Ropivacaine

Renal Impairment This drug and its metabolites are known to be excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Therefore, care should be taken in dose selection, starting at the low end of the dosage range, and it may be useful to monitor renal function [see Clinical Pharmacology] .

Hepatic Impairment Because amide-type local anesthetics such as ropivacaine are metabolized by the liver, these drugs, especially repeat doses, should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations [see Warning and Precautions].

Important Administration Instructions There have been adverse event reports of chondrolysis in patients receiving intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures. NAROPIN is not approved for this use [see Warnings and Precautions] . The rapid injection of a large volume of local anesthetic solution should be avoided and fractional (incremental) doses should always be used.

The smallest dose and concentration required to produce the desired result should be administered. The dose of any local anesthetic administered varies with the anesthetic procedure, the area to be anesthetized, the vascularity of the tissues, the number of neuronal segments to be blocked, the depth of anesthesia and degree of muscle relaxation required, the duration of anesthesia desired, individual tolerance, and the physical condition of the patient.

Patients in poor general condition due to aging or other compromising factors such as partial or complete heart conduction block, advanced liver disease or severe renal dysfunction require special attention although regional anesthesia is frequently indicated in these patients. To reduce the risk of potentially serious adverse reactions, attempts should be made to optimize the patient's condition before major blocks are performed, and the dosage should be adjusted accordingly.

Use an adequate test dose (3 to 5 mL of a short acting local anesthetic solution containing epinephrine) prior to induction of complete block. This test dose should be repeated if the patient is moved in such a fashion as to have displaced the epidural catheter. Allow adequate time for onset of anesthesia following administration of each test dose.

These products are intended for single dose and are free from preservatives. Any solution remaining from an opened container should be discarded promptly.

Continuous infusion ‡ 2 (0.2%) 6 to 14 mL/h 12 to 28 mg/h n/a* n/a* Incremental injections (top-up) ‡ 2 (0.2%) 10 to 15 mL/h 20 to 30 mg/h n/a* n/a* POSTOPERATIVE PAIN MANAGEMENT Lumbar Epidural Administration Continuous infusion § 2 (0.2%) 6 to 14 mL/h 12 to 28 mg/h n/a* n/a* Thoracic Epidural 2 (0.2%) 6 to 14 mL/h 12 to 28 mg/h n/a* n/a* Administration Continuous infusion § Infiltration 2 (0.2%) 1 to 100 2 to 200 1 to 5 2 to 6 (e.g., minor nerve block) 5 (0.5%) 1 to 40 5 to 200 1 to 5 2 to 6 The doses in the table are those considered to be necessary to produce a successful block and should be regarded as guidelines for use in adults.

Individual variations in onset and duration occur. The figures reflect the expected average dose range needed. For other local anesthetic techniques standard current textbooks should be consulted. When prolonged blocks are used, either through continuous infusion or through repeated bolus administration, the risks of reaching a toxic plasma concentration or inducing local neural injury must be considered.

Experience to date indicates that a cumulative dose of up to 770 mg NAROPIN administered over 24 hours is well tolerated in adults when used for postoperative pain management: i.e., 2016 mg. Caution should be exercised when administering NAROPIN for prolonged periods of time, e.g., >70 hours in debilitated patients. For treatment of postoperative pain, the following technique can be recommended: If regional anesthesia was not used intraoperatively, then an initial epidural block with 5 to 7 mL NAROPIN is induced via an epidural catheter.

Analgesia is maintained with an infusion of NAROPIN, 2 mg/mL (0.2%). Clinical studies have demonstrated that infusion rates of 6 to 14 mL (12 to 28 mg) per hour provide adequate analgesia with nonprogressive motor block. With this technique a significant reduction in the need for opioids was demonstrated. Clinical experience supports the use of NAROPIN epidural infusions for up to 72 hours.

Other Administration Considerations Disinfecting agents containing heavy metals, which cause release of respective ions (mercury, zinc, copper, etc.) should not be used for skin or mucous membrane disinfection since they have been related to incidents of swelling and edema. When chemical disinfection of the container surface is desired, either isopropyl alcohol (91%) or ethyl alcohol (70%) is recommended.

It is recommended that chemical disinfection be accomplished by wiping the polypropylene ampule or vial stopper thoroughly with cotton or gauze that has been moistened with the recommended alcohol just prior to use. When a container is required to have a sterile outside, a Sterile-Pak should be chosen. Glass containers may, as an alternative, be autoclaved once.

Stability has been demonstrated using a targeted F 0 of 7 minutes at 121°C. The solubility of ropivacaine is limited at pH above 6. Thus, care must be taken as precipitation may occur if NAROPIN is mixed with alkaline solutions. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Solutions which are discolored or which contain particulate matter should not be administered.