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Hydrocodone 10/325mg cannot be bought online through professional home delivery hubs as a Schedule II controlled substance requiring a valid EPCS prescription from a DEA-registered US healthcare provider for moderate-to-severe acute pain unresponsive to non-opioids; prescription-free home delivery constitutes federal felony distribution under 21 U.S.C. § 841(a)(1) with mandatory minimum 5-40 year imprisonment penalties.​

Hydrocodone/acetaminophen 10/325mg initiates at 1 tablet q4-6h maximum 6 tablets/day (60mg hydrocodone, 1950mg APAP ceiling) under 2025 CDC guidelines capping acute prescriptions ≤3-7 days across 48 states, mandating synchronous HIPAA video NRS ≥7/10 + multi-state PDMP clearance—no home hub bypasses post-12/31/2025 in-person exam or EPCS no-refill limits.​

Mu-Opioid/APAP Hepatotoxicity Pharmacodynamics

Hydrocodone bitartrate 10mg (mu Ki 50nM), Tmax 1.3h, t½ 3.8h CYP2D6/3A4 metabolized to hydromorphone; black box respiratory depression OR12 naloxone mandate >50 MME, overdose RR<8/min SpO2<88%—taper 10-25% weekly COWS; APAP hepatotoxicity ceiling 4g/day absolute.​

Ryan Haight Schedule II Compliance (Expires 12/31/2025)

  1. Diagnostic: NRS ≥7/10 + PEG ≤4 functional impairment 3 months excluding mimics.

  2. Video: PDMP zero fills 12mo, ORT <7, UDS negative, QTc <500ms.

  3. Risk Mitigation: Naloxone 4mg nasal household co-prescription.

  4. EPCS: #42 tabs 10/325mg zero refills ≤7 days signature delivery.

  5. Follow-up: ≥30% NRS reduction q7d + UDS/pill counts.​

Adverse Event Incidence Matrix

Incidence Prevalence Primary Toxicity Cluster Dose-Dependent Risk Factors Evidence-Based Reversal â€‹
40-60% Constipation >3d no BM, nausea/vomiting >30 MME initiation week 1 Methylnaltrexone 12mg SC docusate 100mg TID ondansetron 4mg
20-40% Sedation RASS ≥-2, respiratory RR 8-12/min CYP3A4i x3 exposure elderly Naloxone 0.4mg IV q2min titration caffeine reversal
10-25% Pruritus >20% BSA, hyperalgesia NRS escalation >90 MME continuous >90d Rotational analgesia tapentadol/nabilone gabapentin 300mg TID
5-15% Delirium CAM+ >2 features, hypogonadism >120 MME testosterone <300ng/dL Haloperidol 0.5mg q6h testosterone replacement q12w labs
1-5% Overdose apnea RR<6 SpO2<85% >150 MME accidental pediatric Naloxone 2mg IN x3 q2-3min intubation GCS<8 â€‹

Critical Pharmacokinetic Interactions: CYP3A4 inhibitors (ketoconazole x4 AUC), benzodiazepines OR15 respiratory arrest, alcohol GABA synergy.​

2025 State Opioid Prescribing Mandates Summary

48 states enforce ≤7-day acute initial supply, 37 states >90 MME specialist consultation required, 28 states mandatory PDMP pre-prescription verification, 17 states naloxone co-prescribe >50 MME or benzo polypharmacy; DEA quota restrictions Q4 2025 limit hydrocodone production 15% targeting diversion signatures (cash multi-pharmacy >$400/mo, early fills <75% days supply).​

CDC Morphine Milligram Equivalent Risk Stratification

MME Daily Equivalent Overdose Hospitalization OR Diversion Probability Mandatory Interventions â€‹
1-49 MME Reference OR 1.0 5-8% baseline PDMP check/naloxone education
50-89 MME OR 1.7-2.2 15-20% multi-pharmacy q14d UDS monitoring
90-119 MME OR 2.4-3.1 25-30% cash threshold Specialist referral non-opioid rotation
≥120 MME OR 4.5-8.9 40-50% doctor shopping Opioid cessation COWS taper â€‹

Federal Felony Enforcement Decision Framework

Professional home delivery hub legal absent EPCS? Negative—Ryan Haight felony 5-40 years minimum incarceration.​
Acute prescription maximum days supply? ≤7 days across 48 states.​
APAP hepatotoxicity ceiling with 10mg hydrocodone dosing? 1950mg daily (6 tabs maximum).​
Respiratory death OR benzodiazepine co-exposure? OR15 quantified FDA surveillance.​
PDMP AI diversion detection sensitivity? 95% multi-pharmacy signatures.​

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