Each teaspoonful (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. TUSSIONEX Pennkinetic Extended- Release Suspension provides up to 12-hour relief per dose. 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.

Chlorpheniramine Polistirex

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

Inactive Ingredients

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.

Last updated on RxList: 3/19/2008

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.

It is important that TUSSIONEX is measured with an accurate measuring device (see PRECAUTIONS, Information for Patients). A household teaspoon is not an accurate measuring device and could lead to overdosage, especially when half a teaspoon is to be measured. It is strongly recommended that an accurate measuring device be used. A pharmacist can provide an appropriate measuring device and can provide instructions for measuring the correct dose.

Shake well before using.

Adults and Children 12 Years and Older

5 mL (1 teaspoonful) every 12 hours; do not exceed 10 mL (2 teaspoonfuls) in 24 hours.

Children 6-11Years of Age

2.5 mL (½ teaspoonful) every 12 hours; do not exceed 5 mL (1 teaspoonful) in 24 hours.

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

TUSSIONEX Pennkinetic (hydrocodone polistirex and chlorpheniramine polistirex) Extended- Release Suspension is a gold-colored suspension.

NDC 53014-548-67 473 mL bottle

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) [see USP Controlled Room Temperature].

TUSSIONEX Pennkinetic Extended-Release Suspension Manufactured for: UCB, Inc. Smyrna, GA 30080. Rev. 01/2008. FDA rev date: 3/11/2008

Last updated on RxList: 3/19/2008

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.

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.

Last updated on RxList: 3/19/2008

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).

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.

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.

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.

Last updated on RxList: 3/19/2008

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.

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.

Last updated on RxList: 3/19/2008

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.

Last updated on RxList: 3/19/2008

As with all narcotics, 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; patients should be cautioned accordingly. 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, especially when a half a teaspoon is measured. A pharmacist can recommend an appropriate measuring device and can provide instructions for measuring the correct dose.

Shake well before using.

Keep out of the reach of children.

Last updated on RxList: 3/19/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

NARCOTIC ANTITUSSIVE/ANTIHISTAMINE - ORAL

USES: This combination product is used to treat symptoms caused by the common cold, flu, allergies, hay fever, or other breathing illnesses (e.g., sinusitis, bronchitis). This product contains a narcotic cough suppressant (antitussive) that affects a certain part of the brain, reducing the urge to cough. Antihistamines relieve watery eyes, itchy eyes/nose/throat, runny nose, and sneezing.

Do not use this medication in children younger than 6 years unless specifically directed by the doctor. To decrease the risk for serious side effects, carefully follow all of the doctor's dosage directions. Do not give other cough and cold medication that might contain the same or similar ingredients (see also Drug Interactions section). Ask your doctor or pharmacist about other ways to relieve cough and cold symptoms (e.g., giving saline nose drops/spray, using a humidifier or infant nasal suction bulb).

HOW TO USE: Take this medication by mouth with or without food with a full glass of water (8 ounces or 240 milliliters) or as directed by your doctor. This medication may be taken with food or milk if stomach upset occurs. Do not take the sustained-release products more often than every 12 hours.

If you are using the liquid form, use a medication measuring device or spoon to carefully measure the prescribed dose. Do not use a household spoon because you may not get the correct dose. If your liquid form is a suspension, shake the bottle well before each dose.

If you are using sustained-release tablets or capsules, swallow the medication whole. Do not crush, chew, or break the tablets or capsules. If you are using a sustained-release liquid that contains hydrocodone polistirex, do not mix the liquid with other liquids or medications. Doing so can destroy the long action of the drug and may increase side effects.

This medication may cause dependence, especially if it has been used regularly for an extended time (more than a few weeks) or if it has been used in high doses. In such cases, if you suddenly stop this drug, withdrawal reactions may occur. Such reactions can include anxiety, restlessness, sweating, shaking chills, nausea, vomiting, and diarrhea. Report any such reactions to your doctor immediately. When stopping extended, regular treatment with this drug, gradually reducing the dosage as directed will help prevent withdrawal reactions. Consult your doctor or pharmacist for more details.

Though it is very unlikely to occur, this medication can also result in abnormal drug-seeking behavior (addiction/habit forming). Do not increase your dose, take it more frequently, or use it for a longer time than prescribed. Properly stop the medication when so directed. This will lessen the chances of becoming addicted.

When used for an extended time, this medication may not work as well and may require different dosing. Talk with your doctor if this medication stops working well.

Inform your doctor if your condition persists for more than 1 week, if it worsens, or if it occurs with fever, rash, or persistent headache. These may be symptoms of a serious medical problem and should be checked by a doctor.

SIDE EFFECTS: Drowsiness, dizziness, headache, blurred vision, upset stomach, nausea, constipation, or dry mouth/nose/throat may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water, or use a saliva substitute. This medication can dry up and thicken mucus in your lungs, making it more difficult to breathe and clear your lungs. To help prevent this effect, drink plenty of fluids unless otherwise directed by your doctor.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: mental/mood changes (e.g., confusion, hallucinations), ringing in the ears, slow/shallow breathing, trouble urinating.

Tell your doctor immediately if any of these rare but very serious side effects occur: easy bruising/bleeding, fast/slow/irregular heartbeat, seizure.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking this product, tell your doctor or pharmacist if you are allergic to it; or to tartrazine; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: abdominal problems (e.g., chronic constipation, ileus, pancreatitis), adrenal gland problem (e.g., Addison's disease), certain brain disorders (e.g., head injury, tumor, increased intracranial pressure), breathing problems (e.g., asthma, emphysema), diabetes, a certain eye problem (glaucoma), heart problems, high blood pressure, kidney problems, liver disease, mental/mood problems (e.g., depression, psychosis), seizures, stomach/intestinal problems (e.g., ulcers, blockage), underactive thyroid (hypothyroidism), urination problems (e.g., trouble urinating due to enlarged prostate, urinary retention), use/abuse of drugs/alcohol.

This drug may make you dizzy or drowsy or cause blurred vision; use caution engaging in activities requiring alertness such as driving or using machinery. Limit the use of alcohol and certain other drowsiness-causing medications. (See also Drug Interactions.) To minimize dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

This medicine may contain aspartame. If you have phenylketonuria (PKU) or any other condition that requires you to restrict your intake of aspartame (or phenylalanine), consult your doctor or pharmacist regarding the safe use of this medicine.

This medication may contain sugar and/or alcohol. Caution is advised if you have diabetes, alcohol dependence, or liver disease. Ask your doctor or pharmacist about the safe use of this product.

The elderly may be more sensitive to the effects of this drug, especially dizziness, drowsiness, mental/mood changes, and low blood pressure.

Do not give this medication to a child younger than 6 years unless the doctor directs you to do so. Children may be more sensitive to the effects of the narcotic cough suppresant, especially breathing problems. Children may also be more sensitive to the effects of antihistamines. In young children, antihistamines may cause agitation/excitement instead of drowsiness.

During pregnancy, this medication should be used only if clearly needed. It is not recommended for use in high doses or for long periods during the last 3 months of pregnancy due to increased risk for serious side effects in a newborn baby (e.g., withdrawal symptoms such as irritability, abnormal/persistent crying, diarrhea, seizures). Tell your doctor immediately if you notice any of these symptoms in your newborn. Discuss the risks and benefits with your doctor.

This medication may pass into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop or change the dosage of any medicine before checking with them first.

Before taking this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: anticholinergic drugs (e.g., benztropine, belladonna alkaloids), cimetidine, MAO inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine), narcotic antagonists (e.g., naltrexone, naloxone), scopolamine, tricyclic antidepressants (e.g., amitriptyline, desipramine).

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., carbamazepine), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, risperidone, trazodone). Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain drowsiness-causing ingredients. Ask your pharmacist about the safe use of those products.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include: confusion, cold/clammy skin, fast/slow/irregular heartbeat, slow/shallow breathing, seizures, loss of consciousness.

NOTES: Do not share this medication with others. It is against the law.

Do not take this medication for several days before allergy testing because test results can be affected.

MISSED DOSE: If you are prescribed this medication on a regular schedule and miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store in a tightly closed container at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Do not freeze. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.