistically significant versus placebo

The percentage of patients (y-axis) who achieved ≥ 50% reduction in weekly seizure rates from baseline in partial onset seizure frequency over the entire randomized treatment period (titration + evaluation period) within the two treatment groups (x-axis) is presented in Figure 4.

Figure 4: Responder Rate (≥ 50% Reduction from Baseline) in Study 4

Effectiveness In Partial Onset Seizures In Pediatric Patients 1 Month To <4 Years With Epilepsy

The effectiveness of KEPPRA as adjunctive therapy in pediatric patients was established in one multicenter, randomized double-blind, placebo-controlled study (Study 5), conducted at 62 sites in North America, South America, and Europe in pediatric patients 1 month to less than 4 years of age with partial seizures, uncontrolled by standard epileptic drugs (AEDs). Eligible patients on a stable dose of 1-2 AEDs, who experienced at least 2 partial onset seizures during the 48-hour baseline video EEG were randomized to receive either KEPPRA or placebo. The enrolled population included 116 patients (KEPPRA N=60, placebo N=56) with refractory partial onset seizures, whether or not secondarily generalized. Randomization was stratified by age range as follows: 1 month to less than 6 months of age (N=4 treated with KEPPRA), 6 months to less than 1 year of age (N=8 treated with KEPPRA), 1 year to less than 2 years of age (N=20 treated with KEPPRA), and 2 years to less than 4 years of age (N=28 treated with KEPPRA). The study consisted of a 5-day evaluation period which included a 1-day titration period followed by a 4-day maintenance period. KEPPRA dosing was determined by age and weight as follows: children 1 month to less than 6 months old were randomized to a target dose of 40 mg/kg/day, and children 6 months to less than 4 years old were randomized to a target dose of 50 mg/kg/day. The primary measure of effectiveness was the responder rate (percent of patients with ≥ 50% reduction from baseline in average daily partial onset seizure frequency) assessed by a blinded central reader using a 48-hour video EEG performed during the last two days of the 4-day maintenance period. A total of 109 patients were included in the efficacy analysis. A statistically significant difference between KEPPRA and placebo was observed (see Figure 5). The treatment effect associated with KEPPRA was consistent across age groups.

Figure 5: Responder Rate for All Patients Ages 1 Month to < 4 Years (≥ 50% Reduction from Baseline) in Study 5

Myoclonic Seizures In Patients With Juvenile Myoclonic Epilepsy

Effectiveness Of Myoclonic Seizures In Patients ≥12 Years Of Age With Juvenile Myoclonic Epilepsy (JME)

The effectiveness of KEPPRA as adjunctive therapy (added to other antiepileptic drugs) in patients 12 years of age and older with juvenile myoclonic epilepsy (JME) experiencing myoclonic seizures was established in one multicenter, randomized, double-blind, placebo-controlled study (Study 6), conducted at 37 sites in 14 countries. Of the 120 patients enrolled, 113 had a diagnosis of confirmed or suspected JME. Eligible patients on a stable dose of 1 antiepileptic drug (AED) experiencing one or more myoclonic seizures per day for at least 8 days during the prospective 8-week baseline period were randomized to either KEPPRA or placebo (KEPPRA N=60, placebo N=60). Patients were titrated over 4 weeks to a target dose of 3000 mg/day and treated at a stable dose of 3000 mg/day over 12 weeks (evaluation period). Study drug was given in 2 divided doses.

The primary measure of effectiveness was the proportion of patients with at least 50% reduction in the number of days per week with one or more myoclonic seizures during the treatment period (titration + evaluation periods) as compared to baseline. Table 14 displays the results for the 113 patients with JME in this study.

Table 14: Responder Rate (≥ 50% Reduction from Baseline) in Myoclonic Seizure Days per Week for Patients with JME in Study 6

Placebo
(N=59)
KEPPRA
(N=54)
Percentage of responders 23.7% 60.4%*
*statistically significant versus placebo

Primary Generalized Tonic-Clonic Seizures

Effectiveness In Primary Generalized Tonic-Clonic Seizures In Patients ≥ 6 Years Of Age

The effectiveness of KEPPRA as adjunctive therapy (added to other antiepileptic drugs) in patients 6 years of age and older with idiopathic generalized epilepsy experiencing primary generalized tonic-clonic (PGTC) seizures was established in one multicenter, randomized, double-blind, placebo-controlled study (Study 7), conducted at 50 sites in 8 countries. Eligible patients on a stable dose of 1 or 2 antiepileptic drugs (AEDs) experiencing at least 3 PGTC seizures during the 8-week combined baseline period (at least one PGTC seizure during the 4 weeks prior to the prospective baseline period and at least one PGTC seizure during the 4-week prospective baseline period) were randomized to either KEPPRA or placebo. The 8-week combined baseline period is referred to as “baseline” in the remainder of this section. Patients were titrated over 4 weeks to a target dose of 3000 mg/day for adults or a pediatric target dose of 60 mg/kg/day and treated at a stable dose of 3000 mg/day (or 60 mg/kg/day for children) over 20 weeks (evaluation period). Study drug was given in 2 equally divided doses per day. The primary measure of effectiveness was the percent reduction from baseline in weekly PGTC seizure frequency for KEPPRA and placebo treatment groups over the treatment period (titration + evaluation periods). The population included 164 patients (KEPPRA N=80, placebo N=84) with idiopathic generalized epilepsy (predominately juvenile myoclonic epilepsy, juvenile absence epilepsy, childhood absence epilepsy, or epilepsy with Grand Mal seizures on awakening) experiencing primary generalized tonic-clonic seizures. Each of these syndromes of idiopathic generalized epilepsy was well represented in this patient population.

There was a statistically significant decrease from baseline in PGTC frequency in the KEPPRA-treated patients compared to the placebo-treated patients.

Table 15: Median Percent Reduction from Baseline in PGTC Seizure Frequency per Week in Study 7

The percentage of patients (y-axis) who achieved ≥ 50% reduction in weekly seizure rates from baseline in PGTC seizure frequency over the entire randomized treatment period (titration + evaluation period) within the two treatment groups (x-axis) is presented in Figure 6.

Figure 6: Responder Rate (≥ 50% Reduction from Baseline) in PGTC Seizure Frequency per Week in Study 7

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