Each 5 mL (teaspoonful) of Clemastine Fumarate Syrup for oral administration contains clemastine 0.5 mg (present as clemastine fumarate 0.67 mg). Other ingredients: Alcohol 5.5%, Flavors, Maleic Acid, Methylparaben, Propylene Glycol, Propylparaben, Purified Water, Saccharin Sodium, Sodium Hydroxide, and Sorbitol. Clemastine fumarate belongs to the benzhydryl ether group of antihistaminic compounds. The chemical name is (+)-(2R)-2-[2-[[(R)-p-Chloro-α-methyl-α-phenylbenzyl]-oxy]ethyl]-1-methylpyrrolidine fumarate and has the following structural formula:

Clemastine fumarate occurs as a colorless to faintly yellow, odorless, crystalline powder. Clemastine Fumarate Syrup has an approximate pH of 6.2.

Clemastine Fumarate Syrup is indicated for the relief of symptoms associated with allergic rhinitis such as sneezing, rhinorrhea, pruritus and lacrimation. Clemastine Fumarate Syrup is indicated for use in pediatric populations (age 6 years through 12) and adults (see DOSAGE AND ADMINISTRATION).

It should be noted that clemastine is indicated for the relief of mild uncomplicated allergic skin manifestations of urticaria and angioedema at the 2 mg dosage level only.

DOSAGE SHOULD BE INDIVIDUALIZED ACCORDING TO THE NEEDS AND RESPONSE OF THE PATIENT.

Pediatric

Adults and Children 12 Years and Over

For Symptoms of Allergic Rhinitis - The starting dose is 2 teaspoonfuls (1 mgclemastine) twice daily. Dosage may be increased as required, but not to exceed 12 teaspoonfuls daily (6 mg clemastine).

For Urticaria and Angioedema - The starting dose is 4 teaspoonfuls (2 mg clemastine) twice daily, not to exceed 12 teaspoonfuls daily (6 mg clemastine).

Clemastine Fumarate Syrup: clemastine 0.5 mg/5 mL (present as clemastine fumarate 0.67 mg/5 mL). A clear, colorless liquid with a citrus flavor, in 120 mL bottle.

Store at controlled room temperature, between 20° and 25°C (68° and 77°F) (see USP).

Manufactured By: TEVA PHARMACEUTICALS USA, Sellersville, PA 18960. Rev. 4/2003. FAD Rev date: 08/30/01

The most frequent adverse reactions are italicized:

Nervous System

Sedation, sleepiness, dizziness, disturbed coordination, fatigue, confusion, restlessness, excitation, nervousness, tremor, irritability, insomnia, euphoria, paresthesia, blurred vision, diplopia, vertigo, tinnitus, acute labyrinthitis, hysteria, neuritis, convulsions.

Gastrointestinal System

Epigastric distress, anorexia, nausea, vomiting, diarrhea, constipation.

Respiratory System

Thickening of bronchial secretions, tightness of chest and wheezing, nasal stuffiness.

Cardiovascular System

Hypotension, headache, palpitations, tachycardia, extrasystoles.

Hematologic System

Hemolytic anemia, thrombocytopenia, agranulocytosis.

Genitourinary System

Urinary frequency, difficult urination, urinary retention, early menses.

General

Urticaria, drug rash, anaphylactic shock, photosensitivity, excessive perspiration, chills, dryness of mouth, nose and throat.

Additive CNS depression may occur when antihistamines are administered concomitantly with other CNS depressants including barbiturates, tranquilizers, and alcohol. Patients receiving antihistamines should be advised against the concurrent use of other CNS depressant drugs.

Monoamine oxidase (MAO) inhibitors prolong and intensify the anticholinergic effects of antihistamines.

Antihistamines should be used with considerable caution in patients with: narrow angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy, and bladder neck obstruction.

Use with CNS Depressants

Clemastine has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc.).

Use in Activities Requiring Mental Alertness

Patients should be warned about engaging in activities requiring mental alertness such as driving a car or operating appliances, machinery, etc.

Use in the Elderly (approximately 60 years or older)

Antihistamines are more likely to cause dizziness, sedation, and hypotension in elderly patients.

General

Clemastine fumarate should be used with caution in patients with: history of bronchial asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease, and hypertension.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Pregnancy

Teratogenic Effects

Nursing Mothers

Although quantitative determinations of antihistaminic drugs in breast milk have not been reported, qualitative tests have documented the excretion of diphenhydramine, pyrilamine, and tripelennamine in human milk.

Because of the potential for adverse reactions in nursing infants from antihistamines, a decision should be made whether to discontinue nursing or to discontinue the drug.

Pediatric Use

The safety and efficacy of Clemastine Fumarate Syrup has been confirmed in the pediatric population (age 6 years through 12). Safety and dose tolerance studies have confirmed pediatric patients 6 through 11 years tolerated dosage ranges of 0.75 to 2.25 mg clemastine. In pediatric patients particularly, antihistamines in overdosage may produce hallucinations, convulsions and death. Symptoms of antihistamine toxicity in pediatric patients may include fixed dilated pupils, flushed face, dry mouth, fever, excitation, hallucinations, ataxia, incoordination, athetosis, tonic-clonic convulsions, and postictal depression (see OVERDOSAGE).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Pregnancy

Teratogenic Effects

Nursing Mothers

Although quantitative determinations of antihistaminic drugs in breast milk have not been reported, qualitative tests have documented the excretion of diphenhydramine, pyrilamine, and tripelennamine in human milk.

Because of the potential for adverse reactions in nursing infants from antihistamines, a decision should be made whether to discontinue nursing or to discontinue the drug.

Pediatric Use

The safety and efficacy of Clemastine Fumarate Syrup has been confirmed in the pediatric population (age 6 years through 12). Safety and dose tolerance studies have confirmed pediatric patients 6 through 11 years tolerated dosage ranges of 0.75 to 2.25 mg clemastine. In pediatric patients particularly, antihistamines in overdosage may produce hallucinations, convulsions and death. Symptoms of antihistamine toxicity in pediatric patients may include fixed dilated pupils, flushed face, dry mouth, fever, excitation, hallucinations, ataxia, incoordination, athetosis, tonic-clonic convulsions, and postictal depression (see OVERDOSAGE).

Antihistamine overdosage reactions may vary from central nervous system depression to stimulation. In children, stimulation predominates initially in a syndrome which may include exclient, hallucinations, ataxia, incoordination, muscle twitching, athetosis, hyperthermia, cyanosis convulsions, tremors, and hyperreflexia followed by postictal depression and cardio-respiratory arrest. Convulsions in children may be preceded by mild depression. Dry mouth, fixed dilated pupils, flushing of the face, and fever are common. In adults, CNS depression, ranging from drowsiness to coma, is more common. The convulsant dose of antihistamines lies near the lethal dose. Convulsions indicate a poor prognosis.

In both children and adults, coma and cardiovascular collapse may occur. Deaths are reported especially in infants and children.

There is no specific therapy for acute overdosage with antihistamines. The latent period from ingestion to appearance of toxic effects is characteristically short (1/2-2 hours). General symptomatic and supportive measures should be instituted promptly and maintained for as long as necessary.

Since overdoses of other classes of drugs (i.e. tricyclic antidepressants) may also present anticholinergic symptomatology, appropriate toxicological analysis should be performed as soon as possible to identify the causative agent.

In the conscious patient, vomiting should be induced even though it may have occurred spontaneously. If vomiting cannot be induced, gastric lavage is indicated. Adequate precautions must be taken to protect against aspiration, especially in infants and children. Charcoal slurry or other suitable agents should be instilled into the stomach after vomiting or lavage. Saline cathartics or milk of magnesia may be of additional benefit.

In the unconscious patient, the airway should be secured with a cuffed endotracheal tube before attempting to evacuate the gastric spans. Intensive supportive and nursing care is indicated, as for any comatose patient.

If breathing is significantly impaired, maintenance of an adequate airway and mechanical support of respiration is the most effective means of providing adequate oxygenation.

Hypotension is an early sign of impending cardiovascular collapse and should be treated vigorously. Although general supportive measures are important, specific treatment with intravenous infusion of a vasopressor titrated to maintain adequate blood pressure may be necessary.

Do not use with CNS stimulants.

Convulsions should be controlled by careful administration of diazepam or a short-acting barbiturate, repeated as necessary. Physostigmine may also be considered for use in controlling centrally mediated convulsions.

Ice packs and cooling sponge baths, not alcohol, can aid in reducing the fever commonly seen in children. A more detailed review of antihistamine toxicology and overdose management is available in Gosselin, R.E., et. al., "Clinical Toxicology of Commercial Products."

Antihistamines are contraindicated in patients hypersensitive to the drug or to other antihistamines of similar chemical structure (see PRECAUTIONS: DRUG INTERACTIONS).

Antihistamines should not be used in newborn or premature infants. Because of the higher risk of antihistamines for infants generally and for newborns and prematures in particular, antihistamine therapy is contraindicated in nursing mothers (see PRECAUTIONS-Nursing Mothers).

Clemastine fumarate is an antihistamine with anticholinergic (drying) and sedative side effects. Antihistamines competitively antagonize various physiological effects of histamine including increased capillary permeability and dilatation, the formation of edema, the "flare" and "itch" response, and gastrointestinal and respiratory smooth muscle constriction. Within the vascular tree, H₁-receptor antagonists inhibit both the vasoconstrictor and vasodilator effects of histamine. Depending on the dose, H₁-receptor antagonists can produce CNS stimulation or depression. Most antihistamines exhibit central and/or peripheral anticholinergic activity. Antihistamines act by competitively blocking H₁-receptor sites. Antihistamines do not pharmacologically antagonize or chemically inactivate histamine, nor do they prevent the release of histamine.

Pharmacokinetics

Antihistamines are well-absorbed following oral administration. Chlorpheniramine maleate, clemastine fumarate, and diphenhydramine hydrochloride achieve peak blood levels within 2-5 hours following oral administration. The absorption of antihistamines is often partially delayed by the use of controlled release dosage forms. In these instances, plasma concentrations from identical doses of the immediate and controlled release dosage forms will not be similar. Tissue distribution of the antihistamines in humans has not been established. Antihistamines appear to be metabolized in the liver chiefly via mono- and didemethylation and glucuronide conjugation. Antihistamine metabolites and small amounts of unchanged drug are excreted in the urine. Small amounts of the drugs may also be excreted in breast milk.

In normal human subjects who received histamine injections over a 24-hour period, the antihistaminic activity of clemastine reached a peak at 5-7 hours, persisted for 10-12 hours and, in some cases, for as long as 24 hours. Pharmacokinetic studies in man utilizing ³H and ¹⁴C labeled compound demonstrates that: clemastine is rapidly absorbed from the gastrointestinal tract, peak plasma concentrations are attained in 2-4 hours, and urinary excretion is the major mode of elimination.

Patients taking antihistamines should receive the following information and instructions:

• Antihistamines are prescribed to reduce allergic symptoms.
• Patients should be questioned regarding a history of glaucoma, peptic ulcer, urinary retention, or pregnancy before starting antihistamine therapy.
• Patients should be told not to take alcohol, sleeping pills, sedatives, or tranquilizers while taking antihistamines.
• Antihistamines may cause drowsiness, dizziness, dry mouth, blurred vision, weakness, nausea, headache, or nervousness in some patients.
• Patients should avoid driving a car or working with hazardous machinery until they assess the effects of this medicine.
• Patients should be told to store this medicine in a tightly closed container in a dry, cool place away from heat or direct sunlight and out of the reach of children.

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.

CLEMASTINE - ORAL

(KLEM-ast-een)

COMMON BRAND NAME(S): Tavist

USES: Clemastine is an antihistamine used to relieve symptoms of allergy, hay fever, and the common cold. These symptoms include rash, watery eyes, itchy eyes/nose/throat/skin, cough, runny nose, and sneezing. This medication works by blocking a certain natural substance (histamine) that your body makes during an allergic reaction. By blocking another natural substance made by your body (acetylcholine), it helps dry up some body fluids to relieve symptoms such as watery eyes and runny nose.

This medication is not recommended for use in newborn babies due to increased risk for serious side effects (e.g., seizures).

HOW TO USE: If you are taking the over-the-counter product, read all directions on the product package before taking this medication. If you have any questions, consult your pharmacist. If your doctor has prescribed this medication, take it as directed.

Take the tablet or liquid form by mouth with or without food. Follow the directions for dosing on the label, or take as directed by your doctor. This medication may be taken with food or milk if stomach upset occurs.

If you are using the liquid form, use a medication-measuring device to carefully measure the prescribed dose. Do not use a household spoon.

Your dosage is based on your age, medical condition, and response to therapy. Do not increase your dose or take this medication more often than recommended by your doctor or the package instructions without your doctor's approval. Take this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time(s) each day.

If your condition persists or worsens, or if you think you may have a serious medical problem, seek immediate medical attention.

SIDE EFFECTS: Drowsiness, dizziness, headache, constipation, stomach upset, blurred vision, trouble walking/clumsiness, or dry mouth/nose/throat may occur. These effects may decrease as your body adjusts to the medication. If any of these effects persist or worsen, contact 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. Clemastine 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.

If your doctor has prescribed this drug, remember that 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., hallucinations, irritability, nervousness), ringing in the ears, trouble urinating.

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

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 taking clemastine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. Check the label for any inactive ingredients you may be allergic to.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: breathing problems (e.g., asthma, emphysema), a certain eye problem (glaucoma), heart problems, high blood pressure, liver disease, seizures, stomach problems (e.g., ulcers, blockage), overactive thyroid (hyperthyroidism), urination problems (e.g., trouble urinating due to enlarged prostate, urinary retention).

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

Liquid preparations of this product 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, and low blood pressure.

Do not give this medication to a child younger than 6 years unless directed to do so by a doctor. Children may be more sensitive to the effects of antihistamines. In young children, this medication may cause agitation/excitement instead of drowsiness.

If you are pregnant, consult your doctor before using this medication. Discuss the risks and benefits with your doctor.

This medication passes into breast milk and may 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: If you are taking this medication under your doctor's direction, 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 prescribed medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: antispasmodics (e.g., atropine, belladonna alkaloids), anticholinergics (e.g., benztropine, trihexyphenidyl), scopolamine.

Tell your doctor or pharmacist if you have taken MAO inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine) within the last 2 weeks.

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, amitriptyline, 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. Canada residents can call a provincial poison control center. Symptoms of overdose may include: large pupils, flushing, fever, hallucinations, weakness, shaking (tremor), muscle twitching, loss of consciousness, seizures. In children, excitement may occur first, followed by loss of coordination, drowsiness, loss of consciousness, seizures.

NOTES: If your doctor has prescribed this medication, do not share it with others.

Keep all regular medical and laboratory appointments.

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

MISSED DOSE: If you are taking this medication on a regular schedule and miss a dose, take it as soon as you remember. If it is near the time of your 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 (between 15-30 degrees C) away from light and moisture. Do not store in the bathroom. Do not freeze liquid forms of this medication. 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.