TYCOLET
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TYCOLET (TYCOLET).
Acetaminophen: COX-1/COX-2 inhibitor in CNS; Paracetamol: analgesic and antipyretic via central inhibition of prostaglandin synthesis.
| Metabolism | Hepatic glucuronidation (UGT1A1, UGT1A6, UGT1A9), sulfation (SULT1A1, SULT1A3), and cytochrome P450 oxidation (CYP2E1, CYP3A4) to toxic metabolite NAPQI. |
| Excretion | Renal: 70-80% unchanged; Biliary/fecal: 10-15% as metabolites. |
| Half-life | Terminal elimination half-life is 2-4 hours; prolonged in renal impairment (up to 12-24 hours in ESRD). |
| Protein binding | 20-25% bound to albumin. |
| Volume of Distribution | 0.8-1.2 L/kg; indicates distribution into total body water. |
| Bioavailability | Oral: 85-90% with first-pass metabolism of 10-15%; IV: 100%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-15 minutes; Intramuscular: 10-20 minutes. |
| Duration of Action | 4-6 hours for analgesia; extended with hepatic impairment or high doses. |
| Molecular Weight | 345.4 |
500-1000 mg orally or intravenously every 4-6 hours, maximum 4 g/day.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-50 mL/min: 500 mg every 6 hours; CrCl 10-29 mL/min: 500 mg every 8 hours; CrCl <10 mL/min: 500 mg every 12 hours. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: maximum 2 g/day; Child-Pugh C: maximum 1 g/day. |
| Pediatric use | 10-15 mg/kg/dose orally or intravenously every 4-6 hours, maximum 75 mg/kg/day. |
| Geriatric use | Start at lower end of dosing range; consider weight and comorbidities. Maximum 3 g/day in frail elderly. |
| 1st trimester | Avoid due to potential teratogenicity; animal studies show fetal abnormalities. |
| 2nd trimester | Use only if benefit outweighs risk; limited human data suggest possible fetal effects. |
| 3rd trimester | Avoid in third trimester due to risk of premature closure of ductus arteriosus and neonatal complications. |
Clinical note
Comprehensive clinical and safety monograph for TYCOLET (TYCOLET).
| Placental transfer | Crosses placenta; animal studies show fetal plasma levels 50-80% of maternal levels. |
| Breastfeeding | Excreted in breast milk in small amounts; potential for adverse effects in nursing infants such as diarrhea or rash. Use with caution and monitor infant. |
| Lactation Rating |
■ FDA Black Box Warning
Risk of severe liver injury; do not exceed maximum daily dose (4000 mg/day for adults).
| Serious Effects |
Hypersensitivity to drugActive peptic ulcer diseaseSevere hepatic impairment
| Precautions | Hepatotoxicity in overdose or with chronic alcohol use; severe hypersensitivity reactions (Stevens-Johnson syndrome); use caution in G6PD deficiency. |
| Food/Dietary | Avoid alcohol consumption due to increased risk of hepatotoxicity from acetaminophen. Grapefruit juice may alter codeine metabolism; limit intake. High-fiber foods can help prevent constipation caused by codeine. Maintain adequate fluid intake. |
| Clinical Pearls |
Loading safety data…
| L3 – Moderately Safe |
| Teratogenic Risk | First trimester: Use only if benefit outweighs risk due to lack of controlled studies; animal data show no fetal harm. Second/third trimester: No known specific teratogenic effects; caution with use near term due to potential adverse effects (e.g., pulmonary hypertension in neonate). |
| Fetal Monitoring | Monitor maternal liver function tests periodically; fetal monitoring for growth restriction if used long-term. |
| Fertility Effects | No known adverse effects on fertility in animal studies; human data limited. |
| TYCOLET is a combination of acetaminophen and codeine. Use caution in patients with hepatic impairment due to acetaminophen; maximum daily dose of acetaminophen is 4000 mg from all sources. Codeine is a prodrug requiring CYP2D6 metabolism; ultrarapid metabolizers risk toxicity. Avoid in children post-tonsillectomy/adenoidectomy for obstructive sleep apnea due to respiratory depression risk. Monitor for constipation; prescribe stool softeners prophylactically. |
| Patient Advice | Do not exceed 4000 mg of acetaminophen per day from all products to avoid liver damage. · Codeine can cause drowsiness; avoid driving or operating heavy machinery until you know how it affects you. · Take with food or milk to reduce gastrointestinal upset. · Avoid alcohol while taking this medication to prevent liver damage. · Do not take with other medications containing acetaminophen (e.g., Tylenol, cold and flu products). · Stop and seek medical help if you experience signs of an allergic reaction (rash, itching, swelling) or severe constipation. · Codeine is habit-forming; take only as prescribed and do not share with others. |