Today's drug is levetiracetam.
What is levetoracetam indicated for?
INDICATIONS :
- It is indicated as adjunctive therapy in the treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.
- It is indicated as adjunctive therapy in the treatment of myoclonic seizures (sudden, brief, shock-like muscle contraction) in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy (epilepsy that typically begins during adolescence or late childhood and is marked by myoclonic seizures which occur shortly after awakening and are often followed by tonic-clonic seizures or sometimes by absence seizure).
- It is also indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures (a seizure of the entire body, characterized by muscle rigidity, violent rhythmic contractions, and loss of consciousness, with abnormal electric activity in neurons) in adults and children 6 years of age and older with idiopathic generalized epilepsy.
MECHANISMS OF ACTION :
- It is an anticonvulsant used in the treatment of partial seizures.
- The precise mechanism of anticonvulsant effect is unknown.
How is levetiracetam being used?
ROUTE OF ADMINISTRATION :
- It can be taken orally as tablets or intravenously.
- It is administered intravenously as adjunct in patients with partial seizures and as monotherapy for patients with partial seizures with or without secondary generalisation.
- It can be taken orally with or without food.
- Levetiracetam tablets should be swallowed whole. The tablets should not be chewed or crushed.
Is there any contraindication?
CONTRAINDICATIONS :
- This product should not be administered to patients who have previously exhibited hypersensitivity to levetiracetam.
Are there any possible side effects?
SIDE EFFECTS :
SIDE EFFECTS :
- Somnolence (a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods.)
- Asthenia (aka weakness)
- Dizziness & vertigo (feeling that the environment is moving or spinning),
- Depression, emotional instability, hostility (a form of angry internal rejection or denial in psychology), nervousness
- Ataxia (a lack of coordination while performing voluntary movements), tremor (unintentional trembling or shaking movements in one or more parts of your body), amnesia (condition in which one's memory is lost)
- Headache, nausea, dyspepsia (upset stomach or indigestion), diarrhoea, anorexia, rash, diplopia.
What precautions are necessary?
PRECAUTIONS :
(i) Psychiatric Reactions
- In some patients taking levetiracetam causes behavioral abnormalities such as aggressive behaviour. Some patients also experienced non-psychotic behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, hyperkinesias, irritability, nervousness, neurosis, and personality disorder).
- The above psychiatric signs symptoms should be monitored.
(ii) Suicidal Behavior and Ideation
- Antiepileptic drugs (AEDs), including levetiracetam, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
- Anyone considering prescribing levetiracetam or any other AED must balance the risk of suicidal thoughts or behaviors with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
- Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
(iii) Somnolence and Fatigue
- In some patients, levetiracetam causes somnolence and fatigue.
- Somnolence and asthenia occurred most frequently within the first 4 weeks of treatment.
- Patients should be monitored for these signs symptoms and advised not to drive or operate machinery until they have gained sufficient experience on levetiracetam to gauge whether it adversely affects their ability to drive or operate machinery.
(iv) Serious Dermatological Reactions
- Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in both children and adults treated with levetiracetam.
- The median time of onset is reported to be 14 to 17 days, but cases have been reported at least four months after initiation of treatment.
- Recurrence of the serious skin reactions following rechallenge with levetiracetam has also been reported.
- Levetiracetam should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related.
- If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered.
(v) Coordination Difficulties
- Coordination difficulties were only observed in the adult partial onset seizure studies.
- These events occurred most frequently within the first 4 weeks of treatment.
- Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on levetiracetam to gauge whether it could adversely affect their ability to drive or operate machinery.
(vi) Withdrawal Seizures
- Antiepileptic drugs, including levetiracetam, should be withdrawn gradually to minimize the potential of increased seizure frequency.
(vii) Hematologic Abnormalities
Partial Onset Seizures
Adults
- Minor, but statistically significant, decreases compared to placebo in total mean RBC count (0.03 x 106/mm³), mean hemoglobin (0.09 g/dL), and mean hematocrit (0.38%), were seen in levetiracetam-treated patients in controlled trials.
- A total of 3.2% of treated and 1.8% of placebo patients had at least one possibly significant ( ≤ 2.8 x 109/L) decreased WBC, and 2.4% of treated and 1.4% of placebo patients had at least one possibly significant ( ≤ 1.0 x 109/L) decreased neutrophil count. Of the treated patients with a low neutrophil count, all but one rose towards or to baseline with continued treatment. No patient was discontinued secondary to low neutrophil counts.
Pediatric Patients 4 Years To < 16 Years
- Statistically significant decreases in WBC and neutrophil counts were seen in levetiracetam-treated patients as compared to placebo. The mean decreases from baseline in the levetiracetam-treated group were -0.4 × 109/L and 0.3 × 109/L, respectively, whereas there were small increases in the placebo group. Mean relative lymphocyte counts increased by 1.7% in levetiracetam-treated patients, compared to a decrease of 4% in placebo patients (statistically significant).
- In the controlled trial, more levetiracetam-treated patients had a possibly clinically significant abnormally low WBC value (3.0% levetiracetam-treated versus 0% placebo), however, there was no apparent difference between treatment groups with respect to neutrophil count (5.0% levetiracetam-treated versus 4.2% placebo). No patient was discontinued secondary to low WBC or neutrophil counts.
- In the controlled cognitive and neuropsychological safety study, two subjects (6.1%) in the placebo group and 5 subjects (8.6%) in the levetiracetam-treated group had high eosinophil count values that were possibly clinically significant ( ≥ 10% or ≥ 0.7X109/L).
(viii) Juvenile Myoclonic Epilepsy
- Although there were no obvious hematologic abnormalities observed in patients with JME, the limited number of patients makes any conclusion tentative. The data from the partial seizure patients should be considered to be relevant for JME patients.
(ix) Blood Pressure Increases
- In a randomized, placebo-controlled study in patients aged 1 month to < 4 years of age, a significantly higher risk of at least one measured increase in diastolic blood pressure was observed in the levetiracetam-treated patients (17%) compared to the placebo-treated patients (2%). There was no overall difference in mean diastolic blood pressure between the treatment groups. This disparity between the levetiracetam and placebo treatment groups was not observed in the studies of older children or in adults.
(x) Seizure Control During Pregnancy
- Physiological changes may gradually decrease plasma levels of levetiracetam throughout pregnancy. This decrease is more pronounced during the third trimester. It is recommended that patients be monitored carefully during pregnancy. Close monitoring should continue through the postpartum period especially if the dose was changed during pregnancy
DRUG INTERACTIONS :
- No significant pharmacokinetic interactions were observed between levetiracetam or its major metabolite and concomitant medications via human liver cytochrome P450 isoforms, epoxide hydrolase, UDP-glucuronidation enzymes, P-glycoprotein, or renal tubular secretion .
Pregnancy and breastfeeding:
- Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
- Levetiracetam is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from levetiracetam, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
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