Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Natesto was evaluated in a multicenter, open-label, 90-day clinical study. Patients could continue treatment with Natesto in two, open-label extension periods for an additional 90 and 180 days, respectively. A total of 306 hypogonadal men with morning testosterone concentrations ≤ 300 ng/dL received Natesto. Of these, 78 received Natesto at a dose of 11 mg three times daily.
90-Day Clinical Study
Among the 78 patients who received Natesto three times daily in the 90-day clinical study, the most common adverse reactions were: prostate specific antigen (PSA) increased, headache, rhinorrhea, epistaxis, nasal discomfort, nasopharyngitis, upper respiratory tract infection (URI), sinusitis, bronchitis and nasal scab. PSA increased was considered an adverse reaction by meeting one of two pre-specified criteria: (1) increase from baseline serum PSA greater than 1.4 ug/L, or (2) serum PSA greater than 4.0 ug/L.
Table 1 shows adverse reactions reported by ≥ 3% of patients treated with 11 mg three times daily in the 90-day clinical study.
Table 1: Adverse Reactions Reported by ≥ 3% of
Patients Treated with Natesto (11 mg of testosterone) Three Times Daily in the
90-Day Clinical Study
|Adverse Reactions||Natesto (11 mg of Testosterone) Three Times Daily
(N=78) n (%)
|PSA increased||4 (5.1)|
|Nasal discomfort||3 (3.8)|
|Upper respiratory tract infection||3 (3.8)|
|Nasal scab||3 (3.8)|
Adverse reactions reported by > 2% but < 3% of patients in the 90-day clinical study include: blood pressure increased, dysgeusia, nasal dryness, nasal congestion, and cough.
Among the 78 patients who received Natesto three times daily in the 90-day clinical study, a total of 69 patients received Natesto three times daily in the first 90-day extension period. Among these 69 patients, the most common adverse reactions were: nasopharyngitis, PSA increased, parosmia, nasal discomfort, rhinorrhea and nasal scab.
Table 2 shows adverse reactions reported by ≥ 3% of patients who received Natesto three times daily in both the 90-day clinical study and in the 90-day extension period.
Table 2: Adverse Reactions Reported by ≥ 3% of
Patients in Both the 90-Day Clinical Study and in the 90-Day Extension Period
|Adverse Reactions||Natesto 11 mg TID
(N=69) n (%)
|PSA increased||4 (5.8)|
|Nasal discomfort||4 (5.8)|
|Nasal Scab||4 (5.8)|
|Upper respiratory tract infection||3 (4.3)|
|Procedural pain||3 (4.3)|
|Pain in extremity||3 (4.3)|
A total of 18 patients received Natesto three times daily in all three treatment periods, including the 90-day clinical study, the first 90-day extension period, and the second 180-day extension period. Among these 18 patients, the following adverse reactions were reported in more than one patient each: nasopharyngitis, parosmia, PSA increased, nasal discomfort, nasal scab and hypertension. The following adverse reactions were reported in one patient each: nausea, nasal excoriation, thyroid stimulating hormone increased, decreased appetite, myalgia, anosmia, testicular atrophy, epistaxis, nasal septum disorder, nasal discomfort, and rhinorrhea.
In patients who received Natesto three times daily, mean serum PSA concentrations increased by 0.2 ng/mL, 0.1 ng/mL, and 0.2 ng/mL after 90, 180 and 360 days, respectively.
Discontinuations due to Adverse Reactions
Among all subjects (n=306) who received Natesto at any dose in the 90-day clinical study and its 90-and 180-day extension periods, a total of 6 subjects withdrew from treatment for the following adverse reactions, reported by 1 subject each: nasal discomfort, headache, dysgeusia, PSA increased, allergic reaction (hives, swollen lips and tongue), and 1 patient with myalgia, arthralgia, fever, chills and petechiae.
Among all subjects (n=306) who received Natesto at any dose in the 90-day clinical study and its 90-and 180-day extension periods, a total of 4 subjects had a hematocrit level > 55%. These 4 patients had baseline hematocrits of 48% and 51%. In no case did hematocrit exceed 58%.
Nasal Adverse Reactions
Among all subjects (n=306) who received Natesto at any dose in the 90-day clinical study and its 90-and 180-day extension periods, the following nasal adverse reactions were reported: nasopharyngitis (8.2%), rhinorrhea (7.8%), epistaxis (6.5%), nasal discomfort (5.9%), parosmia (5.2%), nasal scab (5.2%), upper respiratory infection (4.2%), nasal dryness (4.2%), and nasal congestion (3.9%).
The following adverse reactions have been identified during post-approval use of testosterone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Vascular Disorders: Venous thromboembolism [see WARNINGS AND PRECAUTION]
Read the Natesto (testosterone nasal gel) Side Effects Center for a complete guide to possible side effects
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, may necessitate a decrease in the dose of anti-diabetic medication.
Changes in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ration (INR) and prothrombin time is recommended in patients taking warfarin, especially at the initiation and termination of androgen therapy.
The concurrent use of testosterone with corticosteroids may result in increased fluid retention and requires monitoring particularly in patients with cardiac, renal, or hepatic disease.
A 2.6% decrease in mean AUC(0-24) and 3.6% decrease in mean Cmax of total testosterone was observed in males with symptomatic seasonal rhinitis when treated with oxymetazoline 30 minutes prior to Natesto compared to when left untreated. Oxymetazoline does not impact the absorption of testosterone when concomitantly administered with Natesto [see CLINICAL PHARMACOLOGY]. Drug interaction potential with other nasally administered drugs other than oxymetazoline has not been studied.
Drug Abuse And Dependence
Natesto contains testosterone, a Schedule III controlled substance in the Controlled Substances Act.
Anabolic steroids, such as testosterone, are abused. Abuse is often associated with adverse physical and psychological effects.
Although drug dependence is not documented in individuals using therapeutic doses of anabolic steroids for approved indications, dependence is observed in some individuals abusing high doses of anabolic steroids. In general, anabolic steroid dependence is characterized by any three of the following:
- Taking more drug than intended
- Continued drug use despite medical and social problems
- Significant time spent in obtaining adequate amounts of drug
- Desire for anabolic steroids when supplies of the drug are interrupted
- Difficulty in discontinuing use of the drug despite desires and attempts to do so
- Experience of withdrawal syndrome upon discontinuation of anabolic steroid use
Last reviewed on RxList: 9/8/2015
Additional Natesto Information
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