Tussiclear dh

Overdose

No human overdosage data are available for Tussiclear DH Oral Solution.

Overdosage with hydrocodone is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, dizziness, ringing in the ears, confusion, blurred vision, eye problems, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdose, apnea, circulatory collapse, cardiac arrest and death may occur.

Overdosage with guaifenesin can cause depression of the central nervous system. While present in polypharmacy overdoses, one case of overdose with only significant levels of guaifenesin has been reported. Symptoms included slurred speech, shallow respirations, reduced heart rate with rhythm sinus bradycardia, followed by asystole.

Treatment of overdosage consists of discontinuation of Tussiclear DH Oral Solution together with institution of appropriate therapy. Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The opioid antagonist naloxone hydrochloride is a specific antidote for respiratory depression which may result from overdosage or unusual sensitivity to opioids including hydrocodone. Therefore, an appropriate dose of naloxone hydrochloride should be administered, preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation. For further information, see full prescribing information for naloxone hydrochloride. An antagonist should not be administered in the absence of clinically significant respiratory depression. Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Gastric emptying may be useful in removing unabsorbed drug.

Contraindications

• Patients with known hypersensitivity to hydrocodone bitartrate, guaifenesin, or any of the inactive ingredients of Tussiclear DH Oral Solution.
• Patients receiving MAOI therapy or within 14 days of stopping such therapy.

Undesirable effects

Use of hydrocodone bitartrate is associated with the following:

• Respiratory depression
• Drug dependence
• Increased intracranial pressure
• Decreased mental alertness with impaired mental and/or physical abilities
• Paralytic ileus

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The most common adverse reactions experienced by subjects taking a single dose of Tussiclear DH Oral Solution in the clinical setting include the following: Central Nervous System: headache, dizziness, sedation (somnolence); Gastrointestinal System: nausea, diarrhea; Cardiovascular System: decreased blood pressure; Vascular System: hot flush.

Therapeutic indications

Tussiclear DH Oral Solution is indicated for symptomatic relief of cough and to loosen mucus associated with the common cold.

Not indicated for pediatric patients under 18 years of age.

Pharmacokinetic properties

Systemic exposure (in terms of peak plasma concentrations and area under plasma concentration versus time curve) of hydrocodone bitartrate and guaifenesin after single dose administration of 10 mL Tussiclear DH Oral Solution are equivalent to respective reference solutions of 5 mL hydrocodone bitartrate (5 mg/5 mL), and 10 mL guaifenesin (200 mg/5 mL).

Following a single 10 mL oral dose of Tussiclear DH Oral Solution administered to 36 healthy adults (19-74 years), the geometric mean Cmax and AUC0-inf for hydrocodone were 12.6 ng/ml and 80.9 ng·hr/ml, respectively. The median time to maximum concentration for hydrocodone was about 1.25 hours. Food has no significant effect on the extent of absorption of hydrocodone. The mean plasma half-life of hydrocodone is approximately 5 hours.

Following a single 10 mL oral dose of Tussiclear DH Oral Solution administered to 57 healthy adults (19-74 years), the geometric mean Cmax and AUC0-inf for guaifenesin were 3.7 mcg/ml and 4.2 mcg·hr/ml, respectively. The median time to maximum concentration was about 20 minutes. The effect of food on guaifenesin systemic exposure is not considered to be clinically meaningful. The mean plasma half-life of guaifenesin is approximately 1 hour.

Name of the medicinal product

Qualitative and quantitative composition

Special warnings and precautions for use

Included as part of the PRECAUTIONS section.

Hydrocodone bitartrate, one of the active ingredients in Tussiclear DH 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 Tussiclear DH Oral Solution because of the potential for respiratory depression. If respiratory depression occurs, it may be antagonized by the use of naloxone hydrochloride and other supportive measures when indicated.

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 Tussiclear DH Oral Solution. Prescribe and administer Tussiclear DH Oral Solution with the same degree of caution appropriate to the use of other opioid drugs.

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 Tussiclear DH Oral Solution should be avoided in these patients.

Hydrocodone bitartrate, one of the active ingredients in Tussiclear DH 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 Tussiclear DH Oral Solution. Concurrent use of Tussiclear DH Oral Solution with alcohol or other central nervous system depressants should be avoided because additional impairment of central nervous system performance may occur.

Tussiclear DH 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.

The concurrent use of anticholinergics with hydrocodone may produce paralytic ileus. Exercise caution when using Tussiclear DH Oral Solution in patients taking anticholinergic medications.

Tussiclear DH 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 may increase the effect of either the antidepressant or hydrocodone.

Tussiclear DH Oral Solution should not be used in patients with a persistent or chronic cough such as occurs with smoking, asthma, chronic bronchitis, or emphysema, or where cough is accompanied by excessive phlegm (mucus).

Patients should be advised to measure Tussiclear DH 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. Patients should be advised to ask their pharmacist to recommend an appropriate measuring device and for instructions for measuring the correct dose.

Tussiclear DH Oral Solution should be used with caution in patients with diabetes, thyroid disease, Addison's disease, prostatic hypertrophy or urethral stricture, and asthma.

Tussiclear DH Oral Solution should be used with caution in patients with severe renal impairment..

Tussiclear DH Oral Solution should be used with caution in patients with severe hepatic impairment.

Advise patients not to increase the dose or dosing frequency of Tussiclear DH Oral Solution because serious adverse events such as respiratory depression may occur with overdosage.

Advise patients to measure Tussiclear DH 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, especially when half a teaspoon is measured. Patients should be advised to ask their pharmacist to recommend an appropriate measuring device and for instructions for measuring the correct dose.

Advise patients to avoid the use of alcohol and other central nervous system depressants while taking Tussiclear DH Oral Solution because additional reduction in mental alertness may occur.

Advise patients to avoid engaging in hazardous tasks that require mental alertness and motor coordination such as operating machinery or driving a motor vehicle as Tussiclear DH Oral Solution may produce marked drowsiness.

Caution patients that Tussiclear DH Oral Solution contains hydrocodone bitartrate and can produce drug dependence.

Carcinogenicity, mutagenicity, and reproductive studies have not been conducted with Tussiclear DH Oral Solution; however, published information is available for the individual active ingredients or related active ingredients. Hydrocodone: 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 23 and 65 times, respectively, the MRHDD of hydrocodone on a mg/m² basis). Guaifenesin: Carcinogenicity, genotoxicity, or reproductive toxicology studies have not been conducted with guaifenesin.

Pregnancy Category C

There are no adequate and well controlled studies of Tussiclear DH Oral Solution in pregnant women. Reproductive toxicity studies have not been conducted with Tussiclear DH Oral Solution; however, studies are available with an individual active ingredient or related active ingredient. Hydrocodone was teratogenic in hamsters. Codeine, an opiate related to hydrocodone, increased resorptions and decreased fetal weight in rats. Because animal reproduction studies are not always predictive of human response, Tussiclear DH 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 27 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 40 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 20 and 100 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. Nonteratogenic Effects: 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.

As with all opioids, administration of Tussiclear DH 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 Tussiclear DH Oral Solution is administered to nursing mothers. Hydrocodone is known to be excreted in human milk. No studies have been performed to determine if guaifenesin is excreted into breastmilk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Tussiclear DH 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 Tussiclear DH Oral Solution in pediatric patients under 18 years of age has not been established. The use of hydrocodone in children less than 6 years of age is associated with fatal respiratory depression.

Clinical studies have not been conducted with Tussiclear DH Oral Solution in geriatric populations. Other reported clinical experience with the individual active ingredients of Tussiclear DH 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.

Tussiclear DH Oral Solution should be given with caution in patients with severe impairment of renal function.

Tussiclear DH Oral Solution should be given with caution in patients with severe impairment of hepatic function.

Dosage (Posology) and method of administration

10 mL every 4 to 6 hours, not to exceed 6 doses (60 mL) in 24 hours.

Administer Tussiclear DH Oral Solution by the oral route only. Measure Tussiclear DH Oral Solution with an accurate milliliter measuring device. Do not use a household teaspoon to measure the dose.