1. NAME OF THE MEDICINAL PRODUCT

Vasopressin Injection USP 20IU/ml Taj Pharma

  1. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml of Injection contains:
Vasopressin……………………………20IU
Excipients……………………………………..q.s.

For the full list of excipients, see section 6.1.

  1. PHARMACEUTICAL FORM

Solution for injection

Clear, sterile solution.

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

For use in diabetes insipidus, when this is not of nephrogenic origin and control of bleeding from oesophageal varices.

4.2 Posology and method of administration

Posology

Adults

Diabetes Insipidus:

A dose of 0.25ml to 1ml (5 to 20 units) by subcutaneous or intramuscular injection every four hours.

Oesophageal Varices:

For the initial control of variceal bleeding Vasopressin should be given intravenously. Vasopressin, 20 units diluted in 100ml dextrose 5% w/v may be infused over a 15 minute period.

Elderly (over 65 years)

As for adults, no clinical or pharmacokinetic data specific to this age group are available. However, the drug has been successfully used at normal dosage in the elderly.

Paediatric population

Not recommended in children below 18 years.

Method of administration

Subcutaneous, intravenous or intramuscular injection.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Anaphylaxis to the active substance or to the excipients listed in section 6.1.

Patient with coronary artery disease or those intended to receive halogenated anaesthetic agents.

Chronic nephritis with nitrogen retention contraindicates the use of Vasopressin 20 International Units /ml injection until reasonable nitrogen blood levels have been attained.

Vascular disease (especially disease of coronary arteries), chronic nephritis (until reasonable blood nitrogen concentrations attained).

4.4 Special Warnings and precautions for use

This drug should not be used in patients with systemic hypertension or vascular disease, especially disease of the coronary arteries, except with extreme caution. In such patients, even small doses may precipitate pain, and with larger doses, the possibility of myocardial infarction should be considered. If this drug must be used in patients with peripheral vascular disease then the skin should be observed carefully for signs of ischaemia.

Vasopressin may produce water intoxication. The early signs of drowsiness, listlessness and headaches should be recognised to prevent terminal coma and convulsions.

Adjustment of dosage in cases immediately post-hypophysectomy should be controlled on the basis of measurements of urine osmolality.

Vasopressin should be used cautiously in the presence of epilepsy, migraine, asthma, heart failure or any state in which a rapid addition to extracellular water may produce hazard for an already overburdened system.

Regular monitoring of blood urea nitrogen (BUN) levels is required in patients with chronic nephritis to ensure an adequate level is maintained (see section 4.3).

4.5 Interaction with other medicinal products and other forms of interaction

The following drugs may potentiate the antidiuretic effect of vasopressin when used concurrently: carbamazepine, chlorpropamide, clofibrate, fludrocortisone, urea or tricyclic antidepressants.

The following drug may decrease the antidiuretic effect of vasopressin when given concurrently: demeclocycline, noradrenaline, lithium, heparin, alcohol.

Ganglion blocking agents may produce a marked increase in sensitivity to the pressor effect of vasopressin.

4.6 Fertility, Pregnancy and lactation

Pregnancy

No animal reproduction studies on Vasopressin are available.

Oxytocic effect in third trimester has been reported. However, Vasopressin has been used successfully during pregnancy for the treatment of diabetes insipidus with no adverse effects on the foetus being reported. Nevertheless, as with all medicines, use during pregnancy should be avoided if possible and the potential benefit to the patient weighed against any possible risk to the foetus.

Breast-feeding

Vasopressin has been administered to breast-feeding women without apparent adverse effect on the infant.

4.7 Effects on ability to drive and use machines

Vasopressin can have an influence on driving as it may cause vertigo (see section 4.8).

4.8 Undesirable Effects

The following undesirable effects have been observed and reported during treatment with Vasopressin with the following frequency:

Not known – cannot be estimated from the available data.

Immune system disorders

  • Hypersensitivity
  • Anaphylaxis

Metabolism and nutrition disorders

  • Hyper hydration/ water intoxication

Nervous system disorders

  • Headache
  • Vertigo
  • Tremor

Cardiac disorder

  • Chest pain due to angina
  • Cardiac arrest

Vascular disorders

  • Peripheral ischaemia
  • Pallor
  • Hypertension

Respiratory, thoracic and mediastina disorders

  • Bronchospasm

Gastrointestinal disorders

  • Flatulence
  • Nausea
  • vomiting
  • diarrhea
  • Abdominal pain

Skin and subcutaneous tissue disorders

  • Gangrene
  • Hyperhidrosis
  • urticaria

Renal and urinary disorders

  • Fluid retention

General disorders and administration site conditions

  • Non-cardiac chest pain

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

If water intoxication occurs, no fluids should be given. In severe cases, small amounts of hypertonic saline may be administered. Urea and mannitol infusions may be helpful in cases of cerebral oedema. If a patient should experience anginal pain after administration of Vasopressin, amyl nitrite by inhalation or glyceryl trinitrate sublingually, may be given.

  1. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Vasopressin and analogues

Mechanism of action

The antidiuretic action of Vasopressin is ascribed to increase in reabsorption of water by the renal tubules. Vasopressin can cause contraction of smooth muscle of the gastrointestinal tract, gall bladder, urinary bladder and all parts of the vascular bed, especially the capillaries, small arterioles and venules with less effect on the smooth musculature of the large veins. The direct effect on the contractile elements is neither antagonised by adrenergic blocking agents nor prevented by vascular denervation.

5.2 Pharmacokinetic properties

Absorption

Following subcutaneous or intramuscular administration of Vasopressin injection, the duration of antidiuretic activity is variable, but effects are usually maintained for 2-8 hours.

Biotransformation

The majority of the dose of Vasopressin is metabolised and rapidly destroyed in the liver and kidneys. Vasopressin has a plasma half-life of about 10 to 20 minutes.

Elimination

Approximately 5% of a subcutaneous dose of Vasopressin is excreted unchanged in the urine four hours after dosing.

5.3 Preclinical safety data

Preclinical safety data does not add anything of further significance to the prescriber.

  1. PHARMACEUTICAL PARTICULARS

    6.1 List of excipients

Glacial acetic acid, water for injection

 6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

24 months.

6.4 Special precautions for storage
Store in a refrigerator (2°C and 8°C). Do not freeze.

Keep the ampoules in the outer carton in order to protect from light.

6.5 Nature and contents of container

Clear OPC/blue glass ampoules with white and blue rings above the OPC.

The white and blue rings are for product identification and should not be taken as break rings. The ampoules should be open cut at the OPC

Available in packs of 10 x1ml ampoules.

6.6 Special precautions for disposal and other handling

For single use only.

If only part used, discard the remaining solution.

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

  1. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

VASOPRESSIN INJECTION USP
20IU/ML
TAJ PHARMA

PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

Vasopressin

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet (see section 4).

WHAT IS IN THIS LEAFLET

  1. What Vasopressin injection is and what it is used for
  2. What you need to know before you take Vasopressin injection
  3. How Vasopressin injection will be given to you
  4. Possible side effects
  5. How to store Vasopressin injection
  6. Contents of the pack and other information1. WHAT VASOPRESSIN INJECTION IS AND WHAT IT IS USED FOR

Vasopressin injection contains argipressin which is similar to a naturally occurring hormone in your body. It is an ‘antidiuretic’ which helps to prevent excess loss of water in your urine and also narrows some blood vessels in the body.

Vasopressin is used to treat:

  • diabetes insipidus. This is a rare form of diabetes causing production of large quantities of urine. Vasopressin increases the amount of water absorbed back into your kidneys.
  • bleeding from enlarged veins in the oesophagus (food pipe).
  1. WHAT YOU NEED TO KNOW BEFORE YOU TAKE VASOPRESSIN INJECTION

You should not be given Vasopressin injection:
· if you are allergic to argipressin or any other ingredients of this medicine(listed in section 6)
· if you suffer from a severe allergic reaction(anaphylactic shock) to argipressin or any of the other ingredients of this medicine (listed in section 6)
· if you suffer from any diseases or condition associated with your blood vessels, especially the blood vessels of your heart
· if you are intended to receive halogenated anaesthetic agents during surgical procedures
· if you suffer from a certain type of kidney disease called chronic nephritis with nitrogen retention (your doctor will advise you).

Speak to your doctor if one of these applies to you before you are given this medicine.

Warnings and Precautions
Talk to your doctor or nurse before you are given vasopressin injection:
· if you suffer from asthma or other allergic conditions
· if you suffer from migraine
· if you suffer from epilepsy (fits)
· if you suffer from high blood pressure, heart or kidney disease (you may need to have regular blood tests)
· if you suffer from obstruction of the blood vessels of the heart(e.g. coronary artery)
· if you have undergone removal of pituitary gland (dosage will depend on urine concentration).

Other medicines and Vasopressin injection
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
This is extremely important because some medicines can strengthen or weaken the effects of others.
In particular, tell your doctor if you are taking any of the following:
· medicines which control seizures (carbamezepine)
· other medicines to treat diabetes (chloropropamide)
· medicines used in corticosteroid replacement therapy (fludrocortisones)
· medicines to treat depression (e.g. amitriptyline, imipramine etc.)
· antibiotics (demeclocycline)
· medicines which prevent blood clotting (heparin)
· medicines used to treat mania (lithium)
· medicines used for severe low blood pressure or cardiac arrest (noradrenaline)
· medicines containing urea (in some skin and ear preparations)
· lipid lowering agent (clofibrate)
medicines which may be used in emergency for treating hypertension (hexamethonium)

Vasopressin injection with food, drink and alcohol
· Do not drink alcohol before you are given vasopressin injection.

Pregnency and breast feeding

“If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor, pharmacist or nurse before you are given this medicine. As with all drugs, Vasopressin should only be given in pregnancy and when breast-feeding if absolutely necessary.Your doctor will guide you.

Driving and using machines

Vasopressin can affect your ability to drive and use machinery safely, as you may feel dizzy after receving your injection. Speak to your doctor for further advice.

  1. 3. HOW VASOPRESSIN INJECTION WILL BE GIVEN TO YOU

It is most likely that you will be in hospital when you are given Vasopressin.

For the treatment of diabetes insipidus:

Injected under the skin or into a muscle every four hours. Your doctor will decide on the most suitable dose and way to give it to you depending on your symptoms.

For the treatment of bleeding in the

oesophagus: The dose is diluted in a sugar solution and slowly dripped through a needle into a vein. Your doctor will decide on the most suitable dose and way to give it to you depending on your symptoms.

Use in children and adolescents
Vasopressin is not recommended in children below 18 years.

Elderly
No dose change, give as per adults.

If you think you have been given more Vasopressin injection than you should have
As the injection will be administered by a doctor, it is unlikely that you will be given more than is necessary. However, if you think that you have been given too much, tell your doctor immediately. If you experience chest pain after receiving this medicine, inform your doctor immediately.
If you have any further questions on the use of this product, ask your doctor or nurse.

  1. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can have side effects, although not everybody gets them.
All medicines can cause allergic reactions although serious allergic reactions are rare. Any sudden wheeziness, difficulty in breathing, swellingof the eyelids, face or lips, rash or itching (especially affecting your whole body) should be reported to a doctor immediately as this can also result in a heart attack if not treated straight away.
Vasopressin can cause ‘water intoxication’. Signs of this are drowsiness, being uninterested in anything (listless) and headaches. If you notice any of these signs, tell the nurse or your doctor straightaway. If it is not corrected, water intoxication can lead to fits or even coma.

Other side effects include:
Not known:frequency cannot be estimated from the available data
·  Gangrene- with symptoms of redness, swelling, loss of sensation/ sever pain which can cause dead, black areas of skin- in areas such as fingers or toes
· Decreased oxygen in a tissue-with symptomsof pain, pale skin, tingling skin (usually because of decreased blood flow)
· Nettle rash or hives-Itchy red bumps on the skin
· Repeated desire to pass stools(diarrohea)
· Abnormal collection of fluid in the body or ‘bloating’
· Paleness of the lips
· Wheezing
· Dizziness
· Feeling sick or being sick
· passing wind
· pounding in the head or a headache
· stomach ache
· Excessive sweating
· Shakiness.
In patients with disease of the heart or circulation, Vasopressin  may give rise to angina (chest pain)

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

  1. HOW TO STORE VASOPRESSIN INJECTION

Keep this medicine out of the sight and reach of children

The storage of Vasopressin injection will not be your responsibility.

Store in a refrigerator (2ºC – 8 ºC). Keep the ampoules in the outer carton in order to protect from light. Don not freeze.
For single use only.

If only part used, discard the remaining solution. Do not use this medicine after the expiry date which is stated on the label and carton. The expiry date refers to the last day of the month.

Don not throw away any medicines via wastewater or household waste. Ask you pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

  1. CONTENTS OF THE PACK AND FURTHER INFORMATION

What Vasopressin injection contain
Each ml of Injection contains:
Vasopressin……………………………20IU

argipressin(vasopressin) which is equivalent to 0.4mg argipressin, based on 50 international per mg).

The other ingredients are glacial acetic acid and sufficient water for injection is used to make the final volume of 1ml.

What Vasopressin injection looks like and contents of the pack

Vasopressin is a clear, sterile solution. It is a solution for injection which comes in a small glass bottle(ampoule), containing 20 IU of the active ingredient, argipressin. Each ampoule has a blue OPC (one-point-cut) where the ampoule is opened and two (white and blue) product identification rings.

Each ml contains
Vasopressin USP        20 Units
Water for Injection             q.s.
Excipients                            q.s.
It is available in packs of ten 1 ml ampoules.

  1. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com