Drugs in Perspective: Aptiom (eslicarbazepine acetate)

July 11, 2014
Abimbola Farinde, PharmD, MS, FASCP, FACA

Aptiom (eslicarbazepine acetate) is an oral antiepileptic tablet that was approved by FDA on November 8, 2013, as an add-on medication to treat seizure disorders that can be associated with epilepsy.

Seizures are recognized as the result of a brain problem and can occur as a result of the appearance of abnormal electrical activity in the human brain.1 The image that is normally conjured up when people think of seizures are sudden convulsive or involuntary contractions that can vary from mild to severe. Seizures can be categorized as focal seizures (partial seizures) or generalized seizures.1,2 Seizures are associated with a variety of causes, such as fevers, medications, head injuries, and particular diseases. Individuals who suffer from recurrent seizures as a result of a brain disorder have epilepsy that can be characterized by an enduring predisposition to generate these types of seizures.2,3

Aptiom (eslicarbazepine acetate) is an oral antiepileptic tablet that was approved by FDA on November 8, 2013, as an add-on medication to treat seizure disorders that can be associated with epilepsy.4,5 The precise mechanism of action of Aptiom has not been explained, but it is believed to involve the inhibition of voltage-gated sodium channels.5

It is available in tablet strengths of 200 mg, 400 mg, 600 mg, and 800 mg.5 The dose of Aptiom is typically started at 400 mg once daily and after a week of therapy, the dose can be increased to 800 mg once daily, which is considered to be the recommended maintenance dose.6 In patients with moderate-to-severe renal impairment (creatinine clearance [CrCl] <50 mL/min) the initial dose is 200 mg once daily and after 2 weeks the dose can be increased to 400 mg once daily with a maximum dose of 600 mg once daily.6 No dosage adjustment is necessary in patients with mild-to-moderate hepatic impairment.6

Relevance

Aptiom is recognized as a novel molecular entity or a unique active ingredient, which makes it structurally distinctive from other drugs.7 It is able to undergo fast and complete hydrolysis to eslicarbazepine, which is the metabolite that is believed to be largely responsible for producing its therapeutic effect.8

 

Studies

Three clinical trials involved patients with partial epilepsy that led to the approval of Aptiom. The 3 clinical trials included an 8-week baseline, 2-week titration, and 12-week maintenance phases that helped to establish the efficacy and subsequent approval of Aptiom in patients with partial-onset seizures not adequately controlled with 1 to 3 antiepileptics.5,8 The participants were randomly assigned to receive Aptiom or placebo. The standardized seizure frequency that was observed during the maintenance phase over 28 days was the primary end point. A dose of 400 mg/day was evaluated in studies 1 and 2 and did not show significant treatment effect. Treatment effects were statistically significant with Aptiom 800 mg/day in studies 1 and 2 but not in study 3, and with Aptiom 1200 mg in all 3 studies.5,8 At the end of each study there was an observed reduction in the frequency of seizures in patients treated with Aptiom. A statistically significant effect was identified with Aptiom treatment at doses of 800 mg/day in studies 1 and 2 but not in study 3, and at doses of 1,200 mg/day in all 3 studies versus placebo (Table 1).9

Potential advantages and disadvantages

FDA approval of Aptiom provides another new molecular entity that can be used for the treatment of epileptic seizures.9 It is approved as adjunctive therapy or add-on therapy to a patient’s current medication regimen, so if the first medication fails to produce the desired effects of seizure control, Aptiom can be included in the treatment regimen. A potential disadvantage of the drug is the possible increase of suicidal thoughts or behaviors in patients taking antiepileptic agents, which has been established with this class of drugs. It is important for patients to be monitored for signs of worsening depression, suicidal thoughts or behaviors, or unusual changes in their mood or behavior.10 Use of carbamazepine with Aptiom may require a dosage adjustment and higher doses of Aptiom may be needed if taken concurrently with phenytoin.

Cost

The estimated cost of a 30 count of 200 mg of brand name Aptiom is $539.64, 400 mg (30) is $719.28, 600 mg (60) count is $1,438.56, and 800 mg (30) count is $719.29.11

Place in therapy

FDA approval and subsequent availability of Aptiom provides another therapeutic option to the current broad list of medications, both brand and generic, that are used to provide seizure control. Aptiom is considered to be a novel antiepiletic agent that will offer a newer approach to treating epileptic seizures. It can be used as add-on or adjunctive therapy for those patients who suffer from partial-onset seizures.12

Implications

FDA approval of Aptiom has implications for the future treatment of epileptic seizures treatment. Aptiom is an antiepileptic drug and while its exact mechanism is unknown it has been shown to reduce the number of partial-onset seizures.12 Adding this drug to a patient’s current treatment plan may help to achieve greater seizure control.12

Dr Farinde serves on the faculty at Columbia Southern University, Orange Beach, Ala.

Disclosure information: The author reports no financial disclosures as related to products discussed in this article.

 

 

Table 1Standardized Seizure Frequency during Maintenance Phase over 28 Days and % Reduction from Baseline in Seizure Frequency

Placebo

Aptiom

800 mg

1200 mg

95

88

87

6.6

5.0
(0.047*)

4.3
(0.001*)

-15

-36

-39

99

87

81

8.6

6.2
(0.006*)

6.6
(0.042*)

-6

-33

-28

212

200

184

7.9

6.5
(0.058)

6.0
(0.004*)

-22

-30

-36

*Statistically significant compared to placebo

Abbreviations: LS, least squares

Source: Ref 9

 

 

References

MedlinePlus. Seizures. http://www.nlm.nih.gov/medlineplus/seizures.html. Accessed June 27, 2014.

Science Daily. Seizure. http://www.sciencedaily.com/articles/s/seizure.htm. Accessed June 27, 2014.

Ko D, Benbadis S. Epilepsy and seizures. Medscape. http://emedicine.medscape.com/article/1184846-overview. Accessed June 27, 2014.

FDA. FDA approves Aptiom to treat seizures in adults. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm374358.htm.  Accessed June 27, 2014.

Sunovion ProFile. Aptiom (eslicarbazepine acetate). https://www.sunovionprofile.com/sp/aptiom/about-aptiom.html. Accessed June 27, 2014.

Drugs.com. Aptiom. http://www.drugs.com/pro/aptiom.html. Accessed June 27, 2014.

Drugs@FDA. FDA approved drug products. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed June 27, 2014.

Aptiom [prescribing information]. Marlborough, MA: Sunovion Pharmaceuticals Inc.; November 2013.

Daily Med. Aptiom. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=3d0c9554-eaeb-4694-8089-00133fcadce3#section-14.1. Accessed June 27, 2014.

Business Wire. Once-daily Aptiom (eslicarbazepine acetate) for the adjunctive treatment of partial-onset seizures now available in U.S. pharmacies. http://www.businesswire.com/news/home/20140407005538/en/Once-Daily-Aptiom%C2%AE-eslicarbazepine-acetate-Adjunctive-Treatment-Partial-Onset#.U4Zz6k7n-P8.

Aptiom (eslicarbazepine). Lexi-Comp Online, Lexicomp. Hudson, OH: Lexi-Comp, Inc.; June 28, 2014.

Sunovion. Aptiom (eslicarbazepine acetate). http://www.aptiom.com/. Accessed June 27, 2014.

 

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