Topamax (topiramate) Disease Interactions

There are 6 disease interactions with Topamax (topiramate):

Topiramate (Includes Topamax) ↔ Metabolic Acidosis

Severe Potential Hazard, High plausibility

Applies to: Renal Dysfunction, Acidosis, Pulmonary Impairment, Diarrhea, Alcoholism, Anemia, Asphyxia, Congestive Heart Failure, Dehydration, Myocardial Infarction, Shock, Vomiting, Sepsis, Diabetes Mellitus

The use of topiramate is associated with hyperchloremic, nonanion-gap metabolic acidosis, which is characterized by decreased serum bicarbonate below the normal reference range in the absence of chronic respiratory alkalosis. The condition usually occurs early in treatment and is caused by renal bicarbonate loss due to the inhibitory effect of topiramate on carbonic anhydrase. Bicarbonate decreases are generally mild to moderate, averaging 4 mEq/L at dosages of 400 mg/day in adults and approximately 6 mg/kg/day in pediatric patients. However, metabolic acidosis has been observed at dosages as low as 50 mg/day in adults and in patients as young as 5 months old, especially at dosages above 5 mg/kg/day. Rarely, patients may experience severe decrements to values below 10 mEq/L. Therapy with topiramate should be administered cautiously in patients with conditions that predispose to acidosis, including severe respiratory disease, renal disease, poorly controlled diabetes, alcoholism, congestive heart failure requiring pharmacologic treatment (especially unstable or acute CHF where there is risk of hypoperfusion and hypoxemia), and any condition associated with hypoxemia (e.g., severe anemia, myocardial infarction, asphyxia, shock), dehydration (e.g., severe diarrhea or vomiting), or sepsis. All patients prescribed topiramate should have serum bicarbonate measured at baseline and periodically, and be advised of the significance of nonspecific symptoms such as malaise, anorexia, respiratory distress, increasing somnolence, and gastrointestinal disturbances that may indicate early acidosis. More marked acidosis may be associated with cardiac arrhythmias and stupor. Chronic, untreated metabolic acidosis may increase the risk for nephrolithiasis or nephrocalcinosis, and may also cause osteomalacia, osteoporosis, and reduced growth rates in pediatric patients. If metabolic acidosis develops and persists, consideration should be given to reducing the dosage or discontinuing topiramate. If the decision is made to continue topiramate, alkali treatment should be considered.

References

  1. Stowe CD, Bollinger T, James LP, Haley TM, Griebel ML, Farrar HC "Acute mental status changes and hyperchloremic metabolic acidosis with long-term topiramate therapy." Pharmacotherapy 20 (2000): 105-9
  2. "Product Information. Topamax (topiramate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  3. Philippi H, Boor R, Reitter B "Topiramate and metabolic acidosis in infants and toddlers." Epilepsia 43 (2002): 744-7

Antiepileptics (Includes Topamax) ↔ Suicidal Tendency

Moderate Potential Hazard, Moderate plausibility

Applies to: Depression, Psychosis

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs across multiple indications in either monotherapy or adjunctive therapy for a median treatment duration of 12 weeks (up to a maximum of 24 weeks) showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. The estimated rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% for 16,029 placebo-treated patients, representing an increase of approximately one case for every 530 patients treated. There were four suicides in AED-treated patients and none in placebo-treated patients, although the number is too small to establish any causal relationship. The increased risk of suicidal thoughts or behavior was observed as early as one week after starting AEDs and persisted for the duration of treatment assessed. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Therapy with AEDs should be administered cautiously in patients with depression or other psychiatric disorders. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. For clinically significant or persistent symptoms, a dosage reduction or treatment withdrawal should be considered. If patients have symptoms of suicidal ideation or behavior, treatment should be discontinued.

Topiramate (Includes Topamax) ↔ Hemodialysis

Moderate Potential Hazard, High plausibility

Applies to: hemodialysis

Topiramate is cleared by hemodialysis at a rate that is 4 to 6 times greater than that in a normal individual. A prolonged period of dialysis may cause plasma topiramate level to fall below that required to maintain an anti-seizure effect, thus a supplemental dose may be required in patients undergoing hemodialysis. The actual adjustment should take into account the duration of dialysis, the clearance rate of the dialysis system being used, and the effective renal clearance of topiramate in the patient being dialyzed.

References

  1. "Product Information. Topamax (topiramate)." Ortho Pharmaceutical Corporation, Raritan, NJ.

Topiramate (Includes Topamax) ↔ Liver Disease

Moderate Potential Hazard, Moderate plausibility

Applies to: Liver Disease

Topiramate is partially metabolized by the liver and may accumulate in patients with impaired hepatic function. Following administration of a single 15 mg-92 mg dose of phentermine-topiramate, mean topiramate systemic exposure (AUC) was similar in patients with mild (Child-Pugh score 5 to 6) and moderate (Child-Pugh score 7 to 9) hepatic impairment compared to healthy volunteers. However, higher dosages of topiramate have not been studied. In addition, there are no data on the pharmacokinetics of topiramate in patients with severe hepatic impairment (Child-Pugh score 10 to 15). Therapy with topiramate should be administered cautiously in patients with liver disease.

References

  1. "Product Information. Topamax (topiramate)." Ortho Pharmaceutical Corporation, Raritan, NJ.

Topiramate (Includes Topamax) ↔ Nephrolithiasis

Moderate Potential Hazard, Moderate plausibility

Applies to: Nephrolithiasis, Dehydration, History - Nephrolithiasis

The use of topiramate may infrequently be associated with the development of kidney stones. The reported incidence was 1.5% (32 of 2,086 patients) during premarketing use, which is about 2 to 4 times that expected in a similar, untreated population. Topiramate is a weak carbonic anhydrase inhibitor and may promote stone formation by reducing urinary citrate excretion and increasing urinary pH. Therapy with topiramate should be administered cautiously with adequate hydration in patients with a history of nephrolithiasis. The concomitant use of topiramate with other carbonic anhydrase inhibitors should be avoided. Patients who are dehydrated may be at increased risk for the development of nephrolithiasis and should be encouraged to consume additional amounts of liquid during topiramate therapy.

References

  1. "Product Information. Topamax (topiramate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  2. Shorvon SD "Safety of topiramate: adverse events and relationships to dosing." Epilepsia 37(suppl 2 (1996): s18-22

Topiramate (Includes Topamax) ↔ Renal Dysfunction

Moderate Potential Hazard, High plausibility

Applies to: Renal Dysfunction

Topiramate is primarily eliminated unchanged by the kidney. The clearance of topiramate was reduced by 42% and 54% in subjects with moderate (CrCl = 30 to 69 mL/min/1.73m2) and severe (CrCl <30 mL/min/1.73m2) renal impairment, respectively, compared to subjects with normal renal function (CrCl >70 mL/min/1.73m2). Therapy with topiramate should be administered cautiously in patients with significant renal dysfunction. A 50% reduction in the usual starting and/or maintenance dosage may be necessary in patients with moderate or severe renal impairment in accordance with the individual product package labeling. Such patients will also require a longer time to reach steady-state at any given dosage.

References

  1. "Product Information. Topamax (topiramate)." Ortho Pharmaceutical Corporation, Raritan, NJ.

You should also know about...

Topamax (topiramate) drug Interactions

There are 563 drug interactions with Topamax (topiramate)

Topamax (topiramate) alcohol/food Interactions

There is 1 alcohol/food interaction with Topamax (topiramate)

Drug Interaction Classification

The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.

Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.

Do not stop taking any medications without consulting your healthcare provider.

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