Carbidopa/lev/entac 18.75-75-200mg
It is used to treat Parkinson's disease.
Drug Class
Antiparkinsonian agent
Pharmacologic Class
Dopamine precursor; DOPA decarboxylase inhibitor; Catechol-O-methyltransferase (COMT) inhibitor
Pregnancy Category
Category C
FDA Approved
Apr 2003
DEA Schedule
Not Controlled
Overview
What is this medicine?
This medication combines three drugs to help manage Parkinson's disease symptoms, especially 'wearing-off' periods. Levodopa turns into dopamine in your brain to help control movement. Carbidopa helps more levodopa get to your brain and reduces side effects. Entacapone helps levodopa last longer in your body.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. You can take this medication with or without food. Swallow the tablet whole - do not chew, break, or crush it.
If you take an iron supplement or a multivitamin that contains iron, consult your doctor or pharmacist about how to take it in relation to this medication. Iron may reduce the absorption of this medication in your body.
Your diet can also affect how well your body absorbs this medication. Diets high in protein, fat, or calories, as well as eating acidic foods, may reduce absorption. Discuss your diet with your doctor, especially if you plan to make any changes.
Do not stop taking this medication suddenly without consulting your doctor, as this may increase your risk of side effects. If you need to stop taking this medication, your doctor will instruct you on how to taper off gradually.
Continue taking this medication even when you are not experiencing symptoms. Keeping a diary of your symptoms can be helpful. Take this medication at the same time every day, as directed by your doctor or healthcare provider, even if you feel well.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom. Keep all medications out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about disposing of your medication, consult your pharmacist. You may also want to check if there are any drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. You can take this medication with or without food. Swallow the tablet whole - do not chew, break, or crush it.
If you take an iron supplement or a multivitamin that contains iron, consult your doctor or pharmacist about how to take it in relation to this medication. Iron may reduce the absorption of this medication in your body.
Your diet can also affect how well your body absorbs this medication. Diets high in protein, fat, or calories, as well as eating acidic foods, may reduce absorption. Discuss your diet with your doctor, especially if you plan to make any changes.
Do not stop taking this medication suddenly without consulting your doctor, as this may increase your risk of side effects. If you need to stop taking this medication, your doctor will instruct you on how to taper off gradually.
Continue taking this medication even when you are not experiencing symptoms. Keeping a diary of your symptoms can be helpful. Take this medication at the same time every day, as directed by your doctor or healthcare provider, even if you feel well.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom. Keep all medications out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about disposing of your medication, consult your pharmacist. You may also want to check if there are any drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Take exactly as prescribed. Do not stop taking it suddenly without consulting your doctor, as this can lead to serious withdrawal symptoms.
- You can take it with or without food. However, high-protein meals may reduce the absorption of levodopa, so discuss meal timing with your doctor.
- Be aware of potential dizziness or lightheadedness, especially when standing up quickly (orthostatic hypotension). Rise slowly from a sitting or lying position.
- Avoid driving or operating machinery if you experience drowsiness or sudden sleep episodes.
- Your urine, sweat, or saliva may turn reddish-brown or dark, which is a harmless effect of entacapone.
- Report any new or worsening involuntary movements (dyskinesias) or changes in mood/behavior (e.g., hallucinations, compulsive behaviors) to your doctor.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Individualized, based on levodopa requirements. For 18.75-75-200mg strength, typically 1 tablet taken orally with or without food, up to 8 times daily. Dosing interval should be at least 2 hours.
Condition-Specific Dosing:
Initial Therapy:
Not recommended for initial therapy of Parkinson's disease. Should be used in patients already on carbidopa/levodopa who experience 'wearing-off' phenomena.
Maximum Daily Dose:
Maximum daily dose of entacapone is 1600 mg (equivalent to 8 tablets of 18.75-75-200mg strength).
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended.
Moderate:
No specific dose adjustment recommended.
Severe:
Use with caution. No specific dose adjustment recommended, but monitor for adverse effects.
Dialysis:
Not well studied. Use with caution. Levodopa and entacapone are highly protein bound and not significantly removed by dialysis.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended.
Moderate:
Use with caution. Consider dose reduction, especially for entacapone, as its clearance is reduced.
Severe:
Use with caution. Consider significant dose reduction or avoidance. Monitor for adverse effects.
Pharmacology
Mechanism of Action
Levodopa, a precursor of dopamine, crosses the blood-brain barrier and is converted to dopamine in the brain. Carbidopa, a peripheral DOPA decarboxylase inhibitor, prevents the peripheral conversion of levodopa to dopamine, increasing the amount of levodopa available to the brain and reducing peripheral side effects. Entacapone, a reversible and selective catechol-O-methyltransferase (COMT) inhibitor, prevents the peripheral breakdown of levodopa by COMT, prolonging the half-life of levodopa and increasing its bioavailability to the brain.
Pharmacokinetics
Absorption:
Bioavailability:
Levodopa: ~30% (when given with carbidopa); Carbidopa: ~50%; Entacapone: ~35%
Tmax:
Levodopa: 0.5-2 hours; Carbidopa: 1-2 hours; Entacapone: 1 hour
FoodEffect:
High-protein meals can reduce the absorption of levodopa. Entacapone absorption is not significantly affected by food.
Distribution:
Vd:
Levodopa: 0.9-1.6 L/kg; Carbidopa: 1.1 L/kg; Entacapone: 0.27 L/kg (at steady state)
ProteinBinding:
Levodopa: Not significantly protein bound; Carbidopa: ~36%; Entacapone: >98% (primarily to albumin)
CnssPenetration:
Levodopa: Yes; Carbidopa: Limited; Entacapone: Limited
Elimination:
HalfLife:
Levodopa: ~1.5 hours (with carbidopa); Carbidopa: ~2 hours; Entacapone: 0.4-0.7 hours (initial), 2.4 hours (terminal)
Clearance:
Levodopa: 0.3-0.8 L/kg/hr; Carbidopa: Not available; Entacapone: 0.7 L/kg/hr
ExcretionRoute:
Levodopa: Urine (metabolites); Carbidopa: Urine (unchanged and metabolites); Entacapone: Feces (90-95%), Urine (10-20%)
Unchanged:
Levodopa: <1% (urine); Carbidopa: ~30% (urine); Entacapone: <0.2% (urine)
Pharmacodynamics
OnsetOfAction:
Variable, typically within 30-60 minutes for levodopa effect
PeakEffect:
Variable, typically 1-2 hours after dose
DurationOfAction:
Variable, typically 2-4 hours, prolonged by entacapone
Safety & Warnings
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 immediately or seek emergency medical attention:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
New or worsening behavior or mood changes, including:
+ Depression
+ Thoughts of suicide
Hallucinations (seeing or hearing things that are not there)
Severe dizziness or fainting
Confusion
Vomiting blood or coffee ground-like material
Black, tarry, or bloody stools
Muscle pain or weakness, dark urine, or difficulty urinating
A new skin lump or growth
Changes in the color or size of a mole
Strong, uncontrollable urges (such as eating, gambling, sex, or spending money)
New or worsening trouble controlling body movements
Chest pain or pressure
Shortness of breath
Fever, chills, or sore throat
Unexplained bruising or bleeding
Feeling extremely tired or weak
Sudden, unexplained sleepiness, especially during activities like driving, eating, or talking
If you experience sudden sleepiness, do not drive or engage in activities that require alertness. Contact your doctor immediately.
Neuroleptic Malignant Syndrome (NMS)
NMS is a rare but potentially life-threatening condition that can occur when this medication is stopped suddenly or when the dose is lowered. If you experience any of the following symptoms, contact your doctor immediately:
Fever
Muscle cramps or stiffness
Dizziness
Severe headache
Confusion
Changes in thinking or behavior
Fast or irregular heartbeat
Excessive sweating
Other Possible Side Effects
Most people do not experience severe side effects, but some may occur. If you notice any of the following symptoms, contact your doctor if they bother you or do not go away:
Dizziness, drowsiness, tiredness, or weakness
Constipation, diarrhea, stomach pain, upset stomach, or vomiting
Dry mouth
Headache
Trouble sleeping
Back pain
This is not a comprehensive list of all possible side effects. If you have questions or concerns about side effects, contact 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 immediately or seek emergency medical attention:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
New or worsening behavior or mood changes, including:
+ Depression
+ Thoughts of suicide
Hallucinations (seeing or hearing things that are not there)
Severe dizziness or fainting
Confusion
Vomiting blood or coffee ground-like material
Black, tarry, or bloody stools
Muscle pain or weakness, dark urine, or difficulty urinating
A new skin lump or growth
Changes in the color or size of a mole
Strong, uncontrollable urges (such as eating, gambling, sex, or spending money)
New or worsening trouble controlling body movements
Chest pain or pressure
Shortness of breath
Fever, chills, or sore throat
Unexplained bruising or bleeding
Feeling extremely tired or weak
Sudden, unexplained sleepiness, especially during activities like driving, eating, or talking
If you experience sudden sleepiness, do not drive or engage in activities that require alertness. Contact your doctor immediately.
Neuroleptic Malignant Syndrome (NMS)
NMS is a rare but potentially life-threatening condition that can occur when this medication is stopped suddenly or when the dose is lowered. If you experience any of the following symptoms, contact your doctor immediately:
Fever
Muscle cramps or stiffness
Dizziness
Severe headache
Confusion
Changes in thinking or behavior
Fast or irregular heartbeat
Excessive sweating
Other Possible Side Effects
Most people do not experience severe side effects, but some may occur. If you notice any of the following symptoms, contact your doctor if they bother you or do not go away:
Dizziness, drowsiness, tiredness, or weakness
Constipation, diarrhea, stomach pain, upset stomach, or vomiting
Dry mouth
Headache
Trouble sleeping
Back pain
This is not a comprehensive list of all possible side effects. If you have questions or concerns about side effects, contact 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:
- Severe or persistent diarrhea
- Uncontrolled, involuntary movements (dyskinesias)
- New or worsening hallucinations, delusions, or confusion
- Unusual urges or behaviors (e.g., gambling, hypersexuality, binge eating)
- Excessive daytime sleepiness or sudden onset of sleep
- Severe dizziness or fainting spells
- Muscle stiffness, fever, or confusion (signs of neuroleptic malignant syndrome-like reaction, especially if stopped suddenly)
- Signs of liver problems (e.g., yellowing of skin/eyes, dark urine, persistent nausea/vomiting)
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:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, including:
+ Glaucoma
+ Skin lumps or growths
+ A history of skin cancer
* If you have taken specific antidepressant medications, such as isocarboxazid, phenelzine, or tranylcypromine, within the last 14 days. Taking this medication too soon after these drugs can lead to severe high blood pressure.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine whether it is safe to take this medication with your existing health conditions and other medications. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, including:
+ Glaucoma
+ Skin lumps or growths
+ A history of skin cancer
* If you have taken specific antidepressant medications, such as isocarboxazid, phenelzine, or tranylcypromine, within the last 14 days. Taking this medication too soon after these drugs can lead to severe high blood pressure.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine whether it is safe to take this medication with your existing health conditions and other medications. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. This will help ensure they have a complete understanding of your treatment plan.
To minimize the risk of accidents, avoid driving and other activities that require alertness until you understand how this medication affects you. When changing positions, such as standing up from a sitting or lying down position, do so slowly to reduce the likelihood of dizziness or fainting. Be cautious when navigating stairs to prevent falls.
Regular blood tests and other laboratory evaluations are crucial to monitor your condition. Adhere to your doctor's schedule for these tests, and inform all healthcare providers and laboratory personnel that you are taking this medication, as it may interfere with certain lab results.
You may experience a decrease in the medication's effectiveness as the time approaches for your next dose. If this occurs and causes concern, discuss it with your doctor. It may take several months to achieve the full therapeutic effect of this medication.
Before consuming alcohol, using marijuana or other cannabis products, or taking prescription or over-the-counter medications that may impair your reactions, consult with your doctor.
You may notice a dark discoloration (red, brown, or black) in your saliva, urine, or sweat, which is harmless but may stain your clothing.
If you experience diarrhea or vomiting, consult your doctor promptly to prevent dehydration and electrolyte imbalances.
If you are pregnant, plan to become pregnant, or are breastfeeding, inform your doctor to discuss the potential benefits and risks of this medication to both you and your baby.
To minimize the risk of accidents, avoid driving and other activities that require alertness until you understand how this medication affects you. When changing positions, such as standing up from a sitting or lying down position, do so slowly to reduce the likelihood of dizziness or fainting. Be cautious when navigating stairs to prevent falls.
Regular blood tests and other laboratory evaluations are crucial to monitor your condition. Adhere to your doctor's schedule for these tests, and inform all healthcare providers and laboratory personnel that you are taking this medication, as it may interfere with certain lab results.
You may experience a decrease in the medication's effectiveness as the time approaches for your next dose. If this occurs and causes concern, discuss it with your doctor. It may take several months to achieve the full therapeutic effect of this medication.
Before consuming alcohol, using marijuana or other cannabis products, or taking prescription or over-the-counter medications that may impair your reactions, consult with your doctor.
You may notice a dark discoloration (red, brown, or black) in your saliva, urine, or sweat, which is harmless but may stain your clothing.
If you experience diarrhea or vomiting, consult your doctor promptly to prevent dehydration and electrolyte imbalances.
If you are pregnant, plan to become pregnant, or are breastfeeding, inform your doctor to discuss the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Severe dyskinesias
- Agitation
- Confusion
- Insomnia
- Orthostatic hypotension
- Tachycardia
- Arrhythmias
What to Do:
Seek immediate medical attention. Call 911 or Poison Control at 1-800-222-1222. Management is supportive, including gastric lavage, IV fluids, and careful monitoring of vital signs and cardiac rhythm. Pyridoxine is not effective in reversing levodopa effects when carbidopa is present.
Drug Interactions
Contraindicated Interactions
- Non-selective monoamine oxidase (MAO) inhibitors (e.g., phenelzine, tranylcypromine) - risk of hypertensive crisis. Must be discontinued at least 2 weeks prior to starting.
Major Interactions
- Selective MAO-A inhibitors (e.g., moclobemide) - risk of hypertensive crisis.
- Antipsychotics (e.g., haloperidol, chlorpromazine) - may antagonize the effects of levodopa.
- Metoclopramide - may antagonize the effects of levodopa.
- Iron salts (ferrous sulfate, gluconate) - may reduce levodopa absorption.
- Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone) - may worsen Parkinsonian symptoms.
- Isoniazid - may reduce levodopa efficacy.
Moderate Interactions
- Antihypertensive agents - increased risk of orthostatic hypotension.
- Tricyclic antidepressants (TCAs) - may increase risk of orthostatic hypotension and hypertension.
- Sympathomimetics (e.g., epinephrine, norepinephrine, dopamine) - increased risk of arrhythmias and hypertension.
- Other COMT inhibitors (e.g., tolcapone) - not recommended due to lack of additional benefit and potential for increased adverse effects.
Minor Interactions
- High-protein diet - may reduce levodopa absorption.
Monitoring
Baseline Monitoring
Complete Blood Count (CBC)
Rationale: To establish baseline and monitor for potential hematologic abnormalities (e.g., hemolytic anemia, leukopenia, thrombocytopenia) associated with levodopa.
Timing: Prior to initiation
Liver Function Tests (LFTs)
Rationale: To establish baseline and monitor for potential hepatotoxicity, especially with entacapone.
Timing: Prior to initiation
Renal Function Tests (BUN, Creatinine)
Rationale: To assess baseline renal function, as elimination is partly renal.
Timing: Prior to initiation
Cardiovascular Assessment (BP, HR, ECG)
Rationale: To assess for baseline orthostatic hypotension or cardiac arrhythmias.
Timing: Prior to initiation
Mental Status Examination
Rationale: To establish baseline cognitive and psychiatric status.
Timing: Prior to initiation
Routine Monitoring
Motor Fluctuations (wearing-off, dyskinesias)
Frequency: At each visit, or as needed
Target: Optimal motor control with minimal dyskinesia
Action Threshold: Increased 'off' time, severe dyskinesia, or new onset of dyskinesia requires dose adjustment or addition of other therapies.
Blood Pressure (sitting and standing)
Frequency: Regularly, especially during dose titration
Target: Normotensive, minimal orthostatic drop
Action Threshold: Significant orthostatic hypotension (e.g., >20 mmHg systolic drop) requires dose adjustment or intervention.
Psychiatric Symptoms (hallucinations, delusions, impulse control disorders)
Frequency: At each visit, or as needed
Target: Absence of new or worsening psychiatric symptoms
Action Threshold: New onset or worsening of symptoms requires dose adjustment or psychiatric evaluation.
Liver Function Tests (LFTs)
Frequency: Periodically (e.g., every 6-12 months or as clinically indicated), especially if symptoms of liver dysfunction appear.
Target: Within normal limits
Action Threshold: Significant elevation (e.g., >3x ULN) requires investigation and potential discontinuation.
Complete Blood Count (CBC)
Frequency: Periodically (e.g., every 6-12 months or as clinically indicated).
Target: Within normal limits
Action Threshold: Significant abnormalities require investigation.
Urine color
Frequency: Patient self-monitoring
Target: Normal
Action Threshold: Darkening of urine (harmless, due to entacapone metabolites) should be noted but does not require action unless accompanied by other symptoms.
Symptom Monitoring
- Orthostatic hypotension (dizziness, lightheadedness upon standing)
- Dyskinesia (involuntary movements)
- Nausea/vomiting
- Hallucinations, delusions, confusion
- Impulse control disorders (e.g., pathological gambling, hypersexuality, compulsive shopping, binge eating)
- Diarrhea (can be severe and persistent with entacapone)
- Sleepiness/sudden onset of sleep
- Darkening of urine, sweat, or saliva (harmless, due to entacapone metabolites)
Special Patient Groups
Pregnancy
Category C. Animal studies have shown adverse effects on fetal development. There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for developmental toxicity observed in animal studies.
Second Trimester:
Potential for developmental toxicity observed in animal studies.
Third Trimester:
Potential for developmental toxicity observed in animal studies.
Lactation
Levodopa is excreted in human milk. It is unknown if carbidopa or entacapone are excreted in human milk. Levodopa may inhibit lactation. Due to the potential for serious adverse reactions in breastfed infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
L3 (Moderate risk) - Potential for inhibition of lactation, and unknown effects of carbidopa/entacapone on infant. Monitor infant for adverse effects.
Pediatric Use
Safety and effectiveness have not been established in pediatric patients. Not recommended for use in this population.
Geriatric Use
No specific dose adjustment is generally required based on age alone. However, elderly patients may be more sensitive to the adverse effects of levodopa, such as dyskinesias, hallucinations, and orthostatic hypotension. Initiate at the lower end of the dosing range and titrate carefully.
Clinical Information
Clinical Pearls
- This combination product is intended for patients already on carbidopa/levodopa who experience 'wearing-off' symptoms, not for initial Parkinson's therapy.
- Patients should be advised that their urine, sweat, and saliva may turn reddish-brown or dark due to entacapone metabolites, which is a harmless effect.
- Monitor for impulse control disorders (e.g., pathological gambling, hypersexuality, compulsive shopping, binge eating), which can occur with dopaminergic therapies.
- Diarrhea can be a significant side effect of entacapone; if severe or persistent, consider dose reduction or discontinuation.
- Sudden discontinuation can lead to a neuroleptic malignant syndrome-like reaction (fever, muscle rigidity, altered mental status, autonomic instability). Taper slowly if discontinuation is necessary.
- Advise patients to avoid sudden changes in posture to minimize orthostatic hypotension.
Alternative Therapies
- Dopamine agonists (e.g., pramipexole, ropinirole, rotigotine, apomorphine)
- MAO-B inhibitors (e.g., selegiline, rasagiline, safinamide)
- Amantadine
- Anticholinergics (e.g., benztropine, trihexyphenidyl)
- Adenosine A2A receptor antagonists (e.g., istradefylline)
Cost & Coverage
Average Cost:
Varies widely, typically $150-$500+ per 30 tablets
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (for generic), Tier 3 or Tier 4 (for brand)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.