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Federal Register / Vol. 86, No. 138 / Thursday, July 22, 2021 / Proposed Rules
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documented abuse in the United States of amineptine.
At the 16th French Pharmacovigilance meeting in November 1994, the Fernand Widal Pharmacovigilance Centre reviewed 565 cases of amineptine overconsumption from 1978 to 1993, and reported multiple characteristics of amineptine abuse including: 1
Amineptine abusers typically had a history of alcoholism, drug abuse, and/
or eating disorders; 2 28 percent of the cases of amineptine abuse resulted in neuropsychiatric disorders; 3 11
percent of patients developed acne-like lesions from amineptine use; 4
withdrawal from amineptine abuse was described as extremely difficult; 5 only 30 percent were abstinent after one month of withdrawal and long-term abstinence was uncommon; and 6
most patients obtained amineptine from pharmacists by prescription theft or by fraudulent prescriptions. Collectively, these three reports show that there has been a continued pattern of abuse from 1978 to 1998.
DEA noted that in the WHO 2003
report, the WHOs Expert Committee on Drug Dependence stated that the degree of risk to public health associated with the abuse liability of amineptine is substantial, while noting several adverse effects including hepatotoxicity, severe acne, and anxiety. The committee also noted the limited therapeutic usefulness of amineptine due to the availability of safer antidepressants.
Queries of DEAs System to Retrieve Information from Drug Evidence STRIDE/STARLiMS 7 and the National Forensic Laboratory Information System NFLIS 8 databases on November 17, 2020, did not generate any reports of amineptine, suggesting that it is not trafficked in the United States.
5. The Scope, Duration, and Significance of Abuse: According to the published case reports from 1984 to 2001 in France, Italy, Pakistan, Singapore, and Spain, the majority of the reported cases of amineptine abuse involved patients who were prescribed amineptine for an affective disorder. In these cases, abuse normally began one 7 STRIDE is a database of drug exhibits sent to DEA laboratories for analysis. Exhibits from the database are from DEA, other federal agencies, and law enforcement agencies. On October 1, 2014, STARLiMS replaced STRIDE as DEA laboratory drug evidence data system of record.
8 NFLIS is a national drug forensic laboratory reporting system that systematically collects results from drug chemistry analyses conducted by state and local forensic laboratories across the country.
The NFLIS participation rate, defined as the percentage of the national drug caseload represented by laboratories that have joined NFLIS, is over 97%. NFLIS includes drug chemistry results from completed analyses only.

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year after amineptine was prescribed for the treatment of depression by patients independently increasing their dosage, especially in those with a history of alcoholism, intravenous drug abuse, and eating disorders.
Amineptine abuse appears to be due to its psychostimulant effect. Indeed, reasons cited for its abuse were increased energy, joy, work output, alertness, and psychomotor performance. Presently, although internet searches result in websites with purported amineptine for sale, these sites do not list the formulation, purity, price, and quantity for this purported amineptine. In addition, the 1971
Convention currently controls amineptine internationally as a Schedule II substance. Amineptine is also controlled in Belgium, Canada, the Czech Republic, Denmark, Estonia, Germany, Greece, Hungary, Italy, Latvia, Lithuania, the Netherlands, Norway, Poland, Slovenia, and Sweden.
6. What, if Any, Risk There is to the Public Health: As reported by HHS, there are no known fatalities resulting from amineptine use or abuse. Some of the main public health risks of amineptine are related to its serious adverse effects, such as hepatotoxicity, severe acne, and gastrointestinal acute pancreatitis effects. In addition, neuropsychiatric symptoms including anxiety, insomnia, nervousness, irritability, dysarthria, acute psychosis, delusions, hallucinations, anorexia, agitation, psychotic disorders, and confusion have resulted from abuse of amineptine.
7. Its Psychic or Physiological Dependence Liability: HHS stated that amineptine has been shown to produce physical and psychological dependence as supported by clinical evidence.
While amineptine has no clearly defined withdrawal syndrome, reports of withdrawal symptoms include anxiety, dysphoria, nausea, brief psychotic episodes, tremor, psychomotor agitation, somatic symptoms, and sleep disturbances. In addition, a strong desire to take amineptine was noted in individuals upon withdrawal of the drug, a typical characteristic of psychological dependence.
8. Whether the Substance is an Immediate Precursor of a Substance Already Controlled under the CSA: DEA
and HHS find that amineptine is not an immediate precursor of a substance already controlled under the CSA.
Conclusion: Based on consideration of the scientific and medical evaluation and accompanying recommendation of HHS, and based on DEAs consideration of its own eight-factor analysis, DEA

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finds that these facts and all relevant data constitute substantial evidence of potential for abuse of amineptine. As such, DEA hereby proposes to schedule amineptine as a controlled substance under the CSA.
Proposed Determination of Appropriate Schedule The CSA establishes five schedules of controlled substances known as schedules I, II, III, IV, and V. The CSA
outlines the findings required to place a drug or other substance in any particular schedule. 21 U.S.C. 812b.
After consideration of the analysis and recommendation of the Assistant Secretary for Health of HHS and review of all available data, the Administrator of DEA, pursuant to 21 U.S.C. 812b1, finds that:
1 Amineptine has a high potential for abuse. Amineptine has stimulant and euphoric effects similar to cocaine and amphetamine, which are both schedule II drugs. Amineptine has a high potential for abuse that is equivalent to cocaine and amphetamine and has been abused throughout Europe and Asia.
2 Amineptine has no currently accepted medical use in treatment in the United States. There are no approved New Drug Applications for amineptine and no known therapeutic application for amineptine in the United States.
Therefore, amineptine has no currently accepted medical use in treatment in the United States.9
3 There is a lack of accepted safety for use of amineptine under medical supervision. Clinical experience showed that patients taking amineptine under medical supervision for depression misused and abused the drug by stealing or falsifying prescriptions and taking doses that were 10 to 20 times higher than prescribed. As a result of taking higher doses, many patients developed hepatic, gastrointestinal, cardiovascular, and psychiatric side effects. Amineptine was once marketed in 66 countries throughout Europe, Africa, Asia, and 9 Although there is no evidence suggesting that amineptine has a currently accepted medical use in treatment in the United States, it bears noting that a drug cannot be found to have such medical use unless DEA concludes that it satisfies a five-part test. Specifically, with respect to a drug that has not been approved by FDA, to have a currently accepted medical use in treatment in the United States, all of the following must be demonstrated:
i. the drugs chemistry must be known and reproducible; ii. there must be adequate safety studies; iii. there must be adequate and wellcontrolled studies proving efficacy; iv. the drug must be accepted by qualified experts; and v. the scientific evidence must be widely available. 57 FR
10499 1992, pet. for rev. denied, Alliance for Cannabis Therapeutics v. DEA, 15 F.3d 1131, 1135
D.C. Cir. 1994.

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