Purdue Pharma’s ADHD Drug Approved by FDA

ADHD Drug made by Purdue Pharma

A subsidiary of Purdue Pharma L.P., the notorious maker of Oxycontin, recently received FDA approval to market its newest ADHD drug, Adhansia XR.

The recently created subsidiary, Adlon Therapeutics, is approved to market Adhansia XR to patients as young as 6 years old.

The drug is a central nervous system (CNS) stimulant, and its active ingredient is methyplenidate hydrochloride (MHC).  MHC is the same active ingredient used in other ADHD medications, including Ritalin, Concerta, and others.

After introducing Purdue Pharma, we dive into the drug’s makeup, side effect profile, and background on methyplenidate hydrochloride.

 

About Purdue

Purdue Pharma faces over 1,000 lawsuits from local and state governments.  The plaintiffs accuse Purdue of invigorating the opioid crisis through misleading marketing that misrepresented the dangers and benefits of OxyContin.

Unfortunately, despite all the lawsuits Purdue Pharma faces, the Stamford, CT-based pharmaceuticals company is still actively looking for an advertising agency partner.

 

 

Methyplenidate Hydrochloride (MHC):  Structure and Dosage

 

The Adhansia XR capsules contain multilayered beads, composed of an immediate-release (IR) layer which contains roughly 20% of the methylphenidate dose.  In addition, the capsules contain a controlled release layer with approximately 80% of the methylphenidate dose.

The ADHD drug is available in six capsule strengths: 25 mg, 35 mg, 45 mg, 55 mg, 70 mg, or 85 mg of MHC (1).

Dosages higher than 100 mg daily in adults and 85 mg daily in pediatric patients have not been evaluated in clinical trials and are not advised by Adlon (2).

 

MHC Interactions/Side Effects:

 

MHC and Alcohol

While no deadlly interaction effects with alcohol are listed for Adhansia XR, its clear that drinking should be avoided on the drug.

In various in vitro studies, there was no increase in the rate of release of methylphenidate from ADHANSIA XR at different alcohol concentrations.  However, the listed alcohol concentrations were just 5%, 20%, and 40% at hour 1, and  5% and 20% at hour 2 (3).

However, in an in vivo alcohol interaction study of fasted healthy adults, Adhansia XR 70 mg extended-release capsules with 40% alcohol concentration resulted in a 1.4-fold increase in the peak plasma methylphenidate concentration and a 1.3-fold increase in the extent of absorption (4).

Thus, the medication was released faster with alcohol consumption in human studies (in vivo) versus in tubes (in vitro).

As Adlon advises, consumption of alcohol while taking ADHANSIA XR may result in a more rapid release of the dose of methylphenidate.  So, we’d recommend avoiding drinking altogether.

 

MHC and Growth Suppression

According to Adlon’s release:

“Patients ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated pediatric patients over 36 months (to the ages of 10 to 13 years) were carefully followed-up on weight and height in pediatric” (5).

The follow-ups suggest that consistently medicated patients (i.e., treatment for 7 days per week through the year) have a temporary reduction in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over the 3 year period), without evidence of growth rebound during the development period (6).

 

MHC and Carcinogenesis

The active ingredient in Adhansia XR has a correlation to carcinogenesis: “In a lifetime carcinogenicity study carried out in B6C3F1 mice, methylphenidate caused an increase in hepatocellular adenomas and, in males only, an increase in hepatoblastomas, at a daily dose of approximately 60 mg/kg/day”  (7).

Hepatocellular adenomas are liver tumors that have a small probability of becoming cancerous.  These tumors are often found in women with unusually high levels of estrogen.  More concerningly, hepatoblastoma is an uncommon malignant liver tumor often found in babies and young children.

According to Adlon, the mouse strain used in the studies are sensitive to the development of hepatic tumors, and the significance of these results to humans is unknown.

 

Adhansia XR Side Effects

The most commonly reported side effects for patients who discontinued Adhansia XR were numerous.  They included nausea, bronchitis, gastroenteritis viral, viral infection, blood pressure increased, and hypomania (8).

On the other hand, the most frequent side effects for adults who continued taking Adhansia XR through the study were insomnia, dry mouth, and decreased appetite.

 

Most importantly, the incidence of death, heart attacks, and other heart issues among patients taking CNS stimulants is of concern.  As Adlon warns, “sudden death, stroke and myocardial infarction have occurred in patients treated with CNS stimulants at recommended doses” (9).

CNS stimulants, including Adhansia XR, other methylphenidate-containing products, and amphetamines, also have extremely high potential for abuse and dependence.

 

ADHD Drug Clinical Trials

 

883 patients were exposed to Adhansia XR during 1- to 4-week long, controlled treatment periods.

The trials included 434 adult patients and 449 pediatric patients.

The age breakdown for pediatric patients was as follows: 156 patients of 6 to 12 years, and 293 from 12 to 17 years of age.

The above patients were tested in two clinical trials in adults, one in pediatric patients ages 12 to 17 years, and one in pediatric patients ages 6 to 12 years.

 

Adult Studies:

The descriptions for the adult studies were as follows:

First, there was a 4-week, randomized, double-blind placebo- controlled, safety and efficacy study involving adult patients aged 18 to 72 years who met the DSM-5 criteria for ADHD.

The second clinical trial was a randomized, double-blind, placebo-controlled, crossover design, adult workplace environment (AWE) study of Adhansia XR conducted in adults of 18 to 58 years who met the DSM-5 criteria for ADHD (10).

 

Pediatric Studies:

The studies for pediatric patients included an analog classroom trial over a 13-hour study day in pediatric patients ages 6 to 12 years.  In addition, the other study was a safety and efficacy study in pediatric patients ages 12 to 17 years.

The safety data for adult patients were based on two randomized, double-blind, placebo-controlled studies in doses of 25 mg to 100 mg per day. The safety data for pediatric patients (6 to 17 years) were based on randomized, double-blind, placebo-controlled studies in doses of 25 mg to 85 mg per day (12).

A double-blind, randomized, placebo-controlled crossover study evaluated Adhansia XR in adult patients with ADHD. Efficacy assessments were taken at pre-dose and 1, 2, 5, 8, 11, 14, and 16 hours post-dose.

The assessment used was the mean Permanent Measure of Performance Total scores (PERMP-T).  Specifically, the PERMP-T was averaged across all time points compared to placebo. PERMP-T is a skill-adjusted math test, and gets a combined score by adding PERMP-A (number of math problems Attempted) and PERMP-C (number of math problems Correctly answered) (13).

 

 

Results

Adults taking Adhansia XR achieved statistically significant improvements compared to the placebo group.  Specifically, the treatment group scored greater mean PERMP-T scores averaged across all time points (post-dose score of 281.3 vs. 254.5; difference of 26.80, 95% CI [15.19, 38.41]) compared to the placebo group (14).

For the pediatric studies, the Adhansia XR groups also showed a statistically significant response compared to the placebo groups.

In the pediatric studies, a SKAMP rating scale was used for one of the studies.  A SKAMP rating is  a 13-item teacher-rated scale that assesses evidence of children’s ADHD-like behavior in a classroom setting.  The SKAMP scores improved (lowered) at all time points (at 1, 2, 4, 6, 8, 10, 12, 13 hours) post-dose with Adhansia XR compared to the placebo group.

 

 

Purdue’s ADHD Drug: Conclusion/Analysis

 

The introduction and approval of Adhansia XR are significant for several reasons.

First, it represents Purdue’s efforts to expand its non-opioid pain medication line amidst the company’s negative publicity.  Second, it suggests the company may be protecting itself from litigation risk by producing new drugs through a subsidiary.  Even so, it’s doubtful Purdue or its subsidiaries would be shielded from bankruptcy claims by creditors.

Regarding the safety of Adhansia XR, its link to carcinogenesis, growth suppression, and risk of stroke are of serious concern.  The long-term efficacy and safety of Adhansia XR in patients hasn’t been established either, though this is true for most other ADHD meds too.

Importantly, the active ingredient in Adhansia XR is also the active ingredient in many other ADHD meds, as mentioned above.  Thus, the above concerns are relevant for other mainstream meds, like Ritalin and Concerta.  Unfortunately, prescription medication side effects are to be expected, and must be weighed relative to the drug’s benefits.

 

 

 

 

If you liked this piece, be sure to check out these articles:

 

What Sucks & What Rocks About ADHD

An ADHD Test Made For Adults

Vyvanse: Many Advantages as ADHD Therapy?

A Full List of ADHD Medications

 

 

 

 

References:

 

  1. //app.adlontherapeutics.com/adhansia-xr/fpi.pdf
  2. //www.accessdata.fda.gov/drugsatfda_docs/label/2019/212038Orig1s000lbl.pdf
  3. //app.adlontherapeutics.com/adhansia-xr/fpi.pdf
  4. Ibid.
  5. //www.businesswire.com/news/home/20190301005270/en/Adlon-Therapeutics-L.P.-Announces-FDA-Approval-Adhansia
  6. Ibid.
  7. //app.adlontherapeutics.com/adhansia-xr/fpi.pdf
  8. Ibid.
  9. //www.businesswire.com/news/home/20190301005270/en/Adlon-Therapeutics-L.P.-Announces-FDA-Approval-Adhansia
  10. //app.adlontherapeutics.com/adhansia-xr/fpi.pdf 
  11. Ibid.
  12. Ibid.
  13. //www.businesswire.com/news/home/20190301005270/en/Adlon-Therapeutics-L.P.-Announces-FDA-Approval-Adhansia
  14. Image reference: //www.washingtonpost.com/national/health-science/purdue-pharma-state-of-oklahoma-reach-settlement-in-landmark-opioid-lawsuit/2019/03/26/69aa5cda-4f11-11e9-a3f7-78b7525a8d5f_story.html

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