Bupivacaine Liposome Injectable Suspension (Dermapar) Taj Pharma India

What is Dermapar and how is it used?
Dermapar (bupivacaine liposome) is a non-opioid postsurgical analgesic used in the management of postsurgical pain. Dermapar provides prolonged postsurgical analgesia for up to 72 hours with a single-dose local administration at the surgical site.

What Are Side Effects of Dermapar?
Side effects of Dermapar include:

dizziness,
drowsiness,
nausea,
constipation,
vomiting,
itching,
headache,
back pain, or
swelling in your hands or feet.
Tell your doctor if you have serious side effects of Dermapar including:

ringing in your ears;
feeling restless or anxious;
feeling like you might pass out;
speech or vision problems, a metallic taste in your mouth;
numbness or tingling around your mouth;
tremors, twitching, mood changes;
fast heart rate, feeling short of breath, feeling unusually hot or cold;
numbness, weakness, or loss of movement where the injection was given; or
if you still feel numb several hours after your surgery.
DESCRIPTION
Dermapar is a sterile, non-pyrogenic white to off-white preservative-free aqueous suspension of multivesicular liposomes (DepoFoam® drug delivery system) containing bupivacaine. Bupivacaine is present at a concentration of 13.3 mg/mL. After injection of Dermapar into soft tissue, bupivacaine is released from the multivesicular liposomes over a period of time.

Active Ingredient
Bupivacaine is related chemically and pharmacologically to the amide-type local anesthetics. It is a homologue of mepivacaine and is related chemically to lidocaine. All three of these anesthetics contain an amide linkage between the aromatic nucleus and the amino, or piperidine group. They differ in this respect from the procaine-type local anesthetics, which have an ester linkage. Chemically, Bupivacaine is 1-butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide with a molecular weight of 288.4. Bupivacaine has the following structural formula:

Lipid Formulation
The median diameter of the liposome particles ranges from 24 to 31 μm. The liposomes are suspended in a 0.9% sodium chloride solution. Each vial contains bupivacaine at a nominal concentration of 13.3 mg/mL. Inactive ingredients and their nominal concentrations are: cholesterol, 4.7 mg/mL; 1, 2-dipalmitoyl-sn-glycero-3 phospho-rac-(1-glycerol) (DPPG), 0.9 mg/mL; tricaprylin, 2.0 mg/mL; and 1, 2-dierucoylphosphatidylcholine (DEPC), 8.2 mg/mL. The pH of Dermapar is in the range of 5.8 to 7.4.

Liposomal encapsulation or incorporation in a lipid complex can substantially affect a drug’s functional properties relative to those of the unencapsulated or nonlipid-associated drug. In addition, different liposomal or lipid-complexed products with a common active ingredient may vary from one another in the chemical composition and physical form of the lipid component. Such differences may affect functional properties of these drug products. Do not substitute.

INDICATIONS
Dermapar is indicated for single-dose infiltration in adults to produce postsurgical local analgesia and as an interscalene brachial plexus nerve block to produce postsurgical regional analgesia.

Limitations Of Use
Safety and efficacy has not been established in other nerve blocks.

DOSAGE AND ADMINISTRATION
Important Dosage And Administration Information
Dermapar is intended for single-dose administration only.
Different formulations of bupivacaine are not bioequivalent even if the milligram strength is the same. Therefore, it is not possible to convert dosing from any other formulations of bupivacaine to Dermapar. [see Non-Interchangeability with Other Formulations of Bupivacaine].
DO NOT dilute Dermapar with water for injection or other hypotonic agents, as it will result in disruption of the liposomal particles.
Use suspensions of Dermapar diluted with preservative-free normal (0.9%) saline for injection or lactated Ringer’s solution within 4 hours of preparation in a syringe.
Do not administer Dermapar if it is suspected that the vial has been frozen or exposed to high temperature (greater than 40°C or 104°F) for an extended period.
Inspect Dermapar visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer Dermapar if the product is discolored.
Recommended Dosing In Adults
Local Analgesia via Infiltration
The recommended dose of Dermapar for local infiltration in adults is up to a maximum dose of 266 mg (20 mL), and is based on the following factors:

Size of the surgical site
Volume required to cover the area
Individual patient factors that may impact the safety of an amide local anesthetic
As general guidance in selecting the proper dosing, two examples of infiltration dosing are provided:

In patients undergoing bunionectomy, a total of 106 mg (8 mL) of Dermapar was administered, with 7 mL infiltrated into the tissues surrounding the osteotomy, and 1 mL infiltrated into the subcutaneous tissue.
In patients undergoing hemorrhoidectomy, a total of 266 mg (20 mL) of Dermapar was diluted with 10 mL of saline, for a total of 30 mL, divided into six 5 mL aliquots, injected by visualizing the anal sphincter as a clock face and slowly infiltrating one aliquot to each of the even numbers to produce a field block.
Regional Analgesia Via Interscalene Brachial Plexus Nerve Block
The recommended dose of Dermapar for interscalene brachial plexus nerve block in adults is 133 mg (10 mL), and is based upon one study of patients undergoing either total shoulder arthroplasty or rotator cuff repair.

Injection Instructions
Dermapar should be injected slowly (generally 1 to 2 mL per injection) with frequent aspiration to check for blood and minimize the risk of inadvertent intravascular injection. Do not exceed a maximum dosage of 266 mg (20 mL, 1.3% of undiluted drug) for infiltration and 133 mg (10 mL) for interscalene brachial plexus nerve block.

Administer Dermapar undiluted or diluted to increase volume up to a final concentration of 0.89 mg/mL (i.e., 1:14 dilution by volume) with normal (0.9%) saline or lactated Ringer’s solution.
Invert vials of Dermapar multiple times to re-suspend the particles immediately prior to withdrawal from the vial.
Administer Dermapar with a 25 gauge or larger bore needle to maintain the structural integrity of the liposomal bupivacaine particles.
Compatibility Considerations
Some physicochemical incompatibilities exist between Dermapar and certain other drugs. Direct contact of Dermapar with these drugs results in a rapid increase in free (unencapsulated) bupivacaine, altering Dermapar characteristics and potentially affecting the safety and efficacy of Dermapar. Therefore, admixing Dermapar with other drugs prior to administration is not recommended [See DRUG INTERACTIONS].

Non-bupivacaine based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from Dermapar if administered together locally. The administration of Dermapar may follow the administration of lidocaine after a delay of 20 minutes or more.
Bupivacaine HCl administered together with Dermapar may impact the pharmacokinetic and/or physicochemical properties of Dermapar, and this effect is concentration dependent. Therefore, bupivacaine HCl and Dermapar may be administered simultaneously in the same syringe, and bupivacaine HCl may be injected immediately before Dermapar as long as the ratio of the milligram dose of bupivacaine HCl solution to Dermapar does not exceed 1:2. The toxic effects of these drugs are additive and their administration should be used with caution including monitoring for neurologic and cardiovascular effects related to local anesthetic systemic toxicity [See WARNINGS AND PRECAUTIONS and OVERDOSAGE].
When a topical antiseptic such as povidone iodine (e.g., Betadine®) is applied, the site should be allowed to dry before Dermapar is administered into the site. Dermapar should not be allowed to come into contact with antiseptics such as povidone iodine in solution.
Studies conducted with Dermapar demonstrated that the most common implantable materials (polypropylene, PTFE, silicone, stainless steel, and titanium) are not affected by the presence of Dermapar any more than they are by saline. None of the materials studied had an adverse effect on Dermapar.

When administered in recommended doses and concentrations, bupivacaine HCl does not ordinarily produce irritation or tissue damage and does not cause methemoglobinemia.

Non-Interchangeability With Other Formulations Of Bupivacaine
Different formulations of bupivacaine are not bioequivalent even if the milligram dosage is the same. Therefore, it is not possible to convert dosing from any other formulations of bupivacaine to Dermapar and vice versa.

HOW SUPPLIED
Dosage Forms And Strengths
Dermapar (bupivacaine liposome injectable suspension) is a white to off-white, milky aqueous suspension that is available in the following vial sizes:

266 mg/20 mL (13.3 mg/mL) single-dose vial
133 mg/10 mL (13.3 mg/mL) single-dose vial
Storage And Handling
Dermapar (bupivacaine liposome injectable suspension) is a white to off-white milky aqueous suspension that is available in the following single-dose vials.

266 mg/20 mL (13.3 mg/mL) single-dose vial, (NDC 65250-266-20) packaged in cartons of 10 (NDC 65250-266-09) and cartons of 4 (NDC 65250-266-04) 133 mg/10 mL (13.3 mg/mL) single-dose vial, (NDC 65250-133-10) packaged in cartons of 10 (NDC-65250-133-09) and cartons of 4 (NDC 65250-133-04)

Storage
Store Dermapar vials refrigerated between 2°C to 8°C (36°F to 46°F). Dermapar may be held at a controlled room temperature of 20°C to 25°C (68°F to 77°F) for up to 30 days in sealed, intact (unopened) vials. Do not re-refrigerate vials.

Do not freeze or expose Dermapar to high temperatures (greater than 40°C or 104°F) for an extended period. Do not administer Dermapar if it is suspected of having been frozen or exposed to high temperatures. Do not use the vial if the stopper is bulging.