Sinuva

Description

The SINUVA Sinus Implant is a self-expanding, bioabsorbable, drug-eluting implant designed for sinus treatment, supplied with a crimper and a single-use delivery system. It consists of poly(L-lactide-co-glycolide) and poly(L-lactide-co-ε-caprolactone), coated with mometasone furoate, which is embedded in a bioabsorbable polymer matrix containing poly(DL-lactide-co-glycolide) and polyethylene glycol, facilitating the gradual release of the drug.

Mometasone furoate, the active ingredient, is a corticosteroid with the chemical name 9,21-dichloro-11(β),17-dihydroxy-16(α)-methylpregna-1,4-diene-3,20-dione 17 (2-furoate). It appears as a white powder with an empirical formula of C27H30Cl2O6 and a molecular weight of 521.44 Daltons. The inactive ingredients include poly-(DL-lactide-co-glycolide), an amorphous biodegradable polymer, and polyethylene glycol.

The SINUVA Sinus Implant is provided sterile and is packaged in a tray, which is sealed in a foil pouch and placed within a product carton.

Uses and Indications

SINUVA Sinus Implant is indicated for the treatment of chronic rhinosinusitis with nasal polyps in adult patients aged 18 years and older who have undergone ethmoid sinus surgery.

There are no teratogenic or nonteratogenic effects associated with the use of SINUVA Sinus Implant.

Dosage and Administration

The SINUVA Sinus Implant is to be loaded into a Delivery System and placed in the ethmoid sinus under endoscopic visualization. This procedure should be performed by physicians who are trained in otolaryngology to ensure proper placement and technique.

Once inserted, the implant is designed to remain in the sinus for a duration of up to 90 days, during which it gradually releases the corticosteroid. It is essential for healthcare professionals to monitor the implant and assess the patient's response to treatment.

The implant should be removed by 90 days post-insertion or earlier if deemed necessary by the physician. Removal should be conducted using standard surgical instruments to ensure patient safety and minimize complications.

Contraindications

Use of the SINUVA Sinus Implant is contraindicated in patients with known hypersensitivity to mometasone furoate or any of the components of the implant. Due to the potential for severe allergic reactions, administration in these patients may pose significant health risks.

Warnings and Precautions

Healthcare professionals are advised to exercise caution and implement appropriate monitoring when using the SINUVA Sinus Implant.

Nasal Mucosa Monitoring It is essential to monitor the nasal mucosa adjacent to the SINUVA Sinus Implant for any signs of bleeding (epistaxis), irritation, infection, or perforation. The use of this implant is contraindicated in patients with nasal ulcers or trauma, as these conditions may exacerbate complications.

Vision Changes and Ocular History Patients presenting with changes in vision or those with a history of increased intraocular pressure, glaucoma, or cataracts should be monitored closely. Any alterations in ocular health may necessitate further evaluation and intervention.

Hypersensitivity Reactions The use of corticosteroids associated with the SINUVA Sinus Implant has been linked to hypersensitivity reactions, which may manifest as rash, pruritus, or angioedema. Healthcare providers should remain vigilant for these adverse effects and manage them accordingly.

Infection Risks There is a potential risk for the worsening of existing infections, including tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. Additionally, susceptible patients may experience a more serious or even fatal course of chickenpox or measles. Caution is advised when treating patients with a history of these infections due to the risk of exacerbation.

Corticosteroid Effects In the event that corticosteroid effects such as hypercorticism or adrenal suppression are observed in patients, the removal of the sinus implant should be considered. This action may be necessary to mitigate the adverse effects associated with prolonged corticosteroid exposure.

Healthcare professionals are encouraged to remain vigilant and proactive in monitoring these parameters to ensure patient safety and optimal outcomes.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. Common adverse reactions observed in clinical trials include bronchitis, nasopharyngitis, otitis media, headache, presyncope, asthma, and epistaxis. The frequency of these reactions in clinical trial participants was as follows: asthma (4.7%), headache (3.5%), epistaxis (2.4%), presyncope (2.4%), bronchitis (2.0%), otitis media (2.0%), and nasopharyngitis (1.2%).

In addition to these common reactions, other adverse events reported in the treatment group included hypersensitivity reactions (4%, n=2), chronic rhinosinusitis (11%, n=6), and upper respiratory tract infections (8%, n=4). Notably, in a repeat placement study, acute sinusitis was reported in 29% (n=12) of subjects, while upper respiratory infections occurred in 17% (n=7). Epistaxis and nasal discomfort or rhinalgia were each reported in 12% (n=5) of participants, and headache was noted in 7% (n=3).

Postmarketing experiences have also identified additional adverse reactions, including implant migration, lack of efficacy, nasal pain, headache, and epistaxis.

Warnings associated with the treatment include the potential for hypersensitivity reactions, which may manifest as rash, pruritus, and angioedema. There is also a risk of worsening existing infections, such as tuberculosis and various fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. Furthermore, corticosteroid effects, including hypercorticism and adrenal suppression, should be considered.

Precautions should be taken to monitor the nasal mucosa for signs of bleeding (epistaxis), irritation, infection, or perforation. The treatment is not recommended for patients with nasal ulcers or trauma.

Drug Interactions

The SINUVA Sinus Implant has not undergone formal drug-drug interaction studies. However, an evaluation of its concurrent administration with other commonly used nasal medications did not reveal any unusual adverse reactions, suggesting a favorable safety profile in this context.

In terms of pharmacokinetic interactions, co-administration with ketoconazole, a potent CYP 3A4 inhibitor, may lead to increased plasma concentrations of mometasone furoate. Clinicians should consider monitoring patients for potential effects related to elevated levels of mometasone furoate when these agents are used together. No specific dosage adjustments are recommended; however, careful observation is advised to mitigate any potential risks associated with increased exposure.

Packaging & NDC

The table below lists all NDC Code configurations of Sinuva (mometasone furoate), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of the SINUVA Sinus Implant have not been established in pediatric patients under 18 years of age. Therefore, its use in this population is not recommended.

Geriatric Use

Elderly patients, defined as those 65 years of age or older, were represented by a total of 33 individuals who received the SINUVA Sinus Implant in two controlled randomized clinical trials. However, the clinical studies did not include a sufficient number of subjects aged 65 and over to ascertain whether their response to the treatment differs from that of younger patients.

Given the limited data available, healthcare providers should exercise caution when prescribing SINUVA to geriatric patients. It is advisable to monitor this population closely for any potential differences in efficacy or safety profiles compared to younger individuals. Additionally, consideration should be given to the possibility of requiring dosage adjustments based on the individual health status and comorbidities commonly present in elderly patients.

Pregnancy

There are no randomized clinical studies of SINUVA Sinus Implant or mometasone furoate in pregnant women. The active pharmaceutical ingredient, mometasone furoate, is systemically available when administered topically or inhaled. Animal reproduction studies have demonstrated that subcutaneous administration of mometasone furoate to pregnant mice, rats, or rabbits resulted in increased fetal malformations and decreased fetal survival and growth at doses producing exposures approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m² or AUC basis.

Experience with oral corticosteroids indicates that rodents may be more susceptible to teratogenic effects from corticosteroid exposure than humans. The estimated background risk of major birth defects and miscarriage for the indicated population remains unknown. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

In an embryofetal development study involving pregnant mice dosed throughout the organogenesis period, mometasone furoate was associated with cleft palate at an exposure approximately one-third of the MRHD and decreased fetal survival at an exposure equivalent to the MRHD. Similarly, in pregnant rats, exposure to mometasone furoate during organogenesis resulted in fetal umbilical hernia at approximately 6 times the MRHD and delays in fetal ossification at approximately 3 times the MRHD. Another reproductive toxicity study in pregnant rats indicated that dosing throughout pregnancy or late in gestation led to prolonged and difficult labor, fewer live births, lower birth weight, and reduced early pup survival at an exposure approximately 8 times the MRHD.

Embryofetal development studies conducted with pregnant rabbits revealed that mometasone furoate caused multiple malformations in fetuses at an exposure approximately 3 times the MRHD, as well as increased fetal resorptions and cleft palate and/or head malformations at an exposure approximately 1/2 of the MRHD. At an exposure approximately 2 times the MRHD, most litters were aborted or resorbed, while no effects were observed at an exposure approximately 1/10 of the MRHD. Given these findings, healthcare professionals should carefully consider the potential risks when prescribing this medication to pregnant patients.

Lactation

There are no available data on the presence of SINUVA Sinus Implant in human milk, nor on the effects on breastfed infants or milk production. Systemic absorption of a single inhaled 400 mcg dose of mometasone was less than 1%. It is not known if mometasone furoate is excreted in human milk; however, other inhaled corticosteroids, similar to mometasone furoate, have been detected in human milk.

When considering the use of SINUVA Sinus Implant in lactating mothers, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for the implant and any potential adverse effects on the breastfed infant.

Renal Impairment

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in these patients to ensure safety and efficacy.

Hepatic Impairment

Patients with hepatic impairment may experience increased concentrations of mometasone furoate, which appear to correlate with the severity of liver dysfunction. Therefore, careful consideration should be given when prescribing this medication to individuals with compromised liver function.

Monitoring of liver function is recommended for patients with hepatic impairment to assess the need for dosage adjustments or additional clinical interventions. It is essential to evaluate the patient's overall health status and liver function regularly to ensure safe and effective use of mometasone furoate in this population.

Overdosage

There are currently no data available regarding the effects of acute or chronic overdosage with the SINUVA Sinus Implant. However, it is important to note that chronic overdosage may lead to signs and symptoms associated with hypercorticism.

Healthcare professionals should remain vigilant for any indications of hypercorticism in patients who may have experienced chronic overdosage. Symptoms may include, but are not limited to, weight gain, hypertension, glucose intolerance, and changes in mood or behavior.

In the event of suspected overdosage, it is recommended that healthcare providers assess the patient’s clinical status and consider appropriate management strategies. Monitoring and supportive care may be necessary to address any emerging symptoms related to hypercorticism.

Nonclinical Toxicology

In a 2-year carcinogenicity study conducted in Sprague Dawley rats, mometasone furoate did not demonstrate a statistically significant increase in tumor incidence at inhalation doses up to 67 mcg/kg, which is approximately 14 times the maximum recommended human dose (MRHD) based on area under the curve (AUC). Similarly, a 19-month carcinogenicity study in Swiss CD-1 mice revealed no statistically significant increase in tumor incidence at inhalation doses up to 160 mcg/kg, approximately 9 times the MRHD on an AUC basis.

Mometasone furoate was found to increase chromosomal aberrations in an in vitro assay using Chinese hamster ovary cells; however, this effect was not observed in an in vitro assay using Chinese hamster lung cells. The compound was not mutagenic in the Ames test or the mouse lymphoma assay, and it did not exhibit clastogenic effects in an in vivo mouse micronucleus assay, a rat bone marrow chromosomal aberration assay, or a mouse male germ-cell chromosomal aberration assay. Additionally, mometasone furoate did not induce unscheduled DNA synthesis in vivo in rat hepatocytes.

In reproductive studies involving rats, no impairment of fertility was observed at subcutaneous doses up to 15 mcg/kg, which is approximately 8 times the MRHD on an AUC basis.

Postmarketing Experience

During postapproval use of the SINUVA sinus implant, several adverse reactions have been identified. These include implant migration, lack of efficacy, nasal pain, headache, and epistaxis.

The reports of these reactions have been collected voluntarily from a population of uncertain size, which limits the ability to reliably estimate their frequency or establish a causal relationship to the drug experience.

Patient Counseling

Patients should be encouraged to use saline irrigations or sprays regularly to maintain nasal health. It is important to inform patients that the SINUVA Sinus Implant is bioabsorbable and is designed to soften over time. As the Implant softens and polyps decrease, it may be expelled from the nose either spontaneously or through actions such as sneezing or forceful nose blowing.

Patients should be advised to contact a healthcare professional immediately if they experience any of the following symptoms: excessive nasal bleeding, signs of infection such as significant pain or discomfort, persistent headache, or increased sinus discharge. Additionally, they should be informed of symptoms that may suggest the Implant has migrated posteriorly, including irritation or a choking sensation in the back of the throat or swallowing the Implant.

It is essential to communicate that there are risks associated with the insertion and removal of the SINUVA Sinus Implant, which are similar to those associated with other endoscopic sinus procedures. Patients should be made aware that treatment with the SINUVA Sinus Implant may lead to local adverse reactions, including nosebleeds (epistaxis), injury to the nerves or blood vessels of the middle turbinate or septum, and infections such as bacterial or candida infections.

Healthcare providers should advise patients who have experienced recent nasal septum ulcers, nasal surgery, or nasal trauma to refrain from using a nasal corticosteroid until healing has occurred, due to the potential inhibitory effect of corticosteroids on wound healing. Furthermore, hypersensitivity reactions, including rash, pruritus, and angioedema, have been reported with the use of mometasone furoate; patients should be instructed to remove the SINUVA Sinus Implant if such reactions occur.

Patients on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and to consult their physician without delay if exposed. Lastly, patients should be informed about the potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex.

Storage and Handling

The SINUVA Sinus Implant is supplied in a configuration that includes specific packaging details. It should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C and 30°C (59°F to 86°F). Proper storage conditions are essential to maintain the integrity of the product.

Additional Clinical Information

During postmarketing surveillance of the SINUVA sinus implant, several adverse reactions have been reported. These include implant migration, lack of efficacy, nasal pain, headache, and epistaxis. It is important to note that these reactions are reported voluntarily from a population of uncertain size, which complicates the ability to reliably estimate their frequency or establish a causal relationship to the drug experience. Clinicians should be aware of these potential adverse effects when considering treatment options for patients.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Sinuva as submitted by Intersect ENT, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)