Ropivacaine-injection

Name: Ropivacaine-injection

ropivacaine Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common or rare
  • Burning or prickling sensation
  • fever
  • itching

Check with your doctor as soon as possible if any of the following side effects occur:

Less common or rare
  • Back pain
  • difficulty urinating
  • headache
  • pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Ropivacaine Injection Description

Ropivacaine hydrochloride injection, USP contains ropivacaine hydrochloride which is a member of the amino amide class of local anesthetics. Ropivacaine hydrochloride injection, USP is a clear, colorless, sterile, isotonic solution free from visible particles 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 hydrochloride USP 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 hydrochloride 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 0.1M 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.


Ropivacaine hydrochloride injection, USP is preservative-free and is available in single dose containers in 2 mg/mL (0.2%), 5 mg/mL (0.5%), 7.5 mg/mL (0.75%), and 10 mg/mL (1%) concentrations. The specific gravity of ropivacaine hydrochloride injection, USP solutions range from 1.002 to 1.005 at 25°C.

Precautions

General

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 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.

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.

Epidural Anesthesia

During epidural administration, ropivacaine hydrochloride 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.

Use in Brachial Plexus Block

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.

Use in Peripheral Nerve Block

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.

Use in Head and Neck Area

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).

Use in Ophthalmic Surgery

The use of ropivacaine hydrochloride in retrobulbar blocks for ophthalmic surgery has not been studied. Until appropriate experience is gained, the use of ropivacaine hydrochloride for such surgery is not recommended.

Information for Patients

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 ropivacaine hydrochloride package insert.

Drug Interactions

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).

Ropivacaine hydrochloride 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 ropivacaine hydrochloride, can interact with ropivacaine hydrochloride 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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.

Pregnancy Category B

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/m2 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 ropivacaine hydrochloride on the developing fetus. Ropivacaine hydrochloride 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.

Labor and Delivery

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 ropivacaine hydrochloride 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 ropivacaine hydrochloride than in those receiving bupivacaine.

Nursing Mothers

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 ropivacaine hydrochloride 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).

Pediatric Use

The safety and efficacy of ropivacaine hydrochloride in pediatric patients have not been established.

Geriatric Use

Of the 2,978 subjects that were administered ropivacaine hydrochloride 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. Ropivacaine hydrochloride 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).

Adverse Reactions

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 ropivacaine hydrochloride at concentrations up to 1% in clinical trials. Each patient was counted once for each type of adverse event.

Incidence ≥5%

For the indications of epidural administration in surgery, cesarean section, postoperative pain management, peripheral nerve block, and local infiltration, the following treatment-emergent adverse events were reported with an incidence of ≥5% in all clinical studies (N=3988): hypotension (37%), nausea (24.8%), vomiting (11.6%), bradycardia (9.3%), fever (9.2%), pain (8%), postoperative complications (7.1%), anemia (6.1%), paresthesia (5.6%), headache (5.1%), pruritus (5.1%), and back pain (5%).

Incidence 1 to 5%

Urinary retention, dizziness, rigors, hypertension, tachycardia, anxiety, oliguria, hypoesthesia, chest pain, hypokalemia, dyspnea, cramps, and urinary tract infection.

Incidence in Controlled Clinical Trials

The reported adverse events are derived from controlled clinical studies with ropivacaine hydrochloride (concentrations ranged from 0.125% to 1% for ropivacaine hydrochloride and 0.25% to 0.75% for bupivacaine) in the U.S. and other countries involving 3,094 patients. Table 3A and 3B list adverse events (number and percentage) that occurred in at least 1% of ropivacaine hydrochloride-treated patients in these studies. The majority of patients receiving concentrations higher than 5 mg/mL (0.5%) were treated with ropivacaine hydrochloride.

                                                                                            Table 3A

Adverse Events Reported in ≥1% of Adult Patients Receiving Regional or Local Anesthesia (Surgery, Labor, Cesarean Section, Postoperative Pain Management, Peripheral Nerve Block and Local Infiltration)
  Adverse Reaction
Ropivacaine Hydrochloride 
total N=1661
Bupivacaine
total N=1433
N
(%)
N
(%)
  Hypotension
536
(32.3)
408
(28.5)
  Nausea
283
(17)
207
(14.4)
  Vomiting
117
(7)
88
(6.1)
  Bradycardia
96
(5.8)
73
(5.1)
  Headache
84
(5.1)
68
(4.7)
  Paresthesia
82
(4.9)
57
(4)
  Back pain
73
(4.4)
75
(5.2)
  Pain
71
(4.3)
71
(5)
  Pruritus
63
(3.8)
40
(2.8)
  Fever
61
(3.7)
37
(2.6)
  Dizziness
42
(2.5)
23
(1.6)
  Rigors (Chills)
42
(2.5)
24
(1.7)
  Postoperative complications
41
(2.5)
44
(3.1)
  Hypoesthesia
27
(1.6)
24
(1.7)
  Urinary retention
23
(1.4)
20
(1.4)
  Progression of labor poor/failed
23
(1.4)
22
(1.5)
  Anxiety
21
(1.3)
11
(0.8)
  Breast disorder, breast-feeding
21
(1.3)
12
(0.8)
  Rhinitis
18
(1.1)
13
(0.9)

                                                                                             Table 3B

Adverse Events Reported in ≥1% of Fetuses or Neonates of Mothers Who Received Regional Anesthesia (Cesarean Section and Labor Studies)
  Adverse Reaction
Ropivacaine Hydrochloride
total N=639
   Bupivacaine
  total N=573
         N
          (%)
  N
(%)
  Fetal bradycardia
         77
         (12.1)
           68
       (11.9)
  Neonatal jaundice
         49
         (7.7)
           47
        (8.2)
  Neonatal complication-NOS
         42
         (6.6)
           38
        (6.6)
  Apgar score low
         18
         (2.8)
           14
        (2.4)
  Neonatal respiratory disorder
         17
         (2.7)
           18
        (3.1)
  Neonatal tachypnea
         14
         (2.2)
           15
        (2.6)
  Neonatal fever
         13
          (2)
           14
        (2.4)
  Fetal tachycardia
         13
          (2)
           12
        (2.1)
  Fetal distress
         11
         (1.7)
           10
        (1.7)
  Neonatal infection
         10
         (1.6)
             8
        (1.4)
  Neonatal hypoglycemia
           8
         (1.3)
           16
        (2.8)

Incidence <1%

The following adverse events were reported during the ropivacaine hydrochloride clinical program in more than one patient (N=3988), occurred at an overall incidence of <1%, and were considered relevant:

Application Site Reactions – injection site pain

Cardiovascular System – vasovagal reaction, syncope, postural hypotension, non-specific ECG abnormalities

Female Reproductive – poor progression of labor, uterine atony

Gastrointestinal System – fecal incontinence, tenesmus, neonatal vomiting

General and Other Disorders – hypothermia, malaise, asthenia, accident and/or injury

Hearing and Vestibular – tinnitus, hearing abnormalities

Heart Rate and Rhythm – extrasystoles, non-specific arrhythmias, atrial fibrillation

Liver and Biliary System – jaundice

Metabolic Disorders – hypomagnesemia

Musculoskeletal System – myalgia

Myo/Endo/Pericardium – ST segment changes, myocardial infarction

Nervous System – tremor, Horner’s syndrome, paresis, dyskinesia, neuropathy, vertigo, coma, convulsion, hypokinesia, hypotonia, ptosis, stupor

Psychiatric Disorders – agitation, confusion, somnolence, nervousness, amnesia, hallucination, emotional lability, insomnia, nightmares

Respiratory System – bronchospasm, coughing

Skin Disorders – rash, urticaria

Urinary System Disorders – urinary incontinence, micturition disorder

Vascular – deep vein thrombosis, phlebitis, pulmonary embolism

Vision – vision abnormalities

For the indication epidural anesthesia for surgery, the 15 most common adverse events were compared between different concentrations of ropivacaine hydrochloride and bupivacaine. Table 4 is based on data from trials in the U.S. and other countries where ropivacaine hydrochloride was administered as an epidural anesthetic for surgery.

                                                                                                Table 4

Common Events (Epidural Administration)
  Adverse Reaction
Ropivacaine Hydrochloride
Bupivacaine
       5 mg/mL
    total N=256
     7.5 mg/mL
    total N=297
10 mg/mL
total N=207
5 mg/mL
total N=236
7.5 mg/mL
total N=174
N
(%)
N
(%)
N
(%)
 N 
(%)
 N  
(%)
  hypotension
99
(38.7)
146
(49.2)
113
(54.6)
 91
(38.6)
 89
(51.1)
  nausea
34
(13.3)
68
(22.9)
 
 
 41
(17.4)
 36
(20.7)
  bradycardia
29
(11.3)
58
(19.5)
40
(19.3)
 32
(13.6)
 25
(14.4)
  back pain
18
(7)
23
(7.7)
34
(16.4)
 21
(8.9)
 23
(13.2)
  vomiting
18
(7)
33
(11.1)
23
(11.1)
 19
(8.1)
 14
(8)
  headache
12
(4.7)
20
(6.7)
16
(7.7)
 13
(5.5)
 9
(5.2)
  fever
8
(3.1)
5
(1.7)
18
(8.7)
 11
(4.7)
 
 
  chills
6
(2.3)
7
(2.4)
6
(2.9)
 4
(1.7)
 3
(1.7)
  urinary retention
5
(2)
8
(2.7)
10
(4.8)
 10
(4.2)
 
 
  paresthesia
5
(2)
10
(3.4)
5
(2.4)
7
(3)
 
 
  pruritus
 
 
14
(4.7)
3
 (1.4)
 
 
 7
(4)

Using data from the same studies, the number (%) of patients experiencing hypotension is displayed by patient age, drug and concentration in Table 5. In Table 6, the adverse events for ropivacaine hydrochloride are broken down by gender.

                                                                                                    Table 5 

Effects of Age on Hypotension (Epidural Administration) Total N: Ropivacaine Hydrochloride = 760, Bupivacaine = 410
AGE
Ropivacaine Hydrochloride
Bupivacaine
5 mg/mL
7.5 mg/mL
10 mg/mL
5 mg/mL
7.5 mg/mL
 
 N 
         (%)
N
(%)
 N 
         (%)
 N 
          (%)
 N  
          (%)
<65
 68
(32.2)
99
(43.2)
 87
(51.5)
 64
(33.5)
 73
(48.3)
≥65
 31
(68.9)
47
(69.1)
 26
(68.4)
 27
(60)
 16
(69.6)

                                                                                                    Table 6

Most Common Adverse Events by Gender (Epidural Administration) Total N: Females = 405, Males = 355
  Adverse Reaction
Female
Male
N
(%)
N
(%)
  hypotension
220
(54.3)
138
(38.9)
  nausea
119
(29.4)
23
(6.5)
  bradycardia
65
(16)
56
(15.8)
  vomiting
59
(14.6)
8
(2.3)
  back pain
41
(10.1)
23
(6.5)
  headache
33
(8.1)
17
(4.8)
  chills
18
(4.4)
5
(1.4)
  fever
16
(4)
3
(0.8)
  pruritus
16
(4)
1
(0.3)
  pain
12
(3)
4
(1.1)
  urinary retention
11
(2.7)
7
(2)
  dizziness
9
(2.2)
4
(1.1)
  hypoesthesia
8
(2)
2
(0.6)
  paresthesia
8
(2)
10
(2.8)

Systemic Reactions

The most commonly encountered acute adverse experiences that demand immediate countermeasures are related to the central nervous system and the cardiovascular system. These adverse experiences are generally dose-related and due to high plasma levels that may result from overdosage, rapid absorption from the injection site, diminished tolerance or from unintentional intravascular injection of the local anesthetic solution. In addition to systemic dose-related toxicity, unintentional subarachnoid injection of drug during the intended performance of lumbar epidural block or nerve blocks near the vertebral column (especially in the head and neck region) may result in underventilation or apnea (“Total or High Spinal”). Also, hypotension due to loss of sympathetic tone and respiratory paralysis or underventilation due to cephalad extension of the motor level of anesthesia may occur. This may lead to secondary cardiac arrest if untreated. Factors influencing plasma protein binding, such as acidosis, systemic diseases that alter protein production or competition with other drugs for protein binding sites, may diminish individual tolerance.

Epidural administration of ropivacaine hydrochloride has, in some cases, as with other local anesthetics, been associated with transient increases in temperature to >38.5°C. This occurred more frequently at doses of ropivacaine hydrochloride >16 mg/h.

Neurologic Reactions

These are characterized by excitation and/or depression. Restlessness, anxiety, dizziness, tinnitus, blurred vision or tremors may occur, possibly proceeding to convulsions. However, excitement may be transient or absent, with depression being the first manifestation of an adverse reaction. This may quickly be followed by drowsiness merging into unconsciousness and respiratory arrest. Other central nervous system effects may be nausea, vomiting, chills, and constriction of the pupils.

The incidence of convulsions associated with the use of local anesthetics varies with the route of administration and the total dose administered. In a survey of studies of epidural anesthesia, overt toxicity progressing to convulsions occurred in approximately 0.1% of local anesthetic administrations.

The incidence of adverse neurological reactions associated with the use of local anesthetics may be related to the total dose and concentration of local anesthetic administered and are also dependent upon the particular drug used, the route of administration, and the physical status of the patient. Many of these observations may be related to local anesthetic techniques, with or without a contribution from the drug. During lumbar epidural block, occasional unintentional penetration of the subarachnoid space by the catheter or needle may occur. Subsequent adverse effects may depend partially on the amount of drug administered intrathecally as well as the physiological and physical effects of a dural puncture. These observations may include spinal block of varying magnitude (including high or total spinal block), hypotension secondary to spinal block, urinary retention, loss of bladder and bowel control (fecal and urinary incontinence), and loss of perineal sensation and sexual function. Signs and symptoms of subarachnoid block typically start within 2 to 3 minutes of injection. Doses of 15 and 22.5 mg of ropivacaine hydrochloride resulted in sensory levels as high as T5 and T4, respectively. Analgesia started in the sacral dermatomes in 2 to 3 minutes and extended to the T10 level in 10 to 13 minutes and lasted for approximately 2 hours. Other neurological effects following unintentional subarachnoid administration during epidural anesthesia may include persistent anesthesia, paresthesia, weakness, paralysis of the lower extremities, and loss of sphincter control; all of which may have slow, incomplete or no recovery. Headache, septic meningitis, meningismus, slowing of labor, increased incidence of forceps delivery, or cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid have been reported (see DOSAGE AND ADMINISTRATION discussion of Lumbar Epidural Block). A high spinal is characterized by paralysis of the arms, loss of consciousness, respiratory paralysis and bradycardia.

Cardiovascular System Reactions

High doses or unintentional intravascular injection may lead to high plasma levels and related depression of the myocardium, decreased cardiac output, heart block, hypotension, bradycardia, ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation, and possibly cardiac arrest (see WARNINGS, PRECAUTIONS, and OVERDOSAGE).

Allergic Reactions

Allergic type reactions are rare and may occur as a result of sensitivity to the local anesthetic (see WARNINGS). These reactions are characterized by signs such as urticaria, pruritus, erythema, angioneurotic edema (including laryngeal edema), tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, and possibly, anaphylactoid symptomatology (including severe hypotension). Cross-sensitivity among members of the amide-type local anesthetic group has been reported. The usefulness of screening for sensitivity has not been definitively established.

Overdosage

Acute emergencies from local anesthetics are generally related to high plasma levels encountered, or large doses administered, during therapeutic use of local anesthetics or to unintended subarachnoid or intravascular injection of local anesthetic solution (see ADVERSE REACTIONS, WARNINGS, and PRECAUTIONS).

MANAGEMENT OF LOCAL ANESTHETIC EMERGENCIES

Therapy with ropivacaine hydrochloride should be discontinued at the first sign of toxicity. No specific information is available for the treatment of toxicity with ropivacaine hydrochloride; therefore, treatment should be symptomatic and supportive. The first consideration is prevention, best accomplished by incremental injection of ropivacaine hydrochloride, careful and constant monitoring of cardiovascular and respiratory vital signs and the patient’s state of consciousness after each local anesthetic and during continuous infusion. At the first sign of change in mental status, oxygen should be administered.

The first step in the management of systemic toxic reactions, as well as underventilation or apnea due to unintentional subarachnoid injection of drug solution, consists of immediate attention to the establishment and maintenance of a patent airway and effective assisted or controlled ventilation with 100% oxygen with a delivery system capable of permitting immediate positive airway pressure by mask. Circulation should be assisted as necessary. This may prevent convulsions if they have not already occurred.

If necessary, use drugs to control convulsions. Intravenous barbiturates, anticonvulsant agents, or muscle relaxants should only be administered by those familiar with their use. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated. Supportive treatment of circulatory depression may require administration of intravenous fluids, and, when appropriate, a vasopressor dictated by the clinical situation (such as ephedrine or epinephrine to enhance myocardial contractile force).

Should cardiac arrest occur, prolonged resuscitative efforts may be required to improve the probability of a successful outcome.

The mean dosages of ropivacaine producing seizures, after intravenous infusion in dogs, non-pregnant and pregnant sheep were 4.9, 6.1 and 5.9 mg/kg, respectively. These doses were associated with peak arterial total plasma concentrations of 11.4, 4.3 and 5 mcg/mL, respectively.

In human volunteers given intravenous ropivacaine hydrochloride, the mean (min-max) maximum tolerated total and free arterial plasma concentrations were 4.3 (3.4 to 5.3) and 0.6 (0.3 to 0.9) mcg/mL respectively, at which time moderate CNS symptoms (muscle twitching) were noted.

Clinical data from patients experiencing local anesthetic induced convulsions demonstrated rapid development of hypoxia, hypercarbia and acidosis within a minute of the onset of convulsions. These observations suggest that oxygen consumption and carbon dioxide production are greatly increased during local anesthetic convulsions and emphasize the importance of immediate and effective ventilation with oxygen which may avoid cardiac arrest.

If difficulty is encountered in the maintenance of a patent airway or if prolonged ventilatory support (assisted or controlled) is indicated, endotracheal intubation, employing drugs and techniques familiar to the clinician, may be indicated after initial administration of oxygen by mask.

The supine position is dangerous in pregnant women at term because of aortocaval compression by the gravid uterus. Therefore, during treatment of systemic toxicity, maternal hypotension or fetal bradycardia following regional block, the parturient should be maintained in the left lateral decubitus position if possible, or manual displacement of the uterus off the great vessels should be accomplished. Resuscitation of obstetrical patients may take longer than resuscitation of non-pregnant patients and closed-chest cardiac compression may be ineffective. Rapid delivery of the fetus may improve the response to resuscitative efforts.

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL-0.2% (2 mg/mL) - 20 mL Container-Carton (25 Vials)

Rx only             NDC 55150-195-20
Ropivacaine           0.2%
Hydrochloride
Injection, USP
40 mg/20 mL
(2 mg/mL)
For Infiltration, Nerve Block, and
Epidural Administration Only.
Not for Intravenous Administration.
Sterile                             25 x 20 mL
Nonpyrogenic                  Single Dose Vials
AUROMEDICS

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL-1% (10 mg/mL) - 20 mL Container Label

Rx only             NDC 55150-201-20
Ropivacaine     1%
Hydrochloride
Injection, USP
200 mg/20 mL
(10 mg/mL)
For Epidural Administration Only.
Not for Intravenous Administration.
20 mL                Single Dose Vial

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL-1% (10 mg/mL) - 20 mL Container-Carton (25 Vials)

Rx only             NDC 55150-201-20
Ropivacaine      1%
Hydrochloride
Injection, USP
200 mg/20 mL
(10 mg/mL)
For Epidural Administration Only.
Not for Intravenous Administration.
Sterile                              25 x 20 mL
Nonpyrogenic                  Single Dose Vials
AUROMEDICS

ROPIVACAINE HYDROCHLORIDE 
ropivacaine hydrochloride injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:55150-195
Route of Administration INFILTRATION, PERINEURAL, EPIDURAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ROPIVACAINE HYDROCHLORIDE (ROPIVACAINE) ROPIVACAINE HYDROCHLORIDE 2 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
SODIUM CHLORIDE  
HYDROCHLORIC ACID  
SODIUM HYDROXIDE  
WATER  
Packaging
# Item Code Package Description
1 NDC:55150-195-20 25 VIAL, SINGLE-DOSE in 1 CARTON
1 20 mL in 1 VIAL, SINGLE-DOSE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA205612 09/15/2016
ROPIVACAINE HYDROCHLORIDE 
ropivacaine hydrochloride injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:55150-196
Route of Administration INFILTRATION, PERINEURAL, EPIDURAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ROPIVACAINE HYDROCHLORIDE (ROPIVACAINE) ROPIVACAINE HYDROCHLORIDE 2 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
SODIUM CHLORIDE  
HYDROCHLORIC ACID  
SODIUM HYDROXIDE  
WATER  
Packaging
# Item Code Package Description
1 NDC:55150-196-99 1 BOTTLE, GLASS in 1 CARTON
1 100 mL in 1 BOTTLE, GLASS
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA205612 09/15/2016
ROPIVACAINE HYDROCHLORIDE 
ropivacaine hydrochloride injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:55150-197
Route of Administration INFILTRATION, PERINEURAL, EPIDURAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ROPIVACAINE HYDROCHLORIDE (ROPIVACAINE) ROPIVACAINE HYDROCHLORIDE 5 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
SODIUM CHLORIDE  
HYDROCHLORIC ACID  
SODIUM HYDROXIDE  
WATER  
Packaging
# Item Code Package Description
1 NDC:55150-197-20 25 VIAL, SINGLE-DOSE in 1 CARTON
1 20 mL in 1 VIAL, SINGLE-DOSE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA205612 09/15/2016
ROPIVACAINE HYDROCHLORIDE 
ropivacaine hydrochloride injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:55150-198
Route of Administration INFILTRATION, PERINEURAL, EPIDURAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ROPIVACAINE HYDROCHLORIDE (ROPIVACAINE) ROPIVACAINE HYDROCHLORIDE 5 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
SODIUM CHLORIDE  
HYDROCHLORIC ACID  
SODIUM HYDROXIDE  
WATER  
Packaging
# Item Code Package Description
1 NDC:55150-198-30 25 VIAL, SINGLE-DOSE in 1 CARTON
1 30 mL in 1 VIAL, SINGLE-DOSE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA205612 09/15/2016
ROPIVACAINE HYDROCHLORIDE 
ropivacaine hydrochloride injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:55150-199
Route of Administration PERINEURAL, EPIDURAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ROPIVACAINE HYDROCHLORIDE (ROPIVACAINE) ROPIVACAINE HYDROCHLORIDE 7.5 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
SODIUM CHLORIDE  
HYDROCHLORIC ACID  
SODIUM HYDROXIDE  
WATER  
Packaging
# Item Code Package Description
1 NDC:55150-199-20 25 VIAL, SINGLE-DOSE in 1 CARTON
1 20 mL in 1 VIAL, SINGLE-DOSE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA205612 09/15/2016
ROPIVACAINE HYDROCHLORIDE 
ropivacaine hydrochloride injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:55150-200
Route of Administration EPIDURAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ROPIVACAINE HYDROCHLORIDE (ROPIVACAINE) ROPIVACAINE HYDROCHLORIDE 10 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
SODIUM CHLORIDE  
HYDROCHLORIC ACID  
SODIUM HYDROXIDE  
WATER  
Packaging
# Item Code Package Description
1 NDC:55150-200-10 25 VIAL, SINGLE-DOSE in 1 CARTON
1 10 mL in 1 VIAL, SINGLE-DOSE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA205612 09/15/2016
ROPIVACAINE HYDROCHLORIDE 
ropivacaine hydrochloride injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:55150-201
Route of Administration EPIDURAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ROPIVACAINE HYDROCHLORIDE (ROPIVACAINE) ROPIVACAINE HYDROCHLORIDE 10 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
SODIUM CHLORIDE  
HYDROCHLORIC ACID  
SODIUM HYDROXIDE  
WATER  
Packaging
# Item Code Package Description
1 NDC:55150-201-20 25 VIAL, SINGLE-DOSE in 1 CARTON
1 20 mL in 1 VIAL, SINGLE-DOSE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA205612 09/15/2016
Labeler - AuroMedics Pharma LLC (968961354)
Establishment
Name Address ID/FEI Operations
Aurobindo Pharma Limited 650498244 ANALYSIS(55150-195, 55150-196, 55150-197, 55150-198, 55150-199, 55150-200, 55150-201), MANUFACTURE(55150-195, 55150-196, 55150-197, 55150-198, 55150-199, 55150-200, 55150-201)
Revised: 06/2017   AuroMedics Pharma LLC
(web3)