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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 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 most commonly observed adverse events seen with Lazanda are typical of opioid side effects, such as nausea, constipation, somnolence, and headache. Expect opioid side effects and manage them accordingly.
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 cancer-related 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%
|System Organ Class MeDRA preferred term, n (%)||100 mcg
|Nausea||19 (4)||6 (2)||6 (2)||5 (3)||35 (7)|
|Vomiting||14 (3)||10 (3)||9 (3)||1 (1)||33 (6)|
|Nervous system disorders|
|Dizziness||14 (3)||11 (3)||6 (2)||4 (2)||31 (6)|
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%
|System Organ Class MeDRA preferred term, n (%)||100 mcg
|Vomiting||8 (13)||5 (7)||9 (8)||12(11)||34 (10)|
|Nausea||4 (7)||6 (9)||4 (4)||9 (8)||23 (7)|
|Constipation||6 (10)||1 (1)||8 (7)||5 (5)||20 (6)|
|General disorders and administration site conditions|
|Pyrexia||3 (5)||5 (7)||8 (7)||6 (6)||22 (6)|
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.
Adverse Events ( ≥ 1%)
Cardiac Disorders: cardiorespiratory arrest
General Disorders and Administration Site Conditions: pyrexia, fatigue, edema peripheral, asthenia, edema
Hepatobiliary Disorders: jaundice
Immune System Disorders: hypersensitivity
Injury, Poisoning and Procedural Complications: fall
Investigations: weight decreased, blood alkaline phosphatase increased
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
Vascular Disorders: hypertension, deep vein thrombosis
Read the Lazanda (fentanyl nasal spray) Side Effects Center for a complete guide to possible side effects
Metabolic Drug Interactions
Fentanyl is metabolized mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4); therefore potential interactions may occur when Lazanda is given concurrently with agents that affect CYP3A4 activity.
The concomitant use of Lazanda 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 Lazanda who begin therapy with, or increase the dose of, CYP3A4 inhibitors are to be carefully monitored for signs of opioid toxicity over an extended period of time. Increase dose conservatively [see WARNINGS AND PRECAUTIONS].
The concomitant use of Lazanda 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 Lazanda. Patients receiving Lazanda who stop therapy with, or decrease the dose of, CYP3A4 inducers may experience sudden increase in fentanyl plasma concentrations and are to be monitored for signs of increased Lazanda activity. Adjust the dose of Lazanda accordingly.
Non-metabolic Drug Interactions
Agents used to treat Allergic Rhinitis
The presence of allergic rhinitis is not expected to affect Lazanda absorption. However, co-administration of a vasoconstrictive nasal decongestant such as oxymetazoline to treat allergic rhinitis leads to lower peak plasma concentrations and a delayed Tmax of fentanyl that may cause Lazanda to be less effective in patients with allergic rhinitis who use such decongestants, thus potentially impairing pain management. Additionally, in view of the possibility that the titration of a patient while they are experiencing an acute episode of rhinitis could lead to incorrect dose identification (particularly if they are using a vasoconstrictive decongestant), titration under these circumstances must be avoided [see CLINICAL PHARMACOLOGY].
Concomitant use of Lazanda with an MAO inhibitor, or within 14 days of discontinuing an MAO inhibitor, is not recommended.
Drug Abuse And Dependence
Lazanda contains fentanyl, which is a Schedule II controlled substance. Schedule II substances such as fentanyl, hydromorphone, methadone, morphine, oxycodone, and oxymorphone have a high potential for abuse and addiction. Lazanda may be subject to misuse and criminal diversion.
Abuse And Addiction
Manage the handling of Lazanda to minimize the risk of abuse, including 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 and addiction should 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 nonmedical purposes, often in combination with other psychoactive substances. Since Lazanda may be abused or diverted for nonmedical use, careful record keeping of prescribing information, including quantity, frequency, and renewal requests, is strongly advised.
Proper assessment of patients, proper prescribing practices, periodic reevaluation 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 when treating a patient with cancer and chronic pain, and fear of tolerance and physical dependence should not deter using doses that adequately relieve the pain. Guide the administration of Lazanda by the response of the patient.
Opioid analgesics may cause physical dependence. Physical dependence results 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 (e.g., 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, initially manifests as a shortened duration of analgesic effect, and subsequently as decreases in the intensity of analgesia.
Read the Lazanda Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 1/27/2015
Additional Lazanda Information
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