Dosing and uses of Natesto (testosterone intranasal)
Adult dosage forms and strengths
intranasal gel: Schedule III
- 5.5mg/actuation
Testosterone Deficiency
Prior to initiating therapy, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range
Indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone
11 mg (2 sprays [ie, 1 spray in each nostril]) TID (total daily dose of 33 mg)
Indications
- Primary hypogonadism (congenital or acquired): Testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter syndrome, chemotherapy, or toxic damage from alcohol or heavy metals; these men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range
- Hypogonadotropic hypogonadism (congenital or acquired): Idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation; these men have low testosterone serum concentrations but have gonadotropins in the normal or low range
Monitoring
- Monitor serum total testosterone concentrations periodically, starting as soon as 1 month after initiating treatment
- When total serum testosterone concentration consistently >1050 ng/dL, discontinue therapy
- If the total testosterone concentration is consistently <300 ng/dL, consider an alternative treatment
Administration
Blow nose prior to use
Administer 3 times daily; once in the morning, once in the afternoon, and once in the evening (6-8 hr apart), preferably at the same time each day
Patients should be instructed to completely depress the pump 1 time in each nostril to receive the total dose
Use a clean, dry tissue to wipe actuator tip, then replace the cap on the dispenser
Press on the nostrils at a point just below the bridge of the nose and lightly massage
Refrain from blowing the nose or sniffing for 1 hr after administration
Do not administer to other parts of the body
Not recommended for use with intranasal drugs (except for sympathomimetic decongestants)
Discontinue temporarily if severe rhinitis occurs
Prime the pump
- Before using for the first time, instruct patient to prime the pump by inverting the pump, depressing the pump 10 times, and discarding any small amount of product dispensed directly into a sink and then washing the gel away thoroughly with warm water
- The tip should be wiped with a clean, dry tissue
- If the patient gets gel on his hands, it is recommended that he wash his hands with warm water and soap This priming should be done only prior to the first use of each dispenser
Limitation of use
Limitations of use: Safety and efficacy of testosterone in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.
Safety and efficacy of testosterone in males less than 18 years old have not been established
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Natesto (testosterone intranasal) adverse (side) effects
1-10%
Nasopharyngitis (8.2%)
Rhinorrhea (7.8%)
Epistaxis (6.5%)
Nasal discomfort (5.9%)
Increased PSA (5.1-5.8%)
Nasal scab (5.2%)
Parosmia (5.2%)
Headache (3.8-4.3%)
Upper respiratory tract infection (4.2%)
Nasal dryness (4.2%)
Nasal congestion (3.9%)
Bronchitis (3.8%)
Sinusitis (3.8%)
ncreased blood pressure (2-3%)
Dysgeusia (2-3%)
Cough (2-3%)
Postmarketing Reports
Vascular disorders: Venous thromboembolism
Myocardial infarction, stroke
Warnings
Contraindications
Men with carcinoma of the breast
Men with known or suspected prostate cancer
Pregnant or breast-feeding women; testosterone may cause fetal harm
Cautions
Anabolic steroids, such as testosterone, are abused and physical and psychological effects can occur with high doses; drug dependence has not been documented using therapeutic replacement doses
Nasal adverse reactions reported, including nasopharyngitis, rhinorrhea, epistaxis, nasal discomfort, and nasal scabbing
Monitor for nasal signs and symptoms; not recommended for patients with chronic nasal conditions or alterations in nasal anatomy (eg, nasal or sinus surgery, nasal fracture within previous 6 months, deviated anterior nasal septum, mucosal inflammatory disorders [Sjogren syndrome], sinus disease)
Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms
Increased hematocrit (polycythemia), reflective of increased red blood cell mass, may require discontinuation; increases risk for thromboemolism
Venous thromboembolism, including DVT and PE reported in patients using testosterone products; these observations have included patients with and without polycythemia; evaluate signs or symptoms consistent with DVT or PE; if venous thromboembolic event suspected, discontinue treatment with testosterone and initiate appropriate workup and management
Women and children should not use testosterone intranasaL
Prolonged use of high doses of orally active 17-alpha-alkyl androgens (methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatitis, hepatic neoplasms, cholestatic hepatitis, and jaundice)
Edema with or without CHF may be a complication in patients with preexisting cardiac, renal, or hepatic disease
Exogenous administration of androgens may lead to azoospermia
Gynecomastia may develop and may persist in patients being treated with androgens
Sleep apnea may occur in those with risk factors
Androgens should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria)
Androgens may decrease concentrations of thyroxine-binding globulins, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4
Monitor serum testosterone, prostate-specific antigen (PSA), hemoglobin, hematocrit, liver function tests, and lipid concentrations periodically
Some postmarketing studies have shown an increased risk of myocardial infarction and stroke associated with the use of testosterone replacement therapy
Pregnancy and lactation
Pregnancy category: X
Lactation: Contraindicated; unknown if excreted into human breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Natesto (testosterone intranasal)
Mechanism of action
Endogenous androgen; promotes growth and development of male sex organs and maintains secondary sex characteristics in androgen-deficient males
Absorption
Peak plasma time: 40 minutes
Average daily plasma concentration: 421 ng/dL
Provides circulating testosterone concentrations that approximate normal concentrations (ie, 300-1,050 ng/dL)
Serum total testosterone concentrations decreased by 21-24% in males with symptomatic allergic rhinitis, whether treated with nasal decongestants (eg, oxymetazoline) or left untreated
Distribution
Protein bound in the serum to sex hormone-binding globulin (SHBG) and albumin
~40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free), and the rest is loosely bound to albumin and other proteins
Metabolism
Metabolized in liver to various 17-keto steroids through 2 different pathways
Major active metabolites are estradiol and dihydrotestosterone (DHT)
DHT concentrations increased in parallel with testosterone concentrations; after 90 days, the mean DHT/testosterone ratio was 0.09 (within the normal range)
Elimination
Half-life: 10-100 minutes
Excretion (data from IM administration): 90% urine (as glucuronic and sulfuric acid conjugates); 6% feces (unconjugated form)
