Iloprost solution for inhalation

Iloprost is a synthetic prostacyclin analog. This product has the following pharmacological effects: inhibiting platelet aggregation, platelet adhesion and its release reaction. Dilate small arteries and small veins. Increase capillary density and reduce the increase in vascular permeability caused by inflammatory mediators such as 5-hydroxytryptamine or histamine in the microcirculation. Promote endogenous fibrinolytic activity. Anti-inflammatory effects, such as inhibiting the adhesion of leukocytes after endothelial injury and the aggregation of leukocytes in damaged tissues, and reducing the release of tumor necrosis factor. After inhalation, it can directly dilate the pulmonary artery vascular bed, sustainably reduce pulmonary artery pressure and pulmonary vascular resistance, increase cardiac output, and significantly improve mixed venous oxygen saturation. It has little effect on systemic vascular resistance and arterial pressure. Systemic toxicity Acute toxicity studies have found that oral or single intravenous administration of iloprost at a dose that exceeds the intravenous therapeutic dose by 2 orders of magnitude (100 times) can cause severe poisoning symptoms or death. Like prostacyclin, iloprost has hemodynamic effects (vasodilation, skin redness, hypotension, inhibition of platelet function, respiratory distress), as well as common poisoning symptoms such as apathy, abnormal gait and posture changes. Continuous intravenous/subcutaneous injection of iloprost in rodents or non-rodents, at doses exceeding 14-47 times the human systemic therapeutic dose (calculated based on plasma drug concentration), for 26 weeks, did not show any tissue toxicity. Only the expected pharmacological effects such as hypotension, skin redness, dyspnea, and accelerated intestinal motility appeared. Potential genotoxicity and carcinogenicity In in vitro experiments with bacteria and mammalian cells, iloprost was not found to cause gene mutations. In addition, toxic doses of iloprost did not cause human lymphocyte aberrations, and there was no teratogenic effect in the micronucleus test. In carcinogenicity studies on rats and mice, iloprost was not found to have potential carcinogenicity. Reproductive Toxicity In embryo-fetotoxicity studies in rats, continuous intravenous administration of iloprost resulted in some pups developing a single phalanx abnormality in the forepaw, which was not related to the dose of iloprost. Similar embryotoxicity studies in rabbits and monkeys did not result in dysmorphic development of the digits or other significant structural abnormalities in pups at the maximum dose of iloprost. In studies in rats, very small amounts of iloprost were found in breast milk. Local Tolerance, Contact Sensitization, and Antigenic Potential In studies of iloprost inhalation in rats, no significant local irritation of the upper and lower respiratory tracts was observed when 20 micrograms/mL of iloprost was administered for 26 weeks. No allergenic potential was found in skin sensitization (maximum test) and antigenicity studies in guinea pigs.

Treatment of moderate primary pulmonary hypertension.

Adults should start with 2.5 micrograms per inhalation (the dose provided by the mouthpiece in the inhalation device). The dose of iloprost can be gradually increased to 5.0 micrograms according to the needs and tolerance of different patients. Iloprost should be inhaled 6-9 times a day according to the needs and tolerance of different patients. Depending on the drug dose required by the mouthpiece and nebulizer, each inhalation time should be approximately 5-10 minutes. The clearance rate of iloprost is reduced in patients with renal or hepatic dysfunction, abnormal liver function, and patients with renal failure requiring hemodialysis, and a reduction in the dosage should be considered (see [Precautions] and [Pharmacokinetics]). Children and adolescents (under 18 years old) There is currently no experience in the use of iloprost in children or adolescents. Unless there is data to support it, this drug cannot be used in patients under 18 years old (see [Precautions]). Treatment course: long-term treatment. Use of nebulizer: If a certain nebulizer can meet the following standards, it is considered suitable for the nebulization of this drug solution: the median aerodynamic diameter (MMAD) or median diameter (MMD) of the droplets is 3-4m; the output dose of the mouthpiece is: 2.5 or 5ug of iloprost each time; the nebulization time of a dose of 2.5 or 5ug of iloprost: about 4-10 minutes (in order to avoid systemic side effects, the output of iloprost within 4 minutes should not exceed 5ug). In order to minimize accidental exposure, it is recommended to use a nebulizer equipped with a filter or inhalation trigger device when inhaling iloprost, and keep the room well ventilated. Inhale the prepared solution with an appropriate device (nebulizer). Continue the previous treatment and make individual adjustments (see [Drug Interactions]).

In addition to local adverse reactions due to inhaled medication, such as increased cough, the adverse reactions of inhaled iloprost are mainly related to the pharmacological properties of prostacyclin. The most common adverse reactions in clinical trials include vasodilation, headache and increased cough. Very common adverse reactions (may occur in 10 or more patients in 100 patients): hot flashes or facial redness due to vasodilation; increased cough; decreased blood pressure (hypotension). Common adverse reactions (may occur in 1-10 patients in 100 patients): headache; cheek muscle spasm (difficulty opening and closing the mouth); syncope: syncope is a common symptom of this disease. There was no significant difference in the incidence of syncope between the iloprost treatment group and the control group in clinical trials, but it may also occur when using this drug. Please refer to the precautions section. Other possible reactions: If the patient takes anticoagulants (anticoagulants), minor bleeding may occur. Because most patients with pulmonary hypertension take anticoagulants, bleeding events (mostly hematomas) are common. The frequency of bleeding events in the iloprost group was not significantly different from that in the placebo control group.

The following patients are contraindicated: Allergic to iloprost or any excipients. Diseases with increased risk of bleeding (such as active peptic ulcer, trauma, intracranial hemorrhage or other bleeding), which may increase the risk of bleeding due to the effect of this drug on platelets. Patients with heart disease, such as: severe arrhythmias, severe coronary heart disease, unstable angina, myocardial infarction within 6 months of onset, uncompensated heart failure that is not controlled and treated or not under close monitoring, congenital or acquired valvular heart disease with clinically significant myocardial dysfunction caused by non-pulmonary hypertension. Obvious pulmonary edema with dyspnea. Cerebrovascular events (such as transient ischemic attack, stroke) or other cerebral blood supply disorders in the past 3 months. Pregnancy, breastfeeding.

Precautions during pregnancy and lactation: Do not use if you are pregnant or lactating

Iloprost can enhance the antihypertensive effect of drugs such as beta-receptor blockers, calcium ion antagonists, vasodilators and angiotensin converting enzyme inhibitors. Because iloprost has the effect of inhibiting platelet function, it can increase the risk of bleeding when used in combination with anticoagulants (such as heparin, coumarin anticoagulants) or other drugs that inhibit platelet aggregation (such as acetylsalicylic acid, nonsteroidal anti-inflammatory drugs, phosphodiesterase inhibitors and nitrovasodilators). The interaction between intravenous infusion of iloprost and digoxin, acetylsalicylic acid and tissue plasminogen activator (t-PA) was studied. The results showed that intravenous infusion of iloprost did not affect the pharmacokinetics of patients after multiple oral digoxin, nor did it affect the pharmacokinetics of t-PA given at the same time. Animal experiments have found that iloprost may lead to a decrease in the steady-state blood concentration of t-PA. Animal experiments have shown that pre-administration of glucocorticoids can reduce the vasodilatory effect of iloprost, but does not affect the inhibitory effect on platelet aggregation. The significance of this finding for the drug's use in humans is unclear.

Keep in a light-proof and airtight container. Valid for 2 years.

2 ml: 20 μg