DailyMed Label: Naropin

DailyMed Label: Naropin

2024

DailyMed Prescription

Naropin

ROPIVACAINE HYDROCHLORIDE

Fresenius Kabi USA, LLC

NDC: 63323-288

NDC: 63323-288

NDC: 63323-288

NDC: 63323-288

NDC: 63323-288

Naropin ® Injection contains ropivacaine HCl which is a member of the amino amide class of local anesthetics.  Naropin Injection is a sterile, isotonic solution that contains the enantiomerically pure drug substance, sodium chloride for isotonicity and water for injection. Sodium hydroxide and/or hydrochloric acid may be used for pH adjustment.  It is administered parenterally. Ropivacaine HCl is chemically described as S-(-)-1-propyl-2',6'-pipecoloxylidide hydrochloride monohydrate.  The drug substance is a white crystalline powder, with the following structural formula:   At 25°C ropivacaine HCl has a solubility of 53.8 mg/mL in water, a distribution ratio between n-octanol and phosphate buffer at pH 7.4 of 14:1 and a pKa of 8.07 in 0.1 M KCl solution.  The pKa of ropivacaine is approximately the same as bupivacaine (8.1) and is similar to that of mepivacaine (7.7).  However, ropivacaine has an intermediate degree of lipid solubility compared to bupivacaine and mepivacaine. Naropin Injection is preservative-free and is available in single dose containers in 2 (0.2%), 5 (0.5%), 7.5 (0.75%) and 10 mg/mL (1%) concentrations.  The specific gravity of Naropin Injection solutions range from 1.002 to 1.005 at 25°C. structure

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

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. 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 DOSAGE AND ADMINISTRATION ). 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. 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. Table 7 Dosage Recommendations Conc. Volume Dose Onset Duration mg/mL (%) mL mg min hours SURGICAL ANESTHESIA Lumbar Epidural 5 (0.5%) 15 to 30 75 to 150 15 to 30 2 to 4 Administration 7.5 (0.75%) 15 to 25 113 to 188 10 to 20 3 to 5 Surgery 10 (1%) 15 to 20 150 to 200 10 to 20 4 to 6 Lumbar Epidural 5 (0.5%) 20 to 30 100 to 150 15 to 25 2 to 4 Administration 7.5 (0.75%) 15 to 20 113 to 150 10 to 20 3 to 5 Cesarean Section Thoracic Epidural 5 (0.5%) 5 to 15 25 to 75 10 to 20 n/a = Not Applicable         Administration 7.5 (0.75%) 5 to 15 38 to 113 10 to 20 n/a       Surgery Major Nerve Block = The dose for a major nerve block must be adjusted according to site of administration and patient status.  Supraclavicular brachial plexus blocks may be associated with a higher frequency of serious adverse reactions, regardless of the local anesthetic used (see PRECAUTIONS).         5 (0.5%) 35 to 50 175 to 250 15 to 30 5 to 8 (e.g., brachial plexus block) 7.5 (0.75%) 10 to 40 75 to 300 10 to 25 6 to 10 Field Block 5 (0.5%) 1 to 40 5 to 200 1 to 15 2 to 6 (e.g., minor nerve blocks and infiltration) LABOR PAIN MANAGEMENT Lumbar Epidural Administration Initial Dose 2 (0.2%) 10 to 20 20 to 40 10 to 15 0.5 to 1.5 Continuous infusion = Median dose of 21 mg per hour was administered by continuous infusion or by incremental injections (top-ups) over a median delivery time of 5.5 hours.         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 = Cumulative doses up to 770 mg of Naropin over 24 hours (intraoperative block plus postoperative infusion);  Continuous epidural infusion at rates up to 28 mg per hour for 72 hours have been well tolerated in adults, i.e., 2016 mg plus surgical dose of approximately 100 to 150 mg as top-up.          2  (0.2%)  6 to 14 mL/h   12 to 28 mg/h  n/a        n/a        Thoracic Epidural Administration   2  (0.2%)  6 to 14 mL/h  12 to 28 mg/h  n/a        n/a        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.

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

The safe and effective use of local anesthetics depends on proper dosage, correct technique, adequate precautions and readiness for emergencies. Resuscitative equipment, oxygen and other resuscitative drugs should be available for immediate use (see  WARNINGS and ADVERSE REACTIONS ).  The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse events.  Injections should be made slowly and incrementally, with frequent aspirations before and during the injection to avoid intravascular injection.  When a continuous catheter technique is used, syringe aspirations should also be performed before and during each supplemental injection.  During the administration of epidural anesthesia, it is recommended that a test dose of a local anesthetic with a fast onset be administered initially and that the patient be monitored for central nervous system and cardiovascular toxicity, as well as for signs of unintended intrathecal administration before proceeding.  When clinical conditions permit, consideration should be given to employing local anesthetic solutions, which contain epinephrine for the test dose because circulatory changes compatible with epinephrine may also serve as a warning sign of unintended intravascular injection.  An intravascular injection is still possible even if aspirations for blood are negative.  Administration of higher than recommended doses of Naropin to achieve greater motor blockade or increased duration of sensory blockade may result in cardiovascular depression, particularly in the event of inadvertent intravascular injection. Tolerance to elevated blood levels varies with the physical condition of the patient.  Debilitated, elderly patients and acutely ill patients should be given reduced doses commensurate with their age and physical condition.  Local anesthetics should also be used with caution in patients with hypotension, hypovolemia or heart block. Careful and constant monitoring of cardiovascular and respiratory vital signs (adequacy of ventilation) and the patient's state of consciousness should be performed after each local anesthetic injection.  It should be kept in mind at such times that restlessness, anxiety, incoherent speech, light-headedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, depression, or drowsiness may be early warning signs of central nervous system toxicity.  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.  Local anesthetics should also be used with caution in patients with impaired cardiovascular function because they may be less able to compensate for functional changes associated with the prolongation of A-V conduction produced by these drugs. Many drugs used during the conduct of anesthesia are considered potential triggering agents for malignant hyperthermia (MH).  Amide-type local anesthetics are not known to trigger this reaction.  However, since the need for supplemental general anesthesia cannot be predicted in advance, it is suggested that a standard protocol for MH management should be available. During epidural administration, Naropin should be administered in incremental doses of 3 to 5 mL with sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection.  Syringe aspirations should also be performed before and during each supplemental injection in continuous (intermittent) catheter techniques.  An intravascular injection is still possible even if aspirations for blood are negative.  During the administration of epidural anesthesia, it is recommended that a test dose be administered initially and the effects monitored before the full dose is given.  When clinical conditions permit, the test dose should contain an appropriate dose of epinephrine to serve as a warning of unintentional intravascular injection.  If injected into a blood vessel, this amount of epinephrine is likely to produce a transient "epinephrine response" within 45 seconds, consisting of an increase in heart rate and systolic blood pressure, circumoral pallor, palpitations and nervousness in the unsedated patient.  The sedated patient may exhibit only a pulse rate increase of 20 or more beats per minute for 15 or more seconds.  Therefore, following the test dose, the heart should be continuously monitored for a heart rate increase.  Patients on beta-blockers may not manifest changes in heart rate, but blood pressure monitoring can detect a rise in systolic blood pressure.  A test dose of a short-acting amide anesthetic such as lidocaine is recommended to detect an unintentional intrathecal administration.  This will be manifested within a few minutes by signs of spinal block (e.g., decreased sensation of the buttocks, paresis of the legs, or, in the sedated patient, absent knee jerk). An intravascular or subarachnoid injection is still possible even if results of the test dose are negative.  The test dose itself may produce a systemic toxic reaction, high spinal or epinephrine-induced cardiovascular effects. Ropivacaine plasma concentrations may approach the threshold for central nervous system toxicity after the administration of 300 mg of ropivacaine for brachial plexus block.  Caution should be exercised when using the 300 mg dose (see OVERDOSAGE ). The dose for a major nerve block must be adjusted according to the site of administration and patient status.  Supraclavicular brachial plexus blocks may be associated with a higher frequency of serious adverse reactions, regardless of the local anesthetic used. Major peripheral nerve blocks may result in the administration of a large volume of local anesthetic in highly vascularized areas, often close to large vessels where there is an increased risk of intravascular injection and/or rapid systemic absorption, which can lead to high plasma concentrations. Small doses of local anesthetics injected into the head and neck area may produce adverse reactions similar to systemic toxicity seen with unintentional intravascular injections of larger doses.  The injection procedures require the utmost care.  Confusion, convulsions, respiratory depression, and/or respiratory arrest, and cardiovascular stimulation or depression have been reported.  These reactions may be due to intra-arterial injection of the local anesthetic with retrograde flow to the cerebral circulation.  Patients receiving these blocks should have their circulation and respiration monitored and be constantly observed.  Resuscitative equipment and personnel for treating adverse reactions should be immediately available.  Dosage recommendations should not be exceeded (see DOSAGE AND ADMINISTRATION ). The use of Naropin in retrobulbar blocks for ophthalmic surgery has not been studied.  Until appropriate experience is gained, the use of Naropin for such surgery is not recommended. When appropriate, patients should be informed in advance that they may experience temporary loss of sensation and motor activity in the anesthetized part of the body following proper administration of lumbar epidural anesthesia.  Also, when appropriate, the physician should discuss other information including adverse reactions in the Naropin package insert. Inform patients that use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly. Advise patients or caregivers to seek immediate medical attention if they or someone in their care experience the following signs or symptoms: pale, gray, or blue colored skin (cyanosis); headache; rapid heart rate; shortness of breath; lightheadedness; or fatigue. Specific trials studying the interaction between ropivacaine and class III antiarrhythmic drugs (e.g., amiodarone) have not been performed, but caution is advised (see WARNINGS ). 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.  Cytochrome P4501A2 is involved in the formation of 3-hydroxy ropivacaine, the major metabolite.  In vivo , the plasma clearance of ropivacaine was reduced by 70% during coadministration of fluvoxamine (25 mg bid for 2 days), a selective and potent CYP1A2 inhibitor.  Thus strong inhibitors of cytochrome P4501A2, such as fluvoxamine, given concomitantly during administration of Naropin, can interact with Naropin leading to increased ropivacaine plasma levels.  Caution should be exercised when CYP1A2 inhibitors are coadministered.  Possible interactions with drugs known to be metabolized by CYP1A2 via competitive inhibition such as theophylline and imipramine may also occur.  Coadministration of a selective and potent inhibitor of CYP3A4, ketoconazole (100 mg bid for 2 days with ropivacaine infusion administered 1 hour after ketoconazole) caused a 15% reduction in in vivo plasma clearance of ropivacaine. 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 Long-term studies in animals of most local anesthetics, including ropivacaine, to evaluate the carcinogenic potential have not been conducted. Weak mutagenic activity was seen in the mouse lymphoma test.  Mutagenicity was not noted in the other assays, demonstrating that the weak signs of in vitro activity in the mouse lymphoma test were not manifest under diverse in vivo conditions. Studies performed with ropivacaine in rats did not demonstrate an effect on fertility or general reproductive performance over 2 generations. Reproduction toxicity studies have been performed in pregnant New Zealand white rabbits and Sprague-Dawley rats.  During gestation days 6 to 18, rabbits received 1.3, 4.2, or 13 mg/kg/day subcutaneously.  In rats, subcutaneous doses of 5.3, 11 and 26 mg/kg/day were administered during gestation days 6 to 15.  No teratogenic effects were observed in rats and rabbits at the highest doses tested.  The highest doses of 13 mg/kg/day (rabbits) and 26 mg/kg/day (rats) are approximately 1/3 of the maximum recommended human dose (epidural, 770 mg/24 hours) based on a mg/m 2 basis.  In 2 prenatal and postnatal studies, the female rats were dosed daily from day 15 of gestation to day 20 postpartum.  The doses were 5.3, 11 and 26 mg/kg/day subcutaneously.  There were no treatment-related effects on late fetal development, parturition, lactation, neonatal viability, or growth of the offspring. In another study with rats, the males were dosed daily for 9 weeks before mating and during mating.  The females were dosed daily for 2 weeks before mating and then during the mating, pregnancy, and lactation, up to day 42 post coitus.  At 23 mg/kg/day, an increased loss of pups was observed during the first 3 days postpartum.  The effect was considered secondary to impaired maternal care due to maternal toxicity. There are no adequate or well-controlled studies in pregnant women of the effects of Naropin on the developing fetus.  Naropin should only be used during pregnancy if the benefits outweigh the risk. Teratogenicity studies in rats and rabbits did not show evidence of any adverse effects on organogenesis or early fetal development in rats (26 mg/kg sc) or rabbits (13 mg/kg).  The doses used were approximately equal to total daily dose based on body surface area.  There were no treatment-related effects on late fetal development, parturition, lactation, neonatal viability, or growth of the offspring in 2 perinatal and postnatal studies in rats, at dose levels equivalent to the maximum recommended human dose based on body surface area.  In another study at 23 mg/kg, an increased pup loss was seen during the first 3 days postpartum, which was considered secondary to impaired maternal care due to maternal toxicity. Local anesthetics, including ropivacaine, rapidly cross the placenta, and when used for epidural block can cause varying degrees of maternal, fetal and neonatal toxicity (see  CLINICAL PHARMACOLOGY and PHARMACOKINETICS ).  The incidence and degree of toxicity depend upon the procedure performed, the type and amount of drug used, and the technique of drug administration.  Adverse reactions in the parturient, fetus and neonate involve alterations of the central nervous system, peripheral vascular tone and cardiac function. Maternal hypotension has resulted from regional anesthesia with Naropin for obstetrical pain relief. Local anesthetics produce vasodilation by blocking sympathetic nerves.  Elevating the patient's legs and positioning her on her left side will help prevent decreases in blood pressure.  The fetal heart rate also should be monitored continuously, and electronic fetal monitoring is highly advisable.  Epidural anesthesia has been reported to prolong the second stage of labor by removing the patient's reflex urge to bear down or by interfering with motor function.  Spontaneous vertex delivery occurred more frequently in patients receiving Naropin than in those receiving bupivacaine. Some local anesthetic drugs are excreted in human milk and caution should be exercised when they are administered to a nursing woman.  The excretion of ropivacaine or its metabolites in human milk has not been studied.  Based on the milk/plasma concentration ratio in rats, the estimated daily dose to a pup will be about 4% of the dose given to the mother.  Assuming that the milk/plasma concentration in humans is of the same order, the total Naropin dose to which the baby is exposed by breast-feeding is far lower than by exposure in utero in pregnant women at term (see PRECAUTIONS ). The safety and efficacy of Naropin in pediatric patients have not been established. Of the 2,978 subjects that were administered Naropin Injection in 71 controlled and uncontrolled clinical studies, 803 patients (27%) were 65 years of age or older which includes 127 patients (4%) 75 years of age and over.  Naropin Injection was found to be safe and effective in the patients in these studies.  Clinical data in one published article indicate that differences in various pharmacodynamic measures were observed with increasing age.  In one study, the upper level of analgesia increased with age, the maximum decrease of mean arterial pressure (MAP) declined with age during the first hour after epidural administration, and the intensity of motor blockade increased with age. 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.  Elderly patients are more likely to have decreased hepatic, renal, or cardiac function, as well as concomitant disease.  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 PHARMACOKINETICS , Elimination ).

Naropin (ropivacaine HCl Injection, USP) is supplied as follows: Product Code Unit of Sale Strength Each NP278827 NDC 63323-288-27 Unit of 5 1% 200 mg per 20 mL (10 mg per mL) NDC 63323-288-25 20 mL Plastic Ampule 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. 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 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. Solutions should be stored at 20º to 25°C (68º to 77°F) [see USP Controlled Room Temperature]. The container closure is not made with natural rubber latex. These products are intended for single dose and are free from preservatives. Any solution remaining from an opened container should be discarded promptly.  In addition, continuous infusion bottles should not be left in place for more than 24 hours. NAROPIN is a trademark of Fresenius Kabi USA, LLC. Novaplus is a registered trademark of Vizient, Inc.

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: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone.

PACKAGE LABEL - PRINCIPAL DISPLAY - Naropin 20 mL Ampule Label NDC 63323-288-25        NP278827 Naropin ® (ropivacaine HCl Injection, USP) 1%  200 mg per 20 mL  (10 mg per mL) NOT FOR INHALATION. 20 mL ampule Rx only       PACKAGE LABEL - PRINCIPAL DISPLAY - Naropin 20 mL Ampule Lidding Label NDC 63323-288-25        NP278827 Naropin ® (ropivacaine HCl Injection, USP) Sterile-Pak 1%  200 mg per 20 mL  (10 mg per mL) For Epidural Administration Only. Not for Intravenous Administration.       PACKAGE LABEL - PRINCIPAL DISPLAY - Naropin 20 mL Ampule Carton Panel NDC 63323-288-27        NP278827 Naropin ® (ropivacaine HCl Injection, USP) 1%  200 mg per 20 mL  (10 mg per mL) For Epidural Administration Only. Not for Intravenous Administration. Contains Five Presterilized 20 mL Plastic Ampule Units NOT FOR INHALATION. Rx only np278827-amp np278827-ldg np278827-box