IVRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IVRA (IVRA).
Ivermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells, leading to increased chloride ion influx and hyperpolarization, resulting in paralysis and death of the parasite. It also interacts with gamma-aminobutyric acid (GABA)-gated chloride channels.
| Metabolism | Primarily metabolized by CYP3A4 in the liver; also a substrate for P-glycoprotein (P-gp) transporter. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 10-20% of elimination; fecal/biliary excretion is the primary route (60-70% as metabolites, primarily unchanged drug via bile). |
| Half-life | Terminal elimination half-life is approximately 12-15 hours in healthy adults; prolonged in hepatic impairment (up to 30 hours) and in elderly patients. |
| Protein binding | Approximately 85-90% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.6-0.8 L/kg, indicating distribution into total body water with some extravascular binding; increased in heart failure or severe hepatic disease. |
| Bioavailability | Oral: 70-80% (extensive first-pass metabolism reduces from 90% absorbed); Intravenous: 100%. |
| Onset of Action | Intravenous: 2-5 minutes; Oral: 30-60 minutes; Onset correlates with plasma concentrations reaching therapeutic threshold. |
| Duration of Action | 6-8 hours after single IV dose; up to 12 hours after oral dosing; prolonged with higher doses or in hepatic dysfunction. |
| Molecular Weight | 300 |
Intravenous 500 mg every 6 hours.
| Dosage form | SOLUTION |
| Renal impairment | GFR >60 mL/min: 500 mg q6h; GFR 30-60: 250 mg q6h; GFR 15-30: 250 mg q12h; GFR <15: 250 mg q24h. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 250 mg q6h; Child-Pugh C: 250 mg q12h. |
| Pediatric use | 10 mg/kg IV every 6 hours; maximum 500 mg per dose. |
| Geriatric use | Same as adult; monitor renal function and adjust per GFR. |
| 1st trimester | No adequate studies; use only if benefit outweighs risk. |
| 2nd trimester | No adequate studies; use only if benefit outweighs risk. |
| 3rd trimester | No adequate studies; use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for IVRA (IVRA).
| Placental transfer | Unknown; assumed to cross placenta based on molecular weight. |
| Breastfeeding | Not recommended due to potential drug excretion into breast milk and unknown effects on infant. |
| Lactation Rating | L5 |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to any componentSevere hepatic impairmentConcurrent use with monoamine oxidase inhibitors
| Precautions | Potential for severe adverse reactions (Mazzotti reaction) in onchocerciasis patients; neurotoxicity (especially in elderly or patients with high drug levels); avoid use in patients with impaired hepatic function; caution with concomitant use of CNS depressants; not recommended in pregnancy (Category C). |
| Food/Dietary | No food interactions with IVRA technique; however, lidocaine administration may be affected by grapefruit juice (inhibits metabolism) — avoid grapefruit juice before procedure. |
Loading safety data…
| Teratogenic Risk | IVRA is contraindicated in pregnancy. First trimester: high risk of major congenital malformations (neural tube defects, cleft palate). Second and third trimesters: risk of fetal nephrotoxicity, oligohydramnios, and premature ductus arteriosus closure. |
| Fetal Monitoring | Monitor fetal ultrasound for oligohydramnios and ductus arteriosus patency if inadvertent exposure. Maternal renal function and coagulation parameters should be assessed. |
| Fertility Effects | May impair female fertility by inhibiting ovulation (reversible upon discontinuation). No known effect on male fertility. |
| Clinical Pearls |
| IVRA (intravenous regional anesthesia) is not a drug but a technique. For Bier block using lidocaine, use 0.5% preservative-free lidocaine, 3 mg/kg for upper extremity. Avoid in patients with sickle cell disease or severe hypertension. Monitor for tourniquet pain after 30 minutes; deflate tourniquet gradually to prevent systemic toxicity. |
| Patient Advice | You will receive local anesthetic injected into a vein in your arm after a tourniquet is applied. · The tourniquet will be kept inflated during the procedure to keep the medication in the arm. · You may feel a burning sensation when the medication is injected, which is normal. · Do not remove the tourniquet yourself; it will be deflated slowly by the doctor to prevent side effects. · Report any chest discomfort, ringing in ears, or metallic taste immediately. |