Ilomedin amp

Document Sample
Ilomedin amp Powered By Docstoc
					Ilomedin amp
Description Each 0.5 mL aqueous solution contains iloprost trometamol 0.067 mg (equivalent to iloprost 0.05 mg). Each 1 mL aqueous solution contains iloprost trometamol 0.134 mg (equivalent to iloprost 0.1 mg). Ilomedin also contains trometamol, ethanol 96% (v/v), sodium chloride, hydrochloric acid 1N and water for injection as excipients. Actions Iloprost is a prostacyclin analogue. Pharmacology: The following pharmacological effects have been observed: Inhibition of aggregation, platelet adhesion and release reaction; dilatation of arterioles and venules, increase of capillary density and reduction of increased vascular permeability in the microcirculation; activation of fibrinolysis, inhibition of adhesion and immigration of leucocytes after an endothelial lesion, and reduced release of oxygen free radicals. The exact mechanism of action is unknown. Pharmacokinetics: Steady-state plasma levels are achieved as early as 10-20 min after the start of an IV infusion. The steady-state plasma levels are linearly related to the infusion rate. Plasma levels of about 135 ± 24 pg/mL are obtained at an infusion rate of 3 ng/kg/min. The plasma concentration of iloprost falls very quickly after the end of the infusion because of the high rate of metabolism. The metabolic clearance of the substance from plasma is about 20 ± 5 mL/kg/min. The half-life of the terminal disposition phase from plasma is 0.5 hrs, as a result of which the substance levels falls to <10% of the equilibrium concentration just 2 hrs after the end of infusion. Pharmacokinetics of iloprost are independent of the age or sex of the patients. However, in patients with liver cirrhosis and in patients with chronic renal failure requiring dialysis, the clearance of iloprost is reduced by a factor of 2-4. Interactions with other drugs at the levels of plasma protein-binding are improbable because the greater portion of iloprost is bound to the albumin of blood plasma (protein-binding: 60%) and only very low iloprost concentrations are achieved. An effect of iloprost therapy on the biotransformation of other drugs is likewise extremely unlikely because of the metabolic pathways and the low absolute dose. Iloprost is metabolised principally via β-oxidation of the carboxyl side chain. No unchanged substance is eliminated. The main metabolite is tetranor-iloprost, which is found in the urine in free and conjugated form in 4-diastereoisomers. Tetranor-iloprost is pharmacologically inactive. Eighty percent of the iloprost metabolites are excreted via the kidneys and 20% with the bile. The metabolites are eliminated from plasma and with urine in 2 phases for which half-lives of about 2 and 5 hrs (plasma) and 2 and 18 hrs (urine) have been calculated. Iloprost is 100% bioavailable with IV administration. Toxicology: Preclinical Safety Data: Basing on studies in animals, the risk of acute toxicity in man appears to be low if one takes into account the absolute

total dose given to patients during therapeutic use and the maximum amount of substance present in an ampoule, particularly as the preparation is administered only under clinical conditions. In systemic toxicity studies with repeated (continuous) IV infusion, a slight reduction of the blood pressure occurred at doses >14 ng/min and severe undesired effects (hypotension, disturbance of respiratory function) appeared only after extremely high dosages (2 orders of magnitude above therapeutic dose) compared with the therapeutic dosage. In vitro and in vivo studies for genotoxic effects have not produced any evidence for a mutagenic potential. Indications Treatment of advanced thromboangitis obliterans (Buerger's disease) with critical limb ischemia in cases where re-vascularisation is not indicated. Treatment of patients with severe peripheral arterial occlusive disease (PAOD), particularly those at risk of amputation and in whom surgery or angioplasty is not possible. Treatment of patients with severe disabling Raynaud's phenomenon unresponsive to other therapies. Dosage Ilomedin should be used only under strict monitoring in hospitals or outpatient clinics with adequate facilities. Pregnancy must be excluded before the start of treatment in women. Ilomedin is administered as an IV infusion. The dose is adjusted according to individual tolerability within the range of 0.5-2 ng iloprost/kg body weight/min over 6 hrs daily. The duration of treatment is up to 4 weeks. Shorter treatment periods (3-5 days) are often sufficient in Raynaud's phenomenon to achieve improvement over several weeks. For IV use, the contents of a 0.5-mL and 1 mL-amp of Ilomedin are diluted with 250 and 500 mL respectively, of a sterile physiological saline solution or a 5% glucose solution. The contents of the ampoule and the diluent should be mixed thoroughly. In general, the ready-to-use infusion containing 0.2 mcg/mL iloprost is infused IV over 6 hrs daily via a peripheral vein or a central venous catheter by means of an infusion pump (Infusomat). The infusion solution should be prepared freshly each day to ensure sterility. During the first 2-3 days, the individually tolerated dose is established. For this purpose, treatment should be started at an infusion rate of 10 mL/hr for 30 min. An infusion rate of 10 mL/hr equals 0.5 ng/kg/min for a patient weighing 65 kg body weight. The dose should then be increased at intervals of about 30 min in steps of 10 mL/hr up to 40 mL/hr (up to 50 mL/hr if the patient's body weight is >75 kg). Depending on the occurrence of side effects, eg headache and nausea, or an undesired drop of blood pressure, the infusion rate should be reduced until the tolerable dose is found. If the side effects are severe, the infusion rate should be interrupted. For the rest of the treatment period, therapy

should be continued with the dose found to be tolerable in the first 2-3 days. The blood pressure and heart rate must be measured at the start of the infusion and after every increase of the dose. It should be borne in mind that in patients with renal failure requiring dialysis and in patients with liver cirrhosis, iloprost elimination is reduced. In these patients a dose reduction (eg, ½ the recommended dose) is necessary. Continuous infusion over several days is not recommended because of the possible development of tachyphylaxis of platelet effects and the possibility of rebound platelet hyperaggregability at the end of treatment, although no clinical complications associated with these phenomena have been reported. An infusion pump with a 50-mL injection syringe (eg, the Perfusor) may also be used. In this case, the contents of 1 amp Ilomedin of 1 mL are diluted with 50 mL of sterile physiological saline solution or 5% glucose solution, the contents of 1 amp Ilomedin of 0.5 mL are diluted with 25 mL of sterile physiological saline solution or 5% glucose solution. In the case of an Ilomedin concentration of 2 mcg/mL, the required infusion rate in analogy to the previously described scheme should be 1-5 mL/hr. Overdosage Symptoms: Pronounced facial flush and severe headaches, possibly limb or back pain. Vasovagal reaction with sudden blanching, outbreak of sweating, nausea, vomiting, cramp-like abdominal pain and diarrhoea. Decrease or increase of blood pressure, bradycardia or tachycardia. Treatment: Interruption of the infusion, symptomatic measures. A causal antidote is not known. In the event of myocardial ischaemia provoked by iloprost the administration of 125 g aminophylline IV has been shown to be an effective countermeasure. Contraindication Pregnancy, lactation, hypersensitivity to iloprost. Conditions where the effects of Ilomedin on platelets might increase the risk of haemorrhage (eg, active peptic ulcers, trauma, intracranial haemorrhage). Severe coronary heart disease or unstable angina; myocardial infarction within the last 6 months; acute or chronic congestive heart failure (NYHA II-IV); arrhythmias relevant to the prognosis; suspected pulmonary congestion. Use in pregnancy & lactation: Ilomedin must not be administered to pregnant or lactating women. The use of iloprost during pregnancy is contraindicated because of the occurrence of anomalies of the toes (decreased growth or fusion of individual toes) in individual foetuses in the embryotoxicity study in rats at doses above the lowest dose of 0.01 mg/kg/day (6.9 ng/kg/min). This phenomenon is presumably attributable to haemodynamic changes in the foeto-placental circulation. Precautions Surgery should not be delayed in patients requiring urgent amputation (eg, in infected gangrene).

Patients should be strongly advised to stop smoking. In patients with low blood pressure, care should be taken to avoid further hypotension. The possibility of orthostatic hypotension should be borne in mind in patients getting up from the lying to an upright position after the end of administration. Ilomedin should be used only after dilution. Because of the possibility of interactions, no other drug should be added to the ready-to-use infusion solution. The paravascular infusion of undiluted Ilomedin can lead to local reactions at the injection site. Oral ingestion and contact with mucous membranes must be avoided. On contact with the skin, iloprost may provoke long-lasting but painless erythema. Suitable precautions should therefore be taken to avoid iloprost contact with the skin. In the event of such contact, the affected area should be washed immediately with copious amounts of water or saline. Effects on the Ability to Drive or Operate Machinery: Not applicable. Adverse Reactions The most common and frequently observed side effects at the specified dosage are facial flushing and headache. Malaise, nausea, vomiting, cramp-like abdominal pain, diarrhoea, sweating, sensation of warmth and weakness are likely to occur during prolonged infusion. Pain in the affected limb, paraesthesia, tiredness, increased temperature, fever, chill, states of confusion, apathy, sedation, agitation, lowering or increase of blood pressure, tachycardias, arrhythmias, extrasystoles and restlessness have been reported. All the side effects usually disappear quickly with dose reduction. Arthralgia and allergic reactions may occur. Isolated cases of dyspnoea and bronchial asthma have been reported and individual cases of acute pulmonary oedema or heart failure have been observed in elderly patients with advanced arteriosclerosis. Reddening and pain may occur at the infusion site. In some cases, cutaneous vasodilation may give rise to streaky erythema above the infusion vein. Iloprost may provoke angina, especially in patients with coronary heart disease. Hypotensive episodes occurring at low doses of Ilomedin have been reported in individual cases. Drug Interaction In pharmacological experiments, iloprost has shown an additive effect on the antihypertensive activity of β-receptor blockers, calcium antagonists and vasodilators, and a potentiating effect on the antihypertensive activity of ACE inhibitors. These findings could not be confirmed in human volunteers. Should significant hypotension occur this can be corrected by dose reduction of iloprost. In animal experiments, the vasodilatory effect of iloprost is attenuated when the animals are pre-treated with glucocorticoids, while the inhibitory effect on platelet aggregation remains unaffected. The significance of this finding for use in man is not yet known.

Because iloprost inhibits platelet function, its use with heparin or coumarin-type anticoagulants, which affect other haemostatic mechanisms, theoretically may increase the risk of bleeding. If this occurs, Ilomedin infusion should be stopped. Iloprost has an additive or superadditive effect on platelet function with other inhibitors of platelet aggregation (acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs and phosphodiesterase inhibitors). Incompatibilities: None so far known. Cautions For Usage Ilomedin should be used only after dilution. Because of the possibility of interactions, no other drug should be added to the ready-for-use infusion solution. Storage No special storage conditions are required. Shelf-Life: The ready-for-use infusion solution must be freshly prepared each day in order to guarantee the sterility. The expiration date is based on a stability period of 4 years. Annual Packing/Presentation Amp 0.02 mg


				
DOCUMENT INFO
Shared By:
Categories:
Stats:
views:433
posted:11/4/2009
language:English
pages:5