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Drug Interactions between Diacomit and Fintepla

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

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Interactions between your drugs

Major

fenfluramine stiripentol

Applies to: Fintepla (fenfluramine) and Diacomit (stiripentol)

ADJUST DOSE: Coadministration of fenfluramine with stiripentol and clobazam, with or without valproate, may increase the plasma concentrations of fenfluramine. Over 75% of fenfluramine is metabolized to norfenfluramine prior to elimination, primarily by CYP450 1A2, 2B6 and 2D6, but also to a minor extent by CYP450 2C9, 2C19 and 3A4/5. At therapeutic concentrations, stiripentol may significantly inhibit CYP450 2C19, 2D6 and 3A4, and possibly also CYP450 1A2, 2C8 and 2C9. Induction of CYP450 1A2, 2B6 and 3A4 has also been demonstrated in vitro. Clobazam has been shown to be a weak inhibitor of CYP450 2D6 and weak inducer of CYP450 3A4 in vivo. When a single 0.7 mg/kg dose of fenfluramine oral solution was coadministered with a single dose of a stiripentol, clobazam and valproic acid combination in healthy volunteers, fenfluramine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 18% and 69%, respectively, while the Cmax and AUC of norfenfluramine decreased by 42% and 41%, respectively. The effect of stiripentol plus clobazam on fenfluramine pharmacokinetics is greater when fenfluramine is at steady-state than for the first dose of fenfluramine. Utilizing population pharmacokinetic modeling and simulation on data collected from patients receiving fenfluramine in two clinical studies for the treatment of seizures associated with Dravet syndrome, the coadministration of fenfluramine 0.1 mg/kg twice daily (0.2 mg/kg/day, up to a maximum of 17 mg/day) with stiripentol plus clobazam, with or without valproate, is expected to result in a 166% increase in fenfluramine AUC and a 38% decrease in norfenfluramine AUC at steady state, as compared to fenfluramine administered alone at 0.2 mg/kg/day, up to a maximum of 26 mg/day. Elevated plasma levels of fenfluramine may increase the risk of serious adverse effects such as valvular heart disease, pulmonary arterial hypertension, blood pressure increases, and serotonin syndrome.

MANAGEMENT: For patients taking concomitant stiripentol and clobazam, with or without valproate, who are tolerating fenfluramine at a dosage of 0.1 mg/kg twice daily and require additional seizure reduction, the dosage of fenfluramine may be increased gradually up to a maximum recommended maintenance dosage of 0.2 mg/kg twice daily, not to exceed a total of 17 mg/day, or 13 mg/day in patients with mild (Child-Pugh A) hepatic impairment. Treatment with fenfluramine plus stiripentol and clobazam is not recommended in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment.

References (7)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2020) "Product Information. Fintepla (fenfluramine)." Zogenix, Inc
  3. (2022) "Product Information. Diacomit (stiripentol)." Biocodex USA, SUPPL-3
  4. (2021) "Product Information. Diacomit (Chiesi) (stiripentol)." Chiesi Australia Pty Ltd, 3.0
  5. (2022) "Product Information. Diacomit (stiripentol)." Alan Pharmaceuticals
  6. (2023) "Product Information. Fintepla (fenfluramine)." UCB Pharma Ltd, SUPPL-13
  7. (2024) "Product Information. Fintepla (fenfluramine)." UCB Australia Pty Ltd T/A UCB Pharma Division of UCB Australia

Drug and food interactions

Moderate

fenfluramine food

Applies to: Fintepla (fenfluramine)

GENERALLY AVOID: Alcohol may potentiate the central nervous system and cardiovascular effects of centrally-acting appetite suppressants. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

MANAGEMENT: Concomitant use of centrally-acting appetite suppressants and alcohol should be avoided if possible, especially in patients with a history of cardiovascular disease. Patients should be counselled 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 (3)
  1. Mendelson J, Jones RT, Upton R, Jacob P 3rd (1995) "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther, 57, p. 559-68
  2. (2001) "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn
  3. (2012) "Product Information. Suprenza (phentermine)." Akrimax Pharmaceuticals
Moderate

stiripentol food

Applies to: Diacomit (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.


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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.