Ropivacaine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection, as hydrochloride [preservative free]:

Naropin: 2 mg/mL (10 mL, 20 mL, 100 mL, 200 mL); 5 mg/mL (20 mL, 30 mL, 100 mL [DSC], 200 mL); 7.5 mg/mL (20 mL); 10 mg/mL (10 mL, 20 mL)

Generic: 2 mg/mL (10 mL, 20 mL, 100 mL, 200 mL); 5 mg/mL (20 mL, 30 mL, 100 mL, 200 mL); 7.5 mg/mL (20 mL); 10 mg/mL (10 mL, 20 mL)

Pharmacology

Mechanism of Action

Blocks both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions, which results in inhibition of depolarization with resultant blockade of conduction

Pharmacokinetics/Pharmacodynamics

Distribution

V_d:

Children: Epidural infusion: 2.1 to 4.2 L/kg (Hansen 2000)

Adults: Intravascular infusion: 41 ± 7 L

Metabolism

Hepatic, via CYP1A2 to metabolites

Excretion

Urine (86% as metabolites)

Onset of Action

Anesthesia (route dependent): 3 to 15 minutes

Time to Peak

Serum (dose and route dependent): Caudal:

Infants: Median: 60 minutes (range: 15 to 90 minutes) (Wulf 2000)

Children: Mean: 60 minutes (range: 12 to 249 minutes (Lonnqvist 2000)

Duration of Action

Dose and route dependent: 3 to 15 hours

Half-Life Elimination

Children: Epidural: Terminal phase:4.9 hours (range: 3 to 6.7 hours) (Hansen 2000)

Adults: Epidural: 5 to 7 hours; IV: Terminal: 111 ± 62 minutes (Lee 1989)

Use: Labeled Indications

Acute pain management: For acute pain management administered as an epidural continuous infusion, intermittent bolus (eg, postoperative or labor), or local infiltration.

Surgical anesthesia: For the production of local or regional anesthesia for surgery administered as an epidural block, including cesarean section, major nerve block, or local infiltration.

Contraindications

Hypersensitivity to ropivacaine, amide-type local anesthetics (eg, bupivacaine, mepivacaine, lidocaine), or any component of the formulation

Canadian labeling: Additional contraindications (not in US labeling): Intravenous regional anesthesia (Bier block); obstetric paracervical block anesthesia

Dosage and Administration

Dosing: Adult

Dose varies with procedure, onset and depth of anesthesia desired, vascularity of tissues, duration of anesthesia, and condition of patient: A test dose of short-acting local anesthestic containing epinephrine (eg, 3 to 5 mL) should be administered prior to induction of complete block with ropivacaine. Incremental ropivacaine dosing is recommended. Adults:

Surgical anesthesia:

Lumbar epidural block for surgery:

15 to 30 mL of 0.5% solution

15 to 25 mL of 0.75% solution

15 to 20 mL of 1% solution

Lumbar epidural block for cesarean section:

20 to 30 mL dose of 0.5% solution

15 to 20 mL dose of 0.75% solution

Thoracic epidural block:

5 to 15 mL dose of 0.5% solution

5 to 15 mL dose of 0.75% solution

Major nerve block:

35 to 50 mL dose of 0.5% solution

10 to 40 mL dose of 0.75% solution

Field block: 1 to 40 mL dose of 0.5% solution

Labor pain management: Lumbar epidural: Initial: 10 to 20 mL 0.2% solution; continuous infusion dose: 6 to 14 mL/hour of 0.2% solution with incremental injections of 10 to 15 mL/hour of 0.2% solution

Postoperative pain management:

Peripheral nerve block: Continuous infusion dose: 5 to 10 mL/hour of 0.2% solution (Bagry, 2008; Klein, 2000)

Lumbar or thoracic epidural: Continuous infusion dose: 6 to 14 mL/hour of 0.2% solution

Infiltration/minor nerve block:

1 to 100 mL dose of 0.2% solution

1 to 40 mL dose of 0.5% solution

Dosing: Geriatric

Refer to adult dosing. Use with caution; initial dose reductions may be necessary.

Dosing: Pediatric

Note: Dose varies with procedure, depth of anesthesia, vascularity of tissues, duration of anesthesia, and condition of patient. Consider incremental administration with negative aspiration prior to each injection; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided (Mulroy 2010). Should only be administered under the supervision of a qualified physician experienced in the use of anesthetics. Dosing units variable (mL/kg, mg/kg); use extra precaution to ensure accuracy and minimize potential toxicity.

Central nerve blocks/anesthesia (eg, caudal, lumbar, thoracic): Limited data available:

Caudal block: Infants and Children: Caudal injection: 0.2% (2 mg/mL) solution: 0.5 to 1 mL/kg; some experts suggest a maximum volume of 25 mL (Ivani 1998; Ivani 2002; Jöhr 2015; Kokinsky 2003; Lonnqvist 2000)

Epidural block (eg, lumbar, thoracic): Infants, Children, and Adolescents: Epidural injection 0.2% (2 mg/mL): 0.7 mL/kg. Note: For infants (particularly young infants) if repeat injections necessary, a decreased dose may be necessary to prevent drug accumulation. Some experts suggest if at least 45 minutes since initial dose, reduce dose to ¹/₃ of the initial or if at least 90 minutes since initial dose, then reduce dose to half of the initial. If additional doses are necessary, doses should be reduced to half of the previous dose (Ivani 1999; Miller 2015).

Epidural, continuous infusion:

Infants <3 months: Epidural injection: Bolus: Usual concentration 0.2% (2 mg/mL) solution: Reported range: 0.5 to 1 mL/kg. In some cases, a more dilute solution (eg, 0.1% [1 mg/mL]) may be required to ensure adequate volume and minimize toxicity. Follow with continuous epidural infusion of 0.2% (2 mg/mL) solution at 0.2 mg/kg/hour (Bosenberg 2005; Hansen 2000; Miller 2015)

Infants ≥3 months, Children, and Adolescents: Epidural injection: 0.2% (2 mg/mL) solution: Bolus: Reported range: 0.5 to 1 mL/kg administered over several minutes (eg, 3 to 5 minutes) followed by continuous epidural infusion at 0.4 mg/kg/hour; in adults, usual rates are 6 to 14 mL/hour of 0.2% solution (Berde 2008; Bosenberg 2005; Hansen 2000)

Peripheral nerve blocks/ local anesthesia: Limited data available: Note: Dose varies with location of block (ie, procedure), depth of anesthesia, vascularity of tissues, duration of anesthesia, and patient parameters (eg, age, weight, condition).

Single injection: The volume of dose (mL/kg) and concentration of solution are site-specific based upon anatomy and variable among patients and procedure (Coté 2013; Miller 2015).

Infants ≥6 months, Children, and Adolescents: Suggested or reported dose volumes presented; not to exceed a suggested maximum dose of 3 mg/kg/dose based on lean body mass; dosing based on extrapolation from adult experience; additional data necessary to more clearly define pediatric upper dose limit. Note: For infants <6 months, dose reductions (eg, by 30%) have been suggested by experts (Coté 2013; Visoiu 2015).

Head and neck blocks: 0.05 mL/kg

Maxillary nerve: 0.15 mL/kg (Chiono 2014; Sola 2012)

Upper extremity blocks:

Brachial plexus: 0.2 to 0.3 mL/kg

Digital nerve: ≤0.2% (2 mg/mL) solution: 0.05 mL/kg

Trunchal blocks:

Transversus abdominis plane: 0.2 to 0.5 mL/kg (Jöhr 2015)

Ilioinguinal nerve: 0.075 mL/kg

Rectus sheath: 0.1 to 0.2 mL/kg

Lower extremity blocks:

Femoral nerve: 0.2% to 0.5% (2 to 5 mg/mL) solution: 0.2 to 0.4 mL/kg (Coté 2013; Schloss 2014; Veneziano 2016)

Sciatic nerve: 0.2 to 0.3 mL/kg

Continuous peripheral nerve block infusion (CPNB) (Dadure 2009; Duflo 2006; Iliev 2016; Visoiu 2014): Infants ≥6 months, Children, and Adolescents:

Initial bolus: 0.2% (2 mg/mL) solution: Dose dependent on nerve catheter location: Commonly reported dose range: ~0.5 to 1.32 mg/kg; some patients and/or catheter/nerve sites may require a higher bolus dose; a trial evaluating 403 pediatric catheter placements reported an overall median bolus for all catheter sites of 1.32 mg/kg (IQR: 0.82 to 1.95 mg/kg); another trial reporting on 339 pediatric catheter placements reported a mean initial bolus dose of 0.49 to 0.98 mg/kg.

Continuous peripheral nerve block infusion: 0.2% (2 mg/mL) solution: Reported mean rate range: 0.11 to 0.25 mg/kg/hour (most experience reported at 0.2 to 0.25 mg/kg/hour); reported IQR range from 403 pediatric catheter placements: 0.12 to 0.33 mg/kg/hour (depending upon catheter site) with a usual duration <72 hours; majority of experience is postoperative pain management following orthopedic procedures including administration via On-Q pump or Ambu Smart-Infuser

Spinal anesthesia: Limited data available: Infant, Children, and Adolescents ≤17 years: Intrathecal (via LP site; L 3-5): Preservative-free 0.5% (5 mg/mL) isobaric solution: 0.5 mg/kg; maximum dose: 20 mg/dose (Kokki 2005)

Administration

Administered via local infiltration, epidural block and epidural infusion, or intermittent bolus. Prior to ropivacaine administration, a test dose of short-acting local anesthestic with epinephrine (eg, 3 to 5 mL) should be administered. Incremental ropivacaine dosing is recommended. Do not administer large volume of anesthetic rapidly. The On-Q infusion pump is used to slowly administer local anesthetics (eg, bupivacaine, lidocaine, ropivacaine) to or around surgical wound sites and/or in close proximity to nerves for pre- or postoperative regional anesthesia. When infused directly into the shoulder, destruction of articular cartilage (chondrolysis) has occurred. On-Q pumps should never be placed directly into any joint.

Storage

Store at 20°C to 25°C (68°F to 77°F). Infusions should be discarded after 24 hours.

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

Bupivacaine (Liposomal): Local Anesthetics may enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Liposomal bupivacaine should not be administered with local anesthetics. Liposomal bupivacaine may be administered 20 minutes or more after the administration of lidocaine, but the optimal duration of dose separation for other local anesthetics is unknown Avoid combination

CYP1A2 Inhibitors (Moderate): May increase the serum concentration of Ropivacaine. Monitor therapy

CYP1A2 Inhibitors (Strong): May increase the serum concentration of Ropivacaine. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hyaluronidase: May enhance the adverse/toxic effect of Local Anesthetics. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Methemoglobinemia Associated Agents: May enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Neuromuscular-Blocking Agents: Local Anesthetics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Propofol: May increase the serum concentration of Ropivacaine. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Technetium Tc 99m Tilmanocept: Local Anesthetics may diminish the diagnostic effect of Technetium Tc 99m Tilmanocept. Management: Avoid mixing and simultaneously co-injecting technetium Tc 99m tilmanocept with local anesthetics. This interaction does not appear to apply to other uses of these agents in combination. Monitor therapy

Adverse Reactions

>10%:

Cardiovascular: Hypotension (32% to 69%), bradycardia (6% to 20%)

Gastrointestinal: Nausea (13% to 25%), vomiting (7% to 12%)

Neuromuscular & skeletal: Back pain (4% to 16%)

1% to 10%:

Cardiovascular: Chest pain (1% to 5%), hypertension (1% to 5%), tachycardia (1% to 5%)

Central nervous system: Headache (5% to 8%), pain (4% to 8%), paresthesia (2% to 6%), dizziness (3%), chills (≤3%), rigors (≤3%), hypoesthesia (2%), anxiety (1%)

Dermatologic: Pruritus (1% to 5%)

Endocrine & metabolic: Hypokalemia (1% to 5%)

Genitourinary: Oliguria (1% to 5%), urinary retention (1% to 5%), urinary tract infection (1% to 5%), disorder of breast milk secretion (1%), poor progression of labor (1%)

Hematologic & oncologic: Anemia (6%)

Neuromuscular & skeletal: Muscle cramps (1% to 5%)

Respiratory: Dyspnea (1% to 5%), rhinitis (1%)

Miscellaneous: Fever (2% to 9%), postoperative complication (3% to 7%)

<1%, postmarketing, and/or case reports: Accidental injury, agitation, amnesia, angioedema, asthenia, atrial fibrillation, auditory disturbance, blepharoptosis, bronchospasm, cardiac arrhythmia, coma, confusion, cough, deep vein thrombosis, drowsiness, dyskinesia, ECG abnormality, emotional lability, extrasystoles, fecal incontinence, hallucination, Horner's syndrome, hypersensitivity reaction, hypokinesia, hypomagnesemia, hypothermia, hypotonia, insomnia, jaundice, malaise, myalgia, myocardial infarction, nervousness, neuropathy, nightmares, orthostatic hypotension, pain at injection site, paresis, phlebitis, pulmonary embolism, seizure, skin rash, ST segment changes on ECG, stupor, syncope, tenesmus, tinnitus, tremor, urinary incontinence, urination disorder, urticaria, uterine atony, vertigo, visual disturbance

Warnings/Precautions

Concerns related to adverse effects:

• CNS toxicity: Careful and constant monitoring of the patient's state of consciousness should be done following each local anesthetic injection; at such times, restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression, or drowsiness may be early warning signs of CNS toxicity. Treatment is primarily symptomatic and supportive.
• Intra-articular infusion related chondrolysis: Continuous intra-articular infusion of local anesthetics after arthroscopic or other surgical procedures is not an approved use; chondrolysis (primarily in the shoulder joint) has occurred following infusion, with some cases requiring arthroplasty or shoulder replacement.
• Methemoglobinemia: Has been reported with local anesthetics; clinically significant methemoglobinemia requires immediate treatment along with discontinuation of the anesthetic and other oxidizing agents. Onset may be immediate or delayed (hours) after anesthetic exposure. Patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, exposure to oxidizing agents or their metabolites, or infants <6 months of age are more susceptible and should be closely monitored for signs and symptoms of methemoglobinemia (eg, cyanosis, headache, rapid pulse, shortness of breath, lightheadedness, fatigue).
• Respiratory arrest: Local anesthetics have been associated with rare occurrences of sudden respiratory arrest.
• Seizures: Convulsions due to systemic toxicity leading to cardiac arrest have also been reported, presumably following unintentional intravascular injection.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with hypotension, hypovolemia, heart block, or cardiovascular disease; may be at greater risk for toxicity.
• Hepatic impairment: Use with caution in patients with hepatic impairment; may be at greater risk for toxicity.
• Neurological disorders: Use with caution in patients with neurological disorders; may be at greater risk for toxicity.
• Porphyria: Use with caution in patients with acute porphyria; consider use of alternative agents.
• Psychiatric disorders: Use with caution in patients with psychiatric disorders; may be at greater risk for toxicity.
• Renal impairment: Use with caution in patients with severe renal impairment; may be at greater risk for toxicity.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Acutely ill patients: Use with caution in acutely ill; may be at greater risk for toxicity.
• Debilitated patients: Use with caution in debilitated patient; may be at greater risk for toxicity.
• Elderly: Use with caution in the elderly: may be at greater risk for toxicity. Cardiovascular adverse events (bradycardia, hypotension) may be age-related (more common in patients >61 years of age).

Other warnings/precautions:

• Administration: Intravascular injections should be avoided; aspiration should be performed prior to administration; the needle must be repositioned until no return of blood can be elicited by aspiration; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided.
• Rapid administration: Ropivacaine is not recommended for use in emergency situations where rapid administration is necessary.
• Trained personnel: Clinicians using local anesthetic agents should be well trained in diagnosis and management of emergencies that may arise from the use of these agents. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use.

Monitoring Parameters

Heart rate, blood pressure, ECG monitoring (if used with antiarrhythmics)

Pregnancy

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. When used for epidural block during labor and delivery, systemically absorbed ropivacaine may cross the placenta, resulting in varying degrees of fetal or neonatal effects (eg, CNS or cardiovascular depression). Fetal or neonatal adverse events include fetal bradycardia (12%), neonatal jaundice (8%), low Apgar scores (3%), fetal distress (2%), neonatal respiratory disorder (3%). Maternal hypotension may also result from systemic absorption. In cases of hypotension, position pregnant woman in left lateral decubitus position to prevent aortocaval compression by the gravid uterus. Epidural anesthesia may prolong the second stage of labor.

Patient Education

What is this drug used for?

• It is used to numb an area before a procedure.
• It is used to ease pain.

Frequently reported side effects of this drug

• Headache
• Nausea
• Vomiting
• Back pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Acidosis like confusion, fast breathing, fast heartbeat, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy.
• Methemoglobinemia like blue or gray color of the lips, nails, or skin; abnormal heartbeat; seizures; severe dizziness or passing out; severe headache; fatigue; loss of strength and energy; or shortness of breath.
• Severe loss of strength and energy
• Slow heartbeat
• Change in balance
• Burning or numbness feeling
• Numbness or tingling in mouth
• Lightheadedness
• Confusion
• Agitation
• Anxiety
• Trouble speaking
• Metallic taste
• Blurred vision
• Noise or ringing in the ears
• Dizziness
• Passing out
• Tremors
• Twitching
• Fatigue
• Depression
• Seizures
• Trouble breathing
• Slow breathing
• Shallow breathing
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.