Please See Important Safety Information, Including Boxed Warning Below

Clinical Trials – The Proof that Equetro® (carbamazepine) Extended-Release Capsules Effectively Treats Acute Manic and Mixed Episodes of Bipolar I Disorder—without weight-gain1

Overall conclusions of studies that made Equetro® (carbamazepine) Extended-Release Capsules the only carbamazepine product FDA-approved for the indication of Acute Manic and Mixed Episodes of Bipolar I Disorder1

FDA approval for Equetro® (carbamazepine) Extended-Release Capsules for the treatment of Acute Manic and Mixed Episodes of Bipolar I Disorder1,2 was based on four clinical studies (3 placebo-controlled, one open label).

The dosages of Equetro® (carbamazepine) Extended-Release Capsules in these studies ranged from 400-1600mg per day.

These studies concluded1,2:

  1. Improvement in Acute Manic Symptoms (assessed as mean change from baseline and mean Young Mania Rating Scale (YMRS) total scores)
  2. Meaningful Level of Therapeutic Response (as demonstrated by the percentage of patients having a 50% reduction in YMRS total score at endpoint vs. baseline)
  3. Statistically Significant Improvements in both Acute Manic and Mixed Symptoms (based on mean change from baseline and mean YMRS total score in all subpopulations evaluated [gender, age, race, national origin, manic vs. mixed patients])
  4. Improvement in Overall Bipolar I Symptomology (based on Clinical Global Impressions [CGI] for severity and improvement [mixed and manic Bipolar I Disorder])

Additional Commentary on Clinical Trials

A controlled study in Bipolar I Disorder (#417.301)1 demonstrated the efficacy and superiority of twice daily Equetro® (carbamazepine) Extended-Release Capsules over placebo (n=204). In another controlled study (#417.302)1, no significant difference between the two groups was seen (probably due to small sample size [n=59]), although a significant improvement in the symptoms of both the Equetro® (carbamazepine) Extended-Release Capsules and placebo groups was observed. A third controlled study (#417.304)1 was undertaken in a larger patient population (n=239) and, in this larger study, twice-daily Equetro® (carbamazepine) Extended-Release Capsules therapy clearly demonstrated efficacy and superiority over placebo.

Important facts to consider when treating your patients with Bipolar I Disorder:

  1. Equetro® (carbamazepine) Extended-Release Capsules is the only carbamazepine-containing product that has successfully completed FDA trials to establish an approved indication for the treatment of the Manic and Mixed Episodes of Bipolar I Disorder2.

    No other carbamazepine-containing product has gone through the FDA-process to obtain this indication2.
  2. Equetro® (carbamazepine) Extended-Release Capsules utilizes the unique, patented Equetro® extended-release delivery system to assure that appropriate blood levels of carbamazepine are steadily maintained. Unlike other delivery systems, the patented Equetro® extended-release delivery system microbead system is unaffected by food or patient-to-patient differences in digestive motility3-7.
  3. Recent clinical trials demonstrated that Equetro® (carbamazepine) Extended-Release Capsules therapy does not worsen depression1.

*Data on file, Validus Pharmaceuticals LLC.

WARNING

Important Safety Information about Equetro® (carbamazepine) Extended-Release Capsules

Warning Serious Dermatologic Reactions and HLA-B*1502 Allele

Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have been reported during treatment with carbamazepine. These reactions are estimated to occur in 1 to 6 per 10,000 new users in countries with mainly caucasian populations, but the risk in some Asian countries is estimated to be about 10 times higher. Studies in patients of Chinese ancestry have found a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene. HLA-B*1502 is found almost exclusively in patients with ancestry across broad areas of Asia. Patients with ancestry in genetically at-risk populations should be screened for the presence of HLA-B*1502 prior to initiating treatment with Equetro® (carbamazepine) Extended-Release Capsules. Patients testing positive for the allele should not be treated with Equetro® (carbamazepine) Extended-Release Capsules unless the benefit clearly outweighs the risk (see warnings and precautions, laboratory tests).

Aplastic Anemia and Agranulocytosis

Aplastic Anemia and Agranulocytosis have been reported in association with the use of carbamazepine. Data from a population based case-control study demonstrate that the risk of developing these reactions is 5–8 times greater than in the general population. However, the overall risk of these reactions in the untreated general population is low, approximately six patients per one million population per year for Agranulocytosis and two patients per one million population per year for Aplastic Anemia.

Although reports of transient or persistent decreased platelet or white blood cell counts are not uncommon in association with the use of carbamazepine, data are not available to estimate accurately their incidence or outcome. However, the vast majority of the cases of leukopenia have not progressed to the more serious conditions of Aplastic Anemia or Agranulocytosis.

Because of the very low incidence of Agranulocytosis and Aplastic Anemia, the vast majority of minor hematologic changes observed in monitoring of patients on carbamazepine are unlikely to signal the occurrence of either abnormality. Nonetheless, complete pretreatment hematological testing should be obtained as a baseline. If a patient in the course of treatment exhibits low or decreased white blood cell or platelet counts, the patient should be monitored closely. Discontinuation of the drug should be considered if any evidence of significant bone marrow depression develops.

Anti-epileptic drugs (AEDs), including Equetro®, may increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence of worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Please see FULL PRESCRIBING INFORMATION including contraindications, warnings and precautions, and boxed warning for additional safety information on Equetro® (carbamazepine) Extended-Release Capsules.

Please see Medication Guide for additional information.