Indications.

As monotherapy in adults, adolescents and children over 6 years of age in partial epilepsy with or without secondary generalization or in generalized tonicoclonic 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 tonicoclonic seizures, as well as in the treatment of seizures associated with Lennox-Gastaut.

Topiramate is indicated in adults for the prophylactic treatment of migraine after careful evaluation of possible treatment alternatives.

Topiramate is not indicated for the treatment of seizure.

Dosage.

The recommended total daily dose of topiramate for the prophylactic treatment of migraine is 100 mg / day given in 2 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 increments of 1 week. If the patient cannot tolerate the increase in dosage, longer increments may be used.

Some patients may show clinical improvement at the total daily dose of 50 mg / day.

Patients have received total daily doses of up to 200 mg / day.

This dose may be adjusted in some patients, however, caution is advised due to an increased incidence of side effects.

Treatment of children with topiramate is not recommended in this indication.

In moderate to severe renal impairment the dosage of topiramate should be divided by 2.

In case of dialysis, in addition to the daily half-dose treatment, an additional half-dose will be added on the days of dialysis divided for half before and after the dialysis session.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients listed in the Composition section.

Prophylactic treatment of migraine in pregnant women or women of childbearing potential not using effective contraceptive methods

Side effects.

Infections and infestations:

Very common: Nasopharyngitis

Blood and lymphatic system disorders:

Common: anemia

Uncommon: Leukopenia, thrombocytopenia, lymphadenopathy, eosinophilia.

Rare: Neutropenia.

Immune system disorders:

Common: Hypersensitivity

Frequency not known: Allergic edema.

Metabolism and nutrition disorders:

Common: Anorexia, decreased appetite.

Uncommon: Metabolic acidosis, hypokalaemia, increased appetite, polydipsia.

Rare: Hyperchloremic acidosis.

Psychiatric disorders:

Common: Insomnia, speech disturbance, confusion disorder, mood alteration (from depression to aggression)

Uncommon: suicidal ideation with sometimes acting out, psychotic disorders, severe change in mood, hallucinations, loss of libido, apathy, lack of spontaneous speech, sleep disturbances.

Rare: Mania, hypomania, panic disorder, feeling of hopelessness.

Nervous system disorders:

Common: disturbances in attention and / or memory, disturbances in coordination, disturbances in psychomotor functions, convulsions, disturbances in coordination, hypoaesthesia, nystagmus, dysarthria, dysgeusia, intention tremor, sedation.

Uncommon: Decreased level of consciousness, status epilepticus, partial and / or complex seizure, psychomotor hyperactivity, syncope, disturbances of sensitivity, hypogeusia, tingling, hypersalivation, aphasia, dizziness, burning sensation, cerebellar syndrome, dysgraphia, dystonia, peripheral neuropathy.

Rare: Apraxia, sleep disturbances, hyperesthesia, hypo and anosmia, essential tremor, akinesia, lack of response to stimuli.

Eye disorders:

Common: Blurred vision, diplopia, visual disturbances.

Uncommon: Decreased visual acuity, scotoma, myopia, abnormal eye sensation, dry eye, photophobia, blepharospasm, tearing, photopsia, mydriasis, presbyopia.

Rare: Unilateral blindness, transient blindness, glaucoma, accommodation disorder, altered binocular vision, scintillating scotoma, eyelid edema, night blindness, amblyopia.

Frequency not known: Angle closure glaucoma, maculopathy, eye movement disorder, conjunctival edema.

Ear disorders:

Common: Dizziness, tinnitus, ear pain

Uncommon: Deafness, unilateral deafness, sensorineural deafness, ear discomfort, hearing impairment.

Cardiac disorders:

Uncommon: Bradycardia, palpitations.

Vascular disorders:

Uncommon: Orthostatic hypotension, hypotension, flushing, flushing.

Rare: Raynaud's syndrome.

Respiratory, thoracic and mediastinal disorders:

Common: Nasal congestion, rhinorrhea, epistaxis, cough, dyspnea.

Uncommon: Dyspnoea on exertion, dysphonia, sinus hypersecretion.

Gastrointestinal disorders:

Very common: Nausea, diarrhea

Common: Vomiting, constipation, abdominal pain upper, dyspepsia, abdominal pain, dry mouth, stomach discomfort, oral paresthesia, gastritis, abdominal discomfort.

Uncommon: Pancreatitis, flatulence, gastroesophageal reflux disease, lower abdominal pain, oral hypoaesthesia, gingival bleeding, abdominal distension, epigastric discomfort, salivary hypersecretion, mouth pain, odorous breath, glossodynia.

Hepatobiliary disorders:

Rare: Hepatitis, hepatic failure.

Skin and soft tissue disorders:

Common: Alopecia, pruritus, rash.

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

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

Not known: Toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders:

Common: Arthralgia, muscle spasms, myalgia, muscle contraction, muscle weakness, musculoskeletal pain in the chest.

Uncommon: Joint swelling, musculoskeletal stiffness, flank pain, muscle fatigue.

Rare: Sensation of gene in the limbs.

Kidney and urinary tract disorders:

Common: renal lithiasis, dysuria, pollakiuria.

Uncommon: Kidney pain, incontinence, renal colic, hematuria.

Rare: Tubular acidosis, ureteral calculus.

Reproductive system and breast disorders:

Uncommon: Sexual dysfunction

General disorders:

Very common: Fatigue, weight loss.

Common: Fever, asthenia, irritability, disturbed balance, feeling abnormal, malaise.

Uncommon: Hyperthermia, thirst, flu syndrome, asthenia, peripheral coldness, feeling drunk, feeling nervous.

Rare: Facial edema, calcinosis.

Overdose:

Overdose of topiramate may cause: convulsions, drowsiness, slurred speech, blurred vision, diplopia, disturbed ideation, lethargy, impaired coordination, stupor, hypotension, abdominal pain, restlessness, dizziness and depression. In some cases the patient presents with severe metabolic acidosis.

Treatment consists of gastric lavage, administration of activated charcoal, and, if necessary, performing hemodialysis.

Mechanisms of action.

The precise mechanism by which topiramate exerts its anticonvulsant effect and its prophylactic effect in migraine is not known.

it appears that the mechanism of action is through state-dependent blockade of sodium channels. Topiramate increased the frequency with which gamma-aminobutyric acid (GABA) activated GABA receptors, and increased the ability of GABA to induce chloride ion influx into neurons, suggesting that topiramate potentiates the activity of this. inhibitory neurotransmitter.