Drs Godat and Craddock » 2. December. Actiq. It is also available as a generic product known as Oral Transmucosal Fentanyl Citrate (OTFC). This lollipop form of fentanyl is one of five prescription dosage forms of the opiate, the others being fentanyl solution for intravenous injection (no brand name), a film for buccal application (brand name Onsolis. All dose forms of fentanyl citrate are listed as Schedule II controlled substances under the Federal Controlled Substances Act. One Actiq or OTFC lollipop contains 2 grams of sugar in a raspberry flavored additive. It is available in 6 different microgram (mcg) strengths of fentanyl citrate: 2.
Cicadas don’t use antibacterial wing sanitizer, so how do these insects keep their wings free of bacteria? Hint: it’s structural. The wings of the Clanger cicada. The invention comprises a transdermal dosage form comprising an active agent component comprising an active agent and an adverse agent component comprising an adverse.
Only a candy bar-sized patch of skin on her. That's how much he needs to patch the lower half. Search the history of over 505 billion pages on the Internet. From Chocolate to Morphine. Fentanyl also comes as a transdermal patch. 30 shows individual plasma concentrations of fentanyl following the 30 minute application of a 2 cm 2 Duragesic. Can be injected, inhaled, snorted, taken in 'chiclet' or patch form. Warning signs of Fentanyl abuse include: Sleepiness.
Each strength is packaged in boxes of 3. Given that fentanyl is approximately 1. As a result of the repetitive fentanyl dosing using a dose form of high sugar content, Actiq use could cause significant dental problems. Oral adverse reactions reported in clinical trials have included tooth caries, gum hemorrhage, mouth ulceration, oral moniliasis, dry mouth, and cheilitis. Because of the high sugar content (2 grams of hydrated dextrates per unit), frequent consumption may increase the risk of dental decay. The occurrence of dry mouth caused by the fentanyl may add to that risk.
Title: Christian Musician Magazine - Sep/Oct 2014, Author: Worship Musician & Christian Musician Magazine, Name: cm
Case Report and Dental Concerns. Gee et al (“Dental Disease and the Use of Oral Transmucosal Fentanyl: A Case Report,” American Academy of Pain Medicine, 2. February 7- 1. 0, 2. New Orleans Paper # 1.
He had been treated with OTFC for more than three years and during that time developed extensive dental caries, decay, and tooth loss. He was first prescribed OTFC (4. PRN) in November 2. Dosing increased through June 2. The patient reported annual dental prophylaxis and minimal carious history.
Prior records were not available for review. A dental examination in March 2. By June 2. 00. 4, he had undergone extraction of eleven teeth. In May 2. 00. 5, extraction of all remaining teeth was recommended.
The authors of the case study proposed that the sugar content of OTFC was causally related to his advanced decay. They suggested that further studies were warranted to discern a correlation, if any, between the use of OTFC in the management of chronic pain and dental disease. Postmarketing reports of dental decay have been received from patients taking Actiq. In some of these patients, dental decay occurred despite reported routine oral hygiene. Since patients are taking Actiq “as needed” for pain, any given patient could be taking significant numbers of lollipops each day and month. It is not known at this time what the sugar content is, if any, in the Fentora dose form. However, the assumption is it will cause dry mouth because of the fentanyl component.
More on Actiq (oral transmucosal fentanyl)Actiq gained FDA approval for the management of breakthrough cancer pain in patients with malignancies who are already receiving, and who are tolerant to, opioid therapy, such as the fentanyl transdermal patch, morphine, or oxycodone, for their underlying persistent cancer pain. Actiq achieved off- label status as a powerful pain reliever (8. Normally 2. 5% of the drug is taken up through the oral mucosa and the remainder swallowed and absorbed through the GI tract. Two thirds of the swallowed fentanyl is metabolized in the liver to inactive compounds leaving only about 3.
Thus, the drug is much more effective when absorbed through the oral mucosa. It is most effective when consumed in exactly 1. Patients taking Actiq for severe pain are warned not to take more than 1.
It has been reported that some patients with severe chronic pain may be taking up to 3. Uses for Actiq (oral transmucosal fentanyl) in Noncancer Pain. Actiq and Migraine. In a report by Landy SH (Oral Transmucosal Fentanyl Citrate for the Treatment of Migraine Headache Pain in Outpatients: A Case Series,” Headache, 2. They were instructed to self- administer at home and complete a diary recording pain intensity (1.
OTFC. They recorded satisfaction with the effectiveness of OTFC (from 1 to 7 categories) ranging from “very dissatisfied” through “very satisfied” rated at 1. Results of the Landy study: Eighteen patients (1. OTFC. The drug successfully treated migraine episodes in all 1.
The OTFC rapidly reduced pain intensity, with significant improvement within 1. Mean pain intensity significantly declined from 8. Patients satisfaction ratings with OTFC were overwhelmingly positive, with 9. Three patients experienced nausea, two experienced somnolence, and one each experienced itching, vomiting, and dry mouth.
Conclusion of the Landy study: OTFC rapidly and significantly relieved acute migraine pain in outpatients, and was associated with a high patient satisfaction rating. OTFC may be effective for outpatient treatment of acute, refractory migraine headache pain.
Actiq and Decrease in Emergency Room Visits. Tennant F and Hermann L (Pain Medicine, 3(2): 1. June 2. 00. 2) proposed that self treatment with OTFC use may prevent emergency room visits.
To determine if OTFC is effective and safe for at home treatment of emergency pain flares, 9. All additionally used a short- acting oral opioid, suppository, or injectable opioid for self- treatment of emergency flares. All were given OTFC to alternatively substitute for their current opioid to self- treat emergency flares. Patients were surveyed after three or more months of OTFC use, and 8. OTFC. Seventy- one (7.
OTFC had prevented the necessity to attend an emergency room or enter a hospital for pain control. Forty- five (5. 0. OTFC for 3. 75 months and during that period could specifically estimate, based on previous experience, they had avoided 4. Prescription fentanyl citrate in all its dose forms is diverted to the street via pharmacy theft, fraudulent prescriptions, and illicit distribution by patients. In order to curb misuse, many health insurers have begun to require precertification of the prescribers and/or quantity limits for Actiq prescriptions. It is claimed that only a small proportion of people will abuse Actiq and that the majority of users really need and use it legitimately for relief of chronic pain.
In summary, Actiq (oral transmucosal fentanyl) offers a dose form of a powerful opioid offering rapid relief of intense pain and is associated with tooth decay. Its high sugar content and repeated use, both for breakthrough cancer pain and noncancer pain, offer optimal conditions for dental problems. Dental Implants do not get cavities and may be the best way to manage severe tooth decay problems.
Drug information is constantly changing. Promote medication safety in your practice with Lexi- Comp ONLINE for Dentistry.
Patent US8. 77. 83. Tamper resistant transdermal dosage form. BACKGROUND OF THE INVENTION1. Field of the Invention.
The present invention relates to transdermal dosage forms which are useful for preventing or discouraging tampering, abuse, misuse or diversion of a dosage form containing an active pharmaceutical agent, such as an opioid. The present invention also relates to methods of treating a patient with such a dosage form. The application claims the benefit of U. S. Provisional Application No. Apr. Provisional Application No. Apr. 3. 0, 2. 00.
Background of the Invention. Transdermal drug delivery is a well known method for administering pharmaceuticals. Although a transdermal dosage form is intended to deliver drug across the skin, misuse or abuse of such a dosage form can take place by other modes, including oral, buccal, and intravenous. Such misuse may take place following an extraction procedure comprising immersing the transdermal dosage form in a solvent, such as water, alcohol, ethanol, or ether. Transdermal dosage forms comprising both a drug and an antagonist for the drug have been previously proposed.
Lee et al.) describes a transdermal dosage form which comprises a mixture of a drug and an antagonist for the drug. Granger, et al.) describes a transdermal dosage form comprising an opioid, an antagonist for the opioid releasable upon ingestion or solvent immersion of the dosage form, and a barrier means and an impermeable barrier means separating the opioid and the antagonist. There exists a need in the art for improved designs for transdermal dosage forms which provide for the enhanced release of the adverse agent upon exposure of the dosage form to solvents, such as water, alcohol or ether. SUMMARY OF THE INVENTIONIn one embodiment, the present invention relates to a transdermal dosage form comprising an active agent- containing component (an .
The active agent component has a proximal surface, a distal surface, and at least one active agent component channel passing between the proximal and distal surfaces. The barrier is disposed between the distal surface of the active agent component and the adverse agent component. The barrier at least partially dissolves in the presence of and/or is permeable to many solvents, such as water, ethanol, ether, and mixtures thereof, and the barrier is impermeable to diffusion of the active agent and the adverse agent in the absence of a suitable solvent. In one embodiment, the transdermal dosage form further comprises an adhesive component connecting the adverse agent component and the barrier. In another embodiment, the present invention comprises a transdermal dosage form comprising an active agent component comprising a polymeric material and an active agent, an adverse agent component comprising an adverse agent, and a discontinuous barrier. The active agent component defines at least one active agent component channel passing substantially through the active agent component.
The discontinuous barrier is interposed between the active agent component and the adverse agent component. The barrier material is impermeable to diffusion of the active agent and the adverse agent. In still another embodiment, the present invention comprises a transdermal dosage form comprising a skin- contacting component comprising a polymeric material and an active agent, a backing, and a reservoir component comprising an adverse agent. The skin- contacting component has a first skin- contacting surface and a second surface opposed to the skin- contacting surface. The reservoir component is interposed between the skin- contacting component and the backing. The adverse agent in the reservoir component is not in diffusional communication with the skin- contacting component. The active agent in the skin- contacting component is not in diffusional communication with the reservoir component.
The dosage form comprises at least one channel passing between the skin- contacting surface and the reservoir component. In certain embodiments, the present invention relates to a transdermal dosage form comprising an active agent component comprising an active agent and having a proximal surface and a distal surface, an adverse agent component comprising an adverse agent, wherein the adverse agent component is disposed distally of the distal surface of the active agent component, and at least one means for providing fluid communication between the proximal surface of the active agent component and the adverse agent component.
In one embodiment, the present invention relates to a transdermal dosage form comprising an active agent component comprising a plurality of structured active agent elements comprising a polymeric material and an active agent, wherein the structured active agent elements have a first, skin- contacting surface and a second surface opposed thereto, and adverse agent component comprising an adverse agent, and, a barrier disposed between the active agent component and the adverse agent component, wherein the barrier is impermeable to diffusion of active agent and adverse agent, and wherein the barrier extends to and abuts the first, skin- contacting surface of the structured active agent elements at points in between neighboring structure active agent elements. In certain embodiments, the present invention relates to a transdermal dosage form comprising an active agent- containing component (an .
In one embodiment, the porous medium is in fluid communication with a portion of the active agent component. In one embodiment, the adverse agent component is interposed between the active agent component and the backing.
In one embodiment, at least a portion of the adverse agent is contained within a porous medium. In another embodiment, the invention further comprises a barrier component adjacent to the distal surface of the active agent component. In still another embodiment, the porous medium comprises a polymeric film. In certain embodiments, the present invention relates to a transdermal dosage form comprising an active agent component comprising an active agent, an adverse agent component comprising an adverse agent and disposed distally of the active agent component, and means for providing capillary force to a surface of the adverse agent layer in the presence of a liquid. In certain embodiments, the present invention provides a transdermal dosage form that is resistant to tampering through extraction of the active agent from the dosage form by the incorporation of an adverse agent which is also extracted during such tampering.
Such extraction may be performed, for example, in vitro, such as in a laboratory type setting (e. In certain embodiments, the present invention provides a tamper- resistant transdermal dosage form that comprises an adverse agent for an active agent, wherein a significant amount of the adverse agent is not delivered to the skin mucosa surface during intended use, but wherein a sufficient amount of the adverse agent will be released from the dosage form along with the active agent during attempted tampering to blunt or block at least one biological effect of the active agent, such as euphoric effect of an opioid active agent, or to produce one or more unpleasant physiological reactions, such as nausea. The present invention further relates to methods of treating a patient, comprising applying a dosage form of the invention to the skin or mucosa of a patient. In one embodiment of the invention, the patient is treated for pain.
The present invention also includes a method of reducing abuse, misuse or diversion of a dosage form for treating pain, comprising applying a dosage form of the invention to the skin or mucosa of a patient in need thereof. In still another embodiment, the invention relates to a kit for treating pain in a patient, comprising at least one dosage form of the invention and a set of instructions describing the use of the dosage form to treat the patient. In one embodiment of the invention, the kit is for treating a patient's pain. The present invention may be understood more fully by reference to the following detailed description and examples, which are intended to exemplify non- limiting embodiments of the invention. The above summary of the present invention is not intended to describe each disclosed embodiment or every implementation of the present invention. BRIEF DESCRIPTION OF THE DRAWINGSCertain embodiments of the invention will now be described in greater detail below with reference to the attached drawings, wherein: FIGS. FIGS. 2a, b show a schematic cross- section (2a) and a plan view (2b) of an embodiment of the present invention where the skin- contacting component comprises an annular disk with a central air channel.
FIGS. 3a, b show a schematic cross- section (3a) and a plan view (3b) of an embodiment of the present invention where the skin- contacting component comprises a disk with a plurality of cylindrical air channels. FIGS. 4a, b show a schematic cross- section (4a) and a plan view (4b) of an embodiment of the present invention where the skin- contacting component comprises strips separated by air channels. In this embodiment the barrier comprises strips separated by air channels and the barrier is aligned with the skin- contacting component.
FIGS. 5a, b show a schematic cross- section (5a) and a plan view (5b) of an embodiment of the present invention where the skin- contacting component comprises an annular disk with a central air channel. In this embodiment the barrier comprises an annular disk with a central air channel and the barrier is aligned with the skin- contacting component.
FIGS. 6a, b show a schematic cross- section (6a) and a plan view (6b) of an embodiment of the present invention where the skin- contacting component comprises a disk with a plurality of cylindrical air channels. In this embodiment the barrier comprises a disk with a plurality of cylindrical air channels and the barrier is aligned with the skin- contacting component.