You Made the Call
We asked , and you answered ! Here are a few responses from this month ’ s “ You Make the Call .”
For the full description of the clinical dilemma , and to see how the expert responded , turn to page 35 .
Clinical Dilemma :
I have a patient with type 1 von Willebrand disease ( vWD ) who is about to undergo extraction of three impacted wisdom teeth . Her activity level is undetectable , and her factor 8 is 21 %. Is 40 μ / kg 1 hour prior to the procedure , and 20 μ / kg every 8 hours for three days
BRIEF SUMMARY OF PRESCRIBING INFORMATION INJECTAFER ® ( ferric carboxymaltose injection )
Rx Only
INDICATIONS AND USAGE : Injectafer ( ferric carboxymaltose injection ) is an iron replacement product indicated for the treatment of iron deficiency anemia in adult patients :
• who have intolerance to oral iron or who have had unsatisfactory response to oral iron ,
• who have non-dialysis dependent chronic kidney disease .
DOSAGE AND ADMINISTRATION : For patients weighing 50 kg ( 110 lb ) or more : Give Injectafer in two doses separated by at least 7 days . Give each dose as 750 mg for a total cumulative dose not to exceed 1500 mg of iron per course .
For patients weighing less than 50 kg ( 110 lb ): Give Injectafer in two doses separated by at least 7 days . Give each dose as 15 mg / kg body weight for a total cumulative dose not to exceed 1500 mg of iron per course .
Injectafer treatment may be repeated if iron deficiency anemia reoccurs .
Administer Injectafer intravenously , either as an undiluted slow intravenous push or by infusion . When administering as a slow intravenous push , give at the rate of approximately 100 mg ( 2 mL ) per minute . When administered via infusion , dilute up to 750 mg of iron in no more than 250 mL of sterile 0.9 % sodium chloride injection , USP , such that the concentration of the infusion is not less than 2 mg of iron per mL and administer over at least 15 minutes .
Inspect parenteral drug products visually for the absence of particulate matter and discoloration prior to administration . The product contains no preservatives . Injectafer is a single-use vial . Discard unused portion .
Avoid extravasation of Injectafer since brown discoloration of the extravasation site may be long lasting . Monitor for extravasation . If extravasation occurs , discontinue the Injectafer administration at that site .
DOSAGE FORMS AND STRENGTHS : Single-use vials containing 50 mg elemental iron per mL in the following presentation : 750 mg iron / 15 mL
CONTRAINDICATIONS : Hypersensitivity to Injectafer or any of its inactive components . WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions : Serious hypersensitivity reactions , including anaphylactic-type reactions , some of which have been life-threatening and fatal , have been reported in patients receiving Injectafer . Patients may present with shock , clinically significant hypotension , loss of consciousness , and / or collapse . Monitor patients for signs and symptoms of hypersensitivity during and after Injectafer administration for at least 30 minutes and until clinically stable following completion of the infusion . Only administer Injectafer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions . In clinical trials , serious anaphylactic / anaphylactoid reactions were reported in 0.1 % ( 2 / 1775 ) of subjects receiving Injectafer . Other serious or severe adverse reactions potentially associated with hypersensitivity which included , but not limited to , pruritus , rash , urticaria , wheezing , or hypotension were reported in 1.5 % ( 26 / 1775 ) of these subjects .
Hypertension : In clinical studies , hypertension was reported in 3.8 % ( 67 / 1,775 ) of subjects in clinical trials 1 and 2 . Transient elevations in systolic blood pressure , sometimes occurring with facial flushing , dizziness , or nausea were observed in 6 % ( 106 / 1,775 ) of subjects in these two clinical trials . These elevations generally occurred immediately after dosing and resolved within 30 minutes . Monitor patients for signs and symptoms of hypertension following each Injectafer administration .
Laboratory Test Alterations : In the 24 hours following administration of Injectafer , laboratory assays may overestimate serum iron and transferrin bound iron by also measuring the iron in Injectafer .
ADVERSE REACTIONS
Adverse Reactions in Clinical Trials : Because clinical trials are conducted under widely varying conditions , the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice .
In two randomized clinical studies , a total of 1,775 patients were exposed to Injectafer 15 mg / kg body weight up to a maximum single dose of 750 mg of iron on two occasions separated by at least 7 days up to a cumulative dose of 1500 mg of iron . after the procedure , with aminocaproic acid as needed , acceptable prophylaxis ?
I am surprised that a type 1 patient had no measurable activity levels . What are her antigen levels ?
I would usually arrange a DDAVP response trial and use 0.3 msg / kg and cap at 20 mpg . I would use subcutaneous if she is a normal weight and intravenous if she is overweight . I would also makes sure she is lying flat and that if given an intravenous dose that this is given over 45 minutes , if possible . Also , vital signs need to be
Adverse reactions reported by ≥ 1 % of treated patients are shown in the following table . Table 1 . Adverse reactions reported in ≥ 1 % of Study Patients in Clinical Trials 1 and 2
Term
Injectafer ( N = 1775 ) %
Pooled
Comparators a ( N = 1783 ) % measured every 15 minutes , and the patient needs to fluid restrict to 800 mls for 24 hours .
I would use tranexamic acid at 25 mg / kg by mouth every 6 to 8 hours for 24 hours past any signs of local oozing . I would aim for functional levels above 0 . 4 U / l at the time of dental work .
Mary-Frances Scully , MRCP St . John ’ s NL , Canada
This appears to be severe type 1 vWD ( perhaps type 3 ?).
For tooth extraction in this patient , I ’ ll agree with an initial dose of 40 IU / kg administered 30 to 40 minutes pre-extraction , but will also
Oral iron ( N = 253 ) %
Nausea 7.2 1.8 1.2 Hypertension 3.8 1.9 0.4 Flushing / Hot Flush 3.6 0.2 0.0 Blood Phosphorus Decrease 2.1 0.1 0.0 Dizziness 2.0 1.2 0.0 Vomiting 1.7 0.5 0.4 Injection Site Discoloration 1.4 0.3 0.0 Headache 1.2 0.9 0.0 Alanine Aminotransferase Increase 1.1 0.2 0.0 Dysgeusia 1.1 2.1 0.0 Hypotension 1.0 1.9 0.0 Constipation 0.5 0.9 3.2 a
Includes oral iron and all formulations of IV iron other than Injectafer
Other adverse reactions reported by ≥ 0.5 % of treated patients include abdominal pain , diarrhea , gamma glutamyl transferase increased , injection site pain / irritation , rash , paraesthesia , sneezing .
Transient decreases in laboratory blood phosphorus levels (< 2 mg / dL ) have been observed in 27 % ( 440 / 1638 ) of patients in clinical trials .
Adverse Reactions from Post-marketing Experience : The following serious adverse reactions have been most commonly reported from the post-marketing spontaneous reports with Injectafer : urticaria , dyspnea , pruritis , tachycardia , erythema , pyrexia , chest discomfort , chills , angioedema , back pain , arthralgia , and syncope . One case of hypophosphatemic osteomalacia was reported in a subject who received 500 mg of Injectafer every 2 weeks for a total of 16 weeks . Partial recovery followed discontinuation of Injectafer .
DRUG INTERACTIONS : Formal drug interaction studies have not been performed with Injectafer . USE IN SPECIFIC POPULATIONS
Pregnancy Pregnancy Category C : Adequate and well controlled studies in pregnant women have not been conducted . Injectafer should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus .
Nursing Mothers : A study to determine iron concentrations in breast milk after administration of Injectafer ( n = 11 ) or oral ferrous sulfate ( n = 14 ) was conducted in 25 lactating women with postpartum iron deficiency anemia . Mean breast milk iron levels were higher in lactating women receiving Injectafer than in lactating women receiving oral ferrous sulfate .
Pediatric Use : Safety and effectiveness has not been established in pediatric patients .
Geriatric Use : Of the 1775 subjects in clinical studies of Injectafer , 50 % were 65 years and over , while 25 % were 75 years and over . No overall differences in safety or effectiveness were observed between these subjects and younger subjects , and other reported clinical experience has not identified differences in responses between the elderly and younger patients , but greater sensitivity of some older individuals cannot be ruled out .
OVERDOSAGE : Excessive dosages of Injectafer may lead to accumulation of iron in storage sites potentially leading to hemosiderosis . A patient who received Injectafer 18,000 mg over 6 months developed hemosiderosis with multiple joint disorder , walking disability and asthenia . Hypophosphatemic osteomalacia was reported in a patient who received Injectafer 4000 mg over 4 months . Partial recovery followed discontinuation of Injectafer .
CLINICAL STUDIES : The safety and efficacy of Injectafer for treatment of iron deficiency anemia were evaluated in two randomized , open-label , controlled clinical trials ( Trial 1 and Trial 2 ). In these two trials , Injectafer was administered at dose of 15 mg / kg body weight up to a maximum single dose of 750 mg of iron on two occasions separated by at least 7 days up to a cumulative dose of 1500 mg of iron .
PATIENT COUNSELING INFORMATION
• Question patients regarding any prior history of reactions to parenteral iron products .
• Advise patients of the risks associated with Injectafer .
• Advise patients to report any signs and symptoms of hypersensitivity that may develop during and following Injectafer administration , such as rash , itching , dizziness , lightheadedness , swelling and breathing problems .
Injectafer is manufactured under license from Vifor ( International ) Inc , Switzerland .
This is not all the risk information for Injectafer . Please see www . injectafer . com for Full Prescribing Information . commence oral tranexamic acid the day before procedure or , alternatively , administer a calculated intravenous dose ( e . g ., tranexamic acid 1.0 g IV ) shortly before commencement of extraction .
After the procedure , I ’ ll suggest continuing tranexamic acid mouth washes 4 to 6 times per day for the next 3 to 5 days .
Assuming recovery and half-life of the particular vWF concentrate is already known to be satisfactory for this particular patient , I may not necessarily administer further concentrate post-extraction , unless dictated by significant post extraction bleeding .
Patrick Mensah
Haemophilia Centre , Leicester Royal Infirmary Leicester , United Kingdom
This patient most likely has severe type 1 disease , possibly type 3 disease , with very little probability for a DDAVP response . We do not have a documented clinical response for this patient , nor do we know her bleeding history , how many teeth are expected to be extracted , or her response to antifibrinolytic products in the past . Given all this , replacement with vWF concentrate would be preferable . The goal would be to achieve a trough vWF activitiy and FVIII activity levels of > 50 IU / dL . I would recommend factor replacement prior to the procedure and for up to 5 to 10 days after , pending appropriate healing and lack of re-bleeding . An antifibrinolytic , such as epsilon-aminocaproic acid or tranexamic acid , would also be appropriate to have on hand for any delayed bleeding , which can be given in combination with factor concentrate as a loading dose prior to surgery and then as needed for 7 to 10 days post-op .
Jenny Zhou , MD
IN0650BS Rev . 9 / 2015
®
See more reader responses at ashclinicalnews . org / category / training-education / you-make-the-call .
August 2016