Fentanyl-Cimex TTS

When are you taking this medicine?
advertisement

Fentanyl-Cimex TTS uses


1. INDICATIONS AND USAGE

Fentanyl-Cimex TTS is indicated for the short-term management of acute postoperative pain severe enough to require an opioid analgesic in the hospital and for which alternative treatments are inadequate.

Limitations of Use

Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses , reserve Fentanyl-Cimex TTS for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]:


Fentanyl-Cimex TTS is:


Fentanyl-Cimex TTS contains Fentanyl-Cimex TTS, an opioid agonist. Fentanyl-Cimex TTS is indicated for the short-term management of acute postoperative pain severe enough to require an opioid analgesic in the hospital and for which alternative treatments are inadequate. ( 1)

Limitations of Use

Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve Fentanyl-Cimex TTS for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]:


Fentanyl-Cimex TTS is:

advertisement

2. DOSAGE AND ADMINISTRATION

2.1 Important Administration Instructions

Fentanyl-Cimex TTS IS FOR HOSPITAL USE ONLY BY PATIENTS UNDER MEDICAL SUPERVISION AND DIRECTION. PRIOR TO THE PATIENT LEAVING THE HOSPITAL, MEDICAL PERSONNEL MUST REMOVE Fentanyl-Cimex TTS AND DISPOSE OF IT PROPERLY .

ONLY THE PATIENT MAY ACTIVATE Fentanyl-Cimex TTS.

ONLY ONE Fentanyl-Cimex TTS MAY BE APPLIED AT A TIME. If inadequate analgesia is achieved with one Fentanyl-Cimex TTS, either provide additional supplemental analgesic medication or replace with an alternate analgesic medication.

Fentanyl-Cimex TTS should be prescribed only by persons knowledgeable in the administration of potent opioids and in the management of patients receiving potent opioids for treatment of pain. Patients treated with Fentanyl-Cimex TTS should be under the supervision of medical personnel with expertise in the detection and management of hypoventilation including close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status .

Remove and properly dispose of Fentanyl-Cimex TTS prior to MRI, cardioversion, defibrillation, or diathermy .

To reduce the risk for shock, avoid contact with synthetic materials (such as carpeted flooring) while assembling Fentanyl-Cimex TTS and avoid exposing Fentanyl-Cimex TTS to electronic security systems .

Depending on the rated maximum output power and frequency of the transmitter, the recommended separation distance between Fentanyl-Cimex TTS and communications equipment or a Radio Frequency Identification (RFID) transmitter ranges between 0.12 and 23 meters .

See Fentanyl-Cimex TTS Important Device Instructions for additional details, including information on troubleshooting device malfunction, recommended separation distances, and electromagnetic compatibility

2.2 Dosage

Fentanyl-Cimex TTS is for use only after patients have been titrated to an acceptable level of analgesia using another opioid analgesic. Apply one Fentanyl-Cimex TTS to healthy, unbroken/intact, non-irritated, and non-irradiated skin on the chest or upper outer arm ONLY.

Fentanyl-Cimex TTS provides a 40 mcg dose of Fentanyl-Cimex TTS per activation. It is important to instruct patients how to operate Fentanyl-Cimex TTS to self-administer doses of Fentanyl-Cimex TTS as needed to manage their acute, short-term, postoperative pain. Allow only the patient to self-administer doses of Fentanyl-Cimex TTS. Each on-demand dose is delivered over a 10-minute period.

To initiate administration of Fentanyl-Cimex TTS, the patient must press and release the button twice within 3 seconds. One single audible beep indicates the start of delivery of each dose. The green light will start blinking rapidly and the digital display will alternate between a walking circle and the number of doses delivered. When the 10-minute dose is complete, the green light will blink at a slow rate and the display will show the number of doses delivered.

Figure 1A: Fentanyl-Cimex TTS Components

Figure 1B: Assembled Fentanyl-Cimex TTS

A maximum of six 40-mcg doses per hour can be administered by Fentanyl-Cimex TTS. The maximum amount of Fentanyl-Cimex TTS that can be administered from a single Fentanyl-Cimex TTS over 24 hours is 3.2 mg (eighty 40-mcg doses). Each Fentanyl-Cimex TTS operates up to 24 hours or 80 doses, whichever comes first. Use one Fentanyl-Cimex TTS at a time for up to 24 hours or 80 doses, whichever comes first. Fentanyl-Cimex TTS may be used for a maximum of 3 days (72 hours) of therapy for acute postoperative pain, with each subsequent Fentanyl-Cimex TTS applied to a different skin site .

After the 24 hours have elapsed, or 80 doses have been delivered, Fentanyl-Cimex TTS will not deliver any additional doses. The light and audible beep will not function. The digital display will continue to show the number of doses delivered for an additional 12 hours. If the patient tries to initiate a dose, Fentanyl-Cimex TTS will ignore the dose request.

Figure 1a Figure 1b

2.3 Administration of Fentanyl-Cimex TTS

For SINGLE-USE only: operates up to 24 hours or 80 doses, whichever comes first.

FOR TRANSDERMAL USE ONLY

Preparation of Patient Site

1. Choose healthy, unbroken skin on the upper outer arm or chest ONLY. Fentanyl-Cimex TTS may only be applied to one of the three sites shown in Figure 2.

2. Clip excessive hair if necessary. Do not shave as this may irritate skin.

3. Clean the site with alcohol and let it dry. Do not use soaps, lotions, or other agents.

Assembly of Fentanyl-Cimex TTS

DO NOT USE Fentanyl-Cimex TTS IF THE SEAL ON THE TRAY OR DRUG UNIT POUCH IS BROKEN OR DAMAGED.

ALWAYS WEAR GLOVES WHEN HANDLING Fentanyl-Cimex TTS.

Complete these steps before applying Fentanyl-Cimex TTS to the patient:


Application of Fentanyl-Cimex TTS

ALWAYS WEAR GLOVES WHEN HANDLING Fentanyl-Cimex TTS.

Peel off and discard only the clear plastic liner covering the adhesive and hydrogels. Take care not to pull on the red tab while removing the clear plastic liner when preparing to apply Fentanyl-Cimex TTS to the patient. The red tab is only to be used when separating Fentanyl-Cimex TTS for disposal .

Press and hold Fentanyl-Cimex TTS firmly in place, with the sticky side down, onto patient’s skin for at least 15 seconds. Press with your fingers around the edges to be sure Fentanyl-Cimex TTS adheres to the skin. Do not press the dosing button.

Occasionally, Fentanyl-Cimex TTS may loosen from the skin; if this occurs, secure it to patient’s skin by pressing the edges with fingers or securing with a non-allergenic tape to be sure that all edges make complete contact with the skin. If using tape, apply tape along the long edges to secure Fentanyl-Cimex TTS to patient’s skin. Do not tape over the button, the light, or the digital display. Do not tape if evidence of blistered or broken skin.

After taping, if Fentanyl-Cimex TTS beeps again, remove and dispose. Place a new Fentanyl-Cimex TTS on a different skin site. Each Fentanyl-Cimex TTS may be used for up to 24 hours from the time it is assembled or until 80 doses have been administered, whichever comes first.

Operation of Fentanyl-Cimex TTS

A recessed button is located on the top housing of Fentanyl-Cimex TTS. To initiate administration of a Fentanyl-Cimex TTS dose, the patient must press and release the button twice within 3 seconds. Fentanyl-Cimex TTS should only be activated by the patient. One single audible beep indicates the start of delivery of each dose. The green light will start blinking rapidly and the digital display will alternate between a walking circle and the number of doses delivered.

Each dose will be delivered over 10-minutes. During this time Fentanyl-Cimex TTS is locked-out and will not respond to additional button presses. When the 10-minute dose is complete, the green light will return to a slow rate of blinking and the display will show the number of doses delivered. Fentanyl-Cimex TTS is now ready to be used again by the patient. The next dose cannot begin until the previous 10‑minute delivery cycle is complete. Pressing the button during delivery of a dose will not result in additional drug being administered.

A healthcare professional must observe the first dose administered to ensure that the patient understands how to operate Fentanyl-Cimex TTS and that Fentanyl-Cimex TTS is working properly.

Each Fentanyl-Cimex TTS will cease functioning at the end of 24 hours of use, or after 80 doses have been administered, whichever comes first. The green light will turn off and the number of doses delivered will flash on and off. The flashing digital display may be turned off by pressing and holding the dosing button for 6 seconds.

See Fentanyl-Cimex TTS Important Device Instructions for additional details, including information on troubleshooting device malfunction.

Removal of Fentanyl-Cimex TTS

ALWAYS WEAR GLOVES WHEN HANDLING Fentanyl-Cimex TTS.

Fentanyl-Cimex TTS may be removed at any time. However, once Fentanyl-Cimex TTS has been removed, the same Fentanyl-Cimex TTS must not be reapplied.

At the end of 24 hours of use, or after 80 doses have been delivered, Fentanyl-Cimex TTS will deactivate and should be removed from the patient’s skin. With gloves on, remove Fentanyl-Cimex TTS from the patient.

Fentanyl-Cimex TTS contains two hydrogels, one of which contains Fentanyl-Cimex TTS . Ensure both hydrogels remain with the removed Fentanyl-Cimex TTS. If the hydrogel becomes separated from Fentanyl-Cimex TTS during removal, use gloves or tweezers to remove the hydrogel from the skin and properly dispose of in accordance with state and federal regulations for controlled substances. If the patient requires additional analgesia a new Fentanyl-Cimex TTS should be applied. In this case, Fentanyl-Cimex TTS should be applied to a new skin site on the upper outer arm or chest.

One of the hydrogels contains Fentanyl-Cimex TTS; take care not to touch the exposed hydrogel compartments or the adhesive. If a hydrogel drug reservoir is touched accidentally, rinse the area thoroughly with water (do not use soap).

Fig 2 Fig 3abcde image of removing liner Fig 4c Fig 5 Fig 6

2.4 Disposal of Fentanyl-Cimex TTS

ALWAYS WEAR GLOVES WHEN HANDLING Fentanyl-Cimex TTS.

Contact with the hydrogels contained in Fentanyl-Cimex TTS can result in a fatal overdose of Fentanyl-Cimex TTS. Handle the used Fentanyl-Cimex TTS by the sides and top while avoiding contact with the hydrogel. Dispose of Fentanyl-Cimex TTS in accordance with state and federal regulations for controlled substances. The used red bottom housing of Fentanyl-Cimex TTS contains a significant amount of Fentanyl-Cimex TTS that could cause a fatal overdose of Fentanyl-Cimex TTS.

To dispose of a used Fentanyl-Cimex TTS:


Fig 7ab

2.5 Discontinuation of Fentanyl-Cimex TTS

To discontinue use of Fentanyl-Cimex TTS, remove and dispose of Fentanyl-Cimex TTS according to the preceding directions. Do not abruptly discontinue Fentanyl-Cimex TTS in a physically-dependent patient .

2.6 Conversion from Fentanyl-Cimex TTS to Alternate Analgesics

Upon discontinuation of Fentanyl-Cimex TTS, if upon evaluation, conversion to an alternate analgesic is required, titrate the dose of the new analgesic, based upon the patient’s report of pain, until adequate analgesia has been obtained, keeping in mind that the serum Fentanyl-Cimex TTS concentration will decrease slowly following removal of Fentanyl-Cimex TTS . During the period of converting analgesics, monitor the patient for signs of respiratory and central nervous system depression.

advertisement

3. DOSAGE FORMS AND STRENGTHS

Iontophoretic transdermal system provides up to 80 doses (40 mcg each) of Fentanyl-Cimex TTS per activation on-demand .

Iontophoretic transdermal system provides up to 80 doses (40 mcg each) of Fentanyl-Cimex TTS per activation on-demand. ( 3)

4. CONTRAINDICATIONS

Fentanyl-Cimex TTS is contraindicated in patients with:

advertisement

5. WARNINGS AND PRECAUTIONS

5.1 Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, including Fentanyl-Cimex TTS, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status . Carbon dioxide (CO 2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Fentanyl-Cimex TTS, the risk is greatest during the initiation of therapy. Monitor patients closely for respiratory depression, especially within the first 24‑72 hours of initiating therapy with Fentanyl-Cimex TTS.

Accidental exposure to the hydrogel component of Fentanyl-Cimex TTS, especially in children, can result in respiratory depression and death due to an overdose of Fentanyl-Cimex TTS.

Following accidental contact with Fentanyl-Cimex TTS or its components, immediately rinse the affected area thoroughly with water. Do not use soap, alcohol, or other solvent because they may enhance the drug’s ability to penetrate the skin. The individual exposed should be monitored for signs of respiratory or central nervous system depression.

If Fentanyl-Cimex TTS is not handled correctly using gloves, healthcare professionals are at risk of accidental exposure to a fatal overdose of Fentanyl-Cimex TTS.

Fentanyl-Cimex TTS is for hospital use only. Use of Fentanyl-Cimex TTS outside of the hospital setting can lead to accidental exposure in others for whom it is not prescribed, causing fatal respiratory depression. Prior to the patient leaving the hospital, medical personnel must remove Fentanyl-Cimex TTS and dispose of it properly.

5.2 Fentanyl-Cimex TTS Risk Evaluation and Mitigation Strategy Program

Fentanyl-Cimex TTS is available only through a restricted program under a REMS called the Fentanyl-Cimex TTS REMS Program because of the risk of respiratory depression resulting from accidental exposure .

Notable requirements of the Fentanyl-Cimex TTS REMS Program include the following:


Further information about the Fentanyl-Cimex TTS REMS Program is available at www.ionsysrems.com, or by calling 1-877-488-6835.

5.3 Addiction, Abuse, and Misuse

Fentanyl-Cimex TTS contains Fentanyl-Cimex TTS, a Schedule II controlled substance. As an opioid, Fentanyl-Cimex TTS exposes users to the risks of addiction, abuse, and misuse .

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Fentanyl-Cimex TTS. Addiction can occur at recommended dosages and if the drug is misused or abused.

Assess each patient’s risk for opioid addiction, abuse, or misuse, prior to prescribing Fentanyl-Cimex TTS, and monitor all patients receiving Fentanyl-Cimex TTS for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids, such as Fentanyl-Cimex TTS, but use in such patients necessitates intensive counseling about the risks and proper use of Fentanyl-Cimex TTS along with intensive monitoring for signs of addiction, abuse, and misuse.

Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing Fentanyl-Cimex TTS. Contact local State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.

5.4 Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers

Concomitant use of Fentanyl-Cimex TTS with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of Fentanyl-Cimex TTS, and prolong opioid adverse reactions, depression , particularly when an inhibitor is added after a stable dose of Fentanyl-Cimex TTS is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in IONSYS-treated patients may increase Fentanyl-Cimex TTS plasma concentrations and prolong opioid adverse reactions. When using Fentanyl-Cimex TTS with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in IONSYS-treated patients, monitor patients closely at frequent intervals for respiratory depression and sedation .

Concomitant use of Fentanyl-Cimex TTS with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease Fentanyl-Cimex TTS plasma concentrations, decrease opioid efficacy or, possibly lead to a withdrawal syndrome in a patient who had developed physical dependence to Fentanyl-Cimex TTS. When using Fentanyl-Cimex TTS with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur .

5.5 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Fentanyl-Cimex TTS with benzodiazepines or other CNS depressants. Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics .

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.

5.6 Risk of Injury during Magnetic Resonance Imaging (MRI) Procedure

The Fentanyl-Cimex TTS device is considered MR Unsafe. Fentanyl-Cimex TTS contains metal parts and must be removed and properly disposed of before an MRI procedure to avoid injury to the patient and damage to Fentanyl-Cimex TTS. It is unknown if exposure to an MRI procedure increases release of Fentanyl-Cimex TTS from Fentanyl-Cimex TTS. Monitor any patients wearing Fentanyl-Cimex TTS with inadvertent exposure to an MRI for signs of central nervous system and respiratory depression.

5.7 Risk of Fentanyl-Cimex TTS Use during Other Procedures or Near Certain Equipment

Cardioversion, Defibrillation, Radiographic Imaging Procedures other than MRI, or Diathermy

Use of Fentanyl-Cimex TTS during cardioversion, defibrillation, X-ray, CT, or diathermy can damage Fentanyl-Cimex TTS from the strong electromagnetic fields set up by these procedures. Fentanyl-Cimex TTS contains radio-opaque components and may interfere with an X-ray image or CT scan. Remove and properly dispose of Fentanyl-Cimex TTS prior to cardioversion, defibrillation, X-ray, CT, or diathermy .

Synthetic Materials and Electronic Security Systems

Avoid contact with synthetic materials (such as carpeted flooring) to reduce the possibility of electrostatic discharge and damage to Fentanyl-Cimex TTS. Avoid exposing Fentanyl-Cimex TTS to electronic security systems to reduce the possibility of damage to Fentanyl-Cimex TTS. See Fentanyl-Cimex TTS Important Device Instructions for additional details.

Communications Equipment and Radio Frequency Identification Transmitters

Use of Fentanyl-Cimex TTS near communications equipment (e.g., base stations for radio telephones and land mobile radios, amateur radio, AM and FM radio broadcast and TV broadcast Radio) and Radio Frequency Identification (RFID) transmitters can damage Fentanyl-Cimex TTS. Depending on the rated maximum output power and frequency of the transmitter, the recommended separation distance between Fentanyl-Cimex TTS and communications equipment or the RFID transmitter ranges between 0.12 and 23 meters. See Fentanyl-Cimex TTS Important Device Instructions for detailed instructions regarding recommended separation distances.

Other Electromechanical Devices Including Pacemakers or Electrical Monitoring Equipment

The low-level electrical current provided by Fentanyl-Cimex TTS does not result in electromagnetic interference with other electromechanical devices like pacemakers or electrical monitoring equipment.

If exposure to the procedures listed above, electronic security systems, electrostatic discharge, communications equipment, or RFID transmitters occurs, and if Fentanyl-Cimex TTS does not appear to function normally , remove Fentanyl-Cimex TTS and replace with a new Fentanyl-Cimex TTS. See Fentanyl-Cimex TTS Important Device Instructions for additional details including information on troubleshooting device malfunction and electromagnetic compatibility.

5.8 Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

The use of Fentanyl-Cimex TTS in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: IONSYS-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at the recommended dosage of Fentanyl-Cimex TTS .

Elderly, Cachectic, or Debilitated Patients: Life -threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.

Monitor such patients closely; particularly when initiating Fentanyl-Cimex TTS and when Fentanyl-Cimex TTS is used concomitantly with other drugs that depress respiration . Alternatively, consider the use of non-opioid analgesics in these patients.

5.9 Serotonin Syndrome with Concomitant Use of Serotonergic Drugs

Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of Fentanyl-Cimex TTS, the active opioid ingredient of Fentanyl-Cimex TTS, with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) . This may occur at the recommended dosage.

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that. Discontinue Fentanyl-Cimex TTS if serotonin syndrome is suspected.

5.10 Adrenal Insufficiency

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

5.11 Severe Hypotension

Fentanyl-Cimex TTS may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume, or concurrent administration of certain CNS depressant drugs . Monitor these patients for signs of hypotension after initiating Fentanyl-Cimex TTS. In patients with circulatory shock, Fentanyl-Cimex TTS may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of Fentanyl-Cimex TTS in patients with circulatory shock.

5.12 Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

In patients who may be susceptible to the intracranial effects of CO 2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors). Fentanyl-Cimex TTS may reduce respiratory drive, and the resultant CO 2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with Fentanyl-Cimex TTS.

Opioids may also obscure the clinical course in a patient with a head injury.

Avoid the use of Fentanyl-Cimex TTS in patients with impaired consciousness or coma. Fentanyl-Cimex TTS is not suitable for use in patients who are not alert and able to follow directions.

5.13 Risks of Use in Patients with Gastrointestinal Conditions

Fentanyl-Cimex TTS is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

The Fentanyl-Cimex TTS in Fentanyl-Cimex TTS may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.

5.14 Increased Risk of Seizures in Patients with Seizure Disorders

The Fentanyl-Cimex TTS in Fentanyl-Cimex TTS may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during Fentanyl-Cimex TTS therapy.

5.15 Topical Skin Reactions

Topical skin reactions may occur with use of Fentanyl-Cimex TTS and are typically limited to the application site area. If a severe skin reaction is observed, remove Fentanyl-Cimex TTS and discontinue further use.

5.16 Bradycardia

Fentanyl-Cimex TTS may produce bradycardia in some patients. Monitor patients with bradyarrhythmias closely for changes in heart rate, particularly when initiating therapy with Fentanyl-Cimex TTS.

5.17 Withdrawal

Avoid the use of mixed agonist/antagonist or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including Fentanyl-Cimex TTS. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms.

Do not abruptly discontinue Fentanyl-Cimex TTS .

5.18 Hepatic Impairment

Insufficient data are available on the use of Fentanyl-Cimex TTS in patients with impaired hepatic function. Since Fentanyl-Cimex TTS is eliminated by hepatic metabolism and Fentanyl-Cimex TTS clearance may decrease in patients with hepatic disease, monitor patients with hepatic impairment for signs of sedation and respiratory depression .

5.19 Renal Impairment

A clinical pharmacology study with intravenous Fentanyl-Cimex TTS in patients undergoing kidney transplantation has shown that patients with high blood urea nitrogen level had low Fentanyl-Cimex TTS clearance. Monitor for signs of sedation and respiratory depression in patients with renal impairment .

5.20 Neonatal Opioid Withdrawal Syndrome

Prolonged use of Fentanyl-Cimex TTS during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life‑threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available .

advertisement

6. ADVERSE REACTIONS

The following serious adverse reactions are described elsewhere in the labeling:


Most common adverse reactions (frequency ≥ 2%) were headache, hypotension, nausea, vomiting, anemia, dizziness, application site reaction-erythema, pruritus, and urinary retention. ( 6)

To report SUSPECTED ADVERSE REACTIONS, contact The Medicines Company at 1-877-488-6835 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience

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.

In controlled and uncontrolled studies, the safety of Fentanyl-Cimex TTS 40 mcg was evaluated in a total of 2114 patients with acute postoperative pain requiring opioid analgesia.

The most common adverse reactions (≥ 2%) in the placebo-controlled studies, regardless of relationship to study medication, are listed in Table 1.

Adverse Reactions

Fentanyl-Cimex TTS

(n=475)

Placebo

(n=316)

Body as a Whole
Headache

9%

7%
Cardiovascular System

Hypotension


2%


<1%

Digestive System
Nausea

39%


22%


Vomiting


12%


6%

Hemic and Lymphatic System

Anemia


3%


<1%

Nervous System
Dizziness

3%


1%

Skin System
Application site reaction- Erythema

14%

2%

Pruritus


6%


<1%

Urogenital System
Urinary retention

3%


<1%


NOTE: Patients reported as having "Nausea and vomiting" are included in "Nausea" and "Vomiting" in Table 1.

Other Adverse Reactions

Other adverse reactions that were reported (excluding adverse reactions listed in Table 1) in 4 active comparator trials vs. IV PCA morphine in patients treated with Fentanyl-Cimex TTS (n=1288) are described below:

Body as a Whole: abdominal pain, back pain, extremity pain, chest pain, chills, abdomen enlarged, asthenia, abscess, hypothermia

Cardiovascular System: syncope, postural hypotension, vasodilation, hypertension, atrial fibrillation, bradycardia, tachycardia, bigeminy, arrhythmia, myocardial infarct

Digestive System: constipation, flatulence, dyspepsia, ileus, dry mouth, diarrhea

Metabolic and Nutritional System: peripheral edema, healing abnormal, edema, dehydration

Musculoskeletal System: leg cramps and myalgia

Nervous System : insomnia, anxiety, somnolence, confusion, paresthesia, hypesthesia, nervousness, agitation, abnormal dreams, tremor

Respiratory System: hypoxia, hypoventilation, dyspnea, apnea, cough increased, asthma, hiccup, atelectasis, rhinitis, hyperventilation

Skin System: application site reactions including: itching, vesicles, papules/pustules, edema, pain, burning, dry and flaky skin, and vesiculobullous rash, wound site oozing/bleeding, wound site inflammation/erythema, rash, sweating

Special Senses: abnormal vision-blurred vision

Urogenital System: urination impaired, hematuria, urinary tract infection, urinary urgency, dysuria

Scheduled observation of the skin approximately 24 hours after Fentanyl-Cimex TTS removal was included in several studies. Some redness at the skin sites was observed in approximately 60% of patients at this observation. The skin findings included erythema, edema, and papules. The majority of these events were categorized as mild. Two patients were noted to have hyperpigmentation lasting 2-3 weeks at the application site. Three patients noted a rectangular mark at the application site, which persisted for up to 3 months after study completion.

6.2 Post Marketing Experience

The following adverse reactions have been identified during post approval use of Fentanyl-Cimex TTS. 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.

The most commonly observed events were related to application site reactions which included urticaria, application site discharge, erosion, hyperesthesia, pustules, rash and scab, application site bleeding, application site infection, and necrosis.

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 Fentanyl-Cimex TTS.

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

7. DRUG INTERACTIONS

Table 2 includes clinically significant drug interactions with Fentanyl-Cimex TTS.

Inhibitors of CYP3A4
Clinical Impact:

The concomitant use of Fentanyl-Cimex TTS and CYP3A4 inhibitors can increase the plasma concentration of Fentanyl-Cimex TTS, resulting in increased or prolonged opioid effects .

After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the Fentanyl-Cimex TTS plasma concentration will decrease , resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to Fentanyl-Cimex TTS.

Intervention:

If concomitant use is necessary, monitor patients for respiratory depression and sedation at frequent intervals.

If a CYP3A4 inhibitor is discontinued, monitor for signs of opioid withdrawal.

Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir), grape fruit juice.
CYP3A4 Inducers
Clinical Impact:

The concomitant use of Fentanyl-Cimex TTS and CYP3A4 inducers can decrease the plasma concentration of Fentanyl-Cimex TTS , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to Fentanyl-Cimex TTS .

After stopping a CYP3A4 inducer, as the effects of the inducer decline, the Fentanyl-Cimex TTS plasma concentration will increase , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.

Intervention:

If concomitant use is necessary, monitor for signs of opioid withdrawal.

If a CYP3A4 inducer is discontinued, monitor for signs of respiratory depression.

Examples: Rifampin, carbamazepine, phenytoin
Benzodiazepines and Other Central Nervous System (CNS) Depressants
Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines and other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation .
Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol.
Serotonergic Drugs
Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome .
Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation. Discontinue Fentanyl-Cimex TTS if serotonin syndrome is suspected.
Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Monoamine Oxidase Inhibitors (MAOIs)
Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) .
Intervention: The use of Fentanyl-Cimex TTS is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.
Examples: phenelzine, tranylcypromine, linezolid
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics
Clinical Impact: May reduce the analgesic effect of Fentanyl-Cimex TTS and/or precipitate withdrawal symptoms.
Intervention: Avoid concomitant use.
Examples: butorphanol, nalbuphine, pentazocine, buprenorphine
Muscle Relaxants
Clinical Impact: Fentanyl-Cimex TTS may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
Intervention: Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of the muscle relaxant as necessary.
Diuretics
Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.
Anticholinergic Drugs
Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus
Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when Fentanyl-Cimex TTS is used concomitantly with anticholinergic drugs.

Mixed Agonist/Antagonist and Partial Agonist Analgesics: Avoid use with Fentanyl-Cimex TTS because they may reduce the analgesic effect of Fentanyl-Cimex TTS or precipitate withdrawal. ( 7)

8. USE IN SPECIFIC POPULATIONS

Hepatic impairment and/or renal impairment: Monitor for signs of sedation and respiratory depression.

8.1 Pregnancy

Risk Summary

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome . Available data with Fentanyl-Cimex TTS in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.

There are no studies with the use of Fentanyl-Cimex TTS in pregnant women. Limited published data on Fentanyl-Cimex TTS use during pregnancy are insufficient to establish any drug-associated risks. In animal reproduction and developmental studies, at doses within the dosing range of humans, there was an increased risk for early embryonic lethality, decreased pup survival, and delays in developmental landmarks of surviving pups.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly .

Labor or Delivery

Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Fentanyl-Cimex TTS is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including Fentanyl-Cimex TTS, can prolong labor through actions which temporarily reduce the strength, duration and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor and respiratory depression. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

Data

Animal Data

The potential effects of Fentanyl-Cimex TTS on embryo-fetal development were studied in rat and rabbit models.

Published literature reports that administration of Fentanyl-Cimex TTS (0, 0.01, 0.1, or 0.5 mg/kg/day) to pregnant female Sprague-Dawley rats from Gestation Day 7 to 21 via implanted microosmotic minipumps did not produce any evidence of teratogenicity. The high dose is approximately 1.5 times the daily maximum recommended human dose (MRHD) of 3.2 mg/day based on a mg/m 2 body surface area basis and a 60 kg human body weight.

In contrast, the intravenous administration of Fentanyl-Cimex TTS at doses of 0, 0.01, or 0.03 mg/kg (equivalent to 0.03 and 0.09 times, respectively, the MHRD) to pregnant female rats from Gestation Day 6 to 18 resulted in evidence of embryo toxicity and a slight increase in mean delivery time in the 0.03 mg/kg/day group. There was no clear evidence of teratogenicity noted.

Pregnant female New Zealand White rabbits were treated with Fentanyl-Cimex TTS (0, 0.025, 0.1, 0.4 mg/kg) via intravenous infusion from Gestation Day 6 to 18. Fentanyl-Cimex TTS produced a slight decrease in the body weight of the live fetuses at the high dose, which may be attributed to maternal toxicity (decreased body weight and sedation). Under the conditions of the assay, there was no evidence for fentanyl-induced adverse effects on embryo-fetal development at doses up to 0.4 mg/kg (2.4 times the MRHD).

The potential effects of Fentanyl-Cimex TTS on prenatal and postnatal development were examined in the rat model. Pregnant female Wistar rats were treated with 0, 0.025, 0.1, or 0.4 mg/kg/day Fentanyl-Cimex TTS via intravenous infusion (equivalent to 0.08, 0.3, and 1.2 times, respectively, the MRHD) from Gestation Day 6 through 3 weeks of lactation. Fentanyl-Cimex TTS treatment (0.4 mg/kg/day) significantly decreased body weight in male and female pups and also decreased survival in pups at Post-Natal Day 4. Both the mid-dose and high-dose of Fentanyl-Cimex TTS animals demonstrated alterations in some physical landmarks of development (delayed incisor eruption and eye opening) and transient behavioral development (decreased locomotor activity at Post-Natal Day 28 which recovered by Post-Natal Day 50). No adverse effects were observed at 0.08 times the MRHD.

8.2 Lactation

Risk Summary

Limited published literature reports that Fentanyl-Cimex TTS is present in human milk at low levels, which resulted in an estimated infant dose of 0.38% of the maternal weight-adjusted dosage. There are no reports of adverse effects on the breastfed infant and no information on the effects on milk production.

The developmental and health benefits from breastfeeding should be considered along with the mother’s clinical need for Fentanyl-Cimex TTS and any potential effects on the breastfed infant from Fentanyl-Cimex TTS or from the underlying maternal condition.

Clinical Considerations

Infants exposed to Fentanyl-Cimex TTS through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast‑feeding is stopped.

8.3 Females and Males of Reproductive Potential

Infertility

Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible .

8.4 Pediatric Use

The efficacy and safety of Fentanyl-Cimex TTS have not been established in pediatric patients under 18 years of age.

8.5 Geriatric Use

Fentanyl-Cimex TTS 40 mcg has been studied in 499 patients 65 years or older; 174 of whom were 75 years or older. No major differences in safety or effectiveness were observed between these subjects and younger subjects. However, the incidence of the following events was slightly higher in patients ≥65 years compared with patients who were 18 to 64 years of age: hypotension (4% versus 3%), confusion (2% versus <1%), hypokalemia (3% versus 1%), hypoxia (3% versus 2%), and hypoventilation (2% versus <1%).

In a pharmacokinetic study of Fentanyl-Cimex TTS conducted in 63 healthy volunteers (25 subjects older than 65 years), age did not significantly affect the extent of drug absorption. Literature suggests that the clearance of Fentanyl-Cimex TTS may be reduced and the terminal half-life prolonged in the elderly.

Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration and monitor closely for signs of central nervous system and respiratory depression .

Fentanyl-Cimex TTS is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

8.6 Hepatic Impairment

Insufficient data are available on the use of Fentanyl-Cimex TTS in patients with impaired hepatic function. Since Fentanyl-Cimex TTS is eliminated by hepatic metabolism and Fentanyl-Cimex TTS clearance may decrease in patients with hepatic disease, monitor patients with hepatic impairment closely for signs of central nervous system and respiratory depression, especially when initiating treatment with Fentanyl-Cimex TTS.

8.7 Renal Impairment

Approximately 10% of administered Fentanyl-Cimex TTS is excreted unchanged by the kidney. Insufficient data are available on the use of Fentanyl-Cimex TTS in patients with impaired renal function to determine effects on renal clearance of Fentanyl-Cimex TTS. Monitor patients with renal impairment closely for signs of central nervous system and respiratory depression, especially when initiating treatment with Fentanyl-Cimex TTS.

9. DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

Fentanyl-Cimex TTS contains Fentanyl-Cimex TTS, a Schedule II controlled substance.

9.2 Abuse

Fentanyl-Cimex TTS contains Fentanyl-Cimex TTS, a substance with a high potential for abuse similar to other opioids including hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol. Fentanyl-Cimex TTS can be abused and is subject to misuse, addiction, and criminal diversion .

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.

Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.

"Drug-seeking" behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated "loss" of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). "Doctor shopping" (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers should 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 true addiction.

Fentanyl-Cimex TTS, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity and frequency, and renewal requests, as required by state and federal law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of Fentanyl-Cimex TTS

Fentanyl-Cimex TTS is for transdermal use only for patients in the hospital. Abuse of Fentanyl-Cimex TTS poses a risk of overdose and death. This risk is increased with concurrent abuse of Fentanyl-Cimex TTS and alcohol and other central nervous system depressants . Contact with residual Fentanyl-Cimex TTS in hydrogel of the device can result in fatal overdose.

9.3 Dependence

Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal may also be precipitated through the administration of drugs with opioid antagonist activity, (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

Fentanyl-Cimex TTS should not be abruptly discontinued in a physically dependent patient . If Fentanyl-Cimex TTS is abruptly discontinued in a physically‑dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms .

10. OVERDOSAGE

Clinical Presentation

Acute overdose with Fentanyl-Cimex TTS can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations .

Treatment of Overdose

In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques.

The opioid antagonists naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to Fentanyl-Cimex TTS overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to Fentanyl-Cimex TTS overdose.

Because the duration of opioid reversal is expected to be less than the duration of action of Fentanyl-Cimex TTS in Fentanyl-Cimex TTS, carefully monitor the patient until spontaneous respiration is reliably reestablished. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information.

In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist may precipitate acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be initiated with care and by titration with smaller than usual doses of the antagonist.

11. DESCRIPTION

11.1 Chemical Characteristics of Drug Substance and Product

Fentanyl-Cimex TTS is a patient-controlled iontophoretic transdermal system providing on-demand systemic delivery of Fentanyl-Cimex TTS, an opioid agonist, for up to 24 hours or a maximum of 80 doses, whichever comes first.

The chemical name is propanamide, N-phenyl-N-[1-(2-phenylethyl)-4- piperidinyl] monohydrochloride. The structural formula is:

The molecular weight of Fentanyl-Cimex TTS hydrochloride is 372.93, and the empirical formula is C 22H 28N 2O·HCl. The n-octanol:water partition coefficient is 860:1; the pKa is 8.4.

The active ingredient in Fentanyl-Cimex TTS is Fentanyl-Cimex TTS. Fentanyl-Cimex TTS contains 10.8 mg of Fentanyl-Cimex TTS hydrochloride equivalent to 9.7 mg of Fentanyl-Cimex TTS. Fentanyl-Cimex TTS is designed to deliver a 40 mcg dose of Fentanyl-Cimex TTS (equivalent to 44.4 mcg of Fentanyl-Cimex TTS hydrochloride) over a 10-minute period upon each activation of the dose button .

The inactive ingredients in the Fentanyl-Cimex TTS hydrogels consist of cetylpyridinium chloride, USP; citric acid, USP; polacrilin; polyvinyl alcohol; sodium citrate, USP; sodium chloride, USP; sodium hydroxide; and purified water, USP.

Chemical Structure

11.2 System Components and Structure

Each Fentanyl-Cimex TTS is composed of a plastic top housing that contains the battery and electronics and a red plastic bottom housing containing two hydrogel reservoirs and a polyisobutylene skin adhesive. Only one of the hydrogels (the anode, located under the dosing button) contains Fentanyl-Cimex TTS HCl, along with inactive ingredients. The other hydrogel (the cathode) contains only pharmacologically inactive ingredients. The bottom housing has a red tab that is used for Fentanyl-Cimex TTS removal from the skin and during disposal . A siliconized clear, plastic release liner covers the hydrogels and must be removed and discarded prior to placement on the skin. Fentanyl-Cimex TTS is powered by a 3-volt lithium battery.

Figure 8 Fentanyl-Cimex TTS ® (fentanyl iontophoretic transdermal system)

Figure of Fentanyl-Cimex TTS Unit

12. CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Fentanyl-Cimex TTS contains Fentanyl-Cimex TTS, an opioid agonist whose principal therapeutic action is analgesia. Fentanyl-Cimex TTS interacts predominantly with the μ-opioid receptor. These μ-binding sites are discretely distributed in the human brain, spinal cord, and other tissues.

12.2 Pharmacodynamics

Effects on Central Nervous System

Fentanyl-Cimex TTS produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.

Fentanyl-Cimex TTS causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic. Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations.

Effects on Gastrointestinal Tract and Other Smooth Muscle

Fentanyl-Cimex TTS causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.

Effects on the Cardiovascular System

Fentanyl-Cimex TTS produces peripheral vasodilation which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes and sweating and/or orthostatic hypotension.

Effects on the Endocrine System

Opioids inhibit the secretion of ACTH, cortisol, and luteinizing hormone (LH) in humans. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon .

Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date .

Effects on the Immune System

Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive.

Concentration–Efficacy Relationships

When patients titrated themselves to analgesic effect with Fentanyl-Cimex TTS, serum concentrations were in the range of 0.4 to 1.5 ng/mL over the 24-hour dosing period.

The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with potent agonist opioids. The minimum effective analgesic concentration of Fentanyl-Cimex TTS for any individual patient may increase over time due to an increase in pain, the development of a new pain syndrome and/or the development of analgesic tolerance .

Concentration–Adverse Reaction Relationships

There is a relationship between increasing Fentanyl-Cimex TTS plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions.

12.3 Pharmacokinetics

Unless otherwise specified, the clinical pharmacology studies described in this section were performed in healthy adult volunteers. Volunteers were administered naltrexone to antagonize the opioid effects of Fentanyl-Cimex TTS.

Absorption

At the initiation of each dose, an electrical current is activated for 10 minutes, which moves a dose of Fentanyl-Cimex TTS from the drug-containing reservoir through the skin and into the systemic circulation. Compared to IV Fentanyl-Cimex TTS administration, Fentanyl-Cimex TTS concentrations in blood increase slowly with Fentanyl-Cimex TTS activation and continue to increase for approximately 5 minutes after the completion of each 10-minute dose.

The systemic absorption of Fentanyl-Cimex TTS from Fentanyl-Cimex TTS increases as a function of time, and this increase appears to be independent of frequency of dosing. At treatment initiation, the amount of Fentanyl-Cimex TTS absorbed is expected to be approximately 16 mcg. In clinical pharmacokinetic studies, on-demand dosing was initiated immediately after Fentanyl-Cimex TTS application. This resulted in absorption of a 40 mcg Fentanyl-Cimex TTS dose by about 10 hours post treatment initiation. Thereafter, a 40 mcg dose of Fentanyl-Cimex TTS is delivered with each activation.

After delivery of the maximum number of doses in the shortest possible time period (80 consecutive doses delivered over approximately 13 hours), the average Fentanyl-Cimex TTS serum concentration was 1.94 ± 0.43 ng/mL. Pharmacokinetic data from illustrative dosing regimens are represented in Table 3. When Fentanyl-Cimex TTS was applied without activating the current, the average absorption rate for Fentanyl-Cimex TTS over 24 hours was 2.3 mcg/h.

Inter-subject variability in Fentanyl-Cimex TTS AUC following Fentanyl-Cimex TTS treatment (33%) was comparable to IV Fentanyl-Cimex TTS treatment (28%).

The delivery of Fentanyl-Cimex TTS from Fentanyl-Cimex TTS is similar whether applied on the upper outer arm or the chest. When Fentanyl-Cimex TTS is placed on the lower inner arm, the delivery of Fentanyl-Cimex TTS is approximately 20% lower. Other application sites have not been evaluated.

Figure 9: Serum Fentanyl-Cimex TTS Concentration Following 40 mcg Fentanyl-Cimex TTS ® (fentanyl) Compared to IV Fentanyl-Cimex TTS

A: First Hour of a Representative Treatment *

B: Last Hour and Upon Termination of a Representative Treatment *

* Fentanyl-Cimex TTS ® 40 mcg: 2 sequential doses over 20 minutes every hour for 23 hours and 20 minutes; IV: 80 mcg dose over 20 minutes every hour for 23 hours and 20 minutes.

Dosing Regimen
Parameter

48 a doses (two sequential doses every hour for 23 hours and 20 minutes)

80 b sequential doses (one dose every ten minutes for 13 hours and 20 minutes)
AUC per on demand dose (ng/mL) 0.57±0.13 0.51±0.16
Cmax (ng/mL) 1.3±0.3 1.94±0.43

AUC for this dosing regimen is value estimated between 23-24 hours

Average AUC over all doses delivered during the treatment duration (13.33 hours)

a Representative dosing regimen based on number of doses administered by patients in Phase 3 clinical studies

b Maximum theoretical dosing

Distribution

Fentanyl-Cimex TTS administered intravenously exhibits a three-compartment disposition model. In healthy volunteers after IV administration, the estimated initial distribution half-life was about 6 minutes; the second distribution half-life was about 1-hour; and the terminal half-life was about 16 hours. The average volume of distribution for Fentanyl-Cimex TTS at steady state following IV administration is 833 L.

Mean values for unbound fractions of Fentanyl-Cimex TTS in plasma are estimated to be between 13 and 21%. Fentanyl-Cimex TTS binds to erythrocytes, α1 acid glycoproteins, and plasma albumin.

Binding is independent of drug concentration over the therapeutic range. Fentanyl-Cimex TTS plasma protein binding capacity decreases with increasing ionization of the drug. Alterations in blood pH may alter ionization of Fentanyl-Cimex TTS and therefore its distribution between plasma and the central nervous system. Fentanyl-Cimex TTS accumulates in the skeletal muscle and fat and is released slowly into the blood.

Elimination

The average clearance in healthy subjects following IV administration was observed to be 53 L/h. A decline in Fentanyl-Cimex TTS concentration after termination of treatment and the terminal half-life is similar following IV administration of Fentanyl-Cimex TTS and Fentanyl-Cimex TTS. This suggests a negligible contribution from continued absorption of Fentanyl-Cimex TTS remaining in the skin.

Metabolism

In humans, Fentanyl-Cimex TTS is metabolized primarily by cytochrome P450 3A4-mediated N-dealkylation to norfentanyl and other inactive metabolites that do not contribute materially to the observed activity of the drug.

Skin does not metabolize Fentanyl-Cimex TTS administered transdermally. This was determined in a human keratinocyte cell assay.

Excretion

Within 72 hours of IV Fentanyl-Cimex TTS administration, approximately 75% of the dose is excreted in urine, mostly as metabolites, with less than 10% representing unchanged drug. Approximately 9% of the dose is recovered in the feces, primarily as metabolites.

Specific Populations

Age

Age did not affect Fentanyl-Cimex TTS absorption from Fentanyl-Cimex TTS.

Sex

Sex differences have been reported for hepatically metabolized drugs. Generally, those that are metabolized by CYP3A4 appear to be eliminated faster by women in many cases. There have been no reports on gender differences in Fentanyl-Cimex TTS pharmacokinetics.

Race

Race did not affect Fentanyl-Cimex TTS absorption from Fentanyl-Cimex TTS.

Hepatic Impairment

No studies specific to Fentanyl-Cimex TTS in patients with hepatic impairment have been conducted. In the literature, Fentanyl-Cimex TTS appears to be affected more by hepatic blood flow than by hepatocellular function. The plasma concentration time profiles for the control and cirrhotic patients were similar and not significantly different with respective average elimination half-life values of 10.8 mL/min/kg vs. 11.3 mL/min/kg and volume of distribution values of 3.81 L/kg vs. 4.41 L/kg. In addition, the pharmacokinetics of Fentanyl-Cimex TTS in patients with end-stage liver disease who were undergoing hemodialysis to those in normal patients was studied. While differences between groups were not statistically significant, Fentanyl-Cimex TTS clearance values were reported to be lower for the hepatically impaired patients.

Renal Impairment

No studies specific to Fentanyl-Cimex TTS in patients with renal impairment have been conducted. In the literature, the pharmacokinetics of Fentanyl-Cimex TTS in patients with severe renal disease was compared to healthy patients. Plasma Fentanyl-Cimex TTS concentrations decreased faster following an IV Fentanyl-Cimex TTS administration in those with renal disease than in the control group, indicating more rapid clearance in the former. As renal clearance of Fentanyl-Cimex TTS is only 10%, a decrease in renal function would not be expected to have a significant effect on the clearance of Fentanyl-Cimex TTS.

Drug Interaction Studies

CYP3A4 Inhibitors

Fentanyl-Cimex TTS is metabolized mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4). The interaction between ritonavir, a CPY3A4 inhibitor, and Fentanyl-Cimex TTS was investigated in eleven healthy volunteers in a randomized crossover study. Subjects received oral ritonavir or placebo for 3 days. The ritonavir dose was 200 mg three times a day on Day 1 and 300 mg three times a day on Day 2 followed by one morning dose of 300 mg on Day 3. On Day 2, Fentanyl-Cimex TTS was given as a single IV dose at 5 mcg/kg two hours after the afternoon dose of oral ritonavir or placebo. Naloxone was administered to counteract the side effects of Fentanyl-Cimex TTS. The results suggested that ritonavir might decrease the clearance of Fentanyl-Cimex TTS by 67%, resulting in a 174% (range 52%–420%) increase in Fentanyl-Cimex TTS AUC0-∞. The concomitant use of transdermal Fentanyl-Cimex TTS with all CYP3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefazadone, amiodarone, amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, verapamil, or grapefruit juice) may result in an increase in Fentanyl-Cimex TTS plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Carefully monitor patients receiving Fentanyl-Cimex TTS and any CYP3A4 inhibitor for signs of respiratory depression for an extended period of time and discontinue Fentanyl-Cimex TTS if warranted .

CYP3A4 Inducers

Co-administration with agents that induce CYP3A4 activity may decrease plasma concentration of Fentanyl-Cimex TTS following use of Fentanyl-Cimex TTS. Discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in Fentanyl-Cimex TTS plasma concentration.

First Hour of a Representative Treatment image Last Hour and Upon Termination of a Representative Treatment image

13. NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

In a two-year carcinogenicity study conducted in rats, Fentanyl-Cimex TTS was not associated with an increased incidence of tumors at subcutaneous doses up to 0.033 mg/kg/day in males or 0.1 mg/kg/day in females. These lifetime doses in rats are approximately 0.1 and 0.3, respectively, the maximum recommended human dose (MRHD) of 3.2 mg/day by transdermal administration based on a mg/m 2 body surface area comparison and a 60 kg human body weight.

Mutagenesis

Fentanyl-Cimex TTS is not mutagenic in the in vitro bacterial reverse mutation assay (Ames assay), the primary rat hepatocyte unscheduled DNA synthesis assay, the BALB/c 3T3 transformation test, and the in vitro chromosomal aberration assays using either human lymphocytes or Chinese hamster ovary cells.

Impairment of Fertility

The potential effects of Fentanyl-Cimex TTS on male and female fertility were examined in the rat model via two separate experiments. In the male fertility study, male rats were treated with Fentanyl-Cimex TTS doses of 0, 0.025, 0.1, or 0.4 mg/kg/day (equivalent to 0.08, 0.3, 1.2 times, respectively, the MHRD) via continuous intravenous infusion for 28 days prior to mating; female rats were not treated. In the female fertility study, female rats were treated with Fentanyl-Cimex TTS doses of 0, 0.025, 0.1, or 0.4 mg/kg/day (equivalent to 0.08, 0.3, 1.2 times, respectively, the MHRD) via continuous intravenous infusion for 14 days prior to mating until Day 16 of pregnancy; male rats were not treated. Analysis of fertility parameters in both studies indicated that an intravenous dose of Fentanyl-Cimex TTS up to 0.4 mg/kg/day to either the male or the female alone produced no effects on fertility (this dose is approximately 1.2 times the maximum available daily human dose on a mg/m 2 basis). In a separate study, a single daily bolus dose of Fentanyl-Cimex TTS was shown to impair fertility in rats when given in intravenous doses of 0.3 times the MRHD for a period of 12 days.

14. CLINICAL STUDIES

14.1 Placebo-Controlled Trials

The efficacy and safety of Fentanyl-Cimex TTS for treatment of short-term acute pain were evaluated in three placebo-controlled studies in postoperative patients. The patients were predominantly female (70‑83%) and Caucasian (79‑84%), and their mean age was 45‑54 years (range, 18‑90 years). Patients were enrolled while in the recovery room shortly after major surgery (predominantly lower abdominal or orthopedic) if they were expected to require at least 24 hours of parenteral opioid treatment and were not opioid tolerant; their ASA (American Society of Anesthesiologists) physical status was I, II, or III; and their postsurgical recovery was expected to be uncomplicated. Across the trials, 154 patients were ASA I status (21%); 435 patients were ASA II status (60%); and 138 patients were ASA III status (19%). Administration of long-lasting or continuous regional analgesics, or any non-opioid analgesics, was not permitted in the studies. Patients who remained in the studies for three or more hours using Fentanyl-Cimex TTS (or the control) for patient-controlled analgesia (PCA) were considered evaluable.

In the immediate postoperative period, patients were titrated to comfort with IV Fentanyl-Cimex TTS or morphine per hospital protocol. Once comfortable, patients were randomized and Fentanyl-Cimex TTS or matching placebo Fentanyl-Cimex TTS was applied. Patients were instructed to use Fentanyl-Cimex TTS for pain. Supplemental IV Fentanyl-Cimex TTS was administered by bolus injection as needed to achieve comfort up to three hours post-enrollment. The percentage of patients who used rescue medication during these three hours, as well as the mean amount of rescue medication used, is shown in Table 4 below.

Study Fentanyl-Cimex TTS

n=454

Placebo

n=273

Study 1 45% (83 mcg) 52% (102 mcg)
Study 2 48% (100 mcg) 55% (95 mcg)
Study 3 34% (78 mcg) 36% (76 mcg)

After Study Hour 3, Fentanyl-Cimex TTS alone or the placebo treatment alone was used to provide analgesia. Efficacy demonstrated in all three studies as demonstrated by the last mean pain intensity scores recorded during the 24-hour treatment period are presented in Table 5.

Study Fentanyl-Cimex TTS

n=454

Placebo

n=273

p-value
Study 1

(NRS a)


3.4

5.3 <0.0001
Study 2

(VAS b)


31

41 0.0474
Study 3

(VAS b)


21

37 0.0006

a Verbal numerical rating scale 0-10 at 24 hours or at discontinuation

b Visual analogue scale, 0-100 mm at 24 hours or at discontinuation

In each of the three randomized, double-blind, placebo-controlled trials, fewer patients discontinued for lack of efficacy from three hours to twenty-four hours after Fentanyl-Cimex TTS application.


Study


Fentanyl-Cimex TTS

n=454

Placebo

n=273

p-value
Study 1 27% (64/235) 57% (116/204) <0.0001
Study 2 25% (36/142) 40% (19/47) 0.049
Study 3 8% (6/77) 41% (9/22) 0.0001

The efficacy of Fentanyl-Cimex TTS was similar across the range of body mass indices studied (<25 to >40 kg/m 2 Body Mass Index).

Patients who completed 24 hours of Fentanyl-Cimex TTS treatment in the controlled studies used a wide range of the available 80 doses, with a mean of 29 doses per patient (range of 0 to 93 doses). The majority of patients (56.5%) used between 11 to 50 doses. One percent of patients required a second Fentanyl-Cimex TTS within 24 hours, after exhausting the first Fentanyl-Cimex TTS.

16. HOW SUPPLIED/STORAGE AND HANDLING

Fentanyl-Cimex TTS (fentanyl iontophoretic transdermal system) is packaged in a sealed tray containing one Controller and one pouched Drug Unit for assembly. For distribution, there are six sealed trays per carton.

NDC 65293-011-01 (each individual tray contains one Drug Unit and one Controller)

NDC 65293-011-06 (carton of six trays containing Fentanyl-Cimex TTS)

ACCIDENTAL CONTACT WITH THE HYDROGELS (ON THE ADHESIVE SIDE OF Fentanyl-Cimex TTS) CAN RESULT IN FATAL OVERDOSE OF Fentanyl-Cimex TTS. THEREFORE, THE Fentanyl-Cimex TTS MUST ONLY BE HANDLED WHILE WEARING GLOVES.

If there is accidental contact with skin, the affected area should be rinsed thoroughly with water. Do not use soap, alcohol, or other solvents to remove the hydrogel because they may enhance the drug’s ability to penetrate the skin .

Fentanyl-Cimex TTS should be stored at 25°C (77°F); excursions permitted to 15–30°C (59–86°F). Assemble and use immediately after removal from the individually sealed package. Do not use if the seal on the Tray or Drug Unit pouch is broken or damaged.

17. PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Life-Threatening Respiratory Depression


Accidental Exposure


Addiction, Abuse and Misuse


Interactions with Benzodiazepines and Other CNS Depressants

Inform patients and caregivers that potentially fatal additive effects may occur if Fentanyl-Cimex TTS is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a healthcare provider .

Serotonin Syndrome

Inform patients that opioids could cause a rare but potentially life‑threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications .

MAOI Interaction

Inform patients to avoid taking Fentanyl-Cimex TTS while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking Fentanyl-Cimex TTS .

Important Administration Instructions

Advise patients that the level of current (62 microA/cm 2) provided by Fentanyl-Cimex TTS is generally imperceptible to the patient.

Anaphylaxis


Infertility

Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible .

Disposal of Unused Fentanyl-Cimex TTS

Advise patients that only their health care provider should remove Fentanyl-Cimex TTS from them and properly dispose of Fentanyl-Cimex TTS prior to them leaving the hospital.

Manufactured, Distributed and Marketed by:

The Medicines Company

8 Sylvan Way

Parsippany, NJ 07054

Part No. 308-0023 Rev 02

Software Version: 205-0002, SB-SWC-002 Rev. 5, IT101 Controller Software, Version 1.6.715

Printed in USA

Fentanyl-Cimex TTS ® Important Device Instructions

1 Explanation of Standardized Medical Device Symbols

Standardized symbols refer to specific warnings, features, or classifications of the device component of IONSYS® (fentanyl iontophoretic transdermal system). See Table 1 for the symbols and meaning of these symbols.

Symbol Meaning
Do not use
Operating instructions
Caution
Dust-protected

Protected against splashing water

Type body floating (BF) applied part*
Electrostatic discharge (ESD) sensitivity
Magnetic resonance (MR) unsafe
Radio frequency (RF) transmitter

*Body floating (BF) refers to a device that comes into contact with the patient’s body and allows for electrical conductivity.

2 System Components and Structure

Each Fentanyl-Cimex TTS is composed of a plastic top housing that contains the battery and electronics and a red plastic bottom housing containing two hydrogel reservoirs and a polyisobutylene skin adhesive. Only one of the hydrogels (the anode, located under the dosing button) contains Fentanyl-Cimex TTS HCl, along with inactive ingredients. The other hydrogel (the cathode) contains only pharmacologically inactive ingredients. The bottom housing has a red tab that is used only for Fentanyl-Cimex TTS removal from the skin and during disposal. A siliconized clear, plastic release liner covers the hydrogels and must be removed and discarded prior to placement on the skin. Fentanyl-Cimex TTS is powered by a 3-volt lithium battery.

Figure 1 Fentanyl-Cimex TTS ® (fentanyl iontophoretic transdermal system)

3 Fentanyl-Cimex TTS TROUBLESHOOTING

Fentanyl-Cimex TTS delivers an on-demand dose of Fentanyl-Cimex TTS over 10 minutes. The Normal Fentanyl-Cimex TTS Feedback table below illustrates normal audible and visual feedback from Fentanyl-Cimex TTS upon assembly and during patient use.

Mode Audible Feedback Visual Feedback

(Light)

Visual Feedback

(Digital Display)

Assemble Fentanyl-Cimex TTS by snapping the two parts together A single audible beep Light will blink RED momentarily and then start blinking GREEN at a slow rate Display will flash “88” and then transition to steady “0” indicating that Fentanyl-Cimex TTS is ready for use and 0 doses have been delivered
Ready Mode: Fentanyl-Cimex TTS is ready and awaiting patient request for dose None Light will blink GREEN at a slow rate

Display will show the number of doses delivered (steady; not flashing)

Patient initiates a dose by pressing and releasing the button twice within 3 seconds A single audible beep indicates the start of delivery of each dose The light changes from blinking GREEN at a slow rate to blinking GREEN at a fast rate The display alternates between a walking circle and the number of doses delivered
10-minute dose is complete – Fentanyl-Cimex TTS returns to Ready Mode None Light changes from blinking GREEN at a fast rate to blinking GREEN at a slow rate Display will show the number of doses delivered (steady; not flashing)
End of Use: 24 hours or 80 doses have been completed None None. Light will be Off. Display will flash the number of doses delivered

If Fentanyl-Cimex TTS does not appear to function immediately, instruct the patient to attempt to initiate a dose again by firmly pressing and releasing the button twice within 3 seconds (i.e., double-press). A single audible beep will be emitted immediately, confirming that Fentanyl-Cimex TTS is functional. Anytime during use, if Fentanyl-Cimex TTS does not function properly, instruct the patient to call a staff member. Refer to the Error Messages table for possible problems and appropriate course of action. Error messages provide information (e.g., blinking lights, audible beeps) about problems that may occur during operation of Fentanyl-Cimex TTS.

Error Message/Feedback Probable Cause Action Required
Low battery or defective Fentanyl-Cimex TTS
  • Do not use Fentanyl-Cimex TTS.
  • Dispose of Fentanyl-Cimex TTS.
  • Place a new Fentanyl-Cimex TTS on a different skin site.
Poor skin contact
  • If Fentanyl-Cimex TTS appears to be loose or lifting from skin, secure Fentanyl-Cimex TTS to patient’s skin by pressing the edges with fingers or securing with non-allergenic tape.
  • If using tape, apply it along the long edges to secure Fentanyl-Cimex TTS to patient’s skin. Do not cover button or display.
  • After taping, if Fentanyl-Cimex TTS beeps again, remove and dispose. Place a new Fentanyl-Cimex TTS on a different skin site.
  • Do not tape if evidence of blistered or broken skin.
System error
  • Remove Fentanyl-Cimex TTS from patient.
  • Hold down dosing button until beeping stops and display goes blank.
  • Dispose of Fentanyl-Cimex TTS.
  • Place a new Fentanyl-Cimex TTS on a different skin site.
End of use (24 hours or 80 doses elapsed)
  • Remove Fentanyl-Cimex TTS from patient.
  • Hold down dosing button until display goes blank.
  • Dispose of Fentanyl-Cimex TTS.
  • Place a new Fentanyl-Cimex TTS on a different skin site.

Electromagnetic Compatibility testing for Immunity, specifically, Electrostatic Discharge (ESD) testing, demonstrated contact discharges to the hydrogel touch points caused Fentanyl-Cimex TTS to shut down in a safe mode in several cases. A safe mode is a mode in which the controller cannot be activated; thereby, unable to dispense the drug. Therefore, Fentanyl-Cimex TTS that shut down due to an ESD event are non-operable and deemed defective. These ESD events only occurred during the task of assembling the controller and drug units together.

4 ELECTROMAGNETIC COMPATIBILITY

Fentanyl-Cimex TTS is designed to be used only in a hospital environment. In this environment Fentanyl-Cimex TTS was not shown to interfere with nearby electronic equipment, and is immune to interference from other electronic equipment. Fentanyl-Cimex TTS was tested in compliance with IEC 60601-1-2 at test levels for a hospital environment. Table 4, Table 5, and Table 6 list tests performed and provide guidance on the environment.

Some diagnostic or therapeutic procedures (such as MRI, cardioversion, defibrillation, X-ray, CT, or diathermy), and some electronic security systems can exceed the test levels shown in the tables. Remove Fentanyl-Cimex TTS before exposure to MRI, cardioversion, defibrillation, X-ray, CT, or diathermy. Fentanyl-Cimex TTS contains radio-opaque components and may interfere with an X-ray image or CT scan. Avoid exposing Fentanyl-Cimex TTS to electronic security systems. Electrostatic discharge can exceed the test levels shown in the tables. Avoid contact with synthetic materials (such as carpeted flooring) to reduce the possibility of electrostatic discharge. Communications equipment (such as base stations for radio telephones and land mobile radios, amateur radio, AM and FM radio broadcast and TV broadcast and Radio), and Radio Frequency Identification (RFID) transmitters, can exceed the test levels shown in the tables.

Minimize exposure to sources of electromagnetic radiation by adhering to the separation distances found in Table 6. If exposure to the procedures, electronic security systems, electrostatic discharge, communications equipment, or RFID systems occurs, and if Fentanyl-Cimex TTS does not appear to function normally as described in Table 2, Fentanyl-Cimex TTS should be removed and replaced with a new Fentanyl-Cimex TTS.

Fentanyl-Cimex TTS is intended for use in the electromagnetic environment specified below. The health care provider should assure that Fentanyl-Cimex TTS is used in such an environment.
Emission Test Compliance Electromagnetic Environment - Guidance
RF emissions

CISPR 11

Group 1 Fentanyl-Cimex TTS uses RF energy only for its internal function. Therefore, its RF emissions are very low and are not likely to cause any interference in nearby electronic equipment.
RF emissions

CISPR 11

Class B Fentanyl-Cimex TTS is suitable for use in all establishments, including domestic establishments and those directly connected to the public low-voltage power supply network that supplies buildings used for domestic purposes. NOTE: Fentanyl-Cimex TTS is indicated for hospital use only.
Fentanyl-Cimex TTS is intended for use in the electromagnetic environment specified below. The health care provider should assure that Fentanyl-Cimex TTS is used in such an environment.

Immunity Test

IEC 60601

Test Level

Compliance Level Electromagnetic Environment - Guidance
Electrostatic

Discharge (ESD)

IEC 61000-4-2

± 6kV contact

± 8kV air

± 6kV contact

± 8kV air


Floors should be wood, concrete, or ceramic tile. If floors are covered with synthetic material, the relative humidity should be at least 30%.


Power frequency

(50/60Hz) magnetic field

IEC 61000-4-8

3 A/m 3 A/m

Power frequency magnetic fields should be at levels characteristic of a typical location in a typical hospital environment. (a)

Fentanyl-Cimex TTS is MR UNSAFE. Remove Fentanyl-Cimex TTS before an MRI procedure.


Radiated RF

IEC 61000-4-3

3 V/m

80 MHz to 2.5 GHz

3 V/m

80 MHz to 2.5 GHz


RF communications equipment and RFID transmitters should be used no closer to Fentanyl-Cimex TTS than the recommended separation distance calculated from the equation applicable to the frequency of the transmitter.(a)

Recommended separation distance:

Where P is the maximum power output of the transmitter in watts (W) according to the transmitter manufacturer and d is the recommended separation distance in meters (m).

Interference may occur in the vicinity of equipment marked with the following symbol:

(a) Field strengths, as determined by an electromagnetic site survey, must be less than the stated compliance level. Remove Fentanyl-Cimex TTS to prevent exposure to field strengths that exceed the stated compliance level.
Fentanyl-Cimex TTS is intended for use in an electromagnetic environment in which radiated RF disturbances are controlled. The health care provider can help prevent electromagnetic interference by maintaining a minimum distance (meters) between RF transmitters and Fentanyl-Cimex TTS as recommended below, according to the maximum output power (watts) of the transmitter.
Rated maximum output power of transmitter

(watts)

Separation distance according to frequency of transmitter

(meters)

150 kHz to 800 MHz

800 MHz to 2.5 GHz

0.01 0.12 0.23
0.1 0.38 0.73
1 1.2 2.3
10 3.8 7.3
100 12 23

For transmitters rated at a maximum output power not listed above, the recommended separation distance d in meters (m) can be estimated using the equation applicable to the frequency of the transmitter, where P is the maximum output power rating of the transmitter in watts (W) according to the transmitter manufacturer.

NOTE: For 1W RFID transmitters, the recommended separation distance is 2.3 meters.

NOTE: At 800 MHz, the separation distance for the higher frequency range applies.

NOTE: These guidelines may not apply in all situations. Electromagnetic propagation is affected by absorption and reflection from structures, objects, and people.


For questions about Fentanyl-Cimex TTS, including product returns, call 1-877-488-6835.

Manufactured, Distributed and Marketed by:

The Medicines Company

8 Sylvan Way

Parsippany, NJ 07054

December 2016

Part No. 308-0023 Rev 02

Software Version: 205-0002, SB-SWC-002 Rev. 5, IT101 Controller Software, Version 1.6.715

Printed in USA

no reuse image op instrcutions image caution symbol image splash water and dust protected image Type Body floating image esd image unsafe for MRI image RF Trans symbol Image of Fentanyl-Cimex TTS Unit Low battery- defective device error image Pooor skin contact error image System error image End of Use error image esd symbol image MRI unsafe separation distance formula image Radio Frequency Transmitter symbol

Fentanyl-Cimex TTS ® Medication Guide

Fentanyl-Cimex TTS ® (eye-AHN-sis)

(fentanyl iontophoretic transdermal system) CII

Fentanyl-Cimex TTS is:


Important information about Fentanyl-Cimex TTS:

Get emergency help right away if you use too much Fentanyl-Cimex TTS, the active ingredient in Fentanyl-Cimex TTS (overdose). Only you should press the button on Fentanyl-Cimex TTS. When you first start using Fentanyl-Cimex TTS, serious or life-threatening breathing problems that can lead to death may occur.


Do not use Fentanyl-Cimex TTS if you have:


Before using Fentanyl-Cimex TTS, tell your healthcare provider if you have a history of:


Tell your healthcare provider if you are:


Your healthcare provider:


How do I use Fentanyl-Cimex TTS?



Your healthcare provider will check your Fentanyl-Cimex TTS to make sure it is working properly.

When using Fentanyl-Cimex TTS:


Tell your healthcare provider right away if:


While using Fentanyl-Cimex TTS DO NOT:


The possible side effects of Fentanyl-Cimex TTS:


Tell your health care provider immediately if you have:


These are not all the possible side effects of Fentanyl-Cimex TTS. Ask your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov.

Manufactured, Distributed and Marketed by:

The Medicines Company

8 Sylvan Way

Parsippany, NJ 07054

December 2016

Part No. 308-0023 Rev 02

Software Version 205-0002, SB-SWC-002 Rev. 5, IT101 Controller Software, Version 1.6.715

Printed in USA

This Medication Guide has been approved by the U.S. Food and Drug Administration. Issued: 12/2016

Fentanyl-Cimex TTS device image press and release dosing button image

Instructions for Use and Disposal


Fentanyl-Cimex TTS ®

Fentanyl-Cimex TTS iontophoretic transdermal system, 40mcg/activation

For single use only. Up to 24 hours or 80 doses, whichever comes first.

Refer to the Prescribing Information (PI) and the following educational materials for more information about Fentanyl-Cimex TTS:

  • Fentanyl-Cimex TTS Medication Guide
  • Fentanyl-Cimex TTS REMS Safety Brochure: Guide for Nurses and Pharmacists

1. Prepare Patient Site

! ONLY 1 Fentanyl-Cimex TTS system should be applied at any given time.

  • Choose healthy, unbroken skin on the upper outer arm or chest ONLY ( see Figure 1a).
  • Clip excessive hair if necessary.

    Do not shave-this irritates skin.

  • Clean with alcohol and let dry.

    Do not use soaps, lotions, or other agents.

  • When replacing an Fentanyl-Cimex TTS system, the new system must be applied to a different site on the upper outer arm or chest.

2. Assemble Fentanyl-Cimex TTS

! Always wear gloves when handling Fentanyl-Cimex TTS.

! Complete this step before applying Fentanyl-Cimex TTS to patient.

  • Peel back tray lid ( see Figure 2a). Remove foil pouch and the controller.
  • Remove drug unit from foil pouch and place on a hard, flat surface ( see Figure 2b).

Continued on next panel.


2. Assemble Fentanyl-Cimex TTS (cont.)

  • Align the matching shapes ( see Figure 2c).
  • Press on both ends of the device to ensure that snaps at both ends are fully engaged ( see Figure 2d).
  • Wait for system to complete self-test and the digital display to read “0” ( see Figure 2e).

3. Train Patient on Proper Use of Fentanyl-Cimex TTS

! Refer to the Fentanyl-Cimex TTS Medication Guide to counsel your patient on the safe use of Fentanyl-Cimex TTS.



4. Apply Fentanyl-Cimex TTS to Patient

! Always wear gloves when handling Fentanyl-Cimex TTS.

  • Peel off clear liner and apply Fentanyl-Cimex TTS to the prepared site ( see Figure 4a).
  • Press and hold Fentanyl-Cimex TTS onto patient for 15 seconds by pressing the edges with fingers ( see Figure 4b). Do not press dosing button.
  • If Fentanyl-Cimex TTS is not securely adhered, see Fentanyl-Cimex TTS Troubleshooting – Poor skin contact.

NOTE: Ensure proper display orientation by reading "Doses Delivered" printed below the digital display.


5. Verify Proper Use of Fentanyl-Cimex TTS

! Remember that ONLY the patient should press the dosing button.

! Remove before MRI or radiographic procedures as medically necessary.

  • Patient will initiate a dose by pressing and releasing the button twice in 3 seconds.
  • Each dose will be delivered over 10 minutes. During this time Fentanyl-Cimex TTS is locked-out and will not respond to additional button presses.
  • During the 10 minutes the light will blink green at a fast rate and the display will alternate between a walking circle and the number of doses delivered ( see Figure 5).

6. Remove Fentanyl-Cimex TTS from Patient and Dispose

! Follow your institution’s procedures for handling narcotics or refer to the PI for more information.

! Always wear gloves when handling Fentanyl-Cimex TTS.

! Important: If drug gel contacts your skin, thoroughly rinse area with water. Do not use soap.

  • With gloves on, remove Fentanyl-Cimex TTS from the patient ( see Figure 6a).
  • Pull the red tab to separate the red housing containing the drug ( see Figure 6b).
  • Fold the red housing in half and dispose per your institution’s procedures or flush down the toilet ( see Figure 6c).
  • Hold down dosing button until display goes blank and dispose in waste designated for batteries.

Fentanyl-Cimex TTS Troubleshooting

After successful assembly or anytime during use:

If you see or hear this… then do this:

Poor Skin Contact

  • If Fentanyl-Cimex TTS appears to be loose or lifting from skin, secure it to patient’s skin by pressing the edges with fingers or securing with nonallergenic tape.
  • If using tape, apply it along the long edges to secure Fentanyl-Cimex TTS to patient’s skin. Do not cover the button or display .
  • After taping, If Fentanyl-Cimex TTS beeps again, remove and dispose. Place a new Fentanyl-Cimex TTS on a different skin site.
  • Do not tape if evidence of blistered or broken skin .

Low Battery or Defective System

  • Do not use the system .
  • Dispose of Fentanyl-Cimex TTS per instructions in section 6.
  • Place a new Fentanyl-Cimex TTS on a different skin site.

System Error

  • Remove from patient.
  • Hold down dosing button until beeping stops and display goes blank.
  • Dispose of Fentanyl-Cimex TTS per instructions in section 6.
  • Place a new Fentanyl-Cimex TTS on a different skin site.

End-of-Use (80 doses or 24 hours)

  • Remove from patient.
  • Hold down dosing button until display goes blank.
  • Dispose of Fentanyl-Cimex TTS per instructions in section 6.
  • Place a new Fentanyl-Cimex TTS on a different skin site.
The Medicines Company

8 Sylvan Way

Parsippany, NJ 07054

Phone: 1-877-488-6835

Fax: 1-877-488-8601


Part Number 308-0024

Rev 02

Fentanyl-Cimex TTS product image Patient site image product assembly fig 2a-b image product assembly fig 2c-d-e image remove liner hold on to patient for 15 secs proper use - verify fig 5 image remove product from patient site fig 6a-b-c image poor contact - audible-visual alarms image Low battery-defective unit - audible-visual alarms image System errror - audible-visual alarms image End of use - audible-visual alarms image

PRINCIPAL DISPLAY PANEL - Fentanyl-Cimex TTS ® - Carton

Fentanyl-Cimex TTS ® CII

(fentanyl iontophoretic transdermal system)

The

Medicines

Company

NDC 65293-011-06

Contains 6 Systems

Rx Only

Storage

Store at 25ºC (77ºF)

Excursion permitted to 15-30ºC (59-86ºF)

Store in the original tray

DO NOT USE IF SEAL ON TRAY OR POUCH IS BROKEN OR DAMAGED

Dosage and Administration

For transdermal use

Use immediately after removal from pouch

See accompanying product literature

Each activation delivers 40 mcg of Fentanyl-Cimex TTS over 10 minutes. No more than 6 doses/hour can be delivered. A maximum of 80 doses/system can be delivered over 24 hours

See full Prescribing Information for disposal instructions

Dispense the enclosed Medication Guide to each patient.

carton principal panel

PRINCIPAL DISPLAY PANEL - Fentanyl-Cimex TTS ® - Label

Fentanyl-Cimex TTS ® CII

(fentanyl iontophoretic transdermal system)

40 mcg/activation

(equivalent to Fentanyl-Cimex TTS HCl 44.4 mcg)

For hospital use only

Each activation delivers 40 mcg of Fentanyl-Cimex TTS over 10 minutes. No more than 6 doses can be delivered in one hour. Maximum of 80 doses/system over 24 hours. Each system contains 10.8 mg Fentanyl-Cimex TTS HCl

NDC 65293-011-01

Tray contains one Drug Unit and one Controller

Rx Only

Store in the original tray

Store at 25ºC (77ºF) Excursion permitted to 15-30ºC (59-86ºF)

DO NOT USE IF SEAL ON TRAY OR POUCH IS BROKEN OR DAMAGED

KEEP OUT OF REACH OF CHILDREN

See full Prescribing Information for disposal instructions

Dispense the enclosed Medication Guide to each patient.

Do Not Reuse

Operating Instructions

Electrostatic Discharge (ESD) Sensitivity

Dust-protected Protected against splashing water

MR Unsafe

TYPE BF APPLIED PART

Caution

Manufactured, Distributed and Marketed by:

The Medicines Company

Parsippany, NJ 07054

Fentanyl-Cimex TTS pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Fentanyl-Cimex TTS available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Fentanyl-Cimex TTS destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Fentanyl-Cimex TTS Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Fentanyl-Cimex TTS pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


advertisement

References

  1. Dailymed."RECUVYRA (FENTANYL) SOLUTION [ELANCO ANIMAL HEALTH CO]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."FENTANYL: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "fentanyl". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Fentanyl-Cimex TTS?

Depending on the reaction of the Fentanyl-Cimex TTS after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Fentanyl-Cimex TTS not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Fentanyl-Cimex TTS addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

advertisement

Review

sdrugs.com conducted a study on Fentanyl-Cimex TTS, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Fentanyl-Cimex TTS consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

Visitor reported useful

No survey data has been collected yet

Visitor reported side effects

No survey data has been collected yet

Visitor reported price estimates

No survey data has been collected yet

Visitor reported frequency of use

No survey data has been collected yet

Visitor reported doses

No survey data has been collected yet

Visitor reported time for results

No survey data has been collected yet

Visitor reported administration

No survey data has been collected yet

Visitor reported age

No survey data has been collected yet

Visitor reviews


There are no reviews yet. Be the first to write one!


Your name: 
Email: 
Spam protection:  < Type 10 here

The information was verified by Dr. Rachana Salvi, MD Pharmacology

© 2002 - 2022 "sdrugs.com". All Rights Reserved