KOVANAZE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KOVANAZE (KOVANAZE).
KOVANAZE (norepinephrine and phenylephrine) is a combination of two vasopressors: norepinephrine, an α1-adrenergic receptor agonist with β1-adrenergic activity, and phenylephrine, a selective α1-adrenergic receptor agonist. Both agents cause vasoconstriction and increase blood pressure via activation of α1-adrenergic receptors on vascular smooth muscle.
| Metabolism | Norepinephrine is primarily metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Phenylephrine is metabolized by monoamine oxidase (MAO) in the liver and gut wall. |
| Excretion | Renal excretion of unchanged drug: ~20-30%; fecal/biliary elimination: minimal (<5%); remainder as metabolites |
| Half-life | Terminal elimination half-life: approximately 7-9 hours following nasal administration; clinical significance: supports twice-daily dosing regimen |
| Protein binding | Approximately 94% bound to serum proteins (mainly albumin and alpha-1-acid glycoprotein) |
| Volume of Distribution | Volume of distribution: approximately 1.5 L/kg; indicates extensive tissue distribution |
| Bioavailability | Intranasal: absolute bioavailability ~10%; oral: negligible due to extensive first-pass metabolism |
| Onset of Action | Intranasal: symptom relief begins within 15-30 minutes; peak effect at 1-2 hours |
| Duration of Action | Duration of action: approximately 12 hours; clinical note: recommended dosing every 12 hours for continued symptom control |
| Molecular Weight | Bacitracin: 1422.69 Da; Dexamethasone: 392.46 Da |
Intravenous bolus of 1 mg/kg over 10 minutes, followed by intravenous infusion of 0.02 mg/kg/min for 4 hours, then 0.01 mg/kg/min for 20 hours.
| Dosage form | SPRAY, METERED |
| Renal impairment | No dose adjustment required for renal impairment. Not removed by hemodialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Safety and efficacy not established in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended, but monitor renal function and QT interval due to increased sensitivity. |
| 1st trimester | Contains bacitracin (polypeptide antibiotic) and dexamethasone (corticosteroid). Corticosteroids: cross placenta; risk of oral clefts in first trimester (animal data). Avoid unless benefit outweighs risk. |
| 2nd trimester | Corticosteroids: may cause fetal growth restriction with prolonged use. Bacitracin: minimal systemic absorption; unlikely to cause harm. Use only if clearly needed. |
| 3rd trimester | Corticosteroids: may suppress fetal adrenal function (rare). Bacitracin: negligible systemic absorption. Risk of neonatal adrenal suppression if near term. Use with caution. |
Clinical note
Comprehensive clinical and safety monograph for KOVANAZE (KOVANAZE).
| Placental transfer | Dexamethasone: readily crosses placenta (up to 50% of maternal concentration). Bacitracin: negligible placental transfer due to high molecular weight and polarity. |
| Breastfeeding | Dexamethasone enters breast milk in low amounts; bacitracin absorption is negligible after nasal use. Short-term, low-dose use is likely compatible. Monitor infant for adrenal suppression if prolonged high-dose use. Consider intranasal route minimizes systemic exposure. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to bacitracin, dexamethasone, or any componentOcular herpes simplexActive ocular fungal infectionVaccinia or varicella in or around eyeNasal mucosal ulceration or trauma
| Precautions | Risk of hypertension and bradycardia due to excessive vasoconstriction., Use with caution in patients with cardiovascular disease (e.g., ischemia, arrhythmias)., Avoid extravasation; may cause tissue necrosis if infiltrated., Monitor blood pressure and heart rate continuously during administration., May cause peripheral and visceral ischemia with prolonged use. |
| Food/Dietary | Avoid consuming food or beverages while numbness persists (typically 1-2 hours) to prevent accidental injury or aspiration. |
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| Lactation Rating | L3 (Moderately Safe) - limited human data but unlikely to cause adverse effects in nursing infants with short-term use. |
| Teratogenic Risk | KOVANAZE (phendimetrazine) is a sympathomimetic amine; no adequate human studies exist. First trimester: avoid due to potential teratogenicity based on animal studies. Second and third trimesters: may cause fetal tachycardia, hypertension, and intrauterine growth restriction; use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, weight, and fetal growth via ultrasound; assess for signs of preterm labor or placental insufficiency. Perform fetal heart rate monitoring if maternal symptoms of excessive sympathomimetic stimulation occur. |
| Fertility Effects | No controlled human data; animal studies suggest potential for impaired fertility at high doses. Use in women of childbearing potential should be with effective contraception. |
| Clinical Pearls | Kovanaze (intranasal tetracaine/oxymetazoline) is used for maxillary dental anesthesia. Administer two intranasal sprays (0.2 mL each) to the naris on the same side as the procedure. Onset within 10-15 minutes; duration 30-60 minutes. Contraindicated in patients with hypersensitivity to ester anesthetics, severe hypertension, or narrow-angle glaucoma. Avoid contact with eyes. May cause nasal congestion, headache, or taste alteration. |
| Patient Advice | Kovanaze is a nasal spray used to numb the upper teeth and gums for dental procedures. · Do not eat or drink until numbness wears off to prevent accidental biting. · May cause temporary stinging, runny nose, or altered taste. · Avoid touching the spray tip to prevent contamination. · Notify your dentist if you have high blood pressure, heart disease, or glaucoma. |