Skip to main content

Interactions between Foltabs Prenatal Plus DHA and Phensuximide

1 drug interaction and 8 additional warnings found for the following 2 drugs:

Add/remove drugs

Drug interactions

Moderate drug interactions

Moderate:

phensuximide multivitamins, prenatal

Applies to: phensuximide and Foltabs Prenatal Plus DHA (multivitamin, prenatal)
Monitor

Anticonvulsants including, but not limited to, carbamazepine, lamotrigine, phenobarbital, phenytoin, primidone, and valproic acid have been shown to impair folate absorption and increase the metabolism of circulating folate. The precise mechanism of interaction has not been established.

Monitor

Coadministration with folate therapy may reduce the anticonvulsant effects of phenytoin, phenobarbital, primidone, and succinimides. The exact mechanism of interaction is unknown. Available data pertain primarily to phenytoin. Some investigators suggest that folic acid may serve as a cofactor in the metabolism of phenytoin, thus clearance is increased in the presence of folic acid. In one study, administration of folic acid for 14 days reduced the serum levels of phenytoin in normal subjects without significantly altering the bound fraction. Urinary excretion of phenytoin and its metabolite, meta-hydroxydiphenylhydantoin, was increased. In another study, three of four folate-deficient male patients receiving phenytoin monotherapy for epilepsy demonstrated a 7.5% to 47.6% decrease in total phenytoin plasma concentration following the addition of folic acid 1 mg/day for 180 or 300 days. Ratios of urinary metabolites to parent drug increased in these patients, suggesting an increase in phenytoin oxidative metabolism. The interaction is further supported by case reports describing subtherapeutic phenytoin levels and/or breakthrough seizures following the addition of folate therapy, including one case involving folinic acid (leucovorin). Limited data are available for phenobarbital and primidone. In one study, the addition of folic acid 15 mg/day increased the frequency and severity of seizures in 13 of 26 folate-deficient epileptic patients receiving two or more anticonvulsant drugs, including phenytoin, phenobarbital, and primidone. Nine of them required discontinuation of folic acid therapy. No data are available for other hydantoins.

Management

Caution is advised when folate therapy is coadministered with anticonvulsants. Close monitoring for clinical and laboratory evidence of diminished therapeutic response to both treatments is recommended. Patients should be advised to notify their physician if they experience loss of seizure control.

References (22)
  1. Furlanut M, Benetello P, Avogaro A, Dainese R (1978) "Effects of folic acid on phenytoin kinetics in healthy subjects." Clin Pharmacol Ther, 24, p. 294-7
  2. Carl GF, Smith ML (1992) "Phenytoin-folate interactions: differing effects of the sodium salt and the free acid of phenytoin." Epilepsia, 33, p. 372-5
  3. Berg MJ, Fincham RW, Ebert BE, Schottelius DD (1992) "Phenytoin pharmacokinetics: before and after folic acid administration." Epilepsia, 33, p. 712-20
  4. MacCosbe PE, Toomey K (1983) "Interaction of phenytoin and folic acid." Clin Pharm, 2, p. 362-9
  5. Robenberg IH (1972) "Drugs and folic acid absorption." Gastroenterology, 63, p. 353-7
  6. Ch'ien LT, Krumdieck CL, Scott CW Jr, Butterworth CE Jr (1975) "Harmful effect of megadoses of vitamins: electroencephalogram abnormalities and seizures induced by intravenous folate in drug- treated epileptics." Am J Clin Nutr, 28, p. 51-8
  7. Katz M (1973) "Potential danger of self-medication with folic acid." N Engl J Med, 289, p. 1095
  8. Yuen GJ (1984) "Interaction of phenytoin and folic acid: an alternative explanation." Clin Pharm, 3, 116,119
  9. Berg MJ, Rivey MP, Vern BA, Fischer LJ, Schottelius DD (1983) "Phenytoin and folic acid: individualized drug-drug interaction." Ther Drug Monit, 5, p. 395-9
  10. Berg MJ, Fischer LJ, Rivey MP, Vern BA, Lantz RK, Schottelius DD (1983) "Phenytoin and folic acid interaction: a preliminary report." Ther Drug Monit, 5, p. 389-94
  11. Berg MJ, Stumbo PJ, Chenard CA, Fincham RW, Schneider PJ, Schottelius D (1995) "Folic acid improves phenytoin pharmacokinetics." J Am Diet Assoc, 95, p. 352-6
  12. Lewis DP, Van Dyke DC, Willhite LA, Stumbo PJ, Berg MJ (1995) "Phenytoin-folic acid interaction." Ann Pharmacother, 29, p. 726-35
  13. "Product Information. Wellcovorin (leucovorin)." Glaxo Wellcome, Research Triangle Park, NC.
  14. Seligmann H, Potasman I, Weller B, Schwartz M, Prokocimer M (1999) "Phenytoin-folic acid interaction: A lesson to be learned." Clin Neuropharmacol, 22, p. 268-72
  15. Veldhorst-Janssen NM, Boersma HH, de Krom MC, van Rijswijk RE (2004) "Oral tegafur/folinic acid chemotherapy decreases phenytoin efficacy." Br J Cancer, 90, p. 745
  16. Steinweg DL, Bentley ML (2005) "Seizures following reduction in phenytoin level after orally administered folic acid." Neurology, 64, p. 1982
  17. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  18. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  19. Cerner Multum, Inc. "Australian Product Information."
  20. (2008) "Product Information. Levoleucovorin (levoleucovorin)." Spectrum Chemical
  21. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
  22. (2018) "Product Information. L-Methylfolate Calcium (l-methylfolate)." Virtus Pharmaceuticals LLC

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

phensuximide Food/Lifestyle

Applies to: phensuximide
Generally avoid

Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

Management

Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.
Moderate:

multivitamins, prenatal Food/Lifestyle

Applies to: Foltabs Prenatal Plus DHA (multivitamin, prenatal)
Adjust dosing interval

Concomitant use of some oral medications may reduce the bioavailability of orally administered iron, and vice versa. Food taken in conjunction with oral iron supplements may reduce the bioavailability of the iron. However, in many patients intolerable gastrointestinal side effects occur necessitating administration with food.

Management

Ideally, iron products should be taken on an empty stomach (i.e., at least 1 hour before or 2 hours after meals), but if this is not possible, administer with meals and monitor the patient more closely for a subtherapeutic effect. Some studies suggest administration of iron with ascorbic acid may enhance bioavailability. In addition, administration of oral iron products and some oral medications should be separated whenever the bioavailability of either agent may be decreased. Consult the product labeling for specific separation times and monitor clinical responses as appropriate.

References (2)
  1. "Product Information. Feosol (ferrous sulfate)." SmithKline Beecham
  2. (2021) "Product Information. Accrufer (ferric maltol)." Shield Therapeutics

Disease interactions

6 potential interactions Applies to: 6 conditions, including Depression, Psychosis, Lupus Erythematosus, Liver Disease, and Renal Dysfunction.

Bone Marrow Depression/Low Blood Counts

Major:

phensuximide

Phensuximide has a major potential interaction with Bone Marrow Depression/Low Blood Counts.

Hematologic toxicities, some with fatal outcome, have been associated with the use of succinimide anticonvulsants. Leukopenia, agranulocytosis, aplastic anemia, thrombocytopenia, pancytopenia, and eosinophilia have been reported. Therapy with succinimide anticonvulsants should be administered cautiously in patients with preexisting blood dyscrasias and/or bone marrow suppression. Complete blood counts, including platelets, should be performed prior to initiating therapy and periodically during therapy. Marked depression of blood counts may be indication for withdrawal of succinimide therapy.

Depression

Moderate:

phensuximide

Phensuximide 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.

Liver Disease

Major:

phensuximide

Phensuximide has a major potential interaction with Liver Disease.

Succinimide anticonvulsants have produced morphological and functional changes in the liver of animals. In humans, abnormalities in liver and renal function studies have been reported. Therapy with succinimide anticonvulsants should be administered with extreme caution in patients with known hepatic or renal diseases. Periodic urinalysis and liver function tests are recommended for all patients treated with these drugs.

Lupus Erythematosus

Major:

phensuximide

Phensuximide has a major potential interaction with Lupus Erythematosus.

Cases of systemic lupus erythematosus (SLE) have been reported in association with the use of succinimide anticonvulsants, primarily ethosuximide. Some of the patients recovered promptly following discontinuation of the drug, while others continued to have active disease long after. Therapy with succinimide anticonvulsants should be administered cautiously in patients with a history of SLE.

Psychosis

Moderate:

phensuximide

Phensuximide 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.

Renal Dysfunction

Major:

phensuximide

Phensuximide has a major potential interaction with Renal Dysfunction.

Succinimide anticonvulsants have produced morphological and functional changes in the liver of animals. In humans, abnormalities in liver and renal function studies have been reported. Therapy with succinimide anticonvulsants should be administered with extreme caution in patients with known hepatic or renal diseases. Periodic urinalysis and liver function tests are recommended for all patients treated with these drugs.

Report options

Loading...
QR code containing a link to this page

More resources

Foltabs Prenatal Plus DHA

A total of 172 drugs are known to interact with Foltabs Prenatal Plus DHA.

phensuximide

A total of 246 drugs are known to interact with phensuximide.

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.

Medical Disclaimer