Actiq (Fentanyl Citrate Oral Transmucosal) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

See WARNINGS.

Fentanyl is metabolized in the liver and intestinal mucosa to norfentanyl by the cytochrome P450 3A4 isoform. Drugs that inhibit P450 3A4 activity may increase the bioavailability of swallowed fentanyl (by decreasing intestinal and hepatic first pass metabolism) and may decrease the systemic clearance of fentanyl. The expected clinical results would be increased or prolonged opioid effects. Drugs that induce cytochrome P450 3A4 activity may have the opposite effects. However, no in vitro or in vivo studies have been performed to assess the impact of those potential interactions on the administration of Actiq. Thus patients who begin or end therapy with potent inhibitors of CYP450 3A4 such as macrolide antibiotics (e.g., erythromycin), azole antifungal agents (e.g., ketoconazole and itraconazole), and protease inhibitors (e.g., ritanovir) while receiving Actiq should be monitored for a change in opioid effects and, if warranted, the dose of Actiq should be adjusted.

OVERDOSAGE

CLINICAL PRESENTATION

The manifestations of Actiq overdosage are expected to be similar in nature to intravenous fentanyl and other opioids, and are an extension of its pharmacological actions with the most serious significant effect being hypoventilation (see CLINICAL PHARMACOLOGY).

GENERAL

Immediate management of opioid overdose includes removal of the Actiq unit, if still in the mouth, ensuring a patent airway, physical and verbal stimulation of the patient, and assessment of level of consciousness, ventilatory and circulatory status.

TREATMENT OF OVERDOSAGE (ACCIDENTAL INGESTION) IN THE OPIOID NON-TOLERANT PERSON

Ventilatory support should be provided, intravenous access obtained, and naloxone or other opioid antagonists should be employed as clinically indicated. The duration of respiratory depression following overdose may be longer than the effects of the opioid antagonist's action (e.g., the half-life of naloxone ranges from 30 to 81 minutes) and repeated administration may be necessary. Consult the package insert of the individual opioid antagonist for details about such use.

TREATMENT OF OVERDOSE IN OPIOID-TOLERANT PATIENTS

Ventilatory support should be provided and intravenous access obtained as clinically indicated. Judicious use of naloxone or another opioid antagonist may be warranted in some instances, but it is associated with the risk of precipitating an acute withdrawal syndrome.

GENERAL CONSIDERATIONS FOR OVERDOSE

Management of severe Actiq overdose includes: securing a patent airway, assisting or controlling ventilation, establishing intravenous access, and GI decontamination by lavage and/or activated charcoal, once the patient's airway is secure. In the presence of hypoventilation or apnea, ventilation should be assisted or controlled and oxygen administered as indicated.

Patients with overdose should be carefully observed and appropriately managed until their clinical condition is well controlled.

Although muscle rigidity interfering with respiration has not been seen following the use of Actiq, this is possible with fentanyl and other opioids. If it occurs, it should be managed by the use of assisted or controlled ventilation, by an opioid antagonist, and as a final alternative, by a neuromuscular blocking agent.

CONTRAINDICATIONS

Because life-threatening hypoventilation could occur at any dose in patients not taking chronic opiates, Actiq is contraindicated in the management of acute or postoperative pain. The risk of respiratory depression begins to increase with fentanyl plasma levels of 2.0 ng/mL in opioid non-tolerant individuals (see Pharmacokinetics). This product must not be used in opioid non-tolerant patients.

Patients considered opioid tolerant are those who are taking at least 60 mg morphine/day, 50 mcg transdermal fentanyl/hour, or an equianalgesic dose of another opioid for a week or longer.

Actiq is contraindicated in patients with known intolerance or hypersensitivity to any of its components or the drug fentanyl.