OBJECT DRUGS

• Contraceptives, Oral

PRECIPITANT DRUGS

Enzyme Inducers:

• Armodafinil (Nuvigil)
• Barbiturates
• Bexarotene (Targretin)
• Bosentan (Tracleer)
• Carbamazepine (Tegretol, etc.)
• Dabrafenib (Tafinlar)
• Deferasirox (Exjade)
• Dexamethasone (Decadron, etc.)
• Efavirenz (Sustiva)
• Lumacaftor (Orkambi)
• Felbamate (Felbatol)
• Griseofulvin (Fulvicin, etc.)
• Modafinil (Provigil)
• Nelfinavir (Viracept) *
• Nevirapine (Viramune, etc.)
• Oxcarbazepine (Trileptal, etc.)
• Perampanel (Fycompa)
• Phenytoin (Dilantin, etc.)
• Primidone (Mysoline)
• Rifabutin (Mycobutin)
• Rifampin (Rifadin, etc.)
• Rifapentine (Priftin)
• Ritonavir (Norvir)
• Rufinamide (Banzel)
• St. John's wort
• Topiramate (Topamax, etc.)

* Nelfinavir is an inhibitor of CYP3A4, but can substantially reduce concentrations of ethinyl estradiol, possibly by induction of glucuronidation and/or CYP2C9.

Comment:

Enzyme inducers increase the risk of ovulation and unintended pregnancy in women receiving oral contraceptives. Felbamate may reduce levels of gestodene but not ethinyl estradiol. Bexarotene and bosentan are both known teratogens, and patients on these agents must use two reliable forms of contraception. At least one case of unintended pregnancy has been reported in a patient using an implantable hormonal contraceptive (Implanon) who took carbamazepine concurrently. The effect of modafinil appears modest, but could increase the risk of contraceptive failure in some people. Keep in mind that enzyme induction is usually gradual and may take days to weeks for onset and offset, depending on the specific inducer. Rufinamide is a mild inducer of CYP3A4, but may reduce the concentrations of ethinyl estradiol and norethindrone. Perampanel (12 mg/day) reduced levonorgestrel AUC by 40%, so consider the possibility that perampanel can reduce the efficacy of hormonal contraceptives.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative: Use an alternative to the enzyme inducer if possible. If the enzyme inducer is necessary consider adding alternative contraception.
• Anticonvulsants: Agents that may be less likely to interact with oral contraceptives include gabapentin (Neurontin), levetiracetam (Keppra), pregabalin (Lyrica), tiagabine (Gabitril), and valproate (Depakote). Oral contraceptives may substantially reduce plasma concentrations of lamotrigine (Lamictal).
• Oral Contraceptives: Some evidence suggests that enzyme inducers may have less effect on other forms of contraception such as depo-medroxyprogesterone acetate or levonorgestrel-releasing intrauterine systems. Consult current prescribing information.
• Circumvent/Minimize: If enzyme inducers are used with oral contraceptives, contraceptive dose may need to be increased. Nonetheless, increases in oral contraceptive dose do not guarantee contraceptive efficacy. When using oral contraceptives with enzyme inducers, patients should use an alternative method of birth control for one cycle after discontinuation of the inducer.
• Monitor: Menstrual irregularities (spotting, breakthrough bleeding) may be a sign of inadequate contraceptive hormone levels, but absence of menstrual problems does not guarantee adequate contraception.