INNOVAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INNOVAR (INNOVAR).
Innovar is a combination of fentanyl (mu-opioid receptor agonist) and droperidol (butyrophenone antipsychotic that blocks dopamine D2 receptors in the CNS, producing sedation and antiemetic effects).
| Metabolism | Fentanyl: CYP3A4 to norfentanyl; Droperidol: CYP3A4 and CYP1A2 to multiple metabolites. |
| Excretion | Droperidol: ~75% renal as metabolites, ~22% biliary/fecal. Fentanyl: primarily renal as metabolites (85%), ~9% fecal. |
| Half-life | Droperidol: terminal t1/2 2.2–2.5 h (infants 4.5 h). Fentanyl: terminal t1/2 3–7 h (mean ~4 h) in adults; prolonged in elderly (up to 16 h) and hepatic impairment. |
| Protein binding | Fentanyl: ~80–85% bound to albumin and α1-acid glycoprotein. Droperidol: ~85–90% bound to albumin and α1-acid glycoprotein. |
| Volume of Distribution | Fentanyl: Vd 3–5 L/kg (large distribution to tissues, slow elimination). Droperidol: Vd 1.5–2 L/kg (moderate distribution). |
| Bioavailability | Fentanyl: IV 100%; transdermal 92% (after depot formation); transmucosal ~50% (buccal) to 70% (nasal); oral <30% due to first-pass. Droperidol: IV 100%; IM ~85% (well absorbed). |
| Onset of Action | IV: Droperidol 3–10 min, Fentanyl 1–2 min (peak analgesia 5–15 min). IM: Droperidol 10–30 min, Fentanyl 7–15 min. |
| Duration of Action | IV sedation/analgesia: 1–4 h depending on dose. Residual respiratory depression may persist longer (fentanyl redistribution). Droperidol's antiemetic effect lasts up to 12 h with single dose. |
| Molecular Weight | 454.44 |
2-5 mL (droperidol 2.5-5 mg and fentanyl 0.05-0.1 mg) IM/IV every 1-2 hours as needed for neuroleptanalgesia; surgical anesthesia: initial 1 mL/10 kg IM or slow IV, then 0.5 mL increments.
| Dosage form | INJECTABLE |
| Renal impairment | eGFR >60 mL/min: no adjustment; eGFR 30-60: reduce dose by 25-50% due to fentanyl accumulation; eGFR <30: avoid or use with extreme caution, reduce dose by ≥50%, monitor for respiratory depression. |
| Liver impairment | Child-Pugh A: reduce dose by 25%; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated due to impaired fentanyl metabolism and increased sedation risk. |
| Pediatric use | Not FDA-approved for pediatric use; limited data: 0.1 mL/kg (droperidol 0.125 mg/kg + fentanyl 0.0025 mg/kg) IM/IV as single dose; max 1.5 mL. Contraindicated in neonates. |
| Geriatric use | Reduce initial dose by 50-75% (e.g., 0.5-1 mL IM/IV); titrate cautiously; increased risk of hypotension, respiratory depression, and prolonged sedation; monitor renal function. |
| 1st trimester | Contraindicated. Risk of fetal malformations, especially neural tube defects, due to folate antagonism. Considered teratogenic (Pregnancy Category D). |
| 2nd trimester | Contraindicated. Risk of fetal growth restriction and oligohydramnios. Avoid use. |
| 3rd trimester | Contraindicated. Risk of neonatal hemorrhage, folate deficiency, and kernicterus. Avoid use. |
Clinical note
Comprehensive clinical and safety monograph for INNOVAR (INNOVAR).
| Placental transfer | Readily crosses the placenta. Fetal serum concentrations can reach maternal levels. Active transport via folate receptors enhances transfer. |
| Breastfeeding | Excreted into breast milk in low amounts. However, due to potential for serious adverse effects such as kernicterus and hemolysis in neonates, especially those with G6PD deficiency, use is generally contraindicated during breastfeeding. |
■ FDA Black Box Warning
Risk of respiratory depression, especially in elderly, debilitated, or opioid-naive patients; risk of QT prolongation and torsade de pointes with droperidol, including at recommended doses.
| Serious Effects |
Hypersensitivity to methotrexate or any componentSevere renal impairment (CrCl <10 mL/min)Severe hepatic impairmentPreexisting profound bone marrow suppressionBreastfeedingConcurrent live vaccinesAlcoholism or alcoholic liver disease
| Precautions | Monitor respiratory function; avoid in patients with bradycardia, electrolyte abnormalities, or QT prolongation; risk of hypotension, neuroleptic malignant syndrome, and extrapyramidal symptoms. |
| Food/Dietary | Avoid grapefruit juice as it may increase fentanyl levels via CYP3A4 inhibition. No specific food restrictions for droperidol. Maintain adequate hydration to prevent hypotension, but monitor for fluid overload if cardiac compromise. |
Loading safety data…
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | First trimester: Risk of congenital malformations, including cardiac and neural tube defects, associated with droperidol exposure. Second and third trimesters: Risk of extrapyramidal symptoms, neuroleptic malignant syndrome, and neonatal withdrawal. Fentanyl component may cause fetal respiratory depression and intrauterine growth restriction. Use only if maternal benefit outweighs fetal risk. |
| Fetal Monitoring | Maternal: ECG for QT prolongation, blood pressure, heart rate, oxygen saturation, and sedation level. Fetal: Heart rate monitoring, uterine activity, and continuous fetal monitoring during labor. Neonatal: Observation for respiratory depression, extrapyramidal signs, and withdrawal. |
| Fertility Effects | Droperidol may increase prolactin levels, potentially causing menstrual irregularity and decreased fertility. Fentanyl may impair fertility by reducing sperm motility and causing erectile dysfunction in males. Reversible upon discontinuation. |
| Clinical Pearls | Innovar (droperidol + fentanyl) is a neuroleptanalgesic combination; monitor for respiratory depression, hypotension, and extrapyramidal symptoms. Droperidol prolongs QTc interval; avoid in patients with electrolyte disturbances or on QT-prolonging drugs. Fentanyl is a potent mu-opioid agonist; naloxone reversal may be needed. Onset of analgesia is rapid (<2 min IV), duration 30-60 min; droperidol's sedative effect lasts 2-4 hours. Use with caution in elderly, hypovolemic, or compromised patients. |
| Patient Advice | You may feel drowsy and lightheaded; avoid driving or operating machinery for 24 hours. · Report any difficulty breathing, slow or shallow breathing, or severe dizziness immediately. · Avoid alcohol and other sedatives while taking this medication. · Inform your doctor if you have a history of heart rhythm problems, low potassium, or low magnesium. · This drug can cause involuntary muscle movements or restlessness; notify your healthcare provider if these occur. |