Pain Reliever Plus Tablets

Acetaminophen: Believed to act primarily in the central nervous system by inhibiting prostaglandin synthesis, possibly via inhibition of cyclooxygenase (COX-3 or central COX-1/2). It also has antipyretic effects through direct action on the hypothalamic heat-regulating center. Aspirin: Irreversibly inhibits cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, leading to decreased prostaglandin and thromboxane synthesis. This results in anti-inflammatory, analgesic, and antipyretic effects. It also inhibits platelet aggregation by inhibiting thromboxane A2 synthesis. Caffeine: A central nervous system stimulant that acts as a non-selective adenosine receptor antagonist (A1, A2A, A2B, A3). It enhances the analgesic effects of acetaminophen and aspirin, possibly by promoting cerebral vasoconstriction and reducing cerebral blood flow, which can alleviate headache pain. It also has mild diuretic effects.

Serious 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
Signs of bleeding, such as:
+ Vomiting or coughing up blood
+ Vomit that looks like coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that get bigger
+ Uncontrollable bleeding
Confusion
Changes in behavior
Feeling extremely tired or weak
Severe dizziness or fainting
Ringing in the ears, hearing loss, or other changes in hearing
A severe skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis), which can cause severe health problems and may be life-threatening. Symptoms include:
+ Red, swollen, blistered, or peeling skin (with or without fever)
+ Red or irritated eyes
+ Sores in the mouth, throat, nose, or eyes
Severe stomach ulcers or bleeding, which can be increased by taking high doses, smoking, or drinking alcohol. Symptoms include:
+ Severe stomach or back pain
+ Black, tarry, or bloody stools
+ Vomiting blood or coffee ground-like material
+ Unusual weight gain or swelling

Other Possible Side Effects

Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. However, if you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical attention:

Stomach pain or heartburn
Upset stomach

This is not an exhaustive list of 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.

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following conditions to ensure safe treatment:

Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction and its symptoms.
A history of nasal polyps or swelling of the mouth, face, lips, tongue, or throat, unusual hoarseness, or difficulty breathing after taking aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs).
Liver disease, as this may affect the medication's safety and efficacy.
Bleeding problems, which may increase the risk of adverse effects.
Concurrent use of another medication containing the same active ingredient or any other NSAID, as this may lead to increased risk of side effects.
Pregnancy, planned pregnancy, or suspected pregnancy, as this medication may harm the unborn baby if taken after 20 weeks of gestation. If you are between 20 and 30 weeks pregnant, only take this medication under your doctor's guidance. Do not take this medication if you are more than 30 weeks pregnant.

Special Considerations for Children:

If your child or teenager has or is recovering from flu symptoms, chickenpox, or other viral infections, inform your doctor. The risk of Reye's syndrome, a severe condition, may be increased. Do not give this medication to a child or teenager with a viral infection or during recovery.

Interactions with Other Medications and Health Conditions:

This is not an exhaustive list of potential interactions. Inform your doctor and pharmacist about all prescription and over-the-counter medications, natural products, and vitamins you are taking, as well as any health problems you have.
* It is crucial to verify the safety of taking this medication with all your other medications and health conditions. Do not initiate, stop, or modify the dosage of any medication without consulting your doctor.

Important Warnings and Cautions

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.

Dosage and Administration

Do not exceed the dosage prescribed by your doctor, as taking more than recommended may increase your risk of severe side effects. Additionally, do not take this medication for a longer period than specified by your doctor.

Allergies and Interactions

If you are allergic to tartrazine (FD&C Yellow No. 5), consult your doctor before taking this medication, as some products may contain this ingredient. Furthermore, avoid taking other products that contain acetaminophen, and carefully check the labels to prevent excessive acetaminophen intake, which may cause liver problems.

Acetaminophen and Liver Problems

This medication contains acetaminophen, which has been associated with liver problems, including liver transplant or death, particularly when taken in excess of 4,000 mg (milligrams) per day or in combination with other medications containing acetaminophen. To minimize this risk, follow the directions exactly and do not take more acetaminophen in a day than directed. If you are unsure about the safe daily limit, consult your doctor or pharmacist. Some individuals, such as those with liver problems or children, may require a lower acetaminophen dose. If you suspect you have taken too much acetaminophen, contact your doctor immediately, even if you feel well.

Substance Interactions

Before consuming alcohol, discuss the potential risks with your doctor. If you smoke, consult your doctor to assess any potential interactions.

Bleeding Risks and Injury Prevention

This medication may increase your risk of bleeding. To minimize this risk, be cautious and avoid injury. Use a soft toothbrush and an electric razor to reduce the risk of bleeding.

Genetic Considerations

If you have low levels of the enzyme G6PD, you may be at increased risk of anemia. This condition is more common in individuals of African, South Asian, Middle Eastern, and Mediterranean descent.

Caffeine and Chocolate Interactions

Limit your consumption of caffeine (found in tea, coffee, and cola) and chocolate, as combining these substances with this medication may cause nervousness, shakiness, and a rapid heartbeat.

Aspirin Interaction

If you are taking aspirin to prevent a heart attack, consult your doctor to discuss potential interactions.

Lab Test Interactions

This medication may affect certain lab tests. Inform all your healthcare providers and lab workers that you are taking this medication.

Age-Related Considerations

If you are 60 or older, use this medication with caution, as you may be more susceptible to side effects.

Breast-Feeding Considerations

If you are breast-feeding, consult your doctor to discuss any potential risks to your baby.

• Ketorolac (with Aspirin)
• Methotrexate (high-dose, with Aspirin)
• Live attenuated influenza vaccine (LAIV) in children/adolescents (with Aspirin)
• Alcohol (chronic heavy use, with Acetaminophen/Aspirin)
• Other Acetaminophen-containing products
• Other NSAIDs (with Aspirin)

• Anticoagulants (e.g., Warfarin, Heparin, Dabigatran, Rivaroxaban) - increased bleeding risk (Aspirin, Acetaminophen at high doses)
• Antiplatelet agents (e.g., Clopidogrel, Ticagrelor) - increased bleeding risk (Aspirin)
• SSRIs/SNRIs - increased bleeding risk (Aspirin)
• Corticosteroids - increased GI ulceration/bleeding risk (Aspirin)
• Diuretics (e.g., Furosemide, Hydrochlorothiazide) - reduced diuretic effect, increased nephrotoxicity risk (Aspirin)
• ACE inhibitors/ARBs - reduced antihypertensive effect, increased renal impairment risk (Aspirin)
• Methotrexate (low-dose) - increased methotrexate toxicity (Aspirin)
• Sulfonylureas - increased hypoglycemic effect (Aspirin)
• Phenytoin - increased phenytoin levels (Aspirin)
• Valproic acid - increased valproic acid levels (Aspirin)
• Fluvoxamine, Ciprofloxacin, Cimetidine (CYP1A2 inhibitors) - increased caffeine levels
• Ephedrine, Pseudoephedrine, other stimulants - increased CNS/cardiovascular effects (Caffeine)

• Oral contraceptives - decreased caffeine clearance
• Disulfiram - decreased caffeine clearance
• Barbiturates, Carbamazepine, Phenytoin, Rifampin (CYP1A2 inducers) - decreased caffeine levels
• Lithium - increased lithium excretion (Aspirin)
• Probenecid, Sulfinpyrazone - reduced uricosuric effect (Aspirin)
• Beta-blockers - reduced antihypertensive effect (Aspirin), increased caffeine levels (some beta-blockers)

• Antacids - may reduce aspirin absorption
• Cholestyramine - may reduce aspirin absorption

• Signs of liver damage (e.g., dark urine, yellowing of skin/eyes, nausea, vomiting, abdominal pain, fatigue)
• Signs of GI bleeding (e.g., black/tarry stools, coffee-ground vomit, severe abdominal pain)
• Signs of allergic reaction (e.g., rash, itching, hives, swelling of face/lips/tongue, difficulty breathing)
• Signs of renal dysfunction (e.g., decreased urine output, swelling in ankles/feet)
• Signs of salicylism (e.g., tinnitus, dizziness, confusion, hyperventilation)
• Persistent or worsening pain/fever

Generally not recommended during pregnancy, especially in the third trimester. Aspirin (NSAID) use in the third trimester can cause premature closure of the fetal ductus arteriosus, fetal renal dysfunction, and increased maternal/fetal bleeding. Acetaminophen is generally considered safe in pregnancy at recommended doses, but the combination with aspirin and caffeine increases risk. Caffeine crosses the placenta and high doses may be associated with adverse outcomes.

Use with caution. All three components are excreted into breast milk. Acetaminophen is generally considered safe. Aspirin is excreted in small amounts, but there is a theoretical risk of Reye's Syndrome in infants, and it may affect platelet function. Caffeine is excreted into breast milk and can cause irritability, poor sleep, and jitteriness in the infant, especially with high maternal intake.

Contraindicated in children and teenagers (under 16-18 years old, depending on specific product labeling) for viral illnesses (e.g., flu, chickenpox) due to the risk of Reye's Syndrome associated with the Aspirin component. Safety and efficacy in younger children for other indications are not established.

Use with caution. Elderly patients are at increased risk for adverse effects, particularly gastrointestinal bleeding, renal impairment, and cardiovascular events due to the Aspirin component. Start with lower doses and monitor renal function and signs of bleeding closely. Caffeine sensitivity may also be increased.

• Always advise patients to check the active ingredients of other medications (especially cold/flu remedies and other pain relievers) to avoid accidental overdose of acetaminophen or NSAIDs.
• Emphasize the strict adherence to dosing limits due to the risk of severe liver damage from acetaminophen and GI bleeding/renal issues from aspirin.
• Educate patients about the signs of Reye's Syndrome and the contraindication of aspirin in children/teenagers with viral illnesses.
• Counsel on avoiding or limiting alcohol intake while on this medication.
• Patients with a history of ulcers, bleeding disorders, or kidney/liver disease should consult a healthcare professional before use.

• Single-ingredient Acetaminophen (e.g., Tylenol)
• Single-ingredient Ibuprofen (e.g., Advil, Motrin)
• Single-ingredient Naproxen (e.g., Aleve)
• Prescription NSAIDs
• Opioid analgesics (for severe pain, different class)
• Triptans (for migraine-specific treatment)

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 this 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 reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.