Fentanyl (Page 4 of 12)

CONTRAINDICATIONS

Because serious or life-threatening hypoventilation could occur, fentanyl transdermal system is contraindicated:

• in patients who are not opioid-tolerant
• in the management of acute pain or in patients who require opioid analgesia for a short period of time
• in the management of post-operative pain, including use after out-patient or day surgeries, (e.g., tonsillectomies)
• in the management of mild pain
• in the management of intermittent pain (e.g., use on an as needed basis [prn])
• in situations of significant respiratory depression, especially in unmonitored settings where there is a lack of resuscitative equipment
• in patients who have acute or severe bronchial asthma

Fentanyl transdermal system is contraindicated in patients who have or are suspected of having paralytic ileus.

Fentanyl transdermal system is contraindicated in patients with known hypersensitivity to fentanyl or any components of this product.

WARNINGS

Fentanyl transdermal system patches are intended for transdermal use (on intact skin) only. Do not use a fentanyl transdermal system patch if the pouch seal is broken or the patch is cut, damaged, or changed in any way .

The safety of fentanyl transdermal system has not been established in children under 2 years of age. Fentanyl transdermal system should be administered to children only if they are opioid-tolerant and 2 years of age or older (see PRECAUTIONS – Pediatric Use) .

Fentanyl transdermal system is ONLY for use in patients who are already tolerant to opioid therapy of comparable potency. Use in non-opioid tolerant patients may lead to fatal respiratory depression. Overestimating the fentanyl transdermal system dose when converting patients from another opioid medication can result in fatal overdose with the first dose. The mean half-life is approximately 20–27 hours. Therefore, patients who have experienced serious adverse events, including overdose, will require monitoring for at least 24 hours after fentanyl transdermal system removal since serum fentanyl concentrations decline gradually and reach an approximate 50% reduction in serum concentrations 20–27 hours after system removal.

Fentanyl transdermal system should be prescribed only by persons knowledgeable in the continuous administration of potent opioids, in the management of patients receiving potent opioids for treatment of pain, and in the detection and management of hypoventilation including the use of opioid antagonists.

All patients and their caregivers should be advised to avoid exposing the fentanyl transdermal system application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, saunas, hot tubs, and heated water beds, etc., while wearing the system. Patients should be advised against taking hot baths or sunbathing. There is a potential for temperature-dependent increases in fentanyl released from the system resulting in possible overdose and death. A clinical pharmacology trial conducted in healthy adult subjects has shown that the application of heat over the fentanyl transdermal system increased mean fentanyl AUC values by 120% and mean C_max values by 61%.

Based on a pharmacokinetic model, serum fentanyl concentrations could theoretically increase by approximately one-third for patients with a body temperature of 40°C (104°F) due to temperature-dependent increases in fentanyl released from the system and increased skin permeability. Patients wearing fentanyl transdermal systems who develop fever or increased core body temperature due to strenuous exertion should be monitored for opioid side effects and the fentanyl transdermal system dose should be adjusted if necessary.

Death and other serious medical problems have occurred when people were accidentally exposed to fentanyl transdermal system. Examples of accidental exposure include transfer of a fentanyl transdermal system patch from an adult’s body to a child while hugging, accidental sitting on a patch and possible accidental exposure of a caregiver’s skin to the medication in the patch while the caregiver was applying or removing the patch.

Placing fentanyl transdermal system in the mouth, chewing it, swallowing it, or using it in ways other than indicated may cause choking or overdose that could result in death.

Misuse, Abuse and Diversion of Opioids

Fentanyl is an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.

Fentanyl can be abused in a manner similar to other opioids, legal or illicit. This should be considered when prescribing or dispensing fentanyl transdermal system in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.

Fentanyl transdermal system has been reported as being abused by other methods and routes of administration. These practices will result in uncontrolled delivery of the opioid and pose a significant risk to the abuser that could result in overdose and death (see WARNINGS and DRUG ABUSE AND ADDICTION).

Concerns about abuse, addiction, and diversion should not prevent the proper management of pain. However, all patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Healthcare professionals should contact their state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Hypoventilation (Respiratory Depression)

Serious or life-threatening hypoventilation may occur at any time during the use of fentanyl transdermal system especially during the initial 24–72 hours following initiation of therapy and following increases in dose.

Because significant amounts of fentanyl continue to be absorbed from the skin for 20‑27 hours or more after the patch is removed, hypoventilation may persist beyond the removal of fentanyl transdermal system. Consequently, patients with hypoventilation should be carefully observed for degree of sedation and their respiratory rate monitored until respiration has stabilized.

The use of concomitant CNS active drugs requires special patient care and observation.

Respiratory depression is the chief hazard of opioid agonists, including fentanyl the active ingredient in fentanyl transdermal system. Respiratory depression is more likely to occur in elderly or debilitated patients, usually following large initial doses in non-tolerant patients, or when opioids are given in conjunction with other drugs that depress respiration.

Respiratory depression from opioids is manifested by a reduced urge to breathe and a decreased rate of respiration, often associated with the “sighing” pattern of breathing (deep breaths separated by abnormally long pauses). Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. This makes overdoses involving drugs with sedative properties and opioids especially dangerous.

Fentanyl transdermal system should be used with extreme caution in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and in patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. In such patients, even usual therapeutic doses of fentanyl transdermal system may decrease respiratory drive to the point of apnea. In these patients, alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose.

Chronic Pulmonary Disease

Because potent opioids can cause serious or life-threatening hypoventilation, fentanyl transdermal system should be administered with caution to patients with pre-existing medical conditions predisposing them to hypoventilation. In such patients, normal analgesic doses of opioids may further decrease respiratory drive to the point of respiratory failure.

Head Injuries and Increased Intracranial Pressure

Fentanyl transdermal system should not be used in patients who may be particularly susceptible to the intracranial effects of CO₂ retention such as those with evidence of increased intracranial pressure, impaired consciousness, or coma. Opioids may obscure the clinical course of patients with head injury. Fentanyl transdermal system should be used with caution in patients with brain tumors.

Interactions with Other CNS Depressants

The concomitant use of fentanyl transdermal system with other central nervous system depressants, including but not limited to other opioids, sedatives, hypnotics, tranquilizers (e.g., benzodiazepines), general anesthetics, phenothiazines, skeletal muscle relaxants, and alcohol, may cause respiratory depression, hypotension, and profound sedation or potentially result in coma. When such combined therapy is contemplated, the dose of one or both agents should be significantly reduced.