Stimate (desmopressin acetate) for hemophilia

Last updated May 22, 2024, by Lindsey Shapiro, PhD
Fact-checked by Joana Carvalho, PhD

What is Stimate for hemophilia?

Stimate (desmopressin acetate) was a nasal spray developed by Ferring Pharmaceuticals to control bleeding in people with mild hemophilia A that has been recalled and currently is unavailable. The product was sold under the brand name Octim in Europe and Octostim in Canada.

The company suspended production and voluntarily recalled the medication in 2020 due to “superpotency,” which essentially means that the amount of the therapy’s active ingredient, desmopressin, was higher than initially specified in some batches of the product. An ongoing distribution agreement between Ferring and CSL Behring for marketing Stimate in the U.S. ended in 2021.

A number of Ferring’s other nasal spray products that contained desmopressin also were recalled. Injectable medications containing desmopressin for hemophilia are still available.

Ferring previously indicated that should Stimate and its other brand-name products return to the market, it would not be before mid-2024 and would be contingent on approval from regulatory authorities.

In addition to hemophilia A, Stimate was approved to treat patients with some forms of von Willebrand’s disease, another inherited bleeding disorder.

Therapy snapshot

How does Stimate work?

After a blood vessel injury, a series of chain reactions are set in motion to induce blood clotting. This involves several molecules, including clotting factor VIII (FVIII) and von Willebrand factor. Hemophilia A is a bleeding disorder in which patients lack functional FVIII.

Stimate contains desmopressin, a lab-made form of a naturally occurring hormone produced by the brain’s pituitary gland called vasopressin. Also called the antidiuretic hormone, vasopressin’s main role is to enable the body to conserve water by preventing the kidneys from releasing too much water in the urine.

Vasopressin and desmopressin also can increase the levels of FVIII and von Willebrand factor in the bloodstream, helping to control bleeding. While scientists have known this is possible for decades, they have not completely understood how that happens. One theory is that desmopressin triggers the release of blood clotting factors that are stored in endothelial cells, which line blood vessels, and in platelets, small cell fragments involved in blood clotting.

Who with hemophilia could take Stimate?

Stimate was approved by the U.S. Food and Drug Administration in March 1994 to treat adults and children with mild hemophilia A whose FVIII activity levels were greater than 5% of normal. The medication also could be used to stop bleeding during episodes of spontaneous or trauma-induced injuries.

The therapy also was indicated to treat patients with mild-to-moderate classic von Willebrand’s disease. However, it was not indicated for people with severe classic von Willebrand’s disease and other forms of the condition, including type 2b von Willebrand’s disease.

Who should not take Stimate?

Stimate’s prescribing information listed no contraindications to its use.

However, it stated the therapy should be used with caution in patients with excessive thirst or compulsive water drinking, due to the risk of hyponatremia, which occurs when blood sodium levels drop excessively. Patients with kidney diseases, heart failure, and other disorders that increased their susceptibility to hyponatremia also should use Stimate with caution.

The therapy was not recommended for children under 11 months of age.

How was Stimate administered in hemophilia?

Stimate came in a 2.5 mL bottle with a spray pump. A single spray delivered 0.1 mL of the solution, which contained 150 micrograms (mcg) of desmopressin.

The recommended dose for bleed control was one spray into each nostril (300 mcg). For patients weighing less than 50 kg (about 110 pounds), the recommended dose was a single spray in one nostril (150 mcg). If used before surgery in anticipation of potential bleeds that might occur, Stimate should be administered two hours before the procedure. The necessity of additional sprays or other types of medications was determined by a person’s doctor based on lab tests and clinical response.

It was recommended that a person’s fluid intake be restricted in the hour before administration and up to at least one day after administration.

Bottles were stored at room temperature. Prior to using the nasal spray pump, it had to be primed by pressing down four times. Each bottle contained enough solution for 25 sprays. The bottle should have been discarded after 25 sprays, as any remaining liquid may not have had the necessary amount of desmopressin, or at six months after being opened.

Stimate in hemophilia clinical trials

Into-the-vein, or intravenous, formulations of desmopressin have been used since the 1970s to treat hemophilia.

A 1991 study showed that a nasal formulation of desmopressin was just as safe and effective as an intravenous formulation at treating bleeding episodes and preventing bleeds during surgery. FVIII levels adequate for bleed control were achieved in 82% of hemophilia patients.

An open-label, multicenter clinical trial was conducted to evaluate the safety and efficacy of Stimate when used for the control of bleeding episodes in 333 patients with mild hemophilia A, moderate type 1 von Willebrand disease, or symptomatic carriers of hemophilia A.

Overall, 278 patients received 2,170 doses of Stimate. Patients evaluated Stimate’s efficacy as “excellent” or “good” in 95% of the bleeding episodes. It was also rated “excellent” in most cases of preventive use (93%), surgical use (100%), and treatment of excessive menstrual bleeding (91%).

Common side effects of Stimate

Side effects reported in patients treated with Stimate included:

• nasal congestion
• runny nose
• flushing
• nosebleeds
• sore throat
• cough
• upper respiratory infections.

Fluid intake

Desmopressin is a potent antidiuretic, which can lead to higher-than-normal amounts of water in the body. This could cause water intoxication and/or hyponatremia, a possibly fatal condition where sodium levels are too low in the bloodstream. Very rare cases of hyponatremia were reported with Stimate’s use.

When using Stimate nasal spray, patients — especially children and older adults — were advised to reduce their water intake to prevent the possible occurrence of these side effects.

Patients were monitored for signs and symptoms of hyponatremia, including headache, nausea/vomiting, decreased blood sodium levels, weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, appetite loss, irritability, muscle weakness, muscle spasms/cramps, or abnormal mental status (e.g., hallucinations, confusion, decreased consciousness). Severe symptoms may have included seizures, coma, or respiratory arrest.

It also was recommended that Stimate be used with caution in people with polydipsia, or excessive thirst, as well as in those with conditions associated with fluid and electrolyte imbalances, such as cystic fibrosis, heart failure, and kidney disorders, as these people may be more prone to hyponatremia.

Blood Pressure

Desmopressin infrequently affected a person’s blood pressure, including slight elevations or transient drops, and a compensatory increase in heart rate. It was recommended that Stimate be used with caution in people with certain cardiovascular conditions.

Blood clots

There were rare reports of blood clot events following administration of an injectable version of desmopressin in patients prone to develop clots. No causality was determined, but Stimate should have been used with caution in those patients.

Allergic reactions

Severe allergic reactions rarely were observed. A fatal allergic reaction occurred in a patient given intravenous desmopressin. It was not known whether patients given repeated doses of the medication could develop antibodies against desmopressin.

Nasal changes

Since Stimate was delivered as a nasal spray, changes were possible in the mucus membranes lining the nasal passages, such as scarring or swelling, which could lead to unreliable absorption of the medication.

If such effects occurred, Stimate should have been stopped until nasal problems were resolved. In such cases, an injectable formulation of desmopressin should have been considered.

Use in pregnancy and breastfeeding

There were no well-controlled studies assessing Stimate’s use in women during pregnancy or breastfeeding. However, animal studies found no evidence indicating that desmopressin could be harmful to a developing fetus.

Patients who planned to become pregnant or breastfeed when using the medication were advised to discuss the matter with their healthcare team.

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