For the use of a Registered Medical Practitioner or a Hospital or a Institution only.
Petresin is a sterile solution of synthetic vasopressin-8-L-arginine in a suitable diluent. It is substantially free from the oxytocic principle and is standardized to contain 20 pressor units/ml. The molecular formula is C46H65N15O12S2 and molecular weight is 1084.25.
STRUCTURAL FORMULA :
Its structural formula is :
Petresin is a clear colourless solution filled in 1 ml amber ampoule.
Each ml contains :
Water for Injections.I.P. q.s.
Vasopressin is a direct systemic vasoconstrictor (mediated by V1 receptors). Depending on the concentration, the hormone acts on V1 and V2 receptors. The V2 renal receptors are responsible for the antidiuretic effects of vasopressin. Vasopressin also causes vasoconstriction (pressor effect) of the splanchnic and portal vessels (and to a lesser extent of peripheral, cerebral, pulmonary and coronary vessels). During hypotension caused by hypovolemia, plasma vasopressin levels increase and this is important for preserving perfusion pressure. It also vasoconstricts the mesentric circulation at physiological concentrations (<10 pg.ml-1) mediated by the V1 receptor. This effect may be important in restoring vascular tone in patients with septic shock. Vasopressin stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland via V3 receptor. The V3 receptors are responsible for the actions of vasopressin on the central nervous system, where they act as neurotransmitter or a modulator controlling memory, blood pressure, body temperature and release of pituitary hormones. Pharmacologic doses of vasopressin induce a prompt increase in plasma cortisol levels in men, mediated by nitric oxide and cyclic guanosine monophosphate (GMP) via the V3 receptor. The antidiuretic action of vasopressin is ascribed to increasing reabsorption of water by the renal tubules. Vasopressin can cause contraction of smooth muscle of the gastrointestinal tract and of all the parts of the vascular bed, especially the capillaries, small arterioles and venules with less effect on the smooth musculature of the large veins. This effect is via V1 receptors. The direct effect on the contractile elements is neither antagonized by adrenergic blocking agents nor prevented by vascular denervation.
Following subcutaneous or intramuscular administration of vasopressin injection, the duration of antidiuretic activity is variable but effects are usually maintained for 2 to 8 hours and the effective plasma levels achieved is 4.5 to 6 microunits. The majority of the dose of vasopressin is metabolized and rapidly destroyed in the liver and kidneys. Vasopressin is not protein bound and has volume of distribution of 140 ml/kg-1. The plasma half life is 10 to 20 minutes. It is cleared by renal elimination (65 %) and metabolism (35 %) by tissue peptidases.
Cardiopulmonary resuscitation :
Petresin in conjunction with epinephrine is recommended in cardiac arrest.
Vasodilatory shock including septic shock and vasoplegia syndrome
Petresin is indicated in prevention and treatment of postoperative abdominal distension, in emergency treatment of oesophageal varices, in abdominal roentgenography to dispel interfering gas shadows and in neurogenic (central) diabetes insipidus ( ineffective when diabetes insipidus is of renal origin i.e., nephrogenic diabetes insipidus).
Petresin may be administered intravenously, intramuscularly, or subcutaneously.
Instruction for use of Ampoule :
The ampoule used in this product is equipped with O.P.C (One Point Cut) opening system. No ampoule file is needed to open the ampoule. The neck of the ampoule is prescored at the point of constriction. A coloured dot on the ampoule head helps to orient the ampoule. Take the ampoule and face the coloured dot. Let the solution at the head of the ampoule to flow down by shaking or a gentle stroke. The ampoule opens easily by placing the thumb on the coloured dot and gently pressing downwards as shown.
Ten units of Petresin (0.5 ml) will usually elicit full physiologic response in adult patients; 5 units will be adequate in many cases. Petresin should be given intramuscularly at three or four hour intervals as needed. The dosage should be proportionately reduced for children. (For an additional discussion of dosage, consult the sections below.) When determining the dose of Petresin for a given case, the following should be kept in mind : It is particularly desirable to give a dose not much larger than is just sufficient to elicit the desired physiologic response. Excessive doses may cause undesirable side effects -blanching of the skin, abdominal cramps, nausea - which, though not serious, may be alarming to the patient. Spontaneous recovery from such side effects occurs in a few minutes. It has been found that one or two glasses of water given at the time Petresin is administered reduce such symptoms. Vasopressin 20 units dissolved in 100-200 ml of dextrose 5 % solution infused for more than 10 minutes.
Cardiac Arrest : In adult patients with VF, pulseless electrical activity and asystole, administration of 1 mg of epinephrine followed alternately by 40 IU of vasopressin Intravenous and 1 mg of epinephrine every 3 to 5 minutes is recommended regardless of the initial electrocardiographic rhythm.
Paediatric Cardiac Arrest : Dilute 1 unit/kg in 50 ml normal saline. 1 ml/ hr = 0.33 unit/kg/min.
Neonate : No information.
Requirements : Intravenous infusion device for continuous infusion.
Monitoring : ECG monitoring as per cardiac arrest team leader.
Vasodilatory Shock : In vasodilatory shock unresponsive to standard therapy, continuous intravenous infusion of 2 to 6 IU/hr of Petresin is recommended.
Anaphylactic Shock : In anaphylactic shock unresponsive to standard therapy, bolus intravenous injection of 2 to 10 IU and continuous intravenous infusion of 2 to 6 IU/hr of Petresin is recommended.
Haemorrhagic Shock : In haemorrhagic shock unresponsive to standard therapy, bolus intravenous injection of 2 to 10 IU and continuous intravenous infusion titrating to blood pressure with 10 IU/hr of Petresin is recommended.
Septic Shock : In septic shock, fixed low intravenous dose administration, generally 0.01 to 0.04 Units/min. of Petresin and in no case exceeding 0.1 Units/min. is recommended.
Abdominal Distention :
In the average postoperative adult patient, give 5 units (0.25 ml) initially, increase to 10 units (0.5 ml) at subsequent injections if necessary. It is recommended that vasopressin be given intramuscularly and that injections be repeated at three or four-hour intervals as required. Dosage to be reduced proportionately for children. Petresin used in this manner will frequently prevent or relieve postoperative distention. These recommendations apply also to distention complicating pneumonia or other acute toxemias.
Abdominal Roentgenography :
For the average case two injections of 10 units each (0.5 ml) are suggested. These should be given two hours and one-half hour, respectively, before films are exposed. Many roentgenologists advise giving an enema prior to the first dose of Petresin .
Diabetes Insipidus :
Petresin may be given by injection or administered intranasally on cotton pledgets, by nasal spray, or by dropper. The dose by injection is 2 to 10 units (0.1 to 0.5 ml) repeated two or three times daily as needed. When Petresin is administered intranasally by spray or on pledgets, the dosage and interval between treatments must be determined for each patient. The dosage recommended for children is 2.5 to 10 IU by intramuscular/subcutaneous injection repeated 3 to 4 times a day.
Variceal Bleeding :
In the management of variceal bleeding Petresin may be given Intravenous or occasionally direct Intra-arterial infusion. For Intravenous use an initial dose of 20 units in 100 ml of glucose (5 %) injection, infused over 15 minutes has been suggested for initial control of bleeding.
Anaphylaxis or hypersensitivity to the drug or its components. Poor distal limb perfusion hyperbilirubinemia and acute cardiac or bowel ischemia would be contraindications for use of Petresin .
This drug should not be used in patients with vascular disease, especially disease of the coronary arteries, except with extreme caution. In such patients, even small doses may precipitate anginal pain and with larger doses, the possibility of myocardial infarction should be considered. Vasopressin may produce water intoxication. The early signs of drowsiness, listlessness and headaches should be recognized to prevent terminal coma and convulsions. The above mentioned warnings are for general situations. In situations like CPR and shock, where life is at stake, the treating clinician shall use his judgement and discretion in light of recently published literature.
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. Chronic nephritis with nitrogen retention contraindicates the use of vasopressin until reasonable nitrogen blood levels have been attained. Avoid arterial injection.
Teratogenic Effects - Pregnancy category C Animal reproduction studies have not been conducted with vasopressin. It is also not known whether vasopressin can cause foetal harm when administered to a pregnant woman or can affect reproduction capacity. Vasopressin should be given to a pregnant woman only if clearly needed.
Labor and Delivery :
Doses of vasopressin sufficient for an antidiuretic effect are not likely to produce tonic uterine contractions that could be deleterious to the foetus or threaten the continuation of the pregnancy.
Nursing Mothers :
Caution should be exercised when Petresin is administered to a nursing woman.
Information for Patients :
Side effects such as blanching of skin, abdominal cramps and nausea may be reduced by taking 1 or 2 glasses of water at the time of vasopressin administration. These side effects are usually not serious and probably will disappear within a few minutes.
Laboratory Tests :
Electrocardiograms (ECG) and fluid and electrolyte status determinations are recommended at periodic intervals during therapy.
SIDE EFFECTS :
Local or systemic allergic reactions may occur in hypersensitive individuals. The following side effects have been reported following the administration of vasopressin :
Gastrointestinal : Abdominal cramps, nausea, vomiting, passage of gas.
Nervous System : Tremor, vertigo, “ pounding “ in head.
Respiratory : Bronchial constriction.
Skin and Appendages : Sweating, urticaria, cutaneous gangrene. Severe skin necrosis after extravasation of low dose of Petresin administered for catecolamine resistant septic shock has been reported and peripheral administration of low dose Petresin should be discouraged. Because Petresin activates V2 receptors on endothelial Von Willebrand factor, It enhances platelet aggregation and therefore may increase the risk of thrombosis. None in the emergency setting.
In conditions other than CPR and shock, the following symptoms of overdosage are observed :
Water intoxication may be treated with water restriction and temporary withdrawal of vasopressin until polyuria occurs. Severe water intoxication may require osmotic diuresis with mannitol, hypertonic dextrose or urea alone or with furosemide.
Pharmaceutical Precautions :
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to use, whenever solution and container permit.
Store in a refrigerator between 2°C to 8°C (36°F to 46°F),
protected from light.
Do not freeze.
SHELF LIFE :
24 months from the date of manufacture.
Petresin is supplied as 20 pressor units of vasopressin in 1 ml aqueous solution. Such 10 ampoules of 1 ml are packed in a box.
Disclaimer : For the use of a Registered Medical Practitioner or a Hospital or a Institution only. Also it is not intended to be used by healthcare professionals or patients for the purpose of prescribing or administering these products. Questions regarding the complete and current content of product labeling / specification / presentation should be directed to SGPharma.