"The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has recommended restricting the use of codeine for cough and cold in children because there is a risk for serious adverse effects, including respiratory"...
Hydrocodone bitartrate, one of the active ingredients in Vituz Oral Solution, produces dose-related respiratory depression by directly acting on brain stem respiratory centers. Overdose of hydrocodone bitartrate in adults has been associated with fatal respiratory depression, and the use of hydrocodone bitartrate in children less than 6 years of age has been associated with fatal respiratory depression. Exercise caution when administering Vituz Oral Solution because of the potential for respiratory depression. If respiratory depression occurs, discontinue Vituz Oral Solution and use naloxone hydrochloride when indicated to antagonize the effect and other supportive measures as necessary [see OVERDOSAGE].
Hydrocodone can produce drug dependence of the morphine type and therefore, has the potential for being abused. Psychic dependence, physical dependence, and tolerance may develop upon repeated administration of Vituz Oral Solution. Prescribe and administer Vituz with the same degree of caution appropriate to the use of other opioid drugs [see Drug Abuse and Dependence].
Head Injury and Increased Intracranial Pressure
The respiratory depression effects of opioids and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a pre-existing increase in intracranial pressure. Furthermore, opioids produce adverse reactions which may obscure the clinical course of patients with head injuries. The use of Vituz Oral Solution should be avoided in these patients.
Activities Requiring Mental Alertness
Hydrocodone bitartrate and chlorpheniramine maleate, the active ingredients in Vituz Oral Solution, may produce marked drowsiness and impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Advise patients to avoid engaging in hazardous tasks requiring mental alertness and motor coordination after ingestion of Vituz Oral Solution. Concurrent use of Vituz Oral Solution with alcohol or other central nervous system depressants should be avoided because additional impairment of central nervous system performance may occur.
Acute Abdominal Conditions
Vituz Oral Solution should be used with caution in patients with acute abdominal conditions since the administration of hydrocodone may obscure the diagnosis or clinical course of patients with acute abdominal conditions. The concurrent use of other anticholinergics with hydrocodone may produce paralytic ileus [see DRUG INTERACTIONS].
Co-administration with Anticholinergics
The concurrent use of anticholinergics with hydrocodone may produce paralytic ileus. Exercise caution when using Vituz Oral Solution in patients taking anticholinergic medications [see DRUG INTERACTIONS].
Co-administration with MAOIs or Tricyclic Antidepressants
Vituz Oral Solution should not be used in patients receiving MAOI therapy or within 14 days of stopping such therapy. The use of MAOIs or tricyclic antidepressants with hydrocodone bitartrate, one of the active ingredients in Vituz Oral Solution, may increase the effect of either the antidepressant or hydrocodone [see CONTRAINDICATIONS and DRUG INTERACTIONS].
Patients should be advised to measure Vituz Oral Solution with an accurate milliliter measuring device. Patients should be informed that a household teaspoon is not an accurate measuring device and could lead to overdosage, which can result in serious adverse reactions [see OVERDOSAGE]. Patients should be advised to ask their pharmacist to recommend an appropriate measuring device and for instructions for measuring the correct dose.
Vituz Oral Solution should be used with caution in patients with severe renal impairment [see Use In Specific Populations].
Vituz Oral Solution should be used with caution in patients with severe hepatic impairment [see Use in Specific Populations].
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity, mutagenicity, and reproductive studies have not been conducted with Vituz Oral Solution; however, published information is available for the individual active ingredients or related active ingredients.
Carcinogenicity studies were conducted with codeine, an opiate related to hydrocodone. In 2 year studies in F344/N rats and B6C3F1 mice, codeine showed no evidence of tumorigenicity at dietary doses up to 70 and 400 mg/kg/day, respectively (approximately 30 and 80 times, respectively, the MRHDD of hydrocodone on a mg/m² basis).
In 2 year studies in F344/N rats and B6C3F1 mice, chlorpheniramine maleate showed no evidence of tumorigenicity when administered 5 days/week at oral doses up to 30 and 50 mg/kg/day, respectively (approximately 15 times the MRHDD on a mg/m² basis).
Chlorpheniramine maleate was not mutagenic in the in vitro bacterial reverse mutation assay or the in vitro mouse lymphoma forward mutation assay. Chlorpheniramine maleate was clastogenic in the in vitro CHO cell chromosomal aberration assay.
Chlorpheniramine maleate had no effects on fertility in rats and rabbits at oral doses approximately 20 and 25 times the MRHDD on a mg/m² basis, respectively.
Use In Specific Populations
Teratogenic Effects - Pregnancy Category C
There are no adequate and well-controlled studies of Vituz Oral Solution in pregnant women. Reproductive toxicity studies have not been conducted with Vituz Oral Solution; however, studies are available with individual active ingredients or related active ingredients. Hydrocodone was teratogenic in hamsters. Codeine, an opiate related to hydrocodone, increased resorptions and decreased fetal weight in rats. A single retrospective study reported that chlorpheniramine was teratogenic in humans; however, the significance of these findings was not known. Developmental toxicity was also evident with chlorpheniramine in mice and rats. Because animal reproduction studies are not always predictive of human response, Vituz Oral Solution should be used during pregnancy only if the benefit justifies the potential risk to the fetus.
Hydrocodone has been shown to be teratogenic in hamsters when given in a dose approximately 35 times the maximum recommended human daily dose (MRHDD) (on a mg/m² basis at a single subcutaneous dose of 102 mg/kg on gestation day 8). Reproductive toxicology studies were also conducted with codeine, an opiate related to hydrocodone. In a study in which pregnant rats were dosed throughout organogenesis, a dose of codeine approximately 50 times the MRHDD of hydrocodone (on a mg/m² basis at an oral dose of 120 mg/kg/day of codeine) increased resorptions and decreased fetal weight; however, these effects occurred in the presence of maternal toxicity. In studies in which rabbits and mice were dosed throughout organogenesis, doses of codeine up to approximately 25 and 120 times, respectively, the MRHDD of hydrocodone (on a mg/m² basis at oral doses of 30 and 600 mg/kg/day, respectively), produced no adverse developmental effects.
A retrospective study found a small, but statistically significant, association between maternal use of chlorpheniramine and inguinal hernia and eye or ear anomalies in children. Other retrospective studies have found that the frequency of congenital anomalies, in general, was not increased among offspring of women who took chlorpheniramine during pregnancy. The significance of these findings to the therapeutic use of chlorpheniramine in human pregnancy is not known.
In studies with chlorpheniramine in which pregnant rats and rabbits were dosed throughout organogenesis, oral doses up to approximately 20 and 25 times the MRHDD on a mg/m² basis, respectively, produced no adverse developmental effects. However, when mice were dosed throughout pregnancy, a dose approximately 5 times the MRHDD (on a mg/m² basis at an oral dose of 20 mg/kg/day) was embryolethal, and postnatal survival was decreased when dosing was continued after parturition. Embryolethality was also observed when male and female rats were dosed with approximately 5 times the MRHDD (on a mg/m² basis at an oral dose of 10 mg/kg/day) prior to mating.
Babies born to mothers who have been taking opioids regularly prior to delivery will be physically dependent. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting, and fever. The intensity of the syndrome does not always correlate with the duration of maternal opioid use or dose.
Labor and Delivery
As with all opioids, administration of Vituz Oral Solution to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used.
Caution should be exercised when Vituz is administered to nursing mothers. Hydrocodone and chlorpheniramine are excreted in human milk. The clinical significance is unknown; however, the anticholinergic action of chlorpheniramine may suppress lactation if taken prior to nursing. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Vituz Oral Solution, 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.
Safety and effectiveness of Vituz Oral Solution in pediatric patients under 18 years of age have not been established. The use of hydrocodone in children less than 6 years of age has been associated with fatal respiratory depression [see WARNINGS AND PRECAUTIONS].
Clinical studies have not been conducted with Vituz Oral Solution. Other reported clinical experience with the individual active ingredients of Vituz Oral Solution has not identified differences in responses between the elderly and patients younger than 65 years of age. In general, dose selection for an elderly patient should be made with caution, 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.
Vituz Oral Solution should be given with caution in patients with severe impairment of renal function.
Vituz Oral Solution should be given with caution in patients with severe impairment of hepatic function.
Last reviewed on RxList: 3/1/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Vituz Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.