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Drug Interactions between phenobarbital and stiripentol

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

PHENobarbital stiripentol

Applies to: phenobarbital and stiripentol

GENERALLY AVOID: Coadministration with potent inducers of CYP450 1A2, 2C19, and/or 3A4 may significantly decrease the plasma concentrations of stiripentol, which has been shown in vitro to undergo phase I metabolism via these pathways. Pharmacokinetic studies have not been conducted. In a retrospective analysis of 220 stiripentol serum concentrations derived from 75 patients in three German epilepsy centers, concomitant use of phenobarbital or phenytoin (n=7) was associated with a 63% decrease in stiripentol serum concentrations.

GENERALLY AVOID: Coadministration with stiripentol may increase the plasma concentrations of other anticonvulsants that are metabolized by CYP450 2C19 or 3A4 such as carbamazepine, phenobarbital, phenytoin, and primidone. Stiripentol itself is metabolized by these pathways and has been reported to also inhibit multiple CYP450 isoenzymes in vitro, thus both competitive and noncompetitive inhibition may occur. In a small pharmacokinetics study (n=6), stiripentol 1200 mg/day and 2400 mg/day reduced carbamazepine elimination clearance by 39% and 71%, respectively, in one subject, and phenytoin elimination clearance by 37% and 78%, respectively, in five subjects. Phenytoin toxicity was observed in two subjects. Stiripentol 2400 mg/day reduced phenobarbital elimination clearance by 33% and 39% in two subjects.

MONITOR CLOSELY: Coadministration of stiripentol with other anticonvulsants may increase central nervous system adverse effects such as somnolence, dizziness, confusion, difficulty concentrating, and impairment of psychomotor skills.

MANAGEMENT: Concomitant use of stiripentol with potent CYP450 inducers such as carbamazepine, phenobarbital, phenytoin, and primidone should generally be avoided. If coadministration is required, patients should have plasma anticonvulsant concentrations monitored and dosage adjustments made accordingly. Patients should also be monitored for increased adverse effects such as dizziness, drowsiness, lethargy, confusion, diplopia, nystagmus, ataxia, dysarthria, hypothermia, and hypotension.

References (6)
  1. Tran A, Vauzellekervroedan F, Rey E, Pons G, Dathis P, Chiron C, Dulac O, Renard F, Olive G (1996) "Effect of stiripentol on carbamazepine plasma concentration and metabolism in epileptic children." Eur J Clin Pharmacol, 50, p. 497-500
  2. Cazali N, Tran A, Treluyer JM, et al. (2003) "Inhibitory effect of stiripentol on carbamazepine and saquinavir metabolism in human." Br J Clin Pharmacol, 56, p. 526-36
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid
  5. May TW, Boor R, Mayer T, et al. (2012) "Concentrations of stiripentol in children and adults with epilepsy: the influence of dose, age, and comedication." Ther Drug Monit, 34, p. 390-7
  6. (2018) "Product Information. Diacomit (stiripentol)." Biocodex USA

Drug and food interactions

Major

PHENobarbital food

Applies to: phenobarbital

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References (5)
  1. Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
  3. Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
  4. Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
  5. Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102
Moderate

stiripentol food

Applies to: stiripentol

GENERALLY AVOID: Taking stiripentol on an empty stomach may reduce its oral bioavailability. Stiripentol degrades rapidly when exposed to gastric acid in an empty stomach.

GENERALLY AVOID: Alcohol may potentiate the depressant effects of stiripentol on the central nervous system. Concomitant use may result in increased sedation and dizziness as well as impairment of psychomotor skills.

GENERALLY AVOID: It is not known whether stiripentol may reduce theophylline and caffeine metabolism, as data on the potential for inhibition of CYP450 1A2 are limited. Consumption of foods and nutritional products such as cola drinks (which contain significant quantities of caffeine) and chocolate (which contains caffeine and trace amounts of theophylline) may be unsafe during treatment with stiripentol, particularly in children.

MANAGEMENT: Stiripentol should be taken during a meal for optimal absorption; however, it should not be taken with milk, dairy products (e.g., yogurt, soft cream cheese), fruit juice, or carbonated beverages. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them. Food and beverages that may contain caffeine or theophylline such as colas, chocolate, coffee, tea, or energy drinks should also be avoided during treatment with stiripentol.

References (3)
  1. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  2. EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid
  3. (2018) "Product Information. Diacomit (stiripentol)." Biocodex USA

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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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.

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