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Drug Interactions between Dermestril Septem and Noxafil

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

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Interactions between your drugs

Moderate

estradiol posaconazole

Applies to: Dermestril Septem (estradiol) and Noxafil (posaconazole)

MONITOR: Azole antifungal agents may increase the plasma concentrations of estrogens and progestins. The mechanism is decreased clearance of the hormones due to inhibition of CYP450 3A4 activity by azole antifungals. Coadministration of voriconazole (200 mg every 12 hours) and an oral contraceptive containing 35 mcg of ethinyl estradiol and 1 mg of norethindrone increased the steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of ethinyl estradiol by an average of 36% and 61%, respectively, and Cmax and AUC of norethindrone by 15% and 53%, respectively, in healthy volunteers. Fluconazole doses of 150 mg and 200 mg have also been shown to increase the serum concentrations of ethinyl estradiol and levonorgestrel in healthy women receiving low-dose oral contraceptives, while single and multiple doses of fluconazole 50 mg had no significant effect on the pharmacokinetics of a high-dose oral contraceptive containing 150 mcg ethinyl estradiol and norgestrel 300 mcg. Ironically, there have been isolated reports of breakthrough bleeding and unintended pregnancy during use of oral contraceptives with itraconazole, which would suggest decreased rather than increased effect of the contraceptives. However, the association to itraconazole is questionable.

MANAGEMENT: During concomitant therapy with azole antifungal agents, patients should be observed for increased or altered pharmacologic response to estrogens and progestins, and dosage(s) adjusted accordingly as necessary.

References

  1. Lazar JD, Wilner KD "Drug interactions with fluconazole." Rev Infect Dis 12 Suppl 3 (1990): s327-33
  2. Pillans PI, Sparrow MJ "Pregnancy associated with a combined oral contraceptive and itraconazole." N Z Med J 106 (1993): 436
  3. Devenport MH, Crook D, Wynn V, Lees LJ "Metabolic effects of low-dose fluconazole in healthy female users and non-users of oral contraceptives." Br J Clin Pharmacol 27 (1989): 851-9
  4. Sinofsky FE, Pasquale SA "The effect of fluconazole on circulating ethinyl estradiol levels in women taking oral contraceptives." Am J Obstet Gynecol 178 (1998): 300-4
  5. Weisberg E "Interactions between oral contraceptives and antifungals antibacterials - Is contraceptive failure the result?." Clin Pharmacokinet 36 (1999): 309-13
  6. "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals (2002):
View all 6 references

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Drug and food interactions

Moderate

posaconazole food

Applies to: Noxafil (posaconazole)

ADJUST DOSING INTERVAL: Food significantly increases the absorption of posaconazole from the oral suspension but only modestly from the delayed-release tablet. Following single-dose administration, posaconazole mean peak plasma concentration (Cmax) and systemic exposure (AUC) are approximately 2.5 to 3 times higher when the oral suspension is given with a nonfat meal or a nutritional supplement (14 grams of fat) than when given under fasting conditions, and approximately 3.5 to 4 times higher when given during or 20 minutes after a high-fat meal (50 grams of fat) than under fasting conditions. Acidic beverages may also increase posaconazole absorption. In 12 healthy volunteers, administration of a single 400 mg dose of posaconazole suspension with 12 ounces of ginger ale increased posaconazole Cmax by 92% and AUC by 70% compared to administration after fasting. In contrast, the Cmax and AUC of posaconazole increased by just 16% and 51%, respectively, when posaconazole tablets were given as a single 300 mg dose to healthy volunteers after a high-fat meal relative to a fasted state.

GENERALLY AVOID Concomitant use of alcohol and posaconazole administered in the form of delayed-release oral suspension may lead to a faster release of posaconazole. An in vitro dissolution study determined a potential for alcohol-induced dose-dumping with the delayed-release oral suspension of posaconazole.

MONITOR: In 5 study subjects, posaconazole Cmax decreased by 27% to 53% and AUC decreased by 33% to 51% when the oral suspension was administered via a nasogastric tube as opposed to orally.

MANAGEMENT: Posaconazole tablets should be taken with food, whereas posaconazole oral suspension should be administered during or immediately (i.e., within 20 minutes) following a full meal to enhance bioavailability. Patients who cannot eat a full meal should take the suspension with a liquid nutritional supplement or an acidic carbonated beverage such as ginger ale. In patients who cannot eat a full meal or tolerate an oral nutritional supplement or an acidic carbonated beverage and who do not have the option of taking another formulation of posaconazole, alternative antifungal therapy should be considered; otherwise, monitor patients closely for breakthrough fungal infections. Patients receiving posaconazole via a nasogastric tube should also be closely monitored due to increased risk of treatment failure associated with lower plasma exposure. Administration of alcohol with posaconazole from the delayed-release oral suspension formulation is not recommended.

References

  1. "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation (2006):
  2. Sansone-Parsons A, Krishna G, Calzetta A, et al. "Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers." Antimicrob Agents Chemother 50 (2006): 1881-3
  3. Krishna G, Moton A, Ma L, Malavade D, Medlock M, McLeod J "Effect of gastric pH, dosing regimen and prandial state, food and meal timing relative to dose, and gastro-intestinal motility on absorption and pharmacokinetics of the antifungal posaconazole." 18th European Congress of Clinical Microbiology and Infectious Diseases April (2008): 20
  4. Walravens J, Brouwers J, Spriet I, Tack J, Annaert P, Augustijns P "Effect of pH and Comedication on Gastrointestinal Absorption of Posaconazole: Monitoring of Intraluminal and Plasma Drug Concentrations." Clin Pharmacokinet 50 (2011): 725-34
View all 4 references

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Minor

estradiol food

Applies to: Dermestril Septem (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. "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception 53 (1996): 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet 20 (1995): 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

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