Toramig 25/Toramig 50/Toramig 100 Special Precautions

In situations where rapid withdrawal of Topiramate is medically required, appropriate monitoring is recommended (see Dosage & Administration).
As with other AEDs, some patients may experience an increase in seizure frequency or the onset of new types of seizures with Topiramate. These phenomena may be the consequence of an overdose, a decrease in plasma concentrations of concomitantly used AEDs, progress of the disease, or a paradoxical effect.
Adequate hydration while using Topiramate is very important. Hydration can reduce the risk of nephrolithiasis (see as follows). Proper hydration prior to and during activities such as exercise or exposure to warm temperatures may reduce the risk of heat-related adverse reactions (see Adverse Reactions).
Oligohydrosis: Oligohydrosis (decreased sweating) has been reported in association with the use of Topiramate. Decreased sweating and hyperthermia (rise in body temperature) may occur especially in young children exposed to high ambient temperature.
Mood disturbances/depression: An increased incidence of mood disturbances and depression has been observed during Topiramate treatment.
Suicide/suicide ideation: Suicidal ideation and behavior have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomized placebo-controlled trials of AEDs has shown a small increased risk of suicidal ideation and behavior. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for Topiramate.
In double blind clinical trials, suicide related events (SREs) (suicidal ideation, suicide attempts and suicide) occurred at a frequency of 0.5% in Topiramate treated patients (46 out of 8,652 patients treated) and at a nearly 3-fold higher incidence than those treated with placebo (0.2%; 8 out of 4,045 patients treated).
Patients therefore should be monitored for signs of suicidal ideation and behavior and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behavior emerge.
Serious skin reactions: Serious skin reactions (Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)) have been reported in patients receiving Topiramate (see Adverse Reactions). It is recommended that patients be informed about the signs of serious skin reactions. If SJS or TEN are suspected, use of Topiramate tablet should be discontinued.
Nephrolithiasis: Some patients, especially those with a predisposition to nephrolithiasis, may be at increased risk for renal stone formation and associated signs and symptoms such as renal colic, renal pain or flank pain.
Risk factors for nephrolithiasis include prior stone formation, a family history of nephrolithiasis and hypercalciuria (see as follows - Metabolic acidosis). None of these risk factors can reliably predict stone formation during Topiramate treatment. In addition, patients taking other medicinal products associated with nephrolithiasis may be at increased risk.
Decreased renal function: In patients with impaired renal function (CL_CR ≤70 mL/min) Topiramate should be administered with caution as the plasma and renal clearance of Topiramate are decreased. For specific posology recommendations in patients with decreased renal function, see Dosage & Administration.
Decreased hepatic function: In hepatically-impaired patients, Topiramate should be administered with caution as the clearance of Topiramate may be decreased.
Acute myopia and secondary angle closure glaucoma: 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.
Ophthalmologic findings can include myopia, anterior chamber shallowing, ocular hyperemia (redness) and increased intraocular pressure. Mydriasis may or may not be present. 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 1 month of initiating Topiramate therapy. In contrast to primary narrow angle glaucoma, which is rare under 40 years of age, secondary angle closure glaucoma associated with Topiramate has been reported in pediatric patients as well as adults. Treatment includes discontinuation of Topiramate, as rapidly as possible in the judgment of the treating physician, and appropriate measures to reduce intraocular pressure. These measures generally result in a decrease in intraocular pressure.
Elevated intraocular pressure of any etiology, if left untreated, can lead to serious sequelae including permanent vision loss.
A determination should be made whether patients with history of eye disorders should be treated with Topiramate.
Visual field defects: Visual field defects have been reported in patients receiving Topiramate independent of elevated intraocular pressure. In clinical trials, most of these events were reversible after Topiramate discontinuation. If visual field defects occur at any time during Topiramate treatment, consideration should be given to discontinuing the drug.
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. Generally, the decrease in bicarbonate occurs early in treatment although it can occur at any time during treatment. 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 pediatric patients). Rarely, 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, diarrhea, surgery, ketogenic diet, or certain medicinal products) may be additive to the bicarbonate lowering effects of Topiramate.
Chronic, untreated metabolic acidosis increases the risk of nephrolithiasis and nephrocalcinosis, and may potentially lead to osteopenia (see as previously mentioned - Nephrolithiasis).
Chronic metabolic acidosis in pediatric patients can reduce growth rates. The effect of Topiramate on bone-related sequelae has not been systematically investigated in pediatric or adult populations.
Depending on underlying conditions, appropriate evaluation including serum bicarbonate levels is recommended with Topiramate therapy. If signs or symptoms are present (e.g. Kussmaul's deep breathing, dyspnea, anorexia, nausea, vomiting, excessive tiredness, tachycardia or arrhythmia), indicative of metabolic acidosis, measurement of serum bicarbonate is recommended. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing Topiramate (using dose tapering).
Topiramate should be used with caution in patients with conditions or treatments that represent a risk factor for the appearance of metabolic acidosis.
Impairment of cognitive function: Cognitive impairment in epilepsy is multifactorial and may be due to the underlying etiology, due to the epilepsy or due to the anti-epileptic treatment. There have been reports in the literature of impairment of cognitive function in adults on Topiramate therapy which required reduction in dosage or discontinuation of treatment. However, studies regarding cognitive outcomes in children treated with Topiramate are insufficient and its effect in this regard still needs to be elucidated.
Hyperammonemia and encephalopathy: Hyperammonemia with or without encephalopathy has been reported with Topiramate treatment (see Adverse Reactions). The risk for hyperammonemia with Topiramate appears dose-related. Hyperammonemia has been reported more frequently when Topiramate is used concomitantly with Valproic acid (see Interactions).
In patients who develop unexplained lethargy or changes in mental status associated with Topiramate monotherapy or adjunctive therapy, it is recommended to consider hyperammonemic encephalopathy and measuring ammonia levels.
Nutritional supplementation: Some patients may experience weight loss whilst on treatment with Topiramate. It is recommended that patients on Topiramate treatment should be monitored for weight loss. A dietary supplement or increased food intake may be considered if the patient is losing weight while on Topiramate.
Effects on Ability to Drive and Use Machines: Topiramate tablet has minor or moderate influence on the ability to drive and use machines. Topiramate acts on the central nervous system and may produce drowsiness, dizziness or other related symptoms. It may also cause visual disturbances and/or blurred vision. These adverse reactions could potentially be dangerous in patients driving a vehicle or operating machinery, particularly until such time as the individual patient's experience with the medicinal products established.
Women of childbearing potential: Topiramate may cause fetal harm and fetal growth restriction (small for gestational age and low birth weight) when administered to a pregnant woman. The North American Antiepileptic Drug pregnancy registry data for Topiramate monotherapy showed an approximate 3-fold higher prevalence of major congenital malformations (4.3%), compared with a reference group not taking AEDs (1.4%). In addition, data from other studies indicate that, compared with monotherapy, there is an increased risk of teratogenic effects associated with the use of AEDs in combination therapy.
Before the initiation of treatment with Topiramate in a woman of childbearing potential, pregnancy testing should be performed and a highly effective contraceptive method advised (see Interactions). The patient should be fully informed of the risks related to the use of Topiramate during pregnancy (see Contraindications, Use in Pregnancy & Lactation).