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Pharmaceutical Approval Update May 2018

Mary Choy PharmD, BCGP, FASHP

Vancomycin Hydrochloride for Oral Solution (Firvanq)

Manufacturer: CutisPharma, Inc., Wilmington, Massachusetts

Date of Approval: January 26, 2018

Indication: Firvanq is approved for the treatment of Clostridium difficile-associated diarrhea (CDAD) and enterocolitis caused by Staphylococcus aureus, including methicillin-resistant strains. It is a glycopeptide antibacterial indicated in adults and pediatric patients.

Drug Class: Antibacterial

Uniqueness of Drug: Firvanq is the only Food and Drug Administration-approved vancomycin oral liquid treatment option for CDAD, a life-threatening condition that affects more than 500,000 patients in the United States annually. The availability of an oral liquid formulation is expected to improve patient access and reduce the pharmacist burden of having to compound the drug.

Warnings and Precautions

Oral use only. This drug must be given orally for treatment of CDAD and staphylococcal enterocolitis only. Orally administered vancomycin is not effective for the treatment of other types of infections.

Potential for systemic absorption. Clinically significant serum concentrations have been reported in some patients who have taken multiple oral doses of vancomycin hydrochloride for CDAD. Monitoring of serum concentrations may be appropriate in some instances.

Nephrotoxicity. Nephrotoxicity, including reports of renal failure, renal impairment, and increased blood creatinine, has occurred following oral vancomycin hydrochloride therapy in randomized controlled clinical trials and can occur either during or after completion of therapy. This risk is increased in geriatric patients. Renal function should be monitored during and following treatment to detect potential nephrotoxicity.

Ototoxicity. Ototoxicity has occurred in patients receiving vancomycin. Assessment of auditory function may be appropriate in some instances.

Potential for microbial overgrowth. Use of Firvanq may result in the overgrowth of nonsusceptible bacteria. If superinfection occurs during therapy, appropriate measures should be taken.

Dosing and Administration: Prior to administration, the supplied powder must be reconstituted by a health care provider to produce the oral solution.

In adults with CDAD, the recommended dose is 125 mg administered orally four times daily for 10 days. The recommended total daily dose in adults with staphylococcal enterocolitis is 500 mg to 2 g administered orally in three or four divided doses for seven to 10 days.

In patients younger than 18 years of age, the recommended daily dosage for both CDAD and staphylococcal enterocolitis is 40 mg/kg in three or four divided doses for seven to 10 days. The total daily dosage should not exceed 2 g.

Commentary: In two trials, Firvanq 125 mg orally four times daily for 10 days was evaluated in 266 adults with CDAD. Enrolled patients were 18 years of age or older and received no more than 48 hours of treatment with oral vancomycin hydrochloride or oral/intravenous metronidazole in the five days preceding enrollment. CDAD was defined as three or more loose or watery bowel movements within the 24 hours preceding enrollment, and the presence of either C. difficile toxin A or B, or pseudomembranes on endoscopy within the 72 hours preceding enrollment. Patients with fulminant C. difficile disease, sepsis with hypotension, ileus, peritoneal signs, or severe hepatic disease were excluded. The median time to resolution of diarrhea was five days and four days in Trial 1 and Trial 2, respectively. For patients older than 65 years of age, the median time to resolution was six days and four days in Trial 1 and Trial 2, respectively. In patients with diarrhea resolution at the end of treatment with Firvanq, recurrence of CDAD within four weeks occurred in 25 of 107 (23%) and 18 of 102 (18%) in Trial 1 and Trial 2, respectively. The most common adverse reactions occurring at a rate of 10% or greater were nausea (17%), abdominal pain (15%), and hypokalemia (13%).

Sources: CutisPharma, Inc., Firvanq prescribing information

Mary Choy, PharmD, BCGP, FASHP

Dexamethasone Intraocular Suspension 9% (Dexycu)

Manufacturer: Icon Bioscience, Sunnyvale, California

Date of Approval: February 9, 2018

Indication: Dexycu is an intraocular injection indicated for the treatment of postoperative inflammation.

Drug Class: Corticosteroid, anti-inflammatory

Uniqueness of Drug: Dexycu is the first long-acting intracameral product approved by the Food and Drug Administration for treating inflammation following cataract surgery. It delivers a biodegradable, extended-release formulation of dexamethasone into the posterior chamber of the eye via a single injection at the end of surgery, eliminating the burden of self-administering medicated eye drops several times a day in a primarily elderly patient population.

Warnings and Precautions

Increase in intraocular pressure. Prolonged use of corticosteroids, including Dexycu, may result in glaucoma with damage to the optic nerve, defects in visual acuity, and fields of vision. Steroids should be used with caution in the presence of glaucoma.

Delayed healing. The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. In patients affected by diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of corticosteroids.

Exacerbation of infection. The use of Dexycu, as with other ophthalmic corticosteroids, is not recommended in the presence of most active viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, or in the presence of mycobacterial infection of the eye or fungal disease of ocular structures. Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires caution. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. Fungal culture should be taken when appropriate. Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions, steroids may mask infection or enhance existing infection.

Cataract progression. The use of corticosteroids in phakic individuals may promote the development of posterior subcapsular cataracts.

Dosage and Administration: Dexycu should be administered as a single intraocular dose in the posterior chamber of the eye at the end of surgery. The recommended dose is 0.005 mL of dexamethasone 9% (equivalent to 517 mcg). Each kit contains a single administration of Dexycu.

Commentary: Clinical efficacy was evaluated in a randomized, double-masked, placebo-controlled trial in which patients received Dexycu or placebo. A dose of 5 mcL of Dexycu (equivalent to 517 mcg of dexamethasone), a dose equivalent to 342 mcg of dexamethasone, or a vehicle placebo was administered by the physician at the end of the surgical procedure. The primary efficacy endpoint was the proportion of patients with anterior chamber cell clearing (e.g., cell score = 0) on post operative day 8. The percentage of patients who met the endpoint was 20% in the placebo group and 57% and 60% in the 342-mcg and 517-mcg treatment groups, respectively. The percentage of patients receiving rescue medication of ocular steroids or nonsteroidal anti-inflammatory drugs was significantly lower at days 3, 8, 15, and 30 in the 342-mcg and 517-mcg treatment groups compared with placebo. The most common adverse reactions reported in 5% to 15% of patients were increased intraocular pressure, corneal edema, and iritis.

Sources: Icon Bioscience, Dexycu prescribing information

Apalutamide (Erleada)

Manufacturer: Janssen Biotech, Inc., Raritan, New Jersey

Date of Approval: February 14, 2018

Indication: Apalutamide is indicated for the treatment of patients with nonmetastatic castration-resistant prostate cancer (NM-CRPC).

Drug Class: Antiandrogen

Uniqueness of Drug: Apalutamide is the first Food and Drug Administration (FDA)-approved therapy to treat patients with NM-CRPC. According to the National Cancer Institute (NCI), prostate cancer is the second most common form of cancer in men in the U.S. The NCI estimates approximately 161,360 men were diagnosed with prostate cancer in 2017, and 26,730 were expected to die of the disease. Approximately 10% to 20% of prostate cancer cases are castration-resistant, and up to 16% of these patients show no evidence that the cancer has spread at the time of the castration-resistant diagnosis. The FDA approved apalutamide under its priority review program.

Warnings and Precautions

Falls and fractures. Falls and fractures have occurred in patients receiving apalutamide. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. In a randomized study (SPARTAN), falls occurred in 16% of patients treated with apalutamide compared with 9% of patients treated with placebo. Falls were not associated with loss of consciousness or seizure. Fractures occurred in 12% of patients treated with apalutamide and in 7% of patients treated with placebo. Grade 3–4 fractures occurred in 3% of patients treated with apalutamide and in 1% of patients treated with placebo. The median time to onset of fracture was 314 days (range, 20–953 days) for patients treated with apalutamide. Routine bone density assessment and treatment of osteoporosis with bone-targeted agents were not implemented in the SPARTAN study.

Seizure. Seizures have occurred in patients receiving apalutamide. Permanently discontinue apalutamide in patients who develop a seizure during treatment. It is unknown whether antiepileptic medications will prevent seizures with apalutamide. Advise patients of the risk of developing a seizure while receiving apalutamide and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. In the SPARTAN trial, two patients (0.2%) experienced a seizure 354–475 days after initiation of apalutamide. No seizures occurred in patients treated with placebo. Patients with a history of seizure, predisposing factors for seizure, or receiving drugs known to decrease the seizure threshold or to induce seizure were excluded. There is no clinical experience in readministering apalutamide to patients who experienced a seizure.

Dosing and Administration: The recommended dose of apalutamide is 240 mg (four 60-mg tablets) orally once daily. The tablets should be swallowed whole with or without food. Patients should also receive a gonadotropin-releasing hormone (GnRH) analogue concurrently or should have had a bilateral orchiectomy.

Commentary: The FDA approval of apalutamide was based on the SPARTAN trial in which 1,207 patients with NM-CRPC were randomized to apalutamide or placebo. All patients were also treated with hormone therapy, either with GnRH analogue therapy or with surgery to lower the amount of testosterone in their body (surgical castration). The median metastasis-free survival for patients taking apalutamide was 40.5 months compared with 16.2 months for patients on placebo. The most common adverse reactions occurring in 10% or more of patients were fatigue, hypertension, rash, diarrhea, nausea, weight loss, arthralgia, fall, hot flush, decreased appetite, fracture, and peripheral edema.

Sources: Janssen Biotech, Inc., Erleada prescribing information

Author bio: 
Dr. Choy is a freelance medical writer living in New York City.