Minirin

Dosage Forms And Strengths

Desmopressin Acetate Nasal Spray pump delivers 10 mcg (0.1 mL) of desmopressin acetate per spray.

Desmopressin Acetate Nasal Spray is available as a 5 mL bottle with spray pump delivering 50 sprays.

Desmopressin Acetate Nasal Spray is available as a 5 mL bottle containing an aqueous solution with the spray pump delivering 50 sprays of 10 mcg (0.1 mL) (NDC 66993-025-01).

Storage And Handling

Store at Controlled Room Temperature 20 to 25°C (68 to 77°F). STORE BOTTLE IN UPRIGHT POSITION.

Manufactured for: Prasco Laboratories Mason, OH 45040 USA. Revised: May 2018

diabetes insipidus of central origin,

nocturia in adults, associated with nocturnal polyuria (increased urination in adults, exceeding the capacity of the bladder and causing the need to get up at night more than once in order to empty the bladder) - as a symptomatic therapy..

Do not drink the tablet with liquid! The optimal dose of Minirin it is selected individually.

The dosage ratios between the two oral forms of the drug are as follows:

Table 1

Recommended initial dose of Minirin

The recommended starting dose is 120 mcg per night. In the absence of an effect, the dose can be increased to 240 mcg. During treatment, it is necessary to limit the intake of fluids in the evening. The recommended course of continuous treatment is 3 months. The decision to continue treatment is made on the basis of clinical data that will be observed after discontinuation of the drug for 1 week.

The recommended starting dose is 60 mcg per night sublingually (under the tongue). In the absence of an effect for 1 week, the dose is increased to 120 mcg and subsequently to 240 mcg with an increase in the dose with a frequency of no more than 1 time per week.

If there is no adequate clinical effect after 4 weeks of treatment and dose adjustment, it is not recommended to continue taking the drug.

hypersensitivity to desmopressin or other components of the drug,

habitual or psychogenic polydipsia (with a volume of urination of 40 ml / kg / day),

hyponatremia,

renal insufficiency (creatinine Cl >50 ml / min), bladder fibrosis, water-electrolyte balance disorders, potential risk of increased intracranial pressure, risk of thrombosis, pregnancy, elderly age (65 years and older - when used for the treatment of diabetes insipidus).

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Hyponatremia

Excessive fluid intake when urine output is limited by the antidiuretic effect of desmopressin may lead to water intoxication with hyponatremia. Cases of hyponatremia have been reported from postmarketing experience in patients treated with desmopressin acetate. Unless properly diagnosed and treated, hyponatremia can be fatal.

All patients receiving Desmopressin Acetate Nasal Spray should be observed for the following signs or symptoms associated with hyponatremia: headache, nausea/vomiting, decreased serum sodium, weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, loss appetite, irritability, muscle weakness, muscle spasms or cramps and abnormal mental status such as hallucinations, decreased consciousness, and confusion. Severe symptoms due to an extreme decrease in serum sodium and plasma osmolality may include one or a combination of the following: seizure, coma, and/or respiratory arrest.

In order to decrease the risk of water intoxication with hyponatremia, fluid restriction is recommended. Careful fluid intake restriction is particularly important in pediatric and geriatric patients because these patients are at greater risk of developing hyponatremia. More frequent monitoring of serum sodium levels is recommended in the following patients: those with conditions associated with fluid and electrolyte imbalance, such as cystic fibrosis, heart failure, renal disorders, habitual or psychogenic polydipsia or those taking concomitant drugs that may cause hyponatremia.

Desmopressin Acetate Nasal Spray is not an indicated formulation for the treatment of primary nocturnal enuresis due to a higher risk of hyponatremia and hyponatremic convulsions with the use of the nasal spray formulation compared to desmopressin tablets seen in postmarketing reports.

Altered Absorption In Patients With Nasal Mucosa Abnormalities

Chronic administration of Desmopressin Acetate Nasal Spray may result in changes to nasal mucosa. Nasal mucosa abnormalities (such as scarring and edema) due to chronic administration, or due to other causes (nasal blockage, nasal mucosal atrophy, severe atrophic rhinitis, recent nasal surgery such as transsphenoidal hypophysectomy) may cause erratic, unreliable absorption. Avoid use of Desmopressin Acetate Nasal Spray in such patients.

Geriatric Use

Clinical studies of Desmopressin Acetate Nasal Spray did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at a low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy

Because elderly patients are more likely to have renal impairment, care should be taken in dose selection, and monitoring renal function is recommended.

Use of Desmopressin Acetate Nasal Spray in geriatric patients requires careful fluid intake restriction to prevent possible water intoxication with hyponatremia.

Renal Impairment

Desmopressin acetate is substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with renal impairment than patients with normal renal function. Desmopressin Acetate Nasal Spray is contraindicated in patients with estimated CLcr by Cockcroft-Gault equation less than 50 mL/min.

SIDE EFFECTS

The following serious reactions are described below and elsewhere in the labeling:

• Hyponatremia.
• Altered Absorption in Patients with Changes in Nasal Mucosa.

The following adverse reactions have been identified during post-approval use of desmopressin acetate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

Increase in blood pressure, headache, nasal congestion, rhinitis, nosebleed, sore throat, cough, upper respiratory infections, nausea, flushing, and abdominal cramps.

Water intoxication with hyponatremia

Hyponatremic convulsions associated with concomitant use of the following medications: oxybutinin and imipramine.

Severe allergic reactions and anaphylaxis

DRUG INTERACTIONS

Other Drugs That May Increase Risk Of Hyponatremia

The concomitant administration of Desmopressin Acetate Nasal Spray with other drugs that may increase the risk of water intoxication with hyponatremia, (e.g., tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, NSAIDs, lamotrigine, oxybutynin and carbamazepine) requires more frequent serum sodium monitoring.

Other Vasoconstrictors

Desmopressin acetate can elevate blood pressure. Use of large doses of Desmopressin Acetate Nasal Spray with other vasocontrictors may require a reduction of the Desmopressin Acetate dosage.

The use of the drug without concomitant restriction of fluid intake may lead to fluid retention and / or hyponatremia, which may be asymptomatic or accompanied by the following symptoms: headache, nausea and /or vomiting, weight gain, in severe cases — convulsions, which are combined with impaired consciousness up to prolonged loss of consciousness. These symptoms are especially common in children under 1 year of age or the elderly, depending on their general condition.

Table 2

Nocturia

In clinical studies, 35% of patients during the titration period of the dose and 24% of patients on the background of long-term therapy with the drug had adverse reactions. The most common adverse reactions identified in clinical trials involving 632 patients are listed below (Table 3).

Symptoms:

depending on the severity of the overdose, you should reduce the dose of the drug, increase the time between taking the drug during the day, or stop taking the drug. If you suspect brain edema, you need to be immediately hospitalized in the intensive care unit. If seizures occur, immediate intensive care is required. The specific antidote of desmopressin is unknown. Diuretics, such as furosemide, can be used to induce diuresis, while simultaneously monitoring the content of electrolytes in the blood plasma.

The bioavailability of desmopressin in sublingual form at doses of 200, 400 and 800 mcg is about 0.25%.

desmopressin in blood plasma is reached within 0.5-2 hours after taking the drug and is directly proportional to the amount of the dose taken: after taking 200, 400 and 800 mcg C It was 14, 30 and 65 pg / ml, respectively.

Desmopressin does not penetrate the BBB. Desmopressin is excreted by the kidneys, T_1/2 is 2.8 hours.

There is a possibility that other drugs that reduce the tone and motility of the smooth muscles of the intestine may have a similar effect.

When used concomitantly with oxytocin, an increase in the antidiuretic effect and a decrease in uterine perfusion should be taken into account.

Clofibrate may enhance the antidiuretic effect of desmopressin.

With simultaneous use of the drug Minirin with the above drugs, to prevent the development of hyponatremia, it is necessary to regularly determine the concentration of sodium in the blood plasma.

Glibenclamide may reduce the antidiuretic effect of desmopressin.

In a dry place, protected from light, at a temperature not exceeding 25 °C.

Keep out of reach of children.

Do not use after the expiration date indicated on the package.

Sublingual tablets, 60 mcg, 120 mcg and 240 mcg. 10 tablespoons each in an aluminum foil blister.

Limited data on the use of desmopressin in pregnant women with diabetes insipidus (n=53) indicate that desmopressin does not have a negative effect on the course of pregnancy or the health of the pregnant woman, fetus or newborn. Animal studies have not revealed any direct or indirect harmful effects on the course of pregnancy, embryonic or intrauterine development, childbirth or postpartum development.

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By prescription.

It is mandatory to limit to a minimum the intake of fluid for 1 hour before and for 8 hours after taking the drug in patients with primary nocturnal enuresis and nocturia. Failure to follow this rule may lead to the development of side effects. Patients should be carefully instructed about the need to comply with the fluid intake regime. The patient should be warned to avoid fluid overload (including swimming) and stop taking desmopressin against the background of vomiting and diarrhea, until the water balance is restored. Before starting treatment, make sure that the patient agrees to limit fluid intake.

they are used with extreme caution. When using the drug in these cases, it is necessary to determine the concentration of sodium in the blood plasma before the start of taking the drug, 3 days after the start of taking it, and with each increase in the dose. It is necessary to monitor the patient's condition during the entire period of taking the drug Minirin.

The use of the drug in elderly patients (65 years and older) for the symptomatic treatment of nocturia is contraindicated.

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With caution, the drug is used in patients at risk of developing thrombosis.

Influence on the ability to drive vehicles and mechanisms. The drug Minirin^® it does not directly affect the ability to drive vehicles and mechanisms. However, taking into account the possible development of adverse reactions when using the drug, it is necessary to be careful when driving vehicles and engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

• E23. 2 Diabetes insipidus

Sublingual tablets, 120 mcg: