HYDROCODONE-ACETAMINOPHEN (hydrocodone bitartrate/acetaminophen)

There are 5 contraindications. Absolute contraindication.

Contraindication List
Acetaminophen overdose
Acute asthma attack
Acute hepatic failure
Acute hepatitis C
Paralytic ileus

There are 14 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute pancreatitis
Alcohol intoxication
Disease of liver
Drug abuse
Exacerbation of chronic obstructive pulmonary disease
Familial dysautonomia
Gastrointestinal obstruction
History of opioid overdose
Intracranial hypertension
Kidney disease with reduction in glomerular filtration rate (GFr)
Respiratory depression
Shock
Sleep apnea
Systemic mastocytosis

There are 17 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Adrenocortical insufficiency
Alcohol withdrawal delirium
Benign prostatic hyperplasia
Biliary tract disorder
Constipation
Cor pulmonale
Debilitation
Hypercapnia
Hypotension
Lower seizure threshold
Protein-calorie malnutrition
Seizure disorder
Shock
Toxic psychosis
Untreated hypothyroidism
Urethral stricture
Urinary retention

There are 50 severe adverse reactions.

More Frequent	Less Frequent
None.	Abnormal hepatic function tests Angioedema Atelectasis Bradycardia Bronchospastic pulmonary disease CNS depression Dyspnea Laryngeal edema Laryngismus Respiratory depression Tachycardia

Rare/Very Rare

Accidental fall Acute generalized exanthematous pustulosis Acute hepatic failure Adrenocortical insufficiency Agranulocytosis Allergic dermatitis Anaphylaxis Angioedema Biliary spasm Dehydration Depression Disorder of adrenal gland Drug dependence Drug-induced hepatitis Female hypogonadism Hallucinations Hearing loss Hypertension Hypokalemia Ileus Increased cerebrospinal fluid pressure Involuntary muscle movement Ischemic colitis Laryngeal edema Leukopenia Maculopapular rash Male hypogonadism Muscle rigidity Neutropenic disorder Pancreatitis Paralytic ileus Seizure disorder Skin rash Sleep apnea Stevens-johnson syndrome Thrombocytopenic disorder Tinnitus Toxic epidermal necrolysis Urticaria

There are 64 less severe adverse reactions.

More Frequent

Less Frequent

Constipation Dizziness Drowsy General weakness Hypotension Malaise Nausea Sedation Syncope

Acute abdominal pain Acute cognitive impairment Anorexia Arthralgia Back pain Blurred vision Diplopia Dysphoric mood False sense of well-being Fatigue Flushing Gastroesophageal reflux disease Headache disorder Hyperhidrosis Lethargy Mood changes Muscle spasm Myalgia Nervousness Night sweats Opioid dependence Orthostatic hypotension Peripheral edema Symptoms of anxiety Tremor Upper respiratory infection Ureteral spasm Urinary tract infection Visual changes Vomiting Xerostomia

Rare/Very Rare
Androgen deficiency Ataxia Dysgeusia Dysphagia Elevated serum amylase Erectile dysfunction Erythema Gastrointestinal irritation Infertility Insomnia Libido changes Medication overuse headache Migraine Musculoskeletal pain Neck pain Nightmares Non-cardiac chest pain Opioid induced allodynia Opioid induced hyperalgesia Palpitations Paresthesia Pruritus of skin Skin rash Urticaria

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. 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.

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. 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.

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.