Interactions between Ganaxolone and Pralsetinib
1 drug interaction and 14 additional warnings found for the following 2 drugs:
- ganaxolone
- pralsetinib
Drug interactions
Moderate drug interactions
Moderate:
pralsetinib ganaxolone
Applies to: pralsetinib and ganaxolone
Monitor
Coadministration with pralsetinib may alter the plasma concentrations of drugs that are substrates of CYP450 2C8, 2C9, 3A4, and/or 3A5. In vitro studies indicate that pralsetinib is both an inhibitor as well as an inducer of CYP450 2C8, 2C9, 3A4, and 3A5. Therefore, pralsetinib may decrease clearance via inhibition or increase clearance via induction of these isoenzymes, resulting in increased or decreased plasma concentrations of agents that are metabolized by one or more of these isoenzymes. Clinical and pharmacokinetic data are currently lacking.
Management
Caution is advised if pralsetinib is used concomitantly with drugs that are substrates of CYP450 2C8, 2C9, 3A4, and/or 3A5, particularly sensitive substrates or those with a narrow therapeutic range. Some authorities recommend avoiding coadministration of pralsetinib with CYP450 2C8, 2C9, 3A4, and/or 3A5 substrates for which minimal concentration changes may lead to therapeutic failure or serious toxicities. If coadministration is required, dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever pralsetinib is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.
References (4)
- (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Pty Ltd, GAVRETO 20230406
- (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Ltd
- (2023) "Product Information. Gavreto (pralsetinib)." Genentech
- (2021) "Product Information. Gavreto (pralsetinib)." Hoffmann-La Roche Limited
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
pralsetinib Food/Lifestyle
Applies to: pralsetinib
Adjust dosing interval
Food significantly increases the oral bioavailability of pralsetinib. According to the product labeling, administration of pralsetinib (200 mg) with a high-fat meal (approximately 800 to 1000 calories; 50% to 60% from fat) increased mean pralsetinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 104% and 122%, respectively. The median time to maximum concentration (Tmax) was delayed from 4 hours to 8.5 hours, when compared to the fasted state.
Generally avoid
The juice of grapefruit and/or Seville oranges may increase the plasma concentrations of pralsetinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit and Seville oranges. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to pralsetinib may increase the risk of adverse effects such as interstitial lung disease/pneumonitis, liver transaminase elevations, hypertension, and hemorrhage. Some clinical trials have also observed prolongation of the QT interval in patients on pralsetinib, though this was not observed in a study of 34 patients with rearranged during transfection (RET)-altered solid tumors on pralsetinib at the recommended dosage.
Management
Pralsetinib should be administered on an empty stomach, with no food intake recommended for at least 2 hours before and at least 1 hour after taking the medication. Patients should avoid consumption of grapefruit, grapefruit juice, Seville oranges, or Seville orange juice during treatment with pralsetinib.
References (4)
- (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Pty Ltd, GAVRETO 20230406
- (2024) "Product Information. Gavreto (pralsetinib)." Genentech
- (2024) "Product Information. Gavreto (pralsetinib)." Roche Products Ltd
- (2024) "Product Information. Gavreto (pralsetinib)." Hoffmann-La Roche Limited
Moderate food/lifestyle interactions
Moderate:
ganaxolone Food/Lifestyle
Applies to: ganaxolone
Adjust dosing interval
Food enhances the oral bioavailability of ganaxolone. When administered with a high-fat meal, ganaxolone peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3- and 2-fold, respectively, compared to administration under fasted conditions. Ganaxolone was administered with food in the premarketing study population. The efficacy of ganaxolone when administered in the fasted state is unknown.
Generally avoid
Concomitant use of ganaxolone with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.
Management
Ganaxolone must be administered with food according to the manufacturer. 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.
References (1)
- (2022) "Product Information. Ztalmy (ganaxolone)." Marinus Pharmaceuticals, Inc
Disease interactions
12 potential interactions Applies to: 10 conditions, including High Blood Pressure, Depression, Hypokalemia, Psychosis, and Hypocalcemia.
Alcoholism
Moderate:
ganaxolone
Ganaxolone has a moderate potential interaction with Alcoholism.
Ganaxolone can cause somnolence and sedation; other CNS depressants (including alcohol) could potentiate these effects. Caution is advised when using this agent in patients with alcohol disorders. Patients should be monitored for somnolence and sedation, and patients should be advised not to drive or operate machinery until they know how ganaxolone will affect them.
Depression
Moderate:
ganaxolone
Ganaxolone 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.
High Blood Pressure
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with High Blood Pressure.
Hypertension has been reported in patients in treatment with pralsetinib. This drug should not be initiated in patients with uncontrolled hypertension. Caution and close monitoring is advised.
Hypocalcemia
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with Hypocalcemia.
QT prolongation was reported in clinical trials in patients that received pralsetinib. Use with caution in patients with history of arrhythmias, QT prolongation or taking medications that can prolong the QT interval (e.g., strong CYP450 3A4 inhibitors). Monitor QT interval and serum electrolytes before initiation and regularly during treatment. Hypokalemia, hypomagnesemia, and hypocalcemia should be corrected prior and during treatment.
Hypokalemia
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with Hypokalemia.
QT prolongation was reported in clinical trials in patients that received pralsetinib. Use with caution in patients with history of arrhythmias, QT prolongation or taking medications that can prolong the QT interval (e.g., strong CYP450 3A4 inhibitors). Monitor QT interval and serum electrolytes before initiation and regularly during treatment. Hypokalemia, hypomagnesemia, and hypocalcemia should be corrected prior and during treatment.
Liver Disease
Moderate:
ganaxolone
Ganaxolone has a moderate potential interaction with Liver Disease.
The effect of liver dysfunction on the pharmacokinetics of ganaxolone has not been studied; since this drug undergoes hepatic clearance, liver dysfunction can increase ganaxolone exposure. Caution is advised in patients with impaired liver function; they should be monitored for side effects and may require a reduced dosage of ganaxolone.
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with Liver Disease.
Pralsetinib has not been studied in patients with moderate or severe hepatic impairment. Additionally, clinical trials reported hepatotoxicity in some patients receiving treatment. Caution and close monitoring is advised if administering in patients with hepatic impairment.
Long QT Syndrome
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with Long QT Syndrome.
QT prolongation was reported in clinical trials in patients that received pralsetinib. Use with caution in patients with history of arrhythmias, QT prolongation or taking medications that can prolong the QT interval (e.g., strong CYP450 3A4 inhibitors). Monitor QT interval and serum electrolytes before initiation and regularly during treatment. Hypokalemia, hypomagnesemia, and hypocalcemia should be corrected prior and during treatment.
Magnesium Imbalance
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with Magnesium Imbalance.
QT prolongation was reported in clinical trials in patients that received pralsetinib. Use with caution in patients with history of arrhythmias, QT prolongation or taking medications that can prolong the QT interval (e.g., strong CYP450 3A4 inhibitors). Monitor QT interval and serum electrolytes before initiation and regularly during treatment. Hypokalemia, hypomagnesemia, and hypocalcemia should be corrected prior and during treatment.
Psychosis
Moderate:
ganaxolone
Ganaxolone 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
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with Renal Dysfunction.
Pralsetinib has not been studied in patients with severe renal impairment or end-stage renal disease. Caution is advised if administering in these patients.
Minor:
ganaxolone
Ganaxolone has a minor potential interaction with Renal Dysfunction.
The effect of renal dysfunction on the pharmacokinetics of ganaxolone has not been studied; however, since renal excretion is a minor elimination pathway, impaired renal function is unlikely to increase ganaxolone exposures significantly. Caution is recommended in these patients.
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More resources
ganaxolone
A total of 423 drugs are known to interact with ganaxolone.
- Ganaxolone is in the drug class Gabapentinoids.
- Ganaxolone is used to treat Seizures.
pralsetinib
A total of 740 drugs are known to interact with pralsetinib.
- Pralsetinib is in the drug class multikinase inhibitors.
- Pralsetinib is used to treat the following conditions:
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
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