Lorcet (hydrocodone bitartrate/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.

Dosage of hydrocodone bitartrate and hydrocodone polistirex is expressed in terms of hydrocodone bitartrate.

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.

Hydrocodone-containing preparations are administered orally.

Hydrocodone bitartrate is commercially available as single-entity extended-release tablets or capsules and in various fixed-combination oral preparations with acetaminophen, ibuprofen, or aspirin for the management of pain. Hydrocodone bitartrate is also commercially available in various fixed combination preparations with chlorpheniramine or homatropine methylbromide for the management of cough. See the full prescribing information for additional information on fixed combination preparations.

Store hydrocodone extended-release capsules and tablets at 25degreesC (excursions permitted between 15-30degreesC) in tight, light-resistant containers in a secure location.

Hydrocodone bitartrate and hydrocodone polistirex are administered orally.

When the extended-release oral suspension containing hydrocodone polistirex and chlorpheniramine polistirex (e.g., Tussionex(R) Pennkinetic(R)) is used, patients and caregivers should be strongly advised to use an accurate, calibrated dosing device to measure doses of the suspension. Use of a household teaspoon as a measuring device could result in overdosage. The extended-release oral suspension should not be diluted with other liquids or mixed with other drugs, since this may alter resin binding, thereby altering the rate of hydrocodone absorption and possibly resulting in toxicity. The extended-release oral suspension should not be given more frequently than every 12 hours; if cough is not controlled, the clinician should be contacted. The extended-release oral suspension should be shaken well before each use.

No dosing information is available for this tab.

No dosing information is available for this tab.

Concomitant use of opiate agonists and benzodiazepines or other CNS depressants (e.g., anxiolytics, sedatives, hypnotics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opiate agonists, alcohol) may result in profound sedation, respiratory depression, coma, and death. Opiate agonist antitussives should be avoided in patients taking benzodiazepines, other CNS depressants, or alcohol. Concurrent use of anticholinergic agents with hydrocodone may produce paralytic ileus. Concomitant use of opiate agonists with serotonergic drugs can cause serotonin syndrome. (See Drug Interactions in the Opiate Agonists General Statement 28:08.08.)

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Significant respiratory depression.

*Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment.

*Known or suspected GI obstruction, including paralytic ileus.

*Hypersensitivity to hydrocodone or acetaminophen (e.g., anaphylaxis).

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

*Severe hepatic impairment or severe active liver disease.

*Significant respiratory depression.

*Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment.

*Known or suspected GI obstruction, including paralytic ileus.

*Hypersensitivity to hydrocodone or any ingredient in the formulations.

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 light-headedness, dizziness, sedation, nausea and vomiting.

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).

The most common adverse effects reported in patients receiving hydrocodone bitartrate extended-release tablets are constipation, nausea, vomiting, fatigue, upper respiratory tract infection, dizziness, headache, and somnolence; common adverse effects in patients receiving hydrocodone bitartrate extended-release capsules include constipation, nausea, somnolence, fatigue, headache, dizziness, dry mouth, vomiting, pruritus, abdominal pain, peripheral edema, upper respiratory tract infection, muscle spasms, urinary tract infection, back pain, and tremor.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

The safety and effectiveness of hydrocodone/acetaminophen tablets in pediatric patients have not been established.

The safety and effectiveness of hydrocodone/acetaminophen oral solution in the pediatric population below the age of 2 years have not been established. Use of hydrocodone/acetaminophen oral solution in the pediatric patients over the age of 2 years is supported by evidence from adequate and well controlled studies of hydrocodone and acetaminophen combination products in adults, along with additional data which support the development of metabolic pathways in children 2 years of age and over for pediatric dosage information.

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.

The safety and effectiveness of hydrocodone bitartrate extended-release capsules and tablets have not been established in pediatric patients.

There are no adequate and well-controlled studies in pregnant women. Hydrocodone/acetaminophen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly.

Opioids cross the placenta and may produce respiratory depression and psychophysiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid-induced respiratory depression in the neonate. Hydrocodone/acetaminophen is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

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.

Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome.

Available data with extended-release hydrocodone preparations in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.

Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Monitor neonates exposed to opioid analgesics during labor for signs of excessive sedation and respiratory depression.

Safe use of hydrocodone during pregnancy has not been established; therefore, the drug should not be administered to pregnant women unless the possible benefits outweigh the potential risks.

Hydrocodone is present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for hydrocodone/acetaminophen and any potential adverse effects on the breastfed infant from hydrocodone/acetaminophen or from the underlying maternal condition. Infants exposed to hydrocodone/acetaminophen through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

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.

Hydrocodone is present in human milk. Variable concentrations of hydrocodone and hydromorphone (an active metabolite) have been detected in breast milk with administration of immediate-release hydrocodone to nursing mothers in the early post-partum period. Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with hydrocodone.

It is not known whether hydrocodone is distributed into human milk. A decision should be made to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

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.

In general, select dosage with caution for an elderly patient, 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. When used for the management of pain, titrate slowly in geriatric patients and frequently reevaluate the patient for signs of CNS and respiratory depression.

Elderly patients (aged 65 years or older) may have increased sensitivity to hydrocodone/acetaminophen. In general, use caution when selecting a dosage for an elderly patient, 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. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of hydrocodone/acetaminophen slowly in geriatric patients and frequently reevaluate the patient for signs of CNS and respiratory depression. Hydrocodone/acetaminophen is known to be substantially excreted by the kidney, and the risk of adverse 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 regularly evaluate 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.

Geriatric patients may have increased sensitivity to hydrocodone. Use caution when selecting dosage. Respiratory depression is the main risk for geriatric patients treated with opioids and has occurred after administration of large initial doses in patients who were not opioid-tolerant or when opioids were co-administered with other drugs that depress respiration. Titrate dosage slowly and frequently re-evaluate patients for signs of CNS and respiratory depression.