Butalbital-Acetaminophen (butalbital/acetaminophen)

It isessential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

To minimize risk of overdosage, recommended age-appropriate daily dosages of acetaminophen should not be exceeded.

In general, the smallest effective dose should be used. Dosage must be individualized for each patient. Dosage should be reduced in geriatric or debilitated patients and in patients with impaired hepatic function. Because of their higher metabolic rate, children may tolerate comparatively larger doses than adults. Barbiturates should be withdrawn slowly to avoid the possibility of precipitating withdrawal symptoms.

In the treatment of insomnia, consideration should be given to intermittent rather than to daily administration; with daily administration, duration of therapy should be limited to 2 weeks. To prevent rebound in rapid eye movement (REM) sleep, withdrawal of a single therapeutic dose over 5 or 6 days (e.g., decreasing dosage from 3 to 2 doses daily for 1 week) has been recommended when barbiturates are discontinued following prolonged use.

Acetaminophen injection is administered by IV infusion over 15 minutes.

Acetaminophen is also commercially available in fixed-combination with ibuprofen (Combogesic(R)IV) for IV administration. See the full prescribing information for administration of this combination product.

Several commercially available fixed-combination prescription preparations containing acetaminophen are also available for oral use. See the full prescribing information for administration of these combination products.

Acetaminophen is commercially available in various oral and rectal over-the-counter (OTC) preparations as a single ingredient or in combination with other analgesics (e.g., ibuprofen), antihistamines, or decongestants. See the FDA Orange Book and the manufacturer's Drug Facts for further information.

Although most of the barbiturates are administered orally, some barbiturates may be administered rectally, subcutaneously, IM, and/or IV.

No dosing information is available for this tab.

No dosing information is available for this tab.

Concurrent administration of numerous drugs with barbiturates has been reported to affect either the patient's response to the barbiturates or to the other drugs. Most of the reported drug interactions relate to phenobarbital, but the possibility of similar interaction with other barbiturates should be considered.

In addition to the interactions listed, many other drugs have been reported to alter the response to barbiturates and/or have their responses altered by barbiturates; however, in most instances the clinical importance of these interactions has not been established. Since documentation for these interactions may be forthcoming and additional clinically important interactions may be established, caution should be observed when any drug is added to or deleted from any therapeutic regimen which contains a barbiturate, giving consideration to the possible need for dosage adjustment.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Hypersensitivity or intolerance to any component of this product.

*Patients with porphyria.

*Known hypersensitivity to acetaminophen or any ingredient in the formulation.

*Severe hepatic impairment or severe active liver disease.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

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

The most common adverse effects reported in clinical trials in >=5% of patients receiving IV acetaminophen were nausea, vomiting, headache, and insomnia in adults and nausea, vomiting, constipation, and pruritus in pediatric patients.

Common adverse effects associated with oral or rectal administration of acetaminophen include skin rash, hypersensitivity reactions, nephrotoxicity, and hematologic abnormalities (e.g., anemia, leukopenia, neutropenia, and pancytopenia).

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Use of IV acetaminophen for analgesia in pediatric patients >=2 years of age is supported by evidence from adequate and well-controlled studies of IV acetaminophen in adults and additional safety and pharmacokinetic data from 483 pediatric patients ranging in age from neonates to adolescents. Efficacy of IV acetaminophen for analgesia has not been established in pediatric patients <2 years of age.

Use of IV acetaminophen for fever in pediatric patients <2 years of age, including premature neonates (postmenstrual age of at least 32 weeks) is supported by evidence from adequate and well-controlled studies of IV acetaminophen in adults, clinical data in pediatric patients >=2 years of age, and additional safety and pharmacokinetic data from 239 patients <2 years of age, including neonates with a postmenstrual age of at least 32 weeks.

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

Withdrawal seizures were reported in a 2-day-old male infant whose mother had taken a butalbital-containing drug during the last 2 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.

Epidemiologic data regarding oral acetaminophen use in pregnant females have shown no increased risk of major congenital malformations in infants exposed in utero to the medication. In a large population-based prospective cohort study involving more than 26,000 females with live-born singleton infants who were exposed to oral acetaminophen during the first trimester of pregnancy, no increase in the risk of congenital malformations was observed in exposed children compared with a control group of unexposed children; rate of congenital malformations (4.3%) was similar to the rate in the general population. A population-based, case-control study from the National Birth Defects Prevention Study also found no increase in the risk of major birth defects in a group of 11,610 children who had been exposed to acetaminophen during the first trimester of pregnancy compared with a control group of 4,500 children.

Animal reproduction studies in pregnant rats given oral acetaminophen during organogenesis at dosages up to 0.85 times the maximum recommended human daily dosage (4 g daily, based on body surface area comparison) showed evidence of fetotoxicity (reduced fetal weight and length) and a dose-related increase in bone variations (reduced ossification and rudimentary rib changes); the offspring showed no evidence of external, visceral, or skeletal malformations. When pregnant rats received oral acetaminophen throughout gestation at a dosage of 1.2 times the maximum recommended human daily dosage, areas of necrosis occurred in both the liver and kidney of pregnant rats and fetuses; these effects did not occur in animals given acetaminophen at dosages of 0.3 times the maximum recommended human dosage.

In a continuous breeding study in which pregnant mice were given acetaminophen at dosages approximately equivalent to 0.43, 0.87, or 1.7 times the maximum recommended human daily dosage (based on body surface area comparison), a dose-related reduction in body weight of the fourth and fifth litter offspring of the treated mating pair occurred during lactation and following weaning at all dosages studied. Animals receiving the highest dosage had a reduced number of litters per mating pair, male offspring with an increased percentage of abnormal sperm, and reduced birth weights in the next-generation pups.

The manufacturer states that there are no animal reproductive studies with IV acetaminophen.

A correlation between acetaminophen use during pregnancy and neurodevelopmental disorders in children, including autism and attention-deficit/hyperactivity disorder (ADHD), has been observed in studies; however, inconsistent findings have been reported in the literature and a causal relationship has not been established. Results of 2 high-quality studies with sibling controls indicate prenatal exposure to acetaminophen was not associated with an increased risk of a neurodevelopmental diagnosis. There are unmeasured familial confounding factors that may explain the apparent association observed in some studies. Acetaminophen is considered the preferred analgesic/antipyretic for use during pregnancy because of its relatively favorable safety profile compared with other common analgesics. The American College of Obstetricians and Gynecologists (ACOG) supports use of acetaminophen during pregnancy when taken as needed in moderation and after consultation with a doctor. There is no evidence to support any risk associated with appropriate use of acetaminophen during pregnancy. However, untreated maternal fever and pain pose risks such as neural tube defects and preterm birth, necessitating a balanced approach.

Barbiturates can cause fetal harm when administered to pregnant women. Retrospective, case-controlled studies have suggested an association between maternal ingestion of barbiturates and a higher than expected incidence of fetal abnormalities. If a barbiturate is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus.

Based on animal data, repeated or prolonged use of general anesthetics and sedation drugs during the third trimester of pregnancy may result in adverse neurodevelopmental effects in the fetus. The clinical relevance of these animal findings to humans is not known; the potential risk of adverse neurodevelopmental effects should be considered and discussed with pregnant women undergoing procedures requiring general anesthetics and sedation drugs. (See Cautions: Pediatric Precautions.)

Barbiturates have caused postpartum hemorrhage and hemorrhagic disease in neonates. The drug-induced hemorrhagic disease of the neonate is similar to that resulting from vitamin K deficiency and is readily reversible with vitamin K therapy. Neonates born to women who receive barbiturates throughout the last trimester of pregnancy may show withdrawal symptoms. (See Chronic Toxicity: Manifestations.) Neonates whose mothers have received barbiturates during labor should be closely observed for signs of respiratory depression, and treatment for barbiturate overdosage should be instituted if necessary. (See Acute Toxicity: Treatment.) Premature neonates are particularly susceptible to the depressant effects of barbiturates, and the drugs should be administered with caution when delivery of a premature neonate is anticipated.

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, 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.

It is not known if IV acetaminophen is excreted into human milk; however, data suggest following oral administration of acetaminophen, infant exposure is approximately 1-2% of the weight-adjusted maternal daily dosage. Limited published studies report acetaminophen passes rapidly into human milk with similar levels noted in milk and plasma. A case of rash in a breast-fed infant has been reported; the rash resolved when the mother discontinued acetaminophen use and recurred when she resumed acetaminophen therapy. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for acetaminophen and any potential adverse effects on the breast-fed infant from exposure to the medication or to the underlying maternal condition.

Because barbiturates are distributed into the milk of nursing women, nursing should be discontinued if nursing infants of barbiturate-treated women exhibit signs of toxicity.

The manufacturer makes no specific dosage recommendations for geriatric patients. Although no overall differences in efficacy or safety were observed between geriatric and younger patients, and other clinical experience revealed no evidence of age-related differences, the possibility that some older patients may exhibit increased sensitivity to IV acetaminophen cannot be ruled out.

Clinical studies of butalbital/acetaminophen did not include sufficient numbers of patients 65 years of age 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.

When the total number of patients studied in clinical trials of IV acetaminophen is considered, 15% were >=65 years of age, while 5% were >=75 years of age. Although no overall differences in efficacy or safety were observed between geriatric and younger patients, and other clinical experience revealed no evidence of age-related differences, the possibility some older patients may exhibit increased sensitivity to acetaminophen cannot be ruled out.