Fentanyl Buccal Soluble Film
Name: Fentanyl Buccal Soluble Film
Side effects
Clinical Studies Experience
The safety of Onsolis has been evaluated in 306 opioid tolerant patients with breakthrough cancer pain in the efficacy study and an open-label safety study. The mean duration of therapy was 115 days, with 32 patients treated for more than 1 year.
The adverse reactions seen with Onsolis are typical opioid side effects in a population with cancer. Frequently, opioid-associated adverse reactions will cease or decrease in intensity with continued use of Onsolis. Expect opioid side effects and manage them accordingly.
The most serious adverse reactions associated with all opioids including Onsolis are respiratory depression (potentially leading to apnea or respiratory arrest), circulatory depression, hypotension, and shock. Follow all patients for symptoms of respiratory depression.
Because the clinical trials of Onsolis were designed to evaluate safety and efficacy in treating patients with breakthrough pain associated with cancer, all patients were also taking concomitant opioids, such as sustained-release morphine, sustained-release oxycodone or transdermal fentanyl, for their persistent cancer pain. The adverse event data presented here reflect the actual percentage of patients experiencing each adverse event among patients who received Onsolis for breakthrough cancer pain along with a concomitant opioid for persistent cancer pain. There has been no attempt to correct for concomitant use of other opioids, duration of Onsolis therapy, or cancer-related symptoms. Adverse reactions are included regardless of severity.
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.
Table 1 lists, by maximum dose received, adverse reactions with an overall frequency of 5% or greater that occurred during titration. The ability to assign a dose-response relationship to these adverse reactions is limited by the titration schedules used in these studies. Adverse reactions are listed in descending order of frequency within each body system.
Table 1 : Adverse Reactions Which Occurred During Titration at a Frequency of ≥ 5%
| System Organ Class, Preferred Term, n (%) | Onsolis Dose (mcg) | Total (N=306) | |||||
| 200 (N=303) | 400 (N=257) | 600 (N=207) | 800 (N=138) | 1200 (N=79) | > 1200 (N=9) | ||
| Gastrointestinal Disorders | |||||||
| Nausea | 16 (5) | 12 (5) | 6 (3) | 5 (4) | 4 (5) | 0 | 42 (14) |
| Vomiting | 7(2) | 9 (4) | 8 (4) | 2 (1) | 0 | 0 | 26 (8) |
| Nervous System Disorders | |||||||
| Dizziness | 5 (2) | 5 (2) | 6 (3) | 2 (1) | 4 (5) | 0 | 22 (7) |
| Somnolence | 6 (2) | 2 (1) | 4 (2) | 2 (1) | 4 (5) | 1 (11) | 17 (6) |
Table 2 lists, by successful dose, adverse reactions with an overall frequency of ≥ 5% that occurred during long-term treatment (i.e., the double-blind or open-label maintenance periods).
Table 2 : Adverse Reactions Which Occurred During Long-Term Treatment at a Frequency of ≥ 5%
| System Organ Class, Preferred Term, n (%) | Onsolis Dose (mcg) | Total (N=213) | |||||
| 200 (N=23) | 400 (N=59) | 600 (N=79) | 800 (N=91) | 1200 (N=81) | > 1200 (N=28) | ||
| Gastrointestinal | |||||||
| Nausea | 2 (9) | 6 (10) | 8 (10) | 12(13) | 26 (32) | 4 (14) | 56 (26) |
| Vomiting | 1 (4) | 5 (8) | 9 (11) | 8 (9) | 23 (28) | 3 (11) | 45 (21) |
| Constipation | 2 (9) | 4 (7) | 4 (5) | 4 (4) | 6 (7) | 4 (14) | 23(11) |
| Diarrhea | 1 (4) | 1 (2) | 4 (5) | 4 (4) | 10 (12) | 0 | 19 (9) |
| Dry mouth | 1 (4) | 4 (7) | 3 (4) | 2 (2) | 3 (4) | 1 (4) | 14 (7) |
| Abdominal pain | 0 | 0 | 3 (4) | 1 (1) | 7 (9) | 1 (4) | 11 (5) |
| General/administration site | |||||||
| Asthenia | 0 | 6 (10) | 3 (4) | 8 (9) | 7 (9) | 4 (14) | 28 (13) |
| Fatigue | 2 (9) | 6 (10) | 1 (1) | 7 (8) | 7 (9) | 3 (11) | 25(12) |
| Investigations | |||||||
| Weight decreased | 3 (13) | 0 | 2 (3) | 5 (5) | 5 (6) | 1 (4) | 15 (7) |
| Metabolism/nutrition | |||||||
| Dehydration | 1 (4) | 4 (7) | 6 (8) | 5 (5) | 10 (12) | 3 (11) | 28 (13) |
| Decreased appetite | 0 | 4 (7) | 4 (5) | 6 (7) | 2 (2) | 2 (7) | 18 (8) |
| Anorexia | 2 (9) | 1 (2) | 3 (4) | 4 (4) | 6 (7) | 1 (4) | 17 (8) |
| Nervous system | |||||||
| Dizziness | 2 (9) | 4 (7) | 2 (3) | 3 (3) | 10 (12) | 2 (7) | 23(11) |
| Headache | 2 (9) | 1 (2) | 3 (4) | 9 (10) | 7 (9) | 0 | 20 (9) |
| Somnolence | 2 (9) | 0 | 4 (5) | 2 (2) | 3 (4) | 3 (11) | 14 (7) |
| Psychiatric | |||||||
| Confusional state | 1 (4) | 0 | 4 (5) | 4 (4) | 6 (7) | 4 (14) | 18 (8) |
| Depression | 0 | 3 (5) | 1 (1) | 4 (4) | 7 (9) | 3 (11) | 18 (8) |
| Insomnia | 0 | 2 (3) | 2 (3) | 3 (3) | 4 (5) | 2 (7) | 12 (6) |
| Anxiety | 1 (4) | 1 (2) | 2 (3) | 3 (3) | 3 (4) | 1 (4) | 11 (5) |
| Respiratory | |||||||
| Dyspnea | 3 (13) | 4 (7) | 3 (4) | 8 (9) | 6 (7) | 3 (11) | 26 (12) |
| Cough | 1 (4) | 0 | 3 (4) | 5 (5) | 6 (7) | 1 (4) | 15 (7) |
| Vascular | |||||||
| Hypotension | 0 | 3 (5) | 3 (4) | 1 (1) | 3 (4) | 1 (4) | 11 (5) |
In a mucositis study, a group of patients (n=7) with Grade 1 oral mucositis and a matched group of control patients (n=7) without oral mucositis were included in a clinical trial designed to support the safety of Onsolis. The adverse event profile was similar in both subsets of patients. There was no evidence that Onsolis caused or worsened oral mucosal irritation or pain in either study group.
The duration of exposure to Onsolis varied greatly, and included open-label and double-blind studies. The adverse reactions listed below represent those that were reported by ≥ 1% of patients from two clinical trials (the titration and posttitration periods) while receiving Onsolis. Events are classified by system organ class.
Cardiac disorders: tachycardia
Eye disorders: vision blurred, diplopia
Gastrointestinal disorders: nausea, vomiting, constipation, diarrhea, dry mouth, abdominal pain, dyspepsia, dysphagia, abdominal distension, intestinal obstruction, flatulence
General disorders and administration site conditions: asthenia, fatigue, malaise
Injury, poisoning and procedural complications: fall, contusion
Investigations: weight decreased, blood pressure increased
Metabolism and nutrition disorders: dehydration, decreased appetite, anorexia
Nervous system disorders: dizziness, somnolence, headache, lethargy, amnesia, sedation
Psychiatric disorders: confusional state, depression, insomnia, anxiety, hallucination, agitation, mental status changes
Renal and urinary disorders: urinary retention
Respiratory, thoracic and mediastinal disorders: dyspnea, cough
Skin and subcutaneous tissue disorders: pruritus, rash
Vascular disorders: hypotension, hot flush, deep vein thrombosis, hypertension