Retacrit 20000uni Inj, 1ml
WARNING: This drug may raise the chance of heart attack, stroke, heart failure, blood clots, and death. Talk with the doctor.People with some types of cancer have died sooner when using this drug. This drug also raised the chance of tumor growth and the tumor happening again in these people. Talk with the doctor.Your doctor will need to watch your blood cell counts and follow you closely to change the dose to match your body's needs. Talk with your doctor.If you will be having surgery, talk with your doctor. You may need to take another drug to keep you from getting blood clots while you get this drug. @ COMMON USES: It is used to treat anemia.It is used to help lower the need for blood transfusions for certain surgeries.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Hematopoietic Agent; Erythropoiesis-Stimulating Agent (ESA)
Pharmacologic Class
Recombinant Human Erythropoietin
Pregnancy Category
Category C
FDA Approved
Jun 2018
DEA Schedule
Not Controlled
Overview
What is this medicine?
Retacrit is a medicine that helps your body make more red blood cells. It's like a natural substance your body makes, called erythropoietin, which tells your bone marrow to produce red blood cells. This helps treat anemia (low red blood cell count) in certain conditions, like kidney disease or cancer chemotherapy, reducing the need for blood transfusions.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue under the skin or into a vein by a healthcare professional.
Self-Administration
If you are giving yourself the injection, your doctor or nurse will instruct you on the proper technique. It is essential to follow their guidance to ensure safe and effective use.
Important Handling Instructions
- Do not shake the medication.
- Do not use the medication if it has been shaken.
- Wash your hands before and after handling the medication.
- Inspect the solution before use; do not use it if it appears cloudy, is leaking, contains particles, or has changed color.
- Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
Disposal of Used Needles and Supplies
Dispose of used needles and other sharp objects in a designated needle/sharp disposal box. Never reuse needles or other items. Once the disposal box is full, follow local regulations for its proper disposal.
Storage and Disposal
For information on how to store and dispose of this medication, refer to the specific product instructions.
Missing a Dose
If you miss a dose, contact your doctor to determine the best course of action.
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue under the skin or into a vein by a healthcare professional.
Self-Administration
If you are giving yourself the injection, your doctor or nurse will instruct you on the proper technique. It is essential to follow their guidance to ensure safe and effective use.
Important Handling Instructions
- Do not shake the medication.
- Do not use the medication if it has been shaken.
- Wash your hands before and after handling the medication.
- Inspect the solution before use; do not use it if it appears cloudy, is leaking, contains particles, or has changed color.
- Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
Disposal of Used Needles and Supplies
Dispose of used needles and other sharp objects in a designated needle/sharp disposal box. Never reuse needles or other items. Once the disposal box is full, follow local regulations for its proper disposal.
Storage and Disposal
For information on how to store and dispose of this medication, refer to the specific product instructions.
Missing a Dose
If you miss a dose, contact your doctor to determine the best course of action.
Lifestyle & Tips
- Maintain adequate iron intake, as iron is crucial for red blood cell production. Your doctor may prescribe iron supplements.
- Monitor your blood pressure regularly at home, as this medication can cause or worsen high blood pressure.
- Report any unusual symptoms immediately, especially signs of blood clots (e.g., chest pain, shortness of breath, swelling/pain in legs, sudden weakness or numbness).
- Keep all appointments for blood tests and doctor visits to monitor your response and check for side effects.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Highly variable based on indication and patient response. Dosing is individualized to achieve and maintain target hemoglobin levels.
Condition-Specific Dosing:
Anemia of Chronic Kidney Disease (CKD) - IV or SC:
Initial: 50-100 units/kg 3 times per week OR 10,000 units once weekly. Titrate dose to maintain hemoglobin between 10-11 g/dL. Maximize iron stores before and during treatment.
Anemia due to Chemotherapy in Cancer Patients - SC:
Initial: 150 units/kg 3 times per week OR 40,000 units once weekly. Discontinue if no response after 8 weeks. Do not exceed 12 g/dL hemoglobin.
Anemia in Zidovudine-treated HIV-infected Patients - SC or IV:
Initial: 100 units/kg 3 times per week. Titrate dose based on response. Only for patients with endogenous erythropoietin levels ≤ 500 mUnits/mL.
Reduction of Allogeneic Red Blood Cell Transfusions in Surgery Patients - SC:
300 units/kg/day for 10 days (5 days pre-surgery, day of surgery, 4 days post-surgery) OR 600 units/kg once weekly (3 weeks pre-surgery, day of surgery).
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Anemia of Chronic Kidney Disease (CKD): Initial 50 units/kg 3 times per week (IV or SC). Titrate to maintain hemoglobin between 10-12 g/dL.
Adolescent:
Anemia of Chronic Kidney Disease (CKD): Initial 50 units/kg 3 times per week (IV or SC). Titrate to maintain hemoglobin between 10-12 g/dL.
Dose Adjustments
Renal Impairment:
Mild:
No specific adjustment needed; primary indication is CKD-related anemia, so dosing is inherently adjusted based on response.
Moderate:
No specific adjustment needed; primary indication is CKD-related anemia, so dosing is inherently adjusted based on response.
Severe:
No specific adjustment needed; primary indication is CKD-related anemia, so dosing is inherently adjusted based on response.
Dialysis:
Dosing for CKD patients on dialysis is similar to non-dialysis CKD patients, with careful monitoring of hemoglobin and iron status. IV administration is often preferred in dialysis patients.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended.
Moderate:
No specific dose adjustment recommended.
Severe:
No specific dose adjustment recommended; use with caution due to potential for altered pharmacokinetics, though not extensively studied.
Pharmacology
Mechanism of Action
Epoetin alfa-epbx is a biosimilar to epoetin alfa, which is a recombinant human erythropoietin. It stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. It binds to erythropoietin receptors on the surface of erythroid progenitor cells in the bone marrow, stimulating their proliferation, differentiation, and maturation into red blood cells. This process leads to an increase in red blood cell mass and hemoglobin levels.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous: 30-40% (range 20-50%)
Tmax:
Subcutaneous: 5-24 hours
FoodEffect:
Not applicable (parenteral administration)
Distribution:
Vd:
Approximately 4-10 L (similar to plasma volume)
ProteinBinding:
Not extensively protein bound
CnssPenetration:
Limited
Elimination:
HalfLife:
Intravenous: 4-13 hours; Subcutaneous: 13-28 hours
Clearance:
Variable, depends on route of administration and patient population.
ExcretionRoute:
Primarily non-renal clearance via cellular uptake and degradation; minor renal excretion of intact drug.
Unchanged:
<10% (renal excretion)
Pharmacodynamics
OnsetOfAction:
Increase in reticulocyte count typically seen within 7-10 days; increase in hemoglobin usually within 2-6 weeks.
PeakEffect:
Peak hemoglobin response typically observed 2-6 weeks after initiation of therapy or dose adjustment.
DurationOfAction:
Effects on erythropoiesis persist for several days after discontinuation due to the lifespan of red blood cells.
Safety & Warnings
BLACK BOX WARNING
ESAs increase the risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access. In patients with cancer, ESAs may increase the risk of tumor progression or recurrence. To decrease these risks, use the lowest dose necessary to avoid red blood cell transfusions. For patients with chronic kidney disease (CKD), do not exceed a hemoglobin level of 11 g/dL. For patients with cancer, use ESAs only for anemia due to myelosuppressive chemotherapy, and discontinue after completion of a chemotherapy course. For patients undergoing surgery, use ESAs only for patients at high risk for blood loss and who cannot donate autologous blood.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of high blood pressure: severe headache, dizziness, fainting, or changes in vision
Signs of high blood sugar: confusion, drowsiness, excessive thirst or hunger, frequent urination, flushing, rapid breathing, or fruity-smelling breath
Signs of low potassium levels: muscle pain or weakness, muscle cramps, or an irregular heartbeat
Rapid heartbeat
Shortness of breath, significant weight gain, or swelling in the arms or legs
Weakness on one side of the body, difficulty speaking or thinking, balance problems, drooping on one side of the face, or blurred vision
Confusion
Cool or pale arm or leg
Difficulty walking
Dizziness or fainting
Excessive sweating
Seizures
Feeling extremely tired or weak
Pale skin
Depression
If you experience any of the following symptoms, call your doctor immediately, as they may indicate a blood clot:
Chest pain or pressure
Coughing up blood
Shortness of breath
Swelling, warmth, numbness, color change, or pain in a leg or arm
Difficulty speaking or swallowing
In rare cases, a severe skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may occur, which can cause serious health problems and even death. Seek medical help right away if you notice:
Red, swollen, blistered, or peeling skin (with or without fever)
Red or irritated eyes
Sores in your mouth, throat, nose, or eyes
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or persist, contact your doctor:
Irritation at the injection site
Fever or chills
Headache
Upset stomach or vomiting
Cough
Bone, joint, or muscle pain
Muscle spasms
Mouth irritation or mouth sores
Weight loss
Difficulty sleeping
* Common cold symptoms
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of high blood pressure: severe headache, dizziness, fainting, or changes in vision
Signs of high blood sugar: confusion, drowsiness, excessive thirst or hunger, frequent urination, flushing, rapid breathing, or fruity-smelling breath
Signs of low potassium levels: muscle pain or weakness, muscle cramps, or an irregular heartbeat
Rapid heartbeat
Shortness of breath, significant weight gain, or swelling in the arms or legs
Weakness on one side of the body, difficulty speaking or thinking, balance problems, drooping on one side of the face, or blurred vision
Confusion
Cool or pale arm or leg
Difficulty walking
Dizziness or fainting
Excessive sweating
Seizures
Feeling extremely tired or weak
Pale skin
Depression
If you experience any of the following symptoms, call your doctor immediately, as they may indicate a blood clot:
Chest pain or pressure
Coughing up blood
Shortness of breath
Swelling, warmth, numbness, color change, or pain in a leg or arm
Difficulty speaking or swallowing
In rare cases, a severe skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may occur, which can cause serious health problems and even death. Seek medical help right away if you notice:
Red, swollen, blistered, or peeling skin (with or without fever)
Red or irritated eyes
Sores in your mouth, throat, nose, or eyes
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or persist, contact your doctor:
Irritation at the injection site
Fever or chills
Headache
Upset stomach or vomiting
Cough
Bone, joint, or muscle pain
Muscle spasms
Mouth irritation or mouth sores
Weight loss
Difficulty sleeping
* Common cold symptoms
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Sudden chest pain or shortness of breath
- Pain, swelling, warmth, or redness in an arm or leg (signs of a blood clot)
- Sudden numbness or weakness, especially on one side of the body
- Sudden severe headache, confusion, or problems with vision or speech (signs of stroke)
- Uncontrolled high blood pressure (severe headache, blurred vision)
- Seizures
- Severe allergic reactions (rash, itching, swelling of face/tongue/throat, severe dizziness, trouble breathing)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following conditions before starting this medication:
Any allergies you have, including allergies to this drug, its components, or other substances, and describe the symptoms you experienced.
If you have high blood pressure.
If you have active bleeding.
If you have low levels of vitamins or minerals.
If you have a condition called Pure Red Cell Aplasia (PRCA), a type of anemia.
Additionally, if you are using a multi-dose container, tell your doctor:
If you are pregnant or think you might be pregnant. This medication is not recommended during pregnancy.
If you are breastfeeding. You should not breastfeed while taking this medication and for 2 weeks after your last dose.
If the patient is a premature baby or newborn. This form of the medication should not be given to premature babies or newborns.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without consulting your doctor.
It is essential to inform your doctor about the following conditions before starting this medication:
Any allergies you have, including allergies to this drug, its components, or other substances, and describe the symptoms you experienced.
If you have high blood pressure.
If you have active bleeding.
If you have low levels of vitamins or minerals.
If you have a condition called Pure Red Cell Aplasia (PRCA), a type of anemia.
Additionally, if you are using a multi-dose container, tell your doctor:
If you are pregnant or think you might be pregnant. This medication is not recommended during pregnancy.
If you are breastfeeding. You should not breastfeed while taking this medication and for 2 weeks after your last dose.
If the patient is a premature baby or newborn. This form of the medication should not be given to premature babies or newborns.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without consulting your doctor.
Precautions & Cautions
Important Information About Your Medication
It is crucial that you inform all of your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Monitoring Your Health
You will need to have your blood pressure checked regularly, as directed by your doctor, because this medication can cause high blood pressure. Additionally, your doctor will instruct you on when to have blood work done to monitor your health.
Special Considerations
If you have phenylketonuria (PKU), it is essential to discuss this with your doctor, as some products contain phenylalanine.
Safe Use of Your Medication
Do not exceed the dosage prescribed by your doctor, as taking more than the recommended amount can increase the risk of severe side effects. If you accidentally take more of this medication than directed, contact your doctor immediately.
Understanding the Effects of Your Medication
This medication can increase the production of red blood cells in your blood. It is important to be aware that misuse or abuse of this type of medication can lead to serious health issues, including stroke, heart attack, and blood clots. If you have any questions or concerns, discuss them with your doctor.
Multi-Dose Container Precautions
This medication contains benzyl alcohol. If possible, it is recommended to avoid using products with benzyl alcohol in newborns or infants, as serious side effects can occur in these children, especially when combined with other medications containing benzyl alcohol. If you have questions, consult with your doctor.
Single-Dose Container Considerations
If you are pregnant, planning to become pregnant, or are breastfeeding, inform your doctor. You and your doctor will need to discuss the potential benefits and risks of this medication to both you and your baby.
It is crucial that you inform all of your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Monitoring Your Health
You will need to have your blood pressure checked regularly, as directed by your doctor, because this medication can cause high blood pressure. Additionally, your doctor will instruct you on when to have blood work done to monitor your health.
Special Considerations
If you have phenylketonuria (PKU), it is essential to discuss this with your doctor, as some products contain phenylalanine.
Safe Use of Your Medication
Do not exceed the dosage prescribed by your doctor, as taking more than the recommended amount can increase the risk of severe side effects. If you accidentally take more of this medication than directed, contact your doctor immediately.
Understanding the Effects of Your Medication
This medication can increase the production of red blood cells in your blood. It is important to be aware that misuse or abuse of this type of medication can lead to serious health issues, including stroke, heart attack, and blood clots. If you have any questions or concerns, discuss them with your doctor.
Multi-Dose Container Precautions
This medication contains benzyl alcohol. If possible, it is recommended to avoid using products with benzyl alcohol in newborns or infants, as serious side effects can occur in these children, especially when combined with other medications containing benzyl alcohol. If you have questions, consult with your doctor.
Single-Dose Container Considerations
If you are pregnant, planning to become pregnant, or are breastfeeding, inform your doctor. You and your doctor will need to discuss the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Polycythemia (excessively high red blood cell count), which can lead to increased blood viscosity and risk of thrombotic events (e.g., stroke, heart attack, blood clots).
What to Do:
In case of suspected overdose, contact a poison control center or emergency room immediately. Treatment is supportive, focusing on managing symptoms and reducing blood viscosity (e.g., phlebotomy if severe polycythemia occurs). Call 1-800-222-1222.
Drug Interactions
Moderate Interactions
- Androgens (e.g., testosterone): May enhance the erythropoietic effect of epoetin alfa, potentially requiring lower epoetin alfa doses.
- Iron supplements: Essential for optimal response to epoetin alfa; inadequate iron stores will limit efficacy.
Monitoring
Baseline Monitoring
Hemoglobin (Hgb) and Hematocrit (Hct)
Rationale: To establish baseline anemia severity and guide initial dosing.
Timing: Prior to initiation of therapy.
Iron Status (Serum Ferritin, Transferrin Saturation [TSAT])
Rationale: Adequate iron stores are essential for optimal response to epoetin alfa. Iron deficiency will blunt response.
Timing: Prior to initiation of therapy.
Blood Pressure
Rationale: To establish baseline and identify pre-existing hypertension, which can be exacerbated by epoetin alfa.
Timing: Prior to initiation of therapy.
Complete Blood Count (CBC) with differential and platelet count
Rationale: To rule out other causes of anemia and assess overall hematologic status.
Timing: Prior to initiation of therapy.
Routine Monitoring
Hemoglobin (Hgb)
Frequency: Weekly or bi-weekly until stable, then monthly or as clinically indicated.
Target: CKD: 10-11 g/dL; Chemotherapy: Do not exceed 12 g/dL.
Action Threshold: If Hgb rises rapidly (>1 g/dL in 2 weeks) or exceeds target range, reduce or interrupt dose. If Hgb does not increase after 8 weeks of therapy, discontinue.
Blood Pressure
Frequency: Regularly, especially during the initial phase of therapy and with dose adjustments.
Target: Individualized, maintain within patient's normal range.
Action Threshold: If significant increase or uncontrolled hypertension develops, manage aggressively and consider dose reduction or interruption.
Iron Status (Serum Ferritin, TSAT)
Frequency: Monthly or every 3 months, or as clinically indicated.
Target: Ferritin >100 ng/mL (CKD) or >200 ng/mL (dialysis); TSAT >20%.
Action Threshold: If iron stores are low, initiate or increase iron supplementation.
Signs and Symptoms of Thrombotic Events
Frequency: Continuously throughout therapy.
Target: Absence of symptoms.
Action Threshold: Promptly evaluate any new onset of chest pain, shortness of breath, leg pain/swelling, or neurological changes.
Symptom Monitoring
- Headache
- Fatigue
- Dizziness
- Shortness of breath
- Chest pain
- Swelling in legs or arms
- Numbness or weakness on one side of the body
- Vision changes
- Speech difficulties
- Seizures
- Skin rash or itching at injection site
Special Patient Groups
Pregnancy
Category C. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Epoetin alfa has been shown to have adverse effects in animal reproduction studies.
Trimester-Specific Risks:
First Trimester:
Potential for adverse developmental effects observed in animal studies at high doses.
Second Trimester:
Potential for adverse developmental effects observed in animal studies at high doses.
Third Trimester:
Potential for adverse developmental effects observed in animal studies at high doses.
Lactation
It is not known whether epoetin alfa-epbx is excreted in human milk. Endogenous erythropoietin is present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Retacrit and any potential adverse effects on the breastfed child from Retacrit or from the underlying maternal condition. Generally considered L3 (Moderately safe) based on low oral bioavailability and large molecular weight.
Infant Risk:
Low risk, but monitor for potential adverse effects.
Pediatric Use
Safety and efficacy have been established in pediatric patients with CKD-related anemia. Dosing is weight-based. Safety and efficacy in other pediatric populations (e.g., chemotherapy-induced anemia) have not been fully established.
Geriatric Use
No overall differences in safety or effectiveness have been observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may be at increased risk for cardiovascular events and thrombotic events, requiring careful monitoring.
Clinical Information
Clinical Pearls
- Always ensure adequate iron stores (ferritin >100 ng/mL, TSAT >20%) before and during epoetin alfa-epbx therapy, as iron deficiency is the most common cause of treatment failure.
- Monitor hemoglobin levels closely (weekly/bi-weekly initially) to avoid rapid increases or exceeding target ranges, which are associated with increased cardiovascular and thrombotic risks.
- Aggressively manage hypertension, as epoetin alfa-epbx can cause or worsen high blood pressure. Blood pressure should be well-controlled before initiating therapy.
- Educate patients on the signs and symptoms of thrombotic events (e.g., DVT, PE, stroke, MI) and the importance of immediate medical attention if they occur.
- Retacrit is a biosimilar to Epogen/Procrit. It is not interchangeable with other ESAs without prescriber approval and patient education.
- For patients with cancer, use only for anemia due to myelosuppressive chemotherapy, and discontinue after completion of a chemotherapy course. Do not use in patients with myeloid malignancies.
Alternative Therapies
- Other Erythropoiesis-Stimulating Agents (ESAs): Darbepoetin alfa (Aranesp), Methoxy polyethylene glycol-epoetin beta (Mircera).
- Red Blood Cell Transfusions: For immediate correction of severe anemia or when ESAs are contraindicated/ineffective.
- Iron supplementation (oral or IV): Essential adjunctive therapy for most patients receiving ESAs.
- Correction of underlying causes of anemia (e.g., vitamin deficiencies, bleeding).
Cost & Coverage
Average Cost:
Highly variable, typically several hundred to over a thousand USD per 20,000 unit vial depending on supplier and contract. per 20,000 unit vial
Insurance Coverage:
Often covered under Medicare Part B (for CKD) or Part D (for other indications), and commercial plans, but may require prior authorization and be subject to step therapy. Often Tier 3 or 4.
General Drug Facts
If your symptoms or health issues persist or worsen, contact your doctor promptly. It's essential to keep your medication to yourself and not take anyone else's prescription. This medication is accompanied by a Medication Guide, which provides crucial information. Please read it carefully and review it again whenever you refill your prescription. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. Be prepared to provide details about the overdose, including the substance taken, the amount, and the time it occurred.