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Nuromax (Doxacurium Chloride) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis and fertility studies have not been performed. NUROMAX was evaluated in a battery of four short-term mutagenicity tests. It was nonmutagenic in the Ames Salmonella assay, in the mouse lymphoma assay, and in the human lymphocyte assay. In the in vivo rat bone marrow cytogenetic assay, statistically significant increases in the incidence of structural abnormalities, relative to vehicle controls, were observed in male rats dosed with 0.1 mg/kg (0.625 mg/m2) NUROMAX and sacrificed at 6 hours, but not at 24 or 48 hours, and in female rats dosed with 0.2 mg/kg (1.25 mg/m2) NUROMAX and sacrificed at 24 hours, but not at 6 or 48 hours. There was no increase in structural abnormalities in either male or female rats given 0.3 mg/kg (1.875 mg/m2) NUROMAX and sacrificed at 6, 24, or 48 hours. Thus, the incidence of abnormalities in the in vivo rat bone marrow cytogenetic assay was not dose-dependent and, therefore, the likelihood that the observed abnormalities were treatment-related or clinically significant is low.

Pregnancy

Teratogenic Effect

Pregnancy Category C.

Teratology testing in nonventilated, pregnant rats and mice treated subcutaneously with maximum subparalyzing doses of NUROMAX revealed no maternal or fetal toxicity or teratogenic effects. There are no adequate and well-controlled studies of NUROMAX in pregnant women. Because animal studies are not always predictive of human response and the doses used were subparalyzing, NUROMAX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

OVERDOSAGE

Overdosage with neuromuscular blocking agents may result in neuromuscular block beyond the time needed for surgery and anesthesia. The primary treatment is maintenance of a patent airway and controlled ventilation until recovery of normal neuromuscular function is assured. Once evidence of recovery from neuromuscular block is observed, further recovery may be facilitated by administration of an anticholinesterase agent (e.g., neostigmine, edrophonium) in conjunction with an appropriate anticholinergic agent (see Antagonism of Neuromuscular Block below).

Antagonism of Neuromuscular Block

ANTAGONISTS (SUCH AS NEOSTIGMINE) SHOULD NOT BE ADMINISTERED PRIOR TO THE DEMONSTRATION OF SOME SPONTANEOUS RECOVERY FROM NEUROMUSCULAR BLOCK. THE USE OF A NERVE STIMULATOR TO DOCUMENT RECOVERY AND ANTAGONISM OF NEUROMUSCULAR BLOCK IS RECOMMENDED. T4/T1 SHOULD BE > ZERO BEFORE ANTAGONISM IS ATTEMPTED.

In an analysis of patients in whom antagonism of neuromuscular block was evaluated following administration of single doses of neostigmine averaging 0.06 mg/kg (range:  0.05 to 0.075) administered at approximately 25% T1 spontaneous recovery during balanced anesthesia, 71% of patients exhibited T4/T1≥ 0.7 before monitoring was discontinued. For these patients, the mean time to T4/T1≥ 0.7 was 19 minutes (range:  7 to 55). As with other long-acting nondepolarizing neuromuscular blocking agents, the time for recovery of neuromuscular function following administration of neostigmine is dependent upon the level of residual neuromuscular block at the time of attempted reversal; longer recovery times than those cited above may be anticipated when neostigmine is administered at more profound levels of block (i.e., at < 25% T1 recovery).

Patients should be evaluated for adequate clinical evidence of antagonism, e.g., 5-second head lift, and grip strength. Ventilation must be supported until no longer required. As with other neuromuscular blocking agents, physicians should be alert to the possibility that the action of the drugs used to antagonize neuromuscular block may wear off before the effects of NUROMAX on the neuromuscular junction have declined sufficiently.

Antagonism may be delayed in the presence of debilitation, carcinomatosis, and the concomitant use of certain broad-spectrum antibiotics or anesthetic agents and other drugs which enhance neuromuscular block or separately cause respiratory depression (see  PRECAUTIONS - Drug Interactions). Under such circumstances the management is the same as that of prolonged neuromuscular block.

In clinical trials, a dose of 1 mg/kg edrophonium was not as effective as a dose of 0.06 mg/kg neostigmine in antagonizing moderate to deep levels of neuromuscular block (i.e., < 60% T1 recovery). Therefore, the use of 1 mg/kg edrophonium is not recommended for reversal from moderate to deep levels of block. The use of pyridostigmine has not been studied.

CONTRAINDICATIONS

NUROMAX is contraindicated in patients known to have hypersensitivity to it. Use of NUROMAX from multiple-dose vials containing benzyl alcohol as a preservative is contraindicated in patients with a known hypersensitivity to benzyl alcohol.

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