LAZANDA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LAZANDA (LAZANDA).
Fentanyl is a μ-opioid receptor agonist. It binds to μ-opioid receptors in the central nervous system, activating G-protein-coupled receptors to inhibit adenylate cyclase, reduce cAMP production, and modulate ion channels, leading to decreased neurotransmitter release (e.g., substance P, glutamate) and hyperpolarization of neurons, resulting in analgesia and sedation.
| Metabolism | Primarily hepatic via CYP3A4 (major pathway) to norfentanyl (inactive) and other minor metabolites. Approximately 75% excreted in urine as metabolites, with less than 7% as unchanged drug. |
| Excretion | Renal excretion of metabolites (mostly fentanyl metabolites, primarily norfentanyl): approximately 75%; fecal excretion: approximately 9%; less than 10% excreted as unchanged fentanyl in urine. |
| Half-life | Terminal elimination half-life: 6–10 hours (mean approximately 7 hours) following nasal administration; prolonged in hepatic impairment. |
| Protein binding | Approximately 80–85% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Volume of distribution: 3–6 L/kg (mean about 4.5 L/kg), indicating extensive tissue distribution and accumulation in peripheral compartments. |
| Bioavailability | Nasal spray: approximately 60–80% absolute bioavailability relative to intravenous fentanyl; varies with device and technique. |
| Onset of Action | Nasal spray: Onset of analgesia within 5–10 minutes; peak plasma concentration achieved at median 15 minutes (range 5–60 minutes). |
| Duration of Action | Duration of analgesic effect: approximately 1–2 hours for breakthrough pain; may be shorter than oral fentanyl due to faster absorption and elimination. |
100 mcg (one spray) intranasally as needed for breakthrough pain; may repeat once after 15-30 minutes if needed; do not exceed 2 doses per episode and 4 doses per day.
| Dosage form | SPRAY, METERED |
| Renal impairment | No specific dose adjustment recommended for renal impairment; use with caution in severe impairment (CrCl <30 mL/min) due to potential accumulation of metabolites. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce starting dose to 50 mcg. Child-Pugh C: Avoid use; not studied. |
| Pediatric use | Not approved for pediatric patients (safety and efficacy not established). |
| Geriatric use | Start at 50 mcg (half of adult dose) due to increased sensitivity; titrate cautiously. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LAZANDA (LAZANDA).
| Breastfeeding | Lactation risk category L4 (possibly hazardous). Excreted in breast milk; reported M/P ratio ~2.5. Infants exposed may experience sedation, respiratory depression, and withdrawal. Contraindicated in breastfeeding unless benefit outweighs risks; discontinue nursing or drug. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Limited human data, but animal studies show increased risk of skeletal malformations and decreased fetal weight at doses comparable to human exposure. Second and third trimesters: Prolonged use may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression. Avoid use during labor due to risk of neonatal respiratory depression. |
■ FDA Black Box Warning
WARNING: RISK OF SERIOUS HARM, ACCIDENTAL EXPOSURE, AND RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; RISK OF MEDICATION ERRORS; and RISK OF OPIOID ADDICTION, ABUSE, AND MISUSE. See full prescribing information for complete boxed warning.
| Common Effects | Nausea Abdominal pain Diarrhea |
| Serious Effects |
["Patients with significant respiratory depression","Acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment","Known or suspected gastrointestinal obstruction, including paralytic ileus","Known hypersensitivity to fentanyl or any components of the product","Management of acute or postoperative pain including headache/migraine, dental pain, or procedural use","Opioid-non-tolerant patients (not already receiving around-the-clock opioid therapy)"]
| Precautions | ["Addiction, abuse, and misuse","Life-threatening respiratory depression","Accidental exposure can cause fatal overdose","Risks from concomitant use with benzodiazepines or other CNS depressants","Neonatal opioid withdrawal syndrome","Risks of medication errors (e.g., dose confusion between mcg and mg)","Adrenal insufficiency","Severe hypotension","Gastrointestinal effects (e.g., constipation, ileus)","Seizures","Serotonin syndrome with concomitant serotonergic drugs","Impaired driving and operating machinery"] |
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| Fetal Monitoring | Monitor maternal respiratory rate, oxygen saturation, sedation level, and signs of opioid withdrawal. Fetal monitoring includes heart rate patterns and growth ultrasound if used chronically. Assess neonatal for respiratory depression, sedation, and withdrawal symptoms after delivery. |
| Fertility Effects | Animal studies show reduced fertility and implantation rates at high doses. Human data limited; opioid use may impair spermatogenesis and ovarian function. Effects may be reversible upon discontinuation. |