Naropin^® (Solution) Instructions for Use

Marketing Authorization Holder

Aspen Pharma Trading, Limited (Ireland)

Manufactured By

AstraZeneca AB (Sweden)

Or

AstraZeneca, Pty. Ltd. (Australia)

ATC Code

N01BB09 (Ropivacaine)

Active Substance

Ropivacaine (Rec.INN registered by WHO)

Dosage Forms

	Naropin®	Solution for injection 2 mg/1 ml: amp. 10 ml 5 pcs.
		Solution for injection 2 mg/1 ml: amp. 20 ml 5 pcs.
		Solution for injection 2 mg/1 ml: containers 100 ml 5 pcs.
		Solution for injection 7.5 mg/1 ml: amp. 10 ml 5 pcs.
		Solution for injection 7.5 mg/1 ml: amp. 20 ml 5 pcs.
		Solution for injection 10 mg/1 ml: amp. 10 ml 5 pcs.
		Solution for injection 10 mg/1 ml: amp. 20 ml 5 pcs.

Dosage Form, Packaging, and Composition

Solution for injection transparent, colorless.

Excipients : sodium chloride, hydrochloric acid or sodium hydroxide (to pH 4-6), water for injection.

10 ml – plastic ampoules (5) – blister packs (1) – cardboard boxes.

Solution for injection transparent, colorless.

Excipients : sodium chloride – 8.6 mg, 2M sodium hydroxide solution and/or 2M hydrochloric acid solution (to adjust pH to 4-6), water for injection – up to 1 ml.

20 ml – polypropylene ampoules (5) – blister packs (1) – cardboard packs with first opening control.

Solution for injection transparent, colorless.

Excipients : sodium chloride – 8.6 mg, 2M sodium hydroxide solution and/or 2M hydrochloric acid solution (to adjust pH to 4-6), water for injection – up to 1 ml.

100 ml – polypropylene containers (bags) (1) – blister packs (5) – cardboard packs.

Solution for injection transparent, colorless.

Excipients : sodium chloride – 7.5 mg, 2M sodium hydroxide solution and/or 2M hydrochloric acid solution (to adjust pH to 4-6), water for injection – up to 1 ml.

10 ml – polypropylene ampoules (5) – blister packs (1) – cardboard packs with first opening control.

Solution for injection transparent, colorless.

Excipients : sodium chloride, hydrochloric acid or sodium hydroxide (to pH 4-6), water for injection.

20 ml – plastic ampoules (5) – blister packs (1) – cardboard boxes.

Solution for injection transparent, colorless.

Excipients : sodium chloride – 7.1 mg, 2M sodium hydroxide solution and/or 2M hydrochloric acid solution (to adjust pH to 4-6), water for injection – up to 1 ml.

10 ml – polypropylene ampoules (5) – blister packs (1) – cardboard boxes with first opening control.

Solution for injection transparent, colorless.

Excipients : sodium chloride, hydrochloric acid or sodium hydroxide (to pH 4-6), water for injection.

20 ml – plastic ampoules (5) – blister packs (1) – cardboard boxes.

Clinical-Pharmacological Group

Local anesthetic

Pharmacotherapeutic Group

Local anesthetic agent

Pharmacological Action

Local anesthetic of the amide type. It causes anesthesia and has an analgesic effect. In high doses, it causes surgical anesthesia; in lower doses, it causes sensory blockade with limited non-progressive motor blockade.

The mechanism of action is associated with a reversible decrease in the permeability of the nerve fiber membrane to sodium ions. As a result, the rate of depolarization decreases and the excitation threshold increases, leading to a local blockade of nerve impulses.

At a significantly increased dose, it has a depressant effect on the CNS and myocardium (reduces excitability and automaticity, impairs conductivity). Ropivacaine is characterized by a long duration of action. The duration of anesthesia depends on the dose and route of administration but does not depend on the presence of a vasoconstrictor.

Pharmacokinetics

After epidural administration, Ropivacaine is completely absorbed from the epidural space. Absorption is biphasic. The concentration of ropivacaine in blood plasma depends on the dose, route of administration, and vascularity of the injection area.

The pharmacokinetics of ropivacaine are linear; C_max in blood plasma is proportional to the dose.

The V_d of ropivacaine is 47 L. Binding in blood plasma occurs mainly with α₁-acid glycoproteins; the unbound fraction is about 6%.

Long-term epidural administration of ropivacaine leads to an increase in the total ropivacaine content in blood plasma, which is due to a postoperative increase in the level of α₁-acid glycoproteins in the blood. However, the concentration of unbound, pharmacologically active ropivacaine changes to a much lesser extent than its total concentration in blood plasma.

It is actively metabolized in the body, mainly by hydroxylation. The main metabolite is 3-hydroxy-ropivacaine.

T_1/2 in the initial and terminal phases is 14 min and 4 h, respectively. Total plasma clearance is 440 ml/min. After IV administration, about 86% of the dose is excreted in the urine, mainly as metabolites, and only about 1% of the dose is excreted unchanged in the urine. About 37% of 3-hydroxy-ropivacaine is excreted in the urine, mainly as conjugates.

Indications

Anesthesia for surgical interventions: epidural blockade for surgical interventions, including cesarean section; blockade of large nerves and nerve plexuses; blockade of individual nerves and local infiltration anesthesia.

Relief of acute pain syndrome: prolonged epidural infusion or intermittent bolus administration, for example, for postoperative pain relief or labor analgesia; blockade of individual nerves and local infiltration anesthesia.

ICD codes

Dosage Regimen

Determine the dosage individually based on the surgical procedure, anesthesia technique, and the patient’s physical status and cardiac condition.

For epidural anesthesia in lumbar region for surgery, administer 15-20 mL of 7.5 mg/mL solution or 15-25 mL of 5.0 mg/mL solution. For cesarean section, administer a 20-30 mL incremental dose of 5.0 mg/mL solution.

For epidural analgesia in lumbar region for labor pain, initiate with a 10-20 mL bolus of 2.0 mg/mL solution. Follow with continuous infusion or intermittent boluses; a typical infusion rate is 6-14 mL/hour of 2.0 mg/mL solution.

For major nerve block such as brachial plexus, administer 30-40 mL of 7.5 mg/mL solution. For field block, use doses up to 200 mg for the 2 mg/mL and 7.5 mg/mL concentrations, and up to 250 mg for the 10 mg/mL concentration.

Adjust the dose for elderly or debilitated patients. Reduce the dose in patients with severe hepatic impairment or advanced renal failure.

Always administer the lowest effective dose and aspirate frequently to check for intravascular placement. Be prepared to manage systemic toxic reactions.

Adverse Reactions

Allergic reactions skin manifestations, anaphylactic shock.

Most side effects occurring during anesthesia are associated not with the effect of the anesthetic used, but with the technique of performing regional anesthesia. The following adverse effects were most frequently (more than 1%) noted and were considered clinically significant regardless of whether a causal relationship with the use of the anesthetic was established.

Cardiovascular system arterial hypertension, arterial hypotension, bradycardia, tachycardia.

Digestive system nausea, vomiting.

CNS and peripheral nervous system headache, dizziness, paresthesia.

Neuropathy and spinal cord dysfunction (anterior spinal artery syndrome, arachnoiditis) are usually associated with the technique of performing regional anesthesia, not with the action of ropivacaine.

Other increased body temperature, chills, urinary retention.

Contraindications

Children under 12 years of age, hypersensitivity to local anesthetics of the amide type.

Use in Pregnancy and Lactation

Use during pregnancy is possible in cases where the potential benefit of therapy for the mother outweighs the existing risk to the fetus. There is evidence of the absence of negative effects when using ropivacaine in obstetrics for anesthesia or analgesia. Ropivacaine penetrates the placental barrier well. Binding to plasma proteins in the fetus is lower than in the mother.

If use during lactation is necessary, it should be taken into account that Ropivacaine is excreted in breast milk in small amounts.

Use in Hepatic Impairment

Ropivacaine should be administered with caution to patients with progressive liver cirrhosis. In patients with severe liver disease, due to impaired elimination, it may be necessary to reduce the dose of ropivacaine with repeated administrations.

Use in Renal Impairment

Ropivacaine should be administered with caution to patients with significant renal impairment. Usually, in patients with renal impairment, no dose adjustment is required for single administration or short-term infusion. However, acidosis and hypoproteinemia are often observed in chronic renal failure, which increases the risk of systemic toxic effects of ropivacaine. In such cases, the doses of ropivacaine should be reduced.

Pediatric Use

Contraindicated in children under 12 years of age.

Special Precautions

The procedure of regional anesthesia should be performed by an experienced specialist with the availability of equipment and medications for resuscitation. Before performing major blocks, IV catheters should be placed.

Ropivacaine should be administered with caution to patients with severe concomitant diseases (including partial or complete heart block, progressive liver cirrhosis, significant renal impairment). To reduce the risk of developing severe side effects, pre-treatment of concomitant diseases before performing major blocks, as well as adjustment of the used anesthetic dose, is necessary. In patients with severe liver disease, due to impaired elimination, it may be necessary to reduce the dose of ropivacaine with repeated administrations. Usually, in patients with renal impairment, no dose adjustment is required for single administration or short-term infusion. However, acidosis and hypoproteinemia are often observed in chronic renal failure, which increases the risk of systemic toxic effects of ropivacaine. In such cases, the doses of ropivacaine should be reduced.

If ropivacaine is accidentally administered intravascularly, symptoms of intoxication may develop, appearing immediately or after a delay.

Effect on ability to drive vehicles and operate machinery

The use of ropivacaine may lead to temporary impairment of motor functions, coordination of movements, and speed of psychomotor reactions. The period of time after which one can engage in potentially hazardous activities requiring increased attention is determined individually.

Drug Interactions

With simultaneous use of ropivacaine with other local anesthetics or drugs structurally similar to local anesthetics of the amide type, summation of effects is possible.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.