Acetaminophen 650mg ER Tablets
WARNING: Liver problems have happened with the use of acetaminophen. Sometimes, this has led to a liver transplant or death. Most of the time, liver problems happened in people taking more than 4,000 mg (milligrams) of acetaminophen in a day. People were also often taking more than 1 drug that had acetaminophen in it. If you have questions, talk with your doctor. @ COMMON USES: It is used to ease pain and fever.
Drug Class
Analgesic, Antipyretic
Pharmacologic Class
Para-aminophenol derivative
Pregnancy Category
Not available (older classification, now risk summary; generally considered low risk)
FDA Approved
Jan 1970
DEA Schedule
Not Controlled
Overview
What is this medicine?
Acetaminophen 650mg ER is an extended-release medication used to relieve mild to moderate pain and reduce fever. The extended-release formula means it works over a longer period, typically up to 8 hours, providing sustained relief.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication as directed, with or without food. Swallow the tablet whole, without chewing, breaking, or crushing it. Drink a full glass of water with each dose.
Storing and Disposing of Your Medication
Keep your medication at room temperature, away from refrigeration and freezing. Store it in its original container, protected from light, with the lid tightly closed. Choose a dry location, avoiding the bathroom. This will help preserve the medication's effectiveness.
Missing a Dose
If you take this medication regularly and miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses. If you take this medication as needed, follow your doctor's instructions and do not take it more frequently than recommended.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication as directed, with or without food. Swallow the tablet whole, without chewing, breaking, or crushing it. Drink a full glass of water with each dose.
Storing and Disposing of Your Medication
Keep your medication at room temperature, away from refrigeration and freezing. Store it in its original container, protected from light, with the lid tightly closed. Choose a dry location, avoiding the bathroom. This will help preserve the medication's effectiveness.
Missing a Dose
If you take this medication regularly and miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses. If you take this medication as needed, follow your doctor's instructions and do not take it more frequently than recommended.
Lifestyle & Tips
- Do not take more than directed. Exceeding the recommended dose can cause severe liver damage.
- Do not take with other medicines containing acetaminophen. Check all cold, flu, and pain medications for acetaminophen content.
- Limit or avoid alcohol consumption while taking this medication, as it increases the risk of liver damage.
- Store at room temperature away from moisture and heat.
Available Forms & Alternatives
Available Strengths:
- Acetaminophen 120mg Suppositories
- Acetaminophen 650mg Suppositories
- Acetaminophen 500mg Tablets
- Acetaminophen Child 160mg/5ml Susp
- Acetaminophen 500mg X/s Tablets
- Acetaminophen 500mg E/s Caplets
- Acetaminophen 160mg/5ml Solution
- Acetaminophen 325mg Tablets
- Acetaminophen 10mg/ml Inj, 100ml
- Acetaminophen 160mg/5ml Liquid
- Acetaminophen 500mg E/s Tablets
- Acetaminophen Child 160mg/5ml Susp
- Acetaminophen Infant 160mg/5ml Susp
- Acetaminophen 650mg ER Tablets
Dosing & Administration
Adult Dosing
Standard Dose:
1300 mg (two 650 mg tablets) orally every 8 hours
Dose Range:
1300 - 3900 mg
Condition-Specific Dosing:
maximumDailyDose:
3900 mg in 24 hours (six 650 mg tablets)
duration:
Do not use for more than 10 days for pain or 3 days for fever without consulting a physician.
Pediatric Dosing
Neonatal:
Not established (650mg ER formulation not recommended)
Infant:
Not established (650mg ER formulation not recommended)
Child:
Not established (650mg ER formulation not recommended for children under 12 years)
Adolescent:
Not established (650mg ER formulation generally not recommended for adolescents under 18 years due to high single dose and ER nature; consult physician)
Dose Adjustments
Renal Impairment:
Mild:
No specific adjustment needed, but caution with chronic use.
Moderate:
Consider increasing dosing interval to every 8-12 hours for CrCl 10-50 mL/min.
Severe:
Consider increasing dosing interval to every 12-24 hours for CrCl <10 mL/min.
Dialysis:
Acetaminophen is dialyzable. Administer dose after dialysis. Consider increasing dosing interval to every 12-24 hours.
Hepatic Impairment:
Mild:
Use with caution; consider reduced dose or extended interval.
Moderate:
Use with extreme caution; consider reduced dose or extended interval. Avoid if possible.
Severe:
Contraindicated due to risk of hepatotoxicity.
Pharmacology
Mechanism of Action
Acetaminophen's exact mechanism is not fully elucidated but is believed to involve inhibition of prostaglandin synthesis primarily in the central nervous system (CNS), leading to analgesic and antipyretic effects. It may selectively inhibit cyclooxygenase (COX) enzymes, particularly COX-3, in the brain and spinal cord, with minimal peripheral anti-inflammatory activity.
Pharmacokinetics
Absorption:
Bioavailability:
60-90% (oral)
Tmax:
2-4 hours (for 650mg ER formulation, compared to 0.5-2 hours for immediate-release)
FoodEffect:
Food may slightly delay absorption but does not significantly affect the extent of absorption.
Distribution:
Vd:
Approximately 0.9 L/kg
ProteinBinding:
10-25% (at therapeutic concentrations)
CnssPenetration:
Yes
Elimination:
HalfLife:
Approximately 2-3 hours (for immediate-release); 4-6 hours (for 650mg ER formulation)
Clearance:
Approximately 5 mL/min/kg
ExcretionRoute:
Renal (urine)
Unchanged:
Less than 5% (excreted unchanged in urine)
Pharmacodynamics
OnsetOfAction:
Approximately 30-60 minutes (for 650mg ER, slower than IR)
PeakEffect:
2-4 hours (for 650mg ER)
DurationOfAction:
Up to 8 hours (for 650mg ER)
Safety & Warnings
BLACK BOX WARNING
Acetaminophen has been associated with cases of acute liver failure, sometimes resulting in liver transplant or death. Most cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 mg per day, and often involve more than one acetaminophen-containing product. Be aware of the maximum daily dose and advise patients to check labels of all other medications for acetaminophen content. Serious skin reactions (e.g., Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, Acute Generalized Exanthematous Pustulosis) have also been reported.
Side Effects
Urgent Side Effects: Seek Medical Help Immediately
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 medical attention right away:
Signs of an allergic reaction, such as:
+ 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
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Difficulty urinating or changes in urine output
Severe skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis), characterized by:
+ Red, swollen, blistered, or peeling skin (with or without fever)
+ Red or irritated eyes
+ Sores in the 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 do not go away, contact your doctor:
Upset stomach or vomiting
Trouble sleeping
Headache
Constipation
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, 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 or seek medical attention right away:
Signs of an allergic reaction, such as:
+ 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
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Difficulty urinating or changes in urine output
Severe skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis), characterized by:
+ Red, swollen, blistered, or peeling skin (with or without fever)
+ Red or irritated eyes
+ Sores in the 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 do not go away, contact your doctor:
Upset stomach or vomiting
Trouble sleeping
Headache
Constipation
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, 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:
- Signs of liver damage: yellowing of skin or eyes (jaundice), dark urine, clay-colored stools, unusual tiredness, severe stomach pain, nausea, vomiting.
- Signs of allergic reaction: rash, hives, itching, swelling of the face/lips/tongue/throat, severe dizziness, trouble breathing.
- New or worsening pain or fever, or if pain/fever lasts more than a few days.
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.
If you have liver disease, as this may affect the safety and efficacy of the medication.
This list is not exhaustive, and it is crucial to discuss all your medications, health conditions, and concerns with your doctor. This includes:
All prescription and over-the-counter (OTC) medications you are taking
Natural products and vitamins
* Any health problems you have or have had in the past
To ensure your safety, do not start, stop, or change the dose of any medication without first consulting your doctor. It is vital to verify that it is safe to take this medication with all your other medications and health conditions. Your doctor and pharmacist will work together to ensure that you can take this medication safely and effectively.
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.
If you have liver disease, as this may affect the safety and efficacy of the medication.
This list is not exhaustive, and it is crucial to discuss all your medications, health conditions, and concerns with your doctor. This includes:
All prescription and over-the-counter (OTC) medications you are taking
Natural products and vitamins
* Any health problems you have or have had in the past
To ensure your safety, do not start, stop, or change the dose of any medication without first consulting your doctor. It is vital to verify that it is safe to take this medication with all your other medications and health conditions. Your doctor and pharmacist will work together to ensure that you can take this medication safely and effectively.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
To avoid potential liver problems, do not take any other products that contain acetaminophen. Carefully check the labels of all medications and supplements to ensure you are not exceeding the recommended daily dose of acetaminophen.
Follow the dosage instructions provided by your healthcare provider or the medication label exactly. Do not exceed the maximum daily dose of acetaminophen, which is 4,000 mg (milligrams) per day unless your doctor has specifically instructed you to do so. However, some individuals, such as those with liver problems or children, may require a lower dose. If you are unsure about the safe amount of acetaminophen for you to take in a day, consult your doctor or pharmacist. If you accidentally take too much acetaminophen in a day, contact your doctor immediately, even if you feel well.
Before consuming alcohol, discuss the potential risks with your doctor.
This medication may interfere with certain laboratory tests. Be sure to inform all your healthcare providers and laboratory personnel that you are taking this drug.
When administering this medication to children, note that different brands may have varying dosage recommendations. Consult your child's doctor before giving them this medication to ensure the correct dose is used.
If you are pregnant, planning to become pregnant, or breastfeeding, inform your doctor. You and your doctor will need to discuss the potential benefits and risks of taking this medication to you and your baby.
To avoid potential liver problems, do not take any other products that contain acetaminophen. Carefully check the labels of all medications and supplements to ensure you are not exceeding the recommended daily dose of acetaminophen.
Follow the dosage instructions provided by your healthcare provider or the medication label exactly. Do not exceed the maximum daily dose of acetaminophen, which is 4,000 mg (milligrams) per day unless your doctor has specifically instructed you to do so. However, some individuals, such as those with liver problems or children, may require a lower dose. If you are unsure about the safe amount of acetaminophen for you to take in a day, consult your doctor or pharmacist. If you accidentally take too much acetaminophen in a day, contact your doctor immediately, even if you feel well.
Before consuming alcohol, discuss the potential risks with your doctor.
This medication may interfere with certain laboratory tests. Be sure to inform all your healthcare providers and laboratory personnel that you are taking this drug.
When administering this medication to children, note that different brands may have varying dosage recommendations. Consult your child's doctor before giving them this medication to ensure the correct dose is used.
If you are pregnant, planning to become pregnant, or breastfeeding, inform your doctor. You and your doctor will need to discuss the potential benefits and risks of taking this medication to you and your baby.
Overdose Information
Overdose Symptoms:
- Early symptoms (within 24 hours): nausea, vomiting, sweating, abdominal pain, loss of appetite.
- Later symptoms (24-72 hours): signs of liver damage (jaundice, dark urine, right upper quadrant pain), kidney failure, coma, death.
What to Do:
Seek immediate medical attention. Call 911 or Poison Control at 1-800-222-1222. Treatment may include activated charcoal if within 1-2 hours of ingestion, and N-acetylcysteine (NAC) as an antidote, which is most effective when given within 8 hours of overdose.
Drug Interactions
Major Interactions
- Alcohol (chronic heavy use increases risk of hepatotoxicity)
- Warfarin (increased INR and bleeding risk with chronic high-dose acetaminophen)
- Other hepatotoxic drugs (additive liver toxicity)
Moderate Interactions
- Isoniazid (increased risk of hepatotoxicity)
- Phenytoin, Carbamazepine, Phenobarbital (may increase acetaminophen metabolism, potentially increasing NAPQI formation and hepatotoxicity risk)
- Cholestyramine (reduces acetaminophen absorption if given concurrently)
- Lamotrigine (may reduce lamotrigine levels)
Minor Interactions
- Oral contraceptives (may slightly increase acetaminophen clearance)
Monitoring
Baseline Monitoring
Liver function tests (ALT, AST, bilirubin)
Rationale: To establish baseline liver health, especially in patients with pre-existing liver disease or risk factors for hepatotoxicity (e.g., chronic alcohol use).
Timing: Prior to initiating chronic high-dose therapy or in at-risk patients.
Routine Monitoring
Liver function tests (ALT, AST)
Frequency: Periodically, especially with chronic high-dose use (e.g., monthly to quarterly) or if symptoms of liver dysfunction develop.
Target: Within normal limits
Action Threshold: Significant elevation (e.g., >3x ULN) warrants dose reduction or discontinuation and further investigation.
INR (International Normalized Ratio)
Frequency: More frequently (e.g., weekly) when co-administered with warfarin, especially when starting or stopping acetaminophen.
Target: Therapeutic range for warfarin indication
Action Threshold: INR outside target range requires warfarin dose adjustment.
Symptom Monitoring
- Signs of liver damage (e.g., yellowing of skin or eyes, dark urine, clay-colored stools, unusual tiredness, abdominal pain, nausea, vomiting)
- Signs of allergic reaction (e.g., rash, itching, swelling, severe dizziness, trouble breathing)
- Signs of gastrointestinal bleeding (e.g., black, tarry stools; coffee-ground vomit) - less common with acetaminophen than NSAIDs but still important to monitor for general GI health.
Special Patient Groups
Pregnancy
Acetaminophen is generally considered safe for use during pregnancy when used at recommended doses for the shortest duration necessary. However, the extended-release formulation may have less data specifically for pregnancy compared to immediate-release.
Trimester-Specific Risks:
First Trimester:
Low risk; no clear evidence of increased congenital malformations.
Second Trimester:
Low risk.
Third Trimester:
Low risk; some observational studies have suggested a possible association with neurodevelopmental disorders in children exposed prenatally, but causality has not been established and confounding factors are likely. Current consensus supports its use when clinically indicated.
Lactation
Acetaminophen is considered compatible with breastfeeding. It is excreted into breast milk in small amounts, which are generally not considered harmful to the infant.
Infant Risk:
L1 (Safest) - No evidence of adverse effects on the infant; widely used in breastfeeding mothers.
Pediatric Use
The 650mg extended-release formulation is generally not recommended for use in children under 12 years of age due to the high single dose and the extended-release nature, which can complicate dosing and increase the risk of accidental overdose. Pediatric dosing for acetaminophen is typically based on weight and uses immediate-release formulations.
Geriatric Use
No specific dose adjustment is typically required based on age alone. However, elderly patients may have age-related decreases in renal or hepatic function, which would necessitate dose adjustments as per renal/hepatic impairment guidelines. They may also be more susceptible to adverse effects or drug interactions.
Clinical Information
Clinical Pearls
- The 650mg extended-release formulation of acetaminophen (e.g., Tylenol 8 Hour Arthritis Pain) was voluntarily withdrawn from the US market in 2017 due to concerns about dosing errors and potential for liver injury, especially when combined with immediate-release acetaminophen products. While information is provided here, its availability is limited.
- Emphasize to patients the critical importance of checking all other medications (prescription and OTC) for acetaminophen content to avoid accidental overdose.
- Counsel patients on the signs and symptoms of liver damage and to seek immediate medical attention if they occur.
- For chronic pain management, consider the total daily dose and potential for cumulative toxicity, especially in patients with underlying liver disease or chronic alcohol use.
Alternative Therapies
- Immediate-release acetaminophen (various strengths)
- Nonsteroidal Anti-inflammatory Drugs (NSAIDs) such as ibuprofen, naproxen (for pain and fever, with anti-inflammatory action)
- Aspirin (for pain and fever, with anti-inflammatory action, but not for children/adolescents with viral infections)
- Opioid analgesics (for more severe pain, with higher risk profile)
Cost & Coverage
Average Cost:
Not readily available (product largely withdrawn) per 30 tablets
Generic Available:
Yes
Insurance Coverage:
Tier 1 (Generic)
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 is a good idea to consult with your pharmacist. If you have any questions or concerns about this medication, do not 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 detailed information about the overdose, including the medication taken, the amount, and the time it occurred.