آهن دکستران

تزریق داخل وریدی یا عضلانی INFeD برای درمان بیماران مبتلا به فقر آهن ثابت شده که تجویز خوراکی در آنها رضایت بخش نیست یا غیرممکن است، اندیکاسیون دارد.

حساسیت به محصول. تمام کم خونی هایی که با کمبود آهن مرتبط نیستند.

خطر واکنش های نوع آنافیلاکتیک: واکنش های نوع آنافیلاکتیک، از جمله مرگ و میر، به دنبال تجویز تزریقی آهن دکستران رخ داده است. همیشه تجهیزات احیا و پرسنل آموزش دیده در تشخیص و درمان واکنش های نوع آنافیلاکتیک را در طول تجویز INFeD در دسترس داشته باشید. قبل از اولین دوز درمانی، یک دوز آزمایشی INFeD 0.5 میلی لیتری تجویز کنید. (به دوز و مصرف مراجعه کنید. ) اگرچه واکنش ها معمولاً در عرض چند دقیقه آشکار می شوند، حداقل یک ساعت قبل از تجویز دوز درمانی، بیماران را تحت نظر قرار دهید. در طول تمام تجویزهای INFeD، بیماران را از نظر علائم یا نشانه های واکنش های نوع آنافیلاکتیک مشاهده کنید. واکنش‌های کشنده به دنبال دوز آزمایشی آهن دکستران و همچنین در موقعیت‌هایی که دوز آزمایش تحمل می‌شد رخ داده است. از INFeD فقط در بیمارانی استفاده کنید که تحقیقات بالینی و آزمایشگاهی در آنها وضعیت کمبود آهن را نشان داده است که قابل درمان با آهن خوراکی نیست. عواملی که بر خطر واکنش‌های نوع آنافیلاکتیک به محصولات آهن دکستران تأثیر می‌گذارند، به طور کامل شناخته نشده‌اند، اما داده‌های بالینی محدود نشان می‌دهند که این خطر ممکن است در بین بیمارانی که سابقه حساسیت دارویی یا آلرژی‌های دارویی متعدد دارند، افزایش یابد. علاوه بر این، مصرف همزمان داروهای مهارکننده آنزیم مبدل آنژیوتانسین ممکن است خطر واکنش به فرآورده آهن دکستران را افزایش دهد. میزان خطر واکنش های نوع آنافیلاکتیک به دنبال قرار گرفتن در معرض هر محصول خاص آهن دکستران ناشناخته است و ممکن است در بین محصولات متفاوت باشد. محصولات آهن دکستران از نظر خصوصیات شیمیایی متفاوت هستند و ممکن است در اثرات بالینی متفاوت باشند. محصولات آهن دکستران از نظر بالینی قابل تعویض نیستند. واکنش های تاخیری: دوزهای بزرگ داخل وریدی، مانند استفاده با انفوزیون با دوز کل (TDI)، با افزایش بروز عوارض جانبی همراه است. عوارض جانبی اغلب واکنش‌های تاخیری (1-2 روزه) است که با یک یا چند مورد از علائم زیر مشخص می‌شود: آرترالژی، کمردرد، لرز، سرگیجه، تب متوسط ​​تا بالا، سردرد، ضعف، میالژی، تهوع و استفراغ. شروع معمولاً 48-24 ساعت پس از مصرف است و علائم معمولاً در عرض 3-4 روز فروکش می‌کنند. علت این واکنش ها مشخص نیست. هنگام تخمین خطر/فایده درمان باید احتمال بروز واکنش تاخیری در نظر گرفته شود. حداکثر دوز روزانه نباید از 2 میلی لیتر دکستران آهن رقیق نشده تجاوز کند. خطر در بیماران با شرایط زمینه ای: INFeD باید با احتیاط شدید در بیماران مبتلا به اختلال جدی در عملکرد کبد استفاده شود. در مرحله حاد بیماری عفونی کلیه نباید استفاده شود. واکنش‌های نامطلوب پس از تجویز INFeD ممکن است عوارض قلبی عروقی را در بیماران مبتلا به بیماری‌های قلبی عروقی از قبل تشدید کند. سرطان زایی: خطر سرطان زایی ممکن است همراه با تزریق عضلانی کمپلکس های آهن-کربوهیدرات باشد. چنین کمپلکس‌هایی در شرایط تجربی برای تولید سارکوم پیدا شده‌اند، زمانی که دوزهای بزرگ یا دوزهای کوچک به طور مکرر در همان محل تزریق می‌شوند به موش‌ها، موش‌ها و خرگوش‌ها و احتمالاً در همسترها داده می‌شوند. دوره نهفته طولانی بین تزریق یک سرطان زا بالقوه و ظهور یک تومور، اندازه گیری دقیق خطر را در انسان غیرممکن می کند. با این حال، چندین گزارش در متون وجود دارد که تومورهای محل تزریق را در انسان‌هایی که قبلاً کمپلکس‌های آهن-کربوهیدرات تزریقی عضلانی دریافت کرده‌اند، توصیف می‌کنند.

General: Unwarranted therapy with parenteral iron will cause excess storage of iron with the consequent possibility of exogenous hemosiderosis. Such iron overload is particularly apt to occur in patients with hemoglobinopathies and other refractory anemias that might be erroneously diagnosed as iron deficiency anemias. INFeD should be used with caution in individuals with histories of significant allergies and/or asthma. Anaphylaxis and other hypersensitivity reactions have been reported after uneventful test doses as well as therapeutic doses of iron dextran injection. Therefore, administer a test dose prior to the first therapeutic dose of INFeD. (See BOXED WARNING and DOSAGE AND ADMINISTRATION: Administration.) Epinephrine should be immediately available in the event of acute hypersensitivity reactions. (Usual adult dose: 0.5 mL of a 1:1000 solution, by subcutaneous or intramuscular injection.) Note: Patients using beta-blocking agents may not respond adequately to epinephrine. Isoproterenol or similar beta-agonist agents may be required in these patients. Patients with rheumatoid arthritis may have an acute exacerbation of joint pain and swelling following the administration of INFeD. Reports in the literature from countries outside the United States (in particular, New Zealand) have suggested that the use of intramuscular iron dextran in neonates has been associated with an increased incidence of gram-negative sepsis, primarily due to E. Coli. Information For Patients: Patients should be advised of the potential adverse reactions associated with the use of INFeD. Drug/Laboratory Test Interactions: Large doses of iron dextran (5 mL or more) have been reported to give a brown color to serum from a blood sample drawn 4 hours after administration. The drug may cause falsely elevated values of serum bilirubin and falsely decreased values of serum calcium. Serum iron determinations (especially by colorimetric assays) may not be meaningful for 3 weeks following the administration of iron dextran. Serum ferritin peaks approximately 7 to 9 days after an intravenous dose of INFeD and slowly returns to baseline after about 3 weeks. Examination of the bone marrow for iron stores may not be meaningful for prolonged periods following iron dextran therapy because residual iron dextran may remain in the reticuloendothelial cells. Bone scans involving 99m Tc-diphosphonate have been reported to show a dense, crescentic area of activity in the buttocks, following the contour of the iliac crest, 1 to 6 days after intramuscular injections of iron dextran. Bone scans with 99m Tc-labeled bone seeking agents, in the presence of high serum ferritin levels or following iron dextran infusions, have been reported to show reduction of bony uptake, marked renal activity, and excessive blood pool and soft tissue accumulation. Carcinogenesis, Mutagenesis, Impairment Of Fertility: See WARNINGS . Pregnancy: Iron dextran has been shown to be teratogenic and embryocidal in mice, rats, rabbits, dogs, and monkeys when given in doses of about 3 times the maximum human dose. No consistent adverse fetal effects were observed in mice, rats, rabbits, dogs and monkeys at doses of 50 mg iron/kg or less. Fetal and maternal toxicity has been reported in monkeys at a total intravenous dose of 90 mg iron/kg over a 14-day period. Similar effects were observed in mice and rats on administration of a single dose of 125 mg iron/kg. Fetal abnormalities in rats and dogs were observed at doses of 250 mg iron/kg and higher. The animals used in these tests were not iron deficient. There are no adequate and well-controlled studies in pregnant women. INFeD should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Placental Transfer: Various animal studies and studies in pregnant humans have demonstrated inconclusive results with respect to the placental transfer of iron dextran as iron dextran. It appears that some iron does reach the fetus, but the form in which it crosses the placenta is not clear. Nursing Mothers: Caution should be exercised when INFeD is administered to a nursing woman. Traces of unmetabolized iron dextran are excreted in human milk. Pediatric Use: Not recommended for use in infants under 4 months of age. (See DOSAGE AND ADMINISTRATION .) Close

Severe/Fatal: Anaphylactic reactions have been reported with the use of iron dextran injection; on occasions these reactions have been fatal. Such reactions, which occur most often within the first several minutes of administration, have been generally characterized by sudden onset of respiratory difficulty and/or cardiovascular collapse. Because fatal anaphylactic reactions have been reported after administration of iron dextran injection, the drug should be given only when resuscitation techniques and treatment of anaphylactic and anaphylactoid shock are readily available. (See BOXED WARNING and PRECAUTIONS : General, pertaining to immediate availability of epinephrine.) Cardiovascular: Chest pain, chest tightness, shock, cardiac arrest, hypotension, hypertension, tachycardia, bradycardia, flushing, arrhythmias. (Flushing and hypotension may occur from too rapid injections by the intravenous route.) Dermatologic: Urticaria, pruritus, purpura, rash, cyanosis. Gastrointestinal: Abdominal pain, nausea, vomiting, diarrhea. Hematologic/lymphatic: Leucocytosis, lymphadenopathy. Musculoskeletal/soft tissue: Arthralgia, arthritis (may represent reactivation in patients with quiescent rheumatoid arthritis - See PRECAUTIONS : General), myalgia; backache; sterile abscess, atrophy/fibrosis (intramuscular injection site); brown skin and/or underlying tissue discoloration (staining), soreness or pain at or near intramuscular injection sites; cellulitis; swelling; inflammation; local phlebitis at or near intravenous injection site. Neurologic: Convulsions, seizures, syncope, headache, weakness, unresponsiveness, paresthesia, febrile episodes, chills, dizziness, disorientation, numbness, unconsciousness. Respiratory: Respiratory arrest, dyspnea, bronchospasm, wheezing. Urologic: Hematuria. Delayed reactions: Arthralgia, backache, chills, dizziness, fever, headache, malaise, myalgia, nausea, vomiting. (See WARNINGS ). Miscellaneous: Febrile episodes, sweating, shivering, chills, malaise, altered taste.

Overdosage with iron dextran is unlikely to be associated with any acute manifestations. Dosages of iron dextran in excess of the requirements for restoration of hemoglobin and replenishment of iron stores may lead to hemosiderosis. Periodic monitoring of serum ferritin levels may be helpful in recognizing a deleterious progressive accumulation of iron resulting from impaired uptake of iron from the reticuloendothelial system in concurrent medical conditions such as chronic renal failure, Hodgkin’s disease, and rheumatoid arthritis. The LD50 of iron dextran is not less than 500 mg/kg in the mouse.

INFeD (Iron Dextran Injection USP) is a dark brown, slightly viscous sterile liquid complex of ferric hydroxide and dextran for intravenous or intramuscular use. Each mL contains the equivalent of 50 mg of elemental iron (as an iron dextran complex), approximately 0.9% sodium chloride, in water for injection. Sodium hydroxide and/or hydrochloric acid may have been used to adjust pH. The pH of the solution is between 4.5 to 7.0. Therapeutic Class: Hematinic

General: After intramuscular injection, iron dextran is absorbed from the injection site into the capillaries and the lymphatic system. Circulating iron dextran is removed from the plasma by cells of the reticuloendothelial system, which split the complex into its components of iron and dextran. The iron is immediately bound to the available protein moieties to form hemosiderin or ferritin, the physiological forms of iron, or to a lesser extent to transferrin. This iron which is subject to physiological control replenishes hemoglobin and depleted iron stores. Dextran, a polyglucose, is either metabolized or excreted. Negligible amounts of iron are lost via the urinary or alimentary pathways after administration of iron dextran. The major portion of intramuscular injections of iron dextran is absorbed within 72 hours; most of the remaining iron is absorbed over the ensuing 3 to 4 weeks. Various studies involving intravenously administered 59Fe iron dextran to iron deficient subjects, some of whom had coexisting diseases, have yielded half-life values ranging from 5 hours to more than 20 hours. The 5-hour value was determined for 59Fe iron dextran from a study that used laboratory methods to separate the circulating 59Fe iron dextran from the transferrin-bound 59Fe. The 20-hour value reflects a half-life determined by measuring total 59Fe, both circulating and bound. It should be understood that these half-life values do not represent clearance of iron from the body. Iron is not easily eliminated from the body and accumulation of iron can be toxic. In vitro studies have shown that removal of iron dextran by dialysis is negligible.1,2 Six different dialyzer membranes were investigated (polysulfone, cuprophane, cellulose acetate, cellulose triacetate, polymethylmethacrylate and polyacrylonitrile), including those considered high efficiency and high flux.