Low-Dose Naltrexone and Levothyroxine Interaction: What Patients and Prescribers Need to Know

What the naltrexone label covers

The current generic naltrexone hydrochloride tablet label (effective 2026-09-04) is written for the 50 mg tablet. Its drug interactions section covers opioid-containing medicines, disulfiram and thioridazine, and it states that studies to evaluate possible interactions between naltrexone and drugs other than opiates have not been performed [1]. The same section advises caution if naltrexone is given with other drugs [1]. Levothyroxine is not named there.

That label is not an LDN label. LDN means naltrexone at doses far below 50 mg, typically 0.5 to 6 mg per day and most often 4.5 mg per day, used off-label and supplied mainly through compounding pharmacies [3]. No FDA-approved LDN product exists, and FDA says compounded drugs are not FDA-approved and that it does not verify their safety, effectiveness or quality before marketing [4]. The naltrexone labels give no LDN dosing guidance [3][1].

The 898-patient study: what it did and did not show

The most direct evidence comes from a 2020 quasi-experimental before-after study using the Norwegian Prescription Database [2]. The researchers identified 898 patients through reimbursement codes for hypothyroidism and compared cumulative dispensed Defined Daily Doses and the number of users of triiodothyronine (T3) and levothyroxine (LT4) in the year before and the year after the first LDN prescription, in three groups based on LDN exposure [2].

There was no association between starting LDN and the subsequent dispensing of thyroid hormones. If anything, there was a tendency toward increasing LT4 consumption with increasing LDN exposure [2]. The authors concluded that the results do not support claims of efficacy of LDN in hypothyroidism [2].

The outcomes were dispensing measures (cumulative defined daily doses and number of users), not TSH or free T4 [2]. The study does not show what happened to an individual patient's thyroid laboratory values. It shows that, at the prescription-database level, starting LDN was not followed by a drop in thyroid-hormone use.

Levothyroxine absorption: the interactions that are documented

The documented absorption interactions for levothyroxine involve other products. In a 3-month uncontrolled study of 20 adults with hypothyroidism, taking 1,200 mg/day of elemental calcium as calcium carbonate together with levothyroxine lowered free T4 and raised mean TSH from 1.6 to 2.7 mIU/L [5]. In a 12-week uncontrolled study of 14 patients, taking ferrous sulfate 300 mg with thyroxine raised mean TSH from 1.6 to 5.4 mU/L [6].

Acid-reducing drugs also matter. In 10 patients on thyroxine, omeprazole raised TSH in all of them, and a 37% thyroxine dose increase reversed the effect [7].

The naltrexone interaction that matters more: opioids

Naltrexone is a pure opioid antagonist that blocks opioid effects by competitive binding at opioid receptors [1]. The tablet label contraindicates naltrexone in patients receiving opioid analgesics, patients currently dependent on opioids including those maintained on methadone or buprenorphine, and patients in acute opioid withdrawal [1]. Starting it too soon after opioids can precipitate withdrawal. The label recommends a minimum 7 to 10 opioid-free days for patients previously dependent on short-acting opioids, and says patients transitioning from buprenorphine or methadone may be vulnerable for as long as 2 weeks [1].

That contraindication is written without a dose exception, and the label was written for 50 mg tablets, not LDN [1][3]. The label also says patients taking naltrexone may not benefit from opioid-containing medicines such as cough and cold preparations, antidiarrheal preparations and opioid analgesics [1].