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Ropivacaine Hydrochloride 5 mg/mL Injection — NDC 70121-1735-07 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Ropivacaine Hydrochloride 5 mg/mL Injection — NDC 70121-1735-7 (Billing 70121-1735-07)

by Amneal Pharmaceuticals LLC · 10 POUCH in 1 CARTON / 1 BAG in 1 POUCH / 200 mL in 1 BAG

This is a package of Ropivacaine Hydrochloride 5 mg/mL Injection from Amneal Pharmaceuticals LLC, marketed since Mar 2023 and currently FDA-listed.

NDC 70121-1735-07
🏷️ FDA NDC (as labeled) 70121-1735-7 billing pads the package segment with a zero
This package
Contains200 mL in 1 bag Pack sizes2 compare ↓
Product page 70121-1735-03 Also comes in: 12 pouches 70121-1735-3
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

🚨
Active recall for this product.
Class I · Apr 17, 2025 — Presence of Particulate Matter (Amneal Pharmaceuticals, LLC) · FDA recall D-0402-2025
Lots / codes: Lot #'s: AL240003, AL240004, Exp.: 01/31/2026 · reported May 14, 2025
Check your lot/expiration against the official notice — look up the recall number in the FDA recall database ↗
⚠️
Other active recalls for Ropivacaine Hydrochloride (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Jul 16, 2026 — Presence of Particulate Matter: Hair was found in products (Fresenius Kabi USA, LLC) · FDA recall D-0727-2026
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 70121-1735-7
Product NDC 70121-1735
11-digit billing NDC 70121173507
RxCUI 1734347, 1734355, 1734479, 1734481
UNII V910P86109
UPC 0370121173533, 0370121173434, 0370121173335, 0370121173311 +5 more
Application # ANDA216605
SPL Set ID da1ce22b-6a8e-40a2-afbb-011fa3ed3a8b
Established class (EPC) Amide Local Anesthetic
Physiologic effect Local Anesthesia
Chemical class Amides
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2023-03-17
Route EPIDURAL, INFILTRATION, PERINEURAL
Dosage form INJECTION
Substance ROPIVACAINE HYDROCHLORIDE
TE code (Orange Book) AP · RLD · RS
Quick answers
  • RxCUI (RxNorm): 1734347
Why two NDCs? The FDA registers this code as 70121-1735-7 — a 5-4-1 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the package segment → 70121-1735-07. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Amide Local Anesthetic class.

Pharmacologic class Amide Local Anesthetic
Drug family (ATC) Amides
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

📗 Our plain-language guide HelloPharmacist
  • It numbs part of your body for surgery, such as an epidural for cesarean section, a nerve block or numbing around the incision. It also helps control short-term pain, like after su...
  • A trained clinician gives it as an injection or infusion, so you won't take it at home. It is given slowly in small steps, and your team picks the dose for your procedure.
  • The most common are low blood pressure, nausea, vomiting, a slower heart rate, fever, headache and itching. Your team watches for these and can treat them.
  • Mention ringing in your ears, tingling around the mouth, a metallic taste, dizziness, blurred vision, drowsiness, chest symptoms, trouble breathing, hives or swelling, or bluish sk...
📖 Read our full Ropivacaine guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Try another pack size: 12 pouches
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
70121-1735-07 You're viewing this 10 POUCH in 1 CARTON / 1 BAG in 1 POUCH / 200 mL in 1 BAG 2023-03-17 — Active
70121-1735-03 70121-1735-3 Main listing 12 POUCH in 1 CARTON / 1 BAG in 1 POUCH / 200 mL in 1 BAG 2023-12-04 — Active

Pack size FAQ

What quantity is in this package?
This package is listed by the FDA — 10 pouch in 1 carton / 1 bag in 1 pouch / 200 ml in 1 bag.
What NDC number is used to bill for this package of Ropivacaine Hydrochloride 5 mg/mL Injection?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
ropivacaine hydrochloride 5 mg/mL 25021-0652-82 Sagent 100 ml — AP FDA listed —
Naropin 5 mg/mL 63323-0286-27 Fresenius 25 vials — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mLthis 70121-1735-07 Amneal 10 pouches — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 65145-0108-10 Caplin 10 vials — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 65145-0109-10 Caplin 10 vials — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 71288-0734-21 Meitheal 25 vials — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 85766-0098-01 Sportpharm 1 vial — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 55150-0198-30 Eugia 25 vials — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 70069-0064-01 Somerset 1 vial — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 70069-0063-25 Somerset 25 vials — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 83854-0014-05 Anthea 5 vials — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 68462-0794-62 Glenmark 25 vials — AP FDA listed —
Naropin 5 mg/mL 00404-9924-30 Henry 1 vial — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 55150-0197-20 Eugia 25 vials — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 72603-0218-25 NorthStar 25 vials — AP Discontinued —
Ropivacaine Hydrochloride 5 mg/mL 84549-0164-25 ProPharma 30 ml — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 70121-1734-07 Amneal 10 pouches — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 00143-9197-24 Hikma 100 ml — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 43066-0019-10 Baxter 10 vials — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 43066-0023-10 Baxter 10 vials — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 71288-0735-31 Meitheal 25 vials — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 72572-0707-10 Civica, 10 vials — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 85766-0097-30 Sportpharm 1 vial — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 68462-0778-55 Glenmark 25 vials — AP FDA listed —
Ropivacaine Hydrochloride 5 mg/mL 72603-0217-25 NorthStar 25 vials — AP Discontinued —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2023
On the market since
Mar 2023
📍
2026
Currently FDA-listed
3 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerAmneal Pharmaceuticals LLC
Application holderAMNEAL EU LTD
FDA applicationANDA216605 (ANDA)
Labeler code70121
First marketedMar 2023
Product typeHuman Prescription Drug
Portfolio490 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 111 words ▾

1 INDICATIONS AND USAGE Ropivacaine hydrochloride injection 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.

Ropivacaine hydrochloride is an amide local anesthetic indicated in adults 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.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION See Table 1 for Dosage Recommendations. ( 2.2 )

2.1Important Administration Instructions There have been adverse event reports of chondrolysis in patients receiving intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures. Ropivacaine hydrochloride injection is not approved for this use [ see Warnings and Precautions (5.3) ] . The rapid injection of a large volume of local anesthetic solution should be avoided and fractional (incremental) doses should always be used.

The smallest dose and concentration required to produce the desired result should be administered. The dose of any local anesthetic administered varies with the anesthetic procedure, the area to be anesthetized, the vascularity of the tissues, the number of neuronal segments to be blocked, the depth of anesthesia and degree of muscle relaxation required, the duration of anesthesia desired, individual tolerance, and the physical condition of the patient. 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 mL 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. These products are intended for single-dose and are free from preservatives. Any solution remaining from an opened container should be discarded promptly.

2.2Dosage Recommendations Table 1: 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 * 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 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

1.5Continuous infusion ‡ 2 (0.2%) 6 to 14 mL/hour 12 to 28 mg/hour n/a * n/a * Incremental injections (top-up) ‡ 2 (0.2%) 10 to 15 mL/hour 20 to 30 mg/hour n/a * n/a * POSTOPERATIVE PAIN MANAGEMENT Lumbar Epidural Administration Continuous infusion § 2 (0.2%) 6 to 14 mL/hour 12 to 28 mg/hour n/a * n/a * Thoracic Epidural Administration Continuous infusion § 2 (0.2%) 6 to 14 mL/hour 12 to 28 mg/hour n/a * n/a * 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 * = 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 ( 5.7) ] . ‡ = 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 ov… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 98 words ▾

3 DOSAGE FORMS AND STRENGTHS Ropivacaine hydrochloride injection, USP is a clear, colorless, and preservative-free solution available as: 0.2%, 200 mg per 100 mL (2 mg/mL), 100 mL single-dose, ready-to-use, non-PVC and non-DEHP bag. 0.2%, 400 mg per 200 mL (2 mg/mL), 200 mL single-dose, ready-to-use, non-PVC and non-DEHP bag. 0.5%, 500 mg per 100 mL (5 mg/mL), 100 mL single-dose, ready-to-use, non-PVC and non-DEHP bag.

0.5%, 1,000 mg per 200 mL (5 mg/mL), 200 mL single-dose, ready-to-use, non-PVC and non-DEHP bag. Injection: 2 mg/mL (0.2%) or 5 mg/mL (0.5%), in single-dose ready-to-use, non-PVC and non-DEHP bag. (3)

⛔ Contraindications 35 words ▾

4 CONTRAINDICATIONS Ropivacaine hydrochloride is contraindicated in patients with a known hypersensitivity to ropivacaine or to any local anesthetic agent of the amide type. History of hypersensitivity to local anesthetics of the amide type. (4)

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS 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) In performing ropivacaine hydrochloride blocks, unintended intravenous injection is possible and may result in cardiac arrhythmia or cardia arrest. (5.2) Intra-articular infusions of local anesthetics may cause chondrolysis.

Ropivacaine hydrochloride is not approved for this use. (5.3) Signs of methemoglobinemia may occur. (5.4)

5.1General Warnings and Precautions Prior to receiving major blocks the general condition of the patient should be optimized and the patient should have an intravenous 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 ( 6) and Overdosage ( 10.1) ].

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 (6) ] .

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 anest… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 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. Because clinical trials are conducted under widely conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. 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=3,988): 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 2 and Table 3 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 2: 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 HydrochlorideTotal N=1,661 BupivacaineTotal N=1,433 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 3: Adverse Events Reported in ≥ 1% of Fetuses or Neonates of Mothers Who Received Regional Anesthesia (Cesarean Section and Labor Studies) Adverse Reaction Ropivacaine HydrochlorideTotal N = 639 BupivacaineTotal 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=3,… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS 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 [ see Warnings and Precautions (5.4) ] : 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 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 co-administration 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 co-administered. Possible interactions with drugs known to be metabolized by CYP1A2 via competitive inhibition such as theophylline and imipramine may also occur. Co-administration 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.

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 and Precautions (5.13) ] . Agents structurally related to amide-type local anesthetics: Concurrent use may cause additive effects. (7)

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary There are no available human data on use of ropivacaine injection 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 (see Clinical Considerations) . No teratogenicity was observed at doses up to 0.3 times the maximum recommended human dose of 770 mg/24 hours for epidural use, and equal to the MRHD of 250 mg for nerve block use, based on body surface area (BSA) comparisons and a 60 kg human weight (see Animal data) .

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. Clinical Considerations Labor or 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 ( 12) ] . 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 Adverse reactions Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves.

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 be accomplished. Elevating the patient's legs will also help prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously, and electronic fetal monitoring is highly advisable.

Data Animal data No malformations were reported in embryo-fetal development toxicity studies conducted in pregnant New Zealand white rabbits and Sprague-Dawley rats. During gestation days 6 to 18, rabbits received daily subcutaneous doses of ropivacaine at 1.3, 4.2, or 13 mg/kg/day (equivalent to 0.03, 0.10, and 0.33 times the maximum recommended human dose (MRHD) of 770 mg/24 hours, respectively, and 0.10, 0.32, and 1.0 times the MRHD of 250 mg for nerve block use, respectively based on body surface area (BSA) comparisons and a 60 kg human weight).

Rats received daily subcutaneous doses of 5.3, 11, and 26 mg/kg/day (equivalent to 0.07, 0.14, and 0.33 times the MRHD for epidural use, respectively, and 0.21, 0.43, and 1.0 times the MRHD for nerve block use, respectively, based on BSA comparisons) during GD 6 to 15. No treatment-related effects on late fetal development, parturition, litter size, lactation, neonatal viability, or growth of the offspring were reported in a prenatal and postnatal reproductive and development toxicity study; however functional endpoints were not evaluated.

Female rats were dosed daily subcutaneously from GD 15 to Lactation Day 20 at doses of 5.3, 11, and 26 mg/kg/day (equivalent to 0.07, 0.1, and 0.3 times the MRHD for epidural use, respectively, and 0.21, 0.43, and 1.0 times the MRHD for nerve block use, respectively), with maternal toxicity exhibited at the high dose. No adverse effects in physical developmental milestones or in behavioral tests were reported in a 2-generational reproduction study, in which rats received daily subcutaneous doses of 6.3, 12, and 23 mg/kg/day (equivalent to 0.08, 0.15, and 0.29 tim… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary There are no available human data on use of ropivacaine injection 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 (see Clinical Considerations) . No teratogenicity was observed at doses up to 0.3 times the maximum recommended human dose of 770 mg/24 hours for epidural use, and equal to the MRHD of 250 mg for nerve block use, based on body surface area (BSA) comparisons and a 60 kg human weight (see Animal data) .

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. Clinical Considerations Labor or 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 ( 12) ] . 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 Adverse reactions Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves.

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 be accomplished. Elevating the patient's legs will also help prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously, and electronic fetal monitoring is highly advisable.

Data Animal data No malformations were reported in embryo-fetal development toxicity studies conducted in pregnant New Zealand white rabbits and Sprague-Dawley rats. During gestation days 6 to 18, rabbits received daily subcutaneous doses of ropivacaine at 1.3, 4.2, or 13 mg/kg/day (equivalent to 0.03, 0.10, and 0.33 times the maximum recommended human dose (MRHD) of 770 mg/24 hours, respectively, and 0.10, 0.32, and 1.0 times the MRHD of 250 mg for nerve block use, respectively based on body surface area (BSA) comparisons and a 60 kg human weight).

Rats received daily subcutaneous doses of 5.3, 11, and 26 mg/kg/day (equivalent to 0.07, 0.14, and 0.33 times the MRHD for epidural use, respectively, and 0.21, 0.43, and 1.0 times the MRHD for nerve block use, respectively, based on BSA comparisons) during GD 6 to 15. No treatment-related effects on late fetal development, parturition, litter size, lactation, neonatal viability, or growth of the offspring were reported in a prenatal and postnatal reproductive and development toxicity study; however functional endpoints were not evaluated.

Female rats were dosed daily subcutaneously from GD 15 to Lactation Day 20 at doses of 5.3, 11, and 26 mg/kg/day (equivalent to 0.07, 0.1, and 0.3 times the MRHD for epidural use, respectively, and 0.21, 0.43, and 1.0 times the MRHD for nerve block use, respectively), with maternal toxicity exhibited at the high dose. No adverse effects in physical developmental milestones or in behavioral tests were reported in a 2-generational reproduction study, in which rats received daily subcutaneous doses of 6.3, 12, and 23 mg/kg/day (equivalent to 0.08, 0.15, and 0.29 times the MRHD for epidural use,… [Excerpted — this section continues on DailyMed.]

🆘 Overdosage ~3 min read ▾

10 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 (6) and Warnings and Precautions ( 5.1 , 5.2 , 5.6) ].

10.1Treatment 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, nonpregnant and pregnant sheep were 4.9 mg/kg, 6.1 mg/kg and 5.9 mg/kg, respectively. These doses were associated with peak arterial total plasma concentrations of 11.4 mcg/mL, 4.3 mcg/mL 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) mcg/mL 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 clos… [Excerpted — this section continues on DailyMed.]

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action 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.

12.2Pharmacodynamics Studies in humans have demonstrated that, unlike most other local anesthetics, the presence of epinephrine has no major effect on either the time of onset or the duration of action of ropivacaine. Likewise, addition of epinephrine to ropivacaine has no effect on limiting systemic absorption of ropivacaine. Systemic absorption of local anesthetics can produce effects on the central nervous and cardiovascular systems.

At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance have been reported. Toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure.

Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression or both. Apparent central stimulation is usually manifested as restlessness, tremors and shivering, progressing to convulsions, followed by depression and coma, progressing ultimately to respiratory arrest. However, the local anesthetics have a primary depressant effect on the medulla and on higher centers.

The depressed stage may occur without a prior excited stage. In 2 clinical pharmacology studies (total n=24) ropivacaine and bupivacaine were infused (10 mg/min) in human volunteers until the appearance of CNS symptoms, e.g., visual or hearing disturbances, perioral numbness, tingling and others. Similar symptoms were seen with both drugs.

In 1 study, the mean ± SD maximum tolerated intravenous dose of ropivacaine infused (124 mg ± 38 mg) was significantly higher than that of bupivacaine (99 mg ± 30 mg) while in the other study the doses were not different (115 mg ± 29 mg of ropivacaine and 103 mg ± 30 mg of bupivacaine). In the latter study, the number of subjects reporting each symptom was similar for both drugs with the exception of muscle twitching which was reported by more subjects with bupivacaine than ropivacaine at comparable intravenous doses.

At the end of the infusion, ropivacaine in both studies caused significantly less depression of cardiac conductivity (less QRS widening) than bupivacaine. Ropivacaine and bupivacaine caused evidence of depression of cardiac contractility, but there were no changes in cardiac output. 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. However, no pharmacokinetic differences were observed between elderly and younger patients. In non-clinical pharmacology studies comparing ropivacaine and bupivacaine in several animal species, the cardiac toxicity of ropivacaine was less than that of bupivacaine, although both were considerably more toxic than lidocaine.

Arrhythmogenic and cardio-depressant eff… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 107 words ▾

12.1Mechanism of Action 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.

📦 How Supplied / Storage and Handling 215 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Ropivacaine Hydrochloride Injection USP, 2 mg/mL is clear, colourless solution filled in infusion bag. Each mL contains 2 mg ropivacaine hydrochloride, USP. It is available as follows: Strength Each Unit of Sale 200 mg/100 mL (2 mg/mL) NDC 70121-1732-1 1 Single-dose Infusion Bag in an Overwrap NDC 70121-1732-9 Unit of 24 NDC 70121-1732-3 Unit of 12 400 mg/200 mL (2 mg/mL) NDC 70121-1733-1 1 Single-dose Infusion Bag in an Overwrap NDC 70121-1733-9 Unit of 24 NDC 70121-1733-3 Unit of 12 Ropivacaine Hydrochloride Injection USP, 5 mg/mL is clear, colourless solution filled in infusion bag.

Each mL contains 5 mg ropivacaine hydrochloride, USP. It is available as follows: Strength Each Unit of Sale 500 mg/100 mL (5 mg/mL) NDC 70121-1734-1 1 Single-dose Infusion Bag in an Overwrap NDC 70121-1734-7 Unit of 10 NDC 70121-1734-3 Unit of 12 1,000 mg/200 mL (5 mg/mL) NDC 70121-1735-1 1 Single-dose Infusion Bag in an Overwrap NDC 70121-1735-7 Unit of 10 NDC 70121-1735-3 Unit of 12 The 100 mL and 200 mL infusion bags are not made with natural rubber latex, non-PVC, and Non-DEHP with dual PP ports. Storage Store at 20º to 25°C (68º to 77°F) [see USP Controlled Room Temperature].

These products are intended for single-dose and are free from preservatives. Discard Unused Portion.

📋 Description ~1 min read ▾

11 DESCRIPTION Ropivacaine hydrochloride injection, USP is a sterile, isotonic solution that contains ropivacaine hydrochloride, USP as the active pharmaceutical ingredient. Ropivacaine hydrochloride, USP is a member of the amino amide class of local anesthetics. Ropivacaine hydrochloride injection, USP is administered parenterally by for infiltration, epidural, and nerve block.

Ropivacaine hydrochloride, USP is chemically described as (S)-(–)-1-propylpiperidine-2-carboxylic acid (2,6-dimethylphenyl)amide hydrochloride monohydrate. The drug substance is a white crystalline powder, with the following structural formula: Molecular Formula: C 17 H 26 N 2 O•HCl•H 2 O Molecular Weight: 328.88 g/mol At 25 °C ropivacaine hydrochloride, USP 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 hydrochloride, USP has an intermediate degree of lipid solubility compared to bupivacaine and mepivacaine.

Ropivacaine hydrochloride injection, USP is a clear, colorless, and preservative-free solution, available in single-dose infusion bag in 2 mg/mL (0.2%) and 5 mg/mL (0.5%) concentrations. Each mL contains ropivacaine hydrochloride USP, 2 mg or 5 mg (equivalent to 2.12 mg or 5.29 mg ropivacaine hydrochloride monohydrate) and sodium chloride 8.6 mg or 8.0 mg; respectively, and sodium hydroxide and hydrochloric acid as pH adjusters, in water for injection. The pH is adjusted between 4.0 to 6.0.

The specific gravity of ropivacaine hydrochloride injection, USP solutions range from 1.002 to 1.005 at 25°C. 1

💬 Information for Patients 139 words ▾

17 PATIENT COUNSELING INFORMATION

17.1Information for Patients and Caregivers 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 injection 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. Manufactured by: Amneal Pharmaceuticals Pvt. Ltd.

Mehsana, 382165, INDIA Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807 Rev. 04-2024-03 1

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption The systemic concentration of ropivacaine is dependent on the total dose and concentration of drug administered, the route of administration, the patient's hemodynamic/circulatory condition, and the vascularity of the administration site. From the epidural space, ropivacaine shows complete and biphasic absorption. The half-lives of the 2 phases, (mean ± SD) are 14 minutes ± 7 minutes and 4.2 hours ± 0.9 hour, respectively.

The slow absorption is the rate limiting factor in the elimination of ropivacaine that explains why the terminal half-life is longer after epidural than after intravenous administration. Ropivacaine shows dose-proportionality up to the highest intravenous dose studied, 80 mg, corresponding to a mean ± SD peak plasma concentration of 1.9 mcg/mL ± 0.3 mcg/mL. Table 7: Pharmacokinetic (Plasma Concentration-Time) Data From Clinical Trials Route Epidural Infusion * Epidural Infusion * Epidural Block † Epidural Block † Plexus Block ‡ Intravenous Infusion § Dose (mg) 1,493 ± 10 2,075 ± 206 1,217 ± 277 150 187.5 300 40 N 12 12 11 8 8 10 12 C max (mg/L) 2.4 ± 1 ¶ 2.8 ± 0.5 ¶ 2.3 ± 1.1 ¶ 1.1 ± 0.2 1.6 ± 0.6 2.3 ± 0.8 1.2 ± 0.2 # T max (min) n/a ♠ n/a n/a 43 ± 14 34 ± 9 54 ± 22 n/a AUC 0- (mg.h/L) 135.5 ± 50 145 ± 34 161 ± 90 7.2 ± 2 11.3 ± 4 13 ± 3.3 1.8 ±

0.6CL (L/h) 11.03 13.7 n/a 5.5 ± 2 5 ± 2.6 n/a 21.2 ± 7 t 1/2 (hour) ♥ 5 ± 2.5 5.7 ± 3 6 ± 3 5.7 ± 2 7.1 ± 3 6.8 ± 3.2 1.9 ± 0.5 * Continuous 72 hour epidural infusion after an epidural block with 5 mg/mL or 10 mg/mL. † Epidural anesthesia with 7.5 mg/mL (0.75%) for cesarean delivery. ‡ Brachial plexus block with 7.5 mg/mL (0.75%) ropivacaine. § 20 minute intravenous infusion to volunteers (40 mg). ¶ C max measured at the end of infusion (i.e. at 72 hour). # C max measured at the end of infusion (i.e. at 20 minutes). ♠ n/a=not applicable ♥ t &frac12; is the true terminal elimination half-life.

On the other hand, t &frac12; follows absorption dependent elimination (flip-flop) after non-intravenous administration. In some patients after a 300 mg dose for brachial plexus block, free plasma concentrations of ropivacaine may approach the threshold for CNS toxicity [ see Warnings and Precautions (5.7) ] . At a dose of greater than 300 mg, for local infiltration, the terminal half-life may be longer (> 30 hours).

Distribution After intravascular infusion, ropivacaine has a steady-state volume of distribution of 41 liters ± 7 liters. Ropivacaine is 94% protein bound, mainly to α1-acid glycoprotein. An increase in total plasma concentrations during continuous epidural infusion has been observed, related to a postoperative increase of α1-acid glycoprotein.

Variations in unbound, i.e. pharmacologically active, concentrations have been less than in total plasma concentration. Ropivacaine readily crosses the placenta and equilibrium in regard to unbound concentration will be rapidly reached [ see Warnings and Precautions ( 5) and Use in Specific Population (8.1) ] . Metabolism Ropivacaine is extensively metabolized in the liver, predominantly by aromatic hydroxylation mediated by cytochrome P4501A to 3-hydroxy ropivacaine.

After a single intravenous dose approximately 37% of the total dose is excreted in the urine as both free and conjugated 3-hydroxy ropivacaine. Low concentrations of 3-hydroxy ropivacaine have been found in the plasma. Urinary excretion of the 4 hydroxy ropivacaine, and both the 3-hydroxy N de alkylated (3-OH-PPX) and 4-hydroxy N-de-alkylated (4-OH-PPX) metabolites account for less than 3% of the dose.

An additional metabolite, 2-hydroxy-methyl-ropivacaine, has been identified but not quantified in the urine. The N-de-alkylated metabolite of ropivacaine (PPX) and 3-OH-ropivacaine are the major metabolites excreted in the urine during epidural infusion. Total PPX concentration in the plasma was about half as that of total ropivacaine; however, mean unbound concentrations of PPX were about 7 to 9 times higher than that of unboun… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics ~2 min read ▾

12.2Pharmacodynamics Studies in humans have demonstrated that, unlike most other local anesthetics, the presence of epinephrine has no major effect on either the time of onset or the duration of action of ropivacaine. Likewise, addition of epinephrine to ropivacaine has no effect on limiting systemic absorption of ropivacaine. Systemic absorption of local anesthetics can produce effects on the central nervous and cardiovascular systems.

At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance have been reported. Toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure.

Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression or both. Apparent central stimulation is usually manifested as restlessness, tremors and shivering, progressing to convulsions, followed by depression and coma, progressing ultimately to respiratory arrest. However, the local anesthetics have a primary depressant effect on the medulla and on higher centers.

The depressed stage may occur without a prior excited stage. In 2 clinical pharmacology studies (total n=24) ropivacaine and bupivacaine were infused (10 mg/min) in human volunteers until the appearance of CNS symptoms, e.g., visual or hearing disturbances, perioral numbness, tingling and others. Similar symptoms were seen with both drugs.

In 1 study, the mean ± SD maximum tolerated intravenous dose of ropivacaine infused (124 mg ± 38 mg) was significantly higher than that of bupivacaine (99 mg ± 30 mg) while in the other study the doses were not different (115 mg ± 29 mg of ropivacaine and 103 mg ± 30 mg of bupivacaine). In the latter study, the number of subjects reporting each symptom was similar for both drugs with the exception of muscle twitching which was reported by more subjects with bupivacaine than ropivacaine at comparable intravenous doses.

At the end of the infusion, ropivacaine in both studies caused significantly less depression of cardiac conductivity (less QRS widening) than bupivacaine. Ropivacaine and bupivacaine caused evidence of depression of cardiac contractility, but there were no changes in cardiac output. 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. However, no pharmacokinetic differences were observed between elderly and younger patients. In non-clinical pharmacology studies comparing ropivacaine and bupivacaine in several animal species, the cardiac toxicity of ropivacaine was less than that of bupivacaine, although both were considerably more toxic than lidocaine.

Arrhythmogenic and cardio-depressant effects were seen in animals at significantly higher doses of ropivacaine than bupivacaine. The incidence of successful resuscitation was not significantly different between the ropivacaine and bupivacaine groups.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES Ropivacaine was studied as a local anesthetic both for surgical anesthesia and for acute pain management [ see Dosage and Administration (2) ] . The onset, depth and duration of sensory block are, in general, similar to bupivacaine. However, the depth and duration of motor block, in general, are less than that with bupivacaine.

14.1Epidural Administration in Surgery There were 25 clinical studies performed in 900 patients to evaluate ropivacaine hydrochloride epidural injection for general surgery. Ropivacaine hydrochloride was used in doses ranging from 75 mg to 250 mg. In doses of 100 mg to 200 mg, the median (1st to 3rd quartile) onset time to achieve a T10 sensory block was 10 (5 to 13) minutes and the median (1st to 3rd quartile) duration at the T10 level was 4 (3 to 5) hours [ see Dosage and Administration (2.2) ] .

Higher doses produced a more profound block with a greater duration of effect.

14.2Epidural Administration in Cesarean Section A total of 12 studies were performed with epidural administration of ropivacaine hydrochloride for cesarean section. Eight of these studies involved 218 patients using the concentration of 5 mg/mL (0.5%) in doses up to 150 mg. Median onset measured at T6 ranged from 11 minutes to 26 minutes.

Median duration of sensory block at T6 ranged from 1.7 hours to 3.2 hours, and duration of motor block ranged from 1.4 hours to 2.9 hours. Ropivacaine hydrochloride provided adequate muscle relaxation for surgery in all cases. In addition, 4 active controlled studies for cesarean section were performed in 264 patients at a concentration of 7.5 mg/mL (0.75%) in doses up to 187.5 mg.

Median onset measured at T6 ranged from 4 minutes to 15 minutes. Seventy-seven to 96% of ropivacaine hydrochloride-exposed patients reported no pain at delivery. Some patients received other anesthetic, analgesic, or sedative modalities during the course of the operative procedure.

14.3Epidural Administration in Labor and Delivery A total of 9 double-blind clinical studies, involving 240 patients were performed to evaluate ropivacaine hydrochloride for epidural block for management of labor pain. When administered in doses up to 278 mg as intermittent injections or as a continuous infusion, ropivacaine hydrochloride produced adequate pain relief. A prospective meta-analysis on 6 of these studies provided detailed evaluation of the delivered newborns and showed no difference in clinical outcomes compared to bupivacaine.

There were significantly fewer instrumental deliveries in mothers receiving ropivacaine as compared to bupivacaine. Table 8: Labor and Delivery Meta-analysis: Mode of Delivery Delivery Mode Ropivacaine Hydrochloride n=199 Bupivacaine n=188 n % n % Spontaneous Vertex 116 58 92 49 Vacuum Extractor 26 33 }27* }40 Forceps 28 42 Cesarean Section 29 15 21 11 *p=0.004 versus bupivacaine.

14.4Epidural Administration in Postoperative Pain Management There were 8 clinical studies performed in 382 patients to evaluate ropivacaine hydrochloride 2 mg/mL (0.2%) for postoperative pain management after upper and lower abdominal surgery and after orthopedic surgery. The studies utilized intravascular morphine via PCA as a rescue medication and quantified as an efficacy variable. Epidural anesthesia with ropivacaine hydrochloride 5 mg/mL, (0.5%) was used intraoperatively for each of these procedures prior to initiation of postoperative ropivacaine hydrochloride.

The incidence and intensity of the motor block were dependent on the dose rate of ropivacaine hydrochloride and the site of injection. Cumulative doses of up to 770 mg of ropivacaine were administered over 24 hours (intraoperative block plus postoperative continuous infusion). The overall quality of pain relief, as judged by the patients, in the ropivacaine groups was rated as good or excellent (73% to 100%).

The frequency of motor block was greatest at 4 hours and decreased during the infusion period in all groups. At least 80% of patients… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 212 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term studies in animals to evaluate the carcinogenic potential of ropivacaine have not been conducted. Mutagenesis Weak mutagenic activity was seen in the mouse lymphoma test. However, ropivacaine was negative in an in vitro Ames assay and an in vivo mouse micronucleus assay.

Impairment of Fertility No adverse effects on fertility or early embryonic development were reported in a 2-generational reproduction study in which female rats (F 0 ) were administered subcutaneous doses of 6.3, 12, and 23 mg/kg/day (equivalent to 0.08, 0.15, and 0.29 times the maximum recommended human dose (MRHD) of 770 mg/24 hours for epidural use, respectively, and 0.24, 0.45, and 0.88 times the MRHD of 250 mg for nerve block use, respectively, based on BSA comparisons and a 60 kg human) throughout the mating period and pregnancy, partus, and lactation.

13.2Animal Toxicology and/or Pharmacology The mean dosages of ropivacaine producing seizures, after intravenous infusion in dogs, nonpregnant and pregnant sheep were 4.9 mg/kg, 6.1 mg/kg and 5.9 mg/kg (HED: 5.3 mg/kg, 6.6 mg/kg, and 6.4 mg/kg, based on 75 kg sheep weight and 60 kg human weight), respectively. These doses were associated with peak arterial total plasma concentrations of 11.4 mcg/mL, 4.3 mcg/mL and 5 mcg/mL, respectively.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 141 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term studies in animals to evaluate the carcinogenic potential of ropivacaine have not been conducted. Mutagenesis Weak mutagenic activity was seen in the mouse lymphoma test. However, ropivacaine was negative in an in vitro Ames assay and an in vivo mouse micronucleus assay.

Impairment of Fertility No adverse effects on fertility or early embryonic development were reported in a 2-generational reproduction study in which female rats (F 0 ) were administered subcutaneous doses of 6.3, 12, and 23 mg/kg/day (equivalent to 0.08, 0.15, and 0.29 times the maximum recommended human dose (MRHD) of 770 mg/24 hours for epidural use, respectively, and 0.24, 0.45, and 0.88 times the MRHD of 250 mg for nerve block use, respectively, based on BSA comparisons and a 60 kg human) throughout the mating period and pregnancy, partus, and lactation.

📄 Package Label / Principal Display Panel ~1 min read ▾

PRINCIPAL DISPLAY PANEL Red Cautionary Sticker Label 1 NDC 70121-1732-1 Ropivacaine Hydrochloride Injection USP, 2 mg/mL Rx only Infusion Bag Label Amneal Pharmaceuticals LLC NDC 70121-1732-1 Ropivacaine Hydrochloride Injection USP, 2 mg/mL Rx only Pouch Label Amneal Pharmaceuticals LLC NDC 70121-1732-9 Ropivacaine Hydrochloride Injection USP, 2 mg/mL Rx only 24 x 100 mL Carton Label Amneal Pharmaceuticals LLC NDC 70121-1732-3 Ropivacaine Hydrochloride Injection USP, 2 mg/mL Rx only 12 x 100 mL Carton Label Amneal Pharmaceuticals LLC as 1 1 1 NDC 70121-1733-1 Ropivacaine Hydrochloride Injection USP, 2 mg/mL Rx only Infusion Bag Label Amneal Pharmaceuticals LLC NDC 70121-1733-1 Ropivacaine Hydrochloride Injection USP, 2 mg/mL Rx only Pouch Label Amneal Pharmaceuticals LLC NDC 70121-1733-9 Ropivacaine Hydrochloride Injection USP, 2 mg/mL Rx only 24 x 100 mL Carton Label Amneal Pharmaceuticals LLC NDC 70121-1733-3 Ropivacaine Hydrochloride Injection USP, 2 mg/mL Rx only 12 x 100 mL Carton Label Amneal Pharmaceuticals LLC as 1 1 1 NDC 70121-1734-1 Ropivacaine Hydrochloride Injection USP, 5 mg/mL Rx only Infusion Bag Label Amneal Pharmaceuticals LLC NDC 70121-1734-1 Ropivacaine Hydrochloride Injection USP, 5 mg/mL Rx only Pouch Label Amneal Pharmaceuticals LLC NDC 70121-1734-7 Ropivacaine Hydrochloride Injection USP, 5 mg/mL Rx only 10 x 100 mL Carton Label Amneal Pharmaceuticals LLC NDC 70121-1734-3 Ropivacaine Hydrochloride Injection USP, 5 mg/mL Rx only 12 x 100 mL Carton Label Amneal Pharmaceuticals LLC ty 1 1 1 NDC 70121-1735-1 Ropivacaine Hydrochloride Injection USP, 5 mg/mL Rx only Infusion Bag Label Amneal Pharmaceuticals LLC NDC 70121-1735-1 Ropivacaine Hydrochloride Injection USP, 5 mg/mL Rx only Pouch Label Amneal Pharmaceuticals LLC NDC 70121-1735-7 Ropivacaine Hydrochloride Injection USP, 5 mg/mL Rx only 10 x 100 mL Carton Label Amneal Pharmaceuticals LLC NDC 70121-1735-3 Ropivacaine Hydrochloride Injection USP, 5 mg/mL Rx only 12 x 100 mL Carton Label Amneal Pharmaceuticals LLC kl 1 1 1

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Amneal Pharmaceuticals LLC. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 12 pouches (70121-1735-03). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Amneal Pharmaceuticals LLC is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 70121-1734-07 · Amneal 70121-1743-04 · Amneal →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.