What are the potential drug interactions with ashwagandha, especially in patients with pre-existing medical conditions or those taking multiple medications, such as blood thinners (e.g. warfarin), diabetes medications (e.g. metformin), thyroid medications (e.g. levothyroxine), or blood pressure medications (e.g. beta blockers)?

Ashwagandha Drug Interactions

Ashwagandha does not cause clinically significant cytochrome P450 enzyme inhibition and appears safe to use with most prescription medications, though caution is warranted with thyroid medications, immunosuppressants, and sedatives due to potential pharmacodynamic interactions. 1

Pharmacokinetic Interactions (Drug Metabolism)

Cytochrome P450 Enzymes

• Ashwagandha root and leaf extracts show no reversible inhibition of major drug-metabolizing enzymes (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6, CYP3A4/5) at concentrations up to 100 μg/mL, indicating minimal risk of pharmacokinetic drug interactions through enzyme inhibition. 1
• This is particularly important for older adults who often use multiple medications, as polypharmacy combined with age-related decline in drug metabolism increases adverse event risk. 1

Pharmacodynamic Interactions (Additive Effects)

Thyroid Medications (Levothyroxine)

• Ashwagandha significantly increases thyroid hormone levels (T3, T4) and decreases TSH in subclinical hypothyroid patients, normalizing thyroid indices within 8 weeks at 600 mg daily dosing. 2
• Patients taking levothyroxine should have thyroid function monitored every 4-6 weeks when initiating ashwagandha, as the additive effect may cause hyperthyroidism symptoms (tachycardia, anxiety, weight loss). 2
• Dose reduction of levothyroxine may be necessary if TSH becomes suppressed or free T4 becomes elevated. 2

Blood Pressure Medications (Beta Blockers, ACE Inhibitors, ARBs)

• Ashwagandha combined with Terminalia arjuna (another Ayurvedic herb) lowered systolic blood pressure in healthy adults, suggesting potential additive hypotensive effects. 3
• Monitor blood pressure weekly for the first month when combining ashwagandha with antihypertensive medications, particularly in patients taking multiple blood pressure drugs. 4
• Watch for symptomatic hypotension (dizziness, lightheadedness, falls), especially in older adults where polypharmacy increases fall risk. 4

Diabetes Medications (Metformin, Insulin, Sulfonylureas)

• While no direct interaction studies exist, ashwagandha's potential metabolic effects warrant glucose monitoring when used with antidiabetic medications. 3
• Check fasting glucose and hemoglobin A1c at baseline and 8-12 weeks after starting ashwagandha in diabetic patients. 3

Blood Thinners (Warfarin)

• No specific evidence exists for ashwagandha-warfarin interactions, unlike other botanicals (garlic, ginkgo, ginseng, dong quai, danshen) that increase warfarin effects or coenzyme Q10 and St. John's wort that decrease warfarin effects. 5
• However, botanical medicines should be approached with caution in warfarin-treated patients due to lack of standardization and variable active ingredient content. 5
• Increase INR monitoring frequency to weekly for 3-4 weeks when initiating or discontinuing ashwagandha in warfarin-treated patients, then return to standard monitoring if INR remains stable. 5

CNS Depressants (Benzodiazepines, Opioids, Sedatives)

• Ashwagandha is marketed for sleep promotion and anxiety relief, suggesting potential sedative properties. 1
• Avoid combining ashwagandha with three or more CNS-active medications (benzodiazepines, opioids, antidepressants, antipsychotics, antiepileptics) due to increased fall risk, particularly in older adults. 4
• If combination is necessary, start with lower ashwagandha doses and monitor for excessive sedation, confusion, or falls. 4

Hepatotoxicity Risk

Liver Injury Profile

• Ashwagandha can cause cholestatic or mixed hepatotoxicity with jaundice, pruritus, nausea, and lethargy after 2-12 weeks of use, though this appears rare. 6
• Liver injury is self-limited, with normalization of liver tests within 1-5 months after discontinuation. 6
• Check baseline ALT, AST, alkaline phosphatase, and bilirubin before starting ashwagandha, then repeat at 4 weeks and 12 weeks, especially in patients taking other potentially hepatotoxic medications. 6

High-Risk Patients

• Avoid ashwagandha in patients with pre-existing liver disease or those taking multiple hepatotoxic medications (statins, methotrexate, isoniazid, rifampin). 4, 6
• Discontinue immediately if jaundice, dark urine, severe pruritus, or right upper quadrant pain develops. 6

Polypharmacy Considerations

Older Adults

• Patients taking 5 or more medications average one significant drug problem, and fall risk increases 21% with 4+ medications and 50% with 10+ medications. 4
• Ashwagandha adds complexity to medication regimens in older adults who already face age-related pharmacokinetic changes (reduced clearance, altered distribution). 4
• Systematically review all medications, supplements, and over-the-counter products before adding ashwagandha. 4

Multiple Prescribers and Pharmacies

• Patients often receive prescriptions from multiple providers without shared records, increasing interaction risk. 4
• Document ashwagandha use in the medical record and inform all prescribers and pharmacists to enable interaction screening. 4

Practical Management Algorithm

When a patient wants to start ashwagandha:

1. Obtain complete medication list including prescription drugs, over-the-counter medications, and all supplements. 4

2. Identify high-risk medications:

   • Levothyroxine or other thyroid medications → Monitor TSH, free T4 every 4-6 weeks 2
   • Warfarin → Increase INR monitoring to weekly × 3-4 weeks 5
   • 3+ CNS medications → Consider avoiding or use lowest dose 4
   • Multiple antihypertensives → Monitor BP weekly × 4 weeks 3
   • Hepatotoxic drugs → Check baseline and follow-up liver tests 6

3. Check baseline laboratory tests:

   • Liver function tests (ALT, AST, alkaline phosphatase, bilirubin) in all patients 6
   • TSH and free T4 if taking thyroid medications 2
   • INR if taking warfarin 5
   • Fasting glucose if diabetic 3

4. Start ashwagandha at standard dose (500-600 mg daily) unless patient is frail, elderly, or taking multiple interacting medications—then start at 250-300 mg daily. 2

5. Follow-up monitoring schedule:

   • Week 1-4: Weekly blood pressure if on antihypertensives, weekly INR if on warfarin 5, 3
   • Week 4: Liver function tests, thyroid function if applicable 2, 6
   • Week 8-12: Repeat all baseline labs 2, 6

6. Discontinue immediately if:

   • Jaundice, dark urine, or severe pruritus develops 6
   • INR becomes unstable or bleeding occurs 5
   • Symptomatic hypotension or falls occur 4
   • Signs of hyperthyroidism develop (tachycardia, tremor, anxiety) 2

Common Pitfalls to Avoid

• Do not assume ashwagandha is safe simply because it is "natural"—botanical supplements can cause serious adverse effects and interactions. 5, 6
• Do not rely on patient self-reporting of supplement use—specifically ask about ashwagandha and other Ayurvedic or herbal products at every visit. 4
• Do not ignore the lack of standardization in ashwagandha products—active ingredient content varies significantly between manufacturers, affecting both efficacy and toxicity risk. 5
• Do not combine ashwagandha with other sedating botanicals (valerian, kava, passionflower) without considering cumulative CNS depression. 4