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Dr. Bob is Robert Hsiung, MD,
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Posted by ed_uk on April 23, 2005, at 17:56:02
Have a look at this..........
Topiramate is commonly associated with the development of metabolic acidosis.
http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/topamax_3_hpc_e.html
IMPORTANT DRUG SAFETY INFORMATION
TOPAMAX* (topiramate) use is associated with Metabolic Acidosis
Dear Healthcare Professional:
Janssen-Ortho Inc., following discussions with Health Canada, would like to inform you of emerging important safety information which indicates that TOPAMAX* (topiramate) tablets and sprinkle capsules cause hyperchloremic, non-anion gap metabolic acidosis (decreased serum bicarbonate). TOPAMAX* is approved and marketed as adjunctive therapy for the management of patients (adults and children two years and older) with epilepsy who are not satisfactorily controlled with conventional therapy.
Data on hyperchloremic, non-anion gap metabolic acidosis are derived from placebo-controlled trials and post-marketing experience in over 2.5 million patients. In clinical trials, the rate of occurrence of a persistently decreased serum bicarbonate ranges from 23-67% for patients treated with topiramate and 1-10% for placebo. The incidence of markedly low serum bicarbonate in clinical trials ranges from 3-11% for topiramate and 0 to <1% for placebo.
Generally, decreases in serum bicarbonate occur soon after initiation of topiramate, although they can occur at any time during treatment. Bicarbonate decrements are usually mild-moderate, with an average decrease of 4 mEq/L at daily doses of 400 mg in adults and approximately 6 mg/kg/day in pediatric patients. Rarely, patients can experience decrements to values below 10 mEq/L.
Conditions or therapies that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, surgery, ketogenic diet, or drugs) may be additive to the bicarbonate lowering effects of topiramate.
Some manifestations of acute or chronic metabolic acidosis may include hyperventilation, nonspecific symptoms such as fatigue and anorexia, or more severe sequelae including cardiac arrhythmias or stupor. Chronic, untreated metabolic acidosis may increase the risk for nephrolithiasis or nephrocalcinosis, and may also result in osteomalacia (referred to as rickets in pediatric patients) and/or osteoporosis with an increased risk for fractures. Chronic metabolic acidosis in pediatric patients may also reduce growth rates. A reduction in growth rate may eventually decrease the maximal height achieved. The effect of topiramate on growth and bone-related sequelae has not been systematically investigated.
Measurement of baseline and periodic serum bicarbonate during topiramate treatment is recommended. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing topiramate (using dose tapering). If the decision is made to continue patients on topiramate in the face of persistent acidosis, alkali treatment should be considered.
Data related to Metabolic Acidosis
Hyperchloremic, non-anion gap, metabolic acidosis (i.e. decreased serum bicarbonate below the normal reference range in the absence of chronic respiratory alkalosis) is associated with topiramate treatment. This metabolic acidosis is caused by renal bicarbonate loss due to the inhibitory effect of topiramate on carbonic anhydrase. Such electrolyte imbalance has been observed with the use of topiramate in placebo-controlled clinical trials and in the post-marketing period. Generally, topiramate-induced metabolic acidosis occurs early in treatment although cases can occur at any time during treatment. Bicarbonate decrements are usually mild-moderate (average decrease of 4 mEq/L at daily doses of 400 mg in adults and at approximately 6 mg/kg/day in pediatric patients); rarely, patients can experience severe decrements to values below 10 mEq/L. Conditions or therapies that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, surgery, ketogenic diet, or drugs) may be additive to the bicarbonate lowering effects of topiramate.In adults, the incidence of persistent treatment-emergent decreases in serum bicarbonate (levels of <20 mEq/L at two consecutive visits or at the final visit) in controlled clinical trials for adjunctive treatment of epilepsy was 32% for 400 mg/day, and 1% for placebo. Metabolic acidosis has been observed at doses as low as 50 mg/day. The incidence of a markedly abnormally low serum bicarbonate (i.e., absolute value <17 mEq/L and >5 mEq/L decrease from pretreatment) in these trials was 3% for 400 mg/day, and 0% for placebo. Serum bicarbonate levels have not been systematically evaluated at daily doses greater than 400 mg/day.
In pediatric patients (<16 years of age), the incidence of persistent treatment-emergent decreases in serum bicarbonate in placebo-controlled trials for adjunctive treatment of Lennox-Gastaut Syndrome or refractory partial onset seizures was 67% for TOPAMAX (at approximately 6 mg/kg/day), and 10% for placebo. The incidence of a markedly abnormally low serum bicarbonate (i.e., absolute value <17 mEq/L and >5 mEq/L decrease from pretreatment) in these trials was 11% for TOPAMAX and 0% for placebo. Cases of moderately severe metabolic acidosis have been reported in patients as young as 5 months old, especially at daily doses above 5 mg/kg/day.
Although not approved for the prophylaxis of migraine, the incidence of persistent treatment-emergent decreases in serum bicarbonate in placebo-controlled trials for adults for prophylaxis of migraine was 44% for 200 mg/day, 39% for 100 mg/day, 23% for 50mg/day, and 7% for placebo. The incidence of a markedly abnormally low serum bicarbonate (i.e., absolute value < 17 mEq/L and > 5 mEq/L decrease from pretreatment) in these trials was 11 % for 200 mg/day, 9 % for 100 mg/day, 2 % for 50 mg/day, and < 1 % for placebo.
Safety and effectiveness in patients below the age of 2 years have not been established. Topiramate is associated with metabolic acidosis. Chronic untreated metabolic acidosis in pediatric patients may cause osteomalacia (rickets) and may reduce growth rates. A reduction in growth rate may eventually decrease the maximal height achieved. The effect of topiramate on growth and bone-related sequelae has not been systematically investigated.
Posted by ed_uk on April 23, 2005, at 18:19:09
In reply to Topamax (topiramate) Toxicity, posted by ed_uk on April 23, 2005, at 17:56:02
OK, loss of appetite is a frequent side effect of Topamax. Loss of appetite is one of the symptoms of metabolic acidosis. Could it be that Topamax reduces appetite simply by inducing metabolic acidosis- a biochemical derangement? This would *not* be a healthy means of losing weight!
Topamax is a carbonic anhydrase inhibitor. Acetazolamide is a carbonic anhydrase inhibitor which is used to treat glaucoma.
Topamax and acetazolamide *share* many side effects, some (but not all) of these side effects may be the result of metabolic acidosis.
Common side effects shared by Topamax and acetazolamide...........
Taste disturbances, loss of appetite, weight loss, paresthesia (numbness/tingling), fatigue, kidney stones etc.
Have a look at this.........................
Carbonic anhydrase inhibitor side effects. Serum chemical analysis.
Epstein DL, Grant WM.
Multiple serum chemical values were examined in 92 patients with chronic glaucoma who were treated with the carbonic anhydrase inhibitors (CAIs) acetazolamide or methazolamide, seeking relationships between serum composition and symptomatic side effects. Of the 92 patients, 44 complained of a symptom-complex of malaise, fatigue, weight loss, depression, anorexia, and loss of libido, which we have found most commonly to threaten continuation of therapy. Patients who had this symptom complex were significantly more acidotic than those without it. Ten of 24 patients who had chemical evidence of excessive acidosis reported a dramatic alleviation of symptoms when sodium bicarbonate was administered.
...........In this study, patients' acidosis was treated with sodium bicarbonate, therefore relieving the side effects. Potassium bicarbonate might also be useful.
I wonder.........
..........to what extent could Topamax's side effects be relieved by treating drug-induced acidosis with sodium bicarbonate? (or potassium bicarbonate).........
..........Would this prevent Topamax-induced kidney stones?
Also, might a sodium/potassium bicarbonate supplement prevent Topamax from causing weight loss??? If it did, this would suggest that Topamax causes weight loss by inducing metabolic acidosis.
Metabolic acidosis can be dangerous- as described by Health Canada. Osteoporosis is a potential risk. It may be advisable to monitor clinical chemistry while taking Topamax. If significant metabolic acidosis is detected, several options are available.........
Reduce the dose of Topamax
Discontinue Topamax
Treat the acidosis with sodium bicarbonate and/or potassium bicarbonate..............................................................................................................
Zonisamide (Zonegran) is another anti-epileptic which is known for causing weight loss. Zonegran is also a carbonic anhydrase inhibitor! Metabolic acidosis has been reported with Zonegran.
'Three cases of hypoactivity and poor appetite with zonisamide-induced metabolic acidosis'
Ed.
Posted by not_so_pro_social on April 24, 2005, at 2:16:03
In reply to Re: Topamax (topiramate) Toxicity, posted by ed_uk on April 23, 2005, at 18:19:09
Sorry Ed I have a hangover and its hard to read such long posts:) Could you just say in one word, is it THAT harmful to not take it?
This is the end of the thread.
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