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MINT-LEVETIRACETAM is a brand name for Levetiracetam, supplied as a solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: MINT-LEVETIRACETAM SOLUTION (levetiracetam oral solution) is indicated as: • adjunctive therapy in the management of patients with epilepsy who are not satisfactorily controlled by conventional therapy. 1.1 Pediatrics MINT-LEVETIRACETAM SOLUTION is indicated in pediatric patients as adjunctive therapy in the treatment…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations MINT-LEVETIRACETAM SOLUTION is only available in the form of an oral solution. d). Depending on the clinical response and tolerability, the daily dose may be increased every two weeks by increments of 1000 mg, to a maximum recommended daily dose of 3000 mg daily.
In clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice daily dosing were shown to be effective. Although there was a tendency towards a greater response rate with higher doses, a consistent statistically significant increase in response with increased dose has not been shown.
There are limited safety data from controlled clinical trials at doses higher than 3000 mg/day (approximately 40 patients), therefore these doses are not recommended. Elderly Patients (65 years and older) Dose selection and titration should proceed cautiously in elderly patients, as renal function decreases with age.
Accordingly, adjustment of the dose is recommended in elderly patients with compromised renal function (see below). Dosage Adjustments in Adult Patients with Impaired Renal Function Renal excretion of unchanged drug accounts for approximately 66% of administered levetiracetam dose.
Consistent with this, MINT-LEVETIRACETAM SOLUTION dosage should be reduced in patients with impaired renal function (see Table 1 below). Patients with end stage renal disease should receive supplemental doses following dialysis. To use this dosing table, an estimate of the patient’s creatinine clearance (ClCr) in mL/min is needed.
The ClCr in mL/min may be estimated from serum creatinine (mg/dL). 73 m2) Dosage and Frequency End-stage renal disease patients undergoing dialysis (1) (2) - 500 to 1000 mg once daily (1) A 750 mg loading dose is recommended on the first day of treatment with levetiracetam.
(2)Following dialysis, a 250 to 500 mg supplemental dose is recommended *or according to best clinical judgement Dosage Adjustments in Adult Patients with Impaired Hepatic Function No dose adjustment is needed in patients with mild to moderate hepatic impairment.
In patients with severe hepatic impairment, the creatinine clearance may underestimate the renal insufficiency. 73 m2. Pediatrics Pediatric weight-based dosing for add-on therapy in children aged <12 years and adolescents (12-17 years) weighing <50 kg.
1 Adverse Reaction Overview In well-controlled clinical studies, the most frequently reported adverse events associated with the use MINT-LEVETIRACETAM SOLUTION (Product Monograph) Page 17 of 48 Protected B / Protégé B of levetiracetam in combination with other AEDs, not seen at an equivalent frequency among placebo- treated patients, were somnolence, asthenia, dizziness, infection; and most notably in pediatrics, altered mood and behaviour, as well as decreased appetite.
Of the most frequently reported adverse events, asthenia, somnolence and dizziness appeared to occur predominantly during the first four weeks of treatment with levetiracetam. 2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. Adults The partial onset seizure data below are representative of the adverse event findings from other seizure types.
Central Nervous System Adverse Reactions Levetiracetam use is associated with the occurrence of central nervous system (CNS) adverse events; the most significant of these can be classified into 3 main categories: 1) somnolence and fatigue 2) behavioural/psychiatric, and 3) coordination difficulties.
There was no clear dose response relationship for any of the three categories of CNS adverse events, within the recommended dose range of up to 3000 mg/day. Somnolence/asthenia and coordination difficulties occurred most frequently within the first 4 weeks of treatment, and usually resolved while patients remained on treatment.
In the case of behavioural/psychiatric symptoms (including such adverse events as aggression, agitation, anger, anxiety, emotional lability, hostility, and irritability), approximately half of the patients reported these events within the first 4 weeks, with the remaining events occurring throughout the duration of the trials.
General MINT-LEVETIRACETAM SOLUTION is contraindicated in patients who are hypersensitive to pyrrolidine derivatives. Reactions have included anaphylaxis and angioedema (see 7 WARNINGS AND PRECAUTIONS, Immune) Carcinogenesis and Mutagenesis See section 16 NON-CLINICAL TOXICOLOGY for a discussion on animal data.
Cardiovascular QT Prolongation The effect of levetiracetam on the QTc interval was evaluated in a randomized, double- blind, placebo and positive-controlled, single-dose, four-way crossover study of levetiracetam (1000 mg or 5000 mg) in 52 healthy subjects.
5 h after dosing. Rare cases of ECG QT interval prolongation have been observed during post-marketing surveillance in patients with and without a prior history of cardiac conditions. 5 Post-Market Adverse Reactions). Increase in Blood Pressure in Patients < 4 years of age.
In a randomized, placebo-controlled study in patients 1 month to ˂ 4 years of age, a significantly higher risk of increased diastolic blood pressure was observed in levetiracetam-treated patients (17%), MINT-LEVETIRACETAM SOLUTION (Product Monograph) Page 11 of 48 Protected B / Protégé B compared to the placebo-treated patients (2%).
There was no overall difference in mean diastolic blood pressure between the treatment groups. This disparity between levetiracetam and placebo treatment groups was not observed in the studies of older children or in adults. Monitor patients 1 month to ˂ 4 years of age for increases in diastolic blood pressure.
Dependence/Tolerance As with all antiepileptic drugs, MINT-LEVETIRACETAM SOLUTION should be withdrawn gradually to minimize the potential of increased seizure frequency. g. coordination difficulties). Therefore, patients are advised not to drive or operated machinery or other skilled tasks until it is established that their ability to perform such activities is not affected.
MINT-LEVETIRACETAM SOLUTION is contraindicated: • in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
• in patients who are hypersensitive to other pyrrolidine derivatives (see 7 WARNINGS AND PRECAUTION, Immune)
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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The physician should prescribe the most appropriate pharmaceutical form, presentation and strength according to age, weight and dose. MINT-LEVETIRACETAM SOLUTION is the preferred formulation over tablets for use in infants and children under the age of 6 years, or under 25 kg (see Table 3), and in any patients unable to swallow tablets.
Oral Solution Weight-Based Dosing Calculation for Pediatric Patients The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients: Total daily dose (mL/day) = daily dose ((mg/kg)/day) x patient weight (kg) 100 mg/mL Add-on therapy in infants aged 1 month to <6 months Oral Solution The initial therapeutic dose is 7 mg/kg twice daily.
Depending upon the clinical response and tolerability, the dose can be increased up to 21 mg/kg twice daily. Dose changes should not exceed increases or decreases of 7 mg/kg twice daily every 2 weeks. The lowest effective dose should be used.
Infants should start the treatment with MINT-LEVETIRACETAM SOLUTION 100 mg/mL. To ensure the accuracy of dosing for this age group, administer oral solution using a 1 mL dosing syringe. 5 mL) twice daily Add-on therapy in infants aged 6 months to <4 years; children aged 4 to 11 years, and adolescents aged 12 to 17 years weighing less than 50 kg Oral Solution The initial therapeutic dose is 10 mg/kg twice daily.
Depending upon the clinical response and tolerability, the dose can be increased up to 30 mg/kg twice daily. Dose changes should not exceed increases or decreases of 10 mg/kg twice daily every 2 weeks. The lowest effective dose should be used.
For adolescents aged 12 to 17 years weighing 50 kg or more, see adult dosing recommendations. For accuracy of dosing, use the correct age-appropriate dosing syringe. • For infants aged 6 months to less than 4 years, administer using a 3 mL dosing syringe.
• For children aged 4 […]
See Table 6 for the incidence rate of individual adverse events contained within each category. ) have been reported approximately equally in patients with and without a psychiatric history. Table 6 – Total combined incidence rate for each of the three categories of CNS adverse events in placebo-controlled add-on clinical trials.
Category of CNS Adverse Events Levetiracetam* + Anti-epileptic Therapy (n=672) Placebo + Antiepileptic Therapy (N=351) Somnolence and Fatigue Somnolence 15% 10% Fatigue 14% 10% Behavioural / Psychological Symptoms MINT-LEVETIRACETAM SOLUTION (Product Monograph) Page 18 of 48 Protected B / Protégé B Category of CNS Adverse Events Levetiracetam* + Anti-epileptic Therapy (n=672) Placebo + Antiepileptic Therapy (N=351) Non-psychotic (1) 14% 6% Psychotic (2) 1% 0% Coordination Difficulties 3% 2% Coordination Difficulties (3) *Reflects levetiracetam doses of 1000 mg, 2000 mg, 3000 mg, and 4000 mg per day.
(1) “Non-psychotic behavioural/psychiatric symptoms” encompasses the following terms: agitation, antisocial reaction, anxiety, apathy, depersonalization, depression, emotional lability, euphoria, hostility, euphoria, hostility, nervousness, neurosis, personality disorder, and suicide attempt.
(2) “Psychotic behavioural/psychiatric symptoms” encompasses the following terms: hallucination, paranoid reaction, psychosis, and psychotic depression. (3) “Coordination difficulties” encompasses the following terms: ataxia, abnormal gait, incoordination.
There was no clear dose relationship for any of the three categories of CNS adverse events, within the recommended dose range of up to 3000 mg/day. In a controlled study including a dose of 4000 mg, administered without titration, the incidence rate of somnolence during the first 4 weeks of treatment for patient receiving the high dose was 42%, compared to 21% for patients receiving 2000 mg/day.
Table 7 Incidence (%) of treatment-emergent adverse events in placebo-controlled add-on studies by body system. Adverse events occurred in at least 1% of levetiracetam-treated patients, and occurred more frequently than in placebo-treated patients (Studies N051, N052, N132, and N138).
Adverse Event Levetiracetam (N=769) Placebo (N=439) Body as a Whole Asthenia 14% 10% Infection 13% 7% Digestive System Tooth disorder 2% 1% Hemic and Lymphatic System Ecchymosis 2% 1% Nervous System Amnesia 2% 0% Anxiety 2% 1% Ataxia 3% 1% Depression 4% 2% Dizziness 9% 4% Emotional lability 2% 0% Hostility 2% 1% Nervousness 4% 2% Personality disorder 1% 0% MINT-LEVETIRACETAM SOLUTION (Product Monograph) Page 19 of 48 Protected B / Protégé B Adverse Event Levetiracetam (N=769) Placebo (N=439) Somnolence 15% 10% Thinking abnormal 2% 1% Vertigo 3% 1% Respiratory System Pharyngitis 6% 4% Rhinitis 4% 3% Sinusitis 2% 1% Lack of dose-related incidence of adverse events within therapeutic range Based on the data from the controlled clinical trials, there was no evidence of dose relationship within the recommended dose range of 1000 to 3000 mg/day.
7% receiving placebo either discontinued or had a dose reduction as a result of an adverse event. Table 8 lists the most common (>1%) adverse events that resulted in discontinuation or dose reduction.
Table 8:
Adverse events that most commonly resulted in discontinuation or dose reduction in placebo- controlled studies in patients with epilepsy. 4%) The […]
Hematologic Cases of decreased blood cell counts (neutropenia, agranulocytosis, leucopenia, thrombocytopenia and pancytopenia) have been described in association with levetiracetam administration. Post-market reports include a fatality in a 4-month old, with swelling of the limbs appearing 5 days after treatment initiation as first-line monotherapy treatment initiation.
5 Post-Market Adverse Drug Reactions). Adults Statistically significant decreases compared to placebo were seen in total mean RBC count, mean hemoglobin, and mean hematocrit in levetiracetam-treated patients in controlled trials. 5% each.
2% of placebo patients had at least one possibly significant decrease in hematocrit (≤ 37% in males and 32% in females). 6% of treated vs. 0 x 109/L). Of the levetiracetam treated patients with a low neutrophil count, all but one rose towards or reached 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.
3 x 109/L, respectively, whereas there were small increases in the placebo group. 7% in levetiracetam-treated patients, compared to a decrease of 4% in placebo patients (statistically significant). 2% of placebo-treated patients). No patient was discontinued secondary to low WBC or neutrophil counts.
7 x 109/L). 5 Post-Market Adverse Reactions). For information on dosage adjustment in patients with severe hepatic impairment, see Dosage Adjustments in Adult Patients with Impaired Hepatic Function. Immune Hypersensitivity Reactions Skin and Subcutaneous tissue disorders Serious hypersensitivity reactions with dermatological involvement […]