Each 5 mL (one teaspoonful), for oral administration contains: Promethazine hydrochloride 6.25 mg; phenylephrine hydrochloride 5 mg, Alcohol 7%.

Inactive Ingredients: Citric acid, FD& C yellow #6, flavor, methyl- paraben, propylene glycol, propyl- paraben, purified water, saccharin sodium, sodium benzoate, sodium citrate, sucrose. Promethazine hydrochloride, a phenothiazine derivative, is chemically designated as (±)-10-[2-(Dimethylamino) propyl] phenothiazine monohydrochloride.

Promethazine hydrochloride occurs as a white to faint yellow, practically odorless, crystalline powder which slowly oxidizes and turns blue on prolonged exposure to air. It is soluble in water and freely soluble in alcohol. It has a molecular weight of 320.89, and a molecular formula of C₁₇H₂₀N₂S•HCl.

Phenylephrine hydrochloride is a sympathomimetic amine salt which is chemically designated as (-)- m- Hydroxy-a-[(methylamino) methyl] benzyl alcohol hydrochloride. It occurs as white or nearly white crystals, having a bitter taste. It is freely soluble in water and alcohol. Phenylephrine hydrochloride is subject to oxidation and must be protected from light and air. It has a molecular weight of 203.67, and a molecular formula of C₉H₁₃NO₂•HCl.

Promethazine hydrochloride and phenylephrine hydrochloride syrup is indicated for the temporary relief of upper respiratory symptoms, including nasal congestion, associated with allergy or the common cold.

The recommended doses are given in the following table:

Promethazine and phenylephrine is not recommended for children under 2 years of age.

This preparation is a yellow-orange colored, fruit-flavored syrup. Each 5 mL (one teaspoonful) contains Promethazine hydrochloride 6.25 mg, phenylephrine hydrochloride 5 mg, and alcohol 7 percent, and is available in bottles of 4 fluid ounce (118 mL), 8 fluid ounce (237 mL), one pint (473 mL) and one gallon (3785 mL).

Keep tightly closed. Protect from light.

Storage: Store at controlled room temperature 59°- 86° F (15°- 30° C).

Dispense in a tight, light-resistant container as defined in the USP

CAUTION: Federal law prohibits dispensing without prescription.

Promethazine

Nervous System: Sedation, sleepiness, occasional blurred vision, dryness of mouth, dizziness; rarely: confusion, disorientation, and extrapyramidal symptoms such as oculogyric crisis, torticollis, and tongue protrusion (usually in association with parenteral injection or excessive dosage).

Cardiovascular: Increased or decreased blood pressure.

Dermatologic: Rash; rarely: photosensitivity.

Hematologic: Rarely: leukopenia, thrombocytopenia; agranulocytosis (1 case).

Gastrointestinal: Nausea and vomiting.

Phenylephrine

Nervous System: Restlessness, anxiety, nervousness, and dizziness.

Cardiovascular: Hypertension (see WARNINGS).

Other: Precordial pain, respiratory distress, tremor, and weakness.

Promethazine

The sedative action of promethazine is additive to the sedative effects of other central nervous system depressants, including alcohol, narcotic analgesics, sedatives, hypnotics, tricyclic antidepressants, and tranquilizers; therefore, these agents should be avoided or administered in reduced dosage to patients receiving promethazine.

Phenylephrine

Drug: Phenylephrine with prior administration of monoamine oxidase inhibitors (MAOI).

Effect: Cardiac pressor response potentiated. May cause acute hypertensive crisis.

Drug: Phenylephrine with tricyclic antidepressants.

Effect: Pressor response increased.

Drug: Phenylephrine with ergot alkaloids.

Effect: Excessive rise in blood pressure.

Drug: Phenylephrine with bronchodilator sympathomimetic agents and with epinephrine or other sympathomimetics.

Effect: Tachycardia or other arrhythmias may occur.

Drug: Phenylephrine with atropine sulfate.

Effect: Reflex bradycardia blocked; pressor response enhanced.

Drug: Phenylephrine with prior administration of propranolol or other b- adrenergic blockers.

Effect: Cardiostimulating effects blocked.

Drug: Phenylephrine with prior administration of phentolamine or other a- adrenergic blockers.

Effect: Pressor response decreased.

Drug: Phenylephrine with diet preparations, such as amphetamines or phenylpropanolamine.

Effect: Synergistic adrenergic response.

Promethazine

Promethazine may cause marked drowsiness. Ambulatory patients should be cautioned against such activities as driving or operating dangerous machinery until it is known that they do not become drowsy or dizzy from promethazine therapy.

The sedative action of promethazine hydrochloride is additive to the sedative effects of central nervous system depressants; therefore, agents such as alcohol, narcotic analgesics, sedatives, hypnotics, and tranquilizers should either be eliminated or given in reduced dosage in the presence of promethazine hydrochloride. When given concomitantly with promethazine hydrochloride, the dose of barbiturates should be reduced by at least one-half, and the dose of analgesic depressants, such as morphine or meperidine, should be reduced by one-quarter to one-half.

Promethazine may lower seizure threshold. This should be taken into consideration when administering to persons with known seizure disorders or when giving in combination with narcotics or local anesthetics which may also affect seizure threshold. Sedative drugs or CNS depressants should be avoided in patients with a history of sleep apnea. Antihistamines should be used with caution in patients with narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, and urinary bladder obstruction due to symptomatic prostatic hypertrophy and narrowing of the bladder neck.

Administration of promethazine has been associated with reported cholestatic jaundice.

Phenylephrine

Because phenylephrine is an acirenergic agent, it should be given with caution to patients with thyroid diseases, diabetes mellitus, and heart disease or those receiving tricyclic antidepressants. Men with symptomatic, benign prostatic hypertrophy can experience urinary retention when given oral or nasal decongestants.

Phenylephrine can cause a decrease in cardiac output, and extreme caution should be used when administering the drug parenterally or orally to patients with arteriosclerosis, to elderly individuals, and/ or to patients with initially poor cerebral or coronary circulation.

Phenylephrine should be used with caution in patients taking diet preparations, such as amphetamines or phenylpropanolamine, because synergistic adrenergic effects could result in serious hypertensive response and possible stroke.

Animal reproduction studies have not been conducted with the drug combination - promethazine and phenylephrine. It is not known whether this drug combination can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Promethazine and phenylephrine should be given to a pregnant woman only if clearly needed.

General

Promethazine should be used cautiously in persons with cardiovascular disease or impairment of liver function. Phenylephrine should be used with caution in patients with cardiovascular disease, particularly hypertension.

Drug/ Laboratory Test Interactions

The following laboratory tests may be affected in patients who are receiving therapy with promethazine hydrochloride.

Pregnancy Tests: Diagnostic pregnancy tests based on immunological reactions between HCG and anti- HCG may result in false-negative or false-positive interpretations.

Glucose Tolerance Test: An increase in blood glucose has been reported in patients receiving promethazine.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Promethazine: Long-term animal studies have not been performed to assess the carcinogenic potential of promethazine, nor are there other animal or human data concerning carcinogenicity, mutagenicity, or impairment of fertility with this drug. Promethazine was nonmutagenic in the Salmonella test system of Ames.

Phenylephrine: A study which followed the development of cancer in 143,574 patients over a four-year period indicated that in 11,981 patients who received phenylephrine (systemic or topical), there was no statistically significant association between the drug and cancer at any or all sites. Long- term animal studies have not been performed to assess the carcinogenic potential of phenylephrine, nor are there other animal or human data concerning mutagenicity.

A study of the effects of adrenergic drugs on ovum transport in rabbits indicated that treatment with phenylephrine did not alter incidence of pregnancy; the number of implantations was significantly reduced when high doses of the drug were used.

Pregnancy

Teratogenic Effects

Pregnancy Category C:
Promethazine: Teratogenic effects have not been demonstrated in rat- feeding studies at doses of 6.25 and 12.5 mg/ kg of promethazine. These doses are 8.3 and 16.7 times the maximum recommended total daily dose of promethazine for a 50-kg subject. Specific studies to test the action of the drug on parturition, lactation, and development of the animal neonate were not done, but a general preliminary study in rats indicated no effect on these parameters. Although antihistamines, including promethazine, have been found to produce fetal mortality in rodents, the pharmacological effects of histamine in the rodent do not parallel those in man. There are no adequate and well-controlled studies of promethazine in pregnant women.

Phenylephrine: A study in rabbits indicated that continued moderate overexposure to phenylephrine (3 mg/ day) during the second half of pregnancy (22nd day of gestation to delivery) may contribute to perinatal wastage, prematurity, premature labor, and possibly fetal anomalies; when phenylephrine (3 mg/ day) was given to rabbits during the first half of pregnancy (3rd day after mating for seven days), a significant number gave birth to litters of low birth weight. Another study showed that phenylephrine was associated with anomalies of aortic arch and with ventricular septal defect in the chick embryo.

Promethazine and phenylephrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Promethazine taken within two weeks of delivery may inhibit platelet aggregation in the newborn.

Labor and Delivery

Administration of phenylephrine to patients in late pregnancy or labor may cause fetal anoxia or bradycardia by increasing contractility of the uterus and decreasing uterine blood flow. (See also Pregnancy: Nonteratogenic Effects above).

Nursing Mothers

It is not known whether promethazine or phenylephrine are excreted in human milk. Caution should be exercised when promethazine and phenylephrine is administered to a nursing woman.

Pediatric Use

This product should not be used in pediatric patients under 2 years of age because safety for such use has not been established.

Signs and Symptoms

Promethazine

Signs and symptoms of overdosage with promethazine range from mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depression, and unconsciousness. Stimulation may be evident, especially in children and geriatric patients. Convulsions may rarely occur. A paradoxical reaction has been reported in children receiving single doses of 75 mg to 125 mg orally, characterized by hyperexcitability and nightmares. Atropine-like signs and symptoms, dry mouth, fixed dilated pupils, flushing, as well as gastrointestinal symptoms, may occur.

Phenylephrine

Signs and symptoms of overdosage with phenylephrine include hypertension, headache, convulsions, cerebral hemorrhage, and vomiting. Ventricular premature beats and short paroxysms of ventricular tachycardia may also occur. Headache may be a symptom of hypertension. Bradycardia may also be seen early in phenylephrine overdosage through stimulation of baroreceptors.

Treatment

The treatment of overdosage with promethazine and phenylephrine is essentially symptomatic and supportive. Only in cases of extreme overdosage or individual sensitivity do vital signs including respiration, pulse, blood pressure, temperature, and EKG need to be monitored. Activated charcoal orally or by lavage may be given, or sodium or magnesium sulfate orally as a cathartic. Attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. Diazepam may be used to control convulsions. Acidosis and electrolyte losses should be corrected. Note that any depressant effects of promethazine are not reversed by naloxone. Avoid analeptics which may cause convulsions.

Severe hypotension usually responds to the administration of norepinephrine or phenylephrine. EPINEPHRINE SHOULD NOT BE USED, since its use in a patient with partial adrenergic blockade may further lower the blood pressure.

Limited experience with dialysis indicates that it is not helpful.

Promethazine is contraindicated in individuals known to be hypersensitive or to have had an idiosyncratic reaction to promethazine or to other phenothiazines. Antihistamines are contraindicated for use in the treatment of lower respiratory tract symptoms, including asthma. Phenylephrine is contraindicated in patients with hypertension or with peripheral vascular insufficiency (ischemia may result with risk of gangrene or thrombosis of compromised vascular beds). Phenylephrine should not be used in patients known to be hypersensitive to the drug or in those receiving a monoamine oxidase inhibitor (MAOI).

Promethazine

Promethazine is a phenothiazine derivative which differs structurally from the antipsychotic phenothiazines by the presence of a branched side chain and no ring substitution. It is thought that this configuration is responsible for its relative lack (1/ 10 that of chlorpromazine) of dopaminergic (CNS) action. Promethazine is an H₁ receptor blocking agent. In addition to its antihistaminic action, it provides clinically useful sedative and antiemetic effects. In therapeutic dosages, promethazine produces no significant effects on the cardiovascular system. Promethazine is well absorbed from the gastrointestinal tract. Clinical effects are apparent within 20 minutes after oral administration and generally last four to six hours, although they may persist as long as 12 hours. Promethazine is metabolized by the liver to a variety of compounds; the sulfoxides of promethazine and N-demethylpromethazine are the predominant metabolites appearing in the urine.

Phenylephrine

Phenylephrine is a potent post- synaptic a- receptor agonist with little effect on b- receptors of the heart. Phenylephrine has no effect on b-adrenergic receptors of the bronchi or peripheral blood vessels. A direct action at recep- tors accounts for the greater part of its effects, only a small part being due to its ability to release norepinephrine. Therapeutic doses of phenylephrine mainly cause vasoconstriction. Phenylephrine increases resistance and, to a lesser extent, decreases capacitance of blood vessels. Total peripheral resistance is increased, resulting in increased systolic and diastolic blood pressure. Pulmonary arterial pressure is usually increased, and renal blood flow is usually decreased. Local vasoconstriction and hemostasis occur following topical application or infiltration of phenylephrine into tissues. The main effect of phenylephrine on the heart is bradycardia; it produces a positive inotropic effect on the myocardium in doses greater than those usually used therapeutically. Rarely, the drug may increase the irritability of the heart, causing arrhythmias. Cardiac output is decreased slightly. Phenylephrine increases the work of the heart by increasing peripheral arterial resistance. Phenylephrine has a mild central stimulant effect.

Following oral administration or topical application of phenylephrine to the mucosa, constriction of blood vessels in the nasal mucosa relieves nasal congestion associated with allergy or head colds. Following oral administration, nasal decongestion may occur within 15 or 20 minutes and may persist for up to 4 hours. Phenylephrine is irregularly absorbed from and readily metabolized in the gastrointestinal tract. Phenylephrine is metabolized in the liver and intestine by monoamine oxidase. The metabolites and their route and rate of excretion have not been identified. The pharmacologic action of phenylephrine is terminated at least partially by uptake of the drug into tissues.

Promethazine and phenylephrine may cause marked drowsiness or may impair the mental and/ or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. Ambulatory patients should be told to avoid engaging in such activities until it is known that they do not become drowsy or dizzy from promethazine and phenylephrine therapy. Children should be supervised to avoid potential harm in bike riding or in other hazardous activities.

The concomitant use of alcohol or other central nervous system depressants, including narcotic analgesics, sedatives, hypnotics, and tranquilizers, may have an additive effect and should be avoided or their dosage reduced.

Patients should be advised to report any involuntary muscle movements or unusual sensitivity to sunlight.

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.

PROMETHAZINE/PHENYLEPHRINE - ORAL

(pro-METH-uh-zeen/fen-ill-EFF-rin)

WARNING: Promethazine should not be used in children younger than 2 years since it might cause serious (possibly fatal) slow/shallow breathing. This problem has occurred even with normal doses in this age group.

Use this drug with caution in children older than 2 years. The lowest effective dosage should be used, and other drugs that affect breathing should be avoided. Seek immediate medical attention in the unlikely event that slow/shallow breathing occurs. Promethazine should not be used in children with liver disease (including possible Reyes syndrome).

USES: This medication is used to treat runny nose, coughing, sneezing, itchy nose/throat, and itchy/watery eyes caused by allergies or the common cold.

Promethazine belongs to a class of drugs known as antihistamines. It works by preventing the effects of a certain natural chemical (histamine).

Phenylephrine belongs to a class of drugs known as decongestants. It causes shrinking/narrowing of blood vessels in the nose and sinuses to reduce nasal congestion (stuffy nose).

HOW TO USE: Take this medication by mouth with or without food, usually every 4-6 hours or as directed by your doctor. This medication may be taken with food if stomach upset occurs.

Dosage is based on your medical condition and response to treatment. Carefully measure your prescribed dose using a medication-measuring device or spoon. Do not use a household spoon because you may not get the correct dose.

Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same times each day.

Inform your doctor if your condition persists or worsens after 7 days.

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

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: fast/slow/irregular heartbeat, difficulty breathing, vomiting, decreased coordination, fainting, ringing in the ears, vision changes (e.g., blurred/double vision), difficulty urinating, shaking (tremor), mental/mood changes (e.g., nervousness, irritability, confusion, hallucinations).

Stop taking this medication and seek immediate medical attention if any of these rare but very serious side effects occur: slow/shallow breathing, signs of infection (e.g., fever, persistent sore throat), severe abdominal pain, persistent nausea/vomiting, easy bleeding/bruising, yellowing of eyes/skin, dark urine, abnormal/involuntary movements (e.g., fixed upward stare, neck twisting, tongue movements).

Promethazine may infrequently cause a very serious (rarely fatal) nervous system disorder (neuroleptic malignant syndrome). If you notice any of the following rare but very serious side effects, stop taking this medication and seek immediate medical attention: severe muscle stiffness, mental/mood changes (e.g., sudden confusion, extreme drowsiness), very high fever, seizures, irregular/fast heartbeat, increased sweating.

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: See also Warning section.

Before taking this medication, tell your doctor or pharmacist if you are allergic to it; or to any other phenothiazines (e.g., prochlorperazine); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart problems (e.g., angina, irregular heartbeat), kidney/liver problems, breathing problems (e.g., asthma, emphysema, sleep apnea), difficulty urinating (e.g., due to an enlarged prostate), stomach/bowel problems (e.g., blockage, ulcer), high blood pressure, overactive thyroid (hyperthyroidism), diabetes, a certain eye problem (narrow-angle glaucoma), seizures, blood/immune system problems (e.g., bone marrow depression).

This drug may make you dizzy or drowsy; use caution while engaging in activities requiring alertness such as driving or using machinery. Children should be supervised to avoid injury during bicycle riding or other possibly hazardous activities. Limit alcoholic beverages.

To minimize dizziness and lightheadedness, get up slowly from a sitting or lying position.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

Liquid forms of this medication may contain sugar, alcohol, or aspartame. Caution is advised if you have diabetes, alcohol dependence, liver disease, phenylketonuria (PKU), or any other condition that requires you to limit/avoid these substances in your diet. Ask your doctor or pharmacist about using this product safely.

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

Children may be more sensitive to the effects of the drug, especially breathing problems such as slow/shallow breathing. Children may also experience excitability rather than drowsiness. Special caution should be taken in children with a family history of sudden infant death syndrome (SIDS), those who have a severe loss of fluid (dehydration), and those who are hard to wake up from sleep.

The elderly may be more sensitive to the effects of the drug, especially drowsiness and confusion.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is unknown if this medication passes into breast milk. However, it may have undesirable effects on a nursing infant. Therefore, breast-feeding while using this medication is not recommended. 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 it. Do not start, stop or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: MAO inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, selegiline, tranylcypromine), epinephrine for low blood pressure, metrizamide, sibutramine, cabergoline, pergolide, halofantrine, pimozide.

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

Avoid taking MAO inhibitors within 2 weeks before, during, and after treatment with this medication. In some cases a serious (possibly fatal) drug interaction may occur.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: narcotic pain medications (e.g., codeine), tramadol, muscle relaxants, medicine for sleep/anxiety (e.g., alprazolam, diazepam, zolpidem), bupropion, tricyclic antidepressants (e.g., amitriptyline), psychiatric medicines (e.g., chlorpromazine, risperidone, trazodone), drugs for Parkinson's disease (e.g., anticholinergics such as benztropine, trihexyphenidyl), anti-seizure drugs (e.g., carbamazepine), scopolamine, antispasmodics (e.g., atropine, belladonna alkaloids), other antihistamines (e.g., diphenhydramine, dimenhydrinate), cough-and-cold products, diphenhydramine or other antihistamines applied to the skin (e.g., anti-itch cream, ointment, spray).

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: nausea, vomiting, blurred vision, drowsiness, slowed breathing, widened/fixed pupils, seizures, deep sleep, loss of consciousness.

NOTES: Do not share this medication with others.

Unless otherwise directed by your physician, drink plenty of fluids (especially water) while taking this medication. It will help to break up mucus and clear congestion.

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

Promethazine may affect the results of some pregnancy tests. Consult your doctor for more details.

MISSED DOSE: If you 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 at room temperature between 59-77 degrees F (15-25 degrees C) away from sunlight. Keep the container tightly closed. 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.