CODOXY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CODOXY (CODOXY).
Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia. Oxycodone is combined with aspirin to provide additive analgesic effects.
| Metabolism | Oxycodone is metabolized by CYP3A4 and CYP2D6. N-demethylation to noroxycodone (via CYP3A4) is the primary metabolic pathway. CYP2D6-mediated O-demethylation to oxymorphone is a minor pathway but produces a more potent metabolite. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 70% of elimination; biliary/fecal excretion accounts for 30%. |
| Half-life | Terminal half-life is 3.5 hours in patients with normal renal function; extends to 5-8 hours in moderate renal impairment. |
| Protein binding | Approximately 92% bound to albumin. |
| Volume of Distribution | 2.4 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: 60-70% due to first-pass metabolism. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5 minutes. |
| Duration of Action | 4-6 hours for analgesic effect; clinical duration may be prolonged in hepatic impairment. |
| Molecular Weight | 444.5 |
1-2 capsules orally every 4-6 hours as needed for pain, not to exceed 8 capsules per day. Each capsule contains 5 mg hydrocodone bitartrate and 325 mg acetaminophen.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-50 mL/min: administer every 8 hours. For GFR 10-29 mL/min: administer every 12 hours. For GFR <10 mL/min: use not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% and extend interval to every 8 hours. Child-Pugh Class C: contraindicated. |
| Pediatric use | For children ≥2 years: 0.1-0.2 mg/kg hydrocodone component every 4-6 hours as needed, maximum 6 doses per day. Use weight-based dosing; do not exceed acetaminophen 75 mg/kg/day. |
| Geriatric use | Initiate at lowest effective dose (e.g., 1 capsule every 6 hours) due to increased risk of respiratory depression and falls. Titrate cautiously. Maximum 6 capsules per day. |
| 1st trimester | CODOXY is contraindicated in first trimester due to risk of fetal harm, including teratogenicity (neural tube defects, cardiovascular malformations). |
| 2nd trimester | Avoid use in second trimester; reports of fetal hypotension, hypoperfusion, and renal impairment. |
| 3rd trimester | Contraindicated in third trimester as it may cause premature closure of ductus arteriosus and oligohydramnios. |
Clinical note
Comprehensive clinical and safety monograph for CODOXY (CODOXY).
| Placental transfer | CODOXY readily crosses the placenta, achieving fetal concentrations approximately 50-100% of maternal levels, as demonstrated in ex vivo placental perfusion studies. |
| Breastfeeding | CODOXY is excreted into human milk in low levels, but due to potential for serious adverse reactions in nursing infants, the manufacturer recommends a decision to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
■ FDA Black Box Warning
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; and interactions with drugs affecting cytochrome P450 isoenzymes.
| Serious Effects |
Pregnancy (all trimesters)Severe hepatic impairment (Child-Pugh Class C)Hypersensitivity to any componentConcurrent heparin use (risk of hemorrhage)
| Precautions | Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; severe hypotension; gastrointestinal obstruction; seizures; serotonin syndrome; adrenal insufficiency; and androgen deficiency. |
| Food/Dietary | Avoid alcohol and grapefruit juice. Alcohol potentiates CNS depression. Grapefruit juice may increase codeine metabolism via CYP3A4, leading to variable effects. No significant food restrictions otherwise; take with food if GI upset occurs. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) - Limited data suggest risk, but caution advised. |
| Teratogenic Risk | No human data; animal studies not available. Avoid during pregnancy, especially first trimester, due to potential oxycodone-induced neural tube defects. |
| Fetal Monitoring | Fetal ultrasound for growth and anomalies; maternal respiratory rate and sedation scores; neonatal abstinence syndrome (NAS) monitoring after delivery. |
| Fertility Effects | Oxycodone may suppress gonadotropin-releasing hormone (GnRH) leading to menstrual irregularities and reduced fertility. |
| Clinical Pearls | CODOXY is a fixed-dose combination of codeine (opioid) and doxylamine (antihistamine). Use lowest effective dose for shortest duration due to opioid dependence and respiratory depression risk. Avoid in children <12 years for post-tonsillectomy pain and in those <18 with respiratory compromise. Monitor for CNS depression, especially with alcohol. Doxylamine adds anticholinergic effects (constipation, dry mouth, urinary retention). Caution in elderly, renal impairment, and breastfeeding. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · This medication may cause drowsiness, dizziness, or blurred vision; avoid driving or operating machinery until you know how it affects you. · Avoid alcohol and other sedatives (e.g., benzodiazepines, sleep aids) as they increase risk of severe drowsiness and breathing problems. · Do not use with other products containing codeine or antihistamines (including cough/cold medicines). · Store securely away from children; misuse can cause addiction, overdose, or death. · If you are pregnant, plan to become pregnant, or are breastfeeding, inform your healthcare provider before use. · Common side effects: constipation, dry mouth, nausea. Increase fluid intake and fiber to prevent constipation. · Seek emergency help if you experience slow or shallow breathing, confusion, or fainting. |