Testosterone (nasal)
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Turky Alkathery, M.D. [2]
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Overview
Testosterone (nasal) is a steroid hormone from the androgen group that is FDA approved for the treatment of deficiency or absence of endogenous testosterone. Common adverse reactions include PSA increased, headache, rhinorrhea, epistaxis, nasal discomfort, nasopharyngitis, bronchitis, upper respiratory tract infection, sinusitis, and nasal scab.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
Natesto is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone.
Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s 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. Limitations of use:
Safety and efficacy of Natesto in males less than 18 years old have not been established [see Use in Specific Populations (8.4)].
Dosage
Natesto is a slightly yellow gel for intranasal use and is available in a dispenser with a metered dose pump. One pump actuation delivers 5.5 mg of testosterone.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Testosterone (nasal) in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Testosterone (nasal) in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Testosterone (nasal) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Testosterone (nasal) in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Testosterone (nasal) in pediatric patients.
Contraindications
Natesto is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precaution (5.3)].
Natesto is contraindicated in women who are or who may become pregnant, or who are breast- feeding. Natesto may cause fetal harm when administered to a pregnant woman. Natesto may cause serious adverse reactions in nursing infants. Exposure of a fetus or nursing infant to androgens may result in varying degrees of virilization. If a pregnant woman is exposed to Natesto, she should be apprised of the potential hazard to the fetus [see Warnings and Precautions (5.6) and Use in Specific Populations (8.1, 8.3)].
Warnings
5.1. Nasal Adverse Reactions and Limited Long-Term Information on Nasal Safety Nasal adverse reactions, including nasopharyngitis, rhinorrhea, epistaxis, nasal discomfort and nasal scabbing, were reported in the clinical trial experience with Natesto. All nasal adverse reactions except one (a single case of upper respiratory infection) were reported as mild or moderate in severity; however, long-term clinical trial data on nasal safety is available in a limited number of subjects [see Adverse Reactions (6.2)]. Patients should be instructed to report any nasal symptoms or signs to their health care professional. In that circumstance, health care professionals should determine whether further evaluation (e.g., otorhinolaryngology consultation) or discontinuation of Natesto is appropriate.
5.2. Use in Patients with Chronic Nasal Conditions and Alterations in Nasal Anatomy Due to lack of clinical data on the safety or efficacy, Natesto is not recommended for use in the following patients:
History of nasal disorders; History of nasal or sinus surgery; History of nasal fracture within the previous 6 months or nasal fracture that caused a deviated anterior nasal septum; Mucosal inflammatory disorders (e.g, Sjogren’s syndrome); and Sinus disease. 5.3. Worsening of Benign Prostatic Hyperplasia and Potential Risk of Prostate Cancer Patients with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating treatment. It would be appropriate to re-evaluate patients 3 to 6 months after initiation of treatment and then in accordance with prostate cancer screening practices [see Contraindications (4)]. 5.4. Polycythemia Increases in hematocrit, reflective of increases in red blood cell mass, may require discontinuation of Natesto . Check hematocrit prior to initiating testosterone treatment. It would be appropriate to re-evaluate the hematocrit 3 to 6 months after starting testosterone treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable level. An increase in red blood cell mass may increase the risk of thromboembolic events.
5.5. Venous Thromboembolism There have been postmarketing reports of venous thromboembolic events , including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products such as Natesto. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for (DVT) and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with Natesto and initiate appropriate workup and management [see Adverse Reactions (6.2)].
5.6. Use in Women Due to lack of controlled studies in women and potential virilizing effects, Natesto is not indicated for use in women.
5.7. Potential for Adverse Effects on Spermatogenesis With large doses of exogenous androgens, including Natesto, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH), which could possibly lead to adverse effects on semen parameters, including sperm count.
5.8. Hepatic Adverse Effects 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). Peliosis hepatitis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. Natesto is not known to cause these adverse effects. Nonetheless, patients should be instructed to report any signs or symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly discontinue Natesto while the cause is evaluated.
5.9. Edema Androgens, including Natesto, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required.
5.10. Gynecomastia Gynecomastia may develop and may persist in patients being treated with androgens, including Natesto, for hypogonadism.[see Adverse Reactions (6.1)].
5.11. Sleep Apnea The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity and chronic lung disease.
5.12. Lipids Changes in the serum lipid profile may occur. Monitor the lipid profile periodically, particularly after starting testosterone therapy. Changes in serum lipid profile may require discontinuation of testosterone therapy.
5.13. Hypercalcemia Androgens, including Natesto, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients.
5.14. Decreased Thyroxine-binding Globulin Androgens, including Natesto, may decrease concentrations of thyroxine-binding globulins, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged; however, and there is no clinical evidence of thyroid dysfunction.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Testosterone (nasal) Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Testosterone (nasal) Postmarketing Experience in the drug label.
Drug Interactions
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, may necessitate a decrease in the dose of anti-diabetic medication.
7.2. Oral Anticoagulants 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.
7.3. Corticosteroids 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.
7.4. Oxymetazoline 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 (12.3)]. Drug interaction potential with other nasally administered drugs other than oxymetazoline has not been studied.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): X
Natesto is contraindicated during pregnancy or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure of a fetus to androgens may result in varying degrees of virilization. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Testosterone (nasal) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Testosterone (nasal) during labor and delivery.
Nursing Mothers
Although it is not known how much testosterone transfers into human milk, Natesto is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants.
Pediatric Use
Safety and efficacy of Natesto has not been established in pediatric patients less than 18 years of age. Improper use may result in acceleration of bone age and premature closure of epiphyses.
Geriatic Use
There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing Natesto to determine whether efficacy in those over 65 years of age differs from younger subjects.
Of the 306 patients enrolled in the Phase 3 clinical trial utilizing Natesto, 60 were 65 years of age or older, and 9 were 75 years of age or older. There are insufficient long-term safety data in geriatric patients to assess the potential for increased risks of cardiovascular disease and prostate cancer.
Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH [see Warnings and Precautions (5.3)].
Gender
There is no FDA guidance on the use of Testosterone (nasal) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Testosterone (nasal) with respect to specific racial populations.
Renal Impairment
No studies were conducted in patients with renal impairment.
Hepatic Impairment
No studies were conducted in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Testosterone (nasal) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Testosterone (nasal) in patients who are immunocompromised.
Allergic Rhinitis
Serum total testosterone concentrations were decreased by 21 to 24% in males with symptomatic allergic rhinitis, whether treated with nasal decongestants such as oxymetazoline, or left untreated
Administration and Monitoring
Administration
There is limited information regarding Testosterone (nasal) Administration in the drug label.
Monitoring
There is limited information regarding Testosterone (nasal) Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Testosterone (nasal) and IV administrations.
Overdosage
No cases of overdose with Natesto have been reported in clinical trials. There is 1 report of acute overdosage by injection of testosterone enanthate: testosterone concentrations of up to 11,400 ng/dL were implicated in a cerebrovascular accident.
Treatment of overdosage would consist of discontinuation of Natesto together with appropriate symptomatic and supportive care.
Pharmacology
There is limited information regarding Testosterone (nasal) Pharmacology in the drug label.
Mechanism of Action
Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of the prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, such as facial, pubic, chest, and axillary hair; laryngeal enlargement, vocal cord thickening, alterations in body musculature, and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics.
Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter’s syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).
Structure
Natesto (testosterone) nasal gel is a slightly yellow gel containing 5.5 mg of testosterone in 122.5 mg of Natesto gel for nasal administration. The active pharmacologic ingredient in Natesto is testosterone, an androgen. Testosterone is a white to practically white crystalline powder chemically described as 17β-Hydroxyandrost-4-en-3-one. The structural formula is:
The inactive ingredients are castor oil, oleoyl polyoxylglycerides, and colloidal silicon dioxide.
Pharmacodynamics
No specific pharmacodynamic studies were conducted using Natesto.
Pharmacokinetics
There is limited information regarding Testosterone (nasal) Pharmacokinetics in the drug label.
Nonclinical Toxicology
13.1 Carcinogenesis and Mutagenesis and Impairment of Fertility Carcinogenicity
Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats.
Mutagenesis
Testosterone was negative in the in vitro Ames and in the in vivo mouse micronucleus assays.
Impairment of Fertility
The administration of exogenous testosterone has been reported to suppress spermatogenesis in the rat, dog and non-human primates, which was reversible on cessation of the treatment.
Clinical Studies
There is limited information regarding Testosterone (nasal) Clinical Studies in the drug label.
How Supplied
Natesto (testosterone) nasal gel is available as a metered dose pump containing 11 grams of gel dispensed as 60 metered pump actuations. One pump actuation delivers 5.5 mg of testosterone in 0.122 grams of gel.
NDC 63481-239-01
Storage
Keep Natesto out of reach of children.
Store at 20°C to 25°C (68°F to 77°F). Excursions are permitted to 15°C to 30°C (59°F to 86°F). See USP Controlled Room Temperature.
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Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Use in Men With Known or Suspected Prostate or Breast Cancer
Men with known or suspected prostate or breast cancer should not use Natesto [see Contraindications (4) and Warnings and Precaution (5.3)].
Nasal Adverse Reactions
Nasal adverse reactions, including nasopharyngitis, rhinorrhea, epistaxis, nasal discomfort and nasal scabbing, were reported in clinical trials of Natesto. Advise patients to report any nasal symptoms or signs to their health care professional.
Potential Adverse Reactions With Androgens
Patients should be informed that treatment with androgens may lead to adverse reactions which include:
Changes in urinary habits such as increased urination at night, trouble starting your urine stream, passing urine many times during the day, having an urge that you have to go to the bathroom right away, having urine accident, being unable to pass urine, and having a weak urine flow. Breathing disturbances, including those associated with sleep, or excessive daytime sleepiness. Too frequent or persistent erections of the penis. Nausea, vomiting, changes in skin color, or ankle swelling. Patients Should be Advised of the Following Instructions For Use
Read the Patient Information accompanying each Natesto metered dose pump. Prime the pump by depressing it 10 times prior to its first use. No priming is needed with subsequent uses of that pump. Administer Natesto intranasally and NOT to other parts of the body. Administer Natesto intranasally three times daily, once in the morning, once in the afternoon and once in the evening (6 to 8 hours apart), preferably at the same time each day. Keep Natesto out of the reach of children. Report any changes in their state of health, such as changes in urinary habits, breathing, sleep, mood, nasal irritation or rhinitis. Never share Natesto with anyone.
Precautions with Alcohol
Alcohol-Testosterone (nasal) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
- ®[1]
Look-Alike Drug Names
There is limited information regarding Testosterone (nasal) Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.