Esgic-Plus

butalbital, acetaminophen and caffeine

Dosage Form: tablet

Warning

HEPATOTOXICITY

ACETAMINOPHEN HAS BEEN ASSOCIATED WITH CASES OF ACUTE LIVER FAILURE, AT TIMES RESULTING IN LIVER TRANSPLANT AND DEATH. MOST OF THE CASES OF LIVER INJURY ARE ASSOCIATED WITH THE USE OF ACETAMINOPHEN AT DOSES THAT EXCEED 4000 MILLIGRAMS PER DAY, AND OFTEN INVOLVE MORE THAN ONE ACETAMINOPHEN-CONTAINING PRODUCT.

Esgic-Plus Description

Butalbital, acetaminophen and caffeine is supplied in capsule form for oral administration.

Each capsule contains:

Butalbital ...................50 mg

Warning: May be habit-forming.

Acetaminophen ........500 mg

Caffeine ......................40 mg

In addition, each capsule contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate and microcrystalline cellulose. Capsule shell composed of gelatin (silicon dioxide and sodium lauryl sulfate are added as manufacturing aides to the gelatin), titanium dioxide, D&C Red #33, D&C Yellow #10 and FD&C Red #3. Imprinting ink composed of ammonium hydroxide, simethicone, isopropyl alcohol, n-butyl alcohol, pharmaceutical glaze, (modified) in SD-45 propylene glycol, and titanium dioxide.

Butalbital (5-allyl-5-isobutylbarbituric acid), is a short to intermediate-acting barbiturate. It has the following structural formula:

C11H16N2O3 MW = 224.26

Acetaminophen (4'-hydroxyacetanilide), is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:

C8H9NO2 MW = 151.16

Caffeine (1,3,7-trimethylxanthine), is a central nervous system stimulant. It has the following structural formula:

C8H10N4O2 MW = 194.19

Esgic-Plus - Clinical Pharmacology

This combination drug product is intended as a treatment for tension headache.

It consists of a fixed combination of butalbital, acetaminophen and caffeine. The role each component plays in the relief of the complex of symptoms known as tension headache is incompletely understood.

Pharmacokinetics

The behavior of the individual components is described below.

Butalbital: Butalbital is well absorbed from the gastrointestinal tract and is expected to distribute to most tissues in the body. Barbiturates in general may appear in breast milk and readily cross the placental barrier. They are bound to plasma and tissue proteins to a varying degree and binding increases directly as a function of lipid solubility.

Elimination of butalbital is primarily via the kidney (59% to 88% of the dose) as unchanged drug or metabolites. The plasma half-life is about 35 hours. Urinary excretion products include parent drug (about 3.6% of the dose), 5-isobutyl-5-(2,3-dihydroxypropyl) barbituric acid (about 24% of the dose), 5-allyl-5 (3-hydroxy-2-methyl-1-propyl) barbituric acid (about 4.8% of the dose), products with the barbituric acid ring hydrolyzed with excretion of urea (about 14% of the dose), as well as unidentified materials. Of the material excreted in the urine, 32% is conjugated.

The in vitro plasma protein binding of butalbital is 45% over the concentration range of 0.5 to 20 mcg/mL. This falls within the range of plasma protein binding (20% to 45%) reported with other barbiturates such as phenobarbital, pentobarbital, and secobarbital sodium. The plasma-to-blood concentration ratio was almost unity indicating that there is no preferential distribution of butalbital into either plasma or blood cells (See OVERDOSAGE for toxicity information).

Acetaminophen: Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed thoughout most body tissues. The plasma half-life is 1.25 to 3 hours, but may be increased by liver damage and following overdosage. Elimination of acetaminophen is principally by liver metabolism (conjugation) and subsequent renal excretion of metabolites. Approximately 85% of an oral dose appears in the urine within 24 hours of administration, most as the glucuronide conjugate, with small amounts of other conjugates and unchanged drug (See OVERDOSAGE for toxicity information).

Caffeine: Like most xanthines, caffeine is rapidly absorbed and distributed in all body tissues and fluids, including the CNS, fetal tissues, and breast milk.

Caffeine is cleared through metabolism and excretion in the urine. The plasma half-life is about 3 hours. Hepatic biotransformation prior to excretion, results in about equal amounts of 1-methylxanthine and 1-methyluric acid. Of the 70% of the dose that is recovered in the urine, only 3% is unchanged drug (See OVERDOSAGE for toxicity information).

Indications and Usage for Esgic-Plus

Esgic-Plus® Capsules (butalbital, acetaminophen and caffeine capsules, USP 50 mg/500 mg/40 mg) are indicated for the relief of the symptom complex of tension (or muscle contraction) headache.

Evidence supporting the efficacy and safety of this combination product in the treatment of multiple recurrent headaches is unavailable. Caution in this regard is required because butalbital is habit-forming and potentially abusable.

Contraindications

This product is contraindicated under the following conditions:

• Hypersensitivity or intolerance to any component of this product.


• Patients with porphyria.

Warnings

Butalbital is habit-forming and potentially abusable. Consequently, the extended use of this product is not recommended.

Hepatotoxicity

Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products.

The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen.

Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4000 milligrams of acetaminophen per day, even if they feel well.

Hypersensitivity/anaphylaxis

There have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Instruct patients to discontinue Esgic Plus® Capsules immediately and seek medical care if they experience these symptoms. Do not prescribe Esgic Plus® Capsules for patients with acetaminophen allergy.

Precautions

General

Esgic-Plus® Capsules should be prescribed with caution in certain special-risk patients, such as the elderly or debilitated, and those with severe impairment of renal or hepatic function, or acute abdominal conditions.

Information for Patients/Caregivers

• Do not take Esgic-Plus® Capsules if you are allergic to any of its ingredients.


• If you develop signs of allergy such as a rash or difficulty breathing, stop taking Esgic-Plus® Capsules and contact your healthcare provider immediately.


• Do not take more than 4000 milligrams of acetaminophen per day. Call your doctor if you took more than the recommended dose.

This product may impair mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Such tasks should be avoided while taking this product.

Alcohol and other CNS depressants may produce an additive CNS depression, when taken with this combination product, and should be avoided.

Butalbital may be habit-forming. Patients should take the drug only for as long as it is prescribed, in the amounts prescribed, and no more frequently than prescribed.

For information on use in geriatric patients, see PRECAUTIONS/Geriatric Use.

Laboratory Tests

In patients with severe hepatic or renal disease, effects of therapy should be monitored with serial liver and/or renal function tests.

Drug Interactions

The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors.

Butalbital, acetaminophen and caffeine may enhance the effects of: other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression.

Drug/Laboratory Test Interactions

Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No adequate studies have been conducted in animals to determine whether acetaminophen or butalbital have a potential for carcinogenesis, mutagenesis or impairment of fertility.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Animal reproduction studies have not been conducted with this combination product. It is also not known whether butalbital, acetaminophen and caffeine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. This product should be given to a pregnant woman only when clearly needed.

Nonteratogenic Effects

Withdrawal seizures were reported in a two-day-old male infant whose mother had taken a butalbital containing drug during the last two months of pregnancy. Butalbital was found in the infant’s serum. The infant was given phenobarbital 5 mg/kg, which was tapered without further seizure or other withdrawal symptoms.

Nursing Mothers

Caffeine, barbiturates and acetaminophen are excreted in breast milk in small amounts, but the significance of their effects on nursing infants is not known. Because of potential for serious adverse reactions in nursing infants from butalbital, acetaminophen and caffeine, 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.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 12 have not been established.

Geriatric Use

Clinical studies of butalbital, acetaminophen and caffeine capsules did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Butalbital is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Adverse Reactions

Frequently Observed

The most frequently reported adverse reactions are drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, abdominal pain, and intoxicated feeling.

Infrequently Observed

All adverse events tabulated below are classified as infrequent.

Central Nervous System: headache, shaky feeling, tingling, agitation, fainting, fatigue, heavy eyelids, high energy, hot spells, numbness, sluggishness, seizure. Mental confusion, excitement or depression can also occur due to intolerance, particularly in elderly or debilitated patients, or due to overdosage of butalbital.

Autonomic Nervous System: dry mouth, hyperhidrosis.

Gastrointestinal: difficulty swallowing, heartburn, flatulence, constipation.

Cardiovascular: tachycardia.

Musculoskeletal: leg pain, muscle fatigue.

Genitourinary: diuresis.

Miscellaneous: pruritus, fever, earache, nasal congestion, tinnitus, euphoria, allergic reactions.

Several cases of dermatological reactions, including toxic epidermal necrolysis and erythema multiforme, have been reported.

The following adverse drug events may be borne in mind as potential effects of the components of this product. Potential effects of high dosage are listed in the OVERDOSAGE section.

Acetaminophen: allergic reactions, rash, thrombocytopenia, agranulocytosis.

Caffeine: cardiac stimulation, irritability, tremor, dependence, nephrotoxicity, hyperglycemia.

Drug Abuse and Dependence

Abuse and Dependence

Butalbital: Barbiturates may be habit-forming: Tolerance, psychological dependence, and physical dependence may occur especially following prolonged use of high doses of barbiturates. The average daily dose for the barbiturate addict is usually about 1500 mg. As tolerance to barbiturates develops, the amount needed to maintain the same level of intoxication increases; tolerance to a fatal dosage, however, does not increase more than two-fold. As this occurs, the margin between an intoxication dosage and fatal dosage becomes smaller. The lethal dose of a barbiturate is far less if alcohol is also ingested. Major withdrawal symptoms (convulsions and delirium) may occur within 16 hours and last up to 5 days after abrupt cessation of these drugs. Intensity of withdrawal symptoms gradually declines over a period of approximately 15 days. Treatment of barbiturate dependence consists of cautious and gradual withdrawal of the drug. Barbiturate-dependent patients can be withdrawn by using a number of different withdrawal regimens. One method involves initiating treatment at the patient’s regular dosage level and gradually decreasing the daily dosage as tolerated by the patient.

Overdosage

Following an acute overdosage of butalbital, acetaminophen and caffeine, toxicity may result from the barbiturate or the acetaminophen. Toxicity due to caffeine is less likely, due to the relatively small amounts in this formulation.

Signs and Symptoms

Toxicity from barbiturate poisoning includes drowsiness, confusion, and coma; respiratory depression; hypotension; and hypovolemic shock.

In acetaminophen overdosage: dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necroses, hypoglycemic coma and coagulation defects may also occur. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion.

Acute caffeine poisoning may cause insomnia, restlessness, tremor, delirium, tachycardia and extrasystoles.

Treatment

A single or multiple drug overdose with this combination product is a potentially lethal polydrug overdose, and consultation with a regional poison control center is recommended. Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption.

Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Assisted or controlled ventilation should also be considered

Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have occurred within a few hours of presentation. Serum acetaminophen levels should be obtained immediately if the patient presents 4 hours or more after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels drawn less than 4 hours post-ingestion may be misleading. To obtain the best possible outcome, NAC should be administered as soon as possible where impending or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral administration.

Vigorous supportive therapy is required in severe intoxication. Procedures to limit the continuing absorption of the drug must be readily performed since the hepatic injury is dose dependent and occurs early in the course of intoxication.

USUAL DOSAGE

One capsule every four hours. Total daily dosage should not exceed 6 capsules.

Extended and repeated use of this product is not recommended because of the potential for physical dependence.

How is Esgic-Plus Supplied

Esgic-Plus® Capsules (butalbital, acetaminophen and caffeine capsules USP 50 mg/500 mg/40 mg) are supplied in containers of 100 capsules, NDC 0456-0679-01. Each capsule contains butalbital 50 mg (WARNING:May be habit-forming), acetaminophen 500 mg and caffeine 40 mg. Capsules are red and are imprinted “FOREST 0372” on the cap and “  ESGIC-PLUS®” on the body in white.

Storage

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature.]

Dispense in a tight, light-resistant container with a child-resistant closure.

Rx only

Manufactured by:

MIKART, INC.

Atlanta, GA 30318

Distributed by:

FOREST PHARMACEUTICALS, INC.

Subsidiary of Forest Laboratories, Inc.

St. Louis, MO 63045

Code 822A00

Rev. 05/11

PRINCIPAL DISPLAY PANEL

ESGIC-PLUS  butalbital, acetaminophen and caffeine  capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0456-0679 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength BUTALBITAL (BUTALBITAL) BUTALBITAL 50 mg ACETAMINOPHEN (ACETAMINOPHEN) ACETAMINOPHEN 500 mg CAFFEINE (CAFFEINE) CAFFEINE 40 mg

Inactive Ingredients Ingredient Name Strength CELLULOSE, MICROCRYSTALLINE   CROSCARMELLOSE SODIUM   D&C RED NO. 33   D&C YELLOW NO. 10   FD&C RED NO. 3   GELATIN   MAGNESIUM STEARATE   SILICON DIOXIDE   TITANIUM DIOXIDE

Product Characteristics Color RED Score no score Shape CAPSULE Size 22mm Flavor Imprint Code FOREST;0372;ESGIC;PLUS Contains

Packaging # NDC Package Description Multilevel Packaging 1 0456-0679-01 100 CAPSULE In 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA040085	08/13/1996

Labeler - Forest Laboratories, Inc. (001288281)

Registrant - Mikart, Inc. (030034847)

Establishment
Name	Address	ID/FEI	Operations
Mikart, Inc.		030034847	MANUFACTURE

Establishment
Name	Address	ID/FEI	Operations
Mikart, Inc.		013322387	MANUFACTURE

Revised: 08/2011Forest Laboratories, Inc.

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Compare Esgic-Plus with other medications

• Headache

Amprenavir

Class: HIV Protease Inhibitors
VA Class: AM800
Chemical Name: [3S - [3R*(1R*,2S*)]] - [3 - [[(4 - Aminophenyl)sulfonyl] - (2 - methylpropyl)amino] - 2 - hydroxy - 1 - (phenylmethyl)propyl] tetrahydro-3-furanyl carbamate
Molecular Formula: C₂₅H₃₅N₃O₆S
CAS Number: 161814-49-9
Brands: Agenerase

• 
  

  Because of potential risk of toxicity from the large amount of propylene glycol contained in amprenavir oral solution, the oral solution is contraindicated in infants and children <4 years of age, pregnant women, patients with hepatic or renal failure, and those receiving metronidazole or disulfiram and should be used with caution in others.^{1 46} (See Contraindications and see Propylene Glycol-associated Toxicity under Cautions.)

  
  


• 
  

  Amprenavir oral solution should only be used when amprenavir capsules or other HIV protease inhibitors (PIs) cannot be used.⁴⁶

  
  

Introduction

Antiretroviral; HIV protease inhibitor (PI).^{1 46}

Uses for Amprenavir

Treatment of HIV Infection

In August 2007, the manufacturer of amprenavir announced that sales of the drug would be discontinued as of October 2007.⁷¹ This action was taken because demand for amprenavir had declined substantially and because of the availability of other treatment options (e.g., fosamprenavir oral suspension for the treatment of HIV-1 infection in children).⁷¹ Patients receiving amprenavir should be evaluated for alternative treatment (e.g., an alternative PI or a different antiretroviral regimen).⁷¹

Treatment of HIV-1 infection in conjunction with other antiretrovirals.^{1 14 15 16 46}

When selecting a PI-based regimen for initial therapy in adults, fosamprenavir (with or without low-dose ritonavir) recommended instead of amprenavir (lower pill burden, once-daily regimen possible, better GI tolerance).¹⁴

If selecting amprenavir for use in multiple-drug regimens, consider that amprenavir is less effective than indinavir in PI-naive patients, that mild to moderate adverse GI effects have led to discontinuance of amprenavir during the first 12 weeks of therapy, and that data are limited regarding response to amprenavir in PI-experienced patients.^{1 46}

Amprenavir Dosage and Administration

Administration

Oral Administration

Administer orally.¹ May be given without regard to meals, but avoid high-fat meals since absorption of the drug may be decreased.^{1 14 46}

The liquid-filled capsules and oral solution are not bioequivalent and are not interchangeable on a mg-per-mg basis.^{1 46}

Oral solution should be used only when amprenavir capsules or other PIs cannot be used; switch patients from the oral solution as soon as they are able to take capsules.^{1 46}

Dosage

Must be given in conjunction with other antiretrovirals.^{1 46} If used with ritonavir capsules, dosage adjustment recommended and additional drug interactions must be considered (see Specific Drugs under Interactions.).^{1 46}

Pediatric Patients

Treatment of HIV Infection

Oral

Pediatric Dosage for Treatment of HIV

Age and Weight (kg)	Dosage for Liquid-filled Capsules	Dosage for Oral Solution
4–12 years of age weighing <50 kg	20 mg/kg twice daily or 15 mg/kg 3 times daily (maximum 2.4 g daily)1 15	22.5 mg/kg (1.5 mL/kg) twice daily or 17 mg/kg (1.1 mL/kg) 3 times daily (maximum 2.8 g daily)15 46
13–16 years of age weighing <50 kg	20 mg/kg twice daily or 15 mg/kg 3 times daily (maximum 2.4 g daily)1 15	22.5 mg/kg (1.5 mL/kg) twice daily or 17 mg/kg (1.1 mL/kg) 3 times daily (maximum 2.8 g daily) 15 46
13–16 years of age weighing ≥50 kg	1.2 g twice daily1	1.4 g twice daily14 46
>16 years of age	1.2 g twice daily1	1.4 g twice daily46

Adults

Treatment of HIV Infection

Oral

Liquid-filled Capsules: 1.2 g twice daily.^{1 14}

If used in conjunction with low-dose ritonavir, manufacturer recommends amprenavir 1.2 g once daily with ritonavir 200 mg once daily or amprenavir 600 mg twice daily with ritonavir 100 mg twice daily.¹

Oral Solution: 1.4 g twice daily.^{14 46}

Special Populations

Hepatic Impairment

Dosage recommendations not available for children with hepatic impairment since the drug has not been evaluated in these patients.^{1 46}

Dosage adjustments necessary in adults with hepatic impairment based on Child-Pugh scores; oral solution contraindicated in those with hepatic failure.^{1 46 49}

Liquid-filled Capsules: 450 mg twice daily in adults with Child-Pugh scores 5–8 and 300 mg twice daily in those with Child-Pugh scores 9–12.^{1 49}

Oral Solution: 513 mg (34 mL) twice daily in adults with Child-Pugh scores 5–8 and 342 mg (23 mL) twice daily in those with Child-Pugh scores 9–12.⁴⁶

Renal Impairment

Dosage adjustments not needed.¹

Use oral solution with caution in patients with renal impairment;⁴⁶ oral solution contraindicated in those with renal failure.⁴⁶

Geriatric Patients

Cautious dosage selection; pharmacokinetics have not been studied in this age group.^{1 46}

Cautions for Amprenavir

Contraindications

• 
  

  Known hypersensitivity to amprenavir or any ingredient in the formulation.^{1 46}

  
  


• 
  

  Use of oral solution in infants and children <4 years of age, pregnant women, patients with hepatic or renal failure, and patients receiving disulfiram or metronidazole due to the potential risk of propylene glycol-associated toxicity.^{1 46} (See Specific Drugs under Interactions.)

  
  


• 
  

  Concomitant use with drugs highly dependent on CYP3A4 for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., cisapride, ergot derivatives, pimozide, midazolam, triazolam).^{1 46} (See Specific Drugs under Interactions.)

  
  


• 
  

  Concomitant use of ritonavir-boosted amprenavir with flecainide or propafenone.^{1 46} (See Specific Drugs under Interactions.)

  
  

Warnings/Precautions

Warnings

Interactions

Concomitant use with certain drugs is not recommended (e.g., rifampin, lovastatin, simvastatin, St. John’s wort, fluticasone) or requires particular caution (e.g., sildenafil, tadalafil, vardenafil).¹ (See Specific Drugs under Interactions.)

Propylene Glycol-Associated Toxicity

Possible toxicity from the large amount of propylene glycol in the oral solution;⁴⁶ only limited information available regarding chronic exposure to large amounts of propylene glycol.⁴⁶

Infants and children <4 years of age, women, and certain ethnic populations (Asians, Native Alaskans, Native Americans) may be at increased risk.⁴⁶ (See Contraindications under Cautions.)

Use oral solution only when amprenavir liquid-filled capsules and other PIs cannot be used.⁴⁶ Switch to amprenavir capsules as soon as patient is able to take capsules.^{1 46}

If oral solution is used, monitor for propylene glycol-associated adverse events (e.g., seizures, stupor, tachycardia, hyperosmolality, lactic acidosis, renal toxicity, hemolysis).⁴⁶

Concomitant use of amprenavir oral solution and ritonavir oral solution not recommended because the large amount of propylene glycol in the amprenavir preparation and alcohol in the ritonavir preparation may compete for the same metabolic elimination pathway.⁴⁶

If accidental overdosage of the oral solution occurs, consider the large amount of propylene glycol in the preparation.^{1 46} Monitor for toxicity and manage acid-base abnormalities;^{1 46} propylene glycol can be removed by hemodialysis.⁴⁶

Hyperglycemic and Diabetogenic Effects

Hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of PIs; diabetic ketoacidosis has occurred.^{1 36 46}

Monitor blood glucose and initiate or adjust dosage of insulin or oral hypoglycemic agents as needed.^{1 46}

Dermatologic Reactions

Severe and life-threatening skin reactions, including Stevens-Johnson syndrome, have occurred.^{1 46}

Discontinue if severe or life-threatening rash or moderate rash accompanied by systemic symptoms occurs.^{1 46}

Sensitivity Reactions

Sulfonamide Hypersensitivity

Because amprenavir is a sulfonamide derivative, use with caution in patients with known sulfonamide allergy.^{1 46}

General Precautions

HIV Resistance

Possibility of HIV resistant to amprenavir and possible cross-resistance to other PIs.^{1 46} Effect of amprenavir therapy on subsequent therapy with other PIs unknown.^{1 46}

Hemophilia A and B

Spontaneous bleeding reported with PIs;^{1 37 41 46} causal relationship not established.^{1 46}

Use with caution in patients with a history of hemophilia type A or B.^{1 37 46} Increased hemostatic (e.g., antihemophilic factor) therapy may be needed.^{1 46}

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]); this may necessitate further evaluation and treatment.¹

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and general cushingoid appearance.^{1 27 46}

Lipid Effects

Increases in total serum cholesterol and triglyceride concentrations have occurred with amprenavir with or without ritonavir.^{1 46}

Determine serum triglycerides and cholesterol concentrations prior to and periodically during therapy; manage lipid disorders as clinically appropriate.^{1 46} (See HMG-CoA Reductase Inhibitors under Interactions.)

Vitamin E Content

Each 50-mg amprenavir capsule contains 36 units and each mL of the oral solution contains 46 units of vitamin E.^{41 46} Vitamin E content of usual dosages of these formulations exceeds recommended daily intake.^{1 46}

Supplemental vitamin E should not be taken during amprenavir therapy.^{1 46}

The high vitamin E content of the capsules and oral solution may exacerbate vitamin K deficiency caused by anticoagulant therapy or malabsorption.^{1 46}

Effects of long-term, high-dose vitamin E not well characterized and not specifically studied in HIV-infected individuals.^{1 46}

Specific Populations

Pregnancy

Category C.¹

Antiretroviral Pregnancy Registry at 800-258-4263.¹

The oral solution contraindicated during pregnancy because of potential risk to the fetus from the high propylene glycol content.^{1 46 58} Some experts state safety and pharmacokinetic data insufficient to recommend amprenavir liquid-filled capsules in pregnant women.⁵⁸

Lactation

Distributed into milk in rats;^{1 46} not known whether distributed into human milk.^{1 46}

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.^{1 46}

Pediatric Use

Safety and efficacy not established in children <4 years of age.^{1 15 46}

The oral solution contraindicated in infants and children <4 years of age because of potential risk of toxicity from the high propylene glycol content.^{1 46}

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.^{1 46}

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^{1 46}

Hepatic Impairment

Clearance may be decreased;^{1 46} dosage adjustments necessary.^{1 46 49} (See Hepatic Impairment under Dosage and Administration.)

Use with caution; assess hepatic function prior to and periodically during therapy.^{1 46}

Oral solution contraindicated in those with hepatic failure because of increased risk of propylene glycol-associated adverse events.^{1 46}

Renal Impairment

Effects on amprenavir pharmacokinetics not studied.^{1 46}

Because of increased risk of propylene glycol-associated adverse events, oral solution should be used with caution in those with renal impairment and is contraindicated in those with renal failure.⁴⁶

Common Adverse Effects

Nausea, vomiting, diarrhea, abdominal pain/discomfort, taste disorder, rash, paresthesia (oral/perioral).^{1 27 46}

Interactions for Amprenavir

Amprenavir is metabolized by CYP3A4 and also is an inhibitor of CYP3A4.^{1 46}

Does not inhibit CYP2D6, 1A2, 2C9, 2C19, or P2E1.^{1 46}

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors or substrates of CYP3A4 with possible alteration in metabolism of amprenavir and/or the other drug.^{1 4 46}

Specific Drugs

Drug	Interaction	Comments
Abacavir	Possible increased amprenavir plasma concentrations and AUC;1 46 no effect on abacavir pharmacokinetics1 46 In vitro evidence of synergistic antiretroviral effects1 46	No dosage adjustments recommended41
Alcohol	Increased risk of propylene glycol-associated adverse effects in those receiving oral solution46	Alcoholic beverages should not be consumed while receiving amprenavir oral solution46
Antacids	Possible decreased amprenavir concentrations1 46	Take amprenavir at least 1 hour before or after antacids1 46
Antiarrhythmic agents (amiodarone, systemic lidocaine, quinidine)	Possible increased antiarrhythmic agent concentrations;1 46 potential for serious and/or life-threatening effects (e.g., cardiac arrhythmias) with certain agents1 46	Use concomitantly with caution; antiarrhythmic concentration monitoring recommended1 46
Anticoagulants, oral	Warfarin concentrations affected1 46 High vitamin E content of amprenavir preparations may exacerbate blood coagulation defect of vitamin K deficiency caused by anticoagulants1	Monitor INR1 46
Anticonvulsants (carbamazepine, phenobarbital, phenytoin)	Possible decreased amprenavir concentrations;1 46 possible decreased effectiveness of the antiretroviral1 46	Use concomitantly with caution1 46
Antidepressants, tricyclics	Possible increased concentrations of tricyclic antidepressants (amitriptyline, imipramine) and potential for serious and/or life-threatening effects1 46	Monitor tricyclic antidepressant concentrations1 46
Antifungals, azoles (itraconazole, ketoconazole, voriconazole)	Itraconazole or ketoconazole: Possible increased antifungal concentrations;1 46 possible effect on amprenavir pharmacokinetics1 46 Voriconazole: Possible inhibition of amprenavir metabolism and/or voriconazole metabolism68	Itraconazole or ketoconazole: Monitor for adverse effects of the antifungal;1 46 reduction in antifungal dosage may be needed in those receiving itraconazole or ketoconazole dosages >400 mg daily1 46 Voriconazole: Monitor for toxicities related to voriconazole and/or the PI68
Antimycobacterials, rifamycins (rifabutin, rifampin, rifapentine)	Rifabutin: Decreased amprenavir concentrations; increased concentrations of rifabutin and rifabutin metabolite1 50 46 Rifampin: Decreased amprenavir concentrations;1 46 possible loss of virologic response and possible resistance to the antiretroviral1 46	Rifabutin: Reduce rifabutin dosage to ≥50% of usually recommended dosage; monitor for neutropenia by performing weekly CBC as clinically indicated1 46 Rifampin: Concomitant use contraindicated1 45 46 63 Rifapentine: Concomitant use not recommended14
Benzodiazepines	Possible increased concentrations of midazolam or triazolam; potential for serious and/or life-threatening effects (e.g., prolonged or increased sedation or respiratory depression)1 46 Possible increased concentrations of alprazolam, clorazepate, diazepam, flurazepam1 46	Concomitant use with midazolam or triazolam contraindicated1 46 Clinical importance of interaction with other benzodiazepines unknown; a decrease in benzodiazepine dosage may be needed1 46
Calcium-channel blocking agents (diltiazem, felodipine, nifedipine, nicardipine, nimodipine, verapamil, amlodipine, nisoldipine, isradipine)	Possible increased concentrations of calcium-channel blocking agent1 46	Use concomitantly with caution; clinical monitoring recommended1 46
Cisapride	Possible increased cisapride concentrations; potential for serious and/or life-threatening effects (e.g., cardiac arrhythmias)1 46	Concomitant use contraindicated1 14 46
Clarithromycin	Increased amprenavir concentrations and AUC;1 24 46 possible decreased clarithromycin concentrations and decreased 14-hydroxyclarithromycin concentrations and AUC24	No dosage adjustments recommended1 24 41
Corticosteroids (dexamethasone, fluticasone)	Fluticasone nasal spray/oral inhalation: Increased fluticasone concentrations with amprenavir (with or without low-dose ritonavir) resulting in decreased cortisol concentrations1 46 Dexamethasone: Possible decreased amprenavir concentrations; possible loss of virologic response1 46	Fluticasone nasal spray/oral inhalation: Consider alternative in patients receiving amprenavir (without ritonavir), especially when long-term corticosteroid therapy is anticipated; concomitant use with ritonavir-boosted amprenavir not recommended unless potential benefits outweigh risk of systemic corticosteroid adverse effects1 46 Dexamethasone: Use with caution1 46
Darunavir		Concomitant use of ritonavir-boosted darunavir and amprenavir not recommended pending further accumulation of data70
Delavirdine	Possible increased amprenavir concentrations and AUC1 46 Possible decreased delavirdine concentrations and AUC;1 46 possible loss of virologic response and possible resistance to delavirdine1 46	Should not be used concomitantly1 46
Didanosine	Possible decreased amprenavir concentrations with buffered didanosine preparations1 46 In vitro evidence of synergistic antiretroviral effects1 46	Administer amprenavir at least 1 hour before or after buffered didanosine (pediatric oral solution admixed with antacid)1 46
Disulfiram	Potential risk of toxicity if used concomitantly with amprenavir oral solution because of the large amount of propylene glycol in the solution1 46	Concomitant use of disulfiram and amprenavir oral solution contraindicated1 46
Efavirenz	Possible decreased amprenavir concentrations and AUC;1 43 46 possible increased efavirenz AUC43	Appropriate dosages for concomitant use with respect to safety and efficacy not established1 46
Emtricitabine	In vitro evidence of additive or synergistic antiretroviral effectsb
Ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine)	Possible increased concentrations of ergot alkaloids and potential for serious and/or life-threatening effects such as ergot toxicity (peripheral vasospasm and ischemia of the extremities and other tissues)1 46	Concomitant use contraindicated1 14 46 If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving amprenavir, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible58
Estrogens/Progestins	Hormonal contraceptives: Possible decreased amprenavir concentrations with ethinyl estradiol and norethindrone;1 46 possible loss of virologic response and possible resistance to the antiretroviral1 46	Hormonal contraceptives: Use alternative nonhormonal contraceptives1 46
Fosamprenavir	Possible increased toxicity14	Do not use concomitantly; fosamprenavir is a prodrug of amprenavir14
HMG-CoA reductase inhibitors	Possible decreased clearance and increased concentrations of some HMG-CoA reductase inhibitors with potential for increased risk of myopathy (including rhabdomyolysis)1 46	Concomitant use with lovastatin or simvastatin not recommended;1 46 caution if used with other HMG-CoA reductase inhibitors1 46 If used with atorvastatin, use lowest possible initial atorvastatin dosage with careful monitoring1 46 Consider using HMG-COA reductase inhibitors with low potential for interaction (e.g., pravastatin, fluvastatin, rosuvastatin)1 46 59 60 69
Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)	Potential for increased concentrations of cyclosporine, sirolimus, or tacrolimus1 46	Monitor concentrations of the immunosuppressive agent1 46
Indinavir	Increased plasma concentrations and AUC of amprenavir; decreased plasma concentrations and AUC of indinavir1 46 In vitro evidence of additive antiretroviral effects1 46	Appropriate dosages for concomitant use with respect to safety and efficacy not established1 46
Lamivudine	No evidence of pharmacokinetic interaction1 46	No dosage adjustments recommended41
Lopinavir	Pharmacokinetic interaction may affect both drugs1 46 62	Once-daily lopinavir regimen not recommended with amprenavir62 For treatment-naive adults, manufacturer of lopinavir recommends 400 mg of lopinavir and 100 mg of ritonavir (2 tablets) twice daily; consider a dosage increase to 600 mg of lopinavir and 150 mg of ritonavir (3 tablets) twice daily for treatment-experienced adults when reduced susceptibility to lopinavir is suspected62 Manufacturer of lopinavir recommends that adults receive 533 mg of lopinavir and 133 mg of ritonavir (6.7 mL of the oral solution) twice daily62 For pediatric patients 6 months to 12 years of age, manufacturer of lopinavir recommends that those weighing 7 to <15 kg receive a dosage of 13 mg/kg of lopinavir and 3.25 mg/kg of ritonavir twice daily and those weighing 15–45 kg receive 11 mg/kg of lopinavir and 2.75 mg/kg of ritonavir twice daily; those weighing >45 kg should receive 533 mg of lopinavir and 133 mg of ritonavir (6.7 mL oral solution) twice daily or 400 mg of lopinavir and 100 mg of ritonavir (2 tablets) twice daily62 Pediatric patients ≥12 years of age may receive recommended adult dosage62
Methadone	Decreased amprenavir concentrations and AUC; possible decreased effectiveness of the antiretroviral1 46 Decreased methadone concentrations1 46	Consider alternative antiretroviral agents1 46 If used with amprenavir, monitor and consider possible need to increase methadone dosage1 46
Metronidazole	Potential risk of toxicity if used concomitantly with amprenavir oral solution because of the large amount of propylene glycol in the solution 46	Concomitant use contraindicated46
Nelfinavir	Increased plasma concentrations and AUC of amprenavir1 46 In vitro evidence of additive antiretroviral effects1 46	Appropriate dosages for concomitant use with respect to safety and efficacy not established1 46
Nevirapine	Possible decreased amprenavir concentrations1 46	Appropriate dosages for concomitant use with respect to safety and efficacy not established1 46
Pimozide	Possible increased pimozide concentrations;1 46 potential for serious and/or life-threatening effects (e.g., cardiac arrhythmias)1 46	Concomitant use contraindicated1 14 46
Ritonavir	Increased amprenavir plasma concentrations and AUC;1 46 concomitant low-dose ritonavir used to therapeutic advantage (ritonavir-boosted amprenavir1 Potential for the large amount of propylene glycol in amprenavir oral solution and alcohol in ritonavir oral solution to compete for the same metabolic elimination pathway46 In vitro evidence of additive antiretroviral effects1 46	Reduce amprenavir dosage when used concomitantly with ritonavir; if amprenavir capsules used in adults, use amprenavir 1.2 g once daily with ritonavir 200 mg once daily or amprenavir 600 mg twice daily with ritonavir 100 mg twice daily1 46 Appropriate pediatric dosage of amprenavir capsules used concomitantly with ritonavir not established1 Concomitant use of amprenavir oral solution and ritonavir oral solution not recommended46 If ritonavir and amprenavir used concomitantly, concomitant use of flecainide or propafenone contraindicated1 46
St. John’s wort (Hypericum perforatum)	Possible decreased amprenavir concentrations;1 46 54 55 possible loss of virologic response and possible resistance to the antiretroviral1 46 54 55	Concomitant use not recommended1 14 46 54 55
Saquinavir	Decreased amprenavir concentrations1 46 In vitro evidence of synergistic antiretroviral effects1 46	Appropriate dosages for concomitant use with respect to safety and efficacy not established1 46
Sildenafil	Increased sildenafil concentrations; increased risk of sildenafil-associated adverse effects1 46	Use caution and reduced sildenafil dosage (do not exceed 25 mg every 48 hours); monitor closely for adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)1 46
Tadalafil	Increased tadalafil concentrations; increased risk of tadalafil-associated adverse effects66	Use initial tadalafil dosage of 5 mg and do not exceed a single dose of 10 mg in 72 hours66
Tenofovir	In vitro evidence of additive or synergistic antiretroviral effectsc
Tipranavir	Possible decreased amprenavir concentrations with ritonavir-boosted tipranavir67	Concomitant use not recommended67
Trazodone	Possible increased trazodone concentrations1 46	Use with caution; consider decreased trazodone dosage1 46
Vardenafil	Possible increased vardenafil concentrations and possible increase in vardenafil-associated adverse effects65	Use initial vardenafil dosage of 2.5 mg and do not exceed a single dose of 2.5 mg in 24 hours65
Vitamin E	Possible excessive vitamin E dosage because of high vitamin E content of amprenavir preparations1 46 High vitamin E doses may exacerbate blood coagulation defect of vitamin K deficiency caused by anticoagulant therapy or malabsorption1	Supplemental vitamin E not recommended1 46
Zidovudine	Possible increased amprenavir AUC;1 46 possible increased zidovudine concentrations and AUC1 46 In vitro evidence of synergistic antiretroviral effects1 46	No dosage adjustments recommended41

Amprenavir Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability has not been established.^{1 46}

Amprenavir not appreciably absorbed from GI tract when given alone;^{40 41} amprenavir formulated with vitamin E rapidly absorbed following oral administration.^{1 48}

Peak amprenavir plasma concentrations attained 1–2 hours after oral administration of capsules or oral solution formulated with vitamin E.^{1 48 46}

Amprenavir liquid-filled capsules and oral solution not bioequivalent; oral solution about 14% less bioavailable compared with capsules.^{1 46}

Food

Oral bioavailability of amprenavir may be decreased if administered with a high-fat meal.^{1 46}

Distribution

Extent

Animal studies indicate distribution into various tissues.²

CSF concentrations <1% of plasma concentrations.⁴¹

Amprenavir crosses the placenta and is distributed into milk in animals.⁴¹ Not known whether drug crosses human placenta or is distributed into human milk.¹⁴

Plasma Protein Binding

90% bound to plasma or serum proteins, principally to α₁-acid glycoprotein.^{1 23 46}

Elimination

Metabolism

Metabolized in liver principally by CYP3A4.^{1 4 46}

Elimination Route

About 14% of an oral dose excreted in urine and 75% eliminated in feces.^{1 41 46} Only minimal amounts eliminated unchanged in urine or feces.^{1 46}

Half-life

7.1–10.6 hours in HIV-infected adults with normal renal and hepatic function.^{1 2 41 46 48}

Special Populations

Peak plasma concentrations and AUC may be increased in patients with hepatic impairment.^{1 46 49}

Pharmacokinetics not studied to date in patients with renal impairment; decreased clearance not expected.^{1 46}

Stability

Storage

Oral

Liquid-filled Capsules

25°C.¹

Solution

25°C.⁴⁶

Actions and SpectrumActions

• 
  

  Pharmacologically related to, but structurally different from, other PIs (e.g., atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir) and other currently available antiretrovirals.^{11 21}

  
  


• 
  

  Active against HIV-1 and, to a lesser extent, HIV-2.^{1 7 11 46}

  
  


• 
  

  Inhibits replication of HIV-1 and HIV-2 by interfering with HIV protease.^{1 7 11 46}

  
  


• 
  

  HIV-1 with reduced susceptibility to amprenavir have been selected in vitro and have emerged during therapy with the drug.^{1 2 5 6 7 8 19 20 46}

  
  


• 
  

  Varying degrees of cross-resistance occur among PIs; only limited data available to date regarding cross-resistance between amprenavir and other PIs.^{1 2 5 6 7 8 9}

Excedrin PM Caplet

Generic Name: acetaminophen and diphenhydramine (a SEET a MIN oh fen and DYE fen HYE dra meen)

Brand Names: Anacin P.M. Aspirin Free, Coricidin Night Time Cold Relief, Excedrin PM, Excedrin PM Caplet, Excedrin PM Express Gels, Headache Relief PM, Legatrin PM, Mapap PM, Midol PM, Night Time Pain, Percogesic Extra Strength, Percogesic Original Strength, Tylenol Cold Relief Caplet, Tylenol Cold Relief Nighttime, Tylenol Cold Relief Nighttime Caplet, Tylenol Extra Strength PM, Tylenol Extra Strength PM Rapid Release Gelcaps, Tylenol Extra Strength PM Vanilla Caplet, Tylenol PM, Tylenol Sore Throat Nighttime, Unisom with Pain Relief

What is Excedrin PM Caplet (acetaminophen and diphenhydramine)?

Acetaminophen is a pain reliever and 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.

The combination of acetaminophen and diphenhydramine is used to treat headache, fever, body aches, runny or stuffy nose, sneezing, itching, watery eyes, and sinus congestion caused by allergies, the common cold, or the flu.

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

What is the most important information I should know about Excedrin PM Caplet (acetaminophen and diphenhydramine)?

Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death. Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You should not use this medicine if you have severe constipation, a blockage in your stomach or intestines, or if you are unable to urinate. Do not use this medicine if you have untreated or uncontrolled diseases such as glaucoma, asthma or COPD, heart disease, or overactive thyroid. Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen and can increase certain side effects of diphenhydramine. 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.

What should I discuss with my healthcare provider before taking Excedrin PM Caplet (acetaminophen and diphenhydramine)?

You should not use this medicine if you have severe constipation, a blockage in your stomach or intestines, or if you are unable to urinate. Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take medicine that contains acetaminophen. Do not use this medicine if you have untreated or uncontrolled diseases such as glaucoma, asthma or COPD, high blood pressure, heart disease, coronary artery disease, or overactive thyroid.

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have:

• 
  

  liver disease, cirrhosis, or a history of alcoholism;

  
  


• 
  

  a blockage in your digestive tract (stomach or intestines);

  
  


• 
  

  kidney disease;

  
  


• 
  

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

  
  


• 
  

  enlarged prostate or urination problems;

  
  


• 
  

  low blood pressure; or

  
  


• 
  

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

  
  

It is not known whether acetaminophen and diphenhydramine will harm an unborn baby. Do not use this medicine without your doctor's advice if you are pregnant. This medication may pass into breast milk and may harm a nursing baby. Antihistamines and decongestants may also slow breast milk production. Do not use this medicine without your doctor's advice if you are breast-feeding a baby.

How should I take Excedrin PM Caplet (acetaminophen and diphenhydramine)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. This medicine is usually taken only for a short time until your symptoms clear up.

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

Measure liquid medicine with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

Do not take for longer than 7 days in a row. Stop taking the medicine and call your doctor if you still have a fever after 3 days of use, you still have pain after 7 days (or 5 days if treating a child), if your symptoms get worse, or if you have a skin rash, ongoing headache, or any redness or swelling.

If you need surgery or medical tests, tell the surgeon or doctor ahead of time if you have taken this medicine within the past few days. Store at room temperature away from moisture and heat. Do not allow liquid medicine to freeze.

What happens if I miss a dose?

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

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1 800 222 1222. An overdose of acetaminophen can be fatal.

The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

Overdose symptoms may also include severe forms of some of the side effects listed in this medication guide.

What should I avoid while taking Excedrin PM Caplet (acetaminophen and diphenhydramine)?

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, and can increase certain side effects of diphenhydramine. This medicine may cause blurred vision or impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

Excedrin PM Caplet (acetaminophen and diphenhydramine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have a serious side effect such as:

• 
  

  chest pain, rapid pulse, fast or uneven heart rate;

  
  


• 
  

  confusion, hallucinations, severe nervousness;

  
  


• 
  

  tremor, seizure (convulsions);

  
  


• 
  

  easy bruising or bleeding, unusual weakness;

  
  


• 
  

  urinating less than usual or not at all; or

  
  


• 
  

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

  
  

Less serious side effects may include:

• 
  

  dizziness, drowsiness;

  
  


• 
  

  mild headache;

  
  


• 
  

  dry mouth, nose, or throat;

  
  


• 
  

  constipation;

  
  


• 
  

  blurred vision;

  
  


• 
  

  feeling nervous; or

  
  


• 
  

  sleep problems (insomnia);

  
  

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.

What other drugs will affect Excedrin PM Caplet (acetaminophen and diphenhydramine)?

Ask a doctor or pharmacist before using this medicine if you regularly use other medicines that make you sleepy (such as narcotic pain medication, sedatives, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety). They can add to sleepiness caused by diphenhydramine.

Tell your doctor about all other medicines you use, especially:

• 
  

  leflunomide (Arava);

  
  


• 
  

  topiramate (Topamax);

  
  


• 
  

  zonisamide (Zonegran);

  
  


• 
  

  diphenhydramine (Benadryl) applied to the skin;

  
  


• 
  

  an antibiotic, antifungal medicine, sulfa drug, or tuberculosis medicine;

  
  


• 
  

  an antidepressant;

  
  


• 
  

  birth control pills or hormone replacement therapy;

  
  


• 
  

  bladder or urinary medications;

  
  


• 
  

  blood pressure medication;

  
  


• 
  

  a bronchodilator;

  
  


• 
  

  cancer medicine;

  
  


• 
  

  cholesterol-lowering medications such as Lipitor, Niaspan, Zocor, Vytorin, and others;

  
  


• 
  

  gout or arthritis medications (including gold injections);

  
  


• 
  

  HIV/AIDS medication;

  
  


• 
  

  medication for nausea and vomiting, stomach ulcers, or irritable bowel syndrome;

  
  


• 
  

  medicines to treat psychiatric disorders;

  
  


• 
  

  an NSAID such as Advil, Aleve, Arthrotec, Cataflam, Celebrex, Indocin, Motrin, Naprosyn, Treximet, Voltaren, others; or

  
  


• 
  

  seizure medication.

  
  

This list is not complete and other drugs may interact with acetaminophen and diphenhydramine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Excedrin PM Caplet resources

• Excedrin PM Caplet Side Effects (in more detail)
• Excedrin PM Caplet Use in Pregnancy & Breastfeeding
• Drug Images
• Excedrin PM Caplet Drug Interactions
• Excedrin PM Caplet Support Group
• 4 Reviews for Excedrin PM Caplet - Add your own review/rating

Compare Excedrin PM Caplet with other medications

• Headache
• Insomnia
• Pain

Where can I get more information?

• Your pharmacist can provide more information about acetaminophen and diphenhydramine.

See also: Excedrin PM Caplet side effects (in more detail)

Corvite 150

Pronunciation: VYE-ta-min/FOE-lik AS-id/EYE-urn/zink
Generic Name: Vitamin B Complex/Vitamin C/Folic Acid/Iron/Zinc
Brand Name: Corvite 150

Accidental overdose of products that contain iron is a leading cause of fatal poisoning in children younger than 6 years old. Keep this and all medicines out of the reach of children. In case of accidental ingestion, call the poison control center or a doctor at once.

Corvite 150 is used for:

Preventing and treating certain types of anemia (eg, caused by low blood iron levels, poor nutrition). It may also be used for other conditions as determined by your doctor.

Corvite 150 is a vitamin, mineral, folic acid, and iron combination. It works by providing vitamins, minerals, folic acid, and iron to the body.

Do NOT use Corvite 150 if:

• you are allergic to any ingredient in Corvite 150


• you have high levels of iron in the blood (eg, hemochromatosis, hemosiderosis)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Corvite 150:

Some medical conditions may interact with Corvite 150. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have any other type of anemia (eg, pernicious anemia)


• if you have stomach or bowel problems (eg, inflammation, Crohn disease, ulcer), metabolism problems, the blood disease porphyria, or a blood disease (eg, thalassemia)


• if you have a bleeding problem, have had multiple blood transfusions, or are receiving dialysis

Some MEDICINES MAY INTERACT with Corvite 150. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Fluorouracil because the risk of its side effects may be increased by Corvite 150


• Doxycycline, hydantoins (eg, phenytoin), mycophenolate, penicillamine, or thyroid hormones (eg, levothyroxine) because their effectiveness may be decreased by Corvite 150.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Corvite 150 may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Corvite 150:

Use Corvite 150 as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Corvite 150 by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.


• If you also take bisphosphonates (eg, alendronate), cefdinir, methyldopa, a quinolone antibiotic (eg, ciprofloxacin), or a tetracycline antibiotic (eg, minocycline), ask your doctor or pharmacist how to take it with Corvite 150.


• If you miss a dose of Corvite 150, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Corvite 150.

Important safety information:

• Do not take more than the recommended dose without checking with your doctor.


• Do not take large doses of vitamins (megadoses or megavitamin therapy) while you use Corvite 150 unless your doctor tells you to.


• Corvite 150 has pyridoxine (vitamin B₆), folic acid, iron, and zinc in it. Before you start any new medicine, check the label to see if it also has pyridoxine, folic acid, iron, or zinc in it. If it does or if you are not sure, check with your doctor or pharmacist.


• Corvite 150 may interfere with certain lab tests, such as tests used to check for blood in the stool. Be sure your doctor and lab personnel know you are taking Corvite 150.


• Corvite 150 should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Corvite 150 while you are pregnant. Corvite 150 is found in breast milk. If you are or will be breast-feeding while you use Corvite 150, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Corvite 150:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; dark or green stools; diarrhea; nausea; stomach pain; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); black, tarry, or bloody stools; severe or persistent stomach pain.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch .

See also: Corvite50 side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include black, tarry, or bloody stools; blue or unusually pale skin; drowsiness or dizziness; fast heartbeat; increased thirst or urination; seizures; severe or persistent nausea, vomiting, diarrhea, or stomach pain; sluggishness; vomiting blood; weakness.

Proper storage of Corvite 150:

Store Corvite 150 at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Corvite 150 out of the reach of children and away from pets.

General information:

• If you have any questions about Corvite 150, please talk with your doctor, pharmacist, or other health care provider.


• Corvite 150 is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Corvite 150. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Corvite 150 resources

• Corvite 150 Side Effects (in more detail)
• Corvite 150 Use in Pregnancy & Breastfeeding
• Corvite 150 Drug Interactions
• Corvite 150 Support Group
• 1 Review for Corvite50 - Add your own review/rating

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