Aranesp

Erythropoietin Agents

Administer subcutaneously or intravenously.
Prior to and during therapy, monitor the patient's iron status including transferrin saturation and serum ferritin. Transferrin saturation should be >= 20% and ferritin should be >= 100 ng/mL. Almost all patients will require iron supplementation during therapy to maintain adequate iron stores.
Darbepoetin alfa is available as a vial and prefilled syringe. The needle shield for the prefilled syringe contains latex.
The prefilled syringe may not be appropriate for patients receiving doses that are not represented by one of the prefilled syringe formulations. If patients or caregivers have difficulty measuring or administering the required dose, consider whether the patient is an appropriate candidate for self-administration or whether the patient would benefit from an alternate darbepoetin alfa presentation.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Do not dilute. Do not administer with other drug solutions.
Do not shake; inactivation of darbepoetin alfa may occur upon shaking.
Protect from light during storage and until administration. Exposure to light may denature darbepoetin alfa.
Do not freeze.
Darbepoetin alfa contains no preservatives. Use one single-use vial per dose. Once a syringe has entered a single-dose vial, the sterility of the product cannot be guaranteed. Do not use the vials or prefilled syringes more than one time. Discard any unused portion. Do not pool unused portions from the vials or prefilled syringes.

May be injected directly into a vein or via the venous return line of the dialysis tubing at the end of a dialysis session. It has been suggested that to prevent adherence to the tubing, darbepoetin alfa should be injected while blood is still in the IV line, followed by flushing with 0.9% Sodium Chloride injection.

Inject darbepoetin alfa subcutaneously taking care not to inject intradermally.
In patients on hemodialysis, subcutaneous administration is not recommended; administer IV instead.

thrombosis / Delayed / 0-5.0
stroke / Early / 0-2.1
pulmonary embolism / Delayed / 0-1.5
intracranial bleeding / Delayed / 0-1.3
myocardial infarction / Delayed / 0-0.6
heart failure / Delayed / Incidence not known
thromboembolism / Delayed / Incidence not known
seizures / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
erythema multiforme / Delayed / Incidence not known
red cell aplasia / Delayed / Incidence not known

hypertension / Early / 31.0-31.0
dyspnea / Early / 17.0-17.0
peripheral edema / Delayed / 17.0-17.0
edema / Delayed / 12.8-12.8
angina / Early / 0-8.0
erythema / Early / 5.0-5.0
anemia / Delayed / Incidence not known
antibody formation / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
encephalopathy / Delayed / Incidence not known

abdominal pain / Early / 13.2-13.2
cough / Delayed / 12.0-12.0
rash / Early / 5.0-5.0
injection site reaction / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
vitamin B6 deficiency / Delayed / Incidence not known

In controlled trials, patients with chronic kidney disease such as renal impairment or renal failure experienced greater risks for mortality, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) such as darbepoetin alfa to target a hemoglobin concentration greater than 11 g/dL. No trial has identified a hemoglobin target concentration, ESA dose, or dosing strategy that does not increase these risks. Use the lowest dose sufficient to reduce the need for red blood cell transfusions. For patients with chronic kidney disease either on or off dialysis, a hemoglobin less than 10 g/dL is advised before darbepoetin alfa initiation. In controlled clinical trials of patients with chronic kidney disease comparing higher hemoglobin targets (13 to 14 g/dL) to lower targets (9 to 11.3 g/dL), ESAs increased the risk of death, myocardial infarction, stroke, congestive heart failure, thrombosis of hemodialysis vascular access, and other thromboembolic events in the higher target groups. Using ESAs to target a hemoglobin concentration greater than 11 g/dL increases the risk of serious adverse cardiovascular reactions and has not been shown to provide additional benefit. Use caution in patients with coexistent cardiac disease, stroke, and cardiovascular disease such as angina. Patients with chronic kidney disease and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. A rate of hemoglobin rise of greater than 1 g/dL over 2 weeks may contribute to these risks; a dose reduction is warranted. During hemodialysis, patients treated with ESAs may require increased anticoagulant therapy with heparin to prevent clotting of the dialysis machine.

Use of erythropoiesis stimulating agents (ESAs) shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies of patients with certain neoplastic disease: breast, non-small cell lung, head and neck, lymphoid, and cervical cancers. ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure. Further, use ESAs only for anemia from myelosuppressive chemotherapy, and use the lowest dose to avoid red blood cell transfusions. Use of the lowest dose to avoid red blood cell transfusions will also help to decrease the risk of serious cardiovascular and thromboembolic reactions; in controlled clinical trials of patients with cancer, darbepoetin alfa and other ESAs increased the risks for death and serious adverse cardiovascular reactions such as myocardial infarction or stroke. Discontinue the ESA after the completion of a chemotherapy course.

In controlled clinical trials, erythropoiesis-stimulating agents (ESAs) increased the risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and the risk of thromboembolism (deep venous thrombosis [DVT]), in patients undergoing orthopedic procedures. However, guidelines suggest it is reasonable to use ESAs with iron supplementation several days before cardiac surgery to increase red cell mass in patients who have preoperative anemia, refuse blood cell transfusion, or are deemed high-risk for postoperative anemia; studies have reported no adverse effects associated with short-term ESA pretreatment.

Aranesp

Rx

Erythropoiesis-stimulating agent
Used for the treatment of anemia due to chronic kidney disease or due to the myelosuppressive effects of chemotherapy
Associated with increased risk of death, myocardial infarction, stroke, venous thromboembolism, vascular access thrombosis, and tumor progression or recurrence

Initially, 0.45 mcg/kg subcutaneously or IV once weekly or 0.75 mcg/kg IV or subcutaneously once every 2 weeks as appropriate; the IV route is recommended for patients on hemodialysis. Initiate treatment when hemoglobin is less than 10 g/dL. If hemoglobin concentration approaches or exceeds 11 g/dL, reduce or interrupt the dose. If the hemoglobin rises more than 1 g/dL in any 2-week period, reduce the dose by 25% or more as needed to reduce rapid responses. In contrast, if the hemoglobin has not increased more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%. For patients who do not respond adequately over a 12-week escalation period, increasing the dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin concentration sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia, and discontinue darbepoetin alfa if responsiveness does not improve.

Initially, 0.45 mcg/kg IV or subcutaneously once every 4 weeks as appropriate. Consider initiating treatment only when the hemoglobin is less than 10 g/dL and the rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion and reducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal. If the hemoglobin is more than 10 g/dL, reduce or interrupt the dose, and use the lowest darbepoetin alfa dose sufficient to reduce the need for RBC transfusions. If the hemoglobin rises more than 1 g/dL in any 2-week period, reduce the dose by 25% or more as needed to reduce rapid responses. In contrast, if the hemoglobin has not increased more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%. For patients who do not respond adequately over a 12-week escalation period, increasing the dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin concentration sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia, and discontinue darbepoetin alfa if responsiveness does not improve.

Initially, 0.45 mcg/kg subcutaneously or IV once weekly; the IV route is recommended for patients on hemodialysis. Initiate treatment when hemoglobin is less than 10 g/dL. If hemoglobin concentration approaches or exceeds 12 g/dL, reduce or interrupt the dose. If the hemoglobin rises more than 1 g/dL in any 2-week period, reduce the dose by 25% or more as needed to reduce rapid responses. In contrast, if the hemoglobin has not increased more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%. For patients who do not respond adequately over a 12-week escalation period, increasing the dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin concentration sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia, and discontinue darbepoetin alfa if responsiveness does not improve.

Initially, 0.45 mcg/kg subcutaneously or IV once weekly or 0.75 mcg/kg subcutaneously or IV once every 2 weeks as appropriate. Initiate treatment when hemoglobin is less than 10 g/dL. If hemoglobin concentration approaches or exceeds 12 g/dL, reduce or interrupt the dose. If the hemoglobin rises more than 1 g/dL in any 2-week period, reduce the dose by 25% or more as needed to reduce rapid responses. In contrast, if the hemoglobin has not increased more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%. For patients who do not respond adequately over a 12-week escalation period, increasing the dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin concentration sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia, and discontinue darbepoetin alfa if responsiveness does not improve.

Estimate the starting dose of darbepoetin alfa based on the total weekly dose of epoetin alfa at the time of conversion. If the patient was receiving epoetin alfa 2 to 3 times per week, administer darbepoetin alfa once per week; if the patient was receiving epoetin alfa once per week, administer darbepoetin alfa once every 2 weeks. Maintain current route of administration (subcutaneous or IV). The following darbepoetin alfa dosage recommendations are estimates based on total amount of epoetin alfa administered per week. EPOETIN ALFA less than 2,500 Units/week: Initial darbepoetin alfa dose 6.25 mcg/week; EPOETIN ALFA 2,500 to 4,999 Units/week: Initial darbepoetin alfa dose 12.5 mcg/week; EPOETIN ALFA 5,000 to 10,999 Units/week: Initial darbepoetin alfa dose 25 mcg/week; EPOETIN ALFA 11,000 to 17,999 Units/week: Initial darbepoetin alfa dose 40 mcg/week; EPOETIN ALFA 18,000 to 33,999 Units/week: Initial darbepoetin alfa dose 60 mcg/week; EPOETIN ALFA 34,000 to 89,999 Units/week: Initial darbepoetin alfa dose 100 mcg/week; EPOETIN ALFA 90,000 Units/week or more: Initial darbepoetin alfa dose 200 mcg/week.

Estimate the starting dose of darbepoetin alfa based on the total weekly dose of epoetin alfa at the time of conversion. If the patient was receiving epoetin alfa 2 to 3 times per week, administer darbepoetin alfa once per week; if the patient was receiving epoetin alfa once per week, administer darbepoetin alfa once every 2 weeks. Maintain current route of administration (subcutaneous or IV). The following darbepoetin alfa dosage recommendations are estimates based on total amount of epoetin alfa administered per week. EPOETIN ALFA less than 1,500 Units/week: Insufficient data to determine dosage; EPOETIN ALFA 1,500 to 2,499 Units/week: Initial darbepoetin alfa dose 6.25 mcg/week; EPOETIN ALFA 2,500 to 4,999 Units/week: Initial darbepoetin alfa dose 10 mcg/week; EPOETIN ALFA 5,000 to 10,999 Units/week: Initial darbepoetin alfa dose 20 mcg/week; EPOETIN ALFA 11,000 to 17,999 Units/week: Initial darbepoetin alfa dose 40 mcg/week; EPOETIN ALFA 18,000 to 33,999 Units/week: Initial darbepoetin alfa dose 60 mcg/week; EPOETIN ALFA 34,000 to 89,999 Units/week: Initial darbepoetin alfa dose 100 mcg/week; EPOETIN ALFA 90,000 Units/week or more: Initial darbepoetin alfa dose 200 mcg/week.

Initially, 2.25 mcg/kg subcutaneously once weekly or 500 mcg subcutaneously every 3 weeks only when the hemoglobin is less than 10 g/dL and only until the chemotherapy course is completed. Adjust the dose to maintain the lowest Hgb concentration sufficient to avoid RBC transfusions. For once weekly dosing, if there is less than 1 g/dL increase in Hgb after 6 weeks AND Hgb is less than 10 g/dL, the dose may be increased to 4.5 mcg/kg once weekly. Do not increase the dose for the every 3 week dosing schedule. Discontinue if there is no response as measured by Hgb concentrations or if RBC transfusions are still required after 8 weeks of therapy. For the once weekly or every 3 weeks dosing regimens, if the Hgb exceeds a concentration needed to avoid transfusion, temporarily withhold doses until the Hgb falls to a concentration where transfusions may be required; reinitiate therapy at a dose 40% below the previous dose. If the rate of Hgb increase is more than 1 g/dL during a 2 week period OR if Hgb reaches a concentration needed to avoid RBC transfusion, reduce the dose by 40% of the previous dose. Alternatively, 200 mcg subcutaneously (approximately 3 mcg/kg) every other week† is a commonly used regimen in clinical practice. For the every other week dosing regimen, it is suggested that the dose be increased to 300 mcg subcutaneously every other week if there is a less than 1 g/dL increase in Hgb after 4 to 6 weeks. There is a dose-response relationship with respect to Hgb response. The minimally effective starting dose with respect to reducing transfusion requirements is 1.5 mcg/kg/week with a plateau observed at 4.5 mcg/kg/week. During clinical trials, the majority of patients (72% to 75%) receiving darbepoetin either once weekly or every three weeks required a reduction in dosage. In a therapeutic substitution trial that included 55 patients previously taking high doses of epoetin alfa (60,000 to 90,000 International Units), 54 of the 55 patients switched to darbepoetin alfa 200 mcg subcutaneously every other week did not require higher doses after 10 weeks.

3 mcg/kg subcutaneously or IV every 2 weeks was effective in increasing hemoglobin (Hgb) in anemic patients (n = 101) receiving pegylated interferon alpha-2b and ribavirin for chronic hepatitis C infection. The dose and frequency was titrated to achieve a target Hgb of 12 g/dL. If Hgb increased by more than 1 g/dL in a 2-week period, the dose was decreased by 25%. If an increase in Hgb was less than 1 g/dL after 4 weeks and iron stores were adequate, the dose was increased by 25%. If the Hgb was increasing and approaching 12 g/dL, the dose of was decreased by 25%. If Hgb exceeded 12 g/dL, darbepoetin was temporarily held until Hgb was 12 g/dL or less, and was then reinitiated at a dose 25% below the previous dose. At study initiation, baseline Hgb was 10.2 +/- 0.4 g/dL. After 81 days of therapy, Hgb increased by 1.9 +/- 1 g/dL to 12.1 +/- 1.1 g/dL (p less than 0.0001). NOTE: In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin concentration more than 11 g/dL. No trial has identified a hemoglobin target concentration, ESA dose, or dosing strategy that does not increase these risks. Individualize dosing and use the lowest dose sufficient to reduce the need for RBC transfusions. Weigh the possible benefits of decreasing transfusions against the increased risks of death and other serious cardiovascular adverse events.

10 mcg/kg/dose subcutaneously once weekly based on limited data. In a study of 102 premature neonates, 33 of whom received darbepoetin alfa (gestational age 27.9 +/- 1.8 weeks), first doses were given at 46 +/- 27 hours of age and dosing continued until 35 completed weeks gestation or discharge. All neonates also received supplemental iron, folate, and vitamin E and were transfused according to a standardized, restrictive transfusion protocol. Treatment groups (darbepoetin alfa or erythropoietin) received fewer transfusions compared to placebo, and there was no significant difference between treatment groups. In supplementary studies, additional short- and long-term benefits such as reduced rates of necrotizing enterocolitis, intraventricular hemorrhage, and periventricular leukomalacia and improved neurodevelopmental outcomes have been reported with early erythropoiesis-stimulating treatments.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Androgens: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to darbepoetin alfa, reducing the amount required to treat anemia.
Danazol: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to darbepoetin alfa, reducing the amount required to treat anemia.
Esterified Estrogens; Methyltestosterone: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to darbepoetin alfa, reducing the amount required to treat anemia.
Lenalidomide: (Moderate) Concomitant use of lenalidomide with erythropoietic agents such as darbepoetin alfa may increase the risk of thrombosis in patients with multiple myeloma patients who are also receiving dexamethasone. Monitor for signs of thromboembolism (e.g., deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) and encourage patients to report symptoms such as shortness of breath, chest pain, or arm or leg swelling.
Methyltestosterone: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to darbepoetin alfa, reducing the amount required to treat anemia.
Oxandrolone: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to darbepoetin alfa, reducing the amount required to treat anemia.
Oxymetholone: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to darbepoetin alfa, reducing the amount required to treat anemia.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to darbepoetin alfa, reducing the amount required to treat anemia.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to darbepoetin alfa, reducing the amount required to treat anemia.
Testosterone: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to darbepoetin alfa, reducing the amount required to treat anemia.
Thalidomide: (Moderate) Thalidomide and darbepoetin alfa should be used cautiously due an increased risk of thromboembolism.

Aranesp Intravenous Inj Sol: 0.3mL, 0.4mL, 0.42mL, 0.5mL, 0.6mL, 0.75mL, 1mL, 10mcg, 25mcg, 40mcg, 60mcg, 100mcg, 150mcg, 200mcg, 300mcg, 500mcg
Aranesp Subcutaneous Inj Sol: 0.3mL, 0.4mL, 0.42mL, 0.5mL, 0.6mL, 0.75mL, 1mL, 10mcg, 25mcg, 40mcg, 60mcg, 100mcg, 150mcg, 200mcg, 300mcg, 500mcg

Varies depending on indication, frequency of administration, and individual response.

Varies depending on indication, frequency of administration, and individual response.

Varies depending on indication, frequency of administration, and individual response.

Varies depending on indication, frequency of administration, and individual response.

Varies depending on indication, frequency of administration, and individual response.

Neonates: Safety and efficacy have not been established.
Premature Neonates: Safety and efficacy have not been established; however, 10 mcg/kg/dose subcutaneously once weekly has been used off-label for anemia of prematurity.

Darbepoetin alfa stimulates erythropoiesis by the same mechanism as endogenous erythropoietin (EPO).[31724] EPO is a glycoprotein that regulates the production of red blood cells by stimulating the division and differentiation of committed erythroid progenitor cells in the bone marrow. In adults, almost 90% of EPO is produced in the kidney with the remainder produced by the liver. During fetal development, EPO is produced in the liver, and prior to birth, at term, production is transferred to the kidney. EPO production in the kidney occurs in interstitial cells in the inner cortex that are in immediate proximity to the proximal tubules. Cells are activated to produce EPO as the hematocrit drops. Renal tubular cells may serve as oxygen sensors transmitting signals to the interstitial cells, possibly because they contain large amounts of heme protein that may function as an intracellular oxygen sensor and transducer.[23683]
 
EPO is required for the transformation of the most mature erythroid progenitor cell, erythroid colony-forming unit (CFU-E), to a proerythroblast. In the absence of EPO, this transformation cannot occur, and the CFU-E will die. EPO activates the synthesis of hemoglobin and other proteins found in normal erythroblasts. EPO also causes a shift of marrow reticulocytes into the circulation. Due to the length of time required for erythropoiesis, a clinically significant increase in hematocrit is usually not observed in less than 2 weeks and may take up to 6 weeks in some patients. EPO has little effect on early erythroid progenitor cells, erythroid burst-forming units (BFU-E), whose growth is more dependent upon interleukin-3 and granulocyte-macrophage colony stimulating factor (GM-CSF). The production and activity of EPO are linked in a negative feedback loop, which maintains optimal red cell mass for oxygen transport. Darbepoetin alfa produces a dose-dependent increase in hemoglobin. The stimulation of erythropoiesis increases the demand for iron, making iron supplementation necessary for many patients.[23683] [31724]

Darbepoetin alfa is administered intravenously or subcutaneously. A dose-dependent response is seen with darbepoetin alfa doses of 0.45 mcg/kg once weekly. Other factors affecting response to therapy include iron stores, baseline hemoglobin, and concurrent medical conditions. As with the endogenous erythropoietin (EPO), darbepoetin alfa does not appear extravascularly in humans. Whether the drug crosses the placenta or is distributed into breast milk has not been evaluated. Metabolism and elimination of endogenous EPO or darbepoetin alfa are not fully understood. While the glycosylation of EPO does not affect its binding to target cells, it plays an important role in preventing the rapid clearance of the hormone from the bloodstream. Non-glycosylated erythropoietin has a half-life of a few minutes. About 10% of the dose appears to be excreted in the urine.
 
Affected cytochrome P450 enzymes and drug transporters: None

The half-life of darbepoetin alfa in adults with chronic kidney disease (CKD) after IV administration is 21 hours; the half-life in pediatric patients with CKD after IV administration is similar. Although the IV route gives a more rapid peak, the delayed systemic absorption from the subcutaneous route of darbepoetin alfa gives a more sustained response. The serum half-life after IV administration is 22.1 hours.

The bioavailability of darbepoetin alfa in adult patients with chronic kidney disease (CKD) after subcutaneous administration is 37% (range: 30% to 50%); a higher bioavailability has been noted in pediatric patients with CKD after subcutaneous administration. The subcutaneous route produces peak plasma concentrations 48 hours (range: 12 to 72 hours) after administration in adult patients with CKD (receiving or not receiving dialysis). Although the IV route gives a more rapid peak, the delayed systemic absorption from the subcutaneous route of darbepoetin alfa gives a more sustained response. The half-life is 46 hours (range: 12 to 89 hours) in adult CKD patients receiving dialysis and 70 hours (35 to 139 hours) in adult CKD patients not receiving dialysis. The clearance is approximately 1.4 times faster in adult patients receiving dialysis, compared to those not receiving dialysis. In adults with cancer, peak plasma concentrations occur at 71 hours (range: 28 to 120 hours) after a subcutaneous dose of 6.75 mg/kg. The half-life in adult cancer patients is 74 hours (range: 24 to 144 hours).

Consider the benefits and risks of darbepoetin alfa for the mother and possible risks to the fetus when prescribing darbepoetin alfa during pregnancy. The limited available data on darbepoetin alfa use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. In animal studies, early post-implantation loss occurred when pregnant rats received darbepoetin alfa at doses approximating the clinical recommended starting doses.[31724]

It is not known if darbepoetin alfa is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.[31724]