Zonalon (doxepin hydrochloride) Cream, 5% is a topical cream. Each gram contains: 50 mg of doxepin hydrochloride (equivalent to 44.3 mg of doxepin).

Doxepin hydrochloride is one of a class of agents known as dibenzoxepin tricyclic antidepressant compounds. It is an isomeric mixture of N,N-dimethyldibenz[b,e]oxepin-Δ^11(6H),γ- propylaminehydrochloride. Doxepin hydrochloride has an empirical formula of C₁₉H₂₁NO•HCl and a molecular weight of 316.

Zonalon Cream also contains sorbitol, cetyl alcohol, isopropyl myristate, glyceryl stearate, PEG-100 stearate, petrolatum, benzyl alcohol, titanium dioxide and purified water.

Last updated on RxList: 12/29/2008

Zonalon Cream is indicated for the short-term (up to 8 days) management of moderate pruritus in adult patients with atopic dermatitis or lichen simplex chronicus. (See DOSAGE AND ADMINISTRATION)

A thin film of Zonalon Cream should be applied four times each day with at least a 3 to 4 hour interval between applications. There are no data to establish the safety and effectiveness of Zonalon Cream when used for greater than 8 days. Chronic use beyond eight days may result in higher systemic levels and should be avoided. Use of Zonalon cream for longer than 8 days may result in an increased likelihood of contact sensitization.

The risk for sedation may increase with greater body surface area application of Zonalon cream (See WARNINGS section). Clinical experience has shown that drowsiness is significantly more common in patients applying Zonalon Cream to over 10% of body surface area; therefore, patients with greater than 10% of body surface area (see WARNINGS section) affected should be particularly cautioned concerning possible drowsiness and other systemic adverse effects of doxepin. If excessive drowsiness occurs, it may be necessary to do one or more of the following: reduce the body surface area treated, reduce the number of applications per day, reduce the amount of cream applied, or discontinue the drug.

Occlusive dressings may increase the absorption of most topical drugs; therefore, occlusive dressings should not be utilized with Zonalon Cream.

Zonalon Cream is available in 30 g (NDC 62436-523-30) and 45 g (NDC 62436-523-45) tubes. Store at or below 27° C (80° F).

Manufactured for: Bioglan Pharma, Inc. Malvern, PA 19355 by: DPT Laboratories, Inc. San Antonio, Texas 78215. FDA Rev date: 12/20/2002

Last updated on RxList: 12/29/2008

Controlled Clinical Trials

Systemic Adverse Effects: In controlled clinical trials of patients treated with Zonalon Cream, the most common systemic adverse event reported was drowsiness. Drowsiness occurred in 71 of 330 (22%) of patients treated with Zonalon Cream compared to 7 of 334 (2%) of patients treated with vehicle cream. Drowsiness resulted in the premature discontinuation of the drug in approximately 5% of patients treated with Zonalon Cream in controlled clinical trials.

Local Site Adverse Effects: In controlled clinical trials of patients treated with Zonalon Cream, the most common local site adverse event reported was burning and/or stinging at the site of application. These occurred in 76 of 330 (23%) of patients treated with Zonalon Cream compared to 54 of 334 (16%) of patients treated with vehicle cream. Most of these reactions were categorized as "mild"; however, approximately 25% of patients who reported burning and/or stinging reported the reaction as "severe". Four patients treated with Zonalon Cream withdrew from the study because of the burning and/or stinging.

The table below presents the adverse events reported at an incidence of ≥ 1 % in either Zonalon or vehicle cream treatment groups during the trials:

Adverse Event	Zonalon N=330	Vehicle N=334
Burning /Stinging	76 (23.0%)	54 (16.2%)
Drowsiness	71 (21.5%)	7 (2.1%)
Dry Mouth1	32 (9.7%)	4 (1.2%)
Pruritus2	13 (3.9%)	20 (6.0%)
Fatigue/Tiredness	10 (3.0%)	5 (1.5%)
Exacerbated Eczema	10 (3.0%)	8 (2.4%)
Other Application Site Reaction3	10 (3.0%)	16 (4.8%)
Dizziness4	7 (2.1%)	3 (0.9%)
Mental Emotional Changes	6 (1.8%)	1 (0.3%)
Taste Perversion5	5 (1.5%)	1 (0.3%)
Edema	4 (1.2%)	1 (0.3%)
Headache	3 (0.9%)	14 (4.2%)
1 Includes reports of "dry lips", "dry throat", and "thirst" 2Includes reports of "Pruritus Exacerbated" 3Includes report of "increased irritation at application site" 4Includes reports of "lightheadedness" and "dizziness/vertigo" 5Includes reports of "bitter taste" and "metallic taste in mouth"

Adverse events occurring in 0.5% to < 1.0% of Zonalon Cream treated patients in the controlled clinical trials included: nervousness/anxiety, tongue numbness, fever, and nausea.

Post Marketing Experience

Twenty-six cases of allergic contact dermatitis have been reported in patients using Zonalon Cream, twenty of which were documented by positive patch test to doxepin 5% cream.

Studies have not been performed examining drug interactions with Zonalon Cream. However, since plasma levels of doxepin following topical application of Zonalon Cream can reach levels obtained with oral doxepin HCl therapy, the following drug interactions are possible following topical Zonalon Cream application:

Drugs Metabolized by P450 2D6

The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7-10% of Caucasians are so-called "poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8-fold increase in plasma AUC of the TCA).

In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).

Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.

MAO Inhibitors: Serious side effects and even death have been reported following the concomitant use of certain drugs with MAO inhibitors. Therefore, MAO inhibitors should be discontinued at least two weeks prior to the cautious initiation of therapy with Zonalon Cream. The exact length of time may vary and is dependent upon the particular MAO inhibitor being used, the length of time it has been administered, and the dosage involved.

Cimetidine: Serious anticholinergic symptoms (i.e., severe dry mouth, urinary retention and blurred vision) have been associated with elevations in the serum levels of tricyclic antidepressant when cimetidine therapy is initiated. Additionally, higher than expected tricyclic antidepressant levels have been observed when they are begun in patients already taking cimetidine.

Alcohol: Alcohol ingestion may exacerbate the potential sedative effects of Zonalon Cream. This is especially important in patients who may use alcohol excessively.

Tolazamide: A case of severe hypoglycemia has been reported in a type II diabetic patient maintained on tolazamide (1 gm/day) 11 days after the addition of oral doxepin (75 mg/day).

Last updated on RxList: 12/29/2008

Drowsiness occurs in over 20% of patients treated with Zonalon Cream, especially in patients receiving treatment to greater than 10% of their body surface area. Patients should be warned about the possibility of sedation and cautioned against driving a motor vehicle or operating hazardous machinery while being treated with Zonalon Cream.

The sedating effects of alcoholic beverages, antihistamines, and other CNS depressants may be potentiated when Zonalon Cream is used.

If excessive drowsiness occurs it may be necessary to reduce the frequency of applications, the amount of cream applied, and/or the percentage of body surface area treated, or discontinue the drug. However, the efficacy with reduced frequency of applications has not been established. Keep this product away from the eyes.

General

Drowsiness: Since drowsiness may occur with the use of Zonalon Cream, patients should be warned of the possibility and cautioned against driving a car or operating dangerous machinery while using this drug. Patients should also be cautioned that their response to alcohol may be potentiated.

Sedating drugs may cause confusion and oversedation in the elderly; elderly patients generally should be observed closely for confusion and oversedation when started on Zonalon Cream. (See PRECAUTIONS -- Geriatric Use.)

Use under occlusion: Occlusive dressings may increase the absorption of most topical drugs; therefore, occlusive dressings should not be utilized with Zonalon Cream.

Contact sensitization: Use of Zonalon Cream can cause Type IV hypersensitivity reactions (contact sensitization) to doxepin.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis, mutagenesis, and impairment of fertility studies have not been conducted with doxepin hydrochloride.

Pregnancy Category B

Reproduction studies have been performed in which doxepin was orally administered to rats and rabbits at doses up to 0.6 and 1.2 times, respectively, the estimated exposure to doxepin that results from use of 16 grams of Zonalon Cream per day (four applications of four grams of cream per day; dose multiples reflect comparisons made following normalization of the data on the basis of body surface area estimates) and have revealed no evidence of harm to rat or rabbit fetuses due to doxepin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Doxepin is excreted in human milk after oral administration. It is possible that doxepin may also be excreted in human milk following topical application of Zonalon Cream.

One case has been reported of apnea and drowsiness in a nursing infant whose mother was taking an oral dosage form of doxepin HCl.

Because of the potential for serious adverse reactions in nursing infants from doxepin, 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 Zonalon Cream in pediatric patients is not recommended. Safe conditions for use of Zonalon Cream in children have not been established. One case has been reported of a 2.5 year old child who developed somnolence, grand mal seizure, respiratory depression, ECG abnormalities, and coma after treatment with Zonalon Cream. A total of 27 grams had been applied over three days for eczema. He was treated with supportive care, activated charcoal, and systemic alkalization and recovered.

Geriatric Use

Clinical studies of Zonalon Cream 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.

The extent of renal excretion of doxepin has not been determined. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selections.

Sedating drugs may cause confusion and oversedation in the elderly; elderly patients generally should be observed closely for confusion and oversedation when started on Zonalon Cream. (See WARNINGS.) An 80-year old male nursing home patient developed probable systemic anticholinergic toxicity which included urinary retention and delirium after Zonalon cream had been applied to his arms, legs and back three times daily for two days.

Last updated on RxList: 12/29/2008

Deaths may occur from overdosage with this class of drugs. As the management is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose; therefore, hospital monitoring is required as soon as possible.

Manifestations: Should overdosage with topical application of Zonalon Cream occur, the signs and symptoms may include: cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity.

Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia, or any of the symptoms listed under ADVERSE REACTIONS.

General Recommendations

General: Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line and initiate gastric decontamination. A minimum of six hours of observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is strongly advised. If signs of toxicity occur at any time during this period, extended monitoring is recommended. There are case reports of patients succumbing to fatal dysrhythmias late after overdose; these patients had clinical evidence of significant poisoning prior to death and most received inadequate gastrointestinal decontamination. Monitoring of plasma drug levels should not guide management of the patient.

Cardiovascular: A maximal limb-lead QRS duration of > /=0.10 seconds may be the best indication of the severity of the overdose. Intravenous sodium bicarbonate should be used to maintain the serum pH in the range of 7.45 to 7.55. If the pH response is inadequate, hyperventilation may also be used. Concomitant use of hyperventilation and sodium bicarbonate should be done with extreme caution, with frequent pH monitoring. A pH > 7.60 or a pCO 2 < 20 mm Hg is undesirable. Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine, bretylium or phenytoin.

Type 1A and 1C antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide).

In rare instances, hemoperfusion may be beneficial in acute refractory cardiovascular instability in patients with acute toxicity. However, hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis generally have been reported as ineffective in tricyclic antidepressant poisoning.

CNS: In patients with CNS depression, early intubation is advised because of the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines, or if these are ineffective, other anticonvulsants (e.g., phenobarbital, phenytoin).

Physostigmine is not recommended except to treat life-threatening symptoms that have been unresponsive to other therapies, and then only in consultation with a poison control center.

Pediatric Management: The principles of management of child and adult overdosages are similar. It is strongly recommended that the physician contact the local poison control center for specific pediatric treatment.

Because doxepin HCl has an anticholinergic effect and because significant plasma levels of doxepin are detectable after topical Zonalon Cream application, the use of Zonalon Cream is contraindicated in patients with untreated narrow angle glaucoma or a tendency to urinary retention.

Zonalon Cream is contraindicated in individuals who have shown previous sensitivity to any of its components.

Last updated on RxList: 12/29/2008

Although doxepin HCl does have H1 and H2 histamine receptor blocking actions, the exact mechanism by which doxepin exerts its antipruritic effect is unknown. Zonalon Cream can produce drowsiness in significant numbers of patients, and this sedation may reduce awareness, including awareness of pruritic symptoms. In 19 pruritic eczema patients treated with Zonalon Cream, plasma doxepin concentrations ranged from nondetectable to 47 ng/mL from percutaneous absorption. Plasma levels from topical application of Zonalon Cream can result in CNS and other systemic side effects. Once absorbed into the systemic circulation, doxepin undergoes hepatic metabolism that results in conversion to pharmacologically-active desmethyldoxepin. Further glucuronidation results in urinary excretion of the parent drug and its metabolites. Desmethyldoxepin has a half-life that ranges from 28 to 52 hours and is not affected by multiple dosing. Plasma levels of both doxepin and desmethyldoxepin are highly variable and are poorly correlated with dosage. Wide distribution occurs in body tissues including lungs, heart, brain, and liver. Renal disease, genetic factors, age, and other medications affect the metabolism and subsequent elimination of doxepin. (See PRECAUTIONS - DRUG INTERACTIONS.)

Last updated on RxList: 12/29/2008

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 12/29/2008

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.

DOXEPIN CREAM - TOPICAL

(dox-EH-pin)

COMMON BRAND NAME(S): Zonalon

USES: This medication is used to relieve troublesome itching from certain skin conditions (e.g., atopic dermatitis, eczema, neurodermatitis). It should be used only for a short time (no more than 8 days). Doxepin is a tricyclic antidepressant. It is not known how this medication decreases itching. Some medication is absorbed into the body when the cream is applied. This medication may work by blocking a certain natural substance (histamine) that your body makes during an allergic reaction. The decrease in itching may be a result of drowsiness or some other effect in the brain that causes you not to notice or be bothered by the itching.

HOW TO USE: Before applying the medication, clean the affected area with mild soap and water, rinse well, and pat dry. Gently rub a small amount of the medication into the affected area in a thin layer, usually 4 times a day. Wait at least 3-4 hours between applications, or use as directed by your doctor. How often the medication is applied and for how long depends on your condition and response to treatment. Usually, this medication is for short-term use only (up to 8 days).

Wash hands immediately after use unless the area being treated includes the hands. This medication is for use on the skin only. Avoid getting the product in your eyes, nose, ears, mouth, or vaginal/anal area. If the medication gets in these areas, rinse immediately with clean water.

Do not cover the area with plastic or waterproof bandages. Covering the treated area may increase the absorption of the medication through the skin and increase the risk of side effects.

Do not use more of this product, use it more often, or keep using it longer than prescribed by your doctor. Your condition will not improve faster and the risk for side effects will increase. Side effects may increase when you use the cream on a larger area of skin (e.g., more than 10 percent of your body surface). Tell your doctor if you have severe drowsiness while using this product. It may be a sign that you are absorbing too much of the medication. Your doctor may tell you to decrease how often you apply the medication, the amount of medication used, or how much skin to spread the medication over. Follow your doctor's directions carefully.

Tell your doctor if your condition does not improve or if it worsens.

SIDE EFFECTS: Burning/stinging at the application site, drowsiness, dizziness, dry mouth, blurred vision, or changes in taste may occur. If any of these effects persist or worsen, tell 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.

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: severe constipation, loss of coordination, ringing in the ears, persistent heartburn, mental/mood changes (e.g., agitation, confusion, depression), muscle weakness/spasms, numbness/tingling of the hands/feet, restlessness, decreased sexual ability/interest, trouble urinating, swelling of the hands/feet, weight gain.

Tell your doctor immediately if any of these rare but very serious side effects occur: easy bruising/bleeding, fast/irregular heartbeat, fainting, persistent nausea/vomiting, signs of infection (e.g., fever, persistent sore throat), pain/redness/swelling of arms or legs, severe stomach/abdominal pain, dark urine, yellowing eyes/skin.

Seek immediate medical attention if any of these rare but very serious side effects occur: slurred speech, vision changes, weakness on one side of the body, seizures.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: 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 using doxepin, tell your doctor or pharmacist if you are allergic to it, or to other tricyclic antidepressants (e.g., amitriptyline); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: certain eye problem (narrow-angle glaucoma), problems urinating (e.g., due to enlarged prostate).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: breathing problems (e.g., bronchitis, emphysema), long-term constipation, long-term heartburn, diabetes, eating disorders (e.g., bulimia), certain eye problem (open-angle glaucoma), heart problems (e.g., irregular heartbeat, QT prolongation in the EKG), kidney problems, liver problems, overactive thyroid (hyperthyroidism), personal or family history of mental/mood conditions (e.g., bipolar disorder, psychosis, suicide), seizures, conditions that may increase your risk of seizures (e.g., other brain disease, alcohol withdrawal).

This drug may make you drowsy or dizzy or cause blurred vision. Use caution while driving, using machinery, or doing any activity that requires alertness and clear vision. Limit alcoholic beverages.

To reduce dizziness and lower the risk of fainting, get up slowly when rising from a sitting or lying position.

Before having surgery, tell your doctor or dentist that you are using this medication.

If you have diabetes, this drug may make your blood sugar levels harder to control. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor immediately if you have symptoms of high or low blood sugar such as fast heartbeat, increased thirst/urination, shakiness, unusual sweating, or hunger. Your anti-diabetic medication or diet may need to be adjusted.

Caution is advised when using this drug in the elderly because they may be more sensitive to its side effects, especially dizziness, drowsiness, confusion, and difficulty urinating.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This medication passes into breast milk and could have undesirable effects on a nursing infant. Therefore, breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your 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 your doctor or pharmacist first.

This drug should not be used with the following medications because very serious, possibly fatal interactions may occur: arbutamine, cisapride, disopyramide, halofantrine, pimozide, sibutramine.

Avoid taking MAO inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, selegiline, tranylcypromine) within 2 weeks before, during, and after treatment with this medication. In some cases a serious, possibly fatal drug interaction may occur.

If you have been taking fluoxetine, wait at least 5 weeks after your last dose before starting this medication.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting doxepin.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: anticholinergics (e.g., atropine, belladonna alkaloids, scopolamine, drugs for Parkinson's disease such as benztropine), inhaled bronchodilators (e.g., albuterol, salmeterol), certain drugs for high blood pressure (e.g., clonidine, guanadrel, guanethidine, reserpine), digoxin, nasal decongestants (e.g., epinephrine, phenylephrine), levodopa, lithium, stimulants (e.g., amphetamine, epinephrine, methylphenidate), sulfonylurea anti-diabetic medication (e.g., chlorpropamide, tolazamide), thyroid medication, valproic acid, drugs affecting liver enzymes that remove doxepin from your body (e.g., alcohol, barbiturates such as phenobarbital, cimetidine, haloperidol, phenothiazines such as thioridazine, St. John's wort, terbinafine, certain drugs for heart rhythm such as flecainide/propafenone/quinidine, certain HIV protease inhibitors such as amprenavir/fosprenavir, certain anti-seizure drugs such as carbamazepine/phenytoin, antidepressants such as amitriptyline/ duloxetine/ fluvoxamine/ paroxetine/ sertraline/ trazodone).

Other drugs besides doxepin that may affect the heart rhythm (QTc prolongation in the EKG) include amiodarone, dofetilide, erythromycin, procainamide, sotalol, and sparfloxacin, among others. QTc prolongation can infrequently result in serious, rarely fatal irregular heartbeat. Consult your doctor or pharmacist for more details and for instructions on how you may decrease the risk of this effect.

Also report the use of drugs which might increase seizure risk when combined with this medication such as bupropion, isoniazid (INH), theophylline, or tramadol, among others. Consult your doctor or pharmacist for details.

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., levetiracetam), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, risperidone, nefazodone).

Check the labels on all your medicines (e.g., antacids, cough-and-cold products, diet aids) because they may contain cimetidine, ingredients that cause drowsiness, or decongestants/stimulants that could increase your heart rate or blood pressure. Ask your pharmacist about using those products safely.

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: This medicine may be harmful if swallowed. If overdose or swallowing 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. Canada residents can call a provincial poison control center. Symptoms of overdose or swallowing may include: confusion, hallucinations, big/wide pupils, fast/irregular heartbeat, severe dizziness, fainting, seizures, loss of consciousness.

NOTES: Do not share this medication with others.

Use this medication only for the condition for which it was prescribed. Tell all your doctors you use this medication.

MISSED DOSE: If you miss a dose, apply 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 apply more to catch up.

STORAGE: Store at room temperature at or below 80 degrees F (27 degrees C) away from light and moisture. Do not store in the bathroom. 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.