Drug Interactions between Aurovela 1/20 and lorlatinib
This report displays the potential drug interactions for the following 2 drugs:
- Aurovela 1/20 (ethinyl estradiol/norethindrone)
- lorlatinib
Interactions between your drugs
ethinyl estradiol lorlatinib
Applies to: Aurovela 1 / 20 (ethinyl estradiol / norethindrone) and lorlatinib
ADDITIONAL CONTRACEPTION RECOMMENDED: Concomitant use with lorlatinib may decrease the plasma concentrations and efficacy of contraceptive hormones. In vitro studies show that lorlatinib is an inducer of CYP450 3A, the isoenzyme primarily responsible for the metabolic clearance of sex hormones. The use of hormonal contraceptives during treatment with lorlatinib can result in contraception failure. Lorlatinib can also cause embryo-fetal harm when administered to a pregnant woman.
MANAGEMENT: Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable during concomitant therapy with lorlatinib. Since the use of lorlatinib is likely associated with embryo-fetal harm, it is particularly important that patients not become pregnant during treatment. Therefore, hormonal contraceptives should not be used as the sole method of birth control in women of childbearing potential treated with lorlatinib. Women of childbearing potential should use a highly effective, non-hormonal method of contraception during treatment with lorlatinib and for 6 months after the last dose. Male patients with female partners of reproductive potential should use effective contraception during treatment with lorlatinib and for 3 months after the last dose.
References (1)
- (2021) "Product Information. Lorbrena (lorlatinib)." Pfizer U.S. Pharmaceuticals Group
norethindrone lorlatinib
Applies to: Aurovela 1 / 20 (ethinyl estradiol / norethindrone) and lorlatinib
ADDITIONAL CONTRACEPTION RECOMMENDED: Concomitant use with lorlatinib may decrease the plasma concentrations and efficacy of contraceptive hormones. In vitro studies show that lorlatinib is an inducer of CYP450 3A, the isoenzyme primarily responsible for the metabolic clearance of sex hormones. The use of hormonal contraceptives during treatment with lorlatinib can result in contraception failure. Lorlatinib can also cause embryo-fetal harm when administered to a pregnant woman.
MANAGEMENT: Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable during concomitant therapy with lorlatinib. Since the use of lorlatinib is likely associated with embryo-fetal harm, it is particularly important that patients not become pregnant during treatment. Therefore, hormonal contraceptives should not be used as the sole method of birth control in women of childbearing potential treated with lorlatinib. Women of childbearing potential should use a highly effective, non-hormonal method of contraception during treatment with lorlatinib and for 6 months after the last dose. Male patients with female partners of reproductive potential should use effective contraception during treatment with lorlatinib and for 3 months after the last dose.
References (1)
- (2021) "Product Information. Lorbrena (lorlatinib)." Pfizer U.S. Pharmaceuticals Group
Drug and food interactions
lorlatinib food
Applies to: lorlatinib
GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of lorlatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
MANAGEMENT: Patients treated with lorlatinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. If coadministration is unavoidable, some authorities recommend reducing the initial dosage of lorlatinib from 100 mg orally once daily to 75 mg orally once daily. In patients who have had a dosage reduction to 75 mg orally once daily due to adverse reactions, the lorlatinib dosage should be further reduced to 50 mg orally once daily upon initiation of a potent CYP450 3A4 inhibitor. After 3 plasma half-lives following discontinuation of the potent CYP450 3A4 inhibitor, the lorlatinib dosage may be increased to that used prior to initiation of the inhibitor.
References (2)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2018) "Product Information. Lorbrena (lorlatinib)." Pfizer U.S. Pharmaceuticals Group
norethindrone food
Applies to: Aurovela 1 / 20 (ethinyl estradiol / norethindrone)
MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.
References (32)
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ethinyl estradiol food
Applies to: Aurovela 1 / 20 (ethinyl estradiol / norethindrone)
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 (2)
- Weber A, Jager R, Borner A, et al. (1996) "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception, 53, p. 41-7
- 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
ethinyl estradiol food
Applies to: Aurovela 1 / 20 (ethinyl estradiol / norethindrone)
The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.
References (1)
- Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80
norethindrone food
Applies to: Aurovela 1 / 20 (ethinyl estradiol / norethindrone)
The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.
References (1)
- Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80
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
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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