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Actiq (Fentanyl Citrate Oral Transmucosal) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Clinical Studies Experience

The safety of ACTIQ has been evaluated in 257 opioid-tolerant chronic cancer pain patients. The duration of ACTIQ use varied during the open-label study. Some patients were followed for over 21 months. The average duration of therapy in the open-label study was 129 days.

The adverse reactions seen with ACTIQ are typical opioid side effects. Frequently, these adverse reactions will cease or decrease in intensity with continued use of ACTIQ, as the patient is titrated to the proper dose. Expect opioid side effects and manage them accordingly.

The most serious adverse reactions associated with all opioids including ACTIQ 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 ACTIQ were designed to evaluate safety and efficacy in treating breakthrough cancer pain, all patients were also taking concomitant opioids, such as sustained-release morphine or transdermal fentanyl, for their persistent cancer pain. The adverse event data presented here reflect the actual percentage of patients experiencing each adverse effect among patients who received ACTIQ 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 ACTIQ therapy, or cancer-related symptoms. Adverse reactions are included regardless of causality or severity.

Because clinical trials are conducted under widely varying conditions, adverse reaction 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.

Three short-term clinical trials with similar titration schemes were conducted in 257 patients with malignancy and breakthrough cancer pain. Data are available for 254 of these patients. The goal of titration in these trials was to find the dose of ACTIQ that provided adequate analgesia with acceptable side effects (successful dose). Patients were titrated from a low dose to a successful dose in a manner similar to current titration dosing guidelines. Table 1 lists, by dose groups, adverse reactions with an overall frequency of 1% or greater that occurred during titration and are commonly associated with opioid administration or are of particular clinical interest. The ability to assign a dose-response relationship to these adverse reactions is limited by the titration schemes used in these studies. Adverse reactions are listed in descending order of frequency within each body system.

Table 1. Percent of Patients with Specific Adverse Events Commonly Associated with Opioid Administration or of Particular Clinical Interest Which Occurred During Titration (Events in 1% or More of Patients)
*Any Dose = A patient who experienced the same adverse event at multiple doses was only counted once.
Dose Group Percentage of Patients Reporting Event
200-
600 mcg
(n=230)
800-
1400 mcg
(n=138)
1600
mcg
(n=54)
>1600
mcg
(n=41)
Any
Dose*
(n=254)
Body As A Whole
   Asthenia 6 4 0 7 9
   Headache 3 4 6 5 6
   Accidental
      Injury
1 1 4 0 2
Digestive
   Nausea 14 15 11 22 23
   Vomiting 7 6 6 15 12
   Constipation 1 4 2 0 4
Nervous
   Dizziness 10 16 6 15 17
   Somnolence 9 9 11 20 17
   Confusion 1 6 2 0 4
   Anxiety 3 0 2 0 3
   Abnormal Gait 0 1 4 0 2
   Dry Mouth 1 1 2 0 2
   Nervousness 1 1 0 0 2
   Vasodilatation 2 0 2 0 2
   Hallucinations 0 1 2 2 1
   Insomnia 0 1 2 0 1
   Thinking
      Abnormal
0 1 2 0 1
   Vertigo 1 0 0 0 1
Respiratory
   Dyspnea 2 3 6 5 4
Skin
   Pruritus 1 0 0 5 2
   Rash 1 1 0 2 2
   Sweating 1 1 2 2 2
Special Senses
   Abnormal Vision 1 0 2 0 2

The following adverse reactions not reflected in Table 1 occurred during titration with an overall frequency of 1% or greater and are listed in descending order of frequency within each body system.

Body as a Whole: Pain, fever, abdominal pain, chills, back pain, chest pain, infection
Cardiovascular: Migraine
Digestive: Diarrhea, dyspepsia, flatulence
Metabolic and Nutritional: Peripheral edema, dehydration
Nervous: Hypesthesia
Respiratory: Pharyngitis, cough increased

The following reactions occurred during titration with an overall frequency of less than 1% and are listed in descending order of frequency within each body system.

Body as a Whole: Flu syndrome, abscess, bone pain
Cardiovascular: Deep thrombophlebitis, hypertension, hypotension
Digestive: Anorexia, eructation, esophageal stenosis, fecal impaction, gum hemorrhage, mouth ulceration, oral moniliasis
Hemic and Lymphatic: Anemia, leukopenia
Metabolic and Nutritional: Edema, hypercalcemia, weight loss
Musculoskeletal: Myalgia, pathological fracture, myasthenia
Nervous: Abnormal dreams, urinary retention, agitation, amnesia, emotional lability, euphoria, incoordination, libido decreased, neuropathy, paresthesia, speech disorder
Respiratory: Hemoptysis, pleural effusion, rhinitis, asthma, hiccup, pneumonia, respiratory insufficiency, sputum increased
Skin and Appendages: Alopecia, exfoliative dermatitis
Special Senses: Taste perversion
Urogenital: Vaginal hemorrhage, dysuria, hematuria, urinary incontinence, urinary tract infection

A long-term extension study was conducted in 156 patients with malignancy and breakthrough cancer pain who were treated for an average of 129 days. Data are available for 152 of these patients. Table 2 lists by dose groups, adverse reactions with an overall frequency of 1% or greater that occurred during the long-term extension study and are commonly associated with opioid administration or are of particular clinical interest. Adverse reactions are listed in descending order of frequency within each body system.

Table 2. Percent of Patients with Adverse Events Commonly Associated with Opioid or of Particular Clinical Interest Which Occurred During Long Term Treatment (Events in 1% or More of Patients)
* Any Dose = A patient who experienced the same adverse event at multiple doses was only counted once.
Dose Group Percentage of Patients Reporting Event
200-
600 mcg
(n=98)
800-
1400 mcg
(n=83)
1600
mcg
(n=53)
>1600
mcg
(n=27)
Any
Dose*
(n=152)
Body As A Whole
   Asthenia 25 30 17 15 38
   Headache 12 17 13 4 20
   Accidental Injury 4 6 4 7 9
   Hypertonia 2 2 2 0 3
Digestive
   Nausea 31 36 25 26 45
   Vomiting 21 28 15 7 31
   Constipation 14 11 13 4 20
   Intestinal Obstruction 0 2 4 0 3
Cardiovascular
   Hypertension 1 1 0 0 1
Nervous
   Dizziness 12 10 9 0 16
   Anxiety 9 8 8 7 15
   Somnolence 8 13 8 7 15
   Confusion 2 5 13 7 10
   Depression 9 4 2 7 9
   Insomnia 5 1 8 4 7
   Abnormal Gait 5 1 0 0 4
   Dry Mouth 3 1 2 4 4
   Nervousness 2 2 0 4 3
   Stupor 4 1 0 0 3
   Vasodilatation 1 1 4 0 3
   Thinking Abnormal 2 1 0 0 2
   Abnormal Dreams 1 1 0 0 1
   Convulsion 0 1 2 0 1
   Myoclonus 0 0 4 0 1
   Tremor 0 1 2 0 1
   Vertigo 0 0 4 0 1
Respiratory
   Dyspnea 15 16 8 7 22
Skin
   Rash 3 5 8 4 8
   Sweating 3 2 2 0 4
   Pruritus 2 0 2 0 2
Special Senses
   Abnormal Vision 2 2 0 0 3
Urogenital
   Urinary Retention 1 2 0 0 2

The following reactions not reflected in Table 2 occurred with an overall frequency of 1% or greater in the long-term extension study and are listed in descending order of frequency within each body system.

Body as a Whole: Pain, fever, back pain, abdominal pain, chest pain, flu syndrome, chills, infection, abdomen enlarged, bone pain, ascites, sepsis, neck pain, viral infection, fungal infection, cachexia, cellulitis, malaise, pelvic pain
Cardiovascular: Deep thrombophlebitis, migraine, palpitation, vascular disorder
Digestive: Diarrhea, anorexia, dyspepsia, dysphagia, oral moniliasis, mouth ulceration, rectal disorder, stomatitis, flatulence, gastrointestinal hemorrhage, gingivitis, jaundice, periodontal abscess, eructation, glossitis, rectal hemorrhage
Hemic and Lymphatic: Anemia, leukopenia, thrombocytopenia, ecchymosis, lymphadenopathy, lymphedema, pancytopenia
Metabolic and Nutritional: Peripheral edema, edema, dehydration, weight loss, hyperglycemia, hypokalemia, hypercalcemia, hypomagnesemia
Musculoskeletal: Myalgia, pathological fracture, joint disorder, leg cramps, arthralgia, bone disorder
Nervous: Hypesthesia, paresthesia, hypokinesia, neuropathy, speech disorder
Respiratory: Cough increased, pharyngitis, pneumonia, rhinitis, sinusitis, bronchitis, epistaxis, asthma, hemoptysis, sputum increased
Skin and Appendages: Skin ulcer, alopecia
Special Senses: Tinnitus, conjunctivitis, ear disorder, taste perversion
Urogenital: Urinary tract infection, urinary incontinence, breast pain, dysuria, hematuria, scrotal edema, hydronephrosis, kidney failure, urinary urgency, urination impaired, breast neoplasm, vaginal hemorrhage, vaginitis

The following reactions occurred with a frequency of less than 1% in the long-term extension study and are listed in descending order of frequency within each body system.

Body as a Whole: Allergic reaction, cyst, face edema, flank pain, granuloma, bacterial infection, injection site pain, mucous membrane disorder, neck rigidity
Cardiovascular: Angina pectoris, hemorrhage, hypotension, peripheral vascular disorder, postural hypotension, tachycardia
Digestive: Cheilitis, esophagitis, fecal incontinence, gastroenteritis, gastrointestinal disorder, gum hemorrhage, hemorrhage of colon, hepatorenal syndrome, liver tenderness, tooth caries, tooth disorder
Hemic and Lymphatic: Bleeding time increased
Metabolic and Nutritional: Acidosis, generalized edema, hypocalcemia, hypoglycemia, hyponatremia, hypoproteinemia, thirst
Musculoskeletal: Arthritis, muscle atrophy, myopathy, synovitis, tendon disorder
Nervous: Acute brain syndrome, agitation, cerebral ischemia, facial paralysis, foot drop, hallucinations, hemiplegia, miosis, subdural hematoma
Respiratory: Hiccup, hyperventilation, lung disorder, pneumothorax, respiratory failure, voice alteration
Skin and Appendages: Herpes zoster, maculopapular rash, skin discoloration, urticaria, vesiculobullous rash
Special Senses: Ear pain, eye hemorrhage, lacrimation disorder, partial permanent deafness, partial transitory deafness
Urogenital: Kidney pain, nocturia, oliguria, polyuria, pyelonephritis

Postmarketing Experience

Adverse reactions are reported voluntarily from a population of uncertain size, and, therefore, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of the reporting, or (3) strength of causal connection to ACTIQ.

The following adverse reactions have been identified during postapproval use of ACTIQ (which contains approximately 2 grams of sugar per unit):

Digestive: Dental decay of varying severity including dental caries, tooth loss, and gum line erosion.

General Disorders and Administration Site Conditions: Application site reactions including irritation, pain, and ulcer.



REPORTS OF SUSPECTED ACTIQ SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Actiq. The information is not vetted and should not be considered as verified clinical evidence.

Possible Actiq side effects / adverse reactions in 42 year old female

Reported by a physician from United States on 2011-10-10

Patient: 42 year old female weighing 70.3 kg (154.7 pounds)

Reactions: Overdose, Toxicity TO Various Agents

Adverse event resulted in: death

Suspect drug(s):
Carisoprodol
    Dosage: every six hours

Fentanyl-100
    Dosage: changes patches q2d
    Indication: Pain
    End date: 2007-06-17

Alprazolam
    Administration route: Oral

Actiq
    Dosage: every 12 hours
    Administration route: Oral
    Indication: Breakthrough Pain

Other drugs received by patient: Strattera; Dextroamphetamine; Lyrica; Promethazine; Lunesta



Possible Actiq side effects / adverse reactions in 89 year old female

Reported by a physician from France on 2011-10-24

Patient: 89 year old female

Reactions: Decubitus Ulcer, Bradypnoea, Somnolence, Drug Prescribing Error

Adverse event resulted in: death

Suspect drug(s):
Actiq

Other drugs received by patient: Previscan



Possible Actiq side effects / adverse reactions in 57 year old female

Reported by a health professional (non-physician/pharmacist) from Spain on 2011-10-26

Patient: 57 year old female

Reactions: Drug Dependence, Drug Abuse

Suspect drug(s):
Actiq



See index of all Actiq side effect reports >>

Drug label data at the top of this Page last updated: 2011-12-28

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