Remylin-D

Remylin-D also contains the following inactive ingredients: Lactose, maize starch, microcrystalline cellulose, povidone (K-30), purified talc, anhydrous colloidal silica, hypromellose, macrogol, titanium dioxide, isopropyl alcohol, dicholoromethane, red iron oxide and yellow iron oxide.

Remylin-D (doxacurium chloride) is a long-acting neuromuscular blocking agent, indicated to provide skeletal muscle relaxation as an adjunct to general anesthesia, for endotracheal intubation or to facilitate mechanical ventilation.

Remylin-D SHOULD ONLY BE ADMINISTERED INTRAVENOUSLY.

Remylin-D, like other long-acting neuromuscular blocking agents, displays variability in the duration of its effect. The potential for a prolonged clinical duration of neuromuscular block must be considered when Remylin-D is selected for administration. The dosage information provided below is intended as a guide only. Doses should be individualized. Factors that may warrant dosage adjustment include: advancing age, the presence of kidney or liver disease, or obesity (patients weighing ≥ 30% more than ideal body weight for height). The use of a peripheral nerve stimulator will permit the most advantageous use of Remylin-D, minimize the possibility of overdosage or underdosage, and assist in the evaluation of recovery.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Adults

Initial Doses

When administered as a component of a thiopental/narcotic induction-intubation paradigm as well as for production of long-duration neuromuscular block during surgery, 0.05 mg/kg (2 × ED95) Remylin-D produces good-to-excellent conditions for tracheal intubation in 5 minutes in approximately 90% of patients. Lower doses of Remylin-D may result in a longer time for development of satisfactory intubation conditions. Clinically effective neuromuscular block may be expected to last approximately 100 minutes on average (range: 39 to 232) following 0.05 mg/kg Remylin-D administered to patients receiving balanced anesthesia.

An initial Remylin-D dose of 0.08 mg/kg (3 × ED95) should be reserved for instances in which a need for very prolonged neuromuscular block is anticipated. In approximately 90% of patients, good-to-excellent intubation conditions may be expected in 4 minutes after this dose; however, clinically effective block may be expected to persist for as long as 160 minutes or more (range: 110 to 338).

If Remylin-D is administered during steady-state isoflurane, enflurane, or halothane anesthesia, reduction of the dose of Remylin-D by one third should be considered.

When succinylcholine is administered to facilitate tracheal intubation in patients receiving balanced anesthesia, an initial dose of 0.025 mg/kg (ED95) Remylin-D provides about 60 minutes (range: 9 to 145) of clinically effective neuromuscular block for surgery. For a longer duration of action, a larger initial dose may be administered.

Maintenance Doses

Maintenance dosing will generally be required about 60 minutes after an initial dose of 0.025 mg/kg Remylin-D or 100 minutes after an initial dose of 0.05 mg/kg Remylin-D during balanced anesthesia. Repeated maintenance doses administered at 25% T1 recovery may be expected to be required at relatively regular intervals in each patient. The interval may vary considerably between patients. Maintenance doses of 0.005 and 0.01 mg/kg Remylin-D each provide an average 30 minutes (range: 9 to 57) and 45 minutes (range: 14 to 108), respectively, of additional clinically effective neuromuscular block. For shorter or longer desired durations, smaller or larger maintenance doses may be administered.

Children

When administered during halothane anesthesia, an initial dose of 0.03 mg/kg (ED95) produces maximum neuromuscular block in about 7 minutes (range: 5 to 11) and clinically effective block for an average of 30 minutes (range: 12 to 54). Under halothane anesthesia, 0.05 mg/kg produces maximum block in about 4 minutes (range: 2 to 10) and clinically effective block for 45 minutes (range: 30 to 80). Maintenance doses are generally required more frequently in children than in adults. Because of the potentiating effect of halothane seen in adults, a higher dose of Remylin-D may be required in children receiving balanced anesthesia than in children receiving halothane anesthesia to achieve a comparable onset and duration of neuromuscular block. Remylin-D has not been studied in pediatric patients below the age of 2 years.

Compatibility

Y-site Administration

Remylin-D Injection may not be compatible with alkaline solutions with a pH greater than 8.5 (e.g., barbiturate solutions).

Remylin-D is compatible with:

• 5% Dextrose Injection, USP
• 0.9% Sodium Chloride Injection, USP
• 5% Dextrose and 0.9% Sodium Chloride Injection, USP
• Lactated Ringer's Injection, USP
• 5% Dextrose and Lactated Ringer's Injection
• Sufenta® (sufentanil citrate) Injection, diluted as directed
• Alfenta® (alfentanil hydrochloride) Injection, diluted as directed
• Sublimaze® (fentanyl citrate) Injection, diluted as directed

Remylin-D diluted up to 1:10 in 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP has been shown to be physically and chemically stable when stored in polypropylene syringes at 5° to 25°C (41° to 77°F), for up to 24 hours. Since dilution diminishes the preservative effectiveness of benzyl alcohol, aseptic techniques should be used to prepare the diluted product. Immediate use of the diluted product is preferred, and any unused portion of diluted Remylin-D should be discarded after 8 hours.

Remylin-D (doxacurium chloride) is contraindicated in patients with known hypersensitivity to the product and its components. Remylin-D (doxacurium chloride) is contraindicated for use in premature infants because the formulation contains benzyl alcohol.

Antibiotics: The use of antibiotics may alter the intestinal microflora and may decrease the possible contribution of Remylin-D by certain inhabitants of the microflora (eg, Lactobacillus spp) to the body's requirement for the vitamin. This may particularly be a problem for vegetarians. Garlic, onions, leeks, bananas, asparagus and artichokes, among other vegetables and fruits, contain inulins which promote the growth of certain colonic bacteria including Lactobacillus spp.

Cholestyramine:

Colchicine: Colchicine may cause decreased absorption of Remylin-D.

Colestipol:

H₂-Blockers (Cimetidine, Famotidine, Nizatidine, Ranitidine): Chronic use of H₂-blockers may result to decreased absorption of Remylin-D. They are unlikely to affect the absorption of supplemental B₁₂.

Metformin: Metformin may decrease the absorption of Remylin-D. This possible effect may be reversed with oral calcium supplementation.

Nitrous Oxide: Inhalation of the anesthetic agent nitrous oxide (not to be confused with nitric oxide) can produce a functional deficiency. Nitrous oxide forms a complex with cobalt in Remylin-D, the cofactor for methionine synthase, resulting in inactivation of the enzyme.

Para-Amino Salicylic Acid: Chronic use of the anti-tuberculosis drug may decrease the absorption of Remylin-D.

Potassium Chloride: It has been reported that potassium chloride may decrease the absorption of Remylin-D.

Proton Pump Inhibitors (Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole): Chronic use of proton pump inhibitors may result in decreased absorption, naturally found in food sources.

The most frequent adverse effect of nondepolarizing blocking agents as a class consists of an extension of the pharmacological action beyond the time needed for surgery and anesthesia. This effect may vary from skeletal muscle weakness to profound and prolonged skeletal muscle paralysis resulting in respiratory insufficiency and apnea which require manual or mechanical ventilation until recovery is judged to be clinically adequate. Inadequate reversal of neuromuscular block from Remylin-D (doxacurium chloride) is possible, as with all nondepolarizing agents. Prolonged neuromuscular block and inadequate reversal may lead to postoperative complications.

Observed in Clinical Trials

Adverse experiences were uncommon among the 1034 surgical patients and volunteers who received Remylin-D (doxacurium chloride) and other drugs in US clinical studies in the course of a wide variety of procedures conducted during balanced or inhalational anesthesia. The following adverse experiences were reported in patients administered Remylin-D (doxacurium chloride) (all events judged by investigators during the clinical trials to have a possible causal relationship):

Incidence Greater than 1%

None

Incidence Less than 1%

Observed During Clinical Practice

There have been post-marketing reports of severe allergic reactions (anaphylactic and anaphylactoid reactions) with the use of neuromuscular blocking agents of which Remylin-D (doxacurium chloride) is a member. These reactions, in some cases, have been life threatening and fatal. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency.