Chemical formula: C₆₅H₈₂N₂O₁₈S₂ Molecular mass: 1,242.5 g/mol PubChem compound: 47320
Atracurium besilate interacts in the following cases:
The use of intravenous corticosteroids with neuromuscular blocking agents has been reported to antagonise neuromuscular blockades. In addition, prolonged co-administration of these agents may increase the risk and/or severity of myopathy resulting in prolonged flaccid paralysis following discontinuation of the neuromuscular blocking agent. The myopathy is usually reversible with recovery in several months.
As with other non-depolarising neuromuscular blocking agents, the magnitude and/or duration of atracurium’s effects may be increased as a result of an interaction with aminoglycosides, polymyxins, spectinomycin, tetracyclines, lincomycin, clindamycin and vancomycin.
The administration of combinations of non-depolarising neuromuscular blocking agents in conjunction with atracurium may produce a degree of neuromuscular blockade in excess of that which might be expected were an equipotent total dose of atracurium administered. Any synergistic effect may vary between different drug combinations.
The onset of neuromuscular blockade is likely to be lengthened and the duration of blockade shortened in patients receiving chronic anticonvulsant therapy (e.g. carbamazepine, phenytoin). However, if the anticonvulsants are given acutely, the neuromuscular blocking effects may be increased.
In common with all non-depolarising neuromuscular blocking agents the magnitude and/or duration of a non-depolarising neuromuscular block may be increased as a result of interaction with chloroquine, d-penicillamine.
As with other non-depolarising neuromuscular blocking agents, the magnitude and/or duration of atracurium’s effects may be increased as a result of an interaction with dantrolene, parenteral magnesium sulphate, chlorpromazine, steroids, ketamine, lithium salts and quinine.
In common with all non-depolarising neuromuscular blocking agents the magnitude and/or duration of a non-depolarising neuromuscular block may be increased as a result of interaction with diltiazem, nicardipine, nifedipine, verapamil.
As with other non-depolarising neuromuscular blocking agents, the magnitude and/or duration of atracurium’s effects may be increased as a result of an interaction with furosemide, thiazides, acetazolamide and possibly mannitol.
As with other non-depolarising neuromuscular blocking agents, the magnitude and/or duration of atracurium’s effects may be increased as a result of an interaction with inhalation anaesthetics: atracurium is potentiated by isoflurane, desflurane, sevoflurane and enflurane anaesthesia, and only marginally potentiated by halothane anaesthesia.
In common with all non-depolarising neuromuscular blocking agents the magnitude and/or duration of a non-depolarising neuromuscular block may be increased as a result of interaction with local anaesthetics such as lidocaine, procainamide, quinidine.
In common with all non-depolarising neuromuscular blocking agents the magnitude and/or duration of a non-depolarising neuromuscular block may be increased as a result of interaction with propranolol, oxprenolol.
A depolarising muscle relaxant such as suxamethonium chloride should not be administered to prolong the neuromuscular blocking effects of non-depolarising blocking agents such as atracurium, as this may result in a prolonged and complex block which can be difficult to reverse with anticholinesterase drugs.
The prior use of suxamethonium reduces the onset (to maximum blockade) by approximately 2 to 3 minutes and may increase the depth of neuromuscular blockade induced by atracurium. Therefore, the initial atracurium dose should be reduced and the reduced dose should not be administered until the patient has recovered from the neuromuscular blocking effects of suxamethonium.
As with other non-depolarising neuromuscular blocking agents, resistance to atracurium may develop in patients suffering from burns. Such patients may require increased doses of atracurium depending on the time elapsed since the burn injury and the extent of the burn.
Atracurium may have profound effects in patients with myasthenia gravis, Eaton-Lambert syndrome, or other neuromuscular diseases in which potentiation of non-depolarising agents has been noted. A reduced dosage of atracurium and the use of a peripheral nerve stimulator for assessing neuromuscular blockade is especially important in these patients. Similar precautions should be taken in patients with severe electrolyte disorders.
In common with all non-depolarising neuromuscular blocking agents the magnitude and/or duration of a non-depolarising neuromuscular block may be increased as a result of interaction with hexamethonium.
Atracurium crosses the placenta but there have been no demonstrated adverse effects in the foetus or newborn infant. Animal studies have indicated that atracurium has no adverse effects on foetal development. As with all neuromuscular blocking agents, the use of atracurium in the first three months of pregnancy should be avoided and it should not be used during the second and third trimesters unless clearly necessary.
Atracurium is suitable for maintenance of muscle relaxation during caesarean section as it does not cross the placenta in clinically significant amounts following recommended doses. In an open study, atracurium besilate (0.3 mg/kg) was administered to 26 pregnant women during delivery by caesarean section. No harmful effects were attributable to atracurium in any of the newborn infants, although small amounts of atracurium were shown to cross the placental barrier. The possibility of respiratory depression in the newborn infant should always be considered following caesarean section during which a neuromuscular blocking agent has been administered.
Anaesthesia during the third trimester of pregnancy exposes the mother to Mendelson syndrome (acid pneumopathy due to gastric acid aspiration). If a muscle relaxant is used at induction of anaesthesia, one should be chosen with a short onset and duration of action and low placental transfer and used in the lowest dose required to induce adequate neuromuscular relaxation. In patients receiving magnesium sulphate, the reversal of neuromuscular blockade may be unsatisfactory and the atracurium dose should be lowered as indicated.
Atracurium has a relatively high molecular weight and is highly ionized at physiologic pH, both factors that markedly reduce transfer into milk. In addition, even though milk is slightly more acidic than plasma, any atracurium transferred into milk would be rapidly degraded. Nevertheless, in view of the potential respiratory depressant effect on the neonate, especially if premature, it is recommended that if breastfeeding is started within 24 hours after administration of atracurium, the neonate is closely monitored.
No fertility data are available.
It is not recommended to use potentially dangerous machinery or drive a car within 24 hours after full recovery from the neuromuscular blocking action of atracurium.
The adverse effects are reported in decreasing order of frequency within each system order class (SOC).
As with most neuromuscular blocking agents, the potential exists for undesirable effects suggestive of histamine release in susceptible patients. In clinical trials (875 patients) reports of skin flushing ranged from 1% at doses up to 0.3 mg/kg, to 29% at doses of 0.6 mg/kg or greater. The incidence of transient hypotension ranged from 1 to 14% respectively for the corresponding dosages.
List for frequency of adverse reactions for Atracurium Besilate 10 mg/ml Solution for injection:
Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 to <1/100), Rare (≥1/10,000 to <1/1000, Very rare (<1/10,000), Not known (cannot be estimated from the available data).
Common: Tachycardia, bradycardia (observed in 1% of patients)
Rare: Severe allergic reactions (e.g. shock, cardiac failure, cardiac arrest)
Common: Reaction at injection site
Very rare: Allergic reactions (i.e. anaphylactic or anaphylactoid responses) Anaphylactoid reactions
Not known: Prolonged block
Common: Wheezing
Uncommon: Broncospasm (0.2% of patients)
Rare: Dysponea, laryngospasm
Very rare: Hypoxemia
Not known: Bronchial secretions
Common: Localized skin reactions, rash, itching
Uncommon: Generalized Erythema, Hives
Rare: Angioneurotic oedema, utricaria
Not known: Inadequate block
Common: Hypertension (observed in approximately 1% of patients), Hypotension, vasodilatation (flushing)-each occurred in approximately 2-3% of patients)
After prolonged administration of atracurium besilate in severely ill patients under intensive care, some incidences of muscle weakness and/or myopathy occurred. Most patients were concomitantly treated with corticosteroids. A causal relationship with atracurium therapy has not been established.
There have been rare reports of seizures in ICU patients who have been receiving atracurium concurrently with several other agents. These patients usually had one or more medical conditions predisposing to seizures (e.g. cranial trauma, cerebral oedema, viral encephalitis, hypoxic encephalopathy, uraemia). In clinical trials, there appears to be no correlation between plasma laudanosine concentration and the occurrence of seizures.
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