NATESTO SIDE EFFECTS
- Generic Name: testosterone nasal gel
- Brand Name: Natesto
- Drug Class: ANDROGENS
SIDE EFFECTS
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) |
| Headache | 3 (3.8) |
| Rhinorrhea | 3 (3.8) |
| Epistaxis | 3 (3.8) |
| Nasal discomfort | 3 (3.8) |
| Nasopharyngitis | 3 (3.8) |
| Bronchitis | 3 (3.8) |
| Upper respiratory tract infection | 3 (3.8) |
| Sinusitis | 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.
Extension Periods
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 (%) |
| Nasopharyngitis | 6 (8.7) |
| Rhinorrhea | 5 (7.2) |
| PSA increased | 4 (5.8) |
| Parosmia | 4 (5.8) |
| Nasal discomfort | 4 (5.8) |
| Nasal Scab | 4 (5.8) |
| Upper respiratory tract infection | 3 (4.3) |
| Bronchitis | 3 (4.3) |
| Procedural pain | 3 (4.3) |
| Pain in extremity | 3 (4.3) |
| Headache | 3 (4.3) |
| Epistaxis | 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.
Increased Hematocrit
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%).
Postmarketing Experience
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.
Cardiovascular Disorders: myocardial infarction, stroke
Vascular Disorders: Venous thromboembolism
SRC: NLM .