Excedrin PM

Acetaminophen is a pain reliever and a fever reducer.

Diphenhydramine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Acetaminophen and diphenhydramine is a combination medicine used to treat headache, runny nose, sneezing, watery eyes, and pain or fever caused by allergies, the common cold, or the flu.

Acetaminophen and diphenhydramine may also be used for purposes not listed in this medication guide.

Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death.

In rare cases, acetaminophen may cause a severe skin reaction. Stop taking this medicine and call your doctor right away if you have skin redness or a rash that spreads and causes blistering and peeling.

Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP.

Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen.

Ask a doctor before taking medicine that contains acetaminophen if you have ever had liver disease, or if you drink more than 3 alcoholic beverages per day.

You should not use this medication if you are allergic to it, or if you have:

• severe constipation, blockage in your stomach or intestines;

• untreated or uncontrolled diseases--glaucoma, asthma, heart disease, overactive thyroid; or

• if you are unable to urinate.

Ask a doctor or pharmacist before taking this medicine if you have any medical condition, especially:

• kidney disease;

• cough with mucus, or cough caused by emphysema or chronic bronchitis;

• an enlarged prostate, problems with urination;

• a history of alcoholism; or

• if you take potassium (Cytra, Epiklor, K-Lyte, K-Phos, Kaon, Klor-Con, Polycitra, Urocit-K).

It is not known whether this medicine will harm an unborn baby. Do not use cold or allergy medicine without a doctor's advice if you are pregnant.

This medicine can pass into breast milk and may harm a nursing baby. Antihistamines may slow breast milk production. Do not use cold or allergy without a doctor's advice if you are breast-feeding a baby.

Always ask a doctor before giving a cold or allergy medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

Since this medicine is used when needed, you may not be on a dosing schedule. If you are on a schedule, use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP.

Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

In rare cases, acetaminophen may cause a severe skin reaction that can be fatal. This could occur even if you have taken acetaminophen in the past and had no reaction. Stop taking this medicine and call your doctor right away if you have skin redness or a rash that spreads and causes blistering and peeling. If you have this type of reaction, you should never again take any medicine that contains acetaminophen.

Stop using the medicine and call your doctor at once if you have:

• fast, pounding, or uneven heartbeats;

• severe dizziness or drowsiness, slow or shallow breathing;

• tremor, restless muscle movements;

• little or no urinating;

• flu symptoms, easy bruising, unusual bleeding, pale skin, feeling light-headed; or

• nausea, pain in your upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• constipation;

• dry eyes, blurred vision, dry mouth or nose;

• mild dizziness or drowsiness, trouble concentrating;

• feeling restless or excited (especially in children); or

• mild skin rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Applies to acetaminophen / diphenhydramine: oral capsule, oral tablet

Applies to acetaminophen / diphenhydramine: oral capsule, oral liquid, oral tablet

Nervous system

Nervous system side effects from diphenhydramine have been reported frequently. These have included depression with drowsiness and sedation in nearly all patients treated. Motor skills may be impaired. Dystonic reactions have been reported after single doses of diphenhydramine.[Ref]

The CNS depressant effect of diphenhydramine parallels its plasma concentrations. The plasma concentration threshold for sedation is 30 to 42 ng/mL, and to cause mental impairment is 58 to 74 ng/mL. Patients should be warned against driving while taking diphenhydramine.

Dystonic reactions have been accompanied by dizziness, mental confusion, rigidity, lip and tongue protrusion, trismus, torticollis, and swallowing difficulties and generally resolve spontaneously. Toxic encephalopathy has been reported in a child with chicken pox treated generously with topical diphenhydramine.

Delirium has been reported in elderly patients with mild dementia following a small oral dose of diphenhydramine.[Ref]

Cardiovascular

Cardiovascular side effects including two cases of hypotension have been reported following the administration of acetaminophen.

Cardiovascular side effects of diphenhydramine have included hypotension, tachycardia, and palpitations.[Ref]

Two cases of hypotension have been reported following the administration of acetaminophen. Both patients experienced significant decreases in blood pressure. One of the two patients required pressor agents to maintain adequate mean arterial pressures. Neither episode was associated with symptoms of anaphylaxis. Neither patient was rechallenged after resolution of the initial episode.[Ref]

Hepatic

Hepatic side effects including severe and sometimes fatal dose dependent hepatitis have been reported in alcoholic patients with the use of acetaminophen. Hepatotoxicity has been increased during fasting. Several cases of hepatotoxicity from chronic acetaminophen therapy at therapeutic doses have also been reported despite a lack of risk factors for toxicity.[Ref]

Alcoholic patients may develop hepatotoxicity after even modest doses of acetaminophen. In healthy patients, approximately 15 grams of acetaminophen is necessary to deplete liver glutathione stores by 70% in a 70 kg person. However, hepatotoxicity has been reported following smaller doses. Glutathione concentrations may be repleted by the antidote N-acetylcysteine. One case report has suggested that hypothermia may also be beneficial in decreasing liver damage during overdose.

In a recent retrospective study of 306 patients admitted for acetaminophen overdose, 6.9% had severe liver injury but all recovered. None of the 306 patients died.

A 19 year old female developed hepatotoxicity, reactive plasmacytosis and agranulocytosis followed by a leukemoid reaction after acute acetaminophen toxicity.[Ref]

Gastrointestinal

One study has suggested that acetaminophen may precipitate acute biliary pain and cholestasis. The mechanism of this effect may be related to inhibition of prostaglandin and alterations in the regulation of the sphincter of Oddi.[Ref]

Gastrointestinal side effects have been rare with the use of acetaminophen, except in alcoholics and after overdose. Cases of acute pancreatitis have been reported rarely with the use of acetaminophen. In clinical trials of caffeine citrate, five cases of necrotizing enterocolitis were reported among the 46 infants exposed to the caffeine citrate injection.

Gastrointestinal side effects of diphenhydramine have been usually mild and included nausea and dry mouth.[Ref]

Renal

Acute tubular necrosis usually occurs in conjunction with liver failure, but has been observed as an isolated finding in rare cases. A possible increase in the risk of renal cell carcinoma has been associated with chronic acetaminophen use as well.

A recent case control study of patients with end-stage renal disease suggested that long term consumption of acetaminophen may significantly increase the risk of end-stage renal disease particularly in patients taking more than two pills per day.[Ref]

Renal side effects have been rare with the use of acetaminophen and have included acute tubular necrosis and interstitial nephritis. Adverse renal effects are most often observed after overdose, after chronic abuse (often with multiple analgesics), or in association with acetaminophen-related hepatotoxicity.[Ref]

Hypersensitivity

Hypersensitivity side effects, including anaphylaxis and fixed drug eruptions, have been reported rarely in association with acetaminophen use.

Hypersensitivity side effects to diphenhydramine have included rash, pruritus and eczema. Photosensitivity reactions have also been reported.[Ref]

Most commonly, hypersensitivity to diphenhydramine has manifested itself in patients receiving systemic drug after being sensitized to it by topical application. Sensitization with systemic administration has also been reported.[Ref]

Hematologic

Hematologic side effects including rare cases of thrombocytopenia associated with acetaminophen have been reported. Methemoglobinemia with resulting cyanosis has also been observed in the setting of acute overdose.

Hematologic side effects such as hemolytic anemia, thrombocytopenia, and agranulocytosis have been rarely caused by antihistamines such as diphenhydramine.[Ref]

Dermatologic

Dermatologic side effects including erythematous skin rashes associated with acetaminophen have been reported, but are rare. Acetaminophen associated bullous erythema and purpura fulminans have also been reported. Acetaminophen has been associated with a risk of rare but potentially fatal serious skin reactions know as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP).[Ref]

Genitourinary

Genitourinary side effects have included urinary retention and dysuria as a result of the anticholinergic effects of diphenhydramine.[Ref]

Respiratory

Respiratory side effects including a case of acetaminophen-induced eosinophilic pneumonia have been reported.[Ref]

Some side effects of Excedrin PM may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.