Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
Codeine vs ALTAVERA
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Codeine is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. It is a prodrug converted to morphine via CYP2D6, which mediates most of its analgesic effects.
Combination of ethinyl estradiol and desogestrel: ethinyl estradiol suppresses gonadotropin release, inhibiting ovulation; desogestrel (progestin) causes cervical mucus thickening and endometrial atrophy, preventing implantation.
FDA-approved for mild to moderate pain where an opioid is appropriate,FDA-approved for cough suppression,Off-label: acute pain, chronic pain (limited use)
Prevention of pregnancy,Treatment of moderate acne vulgaris (in females ≥15 years with no contraindications)
Oral: 30-60 mg every 4-6 hours as needed; maximum 360 mg per day. Intramuscular/Subcutaneous: 30-60 mg every 4-6 hours as needed. Use lowest effective dose for shortest duration.
1 tablet (ethinyl estradiol 0.03 mg / levonorgestrel 0.15 mg) orally once daily for 21 days, followed by 7 placebo days.
The terminal elimination half-life of codeine is approximately 2.5 to 3.5 hours in adults with normal renal function. In patients with renal impairment, the half-life may be prolonged to up to 8 hours, necessitating dose adjustment.
Levonorgestrel: terminal elimination half-life 25±10 hours; ethinyl estradiol: 13±7 hours. Clinical context: steady-state concentrations achieved within 5-7 days; contraceptive efficacy requires consistent daily dosing.
Codeine is metabolized by CYP2D6 to morphine (active), via CYP3A4 to norcodeine (inactive), and via glucuronidation. Morphine is further conjugated via UGT2B7.
Ethinyl estradiol: primarily metabolized by CYP3A4; undergoes sulfation and glucuronidation. Desogestrel: rapidly converted to active metabolite etonogestrel via CYP2C9 and CYP2C19; further metabolism by CYP3A4.
Codeine is eliminated primarily via renal excretion (about 90% as inactive metabolites, mainly codeine-6-glucuronide and norcodeine, with less than 10% as free codeine). Biliary/fecal excretion accounts for approximately 10% of the dose.
Renal excretion of metabolites and unchanged drug: ~30% (levonorgestrel) and ~20% (ethinyl estradiol) in urine; biliary/fecal elimination: ~40-50% as conjugates and metabolites.
Approximately 25% bound to plasma proteins, primarily albumin.
Levonorgestrel: 98-99% bound to sex hormone-binding globulin (SHBG) and albumin; ethinyl estradiol: 98% bound to albumin.
Approximately 3-6 L/kg, indicating extensive distribution into tissues, including brain and breast milk.
Levonorgestrel: Vd ~1.8 L/kg (suggesting extensive tissue distribution). Ethinyl estradiol: Vd ~2.4 L/kg.
Oral bioavailability is about 60-90% (first-pass metabolism reduces systemic exposure; extensive metabolizers may have higher morphine levels). Rectal bioavailability is similar to oral. Intramuscular and subcutaneous routes have nearly 100% bioavailability.
Oral bioavailability: levonorgestrel ~100% (nearly complete); ethinyl estradiol ~45-50% (first-pass hepatic metabolism).
Cr Cl 10-50 m L/min: Administer 75% of normal dose. Cr Cl <10 m L/min: Administer 50% of normal dose. Not recommended in severe renal impairment due to risk of CNS toxicity.
No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal disease or acute renal failure due to potential fluid retention.
Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50% or use alternative. Child-Pugh Class C: Contraindicated. Avoid in severe hepatic impairment due to decreased metabolism and risk of accumulation.
Contraindicated in severe hepatic dysfunction (Child-Pugh class B or C). Use caution in mild to moderate impairment (Child-Pugh A); monitor liver enzymes.
Oral, IM, or SC: 0.5-1 mg/kg/dose every 4-6 hours as needed; maximum 60 mg/dose. Weight-based dosing for children >1 year. Not recommended in children under 12 years for postoperative tonsillectomy/adenoidectomy. Contraindicated in children <12 years for pain, and <18 for cough due to risk of respiratory depression.
Not indicated for use before menarche. For postmenarchal adolescents, same dosing as adults (1 tablet daily, 21/7 regimen) after evaluation of risks.
Start at low end of dosing range (e.g., 30 mg every 4-6 hours) due to increased sensitivity and risk of respiratory depression, falls, and cognitive impairment. Monitor renal function and avoid in patients with Cr Cl <30 m L/min. Consider non-opioid alternatives first.
Not indicated for postmenopausal women. No specific geriatric dosing; consider increased risk of thromboembolism, cardiovascular disease, and metabolic effects in older women of reproductive age.
WARNING: CODEFINE HAS RISKS OF ADDICTION, ABUSE, AND MISUSE, WHICH CAN LEAD TO OVERDOSE AND DEATH. LIFE-THREATENING RESPIRATORY DEPRESSION MAY OCCUR, ESPECIALLY IN CHILDREN, AND RISK IS INCREASED WITH CYP2D6 ULTRA-RAPID METABOLIZERS. PROLONGED USE DURING PREGNANCY CAN RESULT IN NEONATAL OPIOID WITHDRAWAL SYNDROME.
Cigarette smoking increases risk of serious cardiovascular events from combined oral contraceptives. Risk increases with age (especially >35 years) and with number of cigarettes smoked. Women who use combined hormonal contraceptives should be strongly advised not to smoke.
CYP2D6 ultra-rapid metabolizers: risk of morphine toxicity, fatal respiratory depression,Life-threatening respiratory depression in children <12 years; contraindicated in <18 years for tonsillectomy/adenoidectomy,Risk of opioid-induced respiratory depression, especially in elderly, debilitated, or patients with respiratory conditions,Addiction, abuse, and misuse potential,Neonatal opioid withdrawal syndrome if used during pregnancy,Concomitant use with CNS depressants increases risk of hypotension, respiratory depression, and coma,Serotonin syndrome with serotonergic drugs,Severe hypotension, including orthostatic hypotension,Adrenal insufficiency with prolonged use,Increased risk of seizures in patients with seizure disorders,May impair ability to drive or operate machinery
Thrombotic disorders: risk of venous thromboembolism (VTE), stroke, myocardial infarction; discontinue if thrombotic event occurs.,Hepatic disease: discontinue if jaundice or liver function abnormalities develop.,Hypertension: monitor blood pressure; discontinue if uncontrolled.,Carbohydrate metabolism: may affect glucose tolerance; monitor diabetic patients.,Depression: discontinue if significant depression occurs.,Gallbladder disease: increased risk of cholelithiasis.
Hypersensitivity to codeine or any component,Significant respiratory depression,Acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment,Paralytic ileus (known or suspected),Postoperative management in children <18 years after tonsillectomy/adenoidectomy,Children <12 years,Use with MAOIs or within 14 days of stopping MAOIs
Thrombophlebitis or thromboembolic disorders (current or history),Cerebrovascular or coronary artery disease (current or history),Known or suspected breast carcinoma,Estrogen-dependent neoplasia (known or suspected),Undiagnosed abnormal genital bleeding,Cholestatic jaundice of pregnancy or jaundice with prior pill use,Hepatic adenoma or carcinoma (known or suspected),Pregnancy (known or suspected),Hypersensitivity to any component
Avoid alcohol completely; increase risk of CNS depression and hepatotoxicity. Grapefruit juice may inhibit CYP3A4, affecting codeine metabolism; limited data but caution advised. High-fiber foods may help counteract constipation. No significant food restrictions aside from alcohol.
No significant food interactions. Alcohol does not affect efficacy but may increase risk of adverse effects such as nausea. Grapefruit juice has no known interaction. Avoid excessive alcohol consumption due to potential hepatotoxicity.
FDA Pregnancy Category C. First trimester: association with neural tube defects, cleft palate; second/third trimester: risk of fetal dependence, respiratory depression, withdrawal after birth. Avoid in labor due to neonatal respiratory depression.
ALTAVERA contains ethinyl estradiol and levonorgestrel. First trimester: Inadvertent exposure during organogenesis is associated with a very low absolute risk of cardiovascular defects (relative risk 1.2-1.4) and no consistent increase in other major malformations. Second and third trimesters: No known teratogenic effects, but theoretical risks from estrogenic effects (e.g., feminization of male fetus). Postnatal: No increased risk of long-term developmental effects from pregnancy exposure.
Codeine is excreted into breast milk; M/P ratio approximately 2.0. Use with caution; risk of infant opioid toxicity, especially in CYP2D6 ultra-rapid metabolizers. Not recommended for breastfeeding mothers.
Combined oral contraceptives may reduce milk production and quality, especially in early lactation. Ethinyl estradiol transfers into breast milk at low levels (M/P ratio approximately 0.1-0.2), excluding clinical effects in term infants. Levonorgestrel transfer is minimal (M/P ratio ~0.2-0.4). Use is generally avoided in breastfeeding women, especially during the first 6 weeks postpartum. Progestin-only methods are preferred.
Increased clearance and volume of distribution in pregnancy may require higher doses for analgesia; however, avoid due to risks. No standard adjustment; use lowest effective dose for shortest duration if necessary.
Contraindicated in pregnancy. No dose adjustment recommended because use is discontinued upon confirmed or suspected pregnancy. Pharmacokinetic changes in pregnancy (e.g., increased hepatic clearance, altered binding proteins) are not relevant for this indication.
Codeine is a prodrug requiring CYP2D6 metabolism to morphine; poor metabolizers have reduced efficacy, while ultra-rapid metabolizers risk toxicity. Avoid in children <12 years for post-tonsillectomy/adenoidectomy due to fatal respiratory depression. Monitor for constipation; prescribe laxative with chronic use. Contraindicated with MAOIs and within 14 days of their discontinuation. Not effective for acute pain needing immediate relief due to variable conversion.
ALTAVERA is a combined oral contraceptive (COC) containing ethinylestradiol and levonorgestrel. It inhibits ovulation via suppression of gonadotropins. Counsel patients to take at the same time daily to maintain efficacy. Missed pill management: if missed within 12 hours, take immediately; if >12 hours, take last missed pill and use backup contraception for 7 days. Be aware of increased VTE risk, especially in smokers over 35. May reduce effectiveness of lamotrigine; monitor seizure control. Initiate on the first day of menses or first Sunday after onset.
Take exactly as prescribed; do not increase dose or frequency without consulting your doctor.,Do not combine with alcohol, sedatives, or other CNS depressants (e.g., benzodiazepines) due to risk of severe drowsiness, respiratory depression, or coma.,Common side effects include constipation, nausea, dizziness, and drowsiness. Drink plenty of fluids and consider stool softeners for constipation.,Avoid driving or operating machinery until you know how codeine affects you, as it may impair judgment and coordination.,Inform your doctor if you have a history of asthma, breathing problems, liver or kidney disease, or if you are pregnant or breastfeeding.,Do not share this medication with others, especially children; accidental use can be fatal. Store securely out of reach of children.,If you miss a dose, take it as soon as you remember. If near the next dose, skip the missed one; do not double dose.,Do not stop abruptly after prolonged use; taper under medical supervision to avoid withdrawal symptoms (anxiety, sweating, insomnia, diarrhea).
Take one tablet daily at the same time each day, with or without food.,If you miss a pill by less than 12 hours, take it as soon as you remember. If more than 12 hours, take the missed pill and use a backup method (e.g., condoms) for the next 7 days.,Smoking increases your risk of serious cardiovascular side effects, especially if you are over 35 years old. Do not smoke while taking this medication.,Seek immediate medical attention if you experience sudden severe headache, chest pain, leg pain/swelling, or vision changes (symptoms of blood clots).,This medication does not protect against HIV or other sexually transmitted infections.,If you are taking lamotrigine or other anticonvulsants, tell your doctor; your seizure medication may be less effective.,Store at room temperature away from moisture and heat.
"Pirenzepine, a selective M1 muscarinic antagonist, reduces gastrointestinal motility and secretions, while codeine, an opioid agonist, also decreases gastrointestinal motility via mu-opioid receptors. Concurrent use leads to additive anticholinergic and opioid effects, resulting in enhanced risk of severe constipation, paralytic ileus, and central nervous system depression. Clinically, patients may experience exacerbated sedation, respiratory depression, and urinary retention."
"Ropinirole, a non-ergoline dopamine agonist used in Parkinson's disease and restless legs syndrome, may reduce the analgesic efficacy of codeine. This is likely due to pharmacodynamic antagonism at central dopamine and opioid receptors, as well as potential pharmacokinetic interactions that decrease the conversion of codeine to its active metabolite morphine via CYP2D6 inhibition by ropinirole. The resultant blunted opioid response can lead to inadequate pain control, necessitating dose adjustment or alternative therapy."
"Vemurafenib induces CYP3A4, significantly reducing the plasma concentrations of codeine, which is metabolized via CYP3A4 to its active metabolite morphine. This may diminish codeine's analgesic efficacy, potentially leading to inadequate pain control. Additionally, reduced formation of morphine may lower the risk of opioid-related adverse effects."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about Codeine vs ALTAVERA, answered by our medical review team.
Codeine is a Opioid Agonist that works by Codeine is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. It is a prodrug converted to morphine via CYP2D6, which mediates most of its analgesic effects.. ALTAVERA is a Combined Oral Contraceptive that works by Combination of ethinyl estradiol and desogestrel: ethinyl estradiol suppresses gonadotropin release, inhibiting ovulation; desogestrel (progestin) causes cervical mucus thickening and endometrial atrophy, preventing implantation.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between Codeine and ALTAVERA 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 Codeine is: Oral: 30-60 mg every 4-6 hours as needed; maximum 360 mg per day. Intramuscular/Subcutaneous: 30-60 mg every 4-6 hours as needed. Use lowest effective dose for shortest duration.. The standard adult dose of ALTAVERA is: 1 tablet (ethinyl estradiol 0.03 mg / levonorgestrel 0.15 mg) orally once daily for 21 days, followed by 7 placebo days.. 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 Codeine and ALTAVERA 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. Codeine is classified as Category D/X. FDA Pregnancy Category C. First trimester: association with neural tube defects, cleft palate; second/third trimester: risk of fetal dependence, respiratory depression, withdrawal . ALTAVERA is classified as Category C. ALTAVERA contains ethinyl estradiol and levonorgestrel. First trimester: Inadvertent exposure during organogenesis is associated with a very low absolute risk of cardiovascular def. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.