SUCCINYLCHOLINE Drug Interactions: What You Need to Know

7 Drug Interactions

7.1 Drugs that May Affect the Neuromuscular Blocking Action of Succinylcholine Chloride injection Drugs that may enhance the neuromuscular blocking action of succinylcholine include: promazine, oxytocin, aprotinin, certain non-penicillin antibiotics, quinidine, β-adrenergic blockers, procainamide, lidocaine, trimethaphan, lithium carbonate, magnesium salts, quinine, chloroquine, isoflurane, desflurane, metoclopramide, and terbutaline. The neuromuscular blocking effect of succinylcholine may be enhanced by drugs that reduce plasma cholinesterase activity (e.g., chronically administered oral contraceptives, glucocorticoids, or certain monoamine oxidase inhibitors) or by drugs that irreversibly inhibit plasma cholinesterase <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.9)]</span>. If other neuromuscular blocking agents are to be used during the same procedure, consider the possibility of a synergistic or antagonistic effect. Drugs that May Enhance the Neuromuscular Blocking Action of Succinylcholine: promazine, oxytocin, aprotinin, certain non-penicillin antibiotics, quinidine, β-adrenergic blockers, procainamide, lidocaine, trimethaphan, lithium carbonate, magnesium salts, quinine, chloroquine, isoflurane, desflurane, metoclopramide, terbutaline, and drugs that reduce plasma cholinesterase activity. ( 7.1)

See

17 for PATIENT COUNSELING INFORMATION. Revised: 01/2023

ANECTINE is contraindicated in patients with:

• Known or suspected genetic susceptibility to malignant hyperthermia [see WARNINGS, Malignant Hyperthermia ( 5.5 ), CLINICAL PHARMACOLOGY, Pharmacogenomics ( 12.5 )]
• Skeletal muscle myopathies [see WARNINGS, Ventricular Dysrhythmias, Cardiac Arrest, and Death From Hyperkalemic Rhabdomyolysis in Pediatric Patients ( 5.1 )]
• Known hypersensitivity to succinylcholine [see Warnings and Precautions (5.2) ] .
• After the acute phase of injury following major burns, multiple trauma, extensive denervation of the skeletal muscle, or upper neuron injury because succinylcholine administered to such individuals may result in severe hyperkalemia, which may result in cardiac arrest [see Warnings and Precautions (5.4) ] .
• Skeletal muscle myopathies ( 4 )
• Known hypersensitivity to succinylcholine ( 4 )
• After the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury ( 4 )
• Known or suspected genetic susceptibility to malignant hyperthermia ( 4 )

AND PRECAUTIONS Anaphylaxis : Severe anaphylactic reactions to neuromuscular blocking agents, including succinylcholine, have been reported. Some cases have been life-threatening and fatal. Take necessary precautions, such as the immediate availability of appropriate emergency treatment. (5.2) Risk of Death due to Medication Errors : Unintended administration of succinylcholine chloride may result in paralysis, respiratory arrest and death. Confirm proper selection of intended product and avoid confusion with other injectable solutions that are present in critical care and other clinical settings. (5.3) Hyperkalemia : Succinylcholine chloride may induce serious cardiac arrhythmias or cardiac arrest due to hyperkalemia. (5.4)

Malignant

Hyperthermia : Malignant hyperthermia may occur, especially in individuals with known or suspected susceptibility based on genetic factors or family history. Discontinue triggering agents, administer intravenous dantrolene sodium and apply supportive therapies. (5.5) Bradycardia : Intravenous bolus administration may result in profound bradycardia or, rarely, asystole. The incidence is higher following a second dose of succinylcholine. Pre-treatment with anticholinergic agents (e.g., atropine) may reduce the occurrence of bradyarrhythmias. (5.6)

5.1 Ventricular Dysrhythmias, Cardiac Arrest, and Death From Hyperkalemic Rhabdomyolysis in Pediatric Patients There have been reports of ventricular dysrhythmias, cardiac arrest, and death secondary to acute rhabdomyolysis with hyperkalemia in apparently healthy pediatric patients who received succinylcholine. Many of these pediatric patients were subsequently found to have a skeletal muscle myopathy such as Duchenne muscular dystrophy whose clinical signs were not obvious. The syndrome often presented as sudden cardiac arrest within minutes after the administration of succinylcholine. These pediatric patients were usually, but not exclusively, males, and most frequently 8 years of age or younger. There have also been reports in adolescents. There may be no signs or symptoms to alert the practitioner to which patients are at risk. A careful history and physical may identify developmental delays suggestive of a myopathy. A preoperative creatine kinase could identify some but not all patients at risk. When a healthy-appearing pediatric patient develops cardiac arrest within minutes after administration of SUCCINYLCHOLINE CHLORIDE INJECTION, USP, not felt to be due to inadequate ventilation, oxygenation or anesthetic overdose, immediate treatment for hyperkalemia should be instituted. Due to the abrupt onset of this syndrome, routine resuscitative measures are likely to be unsuccessful. Careful monitoring of the electrocardiogram may alert the practitioner to peaked T-waves (an early sign). Administration of intravenous calcium, bicarbonate, and glucose with insulin, with hyperventilation have resulted in successful resuscitation in some of the reported cases. Extraordinary and prolonged resuscitative efforts have been effective in some cases. In addition, in the presence of signs of malignant hyperthermia, appropriate treatment should be initiated concurrently <span class="opacity-50 text-xs">[see Warnings and Precautions (5.5) ]</span>. Because it is difficult to identify which patients are at risk, reserve the use of SUCCINYLCHOLINE CHLORIDE INJECTION, USP in pediatric patients for emergency intubation or instances where immediate securing of the airway is necessary, e.g., laryngospasm, difficult airway, full stomach, or for intramuscular use when a suitable vein is inaccessible.

5.2 Anaphylaxis Severe anaphylactic reactions to neuromuscular blocking agents, including succinylcholine, have been reported. These reactions have, in some cases, been life-threatening and fatal. Due to the potential severity of these reactions, the necessary precautions, such as the immediate availability of appropriate emergency treatment, should be taken. Allergic cross-reactivity between neuromuscular blocking agents, both depolarizing and non-depolarizing, has been reported in this class of drugs. Therefore, assess patients for previous anaphylactic reactions to other neuromuscular blocking agents before administering SUCCINYLCHOLINE CHLORIDE INJECTION, USP.

5.3 Risk of Death due to Medication Errors Administration of SUCCINYLCHOLINE CHLORIDE INJECTION, USP results in paralysis, which may lead to respiratory arrest and death; this progression may be more likely to occur in a patient for whom it is not intended. Confirm proper selection of intended product and avoid confusion with other injectable solutions that are present in critical care and other clinical settings. If another healthcare provider is administering the product, ensure that the intended dose is clearly labeled and communicated.

5.4 Hyperkalemia SUCCINYLCHOLINE CHLORIDE INJECTION, USP may induce serious cardiac arrhythmias or cardiac arrest due to hyperkalemia in patients with electrolyte abnormalities and those who may have digitalis toxicity. SUCCINYLCHOLINE CHLORIDE INJECTION, USP is contraindicated after the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . The risk of hyperkalemia in these patients increases over time and usually peaks at 7 to 10 days after the injury. The risk is dependent on the extent and location of the injury. The precise time of onset and the duration of the risk period are undetermined. Patients with chronic abdominal infection, subarachnoid hemorrhage, or conditions causing degeneration of central and peripheral nervous systems are at an increased risk of developing severe hyperkalemia after SUCCINYLCHOLINE CHLORIDE INJECTION, USP administration. Consider avoiding use of SUCCINYLCHOLINE CHLORIDE INJECTION, USP in these patients or verify the patient’s baseline potassium levels are within the normal range prior to SUCCINYLCHOLINE CHLORIDE INJECTION, USP administration.

5.5 Malignant Hyperthermia In susceptible individuals, succinylcholine may trigger malignant hyperthermia, a skeletal muscle hypermetabolic state leading to high oxygen demand. Fatal outcomes of malignant hyperthermia have been reported. The risk of developing malignant hyperthermia increases with the concomitant administration of succinylcholine and volatile anesthetic agents. SUCCINYLCHOLINE CHLORIDE INJECTION, USP can induce malignant hyperthermia in patients with known or suspected susceptibility based on genetic factors or family history, including those with certain inherited ryanodine receptor (RYR1) or dihydropyridine receptor (CACNA1S) variants. <span class="opacity-50 text-xs">[see Contraindications (4) , Clinical Pharmacology (12.5) ]</span> . Signs consistent with malignant hyperthermia may include hyperthermia, hypoxia, hypercapnia, muscle rigidity (e.g., jaw muscle spasm), tachycardia (e.g., particularly that unresponsive to deepening anesthesia or analgesic medication administration), tachypnea, cyanosis, arrhythmias, hypovolemia and hemodynamic instability. Skin mottling, coagulopathies and renal failure may occur later in the course of the hypermetabolic process. Successful treatment of malignant hyperthermia depends on early recognition of the clinical signs. If malignant hyperthermia is suspected, discontinue all triggering agents (i.e., volatile anesthetic agents and succinylcholine), administer intravenous dantrolene sodium, and initiate supportive therapies. Consult prescribing information for intravenous dantrolene sodium for additional information on patient management. Supportive therapies include administration of supplemental oxygen and respiratory support based on clinical need, maintenance of hemodynamic stability and adequate urinary output, management of fluid and electrolyte balance, correction of acid base derangements, and institution of measures to control rising temperature.

5.6 Bradycardia Intravenous bolus administration of SUCCINYLCHOLINE CHLORIDE INJECTION, USP in pediatric patients (including infants) may result in profound bradycardia or, rarely, asystole. In both adult and pediatric patients the incidence of bradycardia, which may progress to asystole, is higher following a second dose of succinylcholine. The incidence and severity of bradycardia is higher in pediatric patients than adults. Whereas bradycardia is common in pediatric patients after an initial dose of 1.5 mg/kg, bradycardia is seen in adults only after repeated exposure. Pretreatment with anticholinergic agents (e.g., atropine) may reduce the occurrence of bradyarrhythmias.

5.7 Increased in Intraocular Pressure Succinylcholine causes an increase in intraocular pressure. Avoid SUCCINYLCHOLINE CHLORIDE INJECTION, USP in instances in which an increase in intraocular pressure is undesirable (e.g., narrow angle glaucoma, penetrating eye injury) unless the potential benefit of its use outweighs the potential risk.

5.8 Prolonged Neuromuscular Block due to Phase II Block and Tachyphylaxis When SUCCINYLCHOLINE CHLORIDE INJECTION, USP is given over a prolonged period of time, the characteristic depolarization block of the myoneural junction (Phase I block) may change to a block with characteristics superficially resembling a non-depolarizing block (Phase II block). Prolonged respiratory muscle paralysis or weakness may be observed in patients manifesting this transition to Phase II block. Tachyphylaxis occurs with repeated administration <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.2) ]</span> .

When

Phase II block is suspected in cases of prolonged neuromuscular blockade, positive diagnosis should be made by peripheral nerve stimulation, prior to administration of any anticholinesterase drug. Reversal of Phase II block is a medical decision which must be made upon the basis of the patient, clinical pharmacology, and the experience and judgment of the clinician. The presence of Phase II block is indicated by fade of responses to successive stimuli (preferably "train of four"). The use of an anticholinesterase drug such as neostigmine to reverse Phase II block should be accompanied by appropriate doses of an anticholinergic drug to prevent disturbances of cardiac rhythm. After adequate reversal of Phase II block with an anticholinesterase agent, the patient should be continually observed for at least 1 hour for signs of return of muscle relaxation. Reversal should not be attempted unless: (1) a peripheral nerve stimulator is used to determine the presence of Phase II block (since anticholinesterase agents will potentiate succinylcholine-induced Phase I block), and (2) spontaneous recovery of muscle twitch has been observed for at least 20 minutes and has reached a plateau with further recovery proceeding slowly; this delay is to ensure complete hydrolysis of succinylcholine by plasma cholinesterase prior to administration of the anticholinesterase agent. Should the type of block be misdiagnosed, depolarization of the type initially induced by succinylcholine (i.e., Phase I block) will be prolonged by an anticholinesterase agent.

5.9 Risk of Prolonged Neuromuscular Block in Patients with Reduced Plasma Cholinesterase Activity SUCCINYLCHOLINE CHLORIDE INJECTION, USP is not recommended in patients with known reduced plasma cholinesterase (pseudocholinesterase) activity due to the likelihood of prolonged neuromuscular block following administration of SUCCINYLCHOLINE CHLORIDE INJECTION, USP in such patients. Plasma cholinesterase activity may be diminished in the presence of genetic abnormalities of plasma cholinesterase (e.g., patients heterozygous or homozygous for atypical plasma cholinesterase gene), pregnancy, severe liver or kidney disease, malignant tumors, infections, burns, anemia, decompensated heart disease, peptic ulcer, or myxedema. Plasma cholinesterase activity may also be diminished by chronic administration of oral contraceptives, glucocorticoids, or certain monoamine oxidase inhibitors and by irreversible inhibitors of plasma cholinesterase (e.g., organophosphate insecticides, echothiophate, and certain antineoplastic drugs) <span class="opacity-50 text-xs">[see Drug Interactions (7.1) ]</span> . Patients homozygous for atypical plasma cholinesterase gene (1 in 2,500 patients) are extremely sensitive to the neuromuscular blocking effect of succinylcholine. If SUCCINYLCHOLINE CHLORIDE INJECTION, USP is administered to a patient homozygous for atypical plasma cholinesterase, resulting apnea or prolonged muscle paralysis should be treated with controlled respiration.

5.10 Risk of Additional Trauma in Patients with Fractures or Muscle Spasms SUCCINYLCHOLINE CHLORIDE INJECTION, USP should be employed with caution in patients with fractures or muscle spasm because the initial muscle fasciculations may cause additional trauma. Monitor neuromuscular transmission and the development of fasciculations throughout the use of neuromuscular blocking agents.

5.11 Increase in Intracranial Pressure SUCCINYLCHOLINE CHLORIDE INJECTION, USP may cause a transient increase in intracranial pressure; however, adequate anesthetic induction prior to administration of SUCCINYLCHOLINE CHLORIDE INJECTION, USP will minimize this effect.

5.12 Risk of Aspiration due to Increase in Intragastric Pressure Succinylcholine may increase intragastric pressure, which could result in regurgitation and possible aspiration of stomach contents. Evaluate patients at risk for aspiration and regurgitation. Monitor patients during induction of anesthesia and neuromuscular blockade for clinical signs of vomiting and/or aspiration.

5.13 Prolonged Neuromuscular Block in Patients with Hypokalemia or Hypocalcemia Neuromuscular blockade may be prolonged in patients with hypokalemia (e.g., after severe vomiting, diarrhea, digitalisation and diuretic therapy) or hypocalcemia (e.g., after massive transfusions). Correct severe electrolyte disturbances when possible. In order to help preclude possible prolongation of neuromuscular block, monitor neuromuscular transmission throughout the use of SUCCINYLCHOLINE CHLORIDE INJECTION, USP.

5.14 Risks due to Inadequate Anesthesia Neuromuscular blockade in the conscious patient can lead to distress. Use SUCCINYLCHOLINE CHLORIDE INJECTION, USP in the presence of appropriate sedation or general anesthesia. Monitor patients to ensure that the level of anesthesia is adequate. In emergency situations, however, it may be necessary to administer SUCCINYLCHOLINE CHLORIDE INJECTION, USP before unconsciousness is induced.