P-v tussin

Overdose

No human overdosage data are available for P-V Tussin 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, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest, and death may occur.

Overdosage with sympathomimetics, such as pseudoephedrine, may give rise to giddiness, headache, nausea, vomiting, sweating, thirst, tachycardia, precordial pain, palpitations, difficulty in micturition, muscle weakness and tenseness, anxiety, restlessness, and insomnia. Many patients can present a toxic psychosis with delusion and hallucinations. Some may develop cardiac arrhythmias, circulatory collapse, convulsion, coma, and respiratory failure.

Treatment of overdosage consists of discontinuation of P-V Tussin 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

P-V Tussin Oral Solution is contraindicated in:

• Patients with known hypersensitivity to hydrocodone bitartrate, pseudoephedrine hydrochloride, or any of the inactive ingredients of P-V Tussin Oral Solution.
• Patients receiving MAOI therapy or within 14 days of stopping such therapy.
• Patients with narrow angle glaucoma, urinary retention, severe hypertension or severe coronary artery disease.

Undesirable effects

Use of hydrocodone bitartrate, a semisynthetic opioid, may result in the following:

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

Use of pseudoephedrine, a sympathomimetic amine, may result in the following:

• Central nervous system effects such as insomnia, dizziness, weakness, tremor, or convulsions
• Cardiovascular system effects such as arrhythmias, or increased blood pressure, cardiovascular collapse with accompanying hypotension

The most common adverse reactions are central nervous system and cardiovascular reactions and include the following: Sedation, drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, dizziness, psychic dependence, mood changes, nervousness, sleeplessness, tremor or arrhythmia.

Other adverse reactions include:

Gastrointestinal System: Nausea and vomiting (more frequent in ambulatory than in recumbent patients), constipation.

Genitourinary System: Ureteral spasm, spasm of vesicle sphincters, urinary retention.

Cardiovascular System: Fast, slow heartbeat, hypertension, hypotension, orthostatic hypotension, palpitation, shock-like state, syncope.

Dermatological System: Skin rash, pruritus.

Therapeutic indications

P-V Tussin® Oral Solution (hydrocodone bitartrate and pseudoephedrine hydrochloride) is indicated for:

Relief of cough and nasal congestion associated with 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 pseudoephedrine hydrochloride after single-dose administration of 5 mg hydrocodone and 60 mg pseudoephedrine are equivalent to respective reference solutions of 5 mL hydrocodone bitartrate (5 mg/5 mL) and 5 mL pseudoephedrine hydrochloride (60 mg/5 mL).

Hydrocodone had a mean (SD) peak plasma concentration of 10.6 (2.63) ng/mL at 1.4 (0.55) hours. The mean plasma half-life of hydrocodone is approximately 4.9 hours. Pseudoephedrine had a mean (SD) peak plasma concentration of 212 (46.2) ng/mL at 1.8 (0.56) hours. The mean plasma half-life of pseudoephedrine is approximately 5.6 hours.

Name of the medicinal product

Qualitative and quantitative composition

Special warnings and precautions for use

Included as part of the PRECAUTIONS section.

Concomitant use of opioids, including P-V Tussin, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. Because of similar pharmacologic properties, it is reasonable to expect similar risk with concomitant use of opioid cough medications and benzodiazepines, other CNS depressants, or alcohol.

Advise both patients and caregivers about the risks of respiratory depression and sedation if P-V Tussin is used with benzodiazepines, alcohol, or other CNS depressants.

Hydrocodone bitartrate, one of the active ingredients of P-V Tussin 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 administrating P-V Tussin Oral Solution because of the potential for respiratory depression. If respiratory depression occurs, discontinue P-V Tussin Oral Solution and use naloxone hydrochloride when indicated to antagonize the effect and other supportive measures as necessary.

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 P-V Tussin Oral Solution. Prescribe and administer P-V Tussin 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 P-V Tussin Oral Solution should be avoided in these patients.

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

P-V Tussin 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 P-V Tussin Oral Solution in patients taking anticholinergic medications.

P-V Tussin Oral Solution should not be used in patients receiving MAOI therapy or within 14 days of stopping such therapy as an increase in blood pressure or hypertensive crisis, may occur. In addition, the use of MAOIs or tricyclic antidepressants with hydrocodone bitartrate, one of the active ingredients in P-V Tussin Oral Solution, may increase the effect of either the antidepressant or hydrocodone.

The pseudoephedrine hydrochloride contained in P-V Tussin Oral Solution can produce cardiovascular and central nervous system effects in some patients such as insomnia, dizziness, weakness, tremor, or arrhythmias. In addition, central nervous system stimulation with convulsions or cardiovascular collapse with accompanying hypotension has been reported. Therefore, P-V Tussin Oral Solution should be used with caution in patients with cardiovascular disorders, and should not be used in patients with severe hypertension or coronary artery disease.

Patients should be advised to measure P-V Tussin 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.

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

P-V Tussin Oral Solution should be used with caution in patients with severe renal impairment.

P-V Tussin Oral Solution should be used with caution in patients with severe hepatic impairment.

Patients should be advised not to increase the dose or dosing frequency of P-V Tussin Oral Solution because serious adverse events such as respiratory depression may occur with overdosage.

Patients should be advised to measure P-V Tussin 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.

Inform patients and caregivers that potentially fatal additive effects may occur if P-V Tussin Oral Solution is used with benzodiazepines or other CNS depressants, including alcohol. Because of this risk, patients should avoid concomitant use of P-V Tussin Oral Solution with benzodiazepines or other CNS depressants, including alcohol.

Patients should be advised to avoid engaging in hazardous tasks that require mental alertness and motor coordination such as operating machinery or driving a motor vehicle as P-V Tussin Oral Solution may produce marked drowsiness.

Patients should be cautioned that P-V Tussin Oral Solution contains hydrocodone bitartrate and can produce drug dependence.

Patients should be informed that due to its pseudoephedrine component, they should not use P-V Tussin Oral Solution with a MAOI or within 14 days of stopping the use of an MAOI.

Carcinogenicity, mutagenicity, and reproductive studies have not been conducted with P-V Tussin 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).

Two-year feeding studies in rats and mice demonstrated no evidence of carcinogenic potential with ephedrine sulfate, a structurally related drug with pharmacological properties similar to pseudoephedrine, at dietary doses up to 10 and 27 mg/kg, respectively (approximately 0.3 and 0.5 times, respectively, the MRHDD of pseudoephedrine hydrochloride on a mg/m² basis).

Pregnancy Category C.

There are no adequate and well controlled studies of P-V Tussin Oral Solution in pregnant women. Reproductive toxicity studies have not been conducted with P-V Tussin 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, P-V Tussin 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.

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 P-V Tussin 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 P-V Tussin is administered to nursing mothers. Hydrocodone and pseudoephedrine are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from P-V Tussin 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 P-V Tussin 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.

Clinical studies have not been conducted with P-V Tussin Oral Solution. Other reported clinical experience with the individual active ingredients of P-V Tussin 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. The pseudoephedrine contained in P-V Tussin Oral Solution is known to be substantially excreted by the kidney and the risk of toxic 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 monitor renal function.

P-V Tussin Oral Solution should be given with caution in patients with severe impairment of renal function. Pseudoephedrine is primarily excreted unchanged in the urine as unchanged drug with the remainder apparently being metabolized in the liver. Therefore, pseudoephedrine may accumulate in patients with renal impairment.

P-V Tussin Oral Solution should be given with caution in patients with severe impairment of hepatic function.

Dosage (Posology) and method of administration

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

5 mL every 4 to 6 hours as needed, not to exceed 4 doses (20 mL) in 24 hours.