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Drug Interactions between Nuvelle TS Phase I and pacritinib

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

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Interactions between your drugs

Major

estradiol pacritinib

Applies to: Nuvelle TS Phase I (estradiol) and pacritinib

MONITOR CLOSELY: Coadministration of Janus kinase (JAK) inhibitors and combined hormonal contraceptives, hormone replacement therapy (HRT), or estrogen receptor modulators may potentiate the risk of venous thromboembolism (VTE). Serious and sometimes fatal VTE events including pulmonary embolism (PE) and deep vein thrombosis (DVT) have been observed in patients taking JAK inhibitors. In a randomized safety study of patients with rheumatoid arthritis with at least one cardiovascular risk factor (e.g., prior VTE, body mass index greater than or equal to 35 kg/m2, older age, history of chronic lung disease), an increased risk for VTE was observed with tofacitinib compared to tumor necrosis factor (TNF) inhibitors. Similarly, in a meta-analysis evaluating 16 randomized controlled trials for the incidence of venous thromboembolism with JAK inhibitor use (including tofacitinib, upadacitinib, filgotinib, and baricitinib), a potential increase in the risk of VTE, although not clinically significant, was observed compared to placebo or TNF inhibitors. Subgroup analyses showed higher VTE events with tofacitinib compared to TNF inhibitors and with higher doses of JAK inhibitors. Data surrounding the use of JAK inhibitors with hormonal contraceptives, HRT and or estrogen receptor modulators are not available.

MANAGEMENT: Caution and close clinical monitoring are advised when JAK inhibitors are administered in patients with an increased risk for venous thromboembolism (VTE), such as those taking combined hormonal contraceptives, hormone replacement therapy (HRT) and/or estrogen receptor modulators. While not discussed in US product labeling, international labeling for some JAK inhibitors recommends avoiding concomitant use due to their potential to increase the risk of VTE. Other international labeling suggests JAK inhibitors may be administered if necessary, but with additional monitoring. Patients and their caregivers should be advised to seek medical attention if they experience signs and symptoms of VTE. Individual product labeling should be consulted for further guidance.

References

  1. (2011) "Product Information. Jakafi (ruxolitinib)." Incyte Corporation
  2. (2019) "Product Information. Rinvoq (upadacitinib)." AbbVie US LLC
  3. (2022) "Product Information. Cibinqo (abrocitinib)." Pfizer U.S. Pharmaceuticals Group
  4. (2022) "Product Information. Vonjo (pacritinib)." CTI BioPharma Corp.
  5. (2021) "Product Information. Xeljanz (tofacitinib)." Pfizer U.S. Pharmaceuticals Group, SUPPL-28
  6. (2021) "Product Information. Xeljanz (tOFACitinib)." Pfizer Australia Pty Ltd, pfpxeljt11021
  7. (2022) "Product Information. Xeljanz (tofacitinib)." Pfizer Ltd, XJ 5mg 26_0 GB
  8. (2022) "Product Information. Inrebic (fedratinib)." Bristol-Myers Squibb
  9. (2021) "Product Information. Inrebic (fedratinib)." Bristol-Myers Squibb Pharmaceuticals Ltd
  10. (2022) "Product Information. Olumiant (baricitinib)." Lilly, Eli and Company, SUPPL-7
  11. (2023) "Product Information. Litfulo (ritlecitinib)." Pfizer U.S. Pharmaceuticals Group
  12. (2023) "Product Information. Ojjaara (momelotinib)." GlaxoSmithKline
  13. (2023) "Product Information. Olumiant (bARICITinib)." Eli Lilly Australia Pty Ltd, vA9.0_May2023
  14. (2024) "Product Information. Olumiant (baricitinib)." Eli Lilly and Company Ltd
View all 14 references

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Drug and food interactions

Major

pacritinib food

Applies to: pacritinib

GENERALLY AVOID: Theoretically, coadministration with grapefruit juice may increase the plasma concentrations of pacritinib, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for the potent CYP450 3A4 inhibitor, clarithromycin. In a clinical drug interaction study, a single dose of pacritinib (400 mg) was administered following treatment with clarithromycin (500 mg twice daily for 5 days). The peak plasma concentration (Cmax) and systemic exposure (AUC) of pacritinib increased by 30% and 80%, respectively, compared to pacritinib administered alone. Longer treatment with clarithromycin that results in maximal CYP450 3A4 inhibition may increase pacritinib exposure even higher. 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 pacritinib may increase the risk of adverse effects such as diarrhea, thrombocytopenia, infection, and QT prolongation.

Pacritinib pharmacokinetics were not significantly affected when administered with a high-fat meal.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid consumption of grapefruit or grapefruit juice during treatment with pacritinib. Pacritinib may be administered with or without food.

References

  1. (2022) "Product Information. Vonjo (pacritinib)." CTI BioPharma Corp.

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Minor

estradiol food

Applies to: Nuvelle TS Phase I (estradiol)

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

References

  1. Weber A, Jager R, Borner A, et al. (1996) "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception, 53, p. 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T (1995) "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet, 20, p. 219-24

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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.


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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.