TUSSIONEX PENNKINETIC  EXTENDED-RELEASE - hydrocodone bitartrate and chlorpheniramine maleate suspension, extended release
UCB Manufacturing Inc
Tussionex -扑尔敏是一种抗组胺剂，能够降低人体内的天然化学组胺。组胺能生产打喷嚏，发痒，水汪汪的大眼睛，和流鼻涕的症状。
Tussionex是一种麻醉止咳。 扑尔敏和Tussionex的组合是用来治疗鼻塞或流鼻涕，打喷嚏，咳嗽引起的感冒或流感。
扑尔敏Tussionex也可用于其他这种药物指南中未列出的目的。

Tussionex®
Pennkinetic®
(hydrocodone polistirex and chlorpheniramine polistirex)
Extended-Release Suspension

Rx only

DESCRIPTION

Each 5 mL of TUSSIONEX Pennkinetic Extended-Release Suspension contains hydrocodone polistirex equivalent to 10 mg of hydrocodone bitartrate and chlorpheniramine polistirex equivalent to 8 mg of chlorpheniramine maleate. Hydrocodone is a centrally-acting narcotic antitussive. Chlorpheniramine is an antihistamine. TUSSIONEX Pennkinetic Extended-Release Suspension is for oral use only.

Hydrocodone Polistirex

Sulfonated styrene-divinylbenzene copolymer complex with 4,5α-epoxy-3-methoxy-17-methylmorphinan-6-one.

Sulfonated styrene-divinylbenzene copolymer complex with 2-[p-chloro-α-[2-(dimethylamino)ethyl]-benzyl]pyridine.

Ascorbic acid, D&C Yellow No. 10, ethylcellulose, FD&C Yellow No. 6, flavor, high fructose corn syrup, methylparaben, polyethylene glycol 3350, polysorbate 80, pregelatinized starch, propylene glycol, propylparaben, purified water, sucrose, vegetable oil, xanthan gum.

CLINICAL PHARMACOLOGY

Hydrocodone is a semisynthetic narcotic antitussive and analgesic with multiple actions qualitatively similar to those of codeine. The precise mechanism of action of hydrocodone and other opiates is not known; however, hydrocodone is believed to act directly on the cough center. In excessive doses, hydrocodone, like other opium derivatives, will depress respiration. The effects of hydrocodone in therapeutic doses on the cardiovascular system are insignificant. Hydrocodone can produce miosis, euphoria, and physical and psychological dependence.

Chlorpheniramine is an antihistamine drug (H1 receptor antagonist) that also possesses anticholinergic and sedative activity. It prevents released histamine from dilating capillaries and causing edema of the respiratory mucosa.

Hydrocodone release from TUSSIONEX Pennkinetic Extended-Release Suspension is controlled by the Pennkinetic System, an extended-release drug delivery system, which combines an ion-exchange polymer matrix with a diffusion rate-limiting permeable coating. Chlorpheniramine release is prolonged by use of an ion-exchange polymer system.

Following multiple dosing with TUSSIONEX Pennkinetic Extended-Release Suspension, hydrocodone mean (S.D.) peak plasma concentrations of 22.8 (5.9) ng/mL occurred at 3.4 hours. Chlorpheniramine mean (S.D.) peak plasma concentrations of 58.4 (14.7) ng/mL occurred at 6.3 hours following multiple dosing. Peak plasma levels obtained with an immediate-release syrup occurred at approximately 1.5 hours for hydrocodone and 2.8 hours for chlorpheniramine. The plasma half-lives of hydrocodone and chlorpheniramine have been reported to be approximately 4 and 16 hours, respectively.

INDICATIONS AND USAGE

TUSSIONEX Pennkinetic Extended-Release Suspension is indicated for relief of cough and upper respiratory symptoms associated with allergy or a cold in adults and children 6 years of age and older.

CONTRAINDICATIONS

TUSSIONEX Pennkinetic Extended-Release Suspension is contraindicated in patients with a known allergy or sensitivity to hydrocodone or chlorpheniramine.

The use of TUSSIONEX Pennkinetic Extended-Release Suspension is contraindicated in children less than 6 years of age due to the risk of fatal respiratory depression.

WARNINGS

Respiratory Depression

As with all narcotics, TUSSIONEX Pennkinetic Extended-Release Suspension produces dose-related respiratory depression by directly acting on brain stem respiratory centers. Hydrocodone affects the center that controls respiratory rhythm and may produce irregular and periodic breathing. Caution should be exercised when TUSSIONEX Pennkinetic Extended-Release Suspension is used postoperatively and in patients with pulmonary disease, or whenever ventilatory function is depressed. If respiratory depression occurs, it may be antagonized by the use of naloxone hydrochloride and other supportive measures when indicated (see OVERDOSAGE).

Head Injury and Increased Intracranial Pressure

The respiratory depressant effects of narcotics 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, narcotics produce adverse reactions, which may obscure the clinical course of patients with head injuries.

Acute Abdominal Conditions

The administration of narcotics may obscure the diagnosis or clinical course of patients with acute abdominal conditions.

Obstructive Bowel Disease

Chronic use of narcotics may result in obstructive bowel disease especially in patients with underlying intestinal motility disorder.

Pediatric Use

The use of TUSSIONEX Pennkinetic Extended-Release Suspension is contraindicated in children less than 6 years of age (see CONTRAINDICATIONS).

In pediatric patients, as well as adults, the respiratory center is sensitive to the depressant action of narcotic cough suppressants in a dose-dependent manner. Caution should be exercised when administering TUSSIONEX Pennkinetic Extended-Release Suspension to pediatric patients 6 years of age and older. Overdose or concomitant administration of TUSSIONEX Pennkinetic Extended-Release Suspension with other respiratory depressants may increase the risk of respiratory depression in pediatric patients. Benefit to risk ratio should be carefully considered, especially in pediatric patients with respiratory embarrassment (e.g., croup) (see PRECAUTIONS).

PRECAUTIONS

General

Caution is advised when prescribing this drug to patients with narrow-angle glaucoma, asthma, or prostatic hypertrophy.

Special Risk Patients

As with any narcotic agent, TUSSIONEX Pennkinetic Extended-Release Suspension should be used with caution in elderly or debilitated patients and those with severe impairment of hepatic or renal function, hypothyroidism, Addison's disease, prostatic hypertrophy, or urethral stricture. The usual precautions should be observed and the possibility of respiratory depression should be kept in mind.

Information for Patients

Patients should be advised that TUSSIONEX Pennkinetic Extended-Release Suspension 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.

TUSSIONEX Pennkinetic Extended-Release Suspension must not be diluted with fluids or mixed with other drugs as this may alter the resin-binding and change the absorption rate, possibly increasing the toxicity.

Patients should be advised to measure TUSSIONEX Pennkinetic Extended-Release Suspension with an accurate measuring device. A household teaspoon is not an accurate measuring device and could lead to overdosage. A pharmacist can recommend an appropriate measuring device and can provide instructions for measuring the correct dose.

A dosing spoon is provided with the 4 oz (115 mL) packaged product. One side of the spoon is for a 2.5 mL dose. The other side of the spoon is for a 5 mL dose. Instruct the patient to fill to level the side of the spoon for the dose that has been prescribed. The spoon should not be overfilled. Rinse the measuring device or dosing spoon after each use.

Shake well before using.

Keep out of the reach of children.

Cough Reflex

Hydrocodone suppresses the cough reflex; as with all narcotics, caution should be exercised when TUSSIONEX Pennkinetic Extended-Release Suspension is used postoperatively, and in patients with pulmonary disease.

Drug Interactions

Patients receiving narcotics, antihistaminics, antipsychotics, antianxiety agents, or other CNS depressants (including alcohol) concomitantly with TUSSIONEX Pennkinetic Extended-Release Suspension may exhibit an additive CNS depression. When combined therapy is contemplated, the dose of one or both agents should be reduced.

The use of MAO inhibitors or tricyclic antidepressants with hydrocodone preparations may increase the effect of either the antidepressant or hydrocodone.

The concurrent use of other anticholinergics with hydrocodone may produce paralytic ileus.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, mutagenicity, and reproductive studies have not been conducted with TUSSIONEX Pennkinetic Extended-Release Suspension.

Pregnancy

Teratogenic Effects – Pregnancy Category C

Hydrocodone has been shown to be teratogenic in hamsters when given in doses 700 times the human dose. There are no adequate and well-controlled studies in pregnant women. TUSSIONEX Pennkinetic Extended-Release Suspension should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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.

Labor and Delivery

As with all narcotics, administration of TUSSIONEX Pennkinetic Extended-Release Suspension to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used.

Nursing Mothers

It is not known whether this drug is 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 TUSSIONEX Pennkinetic Extended-Release Suspension, 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.

Pediatric Use

The use of TUSSIONEX Pennkinetic Extended-Release Suspension is contraindicated in children less than 6 years of age (see CONTRAINDICATIONS and ADVERSE REACTIONS, Respiratory, Thoracic and Mediastinal Disorders).

TUSSIONEX Pennkinetic Extended-Release Suspension should be used with caution in pediatric patients 6 years of age and older (see WARNINGS, Pediatric Use).

Geriatric Use

Clinical studies of TUSSIONEX did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, 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.

This drug 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.

ADVERSE REACTIONS

Gastrointestinal Disorders

Nausea and vomiting may occur; they are more frequent in ambulatory than in recumbent patients. Prolonged administration of TUSSIONEX Pennkinetic Extended-Release Suspension may produce constipation.

General Disorders and Administration Site Conditions

Death

Nervous System Disorders

Sedation, drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, euphoria, dizziness, psychic dependence, mood changes.

Renal and Urinary Disorders

Ureteral spasm, spasm of vesical sphincters, and urinary retention have been reported with opiates.

Respiratory, Thoracic and Mediastinal Disorders

Dryness of the pharynx, occasional tightness of the chest, and respiratory depression (see CONTRAINDICATIONS).

TUSSIONEX Pennkinetic Extended-Release Suspension may produce dose-related respiratory depression by acting directly on brain stem respiratory centers (see OVERDOSAGE). Use of TUSSIONEX Pennkinetic Extended-Release Suspension in children less than 6 years of age has been associated with fatal respiratory depression. Overdose with TUSSIONEX Pennkinetic Extended-Release Suspension in children 6 years of age and older, in adolescents, and in adults has been associated with fatal respiratory depression.

Skin and Subcutaneous Tissue Disorders

Rash, pruritus.

DRUG ABUSE AND DEPENDENCE

TUSSIONEX Pennkinetic Extended-Release Suspension is a Schedule III narcotic. Psychic dependence, physical dependence and tolerance may develop upon repeated administration of narcotics; therefore, TUSSIONEX Pennkinetic Extended-Release Suspension should be prescribed and administered with caution. However, psychic dependence is unlikely to develop when TUSSIONEX Pennkinetic Extended-Release Suspension is used for a short time for the treatment of cough. Physical dependence, the condition in which continued administration of the drug is required to prevent the appearance of a withdrawal syndrome, assumes clinically significant proportions only after several weeks of continued oral narcotic use, although some mild degree of physical dependence may develop after a few days of narcotic therapy.

OVERDOSAGE

Signs and Symptoms

Serious 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. Although miosis is characteristic of narcotic overdose, mydriasis may occur in terminal narcosis or severe hypoxia. In severe overdosage apnea, circulatory collapse, cardiac arrest and death may occur. The manifestations of chlorpheniramine overdosage may vary from central nervous system depression to stimulation.

Treatment

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 narcotic antagonist naloxone hydrochloride is a specific antidote for respiratory depression which may result from overdosage or unusual sensitivity to narcotics including hydrocodone. Therefore, an appropriate dose of naloxone hydrochloride should be administered, preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation. Since the duration of action of hydrocodone in this formulation may exceed that of the antagonist, the patient should be kept under continued surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. 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.

DOSAGE AND ADMINISTRATION

It is important that TUSSIONEX is measured with an accurate measuring device (see PRECAUTIONS, Information for Patients).

A dosing spoon is provided with the 4 oz (115 mL) packaged product. One side of the spoon is for a 2.5 mL dose. The other side of the spoon is for a 5 mL dose. Fill to level the side of the spoon for the dose that has been prescribed. Do not overfill. Rinse with water after each use.

For prescriptions where a dosing spoon is not provided, a pharmacist can provide an appropriate measuring device and can provide instructions for measuring the correct dose. A household teaspoon is not an accurate measuring device and could lead to overdosage.

Each 5 mL of Tussionex Pennkinetic Extended-Release Suspension contains hydrocodone polistirex equivalent to 10 mg hydrocodone bitartrate, and chlorpheniramine polistirex equivalent to 8 mg chlorpheniramine maleate. Shake well before using. Rinse the measuring device with water after each use.

Adults and Children 12 Years and Older

5 mL every 12 hours; do not exceed 10 mL in 24 hours.

Children 6-11 Years of Age

2.5 mL every 12 hours; do not exceed 5 mL in 24 hours.

This medicine is contraindicated in children under 6 years of age (see CONTRAINDICATIONS).

HOW SUPPLIED

TUSSIONEX Pennkinetic (hydrocodone polistirex and chlorpheniramine polistirex) Extended-Release Suspension, equivalent to 10 mg hydrocodone bitartrate and 8 mg chlorpheniramine maleate per 5 mL, is a gold-colored suspension available as:

• NDC 53014-548-67      473 mL glass bottle
• NDC 53014-548-01      4 oz amber glass bottle containing 115 mL of suspension. Each bottle is supplied with a plastic dosing spoon calibrated for measuring 2.5 mL and 5 mL doses.

For Medical Information

Contact: Medical Affairs Department
Phone: (866) 822-0068
Fax: (770) 970-8859

Storage:

Shake well. Dispense in a well-closed container.

Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

美国FDA提醒：安全合理使用Tussionex
美国食品药品监督管理局（FDA）最近发布了关于Tussionex（氢可酮镇咳药，含氢可酮和氯苯那敏）的安全性通告，通告提醒医生和患者合理、安全使用Tussionex缓释混悬剂。
Tussionex是一种治疗咳嗽的处方药，含有氢可酮和抗组胺药氯苯那敏。氢可酮在Tussionex中是缓解咳嗽的成分，但该成分具有麻醉作用，如服用过量或使用过频会导致呼吸抑制和死亡。故Tussionex不得用于6岁以下的儿童。
FDA收到了关于患者（包括儿童）服用Tussionex出现死亡和致命副作用的报告。报告显示，有医生错误地为6岁以下的儿童开具 Tussionex，以及处方的用药时间间隔少于12小时的现象。此外，患者和医护人员给药过于频繁，从而导致服用过量。大龄儿童、青少年和成人过量服用 Tussionex也会引发致命的呼吸问题和死亡。
FDA向医护人员和患者强调以下安全使用Tussionex的重要信息：
●Tussionex不得用于6岁以下的儿童。FDA收到了关于6岁以下儿童服用Tussionex出现呼吸衰竭致死的报告。
●服用Tussionex的时间间隔不得少于12小时。服用该药间隔时间少于12小时会导致麻醉剂过量。氢可酮过量会引发致命的呼吸问题和死亡。如每隔12小时服用1次Tussionex仍无法缓解咳嗽，患者在加大服用频率之前请先向医生咨询。
●Tussionex处方人员及服用Tussionex的患者应警惕麻醉剂过量而引起的症状，包括：呼吸困难、呼吸浅慢、心跳过慢、嗜睡、皮肤湿冷、行动或言语障碍、虚弱、晕眩或神智不清。如出现以上征兆，患者、家长或医护人员应引起重视并采取必要的措施。
●患者应使用准确测量Tussionex剂量的器具。家庭用的茶匙或汤匙容量各不相同，可能会导致药物过量。请使用为测量液体药品而特别设计的注射器或药勺。
FDA已与Tussionex制药商UCB制药公司协作，对Tussionex的标签进行了修订，添加了关于Tussionex不可用于6岁以下儿童以及需要正确测量剂量的信息。
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产地国家: 美国
原产地英文商品名:
Tussionex 10/8 MG/5ML SUS 115 ML
原产地英文药品名:
hydrocodon polistirex and chlorpheniramine polistirex
中文参考商品译名:
Tussionex 10/8毫克/5毫升 115毫升
中文参考药品译名:
氢可酮镇咳药，含氢可酮和氯苯那敏
生产厂家英文名:
UCB INC