Many medical situations require knowledge about pain management, especially when dealing with the tormenting chronic pain associated with cancer. Physicians have to provide patients with relief from agonizing pain, along with investigating the underlying cause. Opioids are a recognized class of analgesia for pain management with established therapeutic outcomes and side effects. Fentanyl is a strong synthetic short-acting opioid that acts on mu-receptors with greater than 50 to 100-fold potency than morphine, and its primary use is for analgesia and sedation. Opioids have numerous routes of administration; however, the oral route is a preferred method of delivery due to its noninvasive nature. Oral transmucosal fentanyl citrate (OTFC) incorporates fentanyl citrate into lozenges, which slowly dissolve in the mouth and undergo rapid absorption via the oral mucosa. Breakthrough pain (BTP) is a severe episodic flare-up of pain in cancer patients with long-term opioid controlled baseline pain. BTP is a severe, paroxysmal, and brief episode of pain that peaks in intensity in 3 to 52 minutes. BTP results in daily functional impairment, psychological disturbance, and increased utilization of medical resources. The duration, intensity, and pathophysiology of BTP make it difficult to manage. OTFC has received approval from the Food and Drug Administration (FDA) and indicated specifically for the management of BTP in cancer patients due to its rapid onset and short duration of analgesia, which mimic the characteristics of BTP episodes. Two randomized, double-blinded studies demonstrated that OTFC had superior analgesic effects, greater global satisfaction, and faster onset of action in the management of BTP than the usual BTP medications. A study evaluating the efficacy of OTFC for the management of severe pain crisis in cancer patients reported OTFC treatment resulted in reducing the mean pain intensity of patients from 9.0 to 3.0.  This study demonstrated that OTFC prevented the need for hospitalization or parenteral opioids administration for the management of BTP., suggesting that OTFC is an ideal alternative to intravenous opioids for the management of BTP episodes in cancer patients. OTFC rapid onset, coupled with its short duration of analgesia and its noninvasive delivery (oral), makes it ideal to be used for the management of paroxysmal, severe, and brief episodes of BTP.[1][2][3][4][5][6][7][8][9][10]

OTFC can also have a role in non-FDA approved indications in non-cancerous patients as a treatment of moderate to severe postoperative pain. A randomized, double-blinded study investigated potency, pain relief and pain intensity in 133 postoperative patients assigned to one of four treatment groups: high- or low-dose OTFC (800 micrograms vs. 200 micrograms), or high- or low-dose intravenous (IV) morphine (10 milligrams or 2 milligrams). It demonstrated that the higher dosage groups of OTFC and morphine provided superior analgesia than the lower dosage groups of OTFC and morphine. Higher dosage groups of OTFC and morphine produced pain relief with the duration of analgesia lasting 3.5 hours, while lower dosage groups of OTFC and morphine provided pain relief for approximately 2.5 hours. There was no significant difference in pain relief outcomes when comparing similar dosage groups between the two medications. The study demonstrated that the relative potency of OTFC to morphine was between 8 and 14 to 1.[11]

OTFC is a solid formulation of lipophilic fentanyl citrate. Its mechanism of action involves acting as an agonist on mu-receptors in the brain and spinal cord, resulting in therapeutic outcomes of sedation and analgesia. As the lozenges of OTFC dissolve, 25% of the total fentanyl is absorbed across the oral mucosa, while the remainder 75% is swallowed. One-third of the 75% escapes the first-pass metabolism and is slowly absorbed in the intestines. OTFC rapid absorption across the oral mucosa coupled with its fast diffusion across the blood-brain barrier establishes its rapid onset. Delivery of fentanyl as OTFC via the oral mucosa is advantageous due to the nature of the oral mucosa. The oral mucosa is highly permeable and vascular, allowing lipophilic compounds to diffuse across the mucosa into the bloodstream easily. The oral mucosa has a uniform temperature and increased surface area, accentuating the delivery of OTFC.[12][13]

OTFC is available as a sweetened lozenge with a fentanyl citrate base for oral administration by sucking to facilitate oral transmucosal absorption. OTFC is available in six different dosages based on the strength of the fentanyl citrate base: 200, 400, 600, 800, 1200, and 1600 micrograms. In BTP, it is necessary to initially establish control of chronic pain with the use of long-term opioids. Afterward, OTFC is used to treat the episodic breakthrough pains that occur. It is necessary to titrate under supervision to establish the correct dosage for controlling BTP. Start with 200 micrograms; if the BTP remains uncontrolled after 15 minutes, the patient should wait 15 more minutes and then take another lozenge (30 minutes total after the first lozenge). The patient may receive no more than two lozenges per episode of BTP during the titration period to minimize adverse side-effects. If the pain is relieved after the second dose of 200 micrograms, then for the next episode of BTP, one 400 microgram lozenge is used. If pain relief of a BTP episode requires more than two lozenges, an increase of OTFC strength is applied to the next BTP episode. After establishing the correct strength of OTFC for the control of a BTP episode, a limit of 4 units per day is set. OTFC has a rapid onset of analgesia with peak effects occurring at 20 to 40 minutes after administration and lasting 2 to 3 hours.[2][5][14][15]

OTFC is an opioid, and its side effects include nausea, constipation, confusion, dizziness, somnolence, addiction, asthenia, and hypotension. The therapeutic range is 1 to 3 nanograms/milliliters. High plasma levels can lead to respiratory depression and death. Concomitant consumption of another central nervous system (CNS) depressants (i.e., alcohol, heroin, benzodiazepines) may contribute to additive adverse effects; hence, patients with multiple CNS depressant medications require careful monitoring. Similar to all opioids, avoid use in the elderly with a history of falls.[5][16]

OTFC should not be administered to opioid intolerant patients to prevent fatal respiratory depression. Clinicians should not use it with patients who have acute or severe asthmatic patients. It is contraindicated in patients with gastrointestinal obstruction and patients with a known history of hypersensitivity (i.e., anaphylaxis) to fentanyl.