Testosterone undecanoate

Insulin: In patients with diabetes, concomitant use with TLANDO may decrease blood glucose and insulin requirements ( 7.1) . Oral Anticoagulants: Concomitant use with TLANDO may cause changes in anticoagulant activity. Monitor International Normalized Ratio and prothrombin time frequently ( 7.2 ). Corticosteroids: Concomitant use with TLANDO may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease ( 7.3 ). Drugs that May Also Increase Blood Pressure: Concomitant use with TLANDO may lead to additional increases in blood pressure ( 7.4 ).

7.1 Insulin Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, insulin requirements.

7.2 Oral Anticoagulants Changes in anticoagulant activity may be seen with androgens. Frequent monitoring of INR and prothrombin time may be necessary in patients taking anticoagulants, especially at the initiation and termination of androgen therapy.

7.3 Corticosteroids The concurrent use of testosterone with corticosteroids may result in increased fluid retention and should be monitored cautiously, particularly in patients with cardiac, renal or hepatic disease.

7.4 Drugs that May Also Increase Blood Pressure Some prescription drugs and nonprescription analgesic and cold medications can increase blood pressure. Concomitant administration of these medications with TLANDO may lead to additional increases in blood pressure [ see Warnings and Precautions ( 5.4 ) ] .

8.1 Pregnancy Risk Summary TLANDO is contraindicated in pregnant women and not indicated for use in females [ see Contraindications ( 4 )] . Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies (see Data ) and its mechanism of action [ see Clinical Pharmacology ( 12.1 ) ] . Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring.

These studies did not meet current standards for nonclinical development toxicity studies. Data Animal Data In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring.

Structural impairments observed in females included increased anogenital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes. Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring.

Hypertension was observed in pregnant females and offspring in rats exposed to doses approximately twice those used for testosterone replacement therapy.