DOLOGEN (acetaminophen/dexbrompheniramine maleate)

There are 3 contraindications. Absolute contraindication.

Contraindication List
Acetaminophen overdose
Acute hepatic failure
Acute hepatitis C

There are 7 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Angle-closure glaucoma
Benign prostatic hyperplasia
Bladder outflow obstruction
Chronic idiopathic constipation
Disease of liver
Stenosing peptic ulcer
Urinary retention

There are 8 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Coronary artery disease
Hypertension
Hyperthyroidism
Ocular hypertension
Protein-calorie malnutrition
Pyloroduodenal obstruction
Seizure disorder
Shock

There are 22 severe adverse reactions.

More Frequent	Less Frequent
None.	Abnormal hepatic function tests

Rare/Very Rare

Acute generalized exanthematous pustulosis Acute hepatic failure Agranulocytosis Allergic dermatitis Anaphylaxis Angioedema Blood dyscrasias Drug-induced hepatitis Extrasystoles Hallucinations Hemolytic anemia Hypersensitivity drug reaction Hypotension Laryngeal edema Leukopenia Maculopapular rash Neutropenic disorder Seizure disorder Stevens-johnson syndrome Thrombocytopenic disorder Toxic epidermal necrolysis

There are 54 less severe adverse reactions.

More Frequent	Less Frequent
Anticholinergic toxicity Dizziness Drowsy Thick bronchial secretions	Muscle weakness Sedation

Rare/Very Rare

Abdominal distension Accidental fall Acute abdominal pain Acute cognitive impairment Agitation Anorexia Ataxia Blurred vision Chest discomfort Chills Constipation Diarrhea Diplopia Dry nose Dry throat Dyspnea Dysuria Erythema Euphoria Excitement Fatigue Headache disorder Hyperhidrosis Insomnia Irritability Maculopapular rash Malaise Medication overuse headache Migraine Nausea Nervousness Nightmares Palpitations Paresthesia Pruritus of skin Skin photosensitivity Skin rash Symptoms of anxiety Tachycardia Tinnitus Tremor Urinary retention Urticaria Vertigo Visual changes Vomiting Wheezing Xerostomia

There is inadequate experience with use of brompheniramine or dexbrompheniramine in pregnant women to determine whether the potential for harm to the fetus exists. Because of the risk of severe reactions (e.g., seizures) to antihistamines in neonates, brompheniramine or dexbrompheniramine should not be used during the third trimester; the drugs should be used during the first 2 trimesters only when the potential benefits justify the possible risks to the fetus. 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.

It is not known if brompheniramine is distributed into milk. Because of the potential for serious adverse reactions to antihistamines in nursing infants, a decision should be made whether to discontinue nursing or brompheniramine or dexbrompheniramine, taking into account the importance of the drug to the woman. Excessive crying, irritability, and sleep disturbances occurred in one breast-fed infant whose mother was receiving dexbrompheniramine combined with pseudoephedrine; normal behavior in the infant resumed within 12 hours after the mother discontinued the drug and the infant received 2 formula feedings.

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.

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.