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Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of ABSTRAL has been evaluated in 311 opioid-tolerant cancer patients with breakthrough pain.
Two hundred and seventy (270) of these patients were treated in multiple-dose studies. The duration of therapy for patients in multiple-dose studies ranged from 1-405 days with an average duration of 131 days and with 44 patients treated for at least 12 months.
The most commonly observed adverse reactions with ABSTRAL include typical opioid adverse reactions, such as nausea, constipation, somnolence and headache. Expect opioid side effects and manage them accordingly.
The clinical trials of ABSTRAL were designed to evaluate safety and efficacy in treating patients with cancer and breakthrough pain; all patients were taking concomitant opioids, such as sustained-release morphine, sustained-release oxycodone or transdermal fentanyl, for their persistent pain.
The adverse reaction data presented in Table 1 reflect the actual percentage of patients experiencing reactions among patients who received ABSTRAL for breakthrough pain along with concomitant opioid use for persistent pain. There has been no attempt to correct for concomitant use of other opioids, duration of ABSTRAL therapy or cancer-related symptoms.
Table 1 lists adverse reactions with an overall frequency of 5% or greater within the total population that occurred during titration by maximum dose received. The ability to assign ABSTRAL a dose-response relationship to these adverse reactions is limited by the titration schemes used in these studies.
Table 1: Adverse Reactions Which Occurred During
Titration at a Frequency of ≥ 5%
|System Organ Class
|Nausea||1 (4.5)||4 (17.4)||5 (9.1)||1 (2.6)||2 (3.8)||2 (2.5)||15 (5.6)|
|Nervous system disorders|
|Somnolence||0||2 (8.7)||4 (7.3)||2 (5.3)||2 (3.8)||2 (2.5)||12 (4.4)|
|Dizziness||0||0||3 (5.5)||2 (5.3)||0||1 (1.3)||6 (2.2)|
|Headache||0||0||0||1 (2.6)||3 (5.8)||1 (1.3)||5 (1.9)|
Table 2 lists, by successful dose, adverse reactions with an overall frequency of ≥ 5% within the total population that occurred after a successful dose had been determined.
Table 2: Adverse Reactions
Which Occurred During Maintenance Therapy at a Frequency of ≥ 5%
|System Organ Class
Preferred term N (%)
|Nausea||1 (14.3)||0||2 (9.1)||0||1 (2.9)||6 (8.3)||10 (6.0)|
|Stomatitis||0||1 (8.3)||1 (4.5)||0||0||1 (1.4)||3 (1.8)|
|Constipation||0||0||1 (4.5)||2 (10.0)||1 (2.9)||4 (5.6)||8 (4.8)|
|Dry mouth||0||0||0||1 (5.0)||2 (5.7)||0||3 (1.8)|
|Nervous system disorders|
|Headache||0||0||0||2 (10.0)||1 (2.9)||2 (2.8)||5 (3.0)|
|Dysgeusia||1 (14.3)||0||0||0||0||1 (1.4)||2 (1.2)|
|General disorders and administration site conditions|
|Fatigue||0||0||0||1 (5.0)||2 (5.7)||0||3 (1.8)|
|Injury, poisoning and procedural complications|
|Accidental overdose||1 (14.3)||0||0||0||0||0||1 (0.6)|
|Respiratory, thoracic and mediastinal disorders|
|Dyspnoea||0||1 (8.3)||0||0||0||0||1 (0.6)|
|Skin and subcutaneous disorders|
|Hyperhidrosis||1 (14.3)||0||0||0||0||1 (1.4)||2 (1.2)|
The frequencies listed below represent adverse reactions that occurred in ≥ 1% of patients from two clinical trials who experienced that reaction while receiving ABSTRAL. Reactions are classified by system organ class.
Adverse Reactions ( ≥ 1%)
Eye disorders: vision blurred.
Gastrointestinal disorders: abdominal pain, abdominal pain upper, aphthous stomatitis, constipation, dry mouth, dyspepsia, gingival ulceration, impaired gastric emptying, lip ulceration, mouth ulceration, nausea, stomach discomfort, stomatitis, tongue disorder, vomiting.
Immune system disorders: drug hypersensitivity.
Injury, poisoning and procedural complications: accidental overdose.
Metabolism and nutrition disorders: anorexia, decreased appetite.
Reproductive system and breast disorders: erectile dysfunction.
Respiratory, thoracic and mediastinal disorder: dyspnea, oropharyngeal pain, throat tightness.
Vascular disorders: hypotension.
Read the Abstral (fentanyl sublingual tablets) Side Effects Center for a complete guide to possible side effects
Fentanyl is metabolized mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4); therefore potential interactions may occur when ABSTRAL is given concurrently with agents that affect CYP3A4 activity.
The concomitant use of ABSTRAL with CYP3A4 inhibitors (e.g., indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, telithromycin, aprepitant, diltiazem, erythromycin, fluconazole, grapefruit juice, verapamil, or cimetidine) may result in a potentially dangerous increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Patients receiving ABSTRAL who begin therapy with, or increase the dose of, CYP3A4 inhibitors need to be carefully monitored for signs of opioid toxicity over an extended period of time. Increase dosage conservatively.
The concomitant use of ABSTRAL with CYP3A4 inducers (e.g., barbiturates, carbamazepine, efavirenz, glucocorticoids, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's wort, or troglitazone) may result in a decrease in fentanyl plasma concentrations, which could decrease the efficacy of ABSTRAL.
Patients receiving ABSTRAL who stop therapy with, or decrease the dose of, CYP3A4 inducers need to be monitored for signs of increased ABSTRAL activity and the dose of ABSTRAL must be adjusted accordingly.
Drug Abuse And Dependence
ABSTRAL contains fentanyl, a Schedule II substance. Schedule II opioid substances such as fentanyl, hydromorphone, methadone, morphine, oxycodone, and oxymorphone have a high potential for abuse and addiction. ABSTRAL is also subject to misuse and criminal diversion.
Abuse and Addiction
Manage the handling of ABSTRAL to minimize the risk of misuse, including the restriction of access and accounting procedures as appropriate to the clinical setting and as required by law [see HOW SUPPLIED/Storage and Handling].
Concerns about abuse, addiction, and diversion must not prevent the proper management of pain. However, all patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.
Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common. “Drug-seeking” behavior is very common in addicts and drug abusers.
Abuse and addiction are separate and distinct from physical dependence and tolerance. Be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. Since ABSTRAL may be diverted for nonmedical use, careful record keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.
Proper patient assessment, safe prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
Contact your State Professional Licensing Board, or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.
Physical dependence is not ordinarily a concern in the treatment of patients with chronic cancer pain, and fear of tolerance and physical dependence must not deter using opiate doses that adequately relieve the pain. Guide the administration of Abstral by the response of the patient.
Opioid analgesics may cause physical dependence that can result in withdrawal symptoms in patients who abruptly discontinue the drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene) or mixed agonist/antagonist analgesics (pentazocine, butorphanol, buprenorphine, nalbuphine).
Physical dependence usually does not occur to a clinically significant degree until after several weeks of continued opioid usage. Tolerance, in which increasingly larger doses are required in order to produce the same degree of analgesia, is initially manifested by a shortened duration of analgesic effect, and subsequently, by decreases in the intensity of analgesia.
Last reviewed on RxList: 8/7/2013
This monograph has been modified to include the generic and brand name in many instances.
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