- Tramadol US
- Issuing Office:
- Center for Drug Evaluation and Research | CDER
RE: Notice of Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet
DATE: August 16, 2022
This is to advise you that the United States (U.S.) Food and Drug Administration (FDA) has observed that Tramadol US introduces into interstate commerce misbranded and unapproved new drugs in violation of sections 301(a), 301(d), 301(k), 503(b), and 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. §§ 331(a), 331(d), 331(k), 353(b), and 355(a)].
As discussed below, FDA has observed that Tramadol US introduces into interstate commerce unapproved and misbranded opioid drug products. Opioid addiction and abuse have created an immense public health crisis, and the death toll is staggering. Given the severity of the opioid epidemic, the easy availability of opioids via the Internet poses significant risks to U.S. consumers.
FDA has also observed that Tramadol US introduces into interstate commerce misbranded benzodiazepines. Benzodiazepines are drug products with an acknowledged potential for abuse, and it is important to address the public health impact of their nonmedical use. Benzodiazepine nonmedical use is widespread, and individuals frequently co-use benzodiazepines with alcohol, prescription opioids, and illicit drugs. Associated harms of benzodiazepine nonmedical use are substantial, but occur primarily when people use benzodiazepines in combination with other drugs. Further, in cases where benzodiazepines were co-used with other substances, medical outcomes are typically more severe than in cases involving benzodiazepines alone. Polysubstance overdose deaths account for the vast majority of overdose deaths documenting involvement of benzodiazepines. The easy availability of benzodiazepines via the Internet poses additional significant risks to U.S. consumers.
There are inherent risks to consumers who purchase unapproved new drugs and misbranded drugs. Unapproved new drugs do not carry the same assurances of safety and effectiveness as those drugs subject to FDA oversight. Drugs that have circumvented regulatory safeguards may be contaminated, counterfeit, contain varying amounts of active ingredients, or contain different ingredients altogether. Accordingly, FDA requests that Tramadol US cease offering any unapproved and misbranded drugs for sale to U.S. consumers. This is critical to shielding the American public from harm.
Unapproved New Drugs:
Certain products offered for sale by Tramadol US are drugs within the meaning of section 201(g) of the FD&C Act [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and/or because they are intended to affect the structure or function of the body. These drugs are also new drugs as defined by section 201(p) of the FD&C Act [21 U.S.C. § 321(p)], because they are not generally recognized as safe and effective for their labeled uses. With certain exceptions not applicable here, new drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in section 505(a) of the FD&C Act [21 U.S.C. § 355(a)]. No approved applications pursuant to section 505 of the FD&C Act are in effect for these products. Accordingly, their introduction or delivery for introduction into interstate commerce violates sections 301(d) [21 U.S.C. § 331(d)] and 505(a) of the FD&C Act.
For example, Tramadol US offers tramadol marketed as “Tramadol 100mg,” described as used to “help to treat moderate pain and difficulty in adults.” While there are FDA-approved versions of tramadol on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for the “Tramadol 100mg” offered by Tramadol US. FDA-approved tramadol is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate and is only available pursuant to a prescription from a licensed practitioner. FDA-approved tramadol bears a boxed warning, commonly referred to as a “black box warning,” which is the strongest warning FDA requires, indicating that the drug carries a significant risk of serious or even life-threatening adverse effects. The boxed warning addresses risks including addiction, abuse, misuse, life-threatening respiratory depression (breathing problems), and neonatal opioid withdrawal syndrome (withdrawal symptoms in newborn baby). In addition, when taken in conjunction with other central nervous system depressants, including alcohol and benzodiazepines, use may result in coma or death.
Tramadol US also offers oxymorphone, including a product marketed as “Opana ER 15mg.” Tramadol US describes “Opana ER” as “an opioid pain medication belonging to the group of drugs called narcotic analgesics,” and as a medicine that “has the potential to mitigate severe pain.” There are no approved drug applications pursuant to section 505 of the FD&C Act in effect for the “Opana ER 15mg” offered by Tramadol US.1 FDA-approved drug products containing oxymorphone are only available pursuant to a prescription from a licensed practitioner.
A drug is misbranded under section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)] if its labeling fails to bear adequate directions for use. “Adequate directions for use” means directions under which a layperson can use a drug safely and for the purposes for which it is intended (see 21 CFR 201.5). Prescription drugs, as defined in section 503(b)(1) of the FD&C Act [21 U.S.C. § 353(b)(1)] include those that, because of their toxicity or other potentiality for harmful effect, and/or the method of their use, and/or the collateral measures necessary for their use, are not safe for use except under supervision of a practitioner licensed by law to administer them. Prescription drugs, as defined in section 503(b)(1)(A) of the FD&C Act, can be used safely only at the direction, and under the supervision, of a licensed practitioner.
Because the aforementioned drugs are prescription drugs intended for conditions that are not amenable to self-diagnosis and treatment by a layperson, adequate directions cannot be written such that a layperson can use the products safely for their intended use. Consequently, the labeling for these drugs fails to bear adequate directions for use, causing them to be misbranded under section 502(f)(1) of the FD&C Act. In addition, because the drugs are not approved in the U.S., they are also not exempt under 21 CFR 201.115(a) from the requirements of section 502(f)(1) of the FD&C Act. By offering these drugs for sale to U.S. consumers, Tramadol US is causing the introduction of misbranded drugs into interstate commerce in violation of section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].
Additionally, FDA has observed that Tramadol US offers prescription drugs for sale without a prescription. For example, on your website www.yellowxanaxbarsforsale.com, Tramadol US offers alprazolam marketed as “Yellow Xanax Bars” described as “a moderate strength of alprazolam with 2mg of active drug.” In the description for Yellow Xanax Bars, Tramadol US states, “You can order Yellow Xanax online to manage generalized anxiety disorder, panic attacks, and social anxiety disorder.” Tramadol US also states that “Yellow Xanax Bars” are available “Without Prescription.” FDA‐approved alprazolam is a benzodiazepine indicated for the acute treatment of generalized anxiety disorder in adults and treatment of panic disorder with or without agoraphobia in adults and is only available by prescription. FDA‐approved alprazolam bears a boxed warning that includes risks associated with the concomitant use of benzodiazepines and opioids, which may result in profound sedation, respiratory depression, coma, and death. In addition, the boxed warning addresses risks including abuse, misuse, addiction, and physical dependence.
Under U.S. law, prescription drugs can be dispensed only pursuant to a prescription from a healthcare practitioner licensed by law to administer prescription drugs. By offering the aforementioned drug without requiring a prescription, Tramadol US jeopardizes patient safety and misbrands the drug under section 503(b)(1) of the FD&C Act. Dispensing a prescription drug without a prescription is an act which results in the drug being misbranded while held for sale, in violation of section 301(k) of the FD&C Act [21 U.S.C. § 331(k)].
FDA is sending this warning letter to Tramadol US because of the inherent risks to consumers who purchase misbranded and unapproved new drugs. This letter is not intended to identify all the ways in which your products or operations might be in violation of the law. Furthermore, included below is a list of websites identified as part of your network (this is not intended to be all‐inclusive). It is your responsibility to ensure that all products you offer for sale are in compliance with the FD&C Act and its implementing regulations. You should take prompt action to address any violations of the FD&C Act (which may include the offer for sale of similarly misbranded and/or unapproved new drugs other than the drugs noted above). We advise you to review your websites, product labels, and other labeling and promotional materials to ensure that you are not misleadingly representing your products as safe and effective for a use for which they have not been approved by FDA and that you are not distributing misbranded products in violation of the FD&C Act.
Please notify this office in writing within 15 working days describing the specific steps you have taken to address any violations and to prevent their recurrence. Include an explanation of each step being taken to remedy and prevent the recurrence of any violations, as well as copies of related documentation. Failure to adequately address this matter may result in legal action, including, without limitation, seizure and injunction, without further notice. If you cannot complete corrective action within 15 working days, state the reason for the delay and the time within which you will complete the corrections. This letter notifies you of our concerns and provides you with an opportunity to address them. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration within 15 working days.
If you are not located in the U.S., please note that products that appear to be misbranded or unapproved new drugs may be detained or refused admission. We may advise the appropriate regulatory officials in the country from which you operate that your products referenced above appear to be unapproved and misbranded products that cannot be legally sold to consumers in the U.S.
Please direct your response and any inquiries to FDA at FDAInternetPharmacyTaskForce-CDER@fda.hhs.gov.
S.Leigh Verbois, Ph.D.
Director, Office of Drug Security, Integrity, and Response
Office of Compliance
Center for Drug Evaluation and Research
Table of Websites:
1 In December 2020, at the request of Endo Pharmaceuticals, Inc., FDA announced that it was withdrawing approval of the new drug application (NDA) for OPANA (oxymorphone hydrochloride) extended‐release (ER) tablets, 5 milligrams (mg), 7.5 mg, 10 mg, 15 mg, 20 mg, 30 mg, and 40 mg, held by Endo Pharmaceuticals, Inc. (Accessible at https://www.federalregister.gov/documents/2020/12/23/2020-28283/endo-pharmaceuticals-inc-withdrawal-of-approval-of-a-new-drug-application-for-opana-oxymorphone).