Topvex 25/Topvex 50/Topvex 100

Topvex 25: Each Film coated Tablet contains: Topiramate USP 25 mg.
Colour: Erythrosine & Titanium dioxide.
Topvex 50: Each Film coated Tablet contains: Topiramate USP 50 mg.
Colour: Quinolone yellow & Titanium dioxide.
Topvex 100: Each Film coated Tablet contains: Topiramate USP 100 mg.
Colour: Quinolone yellow & Titanium dioxide.
Topiramate is white to off-white powder & freely soluble in dichloromethane. Chemically, it is 2,3:4,5-Di-O-isopropylidene-β-D-fructopyranose sulfamate. Its molecular formula is C₁₂H₂₁NO₈S and molecular weight is 339.36.

Pharmacological Classification: Anticonvulsant (Antiepileptic).
Pharmacology: Pharmacodynamics: Mechanism of Action: Topiramate is an antiepileptic agent classified as a sulfamate-substituted monosaccharide.
Three pharmacological properties of topiramate have been identified that may contribute to its anticonvulsant activity: Topiramate reduces the frequency at which action potentials are generated when the neurons are subjected to a sustained depolarisation indicative of a state-dependent blockade of voltage-sensitive sodium channels.
Topiramate markedly enhances the activity of GABA at some types of GABA receptors, thereby enhancing GABA-induced influx of chloride into neurons.
Topiramate weakly antagonises the excitatory activity of kainate/AMPA subtype of glutamate receptor but has no apparent effect on the activity of N-methyl-D-aspartate (NMDA) at the NMDA receptor subtype.
Topiramate also inhibits some isoenzymes of carbonic anhydrase, This pharmacological effect is generally weak and may not be a major contributing factor to the antiepileptic activity of topiramate.
Pharmacokinetics: Topiramate is well absorbed after oral administration. The relative bioavailability is about 80%. Food does not affect the bioavailability of topiramate. Protein binding is low, 13 to 17%. The time to peak concentration (Tmax) is approximately 2 hours following administration of a 400 mg oral dose. The volume of distribution is 0,6-0,8 L/kg with values for women circa 50% of those for males. In patients with normal renal function, steady state is reached in about 4 days. The pharmacokinetics of topiramate are linear, with dose-proportional increases in plasma concentration over the range of 200 to 800 mg a day. The mean elimination half-life (t_½) is 21 hours, following single or multiple dosing. Approximately 70% of an administered dose is excreted unchanged in the urine and the remainder undergoes metabolism by hydroxylation, hydrolysis and glucuronidation with no one metabolite accounting for more than 5% of an oral dose. Topiramate clearance is reduced by 42% in patients with moderate renal function impairment and by 54% in patients with severe renal impairment as compared with the clearance in subjects with normal renal function. Children exhibit a higher clearance and shorter elimination half-life than adults.
Consequently, the plasma concentration of topiramate for the same mg/kg dose may be lower in children compared to adults. The clearance of topiramate may be decreased in patients with impaired hepatic function.

Topiramate tablets are indicated as adjunctive therapy for adults and children over 4 years old who are inadequately controlled on conventional first line antiepileptic medicines for: partial onset seizures with or without secondarily generalized seizures; seizures associated with Lennox-Gastaut syndrome; primary generalized tonic clonic seizures. For monotherapy in patients with newly diagnosed epilepsy or for conversion to monotherapy in patients with epilepsy; adjunctive therapy for adults and children (>2 years) with partial-onset seizures or generalized tonic-clonic seizures; adjunctive therapy in adults and children for the treatment of seizures associated with Lennox-Gastaut syndrome.
Controlled on conventional first line antiepileptic medicines for:-partial onset seizures with or without secondarily generalized seizures-seizures associated with Lennox-Gastaut syndrome.-primary generalized tonic clonic seizures.

For optimal seizure control, in both adults and children, it is recommended that therapy be initiated at a low dose, followed by titration to an effective dose. It is recommended that film-coated tablets not be broken.
Topiramate can be taken without meals.
Adults: Therapy should begin at 25-50 mg nightly for one week. Subsequently, the dose should be increased at weekly intervals by 25-50 mg/day and taken in two divided doses. Dose titration should be guided by clinical outcome. Some patients may achieve efficacy with once-a-day dosing. The effective dose is usually within the range of 200 mg (minimum dose) to 400 mg daily taken in two divided doses; some patients may require up to 800 mg (maximum dose) daily. It is recommended that therapy be initiated at a low dose, followed by titration to an effective dose.
Since Topiramate is removed from plasma by haemodialysis, an additional dosage equal to approximately one-half of the daily dose should be administered on haemodialysis days. The additional dose should be administered in divided doses at the beginning and completion of the haemodialysis procedure. The additional doses may vary based on the dialysis equipment being used. No dosage adjustment is necessary in elderly patients.
Children 4 years and over: The initial dose for children is 25 mg for the first week, increased at intervals of 1–2 weeks by increments of 1 to 3 mg/kg/day, administered in two divided doses if more than 25 mg per day. The recommended dose thereafter is about 5–9 mg/kg/day in two divided doses. Dose titration should be guided by clinical outcome.

Headache, agitation, drowsiness, lethargy, metabolic acidosis and hypokalemia occurred after overdosing. At very high doses, coma, lasting 20-24 hours followed by full recovery after 3 to 4 days, may occur.
Treatment is symptomatic and supportive. An attempt should be made to remove undigested Topvex from the gastro-intestinal tract using gastric lavage, induction of emesis or activated charcoal. Hemodialysis has been shown to be an effective means to remove Topvex from the body. The patient should be well hydrated.

Hypersensitivity to Topiramate or any components of the preparation. Children under 4 years (as safety and efficacy of Topiramate has not yet been established). Pregnancy and lactation.

A syndrome consisting of acute myopia associated with secondary angle closure glaucoma has been reported in patients receiving Topiramate. Symptoms include acute onset of decreased visual acuity and/or ocular pain. Ophthalmic findings can include myopia, anterior chamber shallowing, ocular hyperemia (redness) and increased intraocular pressure. Mydriasis may or may not occur. This syndrome may be associated with supraciliary effusion resulting in anterior displacement of the lens and iris, with secondary angle closure glaucoma. Symptoms typically occur within one month of initiating Topiramate therapy. Secondary angle closure glaucoma associated with Topiramate has been reported in paediatric patients as well as adult patients. Treatment includes discontinuation of Topiramate, as rapidly as possible and appropriate measures to reduce intraocular pressure.
Metabolic Acidosis: Hyperchloremic, non-anion gap, metabolic acidosis (i.e. decreased serum bicarbonate below the normal reference range in the absence of respiratory alkalosis) is associated with topiramate treatment. This decrease in serum bicarbonate is due to the inhibitory effect of topiramate on renal carbonic anhydrase and consequent renal bicarbonate wasting. These decreases are usually mild to moderate (average decrease of 4 mmol/L at doses of 100 mg/day or above in adults and at approximately 6 mg/kg/day in paediatric patients). However, patients have experienced decreases to values below 10 mmol/L. Conditions or therapies that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhoea, surgery, ketogenic or certain drugs) may be addictive to bicarbonate lowering effects of topiramate. Chronic metabolic acidosis in paediatric patients can reduce growth rate. Chronic metabolic acidosis can lead to nephrolithiasis and increased risk of fractures. Evaluation of bicarbonate levels is recommended with topiramate therapy. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing topiramate.

The adverse events considered at least possibly related to the treatment are listed as follows by body system, organ class and frequency (wherever applicable). Frequencies are defined as very common (>1/10), common (>1/100, =1/10), uncommon (>1/1000, =1/100), rare (>1/10000, =1/1000), very rare (=1/10000) or frequency unknown.
Blood and lymphatic system disorders: Less frequent: Leucopenia.
Frequency unknown: Purpura. Anaemia and thrombocytopenia, alone or in combination with leucopenia. Thrombotic events have been reported although a causal association with Topiramate has not been established.
Immune system disorders: Frequency unknown: Viral infection.
Metabolism and nutritional disorders: Less frequent: Weight decrease, anorexia.
Psychiatric disorders: Frequent: Somnolence, nervousness, psychomotor slowing, difficulty with memory not otherwise specified, confusion, difficulty with concentration/attention, anorexia, depression, mood problems, personality changes, insomnia.
Less frequent: Agitation, cognitive problems not otherwise specific, emotional lability, apathy, psychosis/psychotic symptoms, hallucination, aggressive reaction/behaviour, suicidal ideas or attempts.
Nervous system disorders: Frequent: Paresthesia, ataxia, dizziness, speech disorders/related speech problems, language problems, tremor, hyperkinesias.
Co-ordination problems.
Eye disorders: Frequent: Abnormal vision, diplopia, nystagmus, acute and secondary angle closure glaucoma.
Rare: Conjunctivitis.
Ear and labyrinth disorders: Rare: Tinnitus.
Vascular disorders: Frequency unknown: Hypotension and postural hypotension.
Respiratory, thoracic and mediastinal disorders: Less frequent: Pharyngitis.
Frequency unknown: Rhinitis, pneumonia, Dyspnoea.
Gastro-intestinal disorders: Frequent: Nausea.
Less frequent: Constipation, dyspepsia, abdominal pain.
Frequency unknown: Increased saliva production.
Hepato-biliary disorders: Frequency unknown: Hepatic failure, hepatitis.
Skin and subcutaneous tissue disorders: Less frequent: Gingivitis, increased sweating.
Rare: Pruritus.
Frequency unknown: Bullous skin and mucosal reactions, including erythema multiforme, pemphigus, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Renal and urinary disorders: Less frequent: Nephrolithiasis (kidney stones).
Rare: Dysuria, urinary frequency, incontinence.
Frequency unknown: Renal failure, haematuria.
General disorders and administration site conditions: Frequent: Asthenia, fatigue.
Frequency unknown: Injury.

Effects of Topiramate on other anti-epileptic medicines: If Topiramate is taken concomitantly with other anti-epileptic medicines (phenytoin, carbamazepine, valproic acid, phenobarbital, primidone), there is no effect on their steady-state plasma concentrations, except in very rare cases where the addition of Topiramate to phenytoin may result in an increase of plasma concentrations of phenytoin. Consequently, any patient on phenytoin, taking Topiramate, in addition, should have phenytoin levels monitored.
Effects of other anti-epileptic medicines on Topiramate: Phenytoin and carbamazepine decrease the plasma concentration of Topiramate. The addition or withdrawal of phenytoin or carbamazepine to Topiramate therapy may require an adjustment in dosage of Topiramate. This should be done by titrating to clinical effect.
The withdrawal or addition of valproic acid does not produce clinically significant changes in plasma concentrations of Topiramate and, therefore, dosage adjustment of Topiramate is not necessary.
Digoxin: Serum digoxin levels have decreased with concomitant administration of Topiramate. When Topiramate is added or withdrawn in patients on digoxin therapy, careful attention should be given to the routine monitoring of serum digoxin.
Oral Contraceptives: Efficacy of oral contraceptives may be compromised when used concurrently with Topiramate. Bearing in mind the potential risk of teratogenicity, patients should receive a preparation containing not less than 50 micrograms of oestrogen or use some alternative non-hormonal method of contraception as Topiramate increases plasma clearance of the oestrogenic component significantly. Patients on oral contraceptives are advised to report any change in their bleeding patterns.
Others: Concomitant use of Topiramate with agents predisposing to nephrolithiasis (renal stone formation) should be avoided.

Store at temperatures not exceeding 30°C. Protect from light & moisture.
Shelf-Life: 36 months from the date of manufacturing.

Anticonvulsants

N03AX11 - topiramate ; Belongs to the class of other antiepileptics.

Rx