Desmopressin Acetate Nasal Spray Research Articles

Pharmacologic management of nocturnal polyuria: a contemporary assessment of efficacy, safety, and progress toward individualized treatment.

This narrative review synthesizes current evidence on the medical management of nocturnal polyuria, including antidiuretic replacement therapy as well as other emerging modalities, with particular emphasis on areas of active investigation and future research directions. Relative to earlier formulations, the pharmacological profiles of novel desmopressin acetate nasal spray and orally disintegrating tablet formulations appear favorable in optimizing the balance between efficacy and safety. Additionally, several highly selective small-molecule arginine vasopressin 2 receptor agonists are under active development, while appropriately timed short-acting diuretics, pharmacotherapy for hypertension, nonsteroidal anti-inflammatory drugs, and sex hormone replacement therapy are also a focal point of extensive ongoing nocturnal polyuria research. Emerging laboratory technologies now make feasible a sub-stratification of nocturnal polyuria patients into substrate-based phenotypes for individualized treatment. An increasingly refined understanding of the pathogenesis of nocturnal polyuria, and arginine vasopressin dysregulation in particular, has also introduced new opportunities for point-of-care testing in patients with nocturnal polyuria.

Do independent geriatric outpatients with nocturnal polyuria profit from desmopressin?

To compare the efficacy of desmopressin and placebo in independent geriatric outpatients with nocturnal polyuria (NP). A prospective, randomized, single-center, national, double blind, placebo-controlled, fixed-dose, parallel group comparative trial was carried out. The study included 110 geriatric outpatients, 55patients per treatment group using desmopressin acetate nasal spray (strength: 0.1 mg/ml) once daily of 10 μg/spray blast or placebo. The NP positive geriatric outpatients with >33% nocturnal urine output volume, antidiuretic hormone (ADH) positive or negative were treated over 10days with intranasal spray in the evening time (7p.m.), drug or placebo. On day1 voiding frequency, voiding volumes day and night, serum osmolarity and arginine-vasopressin (AVP) were measured at 7p.m. On days2, 5 and 10 creatinine, blood urea nitrogen (bun), blood count and C‑reactive protein (CrP), vena cava diameter and bioimpedance were measured and astructured interview was implemented (voiding frequency, sleeping behavior and subjective and cognitive behavior). The NP patients showed amean night voiding volume of 50.60%, 39.21% (n = 102) showed alow AVP level at baseline with no correlation to sodium concentration or voiding frequencies. The primary efficacy criterion, a decrease of the nocturnal voiding frequency during the course of the clinical trial as change from baseline at day10 (visit4) was 50% versus 41.40% in the verum versus placebo group, respectively but the differences were not significant. The U‑test showed superiority of AVP-positive NP patients to a positive reaction on desmopressin. Sleeping time hours increased in both groups without significant differences. In this 10-day clinical trial desmopressin was not proven to be therapeutically superior to placebo with respect to micturition frequency or sleeping hours. Independent geriatric outpatients with decreased ADH levels seemed to respond and benefit from active treatment with desmopressin. The unexpected results in the placebo group may be due to the effect of intensive outpatient care and information on NP outpatients with normal AVP levels.

Desmopressin acetate nasal spray for adults with nocturia

ABSTRACTIntroduction: Nocturia impacts 70% of individuals over age 70 years. Nocturnal polyuria is present in up to 88% of adults with nocturia, however, treatment options for reducing nighttime urine production have historically been limited to behavioral modification and off label use of timed diuretics and desmopressin. NoctivaTM (desmopressin acetate nasal spray, DANS, Serenity Pharmaceuticals, LLC) is a novel formulation of desmopressin approved by the Food and Drug Administration for the treatment of nocturia due to nocturnal polyuria in March 2017.Areas covered: Incidence and etiology of nocturia, currently available therapies (approved and off label), and pharmacokinetic, efficacy, and safety data associated with DANS.Expert commentary: DANS has been studied for the treatment of nocturia in adults over age 50 without contraindications to the use of desmopressin. 49% receiving the higher clinical dose experienced ≥50% reduction in nocturnal voids in clinical trials vs. 30% with placebo. Although nadir serum sodium <135 mmol/L was not uncommon (14%), the incidence of sodium ≤125 mmol/L was rare (1%). DANS therefore appears to benefit a significant subset of patients with nocturia while maintaining an acceptable risk profile. Given the risks of hyponatremia, education of patients and prescribers in contraindications and the importance of monitoring are paramount.

Does desmopressin produce more cognitive problems and delirious symptoms in independent geriatric outpatients with nocturnal polyuria (NP)?

ObjectivesTo show a relation between the nocturnal polyuria, its therapy with desmopressin and cognitive alterations and delirious symptoms. MethodologyProspective, randomized, mono-center, mono-national, double-blind, placebo-controlled, fixed-dose, parallel group comparative trial, with 110 patients, 55 patients per treatment group using desmopressin acetate nasal spray, strength: 0.1mg/mL, nasal once a day of 10μg/spray blast. MeasurementNP positive patients (>33% nocturnal urine output volume [ADH positive or negative]) were treated over 10 days with intranasal spray in the evening time (7 p.m.), drug or placebo. On day 2, 5 and 10 the patients were interviewed about voiding frequency, sleeping behavior and subjective and cognitive alterations and delirium. ResultsThere was no correlation to be found between NP and the incidence of delirious symptoms or cognitive alterations. But the Mann-Whitney U-Test showed a superiority for delirious symptoms and forgetfulness under effective treatment with desmopressin (P=0.0279). Delirious symptoms showed to be significantly more frequent under desmopressin treatment in the final assessment (results last value, P=0.0297; changes from baseline, P=0.0340; percentage changes from baseline, P=0.0373). The variance analysis with repeated measures approved no significant augmentation of delirious symptoms under desmopressin. ConclusionIn this 10-day, clinical trial desmopressin was not significantly correlated with more delirious symptoms and forgetfulness in independent geriatric outpatients. NP and the disturbance of sleep were not correlated with delirium or cognitive decline.

Deficiency of antidiuretic hormone: a rare cause of massive polyuria after kidney transplantation.

A 15-year-old boy, who was diagnosed with Alport syndrome and end-stage renal disease, received a renal transplant from a living-related donor. On postoperative day 1, his daily urine output was 10,000 mL despite normal graft function. His laboratory findings including urine, serum osmolality, and antidiuretic hormone levels showed signs similar to central diabetes insipidus, so he was administered desmopressin acetate nasal spray. After administering the desmopressin, urine specific gravity and osmolality increased abruptly, and daily urine output declined to the normal range. The desmopressin acetate was tapered gradually and discontinued 3 months later. Graft function was good, and urine output was maintained within the normal range without desmopressin 20 months after the transplantation. We present a case of a massive polyuria due to transient deficiency of antidiuretic hormone with the necessity of desmopressin therapy immediately after kidney transplantation in a pediatric patient.

Large Cohort of Symptomatic Female Carriers of Hemophilia in an Extended Native American Family

Hemophilia A is an X-linked recessive genetic bleeding disorder resulting in a lack of clotting factor VIII. Although this disorder primarily affects males, a female who inherits one affected X chromosome from a parent becomes a carrier of hemophilia. While it is widely believed that carriers are asymptomatic, some of these women have mild hemophilia, defined by ISTH as a circulating factor VIII level > 0.5 to 0.40 IU/ml or 5 - 40 % of normal. (White et al Thromb Haemost 2001)Data demonstrates hemophilia A carriers have the same risk for bleeding as a male with mild hemophilia A at the corresponding factor level. Carriers report significantly more bleeding events than non-carriers from small wounds and after invasive procedures, and their bleeding tendency is inversely correlated to their factor level. (Plug et al Blood 2006) Carriers have been shown to demonstrate decreased joint range of motion, soft tissue and osteochondral changes on MRI, consistent with subclinical joint bleeds leading to structural abnormalities in their joints. (Gilbert et al Haemophilia 2014). Additionally, carriers have been shown to report higher scores on pictorial blood assessment charts, a semi-quantitative measure of menstrual blood loss. (Kadir et al Haemophilia 1999)We report here a unique patient population from our Owyhee Indian Health Hemophilia Treatment Center Outreach Clinic on the Duck Valley Indian Reservation in Owyhee, NV. On this reservation, a German Immigrant with hemophilia A married 2 women of the Shoshone Indian Tribe, and they had 14 children (8 females and 6 males). The family tree reveals after four generations there are currently 162 descendants with the same hemophilia A gene mutation, which has been identified. Factor VIII levels in the female family members range from 7% to 50%. The male hemophilia A patients are treated on demand with plasma-derived factor VIII products, currently Koate-DVI, for traumatic events, and prophylactically for medical or dental procedures, or surgery. Approximately 20-25% of the female carriers in this population have been treated with plasma-derived FVIII concentrates, currently Koate-DVI, for childbirth and surgeries. Additionally, all female carriers from teenage years to age 30 are treated with desmopressin acetate nasal spray (Stimate) for menorrhagia and are treated with oral aminocaproic acid (Amicar) for nose bleeds and soft tissue bleeds.Carriers of hemophilia A with factor VIII levels in the range observed in this family, particularly when symptomatic, should receive the diagnosis of "mild hemophilia". Their propensity for developing subclinical as well as clinical bleeding needs to be recognized to assure the receive treatment appropriate to their symptomatology. The low levels of FVIII observed in this family are likely due to extreme lyonization associated with their particular gene mutation. Familial low levels of FVIII can also be seen in some forms of type 2 von Willebrand Disease secondary to poor FVIII binding and a shortened half-life. However, since VWD is inherited in an autosomal recessive pattern, males would not selectively have the severity observed here. Optimal diagnostic and therapeutic strategies as well as many other aspects concerning mild hemophilia remain to be clarified. Additional studies to define these findings are underway. DisclosuresBerkowitz:Pfizer: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Speakers Bureau; Baxter: Speakers Bureau. Federizo:Emergent: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees; Baxalta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biogen Idec: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees. Bergman:Kedrion Biopharma: Employment. Ulsh:Kedrion Biopharma: Employment.

Assay of Desmopressin in nasal spray by HPLC – UV detector with one Isocratic pump and system set – up

The aim of this study was to apply high performance liquid chromatography – UV detector to determine desmopressin in pharmaceutical preparation using one pump (isocratic pump) and ODS, 5um column. And Mobil phase acetonitrile: N, N diethyl formamide in ratio of 85:15 which show good quantitative and qualitative analysis in desmopressin acetate nasal spray (Cipla LTD INDIA) New controlled condition for setting-up the system to get a result with high resolution was shown in this study. Keywordsdesmopressin, HPLC method , isocratic pump and system set-up

Oral Contraceptives and DDAVP Nasal Spray: Patterns of Use in Managing vWD-Associated Menorrhagia

The purpose of this study was to examine patterns of use for oral contraceptive and desmopressin acetate nasal spray, both used in managing menorrhagia in adolescents with von Willebrand disease (vWD). Hospital records of adolescents with documented vWD and menorrhagia were reviewed retrospectively. Subjects with vWD type 1 (n = 36) administered either oral contraceptives (OC) or intranasal desmopressin acetate (DDAVP) and followed from 6 months to 4 years were selected for inclusion. Treatment outcomes were examined with respect to effectiveness and safety. Assessing menstrual blood loss using PBAC scores from pretreatment and treatment periods determined effectiveness. Safety was evaluated by monitoring reported adverse events. No significant differences were identified in treatment effectiveness for controlling menorrhagia in vWD adolescents in the OC and intranasal DDAVP group comparisons: 86% versus 77% (P > 0.05), respectively. When combining both treatment groups, the majority of vWD adolescents, 81% (P > 0.05), experienced alleviation of menorrhagia symptoms. Treatment failures were attributed to either the inability of a regimen to control bleeding or to adverse events, including severe headaches and flushing with DDAVP. Safety outcomes were not significantly greater in vWD patients with menorrhagia when OC were compared with intranasal DDAVP. Both medical approaches, OC and DDAVP nasal spray, used in managing menorrhagia in adolescents with documented type I vWD were well tolerated and showed equivalent effectiveness, and no serious adverse events were reported.

Management of abnormal uterine bleeding

Patients treated for dysfunctional uterine bleeding are separated into two groups: those with acute bleeding episodes and those with chronic repetitive bleeding problems. An acute bleeding episode is best controlled with the use of high-dose estrogen. A curettage is indicated for patients with acute bleeding resulting in hypovolemia, and a curettage or hysteroscopically directed biopsies is indicated for women with risk factors for endometrial cancer who have persistent bleeding problems. The management of anovulatory dysfunctional uterine bleeding is determined by the needs of the patient. In the adolescent medroxyprogesterone acetate is administered orally once a day for 10 days each month for ≥3 months, and the patient is monitored closely thereafter. Oral contraceptives are used for women of reproductive age with anovulatory bleeding episodes who also require contraception. Clomiphene citrate is used for women of reproductive age with anovulatory bleeding who want to conceive. Oral medroxyprogesterone acetate is administered 10 days each month for 6 months for the treatment of anovulatory dysfunctional uterine bleeding alone in this age group. For the perimenopausal patient dysfunctional uterine bleeding may be treated by the administration of cyclic progestin or cyclic conjugated equine estrogens for 25 days with the concomitant administration of medroxyprogesterone acetate for days 16 to 25. The perimenopausal patient with dysfunctional uterine bleeding who is a nonsmoker and does not have evidence of vascular disease may also be treated with low-dose combination oral contraceptives. The long-term treatment for women with ovulatory dysfunctional uterine bleeding is the most difficult type of dysfunctional uterine bleeding to manage. The long-term therapy is directed at the reduction in menstrual blood loss. For these patients prolonged progestin use, oral contraceptives, nonsteroidal antiinflammatory drugs, antifibrinolytic agents, danazol, and as a last resort gonadotropin-releasing hormone agonists are part of the therapeutic armamentarium. A combination of two or more of these agents is often required to successfully control the abnormal bleeding. For patients who no longer desire future fertility and have associated pelvic pathologic disorders or for those who fail all medical regimens, surgical therapy may be considered. Either hysterectomy or endometrial ablation has been used. Patients with von Willebrand's disease and excessive menstrual blood loss may be misdiagnosed as having dysfunctional uterine bleeding. von Willebrand's disease is the most common bleeding disorder and is present in approximately 1% of the population. It is much more common than previously recognized. There are improved diagnostic tests to identify this disorder and, most important, there is a high-concentration desmopressin acetate nasal spray available as treatment that does not involve the risk of transmission of hepatitis and human immunodeficiency virus. (Am J Obstet Gynecol 1996;175:787-92.)