Medicinal Products

EPITOMAX 25 mg

Generic Drug Therapeutic Class: Neurology-Psychiatry
active ingredients: Topiramate
laboratory: Janssen Cilag

capsule
Bottle of 28
All forms

Indication

As monotherapy in adults, adolescents and children over 6 years of age in partial epilepsy with or without secondary generalization or in generalized tonic-clonic seizures.

In combination with other antiepileptics in children from 2 years of age, adolescents and adults in partial epilepsy with or without secondary generalization or in generalized tonic-clonic seizures, as well as in the treatment of seizures associated with seizures. Lennox-Gastaut syndrome.

Topiramate is indicated in adults for the prophylactic treatment of migraine after a careful evaluation of possible therapeutic alternatives. Topiramate is not indicated for the treatment of seizures.

Dosage EPITOMAX 25 mg Capsule Bottle of 28

Overview

It is recommended to start the low-dose treatment then increase the doses to the effective dosage. Dosage and dosage increase should be guided by the clinical response.

EPITOMAX is available in the form of film-coated tablets and capsules. It is recommended not to cut the film-coated tablets. The capsule form is available for patients who have difficulty swallowing tablets, for example children and the elderly.

The capsules of EPITOMAX can be swallowed whole or can be administered after careful opening of the capsule and distribution of the entire content on a small amount (teaspoon) of semi-solid food. The drug / food mixture should be swallowed immediately and should not be chewed. It should not be kept for future use.

Monitoring of plasma concentrations to optimize treatment with EPITOMAX is not necessary. In rare cases, the addition of topiramate to phenytoin may necessitate an adjustment of the phenytoin dosage to achieve an optimal clinical response. Addition or withdrawal of phenytoin and carbamazepine to combination therapy with EPITOMAX may require dosage adpatation of EPITOMAX.

EPITOMAX can be given without regard to meals.

In patients with or without a history of seizure or epilepsy, antiepileptic drugs including topiramate should be discontinued gradually to minimize the potential risk of seizure or increased seizure frequency. In clinical trials, daily doses were decreased in weekly increments of 50-100 mg in adults with epilepsy and 25-50 mg in adults receiving topiramate at doses up to 100 mg / day. day in the prophylactic treatment of migraine. In clinical trials in children, topiramate was gradually discontinued over a period of 2 to 8 weeks.

Epilepsy - Monotherapy treatment

Overview

When stopping concomitant antiepileptics for topiramate monotherapy, the effect of this judgment on seizure control should be taken into account. With the exception of tolerance problems requiring abrupt discontinuation of associated antiepileptics, a gradual decrease in antiepileptics associated with the rate of approximately one-third of the dose every two weeks is recommended.

Upon discontinuation of enzyme inducing drugs, topiramate concentrations will increase. A decrease in the dosage of EPITOMAX (topiramate) may be necessary if it is clinically justified.

adults

Dose and dosage adjustment should be guided by the clinical response. Treatment should start with 25 mg in the evening for 1 week. The dosage should then be increased by 25 or 50 mg / day in 1 or 2 week increments administered in 2 doses. When the patient does not tolerate the dose increase, smaller increases or longer steps may be used.

The recommended initial target dosage for topiramate monotherapy is 100 mg / day at 200 mg / day in 2 doses. The maximum recommended daily dose is 500 mg / day in 2 doses. Some patients with refractory forms of epilepsy have tolerated doses of 1000 mg / day of topiramate monotherapy. These dosing recommendations apply to all adults, including the elderly, in the absence of underlying renal insufficiency.

Pediatric population (children over 6 years old)

Dose and dosage adjustment in children should be guided by the clinical response. Treatment of children over 6 years old should start at 0.5 to 1 mg / kg in the evening during the first week. The dosage will then be increased in increments of 0.5 to 1 mg / kg / day, administered in two doses, in increments of 1 to 2 weeks. If the child does not tolerate the dose increase, smaller increases or longer intervals may be used.

The recommended starting dose for treatment with topiramate monotherapy in children over 6 years of age is 100 mg / day depending on the clinical response (corresponding to approximately 2.0 mg / kg / day in at 16 years old).

Treatment of epilepsy in combination with other antiepileptics (partial epilepsy with or without generalization, generalized tonic-clonic seizures, or attacks associated with Lennox-Gastaut syndrome)

adults

Treatment should start with 25-50 mg in the evening for 1 week. The use of lower doses has been reported, but has not been studied systematically. Therefore, in increments of one or two weeks, the dosage will be increased in increments of 25-50 mg / day and administered in 2 doses. The effective dosage may be reached in some patients once a day.

In clinical trials in combination with other antiepileptics, the 200 mg dose was the lowest effective dose. The usual daily dosage is 200-400 mg / day in two doses.

These dosing recommendations apply to all adults, including the elderly, in the absence of underlying renal insufficiency (see Warnings and Precautions for Use section ).

Pediatric population (children aged 2 years and over)

The recommended total daily dosage of EPITOMAX (topiramate) in combination with other antiepileptics is approximately 5 to 9 mg / kg / day in two divided doses. Treatment should begin at 25 mg (or less, in the range 1-3 mg / kg / day) in the evening during the first week. The dosage should then be increased in increments of 1 to 2 weeks, in increments of 1 to 3 mg / kg / day (given in 2 doses), to achieve the clinically optimal dosage.

Daily dosages up to 30 mg / kg / day were studied and were generally well tolerated.

Migraine

adults

The recommended total daily dose of topiramate for the prophylactic treatment of migraine is 100 mg / day in two divided doses. Dosage adjustment should start at 25 mg in the evening for 1 week. The dosage will then be increased in increments of 25 mg / day administered in 1 week increments. If the patient does not tolerate the dose increase, longer bearings may be used.

Some patients may show clinical improvement at the total daily dose of 50 mg / day. Patients received total daily doses of up to 200 mg / day. This dose may be appropriate in some patients, however, caution is recommended due to an increased incidence of side effects.

Pediatric population

EPITOMAX (topiramate) is not recommended for the treatment or prevention of migraine in children in the absence of sufficient safety and efficacy data.

General dosing recommendations in special populations of patients receiving EPITOMAX.

Renal failure patient

In patients with renal impairment (Cl cr ≤ 70 ml / min) topiramate should be used with caution as plasma and renal clearance of topiramate is decreased. Patients with known renal impairment may require a longer period to reach steady state after each dose. Half of the normal initiation and maintenance dose is recommended (see section Pharmacokinetic properties ).

In patients with end-stage renal disease, where topiramate is removed from plasma by hemodialysis, an additional dose of EPITOMAX equivalent to approximately half of the daily dose should be given on days of hemodialysis. The additional dose should be given twice, at the beginning and at the end of the hemodialysis session. The additional dose may be different depending on the characteristics of the hemodialysis equipment used (see section Pharmacokinetic properties ).

Hepatic insufficiency patient

In patients with moderate to severe hepatic impairment, topiramate should be administered with caution as clearance of topiramate is decreased.

Elderly patients

No dose adjustment is necessary in elderly patients with normal renal function.

Against indications

· Hypersensitivity to the active substance or to any of the excipients.

· Prophylactic treatment of migraine in pregnant women or women of childbearing potential who do not use effective contraceptive methods.

Epitomax side effects

The safety of topiramate was assessed from the clinical database of 4111 patients (3 182 on topiramate and 929 on placebo) who participated in 20 double-blind clinical trials and 2, 847 patients who participated in 34 open trials, respectively, with topiramate in combination with other antiepileptics in generalized tonic-clonic seizures, partial epilepsies, seizures associated with Lennox-Gastaut syndrome, as monotherapy in newly or newly diagnosed epilepsy or in the prophylactic treatment of migraine. The majority of adverse reactions (AEs) were mild to moderate in severity. The AEs identified in the clinical trials, and during the post-marketing experience (indicated by "*") are listed by incidence of occurrence in clinical trials in Table 1. The assigned frequencies are as follows:

· Very common: ≥ 1/10

· Frequent: ≥ 1/100 to <1/10

· Uncommon: ≥ 1/1000 to <1/100

· Rare: ≥ 1/10 000 to <1/1000

· Not known: can not be estimated based on available data.

The most common AEs (those with> 5% or greater incidence of placebo in at least 1 indication in double-blind, topiramate-controlled trials) include: anorexia, decreased appetite, bradyphrenia, depression, slurred speech, insomnia, abnormal coordination, attention deficit disorder, dizziness, dysarthria, dysgeusia, hypoesthesia, lethargy, memory disorder, nystagmus, paresthesia, somnolence, tremor, diplopia, blurred vision, diarrhea, nausea, fatigue, irritability, and weight loss.

Table 1: Adverse effects of topiramate

System organ class

Very common

Frequent

Rare

Rare

Not known frequency

Infections and infestations

* Nasopharyngitis.

Blood and lymphatic system disorders

Anemia.

Leukopenia, thrombocytopenia, lymphadenopathy, eosinophilia.

Neutropenia *.

Immune system disorder

Hypersensitivity.

Allergic edema *, conjunctival edema *.

Metabolism and nutrition disorders

Anorexia, decreased appetite.

Metabolic acidosis, hypokalemia, increased appetite, polydipsia.

Hyperchloremic acidosis.

Psychiatric disorders

Depression.

Bradyphrenia, insomnia, expressive language disorder, anxiety, confusion, disorientation, aggression, mood alteration, agitation, mood swings, depressed mood, anger, behavioral disorders.

Suicidal ideation, suicide attempt, hallucination, psychotic disorder, auditory hallucination, visual hallucination, apathy, lack of spontaneous speech, sleep disorder, emotional lability, diminished libido, impatience, crying, dysphemia, euphoric mood, paranoia, perseveration, attack of panic, tears, reading disorder, difficulty falling asleep, emotional dullness, abnormal thinking, loss of libido, indifference, insomnia of the middle of the night, distractibility, early morning awakening, panic reaction, mood elevation .

Mania, panic disorder, feeling of hopelessness *, hypomania

Nervous system disorders

Paresthesia, drowsiness, dizziness

Attention disorders, memory disorder, amnesia, cognitive impairment, mental disorder, impaired psychomotor ability, convulsions, coordination disorders, tremor, lethargy, hypoaesthesia, nystagmus, dysgeusia, balance disorder, dysarthria, tremor of intention, sedation.

Decreased level of consciousness, status of grand epilepticus, visual field disorder, complex partial convulsive seizures, language disorder, psychomotor hyperactivity, syncope, sensory disturbance, salivation, hypersomnia, aphasia, repetitive speech, hypokinesia, dyskinesia, sensation postural dizziness, poor quality of sleep, burning sensation, loss of sensitivity, parosmia, cerebellar syndrome, dysesthesia, hypogeusia, stupor, awkwardness, aura, ageusia, dysgraphia, dysphasia, peripheral neuropathy, presyncope, dystonia, tingling.

Apraxia, circadian rhythm disturbance of sleep, hyperesthesia, hyposmia, anosmia, essential tremor, akinesia, lack of response to stimuli.

Eye disorders

Blurred vision, diplopia, blurred vision.

Decreased visual acuity, scotoma, myopia *, abnormal sensation in the eye *, dry eye, photophobia, blepharospasm, tearing, photopsia, mydriasis, presbyopia.

Unilateral blindness, transient blindness, glaucoma, accommodation disorder, impaired binocular vision, scotomous scotoma, eyelid edema *, night blindness, amblyopia.

Angle-closure glaucoma *, maculopathy *, eye movement disorder *.

Affections of the ear and labyrinth

Dizziness, tinnitus, ear pain.

Deafness, unilateral deafness, sensorineural deafness, atrial discomfort, impaired hearing.

Heart conditions

Bradycardia, sinus bradycardia, palpitations.

Vascular disorders

Orthostatic hypotension, hypotension, flush, vasomotor flush.

Raynaud's syndrome.

Respiratory, thoracic and mediastinal disorders

Dyspnoea, epistaxis, nasal congestion, rhinorrhea, cough.

Exercise dyspnea, paranasal sinus hypersecretion, dysphonia.

Gastrointestinal disorders

Nausea, diarrhea.

Vomiting, constipation, upper abdominal pain, dyspepsia, abdominal pain, dry mouth, gastric discomfort, oral paresthesia, gastritis, abdominal discomfort.

Pancreatitis, flatulence, gastroesophageal reflux, low abdominal pain, oral hypoaesthesia, gingival bleeding, abdominal distension, epigastric discomfort, sensitive adomen, salivary hypersecretion, oral pain, odor breath, glossodynia.

Hepatobiliary disorders

Hepatitis, Hepatic insufficiency.

Skin and subcutaneous tissue disorders

Alopecia, rash, pruritus.

Anhidrosis, facial hypoesthesia, urticaria, erythema, generalized pruritus, macular rash, skin dyschromia, allergic dermatitis, swelling of the face.

Stevens-Johnson * syndrome, erythema multiforme *, abnormal skin odor, periorbital edema *, localized urticaria.

Toxic epidermal necrolysis *.

Musculoskeletal and systemic disorders

Arthralgia, muscle spasms, myalgia, muscle contraction, muscle weakness, musculoskeletal pain of the thorax.

Joint swelling *, musculoskeletal stiffness, flank pain, muscular fatigue.

Sensation of discomfort in the limbs *.

Renal and urinary disorders

Nephrolithiasis, pollakiuria, dysuria.

Urinary calculus, urinary incontinence, hematuria, incontinence, urinary urgency, renal colic, renal pain.

Ureteral calculus, renal tubular acidosis *.

Disorders of reproductive organs and breast

Erection disorder, sexual dysfunction.

General disorders and administration site conditions

Tired.

Fever, asthenia, irritability, balance disorder, abnormal sensation, malaise.

Hyperthermia, thirsty, flu-like syndrome *, asthenia, peripheral coldness, feeling drunk, feeling nervous.

Edema of the face, calcinosis.

investigations

Decrease in weight

Weight gain*.

Presence of crystals in urine, abnormal heel-toe test, decreased white blood cell count, increased liver enzymes.

Decreased serum Bicarbonates.

Socio-environmental characteristics

Difficulty learning.

* identified as AE in spontaneous cases reported after marketing. Its frequency was calculated from data from clinical trials.

Pediatric population

AEs more frequently reported (≥ 2-fold) in children than in adults in double-blind controlled studies include:

· Decreased appetite,

· Increased appetite,

· Hyperchloremic acidosis,

· Hypokalemia,

· Abnormal behavior,

· Aggression,

· Apathy,

· Initial insomnia,

· Suicidal ideation

· Disorders of attention,

· Lethargy,

· Disturbed circadian rhythm of sleep,

· Poor sleep,

· Increased tearing,

Sinus bradycardia,

· Abnormal sensation,

· Disorders of walking.

EIs that have been reported in children, but not in adults in double-blind controlled studies include:

· Eosinophilia,

· Psychomotor hyperactivity,

· fear of heights,

· Vomiting,

· Hyperthermia,

· Pyrexia,

· Learning difficulties.

Reporting of suspected adverse reactions

The reporting of suspected adverse reactions after authorization of the drug is important. It allows continuous monitoring of the benefit / risk ratio of the drug. Health professionals report any suspected adverse reactions via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centers. www.ansm.sante.fr.

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