What is Tylenol (acetaminophen) Number 3?

What is Tylenol Number 3?

Tylenol Number 3 is a Schedule III combination analgesic containing codeine 30 mg and acetaminophen 300 mg per tablet, used for moderate acute pain relief. 1

Composition and Classification

• Active ingredients: Each tablet contains 30 mg of codeine (an opioid analgesic) combined with 300 mg of acetaminophen 1, 2
• DEA Schedule: Currently classified as Schedule III, indicating moderate abuse potential compared to Schedule II opioids like hydrocodone or oxycodone 1
• Dosing interval: Typically prescribed as 1-2 tablets every 4-6 hours as needed for pain 1

Clinical Efficacy

• Codeine/acetaminophen provides approximately 50% reduction in pain scores (3.5 NRS units decrease from baseline pain of 7.6) when used for acute extremity pain 2
• No clinically significant difference exists between Tylenol #3 and hydrocodone/acetaminophen (Vicodin 5/500) for acute pain relief—both reduce pain by similar amounts with comparable side effect profiles 2
• The combination is effective for moderate pain when opioid therapy is warranted, though not superior to hydrocodone combinations despite hydrocodone's Schedule II classification 2

Safety Considerations with Acetaminophen Component

Maximum Dosing Limits

• Single dose maximum: 1000 mg of acetaminophen 3
• Daily maximum: Do not exceed 4000 mg total acetaminophen per day from all sources 1, 3
• Conservative chronic dosing: Consider limiting to ≤3000 mg/day for prolonged use to reduce hepatotoxicity risk 1, 3, 4

Critical Warnings

• Never combine with other acetaminophen-containing products (prescription or over-the-counter) to avoid unintentional overdose 5
• The FDA has mandated that prescription combination products contain ≤325 mg acetaminophen per dosage unit to reduce liver injury risk, though Tylenol #3 predates this requirement with its 300 mg formulation 1
• Hepatotoxicity can occur with repeated supratherapeutic ingestions (>4 g/24 hours), potentially leading to liver failure and death 4

Special Populations

• Liver disease patients: Can generally use 2-3 g/day safely, even with cirrhosis, as acetaminophen is preferred over NSAIDs which carry higher risks of renal failure and GI bleeding 3
• Elderly patients (≥60 years): Consider the lower 3000 mg daily maximum 3

Role in Multimodal Analgesia

• Acetaminophen is most effective when used as part of multimodal analgesia, combined with NSAIDs or opioids like the codeine in Tylenol #3 1
• This combination approach reduces overall opioid requirements and associated side effects 1
• For postoperative pain, acetaminophen in multimodal regimens provides cost-effective outcomes with shorter hospital stays and fewer opioid-related complications 1

Clinical Context for Prescribing

• First-line therapy: For acute low back pain and similar conditions, guidelines recommend against opioids as first-line therapy; reserve for severe, disabling pain not controlled by acetaminophen or NSAIDs alone 1
• Alternative considerations: If hydrocodone products become less accessible due to Schedule II restrictions, Tylenol #3 serves as a clinically reasonable Schedule III substitute with equivalent efficacy 2
• The codeine component provides the opioid analgesia while acetaminophen contributes additive analgesic effects through different mechanisms 1