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Drug Interactions between amitriptyline and givinostat

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

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Interactions between your drugs

Moderate

amitriptyline givinostat

Applies to: amitriptyline and givinostat

GENERALLY AVOID: Givinostat can cause prolongation of the QTc interval. Theoretically, coadministration with other agents that can also prolong the QTc interval may result in additive effects and adverse reactions associated with QT prolongation (e.g., other serious arrhythmias, torsade de pointes, sudden death). The largest mean increase observed in the QTc interval of healthy subjects receiving givinostat at approximately 5 times the dose recommended for Duchenne muscular dystrophy (DMD) in patients weighing 60 kg or more was 13.6 ms (upper confidence interval of 17.1 ms) and occurred 5 hours after dose administration. Clinical trials evaluating the use of givinostat in patients with myeloproliferative neoplasms like polycythemia vera have also documented cases of QTc prolongation. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors including, but not limited to, cardiac disease, uncontrolled hypothyroidism, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation may vary depending on the dosage(s) and specific drug(s) involved.

MANAGEMENT: Coadministration of givinostat with other agents that can prolong the QT interval should generally be avoided. The manufacturer of givinostat recommends avoiding its use in patients at an increased risk for ventricular arrhythmias, including those with congenital long QT syndrome, coronary artery disease, and/or electrolyte disturbances. If concurrent administration cannot be avoided, electrocardiograms (ECGs) should be obtained at baseline and during concomitant use as clinically indicated. Givinostat should be withheld if the QTc interval is greater than 500 ms or if there is a change from baseline of greater than 60 ms. The labeling of any other QTc prolonging medication(s) should also be consulted for additional guidance on therapeutic management in the event of QTc prolongation.

References (3)
  1. (2024) "Product Information. Duvyzat (givinostat)." ITF Therapeutics, LLC
  2. Chifotides HT, bose p, Verstovsek S (2020) "Givinostat: an emerging treatment for polycythemia vera." Expert Opin Investig Drugs, 29, p. 525-36
  3. Italfarmaco Spa (2024) Center for drug evaluation and research. Application number: 217865Orig1s000. Integrated review. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/217865Orig1s000IntegratedR.pdf

Drug and food interactions

Moderate

givinostat food

Applies to: givinostat

ADJUST DOSING INTERVAL: Food increases the systemic exposure of givinostat. An open-label, randomized, crossover, single dose food effect study conducted in 12 healthy males used givinostat liquid filled capsules. Subjects received a single oral dose of givinostat (100 mg) in the fasting state or after a high-fat standard meal, with a washout period of at least 1 week in between. The high-fat standard meal resulted in an increase in systemic exposure (AUC) and maximum plasma concentration (Cmax) of about 40% and 23%, respectively, when compared to the fasted state. Additionally, the time to maximum concentration (Tmax) was delayed slightly from 2 to 3 hours.

MANAGEMENT: Givinostat should be administered with food to increase its absorption. In the case of the oral suspension, this can also help mask its bitter taste.

References (2)
  1. (2024) "Product Information. Duvyzat (givinostat)." ITF Therapeutics, LLC
  2. Italfarmaco Spa (2024) Center for drug evaluation and research. Application number: 217865Orig1s000. Integrated review. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/217865Orig1s000IntegratedR.pdf
Moderate

amitriptyline food

Applies to: amitriptyline

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

References (7)
  1. Dorian P, Sellers EM, Reed KL, et al. (1983) "Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction." Eur J Clin Pharmacol, 25, p. 325-31
  2. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  3. Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R (1983) "Biotransformation of amitriptyline in alcoholic depressive patients." Eur J Clin Pharmacol, 24, p. 615-21
  4. Ciraulo DA, Barnhill JG, Jaffe JH (1988) "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther, 43, p. 509-18
  5. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M (1975) "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther, 17, p. 515-22
  6. Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF (1990) "Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls." J Stud Alcohol, 51, p. 366-72
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA (1982) "Imipramine disposition in alcoholics." J Clin Psychopharmacol, 2, p. 2-7
Moderate

amitriptyline food

Applies to: amitriptyline

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

References (4)
  1. (2024) "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd
  2. jeong sh, Newcombe D, sheridan j, Tingle M (2015) "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal, 7, p. 475-82
  3. Vaughan DP, Beckett AH, Robbie DS (1976) "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol, 3, p. 279-83
  4. Zevin S, Benowitz NL (1999) "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet, 36, p. 425-38

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.

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