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Interactions between Doxacurium and Mesantoin

1 drug interaction and 20 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

mephenytoin doxacurium

Applies to: Mesantoin (mephenytoin) and doxacurium
Monitor

Case reports have suggested that long-term phenytoin administration may decrease the effectiveness of neuromuscular blocker and increase the dosage requirements. One of the proposed mechanisms is hepatic enzyme induction by phenytoin. Conversely, acute phenytoin administration may increase neuromuscular blocking effects by an unknown mechanism. Other hydantoins may interact with other non-depolarizing neuromuscular blockers in a similar fashion.

Management

Close observation for evidence of altered effects of neuromuscular blocking agents is indicated if these drugs must be used together.

References (2)
  1. Plotkin CN, Ornstein E (1986) "Resistance to pancuronium: adult respiratory distress syndrome or phenytoin." Anesth Analg, 65, p. 819-27
  2. Liberman BA, Norman P, Hardy BG (1988) "Pancuronium-phenytoin interaction: a case of decreased duration of neuromuscular blockade." Int J Clin Pharmacol Ther Toxicol, 26, p. 371-4

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

mephenytoin Food/Lifestyle

Applies to: Mesantoin (mephenytoin)
Adjust dosing interval

Phenytoin bioavailability may decrease to subtherapeutic levels when the suspension is given concomitantly with enteral feedings. The mechanism may be related to phenytoin binding to substances in the enteral formula (e.g., calcium, protein) and/or binding to the tube lumen. Data have been conflicting and some studies have reported no changes in phenytoin levels, while others have reported significant reductions.

Monitor

Acute consumption of alcohol may increase plasma phenytoin levels. Chronic consumption of alcohol may decrease plasma phenytoin levels. The mechanism of this interaction is related to induction of phenytoin metabolism by ethanol during chronic administration. Other hydantoin derivatives may be similarly affected by ethanol.

Management

Some experts have recommended interrupting the feeding for 2 hours before and after the phenytoin dose, giving the phenytoin suspension diluted in water, and flushing the tube with water after administration; however, this method may not entirely avoid the interaction and is not always clinically feasible. Patients should be closely monitored for clinical and laboratory evidence of altered phenytoin efficacy and levels upon initiation and discontinuation of enteral feedings. Dosage adjustments or intravenous administration may be required until therapeutic serum levels are obtained. In addition, patients receiving phenytoin therapy should be warned about the interaction between phenytoin and ethanol and they should be advised to notify their physician if they experience worsening of seizure control or symptoms of toxicity, including drowsiness, visual disturbances, change in mental status, nausea, or ataxia.

References (16)
  1. Sandor P, Sellers EM, Dumbrell M, Khouw V (1981) "Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics." Clin Pharmacol Ther, 30, p. 390-7
  2. Holtz L, Milton J, Sturek JK (1987) "Compatibility of medications with enteral feedings." JPEN J Parenter Enteral Nutr, 11, p. 183-6
  3. Sellers EM, Holloway MR (1978) "Drug kinetics and alcohol ingestion." Clin Pharmacokinet, 3, p. 440-52
  4. (2001) "Product Information. Dilantin (phenytoin)." Parke-Davis
  5. Doak KK, Haas CE, Dunnigan KJ, et al. (1998) "Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings." Pharmacotherapy, 18, p. 637-45
  6. Rodman DP, Stevenson TL, Ray TR (1995) "Phenytoin malabsorption after jejunostomy tube delivery." Pharmacotherapy, 15, p. 801-5
  7. Au Yeung SC, Ensom MH (2000) "Phenytoin and enteral feedings: does evidence support an interaction?" Ann Pharmacother, 34, p. 896-905
  8. Ozuna J, Friel P (1984) "Effect of enteral tube feeding on serum phenytoin levels." J Neurosurg Nurs, 16, p. 289-91
  9. Faraji B, Yu PP (1998) "Serum phenytoin levels of patients on gastrostomy tube feeding." J Neurosci Nurs, 30, p. 55-9
  10. Marvel ME, Bertino JS (1991) "Comparative effects of an elemental and a complex enteral feeding formulation on the absorption of phenytoin suspension." JPEN J Parenter Enteral Nutr, 15, p. 316-8
  11. Fleisher D, Sheth N, Kou JH (1990) "Phenytoin interaction with enteral feedings administered through nasogastric tubes." JPEN J Parenter Enteral Nutr, 14, p. 513-6
  12. Haley CJ, Nelson J (1989) "Phenytoin-enteral feeding interaction." DICP, 23, p. 796-8
  13. Guidry JR, Eastwood TF, Curry SC (1989) "Phenytoin absorption in volunteers receiving selected enteral feedings." West J Med, 150, p. 659-61
  14. Krueger KA, Garnett WR, Comstock TJ, Fitzsimmons WE, Karnes HT, Pellock JM (1987) "Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability." Epilepsia, 28, p. 706-12
  15. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  16. Cerner Multum, Inc. "Australian Product Information."

Disease interactions

19 potential interactions Applies to: 18 conditions, including Depression, Vitamin D Deficiency, Weight Loss, Hypokalemia, and Psychosis.

Abnormal Glucose Tolerance

Moderate:

Mesantoin

The mephenytoin in Mesantoin has a moderate potential interaction with Abnormal Glucose Tolerance.

Phenytoin, particularly in high dosages, may cause hyperglycemia by inhibiting insulin release. The drug may also raise serum glucose levels in diabetic patients. Therapy with phenytoin should be administered cautiously in patients with diabetes mellitus, glucose intolerance, or a predisposition to hyperglycemia. Patients with diabetes mellitus should be monitored more closely during phenytoin therapy, and their antidiabetic regimen adjusted accordingly. The same precautions should also be observed with other hydantoin anticonvulsants (i.e. ethotoin and mephenytoin) because of their structural and pharmacological similarities to phenytoin.

Anemia, Folate Deficiency

Moderate:

Mesantoin

The mephenytoin in Mesantoin has a moderate potential interaction with Anemia, Folate Deficiency.

Hydantoin anticonvulsants may interfere with folate metabolism and precipitate macrocytosis and megaloblastic anemia, which usually respond to folic acid therapy. These reactions have been fairly uncommon but may be of concern in patients with megaloblastic anemia or folate deficiency receiving hydantoin therapy.

Bone Marrow Depression/Low Blood Counts

Major:

Mesantoin

The mephenytoin in Mesantoin has a major potential interaction with Bone Marrow Depression/Low Blood Counts.

Hematologic toxicities have been associated with the use of hydantoin anticonvulsants, particularly mephenytoin. Thrombocytopenia, leukopenia, neutropenia, agranulocytosis, pancytopenia and, rarely, hemolytic anemia, aplastic anemia and pure red cell aplasia have been reported. Therapy with hydantoin anticonvulsants should be administered cautiously in patients with preexisting blood dyscrasias and/or bone marrow depression. Complete blood counts, including platelets, should be performed prior to initiating therapy and regularly for several months thereafter. For mephenytoin, the manufacturer recommends performing counts after 2 weeks on a low dosage, after another 2 weeks when full dosage is reached, then monthly for a year, and every 3 months thereafter. Marked depression of blood counts may be indication for withdrawal of hydantoin therapy.

Burns, External

Major:

doxacurium

Doxacurium has a major potential interaction with Burns, External.

Patients with burns may develop resistance to non-depolarizing neuromuscular blocking agents. These patients may experience a shorter duration of action and/or require higher dosages of the drugs. The extent of altered response depends on the duration since and the size of the burn.

Depression

Moderate:

Mesantoin

The mephenytoin in Mesantoin has a moderate potential interaction with Depression.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

Diabetes Mellitus

Moderate:

Mesantoin

The mephenytoin in Mesantoin has a moderate potential interaction with Diabetes Mellitus.

Phenytoin, particularly in high dosages, may cause hyperglycemia by inhibiting insulin release. The drug may also raise serum glucose levels in diabetic patients. Therapy with phenytoin should be administered cautiously in patients with diabetes mellitus, glucose intolerance, or a predisposition to hyperglycemia. Patients with diabetes mellitus should be monitored more closely during phenytoin therapy, and their antidiabetic regimen adjusted accordingly. The same precautions should also be observed with other hydantoin anticonvulsants (i.e. ethotoin and mephenytoin) because of their structural and pharmacological similarities to phenytoin.

Folic Acid/Cyanocobalamin Deficiency

Moderate:

Mesantoin

The mephenytoin in Mesantoin has a moderate potential interaction with Folic Acid/Cyanocobalamin Deficiency.

Hydantoin anticonvulsants may interfere with folate metabolism and precipitate macrocytosis and megaloblastic anemia, which usually respond to folic acid therapy. These reactions have been fairly uncommon but may be of concern in patients with megaloblastic anemia or folate deficiency receiving hydantoin therapy.

Hypokalemia

Major:

doxacurium

Doxacurium has a major potential interaction with Hypokalemia.

Severe acid-base and/or electrolyte abnormalities may potentiate or cause resistance to the neuromuscular blocking action neuromuscular blocking agents. The potency of these agents may be mixed in metabolic acidosis and alkalosis, and in respiratory alkalosis. Since electrolyte imbalance and acid-base imbalance are usually mixed, either enhancement or inhibition may occur. Caution should be taken when using these agents in predisposed patients.

Liver Disease

Major:

doxacurium

Doxacurium has a major potential interaction with Liver Disease.

Neuromuscular blocking agents undergo metabolism by the liver. Elimination and effects may be prolonged in patients with liver disease. Therapy with neuromuscular blocking agents should be administered cautiously in patients with liver disease.

Major:

Mesantoin

The mephenytoin in Mesantoin has a major potential interaction with Liver Disease.

Hydantoin anticonvulsants are primarily metabolized by the liver. Both metabolic activity and plasma protein binding may be significantly altered in patients with liver disease, resulting in elevated drug levels (total and unbound fraction) and increased risk of toxicity. Therapy with hydantoin anticonvulsants should be administered cautiously in patients with impaired hepatic function. Reduced dosages and slower titration may be necessary. In addition, periodic monitoring of liver function is recommended, since the use of anticonvulsants, including hydantoins, has been associated with hepatotoxicity related to drug hypersensitivity. Hepatic failure and death have occurred. Hydantoin therapy should be discontinued and not readministered if evidence of liver damage is observed and felt to be drug-related.

Myasthenia Gravis

Major:

doxacurium

Doxacurium has a major potential interaction with Myasthenia Gravis.

The use of neuromuscular blocking agents may cause prolonged respiratory paralysis. Therapy with neuromuscular blocking agents should be administered cautiously in patients with myasthenia gravis. Use of a peripheral nerve stimulator may be helpful in evaluating the level of neuromuscular blockade.

Paralytic Disorder

Major:

doxacurium

Doxacurium has a major potential interaction with Paralytic Disorder.

Patients with hemiparesis or paraparesis may require higher dosages of non-depolarizing neuromuscular blocking agents in the affected limbs. Neuromuscular monitoring should be performed on a non-paretic limb to avoid inaccurate dosing.

Porphyria

Major:

Mesantoin

The mephenytoin in Mesantoin has a major potential interaction with Porphyria.

The use of phenytoin has rarely been associated with exacerbation of porphyria. Therapy with phenytoin should be administered cautiously in patients with porphyria. The same precaution should also be observed with other hydantoin anticonvulsants (i.e. ethotoin and mephenytoin) because of their structural and pharmacological similarities to phenytoin.

Prematurity/Underweight in Infancy

Major:

doxacurium

Doxacurium has a major potential interaction with Prematurity/Underweight in Infancy.

Parenteral medications formulated in multidose vials often contain benzyl alcohol as a preservative. Their use is considered by drug manufacturers to be contraindicated in neonates, particularly premature infants and infants of low birth weight. When used in bacteriostatic saline intravascular flush and endotracheal tube lavage solutions, benzyl alcohol has been associated with fatalities and severe respiratory and metabolic complications in low-birth-weight premature infants. Thus, single-dose formulations should always be used in infants whenever possible. However, many experts feel that, in the absence of benzyl alcohol-free equivalents, the amount of the preservative present in these formulations should not necessarily preclude their use if they are clearly indicated. The American Academy of Pediatrics considers benzyl alcohol in low doses (such as when used as a preservative in some medications) to be safe for newborns. However, the administration of high dosages of these medications must take into account the total amount of benzyl alcohol administered. The level at which toxicity may occur is unknown.

Psychosis

Moderate:

Mesantoin

The mephenytoin in Mesantoin has a moderate potential interaction with Psychosis.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

Pulmonary Impairment

Major:

doxacurium

Doxacurium has a major potential interaction with Pulmonary Impairment.

Neuromuscular blocking agents can cause respiratory depression and paralysis. Therapy with neuromuscular blocking agents should be administered cautiously in patients with pulmonary impairment. Treatment of respiratory paralysis consists of positive-pressure artificial respiration with oxygen and maintenance of a patent airway until the recovery of normal respiration is assured.

Renal Dysfunction

Moderate:

doxacurium

Doxacurium has a moderate potential interaction with Renal Dysfunction.

Many of the non-depolarizing (competitive) neuromuscular blocking agents undergo significant elimination by the kidney. Their effects may, therefore, be prolonged in patients with renal dysfunction. Therapy with these neuromuscular blocking agents should be administered cautiously and initiated at reduced dosages in renally compromised patients, depending on the level of insufficiency. If possible, alternative agents should be considered. Atracurium, rocuronium and vecuronium do not depend on kidney function for clearance and are often the non-depolarizing muscle relaxants of choice in renal failure.

Vitamin D Deficiency

Moderate:

Mesantoin

The mephenytoin in Mesantoin has a moderate potential interaction with Vitamin D Deficiency.

Phenytoin may interfere with vitamin D metabolism. Hypocalcemia and osteomalacia have been reported. Therapy with phenytoin should be administered cautiously in patients with preexisting vitamin D deficiency. The same precaution should also be observed with other hydantoin anticonvulsants (i.e. ethotoin and mephenytoin) because of their structural and pharmacological similarities to phenytoin.

Weight Loss

Moderate:

doxacurium

Doxacurium has a moderate potential interaction with Weight Loss.

A few of the neuromuscular blocking agents, including doxacurium, mivacurium and pipecuronium, may have prolonged and/or enhanced effects in obese patients (i.e. weight >= 30% over ideal body weight for height). Dosing of these agents should be based on ideal body weight in obese patients.

More resources

doxacurium

A total of 157 drugs are known to interact with doxacurium.

Mesantoin

A total of 456 drugs are known to interact with Mesantoin.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.