What are the interactions between i-pill (levonorgestrel) and promethazine?

I-Pill and Promethazine: Composition and Interaction

I-pill contains levonorgestrel as its active constituent, and while routine pretreatment with antiemetics like promethazine is not recommended, promethazine can be used if vomiting occurs within 3 hours of taking the emergency contraceptive pill. 1

Active Constituent of I-Pill

• I-pill is a levonorgestrel-based emergency contraceptive pill, typically containing 1.5 mg of levonorgestrel as a single dose 1
• Levonorgestrel is a synthetic progestin (gestagen) that works primarily by blocking or delaying ovulation when taken before the LH surge 2, 3, 4
• The medication is effective when taken within 5 days (120 hours) of unprotected intercourse, though efficacy decreases with time 2, 5

Pairing with Promethazine (Antiemetic Use)

Current Guideline Recommendations

• Routine prophylactic use of antiemetics like promethazine before taking levonorgestrel emergency contraception is NOT recommended 1
• This recommendation is based on the fact that levonorgestrel ECPs cause significantly less nausea and vomiting compared to combined estrogen-progestin emergency contraceptive regimens 1
• Many women do not experience nausea or vomiting with levonorgestrel, making routine pretreatment unnecessary 1

When Promethazine Should Be Used

• If vomiting occurs within 3 hours of taking the emergency contraceptive pill, another dose should be taken as soon as possible, and use of an antiemetic should be considered 1
• Pretreatment with antiemetics may be considered on a case-by-case basis depending on clinical judgment and availability 1
• Evidence shows that antiemetics (including meclizine and metoclopramide, which are similar to promethazine) can reduce the severity of nausea when used with emergency contraceptives 1

Important Clinical Considerations

• Women taking antiemetics may experience additional side effects from the antiemetic medication itself, which should be weighed against the benefit 1
• The decision to offer antiemetics should consider that women taking combined estrogen-progestin ECPs are more likely to need them than those taking levonorgestrel-only formulations 1
• Common adverse effects of levonorgestrel itself include nausea, vomiting, headache, breast tenderness, and transient menstrual bleeding pattern changes 2, 6

No Significant Drug Interactions

• There is no evidence of clinically significant pharmacological interactions between levonorgestrel emergency contraception and promethazine
• The main concern with levonorgestrel interactions involves antiretroviral medications (particularly efavirenz) which can decrease levonorgestrel levels 1