"Sabahaddin Akman, owner of the Istanbul, Turkey, firm Ozay Pharmaceuticals, has pleaded guilty to charges of smuggling misbranded and adulterated cancer treatment drugs into the United States.
Akman pleaded guilty in the U.S. District Court"...
Serious or fatal respiratory depression can occur even at recommended doses in patients using Lazanda. Respiratory depression is more likely to occur in patients with underlying respiratory disorders and elderly or debilitated patients, in opioid non-tolerant patients, or when opioids are given in conjunction with other drugs that depress respiration.
Respiratory depression from opioids is manifested by a reduced urge to breathe and a decreased rate of respiration, often associated with a “sighing” pattern of breathing (deep breaths separated by abnormally long pauses). Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. This makes overdoses involving drugs with sedative properties and opioids especially dangerous.
Lazanda And Other Fentanyl Products
Lazanda is NOT equivalent to other fentanyl products used to treat breakthrough pain on a mcg per mcg basis. There are differences in the pharmacokinetics of Lazanda relative to other fentanyl products which could potentially result in clinically important differences in the amount of fentanyl absorbed and could result in a fatal overdose.
When prescribing Lazanda to a patient, DO NOT convert from other fentanyl products. Directions for safely converting patients to Lazanda from other fentanyl products are not currently available. (Note: This includes oral, transdermal, or parenteral formulations of fentanyl). Therefore, for opioid-tolerant patients starting treatment for breakthrough pain, the initial dose of Lazanda is 100 mcg. Individually titrate each patient's dose to provide adequate analgesia while minimizing side effects. [See DOSAGE AND ADMINISTRATION]
When dispensing Lazanda to a patient, DO NOT substitute it for any other fentanyl product prescription.
Information For Patients And Their Caregivers
Patients and their caregivers must be instructed that Lazanda contains medicine in an amount that could be fatal to a child.
Patients and their caregivers must be instructed to keep both used and unused bottles in their child-resistant container and out of the reach of children at all times. Partially used bottles represent a special risk to children. As soon as they are no longer required, all used, unopened or partially used bottles must be completely emptied of accessible fentanyl solution by spraying the remaining contents into the carbon-lined pouch. The sealed pouch and the empty bottle should be put into the child-resistant container before discarding in the trash. Hands must be washed with soap and water immediately after handling the pouch. [see Storage and Handling, Disposal of Lazanda, and Patient/Caregiver Instructions].
Physicians and dispensing pharmacists must question patients and caregivers specifically about the presence of children in the home on a full-time or visiting basis and counsel accordingly regarding the dangers to children of inadvertent exposure to Lazanda.
Lazanda could be fatal to individuals for whom it is not prescribed and for those who are not opioid tolerant.
Additive CNS Depressant Effects
The concomitant use of Lazanda with other CNS depressants, including other opioids, sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, skeletal muscle relaxants, sedating antihistamines, and alcoholic beverages may produce increased depressant effects (e.g., hypoventilation, hypotension, and profound sedation). Concomitant use with potent inhibitors of cytochrome P450 3A4 isoform (e.g., erythromycin, ketoconazole, and certain protease inhibitors) may increase fentanyl levels, resulting in increased depressant effects [see Metabolic Drug Interactions].
Patients on concomitant CNS depressants must be monitored for a change in opioid effects and may require adjustment of the dose of Lazanda.
Effects On Ability To Drive And Use Machines
Opioid analgesics impair the mental and/or physical ability required for the performance of potentially dangerous tasks (e.g., driving a car or operating machinery). Warn patients taking Lazanda of these dangers and counsel them accordingly.
Chronic Pulmonary Disease
Because potent opioids can cause respiratory depression, cautiously adjust the dose of Lazanda in patients with chronic obstructive pulmonary disease or preexisting medical conditions predisposing them to respiratory depression. In such patients, even normal therapeutic doses of Lazanda may further decrease respiratory drive to the point of respiratory failure.
Head Injuries And Increased Intracranial Pressure
Administer Lazanda with extreme caution in patients who may be particularly susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased intracranial pressure or impaired consciousness. Opioids may obscure the clinical course of a patient with a head injury; only use opioids if clinically warranted.
Intravenous fentanyl may produce bradycardia. Use Lazanda with caution in patients with bradyarrhythmias.
Lazanda is not recommended for use in patients who have received MAO inhibitors within 14 days, because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. [see Non-metabolic Drug Interactions].
Transmucosal Immediate Release Fentanyl (TIRF) Risk Evaluation And Mitigation Strategy (REMS) Access Program
Because of the risk of misuse, abuse, addiction, and overdose [see Drug Abuse and Dependence], Lazanda is available only through a restricted program under a REMS called the TIRF REMS Access program. Under the TIRF REMS Access program, outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors must enroll in the program. For inpatient administration (e.g. hospitals, hospices, and long-term care facilities that prescribe for inpatient use) of Lazanda, patient and prescriber enrollment is not required. Required components of the TIRF REMS Access program are:
- Healthcare professionals who prescribe Lazanda must review the prescriber educational materials for the TIRF REMS Access program, enroll in the program, and comply with the REMS requirements.
- To receive Lazanda, outpatients must understand the risks and benefits and sign a Patient-Prescriber Agreement.
- Pharmacies that dispense Lazanda must enroll in the program and agree to comply with the REMS requirements.
- Wholesalers and distributers that distribute Lazanda must enroll in the program and distribute only to authorized pharmacies.
Further information, including a list of qualified pharmacies/distributors, is available at www.tirfremsaccess.com or by calling 1866-822-1483.
Patient Counseling Information
See FDA-approved patient labeling (Medication Guide)
- Before initiating treatment with Lazanda, explain the statements below to patients and/or caregivers. Instruct patients to read the Medication Guide each time Lazanda is dispensed because new information may be available.
- TIRF REMS Access Program
- Outpatients must be enrolled in the TIRF REMS Access program before they can receive Lazanda.
- Allow patients the opportunity to ask questions and discuss any concerns regarding Lazanda or the TIRF REMS Access program.
- As a component of the TIRF REMS Access program, prescribers must review the contents of the Lazanda Medication Guide with every patient before initiating treatment with Lazanda.
- Advise the patient that Lazanda is available only from pharmacies that are enrolled in the TIRF REMS Access program, and provide them with the telephone number and website for information on how to obtain the drug.
- Advise the patient that only enrolled health care providers may prescribe Lazanda.
- Patient must sign the Patient-Prescriber Agreement to acknowledge that they understand the risks of Lazanda.
- Advise patients that they may be requested to participate in a survey to evaluate the effectiveness of the TIRF REMS Access program.
- Instruct patients and their caregivers that the amount of fentanyl contained in a bottle can be fatal to a child. Patients and their caregivers must be instructed to keep Lazanda in its child-resistant container at all times and to store it and the pouch securely and out of the reach of children.
- Instruct patients how to safely dispose of the priming sprays and any remaining fentanyl solution in the pouch provided before disposing of both the empty bottle and the pouch inside the child-resistant container in the trash.
- Instruct patients not to take Lazanda for acute pain, postoperative pain, pain from injuries, headache, migraine, or any other short-term pain, even if they have taken other opioid analgesics for these conditions.
- Instruct patients on the meaning of opioid tolerance and Lazanda is only to be used as a supplemental pain medication for patients with pain requiring regular opioids, who have developed tolerance to the opioid medication and who need additional opioid treatment of breakthrough pain episodes.
- Instruct patients that if they are not taking an opioid medication on a regular around-the-clock basis, they must not take Lazanda.
- Instruct patients that they MUST wait at least 2 hours before treating another episode of breakthrough pain with Lazanda.
- Instruct patients NOT to share Lazanda and that sharing Lazanda with anyone else could result in the other individual's death due to overdose.
- Advise patients that Lazanda contains fentanyl, which is a pain medication similar to hydromorphone, methadone, morphine, oxycodone, and oxymorphone.
- Advise patients that the active ingredient in Lazanda, fentanyl, is a drug that some people abuse. Lazanda is to be taken only by the patient for whom it was prescribed, and protected from theft or misuse in the work or home environments.
- Instruct patients to talk to their doctor if breakthrough pain is not alleviated or worsens after taking Lazanda.
- Instruct patients to use Lazanda exactly as prescribed by their doctor and not to take Lazanda more often than prescribed.
- Caution patients that Lazanda can affect a person's ability to perform activities that require a high level of attention (such as driving or using heavy machinery). Warn patients taking Lazanda of these dangers and counsel accordingly.
- Warn patients not to combine Lazanda with alcohol, sleep aids, or tranquilizers except by order of the prescribing physician, because dangerous additive effects may occur resulting in serious injury or death.
- Inform female patients that if they become pregnant or plan to become pregnant during treatment with Lazanda to ask their doctor about the effects that Lazanda (or any medicine) may have on them and their unborn child.
- Instruct the patient to dispose of the Lazanda bottle and
start a new one if:
- it has been 60 days or more since they first used the bottle of Lazanda
- Physicians and dispensing pharmacists must specifically question patients or caregivers about the presence of children in the home (on a full time or visiting basis) and counsel them regarding the dangers to children from inadvertent exposure.
Disposal of Used Lazanda Bottles
- Instruct patients and caregivers to properly dispose of all unused, partially used and used Lazanda bottles as soon as no longer needed.
- Instruct patients that, to dispose of Lazanda properly, the remaining liquid in all bottles must be sprayed into the pouch provided in the pack for safe disposal as soon as possible. This includes any unwanted therapeutic sprays remaining in the bottle. After the counter has advanced to “8”, the patient should continue to push down on the finger grips a total of four times in order to expel any residual medicine from the bottle. After the 8 therapeutic sprays have been emitted, the patient will not hear a click and the counter will not advance beyond “8”; further sprays emitted will not be full sprays and should always be trapped in the pouch, not used therapeutically.
- Instruct the patient and caregiver to seal the pouch and to place both the empty bottle and the sealed pouch into the child-resistant storage container and discard in the trash. Lazanda must be stored in the specially provided child-resistant container out of the reach of children until proper disposal is possible.
- Instruct the patient and caregiver to wash their hands with soap and water immediately after handling the pouch.
- If the pouch is lost, instruct the patient and caregiver to use a pouch from another Lazanda pack to prime and dispose of unused medicine from the current bottle as well as from the next bottle. If they do not have an empty pouch available, the patient or caregiver can order one by calling 1-866-458-6389. They will receive the replacement pouch in the mail.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of fentanyl.
Fentanyl citrate was not mutagenic in the in vitro Ames reverse mutation assay in S. typhimurium or E. coli, or the mouse lymphoma mutagenesis assay, and was not clastogenic in the in vivo mouse micronucleus assay.
Fentanyl has been shown to impair fertility in rats at doses of 30 mcg/kg subcutaneously. Conversion to human equivalent doses indicates this is within the range of the human recommended dosing for Lazanda.
Use In Specific Populations
There are no adequate and well-controlled studies in pregnant women.
Use Lazanda during pregnancy only if the potential benefit justifies the potential risk to the fetus. No epidemiological studies of congenital anomalies in infants born to women treated with fentanyl during pregnancy have been reported.
Chronic maternal treatment with fentanyl during pregnancy has been associated with transient respiratory depression, behavioral changes, or seizures in newborn infants characteristic of neonatal abstinence syndrome.
In women treated acutely with intravenous or epidural fentanyl during labor, symptoms of neonatal respiratory or neurological depression were no more frequent than would be expected in infants of untreated mothers.
Transient neonatal muscular rigidity has been observed in infants whose mothers were treated with intravenous fentanyl.
Fentanyl is embryocidal in rats as evidenced by increased resorptions in pregnant rats at doses of 30 mcg/kg IV or 160 mcg/kg SC. Conversion to human equivalent doses indicates this is within the range of the human recommended dosing for Lazanda.
Fentanyl citrate was not teratogenic when administered to pregnant animals. Published studies demonstrated that administration of fentanyl (10, 100, or 500 mcg/kg/day) to pregnant rats from day 7 to 21 of their 21 day gestation, via implanted microosmotic minipumps was not teratogenic. The high dose was approximately 3 times the human dose of 800 mcg per pain episode on a mg/m² basis. Intravenous administration of fentanyl (10 or 30 mcg/kg) to pregnant female rats from gestation days 6 to 18 was embryo or fetal toxic and caused a slightly increased mean delivery time in the 30 mcg/kg/day group, but it was not teratogenic.
Labor And Delivery
Fentanyl readily passes across the placenta. Therefore do not use Lazanda during labor and delivery (including caesarean section) since it may cause respiratory depression in the fetus or in the newborn infant.
Fentanyl is excreted in human milk; therefore, do not use Lazanda in women who are nursing because of the risk of sedation and/or respiratory depression in their infants. Symptoms of opioid withdrawal may occur in infants upon cessation of nursing by women using Lazanda.
The safety and efficacy of Lazanda have not been established in patients below the age of 18 years.
Of the 523 opioid tolerant cancer patients with breakthrough cancer pain in clinical studies of Lazanda, 148 (28%) were aged 60 years and over. No clinically meaningful difference was noted in the safety profile of the group aged over 60 years versus that of younger patients in Lazanda clinical trials.
Elderly patients have been shown to be more sensitive to the effects of fentanyl when administered intravenously compared with the younger population. Therefore, exercise caution when individually titrating Lazanda in elderly patients.
Patients With Renal Or Hepatic Impairment
Insufficient information exists to make recommendations regarding the use of Lazanda in patients with impaired renal or hepatic function. Fentanyl is metabolized primarily via the human CYP3A4 isoenzyme system and the inactive metabolite is mostly eliminated in urine. If the drug is used in these patients, it is to be used with caution because of the hepatic metabolism and renal excretion of fentanyl.
It is recommended that Lazanda be titrated to clinical effect for all patients with special care taken in patients with severe renal or hepatic disease.
Both male and female opioid-tolerant cancer patients were studied for the treatment of breakthrough cancer pain. No clinically relevant gender differences were observed in adverse events.
Patients With Allergic (Seasonal) Rhinitis
The pharmacokinetic and safety profiles of Lazanda in individuals with known allergic (seasonal) rhinitis showed no clinically meaningful differences in rate or extent of exposure to fentanyl, or in local tolerability of Lazanda when compared to Asymptomatic (Unchallenged) state. However, when treated for their rhinitis with oxymetazoline, Lazanda absorption was compromised [see Pharmacokinetics].
Last reviewed on RxList: 1/27/2015
This monograph has been modified to include the generic and brand name in many instances.
Additional Lazanda Information
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