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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 2 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 2 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.

Table2: Adverse Reactions Which Occurred During Titration at a Frequency of ≥ 5%

System Organ Class
Preferred term N (%)
100 mcg
(n=22)
200 mcg
(n=23)
300 mcg
(n=55)
400 mcg
(n=38)
600 mcg
(n=52)
800 mcg
(n=80)
Total
(n=270)
Gastrointestinal disorders
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 3 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.

Table3: Adverse Reactions Which Occurred During Maintenance Therapy at a Frequency of ≥ 5%

System Organ Class
Preferred term N (%)
100 mcg
(n=7)
200 mcg
(n=12)
300 mcg
(n=22)
400 mcg
(n=20)
600 mcg
(n=35)
800 mcg
(n=72)
Total
(n=168)
Gastrointestinal disorders
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%)

Cardiac disorders: bradycardia, tachycardia.

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.

General disorders and administration site conditions: asthenia, drug withdrawal syndrome, fatigue, malaise.

Immune system disorders: drug hypersensitivity.

Injury, poisoning and procedural complications: accidental overdose.

Metabolism and nutrition disorders: anorexia, decreased appetite.

Nervous system disorders: amnesia, disturbance in attention, dizziness, dysgeusia, headache, hypoesthesia, lethargy, parosmia, somnolence, tremor.

Psychiatric disorders: affect lability, anxiety, confusional state, depression, disorientation, dysphoria, euphoric mood, insomnia, mental status changes, paranoia, sleep disorder.

Reproductive system and breast disorders: erectile dysfunction.

Respiratory, thoracic and mediastinal disorder: dyspnea, oropharyngeal pain, throat tightness.

Skin and subcutaneous disorders: hyperhidrosis, night sweats, pruritus, rash, skin lesion.

Vascular disorders: hypotension.