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Drug Interactions between haloperidol and ivacaftor / lumacaftor

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

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Interactions between your drugs

Major

haloperidol lumacaftor

Applies to: haloperidol and ivacaftor / lumacaftor

MONITOR CLOSELY: Rifampin and other strong CYP450 3A4 inducers may significantly decrease serum concentrations of haloperidol. The mechanism may be related to induction of the CYP450 3A4 metabolism of haloperidol. In an observational study of 12 schizophrenic patients taking oral haloperidol, the administration of rifampin for 28 days reduced haloperidol plasma levels by a mean of 70%, and scores in the Brief Psychiatric Rating Scale (BPRS) were increased. In the same study, another 5 schizophrenic patients receiving haloperidol and rifampin had rifampin discontinued, which led to a mean 3.3-fold increase in haloperidol blood levels. Another observational study involving schizophrenic patients (n=7) also reported significant reduction of serum haloperidol concentration and reduction in haloperidol half-life from 9.4 hours in the control group to 4.9 hours in the rifampin and haloperidol group.

MANAGEMENT: Close observation for reduced clinical effects is recommended if these drugs must be used together. It may be necessary to adjust haloperidol dosage and/or dosage interval whenever a strong CYP450 3A4 inducer is added to or discontinued from therapy.

References

  1. Takeda M, Nishinuma K, Yamashita S, et al. (1986) "Serum haloperidol levels of schizophrenics receiving treatment for tuberculosis." Clin Neuropharmacol, 9, p. 386-97
  2. Borcherding SM, Baciewicz AM, Self TH (1992) "Update on rifampin drug interactions." Arch Intern Med, 152, p. 711-6
  3. (2002) "Product Information. Haldol (haloperidol)." McNeil Pharmaceutical
  4. (2001) "Product Information. Rifadin (rifampin)." Hoechst Marion Roussel
  5. (2001) "Product Information. Lysodren (mitotane)." Bristol-Myers Squibb
  6. Kim YH, Cha IJ, Shim JC, Shin JG, Yoon YR, Kim YK, Kim JI, Park GH, Jang IJ, Woo JI, Shin SG (1996) "Effect of rifampin on the plasma concentration and the clinical effect of haloperidol concomitantly administered to schizophrenic patients." J Clin Psychopharmacol, 16, p. 247-52
  7. Strayhorn VA, Baciewicz AM, Self TH (1997) "Update on rifampin drug interactions, III." Arch Intern Med, 157, p. 2453-8
  8. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  9. Cerner Multum, Inc. "Australian Product Information."
  10. 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
  11. (2015) "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals
  12. Cerner Multum, Inc (2015) "ANVISA Bulário Eletrônico."
  13. Hesslinger B, Normann C, Langosch J, Klose P, Berger M, Walden J (1999) "Effects of carbamazepine and valproate on haloperidol plasma levels and on psychopathologic outcome in schizophrenic patients." J Clin Psychopharmacol, 19, p. 310-5
View all 13 references

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Moderate

haloperidol ivacaftor

Applies to: haloperidol and ivacaftor / lumacaftor

MONITOR: Coadministration with ivacaftor may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme and/or P-glycoprotein (P-gp) efflux transporter. The mechanism is decreased clearance via these pathways due to inhibition by ivacaftor and its pharmacologically active M1 metabolite. The interaction has been studied with midazolam and digoxin, probe substrates for CYP450 3A4 ad P-gp, respectively. In study subjects, midazolam systemic exposure (AUC) increased by 1.5-fold when it was administered with ivacaftor, suggesting weak inhibition of CYP450 3A4 by ivacaftor. Likewise, digoxin AUC increased by 1.3-fold with ivacaftor, which is also consistent with weak inhibition of P-gp by ivacaftor.

MANAGEMENT: Caution is advised when ivacaftor is used with drugs that are substrates of CYP450 3A4 and/or P-gp, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ivacaftor is added to or withdrawn from therapy.

References

  1. (2012) "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals

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Drug and food interactions

Moderate

haloperidol food

Applies to: haloperidol

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

  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 American Pharmaceuticals Inc
View all 4 references

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Moderate

ivacaftor food

Applies to: ivacaftor / lumacaftor

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ivacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Elexacaftor and tezacaftor are also CYP450 3A4 substrates in vitro and may interact similarly with grapefruit juice, whereas lumacaftor is not expected to interact.

ADJUST DOSING INTERVAL: According to prescribing information, systemic exposure to ivacaftor increased approximately 2.5- to 4-fold, systemic exposure to elexacaftor increased approximately 1.9- to 2.5-fold, and systemic exposure to lumacaftor increased approximately 2-fold following administration with fat-containing foods relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.

MANAGEMENT: Patients treated with ivacaftor-containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit or Seville oranges. All ivacaftor-containing medications should be administered with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products. A typical cystic fibrosis diet will satisfy this requirement.

References

  1. (2012) "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals
  2. (2015) "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals
  3. (2022) "Product Information. Symdeko (ivacaftor-tezacaftor)." Vertex Pharmaceuticals
  4. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
View all 4 references

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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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