Skin does not appear to metabolize fentanyl delivered transdermally. This was determined in a human keratinocyte cell assay and in clinical studies in which 92% of the dose delivered from the system was accounted for as unchanged fentanyl that appeared in the systemic circulation.

Drug Interactions

The interaction between ritonavir and fentanyl 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 tid on Day 1 and 300 mg tid on Day 2 followed by one morning dose of 300 mg on Day 3. On Day 2, fentanyl 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. The results suggested that ritonavir might decrease the clearance of fentanyl by 67%, resulting in a 174% (range 52%-420%) increase in fentanyl AUC_0-∞. Coadministration of ritonavir in patients receiving DURAGESIC® has not been studied; however, an increase in fentanyl AUC is expected. (See BOX WARNING, WARNINGS, DOSAGE AND ADMINISTRATION and PRECAUTIONS.)

Pharmacodynamics

Ventilatory Effects

Because of the risk for serious or life-threatening hypoventilation, DURAGESIC® is CONTRAINDICATED in the treatment of post-operative and acute pain and in patients who are not opioid-tolerant. In clinical trials of 357 patients with acute pain treated with DURAGESIC®, 13 patients experienced hypoventilation. Hypoventilation was manifested by respiratory rates of less than 8 breaths/minute or a pCO₂ greater than 55 mm Hg. In these studies, the incidence of hypoventilation was higher in nontolerant women (10) than in men (3) and in patients weighing less than 63 kg (9 of 13). Although patients with impaired respiration were not common in the trials, they had higher rates of hypoventilation. In addition, post-marketing reports have been received that describe opioid-naive post-operative patients who have experienced clinically significant hypoventilation and death with DURAGESIC®.

While most adult and pediatric patients using DURAGESIC® chronically develop tolerance to fentanyl induced hypoventilation, episodes of slowed respirations may occur at any time during therapy. Hypoventilation can occur throughout the therapeutic range of fentanyl serum concentrations, especially for patients who have an underlying pulmonary condition or who receive usual doses of opioids or other CNS drugs associated with hypoventilation in addition to DURAGESIC®. The use of DURAGESIC® is contraindicated in patients who are not tolerant to opioid therapy. The use of DURAGESIC® should be monitored by clinical evaluation, especially within the initial 24-72 hours when serum concentrations from the initial patch will peak, and following increases in dosage. DURAGESIC® should be administered to children only if they are opioid-tolerant and 2 years of age or older.

See BOX WARNING, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, and OVERDOSAGE for additional information on hypoventilation.

Cardiovascular Effects

Fentanyl may infrequently produce bradycardia. The incidence of bradycardia in clinical trials with DURAGESIC® was less than 1%.

CNS Effects

Central nervous system effects increase with increasing serum fentanyl concentrations.

Bookmark this page: