Ropivacaine

NAROPIN is indicated for the production of local or regional anesthesia for surgery and for acute pain management. Surgical Anesthesia: epidural block for surgery including cesarean section, major nerve block, local infiltration Acute Pain Management: epidural continuous infusion or intermittent bolus, e.g., postoperative or labor, local infiltration NAROPIN is an amide local anesthetic indicated in adults for the production of local or regional anesthesia for surgery and for acute pain management. Surgical Anesthesi a: epidural block for surgery including cesarean section, major nerve block, local infiltration Acute Pain Management: epidural continuous infusion or intermittent bolus, e.g., postoperative or labor, local infiltration

Ropivacaine is a member of the amino amide class of local anesthetics and is supplied as the pure S-(-)-enantiomer. Local anesthetics block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: pain, temperature, touch, proprioception, and skeletal muscle tone.

• See Table 1 for Dosage Recommendations 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. 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.

NAROPIN is contraindicated in patients with a known hypersensitivity to ropivacaine or to any local anesthetic agent of the amide type. History of hypersensitivity to local anesthetics of the amide type.

• Delay in proper management of dose-related toxicity, underventilation, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest and, possibly, death. • In performing NAROPIN blocks, unintended intravenous injection is possible and may result in cardiac arrhythmia or cardia arrest. • Intra-articular infusions of local anesthetics may cause chondrolysis. NAROPIN is not approved for this use. • Signs of methemoglobinemia may occur.

Reactions to ropivacaine are characteristic of those associated with other amide-type local anesthetics. A major cause of adverse reactions to this group of drugs may be associated with excessive plasma levels, which may be due to overdosage, unintentional intravascular injection or slow metabolic degradation. The reported adverse events are derived from clinical studies conducted in the U.S. and other countries. The reference drug was usually bupivacaine. The studies used a variety of premedications, sedatives, and surgical procedures of varying length. A total of 3,988 patients have been exposed to NAROPIN at concentrations up to 1% in clinical trials. Each patient was counted once for each type of adverse event.

Patients who are administered local anesthetics are at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics: Examples of Drugs Associated with Methemoglobinemia Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants Phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine NAROPIN should be used with caution in patients receiving other local anesthetics or agents structurally related to amide- type local anesthetics, since the toxic effects of these drugs are additive.

Solutions should be stored at 20ºC to 25°C (68ºF to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).