ROCULAX

Description Roculax is a nondepolarizing neuromuscular blocking agent, supplied as a sterile, nonpyrogenic, isotonic solution for intravenous injection only. Composition Each ampoule of Roculax contains Rocuronium bromide 10 mg/mL. Pharmacology Pharmacodynamics : Rocuronium bromide acts by competing for cholinergic receptors at the motor end-plate. This action is antagonized by acetylcholinesterase inhibitors, such as neostigmine and edrophonium. The recovery of neuromuscular function is satisfactory. The neuromuscular blocking action of rocuronium bromide may be enhanced in the presence of potent inhalation anaesthetics. Pharmacokinetics : Rocuronium is a nondepolarizing neuromuscular agent with rapid to intermediate onset depending on dose, and intermediate duration. The rapid distribution half-life is 1-2 minutes and the slower distribution half-life is 14-18 minutes. Rocuronium is approximately 30% bound to human plasma proteins. Rocuronium is eliminated primarily by the liver. The metabolite of rocuronium,17desacetyl-rocuronium, has been rarely observed in the plasma or urine of humans administered single doses of 0.5-1 mg/kgBW with or without a subsequent infusion of rocuronium. Indications Roculax is indicated as an adjunct to general anesthesia to facilitate endotracheal intubation, and to provide skeletal muscle relaxation during surgery. Contraindications Roculax is contraindicated in : - Patients known to have hypersensitivity to rocuronium bromide or to bromide ion. - Pregnancy. Warnings and Precautions

Roculax should be administered in carefully adjusted dosages under the supervision of experienced clinicians who are familiar with the drugs actions and the possible complications of its use. Roculax should not be administrated unless facilities for intubation, artificial respiration, oxygen therapy, and an antagonist are immediately available. It is recommended that administration of Roculax employ a peripheral nerve stimulator to monitor drug response, need for additional relaxant, and adequacy of spontaneous recovery or antagonism. Roculax administration must be accompanied by adequate anaesthesia or sedation. In patients with myasthenia gravis, small doses of nondepolarizing neuromuscular blocking agents may have profound effects.

Roculax, which has an acid pH, should not be mixed with alkaline solutions (e.g. barbiturate solutions) in the same syringe or administered simultaneously during intravenous infusion through the same needle. In the use of Roculax, increases or decreases in MAP (Mean Arterial Pressure) and tachycardia may occurred. Most of the pediatric patients developed tachycardia were anaesthetized with halothane and who did not receive atropine for induction. Laryngoscopy and tracheal intubation following Roculax administration were accompanied by transient tachycardia ( 30 % increment) in adult patients under opioid/ N2O/O2 anaesthesia. The tachycardia observed in some patients may result from this vagal blocking activity. Prolonged paralysis and/or skeletal muscle weakness may be noted during initial attempts to wean from the ventilator patients who have chronically received neuromuscular blocking drugs in the ICU. So Roculax should only be used if the specific advantages of the drug outweigh the risk. Roculax is not recommended for rapid induction in cesarean section patients. Roculax should be used with caution in patients with clinically significant hepatic disease because clinial duration and the recovery was moderately prolonged in these patients. Both respiratory and metabolic acidosis prolonged the recovery time. The potency of Roculax was significantly enhanced in metabolic acidosis and alkalosis, but was reduced in respiratory alkalosis. Severe acid-base and/or electrolyte abnormalities may potentiate or cause resistance to the neuromuscular blocking action of Roculax. Extravasation of Roculax may result signs or symptoms of local irritation; the injection or infusion should be terminated immediately and restarted in another vein. Burns, disuse atrophy, denervation, direct muscle trauma, and cerebral palsy may result the development of resistance to nondepolarizing muscle relaxants.

Other nondepolarizing neuromuscular blocking agents exhibit profound neuromuscular blocking effects in cachectic or debilitated patients, patients with neuromuscular diseases, and patients with carcinomatosis. In these patients a decrease from the recommended initial dose should be considered. Roculax may be associated with increased pulmonary vascular resistance so caution in patients with pulmonary hypertension or valvular heart disease. Anaphylactic reactions to neuromuscular blocking agents in general have been reported Because Roculax is always used with other agents and because the occurrence of malignant hyperthermia during anaesthesia is possible, even in the absence of known triggering agents, clinicians should be familiar with early signs, confirmatory diagnosis and treatment of malignant hyperthermia prior to the start of any anaesthesia. Roculax should be used with caution in patients with clinically significant hepatic and/ or billiary tract diseases and/ or renal failure. Conditions associated with prolonged circulation time such as cardiovascular disease, old age, and oedematous state resulting in an increased volume of distribution, may contribute to a slower onset of action. Like other neuromuscular blocking agents, Roculax should be used with extreme caution in patients with a neuromuscular disease or after poliomyelitis since the response to neuromuscular blocking agents may be considerably altered in these cases. In surgery under hypothermic condition, the neuromuscular blocking effect of Roculax is increased and the duration prolonged. Roculax may exhibit a prolonged duration and a prolonged spontaneous recovery in obese patients. Roculax should be given to lactating women only when the physician decides that the benefits outweigh the risk. It is not recommended to use potentially dangerous machinery or drive a car within 24 hours after the full recovery from the neuromuscular blocking action of Roculax.

Adverse Effects Prolonged neuromuscular block is associated with neuromuscular blockers. Adverse experiences with probable or unknown relationship: Cardiovascular : arrhythmia, abnormal electrocardiogram, tachycardia, hypotension, hypertension. Digestive : nausea, vomiting. Respiratory : asthma (bronchospasm, wheezing, or rhonchi), hiccup. Skin and Appendages : allergic reactions (rash, pruritus, anaphylactic and anaphylactoid), injection site edema. Dosage and Administration - Endotracheal Intubation : The dose is 0.6-1.2 mg/kgBW. - Maintenance Dose: The maintenance dose is 0.1- 0.2 mg/kgBW. - Use by Continuous Infusion:

It is recommended to give loading dose of 0.6 mg Roculax/kgBW, when neuromuscular block starts to recover, to start administration by infusion. In adults under i.v anaesthesia, the infusion rate required to maintain neuromuscular block at this level ranges from 5-10 g/kgBW/min (0,3-0,6 mg/kg/h). Continuous monitoring of neuromuscular block is essential since infusion rate requirements vary from patient to patient and with the anaesthetic method used. Pediatrics : The initial dose is 0.6 mg/kgBW. The maintenance dose is 0.075-0.125 mg/kgBW. A continuous infusion of Roculax initiated at a rate of 0.012 mg/kgBW/min may also be used to maintain neuromuscular blockade in pediatric patients. There are no data to support the recommendation for the use of rocuronium bromide in neonates (0-3 months). Geriatrics ( 65 years) and patients with hepatic and/or biliary tract disease and/or renal failure : The dose is 0.6 - 1.2 mg/kgBW. The maintenance dose is 0.075-0.1 mg/kgBW. The recommended infusion rate is 5-6 g/kgBW/min. Obese Patients : When used in overweight or obese patients (defined as patients with a body weight of 30% or more above ideal body weight) doses should be reduced taking into account a lean body mass.

Administration: Roculax administered intravenously either as a bolus injection or as a continuous infusion. Presentation Ampoules 5 mL in box @ 10 ampoules. Roculax should be stored under refrigeration (2 - 8)C. Do not freeze. Upon removal from refrigeration to room temperature storage conditions (25C), use Roculax within 60 days. Do not use solution if particulate matter is present.