Pradox 25/Pradox 50/Pradox 100 Special Precautions

Withdrawal of Topiramate: In patients with or without a history of seizures or epilepsy, AEDs including Topiramate should be gradually withdrawn to minimize the potential for seizures or increased seizure frequency. Daily dosages were decreased in weekly intervals by 50 to 100 mg in adults with epilepsy and by 25 to 50 mg in adults receiving Topiramate at doses up to 100 mg/day for migraine prophylaxis. In children, Topiramate should be gradually withdrawn over a 2 to 8 week period. In situations where rapid withdrawal of Topiramate is medically required, appropriate monitoring is recommended.
Renal impairment: The major route of elimination of unchanged Topiramate and its metabolites is via the kidney. Renal elimination is dependent on renal function and is independent of age. Patients with moderate or severe renal impairment may take 10 to 15 days to reach steady state plasma concentrations as compared to 4 to 8 days in patients with normal renal function. As with all patients, the titration schedule should be guided by clinical outcome (i.e., seizure control, avoidance of side effects) with the knowledge that subjects with known renal impairment may require a longer time to reach stead-state at each dose.
Hydration: Oligohidrosis (decreased sweating) and anhidrosis have 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 temperatures.
Adequate hydration while using Topiramate is very important. Hydration can reduce the risks of nephrolithiasis. Proper hydration prior to and during activities such as exercise or exposure to warm temperatures may reduce the risk of heat-related adverse events.
Mood disturbances/depression: An increased incidence of mood disturbances and depression has been observed during Topiramate treatment.
Suicide/suicidal ideation: Potential for an increase in risk of suicidal thoughts or behaviors.
AEDs, including Topiramate, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. The mechanism of this risk is not known. Patients therefore should be monitored for signs of suicidal ideation and behavior and appropriate treatment should be considered. Patients (and, when appropriate, caregivers of patients) should be advised to seek immediate 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. The majority of cases have occurred in patients concurrently taking other medications that are known to be associated with SJS and TEN. There have also been several cases in patients receiving monotherapy. It is recommended that patients be informed about the signs of serious skin reactions. If SJS or TEN are suspected, use of Topiramate 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. None of these risk factors can reliably predict stone formation during Topiramate treatment. In addition, patients taking other medication associated with nephrolithiasis may be at increased risk.
Hepatic impairment: 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 some or all of the following: myopia, mydriasis, anterior chamber shallowing, ocular hyperemia (redness), choroidal detachments, retinal pigment epithelial detachments, macular striae, and increased intraocular pressure. 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.
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 following Topiramate discontinuation, however some cases were not. In a large proportion of post-marketing case reports reversibility was unknown, but in cases where an outcome was reported, the majority were reversible. If visual problems occur at any time during Topiramate treatment, consideration should be given to discontinuing the drug.
Metabolic acidosis and sequelae: 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. The 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 drugs) may be additive to the bicarbonate lowering effects of Topiramate.
Chronic, untreated metabolic acidosis may increase the risk of nephrocalcinosis.
Chronic metabolic acidosis in pediatric patients can reduce growth rates. The effect of Topiramate on growth and 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 metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing Topiramate (using dose tapering).
Hyperammonemia and encephalopathy: Hyperammonemia with or without encephalopathy has been reported with Topiramate treatment. The risk for hyperammonemia with Topiramate appears dose-related. Hyperammonemia has been reported more frequently when Topiramate is used concomitantly with Valproic acid.
Clinical symptoms of hyperammonemic encephalopathy often include acute alterations in level of consciousness and/or cognitive function with lethargy. In most cases, hyperammonemic encephalopathy abated with discontinuation of treatment. 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.
Women of childbearing potential: PRADOX may cause fetal harm when administered to a pregnant woman.
Before the initiation of treatment with Topiramate in a woman of childbearing potential, pregnancy testing should be performed and a highly effective contraceptive method used. The patient should be fully informed of the risks related to the use of Topiramate during pregnancy.
PRADOX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nutritional supplementation: A dietary supplement or increased food intake may be considered if the patient is losing weight while on this medication.
Effects on ability to drive and use machine: 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 events could potentially be dangerous in patients driving a vehicle or operation machinery, particularly until such time as the individual patient's experience with the drug is established.