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Powder (vial): white, lyophilized powder. Solvent (ampoule): clear, colourless liquid. Each vial of powder contains 1mg terlipressin diacetate (equivalent to terlipressin free base 0.86mg). The concentration of the reconstituted solution is 0.2mg terlipressin diacetate/mL. For full list of excipients see Pharmaceutical Precautions.
Pharmacotherapeutic group: Posterior pituitary lobe hormones (vasopressin and analogues), ATC code: H01B A04. Terlipressin initially has an effect of its own, but is converted by enzymatic cleavage to lysine vasopressin. Doses of 1 and 2mg 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 2mg is more effective than 1mg as the higher dose produces a dependable effect throughout the period of treatment (4 hours).
The pharmacokinetics follows a two-compartment model. It has been found that the half-life is approximately 40 minutes, metabolic clearance is approximately 9mL/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 minutes and reaches a peak value of 60 to 120 minutes after administration of GLYPRESSIN. Because of 100% cross-reaction between terlipressin and lysine vasopressin, there is no specific RIA method for these substances.
Preclinical data reveal no special hazard for humans based on conventional studies of single- and repeat-dose toxicity, and genotoxicity. At dosages relevant to humans, the only effects observed in animals were those attributable to the pharmacological activity of terlipressin. No pharmacokinetic data are available from animals to compare with humans the plasma concentrations at which these effects occurred, but as the route of administration was intravenous, a substantial systemic exposure can be assumed for the animal studies. An embryo-foetal study in rats demonstrated no adverse effects of terlipressin, but in rabbits abortions occurred, probably related to maternal toxicity, and there were ossification anomalies in a small number of foetuses and a single isolated case of cleft palate. No carcinogenicity studies have been performed with terlipressin.
GLYPRESSIN is indicated for the treatment of: bleeding oesophageal varices treatment of type 1 hepatorenal syndrome, characterised by spontaneous acute renal insufficiency, in patients suffering from severe cirrhosis, with ascites
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Bleeding Oesophageal Varices
An intravenous injection of 2mg terlipressin diacetate every 4 hours by bolus injection. The treatment should continue until bleeding has been controlled for 24 consecutive hours or for a maximum period of 48 hours. After the initial injection, subsequent doses can be reduced to 1mg terlipressin diacetate every 4 hours in patients with a body weight of less than 50kg or when necessitated by adverse effects.
Type 1 Hepatorenal Syndrome
3 to 4mg of terlipressin diacetate every 24 hours as 3 or 4 administrations. If serum creatinine does not decrease at least 25% after 3 days, the dose can be increased in a stepwise manner up to a maximum of 2mg terlipressin diacetate/4h. In the other cases, GLYPRESSIN treatment is to be pursued until the obtaining either of a serum creatinine less than 130umol/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. GLYPRESSIN must only be administered intravenously.
Pregnancy Septic shock Hypersensitivity to terlipressin or any other excipients of the product
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 intravenously. Caution should be exercised in treating patients with hypertension, recognised heart disease, or peripheral artery disease. The effectiveness of terlipressin in the treatment of hepatorenal syndrome with concomitant sepsis is unknown. In patients with septic shock with a low cardiac output terlipressin should not be used.
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.
Treatment with GLYPRESSIN during pregnancy is contraindicated. 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 on the foetus. Spontaneous abortion and malformation have been shown in rabbits after treatment with GLYPRESSIN. Information on transfer of GLYPRESSIN to breast milk is insufficient. GLYPRESSIN should not be used in breast feeding women.
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No studies on the effects on the ability to drive and use machines have been performed..
| MedDRA | ||||
| System Organ Class Disorder | COMMON (10-1%) | UNCOMMON (1-0.1%) | RARE (0.1-0.01%) | Not known (Cannot be estimated from the available data) |
| Metabolism | - | Hyponatraemia if fluid not monitored | - | - |
| Nervous system | Headache | - | - | - |
| Cardiac | Bradycardia | Atrial Fibrillation Ventricular extracystoles Tachycardia Chest pain Myocardial Infarction Fluid overload with pulmonary oedema | Torsade de point Cardiac failure | |
| Vascular | Peripheral vasoconstriction Peripheral ischaemia Facial pallor Hypertension | Intestinal ischaemia Peripheral cyanosis Hot flushes | ||
| Respiratory | Respiratory distress Respiratory failure | Dyspnoea | ||
| Gastrointestinal | Transient abdominal cramps Transient diarrhoea | Transient nausea Transient vomiting | ||
| Skin and subcutaneous | Skin necrosis | |||
| Pregnancy, puerperium and perinatal conditions | Uterine hypertonus Decreased uterine blood flow | |||
| General | Injection site necrosis |
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.
The recommended dose (2mg terlipressin diacetate/4 hours) should not be exceeded as the risk of severe circulatory adverse effects is dose-dependent.
Powder: Mannitol (E421); Hydrochloric acid Solvent: Sodium chloride; Hydrochloric acid; Water for injections
In the absence of compatability studies, this medicinal product must not be mixed with other medicinal products.
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3 years This product should be used immediately after reconstitution.
Store below 25 C in original package in order to protect from light. The reconstituted solution must be used immediately after reconstitution.
Prescription Medicine.
GLYPRESSIN lyophilized powder is provided in a 6ml glass vial with a rubber stopper and green/silver coloured snap cap. The diluent is provided in a 5ml glass ampoule. Powder and diluent are provided together. Pack size: 5 x vials + 5 ampoules
Mix solvent with powder for injection via the rubber stopper in the vial. The clear reconstituted solution must be injected intravenously immediately after reconstitution. Any unused drug or waste materials should be disposed of in accordance with local requirements.
Exclusive New Zealand distributors: Pharmaco (NZ) Ltd P O Box 4079 Auckland Telephone (09) 377-3336
16 April 2013 (CCDS 2010/07 v02)
GLYPRESSIN INJECTION - GLYP006 16 April 2013