Striant - Product Information
|Manufacture:||Endo Pharmaceuticals Inc.|
|Class:||Androgens and anabolic steroids|
|Form:||Skin patch (transdermal)|
|Ingredients:||testosterone,anhydrous lactose NF, carbomer 934P, hypromellose USP, magnesium stearate NF, lactose monohydrate NF, polycarbophil USP, colloidal silicon dioxide NF, starch NF, and talc USP.|
Indications and Usage
Striant 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 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 levels and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range.
- Hypogonadotropic hypogonadism (congenital or acquired) –Gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency, or pituitary hypothalamic injury from tumors, trauma, or radiation. These patients have low serum testosterone levels but have gonadotropins in the normal or low range.
Limitations of use:
- Safety and efficacy of Striant in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.
- Safety and efficacy of Striant in males less than 18 years old have not been established [see Use in SpecificPopulations].
Dosage and Administration
Prior to initiating, Striant 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.
The recommended dosage for Striant is the application of one buccal system (30 mg) to the gum region twice daily; morning and evening (about 12 hours apart).
To ensure proper dosing, serum testosterone concentrations should be measured. Morning, pre-dose serum testosterone concentrations should be measured at 4 to 12 weeks after initiation of therapy to ensure proper serum testosterone concentrations are achieved. Striant therapy should be discontinued if serum testosterone concentrations are consistently outside of the normal range (300 to 1050 ng/dL) despite the use of one buccal system applied twice daily.
Striant should be placed in a comfortable position just above the incisor tooth (on either side of the mouth). With each application, Striant should be rotated to alternate sides of the mouth.
Upon opening the packet, the rounded side surface of the buccal system should be placed against the gum and held firmly in place with a finger over the lip and against the product for 30 seconds to ensure adhesion. Striant is designed to stay in position until removed. If the buccal system fails to properly adhere to the gum or should fall off during the 12-hour dosing interval, the old buccal system should be removed and a new one applied.
If the buccal system falls out of position within the first 8 hours of dosing, replace with a new system and continue for a total of 12 hours from the placement of the first system. If the system falls out of position after 8 hours of dosing, a new buccal system should be applied and it may remain in place for 12 hours then continue with the next regularly scheduled dosing.
Patients should take care to avoid dislodging the buccal system. Patients should check to see if Striant is in place following consumption of food or alcoholic/non-alcoholic beverages. Striant should not be chewed or swallowed. To remove Striant, gently slide it downwards from the gum toward the tooth to avoid scratching the gum. The Striant buccal system should be removed before routine morning and evening oral care is performed, followed by application of a new buccal system.
Dosage Forms and Strengths
Each Striant buccal system contains 30 mg of testosterone.
It is white to off-white colored with a flat edge on one side and a convex surface on the other. Striant is debossed on its flat side, as shown below:
- Striant is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions and Adverse Reactions].
- Striant is contraindicated in women who are or may become pregnant, or who are breastfeeding. Striant may cause fetal harm when administered to a pregnant woman. Striant may cause serious adverse reactions in nursing infants. Exposure of a fetus or nursing infant to androgens may result in varying degrees of virilization [see Use in Specific Populations].
Warnings and Precautions
Gum-related Adverse Reactions and Limited Long-Term Information on Oral Safety
Gum-related adverse reactions, including severe gum irritation, were reported in clinical trials of Striant. Long-term clinical trial data on gum safety is available in only a limited number of patients (117 patients, 51 patients and 48 patients with at least 6 months, 1 year, and 2 years of exposure, respectively). It is recommended that patients regularly inspect their own gum region where Striant is applied. Any abnormal finding should be brought promptly to the attention of the patient’s physician. In such circumstances, dental consultation may be appropriate.
Worsening of Benign Prostatic Hyperplasia (BPH) 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 and during treatment with androgens [see Contraindications and Adverse Reactions].
Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events.
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 Striant. 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 Striant and initiate appropriate workup and management [see Adverse Reactions].
Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use Striant.
Use in Women
Due to lack of controlled evaluations in women and potential virilizing effects, Striant is not indicated for use in women.
Potential for Adverse Effects on Spermatogenesis
With large doses of exogenous androgens, including Striant, 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.
Hepatic Adverse Effects
Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with testosterone enanthate, which elevates blood levels for prolonged periods, has produced multiple hepatic adenomas. Testosterone is not known to produce 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 Striant while the cause is evaluated.
Androgens, including Striant, may promote retention of sodium and water. Edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required [see Adverse Reactions].
Gynecomastia may develop and persist in patients being treated with androgens, including Striant, for hypogonadism.
The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients especially those with risk factors such as obesity or chronic lung diseases.
Changes in the serum lipid profile may occur. Monitor the lipid profile periodically, particularly after starting therapy.
Androgens, including Striant, 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.
Decreased Thyroxine-binding Globulin
Androgens, including Striant, may decrease concentrations of thyroxine-binding globulins, resulting in decreased total T4 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.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug can not be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Twelve Week Clinical Trials in Hypogonadal Men
In the Phase 3, open-label study, 98 patients received Striant for up to 12 weeks. Adverse reactions to Striant reported by ≥1% of patients are listed in Table 1.
|Adverse Reaction||Striant (n=98)|
|Gum or Mouth Irritation||9.2%|
Gum irritation generally resolved in 1 to 8 days. Gum tenderness resolved in 1 to 14 days [see Gum-related adverseevents and gum examinations in Adverse Reactions ].
The following adverse reactions to Striant occurred in 1 patient each: acne, anxiety, breast enlargement, breast pain, buccal mucosal roughening, difficulty in micturition, fatigue, gingivitis, gum blister, gustatory sense diminished, hematocrit increased, lipids serum increased, liver function tests abnormal, nose edema, stinging of lips, and toothache.
There was one additional 12-week study in 12 patients. In this study, additional adverse reactions to Striant and reported by 1 patient each included emotional lability and hypertension.
Long-Term Extension Clinical Trials in Hypogonadal Men
In two extension trials, a total of 117 and 51 patients received Striant for at least 6 months and 1 year, respectively.
Of 117 patients treated for at least 6 months, adverse reactions reported by 1 patient each included: anxiety, buccal inflammation, depression, dry mouth, gum redness, hypertension, infection, medication error, nausea, pruritus, renal function abnormal, stomatitis, taste bitter, taste perversion and toothache. Polycythemia and increased serum prostate specific antigen (PSA) were reported in three and two patients, respectively.
In these two extension studies, a total of 48 patients received Striant for at least 2 years. In these patients, adverse reactions included: gingival recession, lip ulceration, stomatitis, rash, prostate cancer, increased PSA, abdominal pain, diarrhea, hypertension aggravated, headache, nervousness, polycythemia, taste perversion, aggressiveness, hyperlipidemia, peripheral edema, and anxiety.
Gum-related Adverse Events and gum Examinations
In the open-label study, all reported gum-related adverse events were collected and gum examinations were conducted at Baseline and every month thereafter.
A total of 16 patients reported 19 gum-related adverse reactions. Of these, ten patients (10.2%) reported 12 reactions of mild intensity, four patients (4.1%) reported 5 reactions of moderate intensity, and two patients (2.0%) reported 2 reactions of severe intensity. Four patients (4.1%) discontinued treatment with Striant due to gum or mouth-related adverse reactions including two with severe gum irritation, one with mouth irritation, and one with “bad taste in mouth.” Gum irritation generally resolved in 1 to 8 days. Gum tenderness resolved in 1 to 14 days.
Monthly gum examinations were conducted to assess for gingivitis, gum edema, oral lesions, ulcerations or leukoplakia. No cases of ulceration or leukoplakia were observed. No new oral lesions were observed. The incidence of gingivitis and gum edema was not increased during treatment.
In the two extension trials, gum examinations were conducted every 3 months while on treatment. In one of these trials, no patient had a gum abnormality, and in the other trial, moderate gingivitis and mild gum edema were reported by 1 patient each.
In these two extension studies, patient-reported information on Striant gum adherence was collected every 3 months for 1 year. At each visit, 37% to 52% of patients reported problems with Striant adhering to the gum. Circumstances surrounding Striant detachment included eating, drinking and oral care. Hot foods and hot beverages were more likely to be associated with detachment than cold food and cold beverages.
The following adverse reactions have been identified during post approval use of Striant. 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: dry mouth, gingival swelling, lip swelling, mouth ulceration, stomatitis, red blood cell increased, dysgeusia, venous thromboembolism, myocardial infarction, and stroke.
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 the international normalized ratio (INR) and prothrombin time are 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 careful monitoring, particularly in patients with cardiac, renal or hepatic disease.
Use in Specific Populations
Pregnancy Category X: Striant is contraindicated in pregnant women or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure of a fetus to androgens such as testosterone may result in varying degrees of virilization. If a woman becomes pregnant while taking Striant, she should be apprised of the potential hazard to the fetus.
Although it is not known how much testosterone transfers into human milk, Striant is contraindicated in nursing women because of the potential for virilization in nursing infants. Testosterone and other androgens may adversely affect lactation.
Safety and effectiveness of Striant in males less than 18 year of age have not been established. Improper use may result in acceleration of bone age and premature closure of the epiphyses.
Of the total number of subjects in clinical studies of Striant, 51 patients (17%) were 65 years of age and older. There is insufficient long-term safety data in geriatric patients to assess the potentially increased risks of cardiovascular disease and prostate cancer.
No studies were conducted in patients with renal impairment.
No studies were conducted in patients with hepatic impairment.
Drug Abuse and Dependence
Striant 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 drugs are interrupted
- Difficulty in discontinuing use of the drug despite desires and attempts to do so
- Experience of a withdrawal syndrome upon discontinuation of anabolic steroid use
There is one report of acute overdosage with testosterone enanthate injection: testosterone levels of up to 11,400 ng/dL were implicated in a cerebrovascular accident.
Oral ingestion of Striant is not expected to result in clinically significant serum testosterone concentrations due to extensive first-pass (hepatic) metabolism.
Treatment of overdosage would consist of discontinuation of Striant together with appropriate symptomatic and supportive care.
How Supplied/Storage and Handling
Striant (testosterone buccal system) mucoadhesive is supplied in transparent blister packs containing 10 doses. It is white to off-white colored with a flat edge on one side and a convex surface on the other.
Striant is debossed on its flat side, as shown below: A
Each Striant buccal system contains 30 mg of testosterone and is supplied as follows:
|NDC Number||Package Size|
|52244-030-60||6 blister packs,
10 buccal systems per blister pack,
30 mg of testosterone per buccal system
Store at 20-25°C (68-77°F) [see USP Controlled Room Temperature]. Protect from heat and moisture. Damaged blister packages should not be used. Discard used Striant buccal systems in household trash in a manner that prevents accidental application or ingestion by children or pets.
Patient Counseling Information
Men With Known or Suspected Prostate or Breast Cancer
Men with known or suspected prostate or breast cancer should not use Striant [see Contraindications and Warnings and Precautions].
Gum-related Adverse Reactions
Gum-related adverse reactions, including severe gum irritation, were reported in clinical trials of Striant. Advise patients to regularly inspect the gum region where they apply Striant and to report any abnormality to their health care professional.
Potential Adverse Reactions With Androgens
Patients should be informed that treatment with androgens, such as Striant, may lead to adverse reactions that include:
- Changes in urinary habits such as increased urination at night, trouble starting their urine stream, passing urine many times during the day, having an urge that they have to go to the bathroom right away, having a 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 These Application Instructions
- Advise patients to carefully read the patient information accompanying each carton of Striant blister packaged tablets.
- Morning and evening oral care should be timed to coincide with removal of the residual old system and application of a new buccal system.
- Before morning and evening oral care, the residual Striant buccal system residual should be removed, then oral care should be performed.
- Following oral care, a new buccal system should be applied.
- Upon opening the packet, the rounded side surface of the buccal system should be placed against the gum and held firmly in place with a finger over the lip and against the product for 30 seconds to ensure adhesion.
- Striant should be placed in a comfortable position just above the incisor tooth (on either side of the mouth). With each application, Striant should be rotated to alternate sides of the mouth.
- Striant is designed to stay in position until removed. If the buccal system fails to properly adhere to the gum or falls off within the first 8 hours of dosing, replace with a new system and continue for a total of 12 hours for the placement of the first system. If the system falls out of position after 8 hours of dosing, a new buccal system should be applied and it may remain in place for 12 hours then continue with the next regularly scheduled dosing.
- Patients should take care to avoid dislodging the buccal system. Patients should check to see if Striant is in place following consumption of food or alcoholic/non-alcoholic beverages. Striant should not be chewed or swallowed.
Manufactured by: Mipharm S.p.A, Milan, Italy
Manufactured for: Actient Pharmaceuticals LLC, Malvern, PA 13955 US Patent No. 6,248,35