Credit: Thinkstock The FDA has approved _ Topamax_ (topiramate) for Migraine prevention in adolescents ages 12 to 17. This makes it the first preventive treatment to be approved by the FDA for this age group. Topamax was first approved in 1996 for seizure disorders and in 2004 for Migraine prevention in adults.
The FDA approval was based on a clinical trial with 103 participants. Adolescents treated with Topamax during the trial, experienced a 72% decrease in Migraine frequency as opposed to 44% in the participants who received a placebo.
Eric Bastings, M.D., deputy director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research commented:
"Migraine headaches can impact school performance, social interactions, and family life. Adding dosing and safety information for the adolescent age group to the drug’s prescribing information will help to inform health care professionals and patients in making treatment choices."1
The most common side effects with the approved dosage of 100 mg used in the trial were:
- paresthesia (a burning or prickling sensation felt in the hands, arms, legs, or feet),
- upper respiratory infection,
- anorexia (loss of appetite), and
- abdominal pain.
Topamax must be dispensed with a Medication Guide that describes important safety information about the drug. Topamax and all anti-epileptic drugs may increase the risk of suicidal thoughts and behavior, and patients should be advised of the need to be alert for the emergence of, or worsening of, the signs and symptoms of depression, or unusual changes in mood or behavior.
Topamax increases the risk of the development of cleft lip and/or cleft palate (oral clefts) in infants born to women who take the drug during pregnancy. The benefits and risks of Topamax should be carefully weighed before using it in women of childbearing age. If the decision is made to use the medication by a woman of childbearing age, effective birth control should be used.
It’s somewhat amazing that this approval was based on a clinical trial with only 103 adolescent participants. The success rates, both with Topamax and with placebo, are unusually high. That alone indicated the need for another trial. Additionally, results of clinical trials and studies generally need to be replicated by at least one other study before action as significant as FDA approval occurs. If the FDA approval was, in part, based on clinical trials with adults, I would question the wisdom of that. Adolescents aren’t just smaller adults, and the age range of 12 to 17 includes some prepubescent adolescents. Adolescent bodies respond differently to medications. That’s one reason medications must be approved by the FDA separately from adult approval.
Every treatment decision made by patients, parents, and doctors should include a review of possible options and the potential side effects of the potential treatments as well as the warnings and precautions listed in the prescribing information. Here are the warnings and precautions from the Topamax prescribing information:2
- Acute myopia and secondary angle closure glaucoma: Untreated elevated intraocular pressure can lead to permanent visual loss. The primary treatment to reverse symptoms is discontinuation of TOPAMAX as rapidly as possible (5.1)
- Visual field defects: These have been reported independent of elevated intraocular pressure. Consider discontinuation of TOPAMAX (5,2)
- Oligohidrosis and hyperthermia: Monitor decreased sweating and increased body temperature, especially in pediatric patients (5.3)
- Metabolic acidosis: Baseline and periodic measurement of serum bicarbonate is recommended. Consider dose reduction or discontinuation of TOPAMAX if clinically appropriate (5.4)
- Suicidal behavior and ideation: Antiepileptic drugs increase the risk of suicidal behavior or ideation (5.5
- Cognitive/neuropsychiatric: TOPAMAX may cause cognitive dysfunction. Patients should use caution when operating machinery including automobiles. Depression and mood problems may occur in epilepsy and migraine populations (5.6 )
- Fetal Toxicity: TOPAMAX use during pregnancy can cause cleft lip and/or palate (5.7)
- Withdrawal of AEDs: Withdrawal of TOPAMAX should be done gradually (5.8)
- Hyperammonemia and encephalopathy associated with or without concomitant valproic acid use: Patients with inborn errors of metabolism or reduced mitochondrial activity may have an increased risk of hyperammonemia. Measure ammonia if encephalopathic symptoms occur (5.10)
- Kidney stones: Use with other carbonic anhydrase inhibitors, other drugs causing metabolic acidosis, or in patients on a ketogenic diet should be avoided (5.11)
- Hypothermia has been reported with and without hyperammonemia during topiramate treatment with concomitant valproic acid use (5.12)
When side effects are experienced, some need to be reported as soon as possible, especially since some can have permanent consequences. This is difficult enough for adults, and one must wonder if some, especially the younger or less mature adolescents between the ages of 12 and 17 can understand and know if they’re experiencing side effects and are capable of immediately reporting them to their parents. Were a doctor to prescribe Topamax for one of my grandchildren in this age range, I’d advise my children to insist that other treatments with fewer potential side effects be tried first. FDA approval for this age range doesn’t change anything. Of more than 100 treatment in use for adult Migraine prevention, only four of them are FDA approved for Migraine.
The bottom line is that parents should insist that doctors discuss all treatment options with them and their children and the treatment decisions should be made WITH parents and children, not FOR them.
1 FDA News Release. “FDA approves Topamax for migraine prevention in adolescents.” U.S. Food and Drug Administration. March 28, 2014.
2Topamax Prescribing Information. Janssen Pharmaceuticals, Inc. January, 2014.
3 Medication Guide Topamax. Janssen Pharmaceuticals, Inc. January, 2014.
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© Teri Robert, 2014 Last updated April 1, 2014.