Glypressin

Glypressin

terlipressin

Manufacturer:

Ferring

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Terlipressin acetate.
Description
One ampoule of 8.5 ml solution contains 1 mg terlipressin acetate, corresponding to 0.85 mg terlipressin free base. The concentration of the solution is 0.1 mg terlipressin free base/ml.
Excipients/Inactive Ingredients: Sodium chloride, acetic acid, sodium acetate and water for injections.
Action
Pharmacotherapeutic Group: Posterior pituitary lobe hormones (vasopressin and analogues). ATC Code: H01B A04.
Pharmacology: Pharmacodynamics: Terlipressin is a dodecapeptide that has three glycyl residues attached to the N-terminal of lysine vasopressin (LVP). Terlipressin acts as a pro-drug and is converted via enzymatic cleavage of its three glycyl residues to the biologically active lysine vasopressin.
The primary pharmacodynamic effects of terlipressin are the vasoconstrictive effects mediated through V1a receptors on vascular smooth muscle in the splanchnic and portal circulation. Moreover, terlipressin can also act via V1a receptors to increase systemic mean arterial pressure and cause a relflexogenic heart rate reduction. Regarding secondary pharmacodynamic effects, terlipressin has shown minimal effects on the fibrinolytic system in cirrhotic patients acting on V2 receptors. V2 mediated antidiuretic effects have been observed with terlipressin corresponding to 3% of the native vasopressin. No consistent effects on serum sodium has been seen in healthy volunteers but there may be a potential risk for hyponatremia associated with terlipressin when treating patients with portal hypertension and actively bleeding oesophageal varices. No influence of V1b receptors has been observed as illustrated by no significant effects observed on adrenocorticotropic hormone and cortisol release. Terlipressin initially has an effect of its own, but is converted by enzymatic cleavage to lysine vasopressin. Doses of 1 and 2 mg effectively reduce the portal venous pressure and produce marked vasoconstriction. The lowering of portal pressure and azygos blood flow is dependent on dose. The effect of the low dose is reduced after 3 hours, while haemodynamic data show that 2 mg is more effective than 1 mg as the higher dose produces a dependable effect throughout the period of treatment (4 hours).
Pharmacokinetics: The pharmacokinetics follows a two-compartment model. It has been found that the distribution and elimination half-life of approximately 8 and 40 minutes, respectively, metabolic clearance is approximately 9 ml/kg/min and the distribution volume is approximately 0.5 l/kg.
The desired concentration of lysine vasopressin in plasma is found initially after approximately 30 min. and reaches a peak value of 60 to 120 min. after administration of GLYPRESSIN. Because of 100% cross-reaction between terlipressin and lysine vasopressin, there is no specific RIA method to differentiate these substances.
Indications/Uses
Bleeding oesophageal varices.
Treatment of type 1 hepatorenal syndrome, characterised by spontaneous acute renal insufficiency, in patients suffering from severe cirrhosis with ascites.
Dosage/Direction for Use
Bleeding oesophageal varices: Adults: Initially an i.v. injection of 2 ampoules of GLYPRESSIN solution for injection (2 mg terlipressin acetate, equivalent to 1.7 mg terlipressin) is given every 4 hours. The treatment should be maintained until bleeding has been controlled for 24 hours, but up to a maximum of 48 hours. After the initial dose, the dose can be adjusted to 1 ampoule of GLYPRESSIN solution for injection (1 mg terlipressin acetate, equivalent to 0.85 mg terlipressin) i.v. every 4 hours in patients with body weight < 50 kg or if adverse effects occur. Consensus statement from the fifth Baveno Congress recommends up to 5 days.
Type 1 hepatorenal syndrome: 3 to 4 ampoules of GLYPRESSIN solution for injection (3-4 mg terlipressin acetate, equivalent to 2.55-3.4 mg terlipressin) every 24 hours as 3 or 4 administrations.
In the absence of any reduction of the serum creatinine after 3 days of treatment, cessation of GLYPRESSIN treatment is advised.
In the other cases, GLYPRESSIN treatment is to be pursued until the obtaining either of a serum creatinine less than 130 µmol/litre or of a drop of at least 30 % in the serum creatinine with respect to the value measured at the time of diagnosis of hepatorenal syndrome.
The standard average duration of treatment is 10 days.
Mode of Administration: Intravenous injection.
Overdosage
The recommended dose (2 mg terlipressin acetate/4 hours) should not be exceeded as the risk of severe circulatory adverse effects is dose-dependent.
In case of severe hypertension it is possible to administer treatment by alpha-blocker vasodilator.
Contraindications
Contraindicated in pregnancy. Hypersensitivity to terlipressin or to any of the excipients.
Special Precautions
Blood pressure, heart rate and fluid balance should be monitored during treatment. To avoid local necrosis at the injection site, the injection must be given i.v. Caution should be exercised in treating patients with hypertension or recognised heart disease. In patients with septic shock with a low cardiac output terlipressin should not be used.
Effects on the Ability to Drive and Use Machines: No studies on the effects on the ability to drive and use machines have been performed.
Use in Children: Particular caution should be exercised in the treatment of children and elderly patients, as experience is limited in these groups.
There is no data available regarding dosage recommendation in these special patient categories.
Use in the Elderly: Particular caution should be exercised in the treatment of children and elderly patients, as experience is limited in these groups.
There is no data available regarding dosage recommendation in these special patient categories.
Use In Pregnancy & Lactation
Treatment with GLYPRESSIN during pregnancy is contraindicated (please refer to Contraindications). GLYPRESSIN has been shown to cause uterine contractions and increased intrauterine pressure in early pregnancy and may decrease uterine blood flow. GLYPRESSIN may have harmful effects on pregnancy and foetus.
Information on transfer of GLYPRESSIN to breast milk is insufficient. GLYPRESSIN should not be used in breast feeding women.
Adverse Reactions
The most commonly reported undesirable effects in clinical trials (frequency 1-10%) are paleness, increased blood pressure, abdominal pain, nausea, diarrhoea and headache.
The antidiuretic effect of GLYPRESSIN may cause hyponatraemia unless the fluid balance is controlled. (See Table.)

Click on icon to see table/diagram/image
Drug Interactions
The hypotensive effect of non-selective beta-blockers on the portal vein is increased with terlipressin. Concomitant treatment with medicinal products with a known bradycardic effect (e.g. propofol, sufentanil) may lower the heart rate and cardiac output. These effects are due to reflexogenic inhibition of cardiac activity via the vagus nerve due to the elevated blood pressure.
Caution For Usage
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage
Store in a refrigerator (2°C-8°C). The ampoules are stored in the outer carton in order to protect from light.
Shelf-Life: 2 years.
ATC Classification
H01BA04 - terlipressin ; Belongs to the class of vasopressin and analogues. Used in posterior pituitary lobe hormone preparations.
Presentation/Packing
Soln for inj (amp) 1 mg/8.5 mL x 5 x 1's.
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