LAZANDA SIDE EFFECTS

SIDE EFFECTS

The following serious adverse reactions are described, or described in greater detail, in other sections:

• Life-Threatening Respiratory Depression.
• Interactions with benzodiazepines and other CNS Depressants.
• Addiction, Abuse, and Misuse.
• Neonatal Opioid Withdrawal Syndrome.
• Serotonin Syndrome.
• Adrenal Insufficiency.
• Severe Hypotension
• Gastrointestinal Adverse Reactions
• Seizures

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials of a drug product 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 LAZANDA has been evaluated in a total of 523 opioid-tolerant patients with breakthrough cancer pain. The average duration of therapy in patients in the long-term study was 73 days, with 153 patients being treated for over 3 months. Patients continuing into the open-label extension period of the safety study have been treated for up to 26 months.

The clinical trials of LAZANDA were designed to evaluate safety and efficacy in treating breakthrough cancer pain; 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 reaction data presented in Table 1 reflect the actual percentage of patients experiencing each adverse effect among patients who received LAZANDA 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 LAZANDA therapy, or cancerrelated symptoms. Adverse events are included regardless of causality or severity. 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 LAZANDA a dose-response relationship to these adverse events is limited by the titration schemes used in these studies.

Table 1: Adverse Reactions That Occurred During Titration at a Frequency of ≥5%

Table 2 lists, by dose, adverse reactions with an overall frequency of ≥5% within the total population that occurred after a final titrated dose had been determined.

Table 2: Adverse Reactions That Occurred During Maintenance Treatment at a Frequency of ≥5%

The adverse reactions listed below represent those that occurred in ≥1% of patients from clinical trials while receiving LAZANDA. Events are classified by system organ class.

Eye disorders: dry eye, swelling, ptosis, strabismus

Blood and Lymphatic System Disorders: anemia, neutropenia

Cardiac Disorders: cardiorespiratory arrest

Gastrointestinal Disorders: vomiting, nausea, constipation, diarrhea, abdominal pain, gastritis, ascites, dry mouth, dyspepsia, mouth ulcer, proctalgia

General Disorders and Administration Site Conditions: pyrexia, fatigue, edema peripheral, asthenia, edema

Hepatobiliary Disorders: jaundice

Immune System Disorders: hypersensitivity

Infections and Infestations: urinary tract infection, pneumonia, nasopharyngitis, infection, rhinitis, upper respiratory tract infection, bronchitis

Injury, Poisoning and Procedural Complications: fall

Investigations: weight decreased, blood alkaline phosphatase increased

Metabolism and Nutrition Disorders: dehydration, decreased appetite, hyperglycemia, anorexia

Musculoskeletal and Connective Tissue Disorders: back pain, pain in extremity, arthralgia

Nervous System Disorders: dizziness, somnolence, headache, dysgeusia

Psychiatric Disorders: anxiety, insomnia, depression, confusional state, disorientation, agitation

Respiratory, Thoracic and Mediastinal Disorders: dyspnea, epistaxis, cough, pharyngolaryngeal pain, nasal discomfort, rhinorrhea, nasal congestion, postnasal drip, pulmonary embolism

Skin and Subcutaneous Tissue Disorders: pruritus, hyperhidrosis, decubitus ulcer, mouth ulceration

Vascular Disorders: hypertension, deep vein thrombosis

Postmarketing Experience

The following adverse reactions have been identified during post approval use fentanyl. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis: Anaphylaxis has been reported with ingredients contained in LAZANDA.

Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids.