Ropivacaine Hydrochloride

Ropivacaine Hydrochloride Injection is indicated for the production of local or regional anesthesia for surgery and for acute pain management.

• See

  Table 1 Dosage Recommendations

  *= Not Applicable
  †= 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 Warnings and Precautions ].
  ‡= 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.
  §= Cumulative doses up to 770 mg of ropivacaine hydrochloride injection 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.
  	Conc.			Volume	Dose	Onset	Duration
  	mg per 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*
  Administration	7.5		(0.75%)	5 to 15	38 to 113	10 to 20	n/a*
  Surgery Major Nerve Block †	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 (e.g., minor nerve blocks and infiltration)	5		(0.5%)	1 to 40	5 to 200	1 to 15	2 to 6
  LABOR PAIN MANAGEMENT
  Lumbar Epidural Administration Initial Dose	2		(0.2%)	10 to 20	20 to 40	10 to15	0.5 to 1.5
  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 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

  for Dosage Recommendations (
  2.2 Dosage Recommendations

  Table 1 Dosage Recommendations

  *= Not Applicable
  †= 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 Warnings and Precautions ].
  ‡= 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.
  §= Cumulative doses up to 770 mg of ropivacaine hydrochloride injection 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.
  	Conc.			Volume	Dose	Onset	Duration
  	mg per 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*
  Administration	7.5		(0.75%)	5 to 15	38 to 113	10 to 20	n/a*
  Surgery Major Nerve Block †	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 (e.g., minor nerve blocks and infiltration)	5		(0.5%)	1 to 40	5 to 200	1 to 15	2 to 6
  LABOR PAIN MANAGEMENT
  Lumbar Epidural Administration Initial Dose	2		(0.2%)	10 to 20	20 to 40	10 to15	0.5 to 1.5
  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 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 ropivacaine hydrochloride injection 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 ropivacaine hydrochloride injection 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 ropivacaine hydrochloride injection is induced via an epidural catheter. Analgesia is maintained with an infusion of ropivacaine hydrochloride injection, 2 mg per 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 ropivacaine hydrochloride injection epidural infusions for up to 72 hours.
  )

Ropivacaine Hydrochloride Injection, USP is a clear, colorless, preservative-free solution available as:

• 0.2%, 200 mg per 100 mL (2 mg per mL), 100 mL single-dose, ready-to-use, polypropylene flexible bag.
• 0.2%, 400 mg per 200 mL (2 mg per mL), 200 mL single-dose, ready-to-use, polypropylene flexible bag.
• 0.5%, 500 mg per 100 mL (5 mg per mL), 100 mL single-dose, ready-to-use, polypropylene flexible bag.
• 0.5%, 1,000 mg per 200 mL (5 mg per mL), 200 mL single-dose, ready-to-use, polypropylene flexible bag.

There are no available human data on use of ropivacaine hydrochloride in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Local anesthetics may cause varying degrees of toxicity to the mother and fetus and adverse reactions include alterations of the central nervous system, peripheral vascular tone, and cardiac function

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U. S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

• 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. (
  5.1 General Warnings and Precautions

  Prior to receiving major blocks the general condition of the patient should be optimized and the patient should have an IV line inserted. All necessary precautions should be taken to avoid intravascular injection. Local anesthetics should only be administered by clinicians who are well versed in the diagnosis and management of dose-related toxicity and other acute emergencies which might arise from the block to be employed, and then only after insuring the

  immediate (without delay)

  availability of oxygen, other resuscitative drugs, cardiopulmonary resuscitative equipment, and the personnel resources needed for proper management of toxic reactions and related emergencies

  [see Adverse Reactions and Overdosage ].

  Delay in proper management of dose-related toxicity, underventilation from any cause, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest and, possibly, death.

  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 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 ropivacaine hydrochloride 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.

  Solutions of ropivacaine hydrochloride should not be used for the production of obstetrical paracervical block anesthesia, retrobulbar block, or spinal anesthesia (subarachnoid block) due to insufficient data to support such use. Intravenous regional anesthesia (bier block) should not be performed due to a lack of clinical experience and the risk of attaining toxic blood levels of ropivacaine.

  It is essential that aspiration for blood, or cerebrospinal fluid (where applicable), be done prior to injecting any local anesthetic, both the original dose and all subsequent doses, to avoid intravascular or subarachnoid injection. However, a negative aspiration does not ensure against an intravascular or subarachnoid injection.
  )
• In performing ropivacaine hydrochloride blocks, unintended intravenous injection is possible and may result in cardiac arrhythmia or cardia arrest. (
  5.2 Unintended Intravenous Injection

  In performing ropivacaine hydrochloride blocks, unintended intravenous injection is possible and may result in cardiac arrhythmia or cardiac arrest. The potential for successful resuscitation has not been studied in humans. There have been rare reports of cardiac arrest during the use of ropivacaine hydrochloride for epidural anesthesia or peripheral nerve blockade, the majority of which occurred after unintentional accidental intravascular administration in elderly patients and in patients with concomitant heart disease. In some instances, resuscitation has been difficult. Should cardiac arrest occur, prolonged resuscitative efforts may be required to improve the probability of a successful outcome.

  Ropivacaine hydrochloride should be administered in incremental doses. It is not recommended for emergency situations, where a fast onset of surgical anesthesia is necessary. Historically, pregnant patients were reported to have a high risk for cardiac arrhythmias, cardiac/circulatory arrest and death when 0.75% bupivacaine (another member of the amino amide class of local anesthetics) was inadvertently rapidly injected intravenously.
  )
• Intra-articular infusions of local anesthetics may cause chondrolysis. Ropivacaine hydrochloride is not approved for this use. (
  5.3 Intra-Articular Infusions and Risk of Chondrolysis

  Intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions. The majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours. There is insufficient information to determine whether shorter infusion periods are not associated with these findings. The time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2nd month after surgery. Currently, there is no effective treatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement.
  ).
• Signs of methemoglobinemia may occur. (
  5.4 Risk of Methemoglobinemia

  Cases of methemoglobinemia have been reported in association with local anesthetic use. Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.

  Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure, and are characterized by a cyanotic skin discoloration and/or abnormal coloration of the blood. Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue ropivacaine hydrochloride and any other oxidizing agents. Depending on the severity of the signs and symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. A more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
  )