In a 36‑year‑old, 36‑week pregnant woman (5′6", 175 lb) taking Wellbutrin XL (bupropion) 450 mg/day, Fioricet (butalbital/acetaminophen/caffeine) regularly, and Adderall IR (mixed amphetamine salts) 80 mg/day, do urine butalbital 6,212 ng/mL and urine amphetamine 855 ng/mL indicate she is adhering to her prescribed medications?

Interpretation of Urine Drug Levels in a Pregnant Patient on Prescribed Psychostimulants and Butalbital

Direct Answer

The urine butalbital level of 6,212 ng/mL is consistent with regular use of prescribed Fioricet, but the amphetamine level of 855 ng/mL is concerning for possible non-adherence to the prescribed 80 mg/day Adderall regimen, as this concentration falls well below expected therapeutic ranges for this high dose. 1, 2, 3

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Interpreting the Butalbital Level

Expected Therapeutic Range

• Butalbital is eliminated nearly 80% unchanged in the urine, making urine concentrations a reasonable marker of recent ingestion 4
• The measured level of 6,212 ng/mL indicates recent butalbital use, consistent with regular Fioricet administration 4
• Normal therapeutic serum concentrations are <10 mg/L (10,000 ng/mL), and urine concentrations are typically higher than serum due to renal concentration 4

Clinical Interpretation

• This level confirms the patient is taking butalbital-containing medication as prescribed 4
• The concentration is within expected ranges for therapeutic use of Fioricet and does not suggest overdose or diversion 4

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Interpreting the Amphetamine Level

Expected Therapeutic Range for 80 mg/day Adderall

• Peak amphetamine urine concentrations following a single 20 mg Adderall dose range from 2,645 to 5,948 ng/mL 2
• With repeated daily 20 mg dosing, peak concentrations range from 5,739 to 19,172 ng/mL 3
• For an 80 mg/day regimen (4× the studied dose), expected peak urine concentrations would be approximately 23,000–77,000 ng/mL, extrapolating from published data 2, 3

Critical Discrepancy

• The measured amphetamine level of 855 ng/mL is dramatically lower than expected for 80 mg/day dosing 2, 3
• This concentration is below the 500 ng/mL GC-MS administrative cutoff used to confirm positive amphetamine results, suggesting minimal recent amphetamine intake 2, 3
• Samples containing ≥500 ng/mL amphetamine are typically seen up to 47.5 hours after a single 20 mg dose and up to 60 hours after repeated dosing 2, 3

Possible Explanations for Low Amphetamine Level

1. Non-Adherence (Most Likely)

• The patient may not be taking the prescribed 80 mg/day dose regularly 1
• The low concentration suggests either sporadic use or significantly reduced dosing 2, 3
• Diversion of ADHD medication is a documented concern, particularly in younger adults 1

2. Timing of Last Dose

• If the patient's last Adderall dose was >48–60 hours before specimen collection, concentrations could fall below detection thresholds 2, 3
• However, with an 80 mg/day regimen taken as prescribed, some amphetamine should be detectable even with delayed timing 3

3. Specimen Dilution

• Urine dilution can artificially lower drug concentrations 1
• Specimen validity testing (creatinine, specific gravity) should be performed to rule out dilution 1
• Creatinine ≤2 mg/dL suggests substitution; 2–20 mg/dL may indicate dilution 1

4. Pregnancy-Related Pharmacokinetic Changes

• Pregnancy increases glomerular filtration rate and volume of distribution, potentially altering drug concentrations
• However, these changes would not account for a >90% reduction in expected amphetamine levels 2, 3

5. Laboratory or Collection Error (Least Likely)

• Laboratory error with GC-MS confirmatory testing is rare but possible 1
• Specimen mix-up or improper handling should be considered only after other explanations are excluded 1

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Critical Clinical Concerns in This Pregnant Patient

High-Dose Stimulant Use in Late Pregnancy

• Adderall 80 mg/day is 4× the typical starting dose and at the upper limit of FDA-approved dosing
• Amphetamine use in pregnancy is associated with increased risks of preterm birth, low birth weight, and neonatal withdrawal (general medical knowledge)
• At 36 weeks gestation, the fetus is at high risk for neonatal abstinence syndrome if the mother is taking high-dose stimulants

Butalbital Use in Pregnancy

• Butalbital is a barbiturate with potential for neonatal dependence and withdrawal
• Regular use near term increases risk of neonatal sedation and respiratory depression

Bupropion 450 mg/day

• This dose is at the maximum FDA-approved limit for Wellbutrin XL
• Bupropion does not typically appear on standard urine drug screens 1

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Recommended Clinical Approach

Immediate Actions

1. Obtain specimen validity testing to rule out dilution or substitution 1

   • Creatinine concentration
   • Specific gravity
   • pH
   • Temperature (if fresh specimen available)

2. Conduct a non-judgmental discussion with the patient 1

   • Ask specifically about adherence to the 80 mg/day Adderall regimen 1
   • Inquire about timing of the last dose relative to urine collection 2, 3
   • Explore barriers to adherence (side effects, cost, concerns about pregnancy) 5
   • Ask about any OTC medications or supplements that could affect results 1, 6

3. Request enantiomer analysis if not already performed 1, 2

   • Adderall contains a 3:1 ratio of d- to l-amphetamine enantiomers 2, 3
   • The presence of l-amphetamine distinguishes Adderall from illicit amphetamine or dextroamphetamine-only preparations 2, 3
   • Enantiomer composition can help differentiate therapeutic use from illicit methamphetamine 1, 2

4. Repeat urine drug testing with observed collection 1

   • Schedule testing without advance notice to prevent anticipatory adherence 5
   • Collect specimen at a time when therapeutic levels should be present (within 24 hours of reported dose) 2, 3

Ongoing Management

1. Reassess the treatment regimen 5

   • The combination of high-dose Adderall (80 mg/day), Wellbutrin XL (450 mg/day), and Fioricet in late pregnancy carries significant maternal and fetal risks
   • Consider consultation with maternal-fetal medicine and addiction medicine specialists
   • Evaluate whether stimulant therapy is essential at this dose in the third trimester

2. Implement adherence monitoring strategies 5

   • More frequent urine drug testing (weekly or biweekly) 1
   • Pill counts at each visit 5
   • Prescription refill monitoring 5
   • Consider switching to a long-acting formulation with lower abuse potential if non-adherence or diversion is confirmed 1

3. Screen for substance use disorder 1

   • Use validated screening tools (e.g., Drug Abuse Screening Test-10) 1
   • Assess for behavioral signs of stimulant misuse (dose escalation, early refill requests, "lost" prescriptions) 1
   • If substance use disorder is identified, refer to addiction specialist 1

4. Prepare for neonatal monitoring

   • Alert obstetric and neonatal teams to maternal medication regimen
   • Plan for neonatal monitoring for withdrawal symptoms (irritability, tremors, feeding difficulties)
   • Ensure neonatal intensive care availability at delivery

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Key Pitfalls to Avoid

• Do not assume the patient is diverting medication based solely on this single test result 1
• Do not make punitive decisions (e.g., discharge from care, reporting to authorities) without confirmatory testing and clinical context 1
• Do not ignore the possibility of specimen validity issues (dilution, timing) that could explain the low amphetamine level 1
• Do not overlook the significant fetal risks of this medication regimen in late pregnancy
• Do not fail to document the complete discussion, findings, and plan in the medical record 7

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Summary of Adherence Assessment

Medication	Prescribed Dose	Urine Level	Interpretation
Butalbital (Fioricet)	Regular use	6,212 ng/mL	Consistent with adherence [4]
Amphetamine (Adderall)	80 mg/day	855 ng/mL	Inconsistent with adherence; suggests non-adherence, sporadic use, or specimen issues [2,3]
Bupropion (Wellbutrin XL)	450 mg/day	Not tested	Cannot assess adherence without specific testing [1]

The patient appears adherent to Fioricet but likely non-adherent to the prescribed high-dose Adderall regimen, requiring immediate clinical follow-up, repeat testing, and reassessment of the treatment plan in the context of late pregnancy. 1, 2, 3