Natesto Drug Interactions: What to Avoid and What to Tell Your Doctor

Natesto (testosterone nasal gel) can interact with several types of medications. Some interactions require additional monitoring, while others mean Natesto or the interacting drug should be used with caution or adjusted. Here is a complete guide to Natesto drug interactions so you can have an informed conversation with your prescriber.

Always Tell Your Doctor About Every Medication You Take

Before starting Natesto, provide your prescriber with a complete list of all medications, including prescription drugs, over-the-counter medicines, vitamins, herbal supplements, and any other testosterone or hormone products. Even if a drug is listed here, your prescriber may still prescribe it with Natesto under close monitoring — the goal is not to avoid the combination but to manage it safely.

Interaction 1 — Warfarin and Other Oral Anticoagulants (Moderate)

Androgens, including testosterone, can alter anticoagulant activity. If you take warfarin (Coumadin) or other blood thinners, your INR (International Normalized Ratio) and prothrombin time may change after starting or stopping Natesto. This can increase your bleeding or clotting risk.

What to do: If you are on warfarin, your prescriber or anticoagulation clinic should monitor your INR more frequently when you start, stop, or change the dose of Natesto. Do not adjust your warfarin dose on your own.

Interaction 2 — Insulin and Diabetes Medications (Moderate)

Androgens including testosterone can decrease blood glucose levels. For patients with diabetes who use insulin or other glucose-lowering medications, starting Natesto may increase the risk of hypoglycemia (low blood sugar).

What to do: Monitor blood glucose more closely when starting Natesto. Your prescriber or diabetes care team may need to adjust your insulin or diabetes medication dosage.

Interaction 3 — Corticosteroids (Moderate)

Using Natesto together with corticosteroids (such as prednisone, dexamethasone, methylprednisolone, triamcinolone) may increase the risk of fluid retention (edema). Both drug classes can promote sodium and water retention independently. The combination may be particularly risky for patients with pre-existing heart disease, kidney disease, or liver disease.

What to do: Use with caution. Report any signs of unusual swelling (especially in the ankles and feet), rapid weight gain, or shortness of breath to your doctor.

Interaction 4 — Other Nasal Medications (Use With Caution)

Natesto is NOT recommended for use with other nasally administered medications, with the exception of sympathomimetic nasal decongestants (specifically oxymetazoline). The drug interaction potential between Natesto and other nasal drugs (nasal corticosteroids, nasal antihistamines, nasal antivirals, etc.) has not been studied.

What to do: If you use a nasal steroid spray (like fluticasone/Flonase) or other nasal medications regularly, tell your prescriber. They may advise using them at different times or may consider whether Natesto is appropriate given your nasal medication regimen.

Interaction 5 — Oxymetazoline (Minor / Manageable)

Oxymetazoline is the active ingredient in nasal decongestants like Afrin. When used 30 minutes before Natesto in patients with seasonal rhinitis, it results in only a 2.6–3.6% reduction in testosterone absorption — clinically insignificant. When used at the same time as Natesto, oxymetazoline does not appear to impact absorption at all.

Note: Oxymetazoline nasal decongestants should not be used for more than 3 days in a row due to the risk of rebound congestion (rhinitis medicamentosa).

Interaction 6 — Thyroid Function Tests (Laboratory Interaction)

Androgens (including Natesto) can decrease concentrations of thyroxine-binding globulins, which causes a decrease in measured total T4 and an increase in resin uptake of T3 and T4 on thyroid function tests. Importantly, free thyroid hormone levels remain unchanged, and there is no clinical evidence of thyroid dysfunction.

What to do: Tell your doctor you are on Natesto if you are having thyroid tests. The results may appear abnormal even when thyroid function is normal. Free T4 and free T3 tests are more reliable in patients on androgens.

Other Medications to Discuss with Your Doctor

5-alpha reductase inhibitors (finasteride, dutasteride): May affect the conversion of testosterone to DHT. Discuss with your prescriber.

Aromatase inhibitors (anastrozole, letrozole): Sometimes used with testosterone therapy to control estrogen conversion. Discuss use and dosing with your prescriber.

Leuprolide and GnRH analogs: Typically contraindicated with testosterone therapy; discuss if relevant to your situation.

Antihypertensives: Monitor blood pressure when starting Natesto, as testosterone can affect blood pressure — monitor and adjust antihypertensive therapy as needed.

Foods and Alcohol

Unlike some oral testosterone formulations (such as Jatenzo), Natesto does not need to be taken with food. There are no known interactions between Natesto and specific foods or drinks. The effect of regular alcohol consumption on Natesto absorption has not been formally studied, though heavy alcohol use can independently suppress testosterone levels.

For more on Natesto side effects and monitoring, see our companion guide to Natesto side effects and what to watch for. And if you need help finding Natesto at a pharmacy near you, medfinder can help.