Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
FLEXERIL vs ALESSE
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Cyclobenzaprine is a centrally acting muscle relaxant that acts primarily at the brainstem, reducing tonic somatic motor activity via inhibition of descending serotonergic pathways. It is structurally related to tricyclic antidepressants and exhibits anticholinergic, sedative, and analgesic effects.
Combination of ethinyl estradiol and levonorgestrel suppresses gonadotropin-releasing hormone (Gn RH) secretion from the hypothalamus, inhibiting pituitary release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thereby preventing ovulation. Additionally, it thickens cervical mucus, impeding sperm penetration, and alters endometrial receptivity.
Adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions (FDA-approved),Off-label: Fibromyalgia, chronic muscle spasm, tension headaches, and as a sleep aid
Prevention of pregnancy,Treatment of moderate acne vulgaris (in women ≥15 years who have achieved menarche and desire contraception),Contraception in women with heavy menstrual bleeding (off-label)
10 mg to 15 mg orally three times a day; maximum daily dose: 30 mg.
One tablet (ethinyl estradiol 20 mcg, levonorgestrel 0.1 mg) orally once daily at the same time each day for 21 days, followed by 7 days of placebo. For initiation, start on the first day of menstrual period or first Sunday after onset of menses.
Terminal elimination half-life is 18 hours (range 8–37 hours) with clinical context: requires dose adjustment in hepatic impairment; steady-state reached in ~3–5 days.
Levonorgestrel: terminal half-life ~17-20 hours (range 11-25 hr). Ethinyl estradiol: biphasic; terminal half-life ~13-27 hours (mean ~17 hr). Clinical context: steady-state achieved within 5-7 days. The half-life supports once-daily dosing with at least 24-hour contraceptive coverage.
Primarily hepatic via CYP3A4, CYP1A2, and CYP2D6; undergoes N-demethylation and glucuronidation. Active metabolite: norcyclobenzaprine.
Ethinyl estradiol is primarily metabolized by CYP3A4 and undergoes conjugation (glucuronidation and sulfation). Levonorgestrel is metabolized by CYP3A4 and reduction, with conjugation to glucuronide and sulfate conjugates.
Primarily hepatic; approximately 50% excreted in urine as metabolites, less than 1% unchanged; 40% excreted in feces via bile.
Renal: ethinyl estradiol (UE2) and levonorgestrel (LNG) metabolites primarily excreted in urine (UE2: ~40% as sulfate and glucuronide conjugates; LNG: ~25% as glucuronides). Fecal/biliary: ~40% (UE2) and ~45% (LNG) eliminated in feces via bile. Unchanged drug excretion is negligible.
~93% bound to plasma proteins, primarily albumin.
Levonorgestrel: 97-99% bound to albumin and sex hormone-binding globulin (SHBG). Ethinyl estradiol: 98-99% bound, primarily to albumin (98.5%), with minor binding to SHBG. Free fractions: LNG ~1%, UE2 ~1.0-1.5%.
~14 L/kg (range 10–20 L/kg), indicating extensive tissue distribution.
Levonorgestrel: Vd ~1.8 L/kg (range 1.5-2.0 L/kg). Ethinyl estradiol: Vd ~2.5-3.5 L/kg (mean ~2.9 L/kg). Indicates extensive tissue distribution, including target organs (ovaries, endometrium, breast). Not clinically adjusted for obesity.
Oral: ~33% due to extensive first-pass metabolism.
Oral: levonorgestrel ~95-100% (highly bioavailable). Ethinyl estradiol ~45-55% (first-pass metabolism reduces bioavailability; interindividual variability due to gut wall and hepatic conjugation). Both are prodrugs requiring hydrolysis for activity.
No specific dosage adjustment guidelines; use with caution in renal impairment due to potential for increased side effects.
No specific GFR-based dose adjustments are recommended; however, use with caution in patients with renal impairment due to potential fluid retention and hypertension.
Contraindicated in hepatic impairment; Child-Pugh class A, B, C: no safe dosage established.
Contraindicated in patients with severe hepatic disease (Child-Pugh class C) or active liver disease. In mild to moderate impairment (Child-Pugh A or B), use only if benefits outweigh risks; no specific dose reduction guidelines are available.
Not recommended for use in children under 15 years old; safety and efficacy not established.
Approved for postmenarchal adolescents; same dosing as adults: one tablet orally once daily for 21 days followed by 7 days of placebo. No weight-based adjustments are recommended.
Use lower starting dose (e.g., 5 mg) and titrate slowly; increased risk of sedation and anticholinergic effects. May not be well tolerated; consider alternative therapy.
Not indicated for use in postmenopausal women; no specific geriatric dosing adjustments are necessary if used off-label, but consider increased risk of thrombotic events in older women.
None
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. The risk increases with age, particularly in women over 35 years, and with heavy smoking (≥15 cigarettes per day). Women over 35 who smoke should not use this medication.
Should not be used for longer than 2-3 weeks (acute use only),May impair mental or physical abilities required for driving or operating machinery,Central nervous system depression additive with alcohol and other CNS depressants,Anticholinergic effects: caution in patients with angle-closure glaucoma, urinary retention, or prostatic hypertrophy,Cardiovascular effects: risk of arrhythmias, especially in patients with preexisting cardiac disease (tachycardia, QT prolongation),Serotonin syndrome risk when used with MAOIs, SSRIs, SNRIs, or other serotonergic drugs,Hepatic impairment: lower doses recommended
Increased risk of thromboembolic disorders (venous and arterial),Cigarette smoking increases risk of cardiovascular events, especially in women over 35,Hepatic neoplasia (benign and malignant),Elevated blood pressure,Gallbladder disease,Carbohydrate and lipid metabolism effects,Headache/migraine,Depression,Uterine bleeding irregularities,Ocular lesions (e.g., retinal thrombosis),Carcinoma of the breast and reproductive organs (close monitoring in current or history of breast cancer)
Concurrent use of MAOIs or within 14 days of MAOI therapy,Acute recovery phase of myocardial infarction,Arrhythmias, heart block, or congestive heart failure,Hyperthyroidism
Breast cancer (current or history),Carcinoma of the endometrium or other estrogen-dependent neoplasia,Thrombophlebitis or thromboembolic disorders (current or history),Cerebrovascular or coronary artery disease (current or history),Valvular heart disease with complications,Severe hypertension,Diabetes with vascular involvement,Headaches with focal neurological symptoms (e.g., migraine with aura),Major surgery with prolonged immobilization,Known or suspected pregnancy,Active liver disease or impaired liver function,Undiagnosed abnormal uterine bleeding,Hypersensitivity to any component,Cigarette smoking in women over 35 years of age
Alcohol should be avoided due to additive CNS depression. No specific food interactions; take with or without food. Grapefruit juice does not significantly interact, but caution with high-fat meals may alter absorption slightly.
No specific food restrictions. Grapefruit juice may slightly increase ethinyl estradiol levels but not clinically significant. High-fat meals do not affect absorption. Avoid excessive alcohol as it may impair compliance.
Pregnancy Category B. Animal studies have not demonstrated fetal risk, but no adequate human studies in pregnant women. Use only if clearly needed. First trimester: no known risk. Second trimester: no known risk. Third trimester: potential for neonatal adverse effects such as respiratory depression and withdrawal if used near term.
Pregnancy category X. Use contraindicated in pregnancy. First trimester exposure associated with cardiovascular defects (e.g., VSD), neural tube defects, and cleft lip/palate. Second and third trimester exposure may cause fetal adrenal suppression, hepatic dysfunction, and virilization of female genitalia due to progestin component (levonorgestrel). Increased risk of ectopic pregnancy if conception occurs during use.
Excreted in breast milk in small amounts (M/P ratio not established). Clinical relevance uncertain; however, due to potential for adverse effects in nursing infants, caution is advised. Alternative therapies preferred, especially when nursing a premature or low-birth-weight infant.
Excreted in breast milk. Levonorgestrel M/P ratio approximately 0.3–0.4. Small amounts of ethinyl estradiol present. May reduce milk production and quality due to estrogen component. Use only if benefit outweighs risk; consider alternative contraception. American Academy of Pediatrics considers it compatible with nursing.
No specific dosing adjustments recommended for pregnancy. Use lowest effective dose and shortest duration due to potential neonatal effects. Pharmacokinetics may be altered in pregnancy; however, no dose adjustment guidelines exist.
Contraindicated. No dose adjustments apply as drug must be discontinued immediately if pregnancy suspected or confirmed. Pharmacokinetic changes in pregnancy (increased clearance, volume of distribution) not relevant due to contraindication.
Flexeril (cyclobenzaprine) is structurally related to tricyclic antidepressants (TCAs) and shares similar anticholinergic and sedative properties. It should not be used longer than 2-3 weeks due to lack of evidence for efficacy beyond that duration. Avoid in patients with hyperthyroidism, heart block, or recent MI. Concomitant use with MAOIs can cause hypertensive crisis. Onset of muscle relaxation is delayed; therapeutic effect may not be apparent until after 2-4 days. Sedation is the most common side effect and can be used to aid sleep.
ALESSE is a combined oral contraceptive (COC) containing ethinyl estradiol (20 mcg) and levonorgestrel (100 mcg). It is indicated for contraception and treatment of acne vulgaris in women aged ≥14. Monitor for thromboembolic events, especially in smokers >35 years. Assess for contraindications including migraines with aura, hypertension, and history of DVT/PE. Advise use of backup contraception if a pill is missed. Start on first day of menses or first Sunday after onset. Check BP at baseline and annually. Counsel on increased risk of VTE, especially in first year.
Do not take for longer than 3 weeks unless directed by your doctor.,This medication may cause drowsiness or dizziness; avoid driving or operating heavy machinery until you know how it affects you.,Avoid alcohol and other CNS depressants (e.g., benzodiazepines, opioids) as they may increase sedation.,Do not stop suddenly if taken regularly; taper dose to avoid withdrawal symptoms like headache or nausea.,Inform your doctor if you have glaucoma, urinary retention, or are taking MAO inhibitors (e.g., phenelzine, tranylcypromine).,Take exactly as prescribed; do not increase dose or frequency.,May cause dry mouth; use sugar-free gum or candy for relief.
Take one pill daily at the same time each day, even if you do not have sex.,Missed pill instructions: if late by <12 hours, take it as soon as remembered and continue schedule. If >12 hours, take missed pill (even if means taking two in one day) and use backup contraception for 7 days.,Possible side effects: nausea, breast tenderness, headache, breakthrough bleeding, especially in first 3 months.,Seek emergency care for signs of blood clot: leg pain/swelling, sudden chest pain, shortness of breath, severe headache, vision changes.,Do not smoke while on ALESSE, especially if over age 35, as it increases risk of serious cardiovascular events.,Inform your healthcare provider of all medications and supplements you take, as some (e.g., rifampin, anticonvulsants, St. John's wort) may reduce effectiveness.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about FLEXERIL vs ALESSE, answered by our medical review team.
FLEXERIL is a Muscle Relaxant that works by Cyclobenzaprine is a centrally acting muscle relaxant that acts primarily at the brainstem, reducing tonic somatic motor activity via inhibition of descending serotonergic pathways. It is structurally related to tricyclic antidepressants and exhibits anticholinergic, sedative, and analgesic effects.. ALESSE is a Estrogen/Progestin Combination Contraceptive that works by Combination of ethinyl estradiol and levonorgestrel suppresses gonadotropin-releasing hormone (Gn RH) secretion from the hypothalamus, inhibiting pituitary release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thereby preventing ovulation. Additionally, it thickens cervical mucus, impeding sperm penetration, and alters endometrial receptivity.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between FLEXERIL and ALESSE depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of FLEXERIL is: 10 mg to 15 mg orally three times a day; maximum daily dose: 30 mg.. The standard adult dose of ALESSE is: One tablet (ethinyl estradiol 20 mcg, levonorgestrel 0.1 mg) orally once daily at the same time each day for 21 days, followed by 7 days of placebo. For initiation, start on the first day of menstrual period or first Sunday after onset of menses.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between FLEXERIL and ALESSE in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. FLEXERIL is classified as Category C. Pregnancy Category B. Animal studies have not demonstrated fetal risk, but no adequate human studies in pregnant women. Use only if clearly needed. First trimester: no known risk. . ALESSE is classified as Category C. Pregnancy category X. Use contraindicated in pregnancy. First trimester exposure associated with cardiovascular defects (e.g., VSD), neural tube defects, and cleft lip/palate. Seco. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.