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Pharmaceutical Approval Update May 2017
Manufacturer: Valeant Pharmaceuticals, Bridgewater, New Jersey
Date of Approval: February 15, 2017
Indication: Brodalumab is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies.
Drug Class: Interleukin inhibitors, monoclonal antibodies, antipsoriatics
Uniqueness of Drug: Brodalumab is a novel human monoclonal antibody that binds to the interleukin (IL)-17 receptor and inhibits inflammatory signaling by blocking the binding of several types of IL-17 to the receptor. By stopping IL-17 from activating the receptor, brodalumab prevents the body from receiving signals that may lead to inflammation. The IL-17 pathway plays a central role in inducing and promoting inflammatory disease processes.
Warnings and Precautions:
Boxed warning: suicidal ideation and behavior. Suicidal ideation and behavior, including completed suicides, have occurred in patients treated with brodalumab. Prior to prescribing brodalumab, weigh the potential risks and benefits in patients with a history of depression and/or suicidal ideation or behavior. Patients with new or worsening suicidal ideation and behavior should be referred to a mental health professional as appropriate. Advise patients and caregivers to seek medical attention for manifestations of suicidal ideation or behavior, new-onset or worsening depression, anxiety, or other mood changes. Because of the observed suicidal behavior in patients treated with brodalumab, it is available only through the restricted Siliq risk evaluation and mitigation strategy program.
Infections. Brodalumab may increase the risk of infections. Consider the risks and benefits prior to initiating brodalumab in patients with a chronic infection or a history of recurrent infections. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infections occur. If a serious infection develops, discontinue brodalumab until the infection resolves.
Tuberculosis (TB). Evaluate patients for TB infection prior to initiating treatment. Do not administer brodalumab to patients with an active TB infection.
Crohn’s disease. Brodalumab is contraindicated in patients who have or develop Crohn’s disease.
Immunizations. Avoid use of live vaccines in patients treated with brodalumab.
Dosage and Administration: The recommended brodalumab dose is 210 mg administered by subcutaneous injection at weeks 0, 1, and 2, followed by 210 mg every two weeks. If an adequate response has not been achieved after 12 to 16 weeks of treatment, consider discontinuing therapy. Continued treatment beyond 16 weeks in patients who have not achieved an adequate response is not likely to result in greater success.
Commentary: The Food and Drug Administration approval of brodalumab is based on data from three phase 3 pivotal studies that demonstrated that the drug has an effective mechanism of action that delivers clinical benefit and could help a significant number of moderate-to-severe plaque psoriasis patients achieve total clearance of their skin disease. At the 210-mg dose, brodalumab demonstrated efficacy in total skin clearance of psoriasis, with approximately twice as many patients receiving brodalumab achieving total skin clearance compared with ustekinumab at week 12 in two replicate comparator trials involving more than 2,400 patients. The most common adverse reactions were arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection-site reactions, influenza, neutropenia, and tinea infections.
Sources: Valeant Pharmaceuticals, Siliq prescribing information
Telotristat Ethyl (Xermelo)
Manufacturer: Lexicon Pharmaceuticals, The Woodlands, Texas
Date of Approval: February 28, 2017
Indication: Telotristat ethyl is indicated for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analogue (SSA) therapy in adults whose condition is inadequately controlled by SSA therapy alone.
Drug Class: Gastrointestinal agents
Uniqueness of Drug: Telotristat ethyl is the first and only orally administered therapy for the treatment of carcinoid syndrome diarrhea in combination with SSA therapy in adults inadequately controlled by SSA therapy alone. It has received orphan drug status and fast-track designation from the Food and Drug Administration. Carcinoid syndrome is a rare and debilitating condition that affects people with metastatic neuroendocrine tumors (mNETs). Telotristat ethyl targets the overproduction of serotonin inside mNET cells, providing a new treatment option for patients suffering from carcinoid syndrome diarrhea.
Warnings and Precautions:
Constipation. Telotristat ethyl reduces bowel movement frequency. Monitor patients for constipation and/or severe persistent or worsening abdominal pain. Discontinue telotristat ethyl if severe constipation or abdominal pain develops.
Dosage and Administration: The recommended dosage of telotristat ethyl in adult patients is 250 mg three times daily for those whose diarrhea is inadequately controlled by SSA therapy alone.
Telotristat ethyl should be taken with food. If a dose is missed, the next dose should be taken at the regular time. Two doses should not be administered at the same time to make up for a missed dose. Discontinue telotristat ethyl if severe constipation develops.
When used in combination with telotristat ethyl, short-acting octreotide must be administered at least 30 minutes after telotristat ethyl.
Commentary: The safety and efficacy of telotristat ethyl were established in a 12-week, double-blind, placebo-controlled trial in 90 adults with well-differentiated mNETs and carcinoid syndrome diarrhea. These patients were having four to 12 daily bowel movements despite the use of SSA at a stable dose for at least three months. Participants remained on their SSA treatment and were randomized to an added placebo or treatment with telotristat ethyl three times daily. Those receiving telotristat ethyl with their SSA treatment experienced a greater reduction in average bowel movement frequency than those on SSA with placebo. Specifically, 33% of participants randomized to telotristat ethyl with SSA experienced an average reduction of two bowel movements per day compared to 4% of patients randomized to placebo with SSA.
The most common adverse reactions reported with telotristat ethyl (at an incidence of 5% or greater) were nausea, headache, increased gamma-glutamyl-transferase levels, depression, flatulence, decreased appetite, peripheral edema, and pyrexia.
Sources: Lexicon Pharmaceuticals, Xermelo prescribing information
Desmopressin Acetate (Noctiva)
Manufacturer: Serenity Pharmaceuticals, Milford, Pennsylvania
Date of Approval: March 3, 2017
Indication: Desmopressin acetate nasal spray is indicated for adults with nocturnal polyuria, also known as nocturia, who awaken at least two times each night to urinate. Nocturnal polyuria was defined in the desmopressin acetate clinical trials as nighttime urine production exceeding one-third of the patient’s 24-hour urine production.
Drug Class: Vasopressin analogue
Uniqueness of Drug: Desmopressin nasal spray is the first drug approved to treat nocturnal polyuria in the United States. The disorder is a symptom that can be caused by a wide variety of conditions, such as congestive heart failure, poorly controlled diabetes mellitus, medications, or diseases of the bladder or prostate.
Warnings and Precautions:
Boxed warning: hyponatremia. Desmopressin nasal spray can cause hyponatremia (low sodium levels in the blood), which in its severest form can be life threatening, leading to seizures, coma, respiratory arrest, or death. Desmopressin nasal spray is contraindicated in patients at increased risk of severe hyponatremia, such as patients with excessive fluid intake, those with illnesses that can cause fluid or electrolyte imbalances, and those using loop diuretics or systemic or inhaled glucocorticoids. Ensure serum sodium concentrations are normal before starting or resuming desmopressin nasal spray. Serum sodium should be measured within seven days and approximately one month after initiating therapy or increasing the dose, and periodically during treatment. In patients 65 years of age and older and those with increased risk of hyponatremia, serum sodium should be monitored frequently. If hyponatremia occurs, desmopressin nasal spray may need to be temporarily or permanently discontinued.
Fluid retention. Desmopressin nasal spray can cause fluid retention, which can worsen underlying conditions that are susceptible to volume status. Therefore, desmopressin nasal spray is contraindicated in patients with New York Heart Association (NYHA) class II–IV congestive heart failure or uncontrolled hypertension. In addition, desmopressin nasal spray is not recommended in patients at risk for increased intracranial pressure or those with a history of urinary retention and should be used with caution (e.g., monitoring of volume status) in patients with NYHA class I congestive heart failure.
Concurrent nasal conditions: Discontinue desmopressin nasal spray in patients with concurrent nasal conditions (e.g., atrophy of nasal mucosa, and acute or chronic rhinitis) that may increase systemic absorption, which increases the risk of hyponatremia. Treatment can be resumed when these conditions resolve.
Dosage and Administration: Before starting desmopressin nasal spray: 1) evaluate the patient for possible causes for the nocturia, including excessive fluid intake prior to bedtime, and optimize the treatment of underlying conditions that may be contributing to the nocturia; and 2) confirm the diagnosis of nocturnal polyuria with a 24-hour urine collection, if one has not been obtained previously.
Only administer desmopressin acetate intranasally. Do not shake the bottle. Prime desmopressin nasal spray before using for the first time by pumping five actuations into the air away from the face. Reprime by pumping two actuations into the air if the product has not been used for more than three days. If a dose is missed, do not double the dose at next use. Two sprays of 0.83-mcg desmopressin acetate are not interchangeable with one spray of desmopressin acetate 1.66 mcg.
For patients younger than 65 years of age who are not at increased risk for hyponatremia, the recommended dose is one 1.66-mcg spray of desmopressin acetate in either the left or right nostril approximately 30 minutes before going to bed.
For patients 65 years of age and older or younger patients at increased risk for hyponatremia, the recommended starting dose is one spray of desmopressin acetate 0.83 mcg in either the left or right nostril approximately 30 minutes before going to bed. After at least seven days of treatment, the dose can be increased to 1.66 mcg, providing the serum sodium is within the normal range during treatment with the 0.83-mcg dose.
Commentary: The efficacy of desmopressin nasal spray was established in two 12-week, randomized, placebo-controlled studies in a total of 1,045 patients 50 years of age and older with nocturia. Although these studies showed a small reduction in the average number of nighttime urinations with desmopressin nasal spray compared with placebo, more patients treated with desmopressin nasal spray were able to at least halve their number of nighttime urinations, and patients treated with desmopressin nasal spray had more nights with one or fewer nighttime urinations. The common adverse reactions in clinical trials occurring in more than 2% of patients included nasal discomfort, nasopharyngitis, nasal congestion, sneezing, hypertension, back pain, epistaxis, bronchitis, and dizziness.
Sources: Serenity Pharmaceuticals, Noctiva prescribing information