Currently Enrolling Trials
Actiq (fentanyl citrate) is an oral transmucosal lozenge. It is a solid formulation of fentanyl, an opioid agonist, intended for oral transmucosal administration.
Actiq is specifically indicated for the management of breakthrough pain in cancer patients 16 years of age and older who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain. Patients considered opioid tolerant are those who are taking, for one week or longer, around-the-clock medicine consisting of at least 60 mg of oral morphine per day, at least 25 mcg of transdermal fentanyl per hour, at least 30 mg of oral oxycodone per day, at least 8 mg of oral hydromorphone per day, at least 25 mg oral oxymorphone per day, at least 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. Patients must remain on around-the-clock opioids while taking Actiq.
• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. • Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse. • Initial dose of Actiq: 200 mcg. Prescribe an initial supply of six 200 mcg Actiq units. • Individually titrate to a tolerable dose that provides adequate analgesia using single Actiq dosage unit per breakthrough cancer pain episode. • No more than two doses can be taken per breakthrough pain episode. • Wait at least 4 hours before treating another episode of breakthrough pain with Actiq • Limit consumption to four or fewer units per day once successful dose is found. • When opioid therapy is no longer required, consider discontinuing Actiq along with a gradual downward of other opioids to minimize possible withdrawal effects.
The FDA approval of Actiq was based on the following:
A clinical trial in 257 opioid tolerant adult cancer patients experiencing breakthrough cancer pain. Breakthrough cancer pain was defined as a transient flare of moderate-to-severe pain occurring in cancer patients experiencing persistent cancer pain otherwise controlled with maintenance doses of opioid medications including at least 60 mg morphine/day, 50 mcg transdermal fentanyl/hour, or an equianalgesic dose of another opioid for a week or longer. In two dose titration studies 95 of 127 patients (75%) who were on stable doses of either long-acting oral opioids or transdermal fentanyl for their persistent cancer pain titrated to a successful dose of Actiq to treat their breakthrough cancer pain within the dose range offered (200, 400, 600, 800, 1200, and 1600 mcg). A “successful” dose was defined as a dose where one unit of Actiq could be used consistently for at least two consecutive days to treat breakthrough cancer pain without unacceptable side effects. In these studies 11% of patients withdrew due to adverse reactions and 14% withdrew due to other reasons. The successful dose of Actiq for breakthrough cancer pain was not predicted from the daily maintenance dose of opioid used to manage the persistent cancer pain and is thus best determined by dose titration.
A double-blind placebo controlled crossover study was performed in cancer patients to evaluate the effectiveness of Actiq for the treatment of breakthrough cancer pain. Of 130 patients who entered the study 92 patients (71%) achieved a successful dose during the titration phase. Actiq was administered beginning at Time 0 minutes and produced more pain relief compared with placebo at 15, 30, 45, and 60 minutes as measured after the start of administration. The differences were statistically significant.
Adverse effects associated with the use of Actiq may include, but are not limited to, the following:
The Actiq drug label comes with the following Black Box Warning:
Serious, life-threatening, and/or fatal respiratory depression has occurred. Monitor closely, especially upon initiation or following a dose increase. Due to the risk of fatal respiratory depression, Actiq is contraindicated in opioid non-tolerant patients and in management of acute or postoperative pain, including headache/migraines. • Accidental ingestion of Actiq , especially by children, can result in a fatal overdose of fentanyl. Keep out of reach of children. Ensure proper storage and disposal. • Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of fentanyl. • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation. • When prescribing, do not convert patients on a mcg per mcg basis from any other fentanyl product to Actiq. • When dispensing, do not substitute with any other fentanyl products. • Actiq exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient’s risk before prescribing and monitor closely for these behaviors and conditions. • Actiq is available only through a restricted program called the TIRF REMS Access program. Outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors are required to enroll in the program. • Prolonged use of Actiq during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Mechanism of Action
Actiq (fentanyl citrate) oral transmucosal lozenge is a solid formulation of fentanyl, an opioid agonist, intended for oral transmucosal administration. The precise mechanism of the analgesic action is unknown although fentanyl is known to be a mu-opioid receptor agonist. Specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and play a role in the analgesic effects of this drug.