| |
PRECAUTIONS
Before taking acetaminophen, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, alcohol dependency, any allergies. Acetaminophen may cause liver damage. Daily use of alcohol, especially when combined with acetaminophen, may increase your risk for liver damage. Check with your doctor or pharmacist for more information. Acetaminophen is often used instead of aspirin. They are equally effective in relieving pain; however, acetaminophen does not reduce swelling and inflammation like aspirin does. There are many brands and forms of acetaminophen on the market. Read the dosing instructions carefully as the amount of acetaminophen may vary among products. Acetaminophen appears to be safe for use during pregnancy. Use only if clearly needed. Acetaminophen is found in breast milk, but side effects in nursing infants have not been reported. Consult you doctor if you are breast-feeding.
DRUG INTERACTIONS
Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: isoniazid, phenobarbital, phenytoin, zidovudine, sulfinpyrazone. Acetaminophen is an ingredient in many over-the-counter products and in some combination prescription medications. Read the labels carefully before taking other pain relievers or cold products to see if they also contain acetaminophen. Consult your pharmacist if you are uncertain if your other prescription or over-the-counter products contain acetaminophen. (Also see adult maximum dose information in Side Effects section).
OVERDOSE
If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include severe nausea, vomiting, excessive sweating, yellowing eyes or skin, dark urine, stomach pain, and extreme fatigue.
NOTES
Acetaminophen does not cause the stomach and intestinal ulcers that aspirin and aspirin-like NSAIDs (e.g., ibuprofen, ketoprofen) may cause.
MISSED DOSE
If you miss a dose, take as soon as remembered; do not take if it is almost time for the next dose, instead, skip the missed dose and resume your usual dosing schedule. Do not "double-up" the dose to catch up.
STORAGE
Store at room temperature between 59 and 86 degrees F (between 15 and 30 degrees C) away from moisture and sunlight. Do not store in the bathroom. Do not freeze liquid forms.
Presentation
Sylenol Tablets Blister of 10 Tablets
DRUG CLASS AND MECHANISM: Acetaminophen belongs to a class of drugs called analgesics (pain relievers) and antipyretics (fever reducers). The exact mechanism of action of acetaminophen is not known. Acetaminophen relieves pain by elevating the pain threshold, that is, by requiring a greater amount of pain to develop before a person feels it. It reduces fever through its action on the heat-regulating center of the brain. Specifically, it tells the center to lower the body's temperature when the temperature is elevated.
Acetanilide was the first aniline derivative serendipitously found to possess analgesic as well as antipyretic properties, and was quickly introduced into medical practice under the name of Antifebrin by A. Cahn and P. Hepp in 1886. But its unacceptable toxic effects, the most alarming being cyanosis due to methemoglobinemia, prompted the search for less toxic aniline derivatives. Harmon Northrop Morse had already synthesized paracetamol at Johns Hopkins University via the reduction of p-nitrophenol with tin in glacial acetic acid in 1877, but it wasn't until 1887 that clinical pharmacologist Joseph von Mering tried paracetamol on patients. In 1893, von Mering published a paper reporting on the clinical results of paracetamol with phenacetin, another aniline derivative. Von Mering claimed that, unlike phenacetin, paracetamol had a slight tendency to produce methemoglobinemia. Paracetamol was then quickly discarded in favor of phenacetin. The sales of phenacetin established Bayer as a leading pharmaceutical company. Overshadowed in part by aspirin, introduced into medicine by Heinrich Dreser in 1899, phenacetin was popular for many decades, particularly in widely advertised over-the-counter “headache mixtures,” usually containing phenacetin, an aminopyrine derivative or aspirin, caffeine, and sometimes a barbiturate.
How should this medicine be used?
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Acetaminophen comes as a tablet, chewable tablet, capsule, suspension or solution (liquid), drops (concentrated liquid), extended-release (long-acting) tablet, and orally disintegrating tablet (tablet that dissolves quickly in the mouth), to take by mouth, with or without food. Acetaminophen also comes as a suppository to use rectally. Acetaminophen is available without a prescription, but your doctor may prescribe acetaminophen to treat certain conditions. Follow the directions on the package or prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take acetaminophen exactly as directed. Do not take more or less of it or take it more often than directed on the package label or prescribed by your doctor. Taking more than the recommended amount may cause damage to your liver.
If you are giving acetaminophen to your child, read the package label carefully to make sure that it is the right product for the age of the child. Do not give children acetaminophen products that are made for adults. Some products for adults and older children may contain too much acetaminophen for a younger child. Drops made for infants are more concentrated (much more medication in each drop) than liquids made for older children. Check the package label to find out how much medication the child needs. If you know how much your child weighs, give the dose that matches that weight on the chart. If you don't know your child's weight, give the dose that matches your child's age. Ask your child's doctor if you don't know how much medication to give your child.
Acetaminophen comes in combination with other medications to treat cough and cold symptoms. Ask your doctor or pharmacist for advice on which product is best for your symptoms. Check nonprescription cough and cold product labels carefully before using two or more products at the same time. These products may contain the same active ingredient(s) and taking them together could cause you to receive an overdose. This is especially important if you will be giving cough and cold medications to a child.
Swallow the extended-release tablets whole; do not split, chew, crush, or dissolve them.
Place the orally disintegrating tablet ('Meltaways') in your mouth and allow to dissolve or chew it before swallowing.
Shake the suspension and drops well before each use to mix the medication evenly. Use the measuring cup provided by the manufacturer to measure each dose of the solution or suspension, and use the dosing device provided to measure each dose of the drops. Use the dosing device to slowly release the drops directly into the child's mouth near the inner cheek. Do not mix the drops with baby formula.
To insert an acetaminophen suppository into the rectum, follow these steps:
* Remove the wrapper.
* Dip the tip of the suppository in water.
* Lie down on your left side and raise your right knee to your chest. (A left-handed person should lie on the right side and raise the left knee.)
* Using your finger, insert the suppository into the rectum, about 1/2 to 1 inch (1.25 to 2.5 centimeters) in infants and children and 1 inch (2.5 centimeters) in adults. Hold it in place for a few moments.
* Stand up after about 15 minutes. Wash your hands thoroughly and resume your normal activities.
Stop taking acetaminophen and call your doctor if your symptoms get worse, you develop new or unexpected symptoms, including redness or swelling, your pain lasts for more than 10 days, or your fever gets worse or lasts more than 3 days. Also stop giving acetaminophen to your child and call your child's doctor if your child develops new symptoms, including redness or swelling, or your child's pain lasts for longer than 5 days, or fever get worse or lasts longer than 3 days.
Do not give acetaminophen to a child who has a sore throat that is severe or does not go away, or that occurs along with fever, headache, rash, nausea, or vomiting. Call the child's doctor right away, because these symptoms may be signs of a more serious condition.
What special precautions should I follow?
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Before taking acetaminophen,
* tell your doctor and pharmacist if you are allergic to acetaminophen, any other medications, or any of the ingredients in the product. Ask your pharmacist or check the label on the package for a list of ingredients.
* do not take two or more products that contain acetaminophen at the same time. Many prescription and nonprescription medications contain acetaminophen in combination with other medications. Read the package labels or ask your doctor or pharmacist to be sure that you do not take more than one product that contains acetaminophen at a time.
* tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, or herbal products you are taking or plan to take. Be sure to mention anticoagulants ('blood thinners') such as warfarin (Coumadin); isoniazid (INH); certain medications for seizures including carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin); medications for pain, fever, coughs, and colds; and phenothiazines (medications for mental illness and nausea). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
* tell your doctor if you have any serious medical condition.
* tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking acetaminophen, call your doctor.
* if you drink three or more alcoholic beverages every day, ask your doctor if you should take acetaminophen. Ask your doctor or pharmacist about the safe use of alcoholic beverages while taking acetaminophen.
* you should know that combination acetaminophen products for cough and colds that contain nasal decongestants, antihistamines, cough suppressants, and expectorants should not be used in children younger than 2 years of age. Use of these medications in young children can cause serious and life-threatening effects or death. In children 2 through 11 years of age, combination cough and cold products should be used carefully and only according to the directions on the label.
* if you have phenylketonuria (PKU, a inherited condition in which a special diet must be followed to prevent mental retardation), you should know that some brands of acetaminophen chewable tablets may be sweetened with aspartame. a source of phenylalanine.
Acetaminophen is the active ingredient in Tylenol. It is also found in many other over-the-counter medications you can buy at the drug store and in prescription drugs your doctor prescribes: Common names include Actifed, Alka-Seltzer Plus, Benadryl, Butalbital, Co-Gesic, Contac, Darvocet, Excedrin, Fioricet, Lortab, Midrin, Norco, Percocet, Robitussin, Sedapap, Sinutab, Sudafed, TheraFlu, Unisom With Pain, Vick's Nyquil and DayQuil, Vicodin, Wygesic, and Zydone.
Acetaminophen is the most widely used pharmaceutical analgesic and antipyretic agent in the United States and the world; it is contained in more than 100 products. As such, acetaminophen is one of the most common pharmaceuticals associated with both intentional and unintentional poisoning.
Acetaminophen is also known as paracetamol and N -acetyl-p-aminophenol (APAP). It is available in the United States as 325-mg and 500-mg immediate-release tablets, and as a 650-mg extended-release preparation marketed for the treatment of arthritis. Various children's dissolvable, chewable, suspension, and elixir formulations of acetaminophen are available. Acetaminophen is a component of many over-the-counter cold and analgesic medications and prescription combinations, including propoxyphene-acetaminophen (eg, Darvocet) and oxycodone-acetaminophen (eg, Percocet). Hepatotoxicity associated with acetaminophen misuse and overdose is well recognized.
In 2009, the US Food and Drug Administration (FDA) announced requirements for nonprescription and prescription containing medication to provide new information regarding acetaminophen-induced hepatotoxicity.1,2 Additionally, the FDA is examining possible removal of acetaminophen from some popular analgesic combination products (eg, Vicodin) and possibly lowering the maximum daily dose. The FDA is currently evaluating whether changes need to be made for acetaminophen regarding the following:
* Safe daily dose for healthy individuals
* Safe daily dose in chronic liver disease
* Safe daily dose when used with alcohol
* Appropriate dose for efficacy
* Package size restrictions
* Pediatric dosing
* Acetaminophen narcotic combinations
Pathophysiology
The maximum recommended daily dose of acetaminophen is 4 g in adults and 90 mg/kg in children. Toxicity is associated with a single acute APAP ingestion of 150 mg/kg or approximately 7-10 g in adults. The ingested amount at which toxicity may occur may be lower in the settings of chronic ethanol use, malnourishment, or diminished nutritional status, fasting, or viral illness with dehydration, or if substances or medications that are known to induce the activity of the CYP oxidative enzymes are being used. When dosing recommendations are followed, the risk of hepatotoxicity is extremely small.
Acetaminophen is rapidly absorbed from the stomach and small intestine and primarily metabolized by conjugation in the liver to nontoxic, water-soluble compounds that are eliminated in the urine.
In acute overdose or when the maximum daily dose is exceeded over a prolonged period, metabolism by conjugation becomes saturated, and excess APAP is oxidatively metabolized by the CYP enzymes (CYP2E1, 1A2, 2A6, 3A4) to a reactive metabolite, N -acetyl-p-benzoquinone-imine (NAPQI). NAPQI has an extremely short half-life and is rapidly conjugated with glutathione, a sulfhydryl donor, and is renally excreted. Under conditions of excessive NAPQI formation, or reduction in glutathione stores by approximately 70%, NAPQI covalently binds to the cysteinyl sulfhydryl groups of cellular proteins, forming NAPQI-protein adducts.
An ensuing cascade of oxidative damage, mitochondrial dysfunction, and the subsequent inflammatory response propagate hepatocellular injury, death, and centrilobular (zone III) liver necrosis. Similar enzymatic reactions occur in extra-hepatic organs, such as the kidney, and can contribute to some degree of extra-hepatic organ dysfunction.
The antidote for acetaminophen poisoning is N -acetylcysteine (NAC). NAC is theorized to work through a number of protective mechanisms. NAC is a precursor of glutathione and as such, increases glutathione conjugation of NAPQI. NAC also enhances sulfate conjugation of unmetabolized APAP. NAC functions as an anti-inflammatory and antioxidant and has positive inotropic effects. NAC increases local nitric oxide concentrations and promotes microcirculatory blood flow, enhancing local oxygen delivery to peripheral tissues. The microvascular effects of NAC therapy are associated with a decrease in morbidity and mortality even when NAC is administered in the setting of established hepatotoxicity.
NAC is maximally hepatoprotective when administered within 8 hours of an ingestion. When indicated, however, NAC should be administered regardless of the time since the overdose. Therapy with NAC has been shown to decrease mortality rates in late-presenting patients with fulminant hepatic failure, even in the absence of measurable serum acetaminophen levels.
No comments:
Post a Comment