Testosterone Formulations Drug-Drug Interaction Table

Labels covered

The two labels are Depo-Testosterone (testosterone cypionate, intramuscular, effective August 21, 2026) and generic testosterone enanthate intramuscular (effective May 8, 2026) [1][2]. Both are injection products labeled for hypogonadism caused by testicular failure or by a pituitary or hypothalamic problem [1][2]. Testosterone is a Schedule III controlled substance [1][2].

Both are esters of testosterone in oil. After an intramuscular injection the ester is absorbed slowly from the oil depot and splits into free testosterone; the cypionate label gives a half-life of about eight days after injection and a dosing interval of two to four weeks [1]. The enanthate label gives the same 50 to 400 mg every two to four weeks and adds that total doses above 400 mg per month are not usually required and that injections more often than every two weeks are rarely indicated [2].

FDA-approved testosterone also comes as gels, patches and buccal systems as well as injections [3]. The interaction sections below come from the two intramuscular labels.

The interactions the labels list

Oral anticoagulants in more detail

The cypionate label says androgens may increase sensitivity to oral anticoagulants and that the anticoagulant dose may require reduction to maintain satisfactory therapeutic hypoprothrombinemia [1]. The enanthate label notes that C-17 substituted testosterone derivatives such as methandrostenolone have been reported to decrease the anticoagulant requirement, and that patients on oral anticoagulants need close monitoring especially when androgens are started or stopped [2].

The cypionate label's adverse reactions section lists suppression of clotting factors II, V, VII and X, and bleeding in patients on concomitant anticoagulant therapy, among hematologic reactions [1].

Neither label specifies how much the anticoagulant dose should change or what INR change to expect.

Insulin and diabetes drugs

Both labels state that in diabetic patients the metabolic effects of androgens may decrease blood glucose and therefore insulin requirements [1][2].

A 24-week randomized trial enrolled 94 men with type 2 diabetes — 50 eugonadal and 44 with hypogonadotropic hypogonadism — and randomized the 44 men with hypogonadism to 250 mg intramuscular testosterone or placebo every two weeks [4]. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp: the glucose infusion rate rose 32% on testosterone and did not change on placebo (P=0.03 for the comparison). The outcome measured was insulin sensitivity during a clamp, not the number of hypoglycemia events [4].

Corticosteroids and ACTH

The enanthate label lists ACTH and corticosteroids as producing an enhanced tendency toward edema, and advises caution when giving these drugs together, especially in patients with hepatic or cardiac disease [2]. The cypionate label's interaction section does not mention corticosteroids, but its warnings say edema, with or without congestive heart failure, can be a serious complication in patients with pre-existing cardiac, renal or hepatic disease [1].

Oxyphenbutazone

Both labels state that concurrent administration of oxyphenbutazone and androgens may result in elevated serum oxyphenbutazone levels [1][2]. Neither label describes a management step beyond that.

Drugs the labels do not name

Neither drug interactions section names ketoconazole, itraconazole, ritonavir, clarithromycin, rifampin, carbamazepine, phenytoin, propranolol or other beta-blockers, cyclosporine, tacrolimus, SSRIs, opioids or antiretroviral drugs [1][2].

The cypionate label does say that inactivation of testosterone occurs primarily in the liver and that testosterone is metabolized to 17-keto steroids through two different pathways, without naming a specific enzyme [1].

Does the formulation change the interaction list?

The lists differ: the enanthate label names ACTH and corticosteroids, while the cypionate label does not list them in its drug interactions section [1][2]. Both share oral anticoagulants, diabetes drugs and oxyphenbutazone, and both are dosed 50 to 400 mg every two to four weeks [1][2]. FDA-approved testosterone also includes gels, patches, buccal systems and oral products [3][8]; the interaction sections quoted here are from the injectable labels.