Levetiracetam

Levetiracetam is a drug used to treat epilepsy. It belongs to a group of drugs called antiepileptics, which work by reducing the number and severity of seizures.

Use & indications

Levetiracetam is used alone (monotherapy), without other anti-epilepsy medications, to treat a certain type of epilepsy (partial seizures that initially affect only one side of the brain) in adults and adolescents 16 years of age and older.

Levetiracetam can also be used as an add-on treatment, meaning it is used in combination with other medications to control seizures that are not well controlled by those other medications alone.

Indications as an add-on treatment include:

• partial seizures with or without secondary generalization in adults, adolescents, children, and infants 1 month of age and older
• myoclonic seizures (brief shock-like twitching of a muscle or muscle group) in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy
• Primary generalized tonic-clonic seizures (pronounced seizures, including loss of consciousness) in adults and adolescents 12 years of age and older with idiopathic generalized epilepsy (a hereditary form of epilepsy)

The dosage of levetiracetam is usually 250, 500, 750, or 1000 mg when taken as film-coated tablets. The dosing interval here is usually 2 intakes per day. Levetiracetam is also available as an oral solution and in the form of concentrates for the preparation of infusion solutions.

Levetiracetam is available by prescription throughout the European Union.

History

Levetiracetam is a modification (derivative) of the substance piracetam, which was used in the past in the treatment of dementia. Levetiracetam was developed by the Belgian pharmaceutical company UCB S.A and patented in 1985.

Pharmacodynamics/Mechanism of action

The exact mechanism by which levetiracetam exerts its antiepileptic effects is unclear, but it is believed that the compound does not act like other common antiepileptic drugs. Current knowledge suggests that binding of levetiracetam to synaptic vesicle protein 2A (SV2A) is a major factor in its effects. SV2A is a membrane-bound protein found on synaptic vesicles and is found throughout the CNS. It appears to play a role in vesicle exocytosis and in modulating synaptic transmission by increasing the amount of secretory vesicles available for neurotransmission. Stimulation of presynaptic SV2A by levetiracetam can inhibit neurotransmitter release, although this effect does not appear to affect normal neurotransmission. That is, levetiracetam exclusively modulates SV2A function under pathophysiologic conditions, thus exerting an effect only when epilepsy is present.

Pharmacokinetics

Levetiracetam is rapidly and almost completely absorbed after oral administration, with absolute oral bioavailability approaching 100%. Levetiracetam and its metabolites are largely unbound to plasma proteins. Levetiracetam is minimally metabolized in the body. The main major metabolite is formed by hydrolysis in tissues. Approximately 66% of the administered dose of levetiracetam is excreted in the urine as unchanged drug, while only 0.3% of the total dose is excreted in the feces. The plasma half-life of levetiracetam is 6-8 hours and is not affected by dose or repeated administration.

Drug Interactions

The lack of metabolism in the liver makes this agent particularly well suited for combination with other antiepileptic drugs and other medications, as this prevents interactions from occurring.

Contraindications

If allergy to levetiracetam or other pyrrolidone derivatives exists, this drug should not be taken.

Side effects

• inflammation of the nasopharynx
• drowsiness
• loss of appetite
• depression, hostility or aggression, anxiety, insomnia, nervousness, or irritability
• cramps (convulsions), balance problems, dizziness (feeling shaky), lack of energy and enthusiasm (lethargy), involuntary tremor (tremor)
• Spinning dizziness;
• Cough;
• abdominal pain, diarrhea (diarrhea)
• Skin rash
• Asthenia
• Decreased platelet count, decreased white blood cell count;
• Weight loss, weight gain;
• Suicide attempt and suicidal ideation, mental disorders, abnormal behavior, hallucination, anger, confusion, panic attack, emotional instability/mood swings, agitation;
• Memory loss (amnesia), impaired memory (forgetfulness), incoordination/ataxia (lack of coordination of movements), tingling (paresthesia), attention deficit (difficulty concentrating);
• Double vision (diplopia), blurred vision;
• Increased/abnormal values in liver function tests;
• Hair loss, eczema, itching;
• Muscle weakness, myalgia (muscle pain);
• Injury
• Infection;
• Decreased numbers of all types of blood cells;
• serious allergic reactions (DRESS, anaphylactic reaction, Quincke's edema)
• Decreased sodium concentration in the blood;
• Suicide, personality disorders (behavioral disorders), abnormal thinking (slow thinking, inability to concentrate);
• Delirium (febrile delirium);
• Encephalopathy (a specific abnormal condition of the brain; see the subsection "Talk to Your Doctor Immediately" for a detailed description of symptoms);
• Worsening of seizures or increase in their frequency;
• Involuntary and unsuppressible spasmodic tightening of muscles affecting the head, trunk, and limbs; difficulty controlling movements; hyperkinesia (overactivity);
• alteration of heart rhythm
• inflammation of the pancreas
• liver failure, liver inflammation
• sudden decrease in kidney function;
• Rhabdomyolysis (breakdown of muscle tissue) and associated increased creatine phosphokinase in the blood. The incidence in Japanese patients is significantly higher than in non-Japanese patients
• Limping or difficulty walking

Pregnancy and Lactation

Levetiracetam should be used during pregnancy only if deemed necessary by the prescribing physician after careful consideration. Breastfeeding is not recommended during treatment.