Testosterone Enanthate and NSAIDs (Ibuprofen, Naproxen): Interaction Guide

Does Testosterone Enanthate Interact With Ibuprofen or Naproxen?

The testosterone enanthate prescribing information has a drug interactions section. It names oral anticoagulants, antidiabetic drugs and insulin, ACTH and corticosteroids, and oxyphenbutazone. It does not name ibuprofen or naproxen [1].

What matters in practice is what the two labels warn about when both drugs are used by the same man.

What Do the Labels Say About Blood Pressure?

The testosterone enanthate label says testosterone can increase blood pressure, which can increase cardiovascular risk over time. It says to monitor blood pressure periodically in men using testosterone products, especially men with hypertension, and that testosterone products are not recommended in patients with uncontrolled hypertension [1].

The ibuprofen label says NSAIDs can lead to new hypertension or worsen existing hypertension. It says blood pressure should be monitored closely during initiation of NSAID treatment and throughout therapy [2].

A 1994 meta-analysis of 38 placebo-controlled randomized trials found NSAIDs raised supine mean blood pressure by 5.0 mm Hg on average (95% CI 1.2 to 8.7) [3]. The ibuprofen label also says NSAIDs may weaken the blood-pressure-lowering effect of ACE inhibitors, and that people taking thiazide or loop diuretics may have an impaired response to them [2].

What About Fluid Retention and Edema?

The testosterone enanthate label says sodium and water retention can cause edema with or without congestive heart failure, and that this may be a serious complication in patients with preexisting cardiac, renal or hepatic disease. It says diuretic therapy may be required and that if testosterone enanthate is restarted, a lower dose should be used [1].

The ibuprofen label says fluid retention and edema have been observed with NSAIDs. It cites a meta-analysis showing about a two-fold increase in hospitalizations for heart failure with COX-2 selective and nonselective NSAIDs compared with placebo. It says to avoid ibuprofen in severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure [2].

Men with heart, kidney or liver disease are the overlap group in both labels [1][2].

What About Kidney Effects?

The ibuprofen label says long-term NSAID use has resulted in renal papillary necrosis and other renal injury [2]. The naproxen label adds that NSAIDs can reduce renal blood flow in people who depend on renal prostaglandins. It lists impaired kidney function, dehydration, low blood volume, heart failure, liver dysfunction, diuretic use, ACE inhibitor or ARB use, and older age as the highest-risk settings. It also says hyperkalemia has been reported with NSAIDs even without kidney impairment.

The testosterone enanthate label warns that edema can be serious in preexisting renal disease [1].

In a 2013 nested case-control study of 487,372 antihypertensive users, current use of an NSAID together with a diuretic plus an ACE inhibitor or ARB was linked to a higher rate of acute kidney injury (rate ratio 1.31, 95% CI 1.12 to 1.53). The rate ratio was 1.82 (95% CI 1.35 to 2.46) in the first 30 days. An NSAID with only one of those drugs was not associated with a higher rate overall [4].

What About GI Bleeding and Anticoagulants?

The ibuprofen label carries a boxed warning for serious gastrointestinal bleeding, ulceration and perforation, and a boxed warning for serious cardiovascular thrombotic events. GI events can be fatal and can occur at any time without warning symptoms. Older adults are at greater risk. A prior ulcer or GI bleed raises the risk more than 10-fold, and oral corticosteroids, anticoagulants, smoking, alcohol, older age and poor health also raise risk [2].

The testosterone enanthate label lists bleeding in patients on concomitant anticoagulant therapy. It says patients receiving oral anticoagulant therapy require close monitoring, especially when androgens are started or stopped [1].

The ibuprofen label says the effects of warfarin and NSAIDs on GI bleeding are synergistic, with a higher risk of serious GI bleeding than either drug alone [2].