Interacting drugs- summary

Desmopressin + Pressor agents

 Although desmopressin pressor activity is very low, use large intranasal doses or parentral doses as large as 0.3mcg/kg cautiously with other presser agents

+ Desmopressin 

Carbamzepine

carbamazepine which potentiates ADH may potentiate the antidiuretic effects of vasopressin, lypressin or desmopressin

Chlorpropamide

chlorpropamide which potentiates ADH, may potentiate the effects of desmopressin

Although the pressor activity of desmopressin is low compared to the antidiuretic activity, use of large doses with other vasopressors should be done with careful monitoring.

Substances which are known to release antidiuretic hormone (tricyclic antidepressants, chlorpromazine and carbamazepine) may cause additive effect and increase the risk of water retension.

Cranial diabetes insipidus, Primary nocturnal enuresis.

Transcient headache, nausea, nasal congestion, rhinitis, flushing, mild abd. cramps, nose bleed, sore throat, cough, & stuffiness have been reported.

Allergic reaction to preservative can occur. Inj site pain, erythema & swelling, BP changes, hypnotic hyponatremia, water intoxication, thrombolic events in predisposed individuals have been reported.

Hypersensitivity to constituents. Psychogenic or habitual polydipsia. Decompensated cardiac failure with ongoing diuretic treatment.

Special Precautions:

Fluid intake should be adjusted paticularly in very young and elderly patients, in order to decrease the potential occurance of water intoxication and hyponatremia. In extreme cases seizure and coma may occur; thus excercise due caution and ingest only enough fluid to satisfy thirst and not more.

Intranasal desmopressin should be avoided in patients with nasal mucosal disease such as scarring, edema and atrophy because of erratic and unreliable drug absorption.

Excercise caution in patients with cardiovascular diseases, edema states, renal impairment, or fluid & electrolyte imbalance

Monitoring- Diabetes mellitus- monitor urine volume.osmolaity and plasma osmolality Hemophilia- determine factor VIII coagulant activity before injecting desmopressin for hemostasis, if the activity is < 5% of normal do not rely on desmopressin.

 Cardiovascular effects- high intranasal dosage has infrequently produced a slight elevation of blood pressure which disappeared with dosage reduction. Use with caution incoronary artery insufficiency or hypotensive cardiovascular disease.

Nasal mucosa changes- eg scarring, edema, discharge blockage, congestion, severe atrophic rhinitis, cranial surgery and nasal packing compromise intrananasal delivery .Consider administering IV.

Thrombotic events- rare reports of thrombobotic events follwing desmopressin injection in patientsbus formation. However use the drug with caution in such patients.

Decreased response- there are repors of an occassional change in response to intranasal desmopressin with time > 6 months,. some patients may show decreased response,other a shortened duration of effects.

Fluid/electrolyte imbalance- usewith caution in patients with conditions associated with fluid and electrolyte imbalnce such as cystic fibrosis, because these patients are prone to hyponatremia.

Warnings-

Hemophilia- not indicated for treatment of hemophilia A with factor VIIiI levels < 5%, for the treatment of hemophilia B or in patients who have factor VIII natibodies . Some patients with Factor VIII between 2% to 5% may be treatable

Test dose- before the initial therapeutic administratioo of thenasal spray,the physician should eartablish that the patient shows an appropiate change in the coagulation profile following a test dose of intranasal administration

Water intoxification- caution very young and elderly patients to ingest only enough fluid to satify thirst to decrease the potential occurance of water intoxification and hyponatremia.

Hypersentivity reactions- anaphylaxis has been reported with IV administration,but not with tablets.

Pregnancy- safety andefficacy foruse during pregnancy has not been established. Use only when clearly needed.

Lactation- safety for use in nursing mothers has not been established.

Children- Safey and efficacy for use in children < 12 years(parentral) or 3 months of age(intranasal) with diabetes insipidus.

   For Diabetes Insipidus and Noctural emeresis

 Overdosage- Symptoms Treatment Headache, abdominal cramps, nausea and facia

l 1. Reduce dosage

2. Decrease the frequency of use or withdraw the drug according to the severity of the drug.

3. There is no specific antidote.

Missed dose-

For nasal solution fromthis medicine- If you miss a dose of this medicine and your dosing schedule is-

One dose a day

1.Use the missed dose as soon as possible

2. Then go back to your regular dosing schedule

3. However, if you do not remember the missed dose until the next day,skip the missed dose and go back to your regular dosing schedule.

4. Do not double doses.

1. If bleeding is not controlled , contact the physician

2. Notify physician if headache, shortness of breath, heartburn, nausea, abdominal cramps, or vulval pain occurs

3. Allergies- Tell your doctor if you have ever had any unusual or allergic reactions to desmopressin or other related medicines. Also tell your doctor if youn are allergic to any other substances such as foods, preservatives or dyes

4. Pregnancy- desmopressin has ben used before and during pregnancy to treat diabetes insipidus and has not been shown to cause birth defects.

5. Breast feeding - not reported to cause ecasaue problems in nursing babies.

6. Children- infants may be more sensitive to the effects of this medicine

7. Elderly- some side effects -confusion, drowsiness, continuing headache, problems with urination likely to occur with elderly patients.

7. Other medicines- tell your doctor if you are taking any of the following- OTC or non prescription medicines

8. Other medical problems- tell your doctor if you have any other medical problems- Cystic fibrosis - excees water retention and serious side effects more likely to occur Heart or blood vessel disease - large doses of desmopression can cause increase in blood pressure Stuffy nose caused by cold or allergy- may prevent nasal desmopressin from being absorbed through the lining of the nose into trhe blood stream

9. Missed dose- If you miss a dose of this medicine take it as soon as possible. However if it is almost time for your next dose go back to your regular dosing schedule. Do not double doses.

Pharmacology:

Antidiuresis is the principal action of desmopressin. It is supposed to bind the V2 receptor linked to an adenyl cyclase system in the collecting tubule to increase water perneability to the liminal membrane. Desmopressin in therapeutic doses has no metabolic actions and does not stimulate ACTH release. It has no significant cardiovascular effects and fails to cause contractions of the gall bladder, ureter or intestines.

Pharmacokinetics: Following intranasal use, the drug is well absobed from the nasal mucosa. Peak plasma concentrations occur after about 4 hrs. There are two components in the plasma half-life. The mean half-life of the first component is 7.8min and that of the second component is 75.5min. The onset of the antidiuretic action and its clinical effect lasts for 10 to 12hrs. Intravenous administration causes antidiuresis in about 30 min with its action continuing for upto 24hrs.

Pregnancy:

Although there are no evidence of harm caused to fetus, it would be prudent to use this drug with due consideration to risk: benefit ratio.

Lactation:

The drug is excreted in small amounts in human milk.

Caution should be excercised when using this drug on nursing mothers.

Children- Safey and efficacy for use in children < 12 years(parentral) or 3 months of age(intranasal) with diabetes insipidus.