Levonorgestrel Interactions
- Amprenavir
- Aprepitant
- Atazanavir
Barbiturates
- Bexarotene
- Bosentan
- Carbamazepine
- Ethotoin
- Felbamate
- Fosamprenavir
- Fosphenytoin
- Griseofulvin
- Indinavir
- Lopinavir; Ritonavir
- Modafinil
- Nelfinavir
- Oxcarbazepine
- Phenytoin
- Pioglitazone
- Primidone
- Rifabutin
- Rifampin
- Rifapentine
- Ritonavir
- St. John’s Wort, Hypericum perforatum
- Tipranavir
- Topiramate
- Troglitazone
- Warfarin
Levonorgestrel Interactions
Hormonal contraceptives may decrease the serum concentrations of amprenavir and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Hormonal contraceptives, including levonorgestrel, should not be administered with amprenavir or fosamprenavir. Data on the effects that other protease inhibitors have on the serum concentrations of estrogens and progestins are complex. Some protease inhibitors increase (i.e., ritonavir, lopinavir; ritonavir, nelfinavir, tipranavir) and others decrease (i.e., atazanavir, indinavir) the metabolism of hormonal contraceptives. The safety and efficacy of hormonal contraceptives may be affected if coadministered with protease inhibitors. Women receiving hormonal contraceptives and anti-retroviral protease inhibitors concurrently should be instructed to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives concurrently with protease inhibitors to use an additional method of contraception to protect against unwanted pregnancy, unless other drug-specific recommendations are made by the manufacturer of the protease inhibitor. Furthermore, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, women who receive hormonal contraceptives concurrently with protease inhibitors should use an additional barrier method of contraception such as condoms.
Drugs that can induce hepatic enzymes can accelerate the rate of metabolism of hormonal contraceptives, including levonorgestrel implants. Pregnancy has been reported during therapy with progestin contraceptives in patients receiving barbiturates (e.g., phenobarbital, primidone), carbamazepine, oxcarbazepine, phenytoin, or rifampin concurrently. Felbamate, fosphenytoin (and possibly ethotoin), griseofulvin, modafinil, other rifamycins (e.g., rifabutin and rifapentine), ritonavir, topiramate, pioglitazone, and troglitazone may also induce hepatic enzymes. An alternate or additional form of contraception should be considered in patients prescribed systemic forms of levonorgestrel who require concomitant therapy with enzyme-inducing anticonvulsants, rifamycins, modafinil, or troglitazone. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of the interacting medication.
St. John’s wort, Hypericum perforatum appears to interact with estrogens and oral contraceptives. One report noted intermenstrual bleeding after the concurrent use of St. John’s wort in 8 premenstrual women who had been on oral contraceptives for long durations of time. Intermenstrual bleeding implies that there may be a loss of contraceptive or hormonal-replacement efficacy. It is thought that St. John’s wort induces hormone metabolism via induction of the hepatic CYP3A4 isoenzyme. The interaction occurred within 1 week of beginning St. John’s wort in five of the cases. In 3 patients for whom follow-up was available, the discontinuation of St. John’s wort resolved the bleeding abnormalities. It is possible that, as with other CYP3A4 inducers, St. John’s wort could also reduce the therapeutic efficacy of progestin-only contraceptives (e.g., levonorgestrel, medroxyprogesterone, and norgestrel). Women should report irregular menstrual bleeding or other hormone-related symptoms to their health care providers if they are taking St. John’s wort concurrently with their hormones. Avoidance of these combinations is recommended.
Oral levonorgestrel-containing emergency contraceptive regimens may interact with warfarin and concurrent use may require patient education and monitoring. A case report of an interaction of warfarin with a levonorgestrel-only oral emergency contraceptive regimen has been described. The patient involved had familial antithrombin deficiency and was stabilized on warfarin as her only medication. The INR increased to 8.1 (without bleeding complications) from 2.1 within 3 days after receiving levonorgestrel. With corrective action, the warfarin was resumed at the usual dose without complication 2 days later. The report speculated that levonorgestrel displaced warfarin from plasma protein binding sites; however, inhibition of hepatic CYP2C9 by levonorgestrel may have decreased the metabolism of warfarin. This is the only report of this type of interaction available.
Concomitant administration of bexarotene capsules and tamoxifen in women with breast cancer resulted in a modest decrease in plasma concentrations of tamoxifen, possibly due to an induction of cytochrome P450 (CYP) 3A4. Based on this interaction, bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of other substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously, unless abstinence is the chosen method, during oral bexarotene therapy. Because of the potential interaction with hormonal contraceptives (e.g., estrogens or progestins), it is strongly recommended that one of the forms of contraception be non-hormonal.
Bosentan is a significant inducer of CYP3A hepatic enzymes. Specific interaction studies have not been performed to evaluate the effect of coadministration of bosentan and hormonal contraceptives (oral contraceptives, estrogens, or progestins), including oral, injectable or implantable agents. Since many of these drugs are metabolized by CYP3A4, there is a possibility of contraceptive failure when bosentan is coadministered. Women should not rely on hormonal contraception alone when taking bosentan; bosentan is teratogenic and is contraindicated during pregnancy.
Upon coadministration with aprepitant, the efficacy of hormonal contraceptives during and for 28 days following the last dose of aprepitant may be reduced. Alternative or back-up methods of contraception should be used during treatment with aprepitant and for 1 month following the last dose of aprepitant. The exact mechanism for this interaction has not been described. Ethinyl estradiol is a CYP3A4 substrate and theoretically may be subject to induced CYP3A4 metabolism by aprepitant, although aprepitant has been shown to moderately inhibit CYP3A4 metabolism of several other CYP3A4 substrates. In a pharmacokinetic study, a daily dose of oral contraceptives containing ethinyl estradiol and norethindrone was administered on Days 1 through 21. Aprepitant was given as a 3-day regimen of 125 mg on Day 8 and 80 mg/day on Days 9 and 10. Ondansetron 32 mg IV on Day 8 and dexamethasone 12 mg PO on Day 8 and 8 mg/day on Days 9, 10, and 11 were also administered. In the study, the AUC of ethinyl estradiol decreased by 19% on Day 10 and there was as much as a 64% decrease in ethinyl estradiol trough concentrations during Days 9 through 21. While there was no effect of aprepitant on the AUC of norethindrone on Day 10, there was as much as a 60% decrease in norethindrone trough concentrations during Days 9 through 21. Since specific studies have not been done with other hormonal contraceptives (e.g., progestins, non-oral combination contraceptives), an alternative or additional non-hormonal method of birth control during treatment and for 28 days after treatment is prudent to avoid potential for contraceptive failure.
[ Last revised: 2/22/2006 1:04:00 PM ]
References
. Yue QY, Bergquist C, Gerden B. Seven cases of decreased effect of warfarin during concomitant treatment with St. John’s wort (letter). Lancet 2000;355:575.
. Ellison J, Thomson AJ, Greer IA. Apparent interaction between warfarin and levonorgestrel used for emerency contraception. BMJ 2000;321:1382.
. Piscitelli SC, Gallicano KD. Interactions among drugs for HIV and opportunistic infections. N Engl J Med 2001;344:984 - 96.
. Hansten PD, Horn JR. Cytochrome P450 Enzymes and Drug Interactions, Table of Cytochrome P450 Substrates, Inhibitors, Inducers and P-glycoprotein and footnotes. In: The Top 100 Drug Interactions - A guide to Patient Management. 2005 Edition. Edmonds, WA: H&H Publications; 2005:157 - 170.
. Tegretol® (carbamazepine) package insert. East Hanover, NJ. Novartis Pharmaceuticals; 2003 Sept.
. Targretin® (bexarotene capsules) package insert. San Diego CA: Ligand Pharmaceuticals Inc.; 2003 April.
. Targretin® gel (bexarotene gel) package insert. San Diego CA: Ligand Pharmaceuticals Inc.; 2002 Feb.
. Actos® (pioglitazone) package insert. Takeda Chemical Industries, Ltd.: Osaka, Japan: 2003 Dec.
. Henderson L, Yue QY, Bergquist C, et al. St John’s wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349 - 56.
. Agenerase® (amprenavir) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2005 Nov.
. Topamax® (topiramate) package insert. Raritan, NJ: Ortho-McNeil Pharmaceutical, Inc.; 2003 Dec.
. Archer JSM, Archer DF. Oral contraceptive efficacy and antibiotic interaction: A myth debunked. J Am Acad Dermatol 2002;46:917 - 23.
. Priftin® (rifapentine) package insert. Kansas City, MO: Aventis Pharmaceuticals Inc.; 2003 Feb.
. Tracleer® (bosentan) package insert. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; 2004 Nov.
. Provigil® (modafinil) package insert. West Chester, PA: Cephalon, Inc; 2004 Feb.
. Dilantin® Kapseals® (extended phenyotin sodium capsules, USP) package insert. Morris Plains, NJ: Parke Davis; 1999 Aug.
. Lexiva® (fosamprenavir calcium) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2005 Nov.
. Trileptal® (oxcarbazepine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2004 March.
. Mycobutin® (rifabutin) package insert. Kalamazoo, MI:Pharmacia & Upjohn, Co.; 2001 Nov.
. Emend® (aprepitant) package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2004 Dec.
. Shane-McWhorter L, Cerveny JD, MacFarlane LL, et al. Enhanced metabolism of levonorgestrel during phenobarbital treatment and resultant pregnancy. Pharmacotherapy 1998;18:1360 - 4.
. Nor-QD® tablets (norethindrone) package insert. Corona, CA: Watson Pharma, Inc.; 2005 Mar.
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