Label: BUTALBITAL, ACETAMINOPHEN, CAFFEINE, AND CODEINE PHOSPHATE - codeine phosphate, butalbital, caffeine and acetaminophen capsule
- NDC Code(s): 54868-5162-0, 54868-5162-1, 54868-5162-2, 54868-5162-3
- Packager: Physicians Total Care, Inc.
- This is a repackaged label.
- Source NDC Code(s): 0591-3220
- Category: HUMAN PRESCRIPTION DRUG LABEL
- DEA Schedule: CIII
- Marketing Status: Abbreviated New Drug Application
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- SPL UNCLASSIFIED SECTION
Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules is supplied in capsule form for oral administration.
Each capsule contains the following active ingredients:
butalbital, USP.......................................50 mg
acetaminophen, USP.........................325 mg
caffeine, USP.........................................40 mg
codeine phosphate, USP.....................30 mg
Butalbital (5-allyl-5-isobutylbarbituric acid) is a short- to intermediate-acting barbiturate. It has the following structural formula:
Acetaminophen (4´-hydroxyacetanilide) is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:
Caffeine (1,3,7-trimethylxanthine) is a central nervous system stimulant. It has the following structural formula:
Codeine phosphate (7,8-Didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol phosphate (1:1) (salt) hemihydrate) is a narcotic analgesic and antitussive. It has the following structural formula:
Inactive Ingredients: colloidal silicon dioxide, magnesium stearate, pregelatinized starch.Close
- CLINICAL PHARMACOLOGY
Butalbital, Acetaminophen, Caffeine and Codeine Phosphate Capsules is a combination drug product intended as a treatment for tension headache.
Butalbital, Acetaminophen, and Caffeine Tablets, USP consists of a fixed combination of butalbital 50 mg, acetaminophen 325 mg, and caffeine 40 mg. 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.
Codeine is readily absorbed from the gastrointestinal tract. It is rapidly distributed from the intravascular spaces to the various body tissues, with preferential uptake by parenchymatous organs such as the liver, spleen and kidney. Codeine crosses the blood-brain barrier, and is found in fetal tissue and breast milk. The plasma concentration does not correlate with brain concentration or relief of pain; however, codeine is not bound to plasma proteins and does not accumulate in body tissues.
The plasma half-life is about 2.9 hours. The elimination of codeine is primarily via the kidneys, and about 90% of an oral dose is excreted by the kidneys within 24 hours of dosing. The urinary secretion products consist of free and glucuronide conjugated codeine (about 70%), free and conjugated norcodeine (about 10%), free and conjugated morphine (about 10%), normorphine (about 4%), and hydrocodone (1%). The remainder of the dose is excreted in the feces.
At therapeutic doses, the analgesic effect reaches a peak within 2 hours and persists between 4 and 6 hours.
See OVERDOSAGE for toxicity information.
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%-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 0.5-20 mcg/mL. This falls within the range of plasma protein binding (20%-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.
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.
Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed throughout most body tissues. The plasma half-life is 1.25-3 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.Close
Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules is indicated for the relief of the symptom complex of tension (or muscle contraction) headache.
Evidence supporting the efficacy and safety of Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules in the treatment of multiple recurrent headaches is unavailable. Caution in this regard is required because codeine and butalbital are habit-forming and potentially abusable.Close
Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules is contraindicated under the following conditions:Close
− Hypersensitivity or intolerance to acetaminophen, caffeine, butalbital, or codeine.
− Patients with porphyria.
In the presence of head injury or other intracranial lesions, the respiratory depressant effects of codeine and other narcotics may be markedly enhanced, as well as their capacity for elevating cerebrospinal fluid pressure. Narcotics also produce other CNS depressant effects, such as drowsiness, that may further obscure the clinical course of the patients with head injuries.
Codeine or other narcotics may obscure signs on which to judge the diagnosis or clinical course of patients with acute abdominal conditions.
Butalbital and codeine are both habit-forming and potentially abusable. Consequently, the extended use of Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules is not recommended.Close
- ADVERSE REACTIONS
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: 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: dry mouth, hyperhidrosis.
Gastrointestinal: difficulty swallowing, heartburn, flatulence, constipation.
Musculoskeletal: leg pain, muscle fatigue.
Miscellaneous: pruritus, fever, earache, nasal congestion, tinnitus, euphoria, allergic reactions.
The following adverse reactions have been voluntarily reported as temporally associated with Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP, a related product containing aspirin, butalbital, caffeine, and codeine.
Central Nervous: abuse, addiction, anxiety, disorientation, hallucination, hyperactivity, insomnia, libido decrease, nervousness, neuropathy, psychosis, sexual activity increase, slurred speech, twitching, unconsciousness, vertigo.
Autonomic Nervous: epistaxis, flushing, miosis, salivation.
Gastrointestinal: anorexia, appetite increased, diarrhea, esophagitis, gastroenteritis, gastrointestinal spasms, hiccup, mouth burning, pyloric ulcer.
Cardiovascular: chest pain, hypotensive reaction, palpitations, syncope.
Skin: erythema, erythema multiforme, exfoliative dermatitis, hives, rash, toxic epidermal necrolysis.
Urinary: kidney impairment, urinary difficulty.
Miscellaneous: allergic reaction, anaphylactic shock, cholangiocarcinoma, drug interaction with erythromycin (stomach upset), edema.
The following adverse drug events may be borne in mind as potential effects of the components of Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules. 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.
Codeine: nausea, vomiting, drowsiness, lightheadedness, constipation, pruritus.
Several cases of dermatological reactions, including toxic epidermal necrolysis and erythema multiforme, have been reported for Butalbital, Acetaminophen, and Caffeine Tablets, USP.Close
- DRUG ABUSE AND DEPENDENCE
Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules is controlled by the Drug Enforcement Administration and is classified under Schedule III.Abuse and Dependence
Codeine can produce drug dependence of the morphine type and, therefore, has the potential for being abused. Psychological dependence, physical dependence, and tolerance may develop upon repeated administration and it should be prescribed and administered with the same degree of caution appropriate to the use of other oral narcotic medications.
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 1,500 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.Close
Following an acute overdosage of Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules, toxicity may result from the barbiturate, the codeine, or the acetaminophen. Toxicity due to the caffeine is less likely, due to the relatively small amounts in this formulation.Signs and Symptoms
Toxicity from barbiturate poisoning include drowsiness, confusion, and coma; respiratory depression; hypotension; and hypovolemic shock. Toxicity from codeine poisoning includes the opioid triad of: pinpoint pupils, depression of respiration, and loss of consciousness. Convulsions may occur. In acetaminophen overdosage: dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necroses, hypoglycemic coma, and thrombocytopenia 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 48-72 hours post-ingestion. In adults hepatic toxicity has rarely been reported with acute overdoses of less than 10 grams, or fatalities with less than 15 grams. Acute caffeine poisoning may cause insomnia, restlessness, tremor, and delirium, tachycardia, and extrasystoles.Treatment
A single or multiple overdose with Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules 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. Vomiting should be induced mechanically, or with syrup of ipecac, if the patient is alert (adequate pharyngeal and laryngeal reflexes). Oral activated charcoal (1 g/kg) should follow gastric emptying. The first dose should be accompanied by an appropriate cathartic. If repeated doses are used, the cathartic might be included with alternate doses as required. Hypotension is usually hypovolemic and should respond to fluids. The value of vasopressor agents such as Norepinephrine or Phenylephrine Hydrochloride in treating hypotension is questionable since they increase vasoconstriction and decrease blood flow. However, if prolonged support of blood pressure is required, Norepinephrine Bitartrate (Levophed®) may be given I.V. with the usual precautions and serial blood pressure monitoring. A cuffed endotracheal tube should be inserted before gastric lavage of the unconscious patient and, when necessary, to provide assisted respiration. If renal function is normal, forced diuresis may aid in the elimination of the barbiturate. Alkalinization of the urine increases renal excretion of some barbiturates, especially phenobarbital.
Meticulous attention should be given to maintaining adequate pulmonary ventilation. In severe cases of intoxication, peritoneal dialysis, or preferably hemodialysis may be considered. If hypoprothrombinemia occurs due to acetaminophen overdose, vitamin K should be administered intravenously.
Naloxone, a narcotic antagonist, can reverse respiratory depression and coma associated with opioid overdose. Naloxone 0.4-2 mg is given parenterally. Since the duration of action of codeine may exceed that of the naloxone, the patient should be kept under continuous surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. A narcotic antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.
If the dose of acetaminophen may have exceeded 140 mg/kg, N-acetyl-cysteine should be administered as early as possible. Serum acetaminophen levels should be obtained, since levels 4 or more hours following ingestion help predict acetaminophen toxicity. Do not await acetaminophen assay results before initiating treatment. Hepatic enzymes should be obtained initially, and repeated at 24-hour intervals.
Methemoglobinemia over 30% should be treated with methylene blue by slow intravenous administration.Toxic doses (for adults)
Butalbital: toxic dose 1 g (20 capsules)Close
Acetaminophen: toxic dose 10 g (30 capsules)
Caffeine: toxic dose 1 g (25 capsules)
Codeine: toxic dose 240 mg (8 capsules)
- DOSAGE AND ADMINISTRATION
One or 2 capsules every 4 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.Close
- HOW SUPPLIED
Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules
Dark blue, opaque cap with a white, opaque body. Cap is imprinted with “WATSON” in light blue. Body is imprinted with “3220” in red.
Bottles of 10 NDC 54868-5162-1,Store and Dispense
Bottles of 90 NDC 54868-5162-2,
Bottles of 100 NDC 54868-5162-0,
Bottles of 30 NDC 54868-5162-3.
Below 30°C (86°F); tight container.
- PRINCIPAL DISPLAY PANEL
Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules
- INGREDIENTS AND APPEARANCE
BUTALBITAL, ACETAMINOPHEN, CAFFEINE, AND CODEINE PHOSPHATE
codeine phosphate, butalbital, caffeine, and acetaminophen capsule capsule
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-5162(NDC:0591-3220) Route of Administration ORAL DEA Schedule CIII Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CODEINE PHOSPHATE (UNII: GSL05Y1MN6) (CODEINE - UNII:Q830PW7520) CODEINE PHOSPHATE 30 mg BUTALBITAL (UNII: KHS0AZ4JVK) (BUTALBITAL - UNII:KHS0AZ4JVK) BUTALBITAL 50 mg CAFFEINE (UNII: 3G6A5W338E) (CAFFEINE - UNII:3G6A5W338E) CAFFEINE 40 mg ACETAMINOPHEN (UNII: 362O9ITL9D) (ACETAMINOPHEN - UNII:362O9ITL9D) ACETAMINOPHEN 325 mg Inactive Ingredients Ingredient Name Strength SILICON DIOXIDE (UNII: ETJ7Z6XBU4) MAGNESIUM STEARATE (UNII: 70097M6I30) STARCH, CORN (UNII: O8232NY3SJ) D&C RED NO. 33 (UNII: 9DBA0SBB0L) FD&C BLUE NO. 1 (UNII: H3R47K3TBD) GELATIN (UNII: 2G86QN327L) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) D&C RED NO. 7 (UNII: ECW0LZ41X8) Product Characteristics Color blue (DARK BLUE) , white (OPAQUE WHITE) Score no score Shape CAPSULE Size 22mm Flavor Imprint Code WATSON;3220 Contains Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:54868-5162-1 10 in 1 BOTTLE 2 NDC:54868-5162-2 90 in 1 BOTTLE 3 NDC:54868-5162-0 100 in 1 BOTTLE 4 NDC:54868-5162-3 30 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA020232 07/06/2009 Labeler - Physicians Total Care, Inc. (194123980) Establishment Name Address ID/FEI Business Operations Physicians Total Care, Inc. 194123980 repack, relabel