POSIMIR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for POSIMIR (POSIMIR).
Bupivacaine, the active ingredient in POSIMIR, is an amide-type local anesthetic that blocks voltage-gated sodium channels in nerve cell membranes, inhibiting the generation and conduction of nerve impulses. POSIMIR is a bupivacaine extended-release liposomal formulation designed for sustained release at the surgical site.
| Metabolism | Primarily hepatic via conjugation with glucuronic acid; major metabolite is 4-hydroxybupivacaine. CYP3A4 and CYP1A2 are involved in minor oxidative metabolism. |
| Excretion | Primarily hepatic metabolism via CYP3A4 and CYP1A2 to inactive metabolites; <5% excreted unchanged in urine. Biliary/fecal excretion accounts for >90% of total clearance. |
| Half-life | Terminal elimination half-life is approximately 27 hours (range 16-38 hours), supporting once-daily dosing in clinical use. |
| Protein binding | Approximately 97% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 1.9 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Not applicable via oral route; only administered as a local infiltration. Systemic bioavailability after local administration is approximately 100% locally, but systemic levels are low due to slow release from the formulation. |
| Onset of Action | Local infiltration: pain relief begins within 1-2 hours post-administration. |
| Duration of Action | Provides analgesia for up to 72 hours following a single local infiltration, based on clinical trials evaluating pain scores and opioid rescue requirements. |
Posimir (bupivacaine) is administered as a single intra-articular injection into the subacromial space following arthroscopic shoulder surgery. The recommended adult dose is 5 mL (66 mg) of the 1.32% solution.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment is required for mild to moderate renal impairment. Safety and efficacy have not been established in severe renal impairment (GFR <30 mL/min), use with caution. |
| Liver impairment | No dose adjustment is required for mild (Child-Pugh A) hepatic impairment. For moderate (Child-Pugh B) impairment, consider cautious use with monitoring for toxicity. Contraindicated in severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. No standard dosing guidelines exist. |
| Geriatric use | No specific dose adjustment is recommended, but elderly patients may have increased sensitivity and reduced clearance. Use with caution, monitoring for cardiac and neurological toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for POSIMIR (POSIMIR).
| Breastfeeding | Bupivacaine is excreted in breast milk in small amounts. The milk-to-plasma ratio (M/P) is approximately 0.3. The relative infant dose is estimated to be <2% of maternal weight-adjusted dose. Generally considered compatible with breastfeeding, but caution is advised in infants with impaired hepatic function. |
| Teratogenic Risk | POSIMIR (bupivacaine) is classified as FDA Pregnancy Category C. Animal studies have shown fetal harm, but adequate human studies are lacking. First trimester: Risk of teratogenicity is unknown; bupivacaine crosses the placenta. Second and third trimesters: Potential for fetal bradycardia, CNS depression, and neurobehavioral effects. Use only if benefit outweighs risk. |
■ FDA Black Box Warning
Not approved for use in: obstetrical paravertebral block, epidural or intrathecal administration. Risk of cardiac arrest and death has been reported with bupivacaine use via these routes.
| Serious Effects |
["Hypersensitivity to bupivacaine or any component of the formulation","Obstetrical paravertebral block","Epidural or intrathecal administration"]
| Precautions | ["Risk of overdose and toxicity with unintentional intravascular injection or excessive dosing.","Do not use in patients with hypersensitivity to bupivacaine or any amide-type local anesthetic.","Not recommended for patients with severe hepatic impairment.","Safety in pediatric patients not established.","Use with caution in patients with cardiovascular disease, especially those with impaired cardiac conduction.","May cause methemoglobinemia in susceptible patients.","Chondrolysis with intra-articular use (not indicated for such use)."] |
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| Fetal Monitoring | Monitor maternal heart rate, blood pressure, and ECG for signs of cardiotoxicity. Fetal heart rate monitoring is recommended due to potential for fetal bradycardia. Assess for signs of local anesthetic systemic toxicity (LAST) including neurological symptoms. |
| Fertility Effects | Animal studies show no impairment of fertility at clinically relevant doses. Human data are lacking. No known significant impact on fertility. |