Promethazine and Phenylephrine

Dosage Form: syrup

Promethazine and Phenylephrine Description

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, methylparaben, propylene glycol, propylparaben, purified water, saccharin sodium, sodium benzoate, sodium citrate, sucrose syrup and sugar.

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 320.88, a molecular formula of C17H20N2S•HCl, and the following structural formula:

Phenylephrine hydrochloride is a sympathomimetic amine salt which is chemically designated as (-)-m-Hydroxy-α-[(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, a molecular formula of C9H13NO2•HCl, and the following structural formula:

Promethazine and Phenylephrine - Clinical Pharmacology

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 dopamine antagonist properties.

Promethazine is an H1 receptor blocking agent. In addition to its antihistaminic action, it provides clinically useful sedative and antiemetic effects.

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 postsynaptic α-receptor agonist with little effect on β-receptors of the heart. Phenylephrine has no effect on β-adrenergic receptors of the bronchi or peripheral blood vessels. A direct action at receptors 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.

Indications and Usage for Promethazine and Phenylephrine

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.

Contraindications

Promethazine is contraindicated in comatose states, and 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).

Warnings

WARNING

PROMETHAZINE HYDROCHLORIDE SHOULD NOT BE USED IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE BECAUSE OF THE POTENTIAL FOR FATAL RESPIRATORY DEPRESSION.

POSTMARKETING CASES OF RESPIRATORY DEPRESSION, INCLUDING FATALITIES, HAVE BEEN REPORTED WITH USE OF PROMETHAZINE HYDROCHLORIDE IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE. A WIDE RANGE OF WEIGHT-BASED DOSES OF PROMETHAZINE HYDROCHLORIDE HAVE RESULTED IN RESPIRATORY DEPRESSION IN THESE PATIENTS.

CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE HYDROCHLORIDE TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER. IT IS RECOMMENDED THAT THE LOWEST EFFECTIVE DOSE OF PROMETHAZINE HYDROCHLORIDE BE USED IN PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER AND CONCOMITANT ADMINISTRATION OF OTHER DRUGS WITH RESPIRATORY DEPRESSANT EFFECTS BE AVOIDED.

Promethazine:

CNS Depression - Promethazine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine HCl (see PRECAUTIONS-Information for Patients and Drug Interactions).

Respiratory Depression - Promethazine may lead to potentially fatal respiratory depression.

Use of Promethazine in patients with compromised respiratory function (e.g., COPD, sleep apnea) should be avoided.

Lower Seizure Threshold - Promethazine may lower seizure threshold. It should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold.

Bone-Marrow Depression - Promethazine should be used with caution in patients with bone-marrow depression. Leukopenia and agranulocytosis have been reported, usually when promethazine HCl has been used in association with other known marrow-toxic agents.

Neuroleptic Malignant Syndrome - A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with promethazine HCl alone or in combination with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias).

The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g. pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.

The management of NMS should include 1) immediate discontinuation of promethazine HCl, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.

Since recurrences of NMS have been reported with phenothiazines, the reintroduction of promethazine HCl should be carefully considered.

Use in Pediatric Patients

PROMETHAZINE PRODUCTS ARE CONTRAINDICATED FOR USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE.

CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE PRODUCTS TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER BECAUSE OF THE POTENTIAL FOR FATAL RESPIRATORY DEPRESSION. RESPIRATORY DEPRESSION AND APNEA, SOMETIMES ASSOCIATED WITH DEATH, ARE STRONGLY ASSOCIATED WITH PROMETHAZINE PRODUCTS AND ARE NOT DIRECTLY RELATED TO INDIVIDUALIZED WEIGHT-BASED DOSING, WHICH MIGHT OTHERWISE PERMIT SAFE ADMINISTRATION. CONCOMITANT ADMINISTRATION OF PROMETHAZINE PRODUCTS WITH OTHER RESPIRATORY DEPRESSANTS HAS AN ASSOCIATION WITH RESPIRATORY DEPRESSION, AND SOMETIMES DEATH, IN PEDIATRIC PATIENTS.

ANTIEMETICS ARE NOT RECOMMENDED FOR TREATMENT OF UNCOMPLICATED VOMITING IN PEDIATRIC PATIENTS, AND THEIR USE SHOULD BE LIMITED TO PROLONGED VOMITING OF KNOWN ETIOLOGY. THE EXTRAPYRAMIDAL SYMPTOMS WHICH CAN OCCUR SECONDARY TO PROMETHAZINE HYDROCHLORIDE ADMINISTRATION MAY BE CONFUSED WITH THE CNS SIGNS OF UNDIAGNOSED PRIMARY DISEASE, e.g., ENCEPHALOPATHY OR REYE’S SYNDROME. THE USE OF PROMETHAZINE PRODUCTS SHOULD BE AVOIDED IN PEDIATRIC PATIENTS WHOSE SIGNS AND SYMPTOMS MAY SUGGEST REYE’S SYNDROME OR OTHER HEPATIC DISEASES.

Excessively large dosages of antihistamines, including promethazine hydrochloride, in pediatric patients may cause sudden death (see OVERDOSAGE). Hallucinations and convulsions have occurred with therapeutic doses and overdoses of promethazine hydrochloride in pediatric patients. In pediatric patients who are acutely ill associated with dehydration, there is an increased susceptibility to dystonias with the use of promethazine HCl.

Other Considerations

Administration of promethazine has been associated with reported cholestatic jaundice.

Phenylephrine

Because phenylephrine is an adrenergic 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 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.

Precautions

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

Drugs having anticholinergic properties should be used with caution in patients with narrow-angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, and bladder-neck obstruction.

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.

Information for Patients

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.

Avoid prolonged exposure to the sun.

Drug Interactions

Promethazine

CNS Depressants Promethazine may increase, prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine HCl. When given concomitantly with promethazine, the dose of barbiturates should be reduced by at least one-half, and the dose of narcotics should be reduced by one-quarter to one-half. Dosage must be individualized. Excessive amounts of promethazine HCl relative to a narcotic may lead to restlessness and motor hyperactivity in the patient with pain; these symptoms usually disappear with adequate control of the pain.

Epinephrine Because of the potential for promethazine to reverse epinephrine’s vasopressor effect, epinephrine should NOT be used to treat hypotension associated with promethazine overdose.

Anticholinergics Concomitant use of other agents with anticholinergic properties should be undertaken with caution.

Monoamine oxidase inhibitors (MAOI) Drug interactions, including an increased incidence of extrapyramidal effects, have been reported when some MAOI and phenothiazines are used concomitantly.

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 ß-adrenergic blockers.

Effect

Cardiostimulating effects blocked.

Drug

Phenylephrine with prior administration of phentolamine or other α-adrenergic blockers.

Effect

Pressor response decreased.

Drug

Phenylephrine with diet preparations, such as amphetamines or phenylpropanolamine.

Effect

Synergistic adrenergic response.

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 HCl. These doses are from approximately 2.1 to 4.2 times the maximum recommended total daily dose of promethazine for a 50-kg subject, depending upon the indication for which the drug is prescribed. Daily doses of 25 mg/kg intraperitoneally have been found to produce fetal mortality in rats.

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 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 administered to a pregnant woman 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 “Nonteratogenic Effects.”

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

PROMETHAZINE HYDROCHLORIDE AND PHENYLEPHRINE HYDROCHLORIDE SYRUP IS CONTRAINDICATED FOR USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE (seeWARNINGS – Black Box WarningandUse in Pediatric Patients).

Promethazine hydrochloride and phenylephrine hydrochloride syrup should be used with caution in pediatric patients 2 years of age and older (see WARNINGS – Use in Pediatric Patients).

Geriatric Use

Clinical studies of promethazine hydrochloride and phenylephrine hydrochloride syrup 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.

Sedating drugs may cause confusion and over-sedation in the elderly; elderly patients generally should be started on low doses of Promethazine Hydrochloride and Phenylephrine Hydrochloride Syrup and observed closely.

Adverse Reactions

Promethazine:

Central Nervous System ⎯ Drowsiness is the most prominent CNS effect of this drug. Sedation, somnolence, blurred vision, dizziness; confusion, disorientation, and extrapyramidal symptoms such as oculogyric crisis, torticollis, and tongue protrusion; lassitude, tinnitus, incoordination, fatigue, euphoria, nervousness, diplopia, insomnia, tremors, convulsive seizures, excitation, catatonic-like states, hysteria. Hallucinations have also been reported.

Cardiovascular - Increased or decreased blood pressure, tachycardia, bradycardia, faintness.

Dermatologic - Dermatitis, photosensitivity, urticaria.

Hematologic - Leukopenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis.

Gastrointestinal - Dry mouth, nausea, vomiting, jaundice.

Respiratory - Asthma, nasal stuffiness, respiratory depression (potentially fatal) and apnea (potentially fatal). (See WARNINGS-Promethazine; Respiratory Depression.)

Other - Angioneurotic edema. Neuroleptic malignant syndrome (potentially fatal) has also been reported. (See WARNINGS-Promethazine; Neuroleptic Malignant Syndrome.)

Paradoxical Reactions - Hyperexcitability and abnormal movements have been reported in patients following a single administration of promethazine HCl. Consideration should be given to the discontinuation of promethazine HCl and to the use of other drugs if these reactions occur. Respiratory depression, nightmares, delirium, and agitated behavior have also been reported in some of these patients.

Phenylephrine:

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

Cardiovascular - Hypertension (see “WARNINGS”).

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

Overdosage

Promethazine:

Signs and symptoms of overdosage with promethazine HCl range from mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depression, unconsciousness, and sudden death. Other reported reactions include hyperreflexia, hypertonia, ataxia, athetosis, and extensor-plantar reflexes (Babinski reflex).

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 and Phenylephrine Dosage and Administration

Promethazine hydrochloride and phenylephrine hydrochloride syrup is contraindicated for children under 2 years of age (seeWARNINGS – Black Box WarningandUse in Pediatric Patients).

The recommended doses are given in the following table:

Adults And Children 12 Years And Over

1 teaspoonful (5 mL) every 4 to 6 hours, not to exceed 6 teaspoonsful (30 mL) in 24 hours.

Children 6 To Under 12 Years Of Age

½ to 1 teaspoonful (2.5 to 5 mL) every 4 to 6 hours, not to exceed 6 teaspoonsful (30 mL) in 24 hours.

Children 2 To Under 6 Years Of Age

¼ to ½ teaspoonful (1.25 to 2.5 mL) every 4 to 6 hours.

How is Promethazine and Phenylephrine Supplied

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) and one pint (473 mL).

Keep tightly closed. Protect from light.

Store at 20 - 25° C (68 - 77° F) [See USP Controlled Room Temperature].

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

Manufactured by

Actavis Mid Atlantic LLC

7205 Windsor Blvd.

Baltimore, MD 21244 USA


FORM NO. 1628


Rev. 9/06


VC2788

PROMETHAZINE HYDROCHLORIDE AND PHENYLEPHRINE HYDROCHLORIDE  promethazine hydrochloride and phenylephrine hydrochloride  syrup

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0472-1628 Route of Administration ORAL DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Promethazine Hydrochloride (Promethazine) Active 6.25 MILLIGRAM  In 5 MILLILITER Phenylephrine Hydrochloride (Phenylephrine) Active 5 MILLIGRAM  In 5 MILLILITER citric acid Inactive   fd&c yellow #6 Inactive   flavor Inactive   methyparaben Inactive   propylene glycol Inactive   propylparaben Inactive   water Inactive   saccharin sodium Inactive   sodium benzoate Inactive   sodium citrate Inactive   sucrose syrup Inactive   alcohol Inactive

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0472-1628-04 118 mL (MILLILITER) In 1 BOTTLE None 2 0472-1628-16 473 mL (MILLILITER) In 1 BOTTLE None

Revised: 12/2008Actavis Mid Atlantic LLC

More Promethazine and Phenylephrine resources

• Promethazine and Phenylephrine Side Effects (in more detail)
• Promethazine and Phenylephrine Dosage
• Promethazine and Phenylephrine Use in Pregnancy & Breastfeeding
• Promethazine and Phenylephrine Drug Interactions
• Promethazine and Phenylephrine Support Group
• 0 Reviews for Promethazine and Phenylephrine - Add your own review/rating

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Artane

Generic Name: trihexyphenidyl (Oral route)

trye-hex-ee-FEN-i-dil

Commonly used brand name(s)

In the U.S.

• Artane


• Trihexane


• Tritane

Available Dosage Forms:

• Tablet


• Capsule, Extended Release


• Elixir

Therapeutic Class: Antiparkinsonian

Pharmacologic Class: Anticholinergic

Uses For Artane

Trihexyphenidyl is used alone or together with other medicines (e.g., levodopa) to treat Parkinson's disease. By improving muscle control and reducing stiffness, this medicine allows more normal movements of the body as the disease symptoms are reduced.

Trihexyphenidyl is also used to control severe muscle reactions and other side effects from certain medicines that are used to treat severe nausea or nervous, mental, or emotional conditions (e.g., haloperidol [Haldol®], loxapine [Loxitane®], prochlorperazine [Compazine®], promethazine [Phenergan®], thiothixene [Navane®]).

This medicine is available only with your doctor's prescription.

Before Using Artane

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

No information is available on the relationship of age to the effects of trihexyphenidyl in the pediatric population. Safety and efficacy have not been established.

Geriatric

No information is available on the relationship of age to the effects of trihexyphenidyl in geriatric patients. However, elderly men are more likely to have age-related prostate problems, and all elderly patients are more likely to have age-related kidney, liver, or heart problems. These conditions may require caution or an adjustment in the dose for patients receiving trihexyphenidyl.

Breast Feeding

Studies suggest that this medication may alter milk production or composition. If an alternative to this medication is not prescribed, you should monitor the infant for side effects and adequate milk intake.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Potassium

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Betel Nut


• Chlorpromazine


• Haloperidol


• Perphenazine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bowel or stomach blockage or


• Enlarged prostate or


• Glaucoma or


• Hypertension (high blood pressure) or


• Urinary blockage—Use with caution. May make these conditions worse.

• Kidney disease or


• Liver disease—Use with caution. Effects may be increased because of slower removal of the medicine from the body.

Proper Use of trihexyphenidyl

This section provides information on the proper use of a number of products that contain trihexyphenidyl. It may not be specific to Artane. Please read with care.

Take this medicine every day exactly as ordered by your doctor in order to improve your condition as much as possible. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

You may take this medicine before or after food, although it is usually taken with meals.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (elixir or tablets):
  
  • For Parkinson's disease:
    
    • Adults—At first, 1 milligram (mg) once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 15 mg per day, given in divided doses 3 or 4 times per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For side effects caused by other medicines:
    
    • Adults—5 to 15 milligrams (mg) per day, given in divided doses 3 or 4 times per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Artane

It is important that your doctor check your progress at regular visits to allow changes in your dose and to check for any unwanted effects.

Before using this medicine, your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor). Trihexyphenidyl may increase your risk of having glaucoma. Check with your doctor right away if you have blurred vision or any change in vision while taking this medicine.

Trihexyphenidyl may cause dryness of the mouth, nose, and throat. For temporary relief of mouth dryness, use sugarless candy or gum, melt bits of ice in your mouth, or use a saliva substitute. However, if your mouth continues to feel dry for more than 2 weeks, check with your medical doctor or dentist. Continuing dryness of the mouth may increase the chance of dental disease, including tooth decay, gum disease, and fungus infections.

Artane Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Rare

• Abdominal or stomach cramps or pain


• bloating


• constipation


• delusions of persecution, mistrust, suspiciousness, or combativeness


• excessive dryness of the mouth


• false beliefs that cannot be changed by facts


• loss of appetite


• nausea or vomiting


• seeing, hearing, or feeling things that are not there


• skin rash


• stomach pain


• swollen, painful, or tender lymph glands on the side of the face or neck

Incidence not known

• Anxiety


• blurred vision


• change in vision


• decrease in frequency of urination


• decrease in urine volume


• difficult urination


• difficulty in passing urine (dribbling)


• disturbed behavior


• dry mouth


• enlarged pupils


• eye pain


• fast, pounding, or irregular heartbeat or pulse


• hyperventilation


• irritability


• loss of vision


• mental confusion


• nervousness


• painful urination


• restlessness


• shaking


• shortness of breath


• trouble sleeping

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Dizziness


• mild nausea


• nervousness

Incidence not known

• Drowsiness


• weakness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Artane side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Artane resources

• Artane Side Effects (in more detail)
• Artane Use in Pregnancy & Breastfeeding
• Drug Images
• Artane Drug Interactions
• Artane Support Group
• 1 Review for Artane - Add your own review/rating

• Artane Concise Consumer Information (Cerner Multum)


• Trihexyphenidyl MedFacts Consumer Leaflet (Wolters Kluwer)


• Trihexyphenidyl Prescribing Information (FDA)


• Trihexyphenidyl Hydrochloride Monograph (AHFS DI)

Compare Artane with other medications

• Cerebral Spasticity
• Extrapyramidal Reaction
• Parkinson's Disease

Humate-P injection

Generic Name: antihemophilic factor (factor VIII) (injection) (an TEE hee moe FIH lick FAC tor)

Brand Names: Advate rAHF-PFM, Alphanate, Helixate, Helixate FS, Hemofil-M, Humate-P, Koate-DVI, Koate-HP, Kogenate, Kogenate FS, Monarc-M, Monoclate-P, Recombinate, Refacto

What is antihemophilic factor (factor VIII)?

Antihemophilic factor (factor VIII) is a naturally occurring protein in the blood that helps blood to clot. A lack of factor VIII is the cause of hemophilia A.

Antihemophilic factor (factor VIII) is used to treat or prevent bleeding in people with hemophilia A.

Antihemophilic factor (factor VIII) may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about antihemophilic factor (factor VIII)?

Some forms of this medication are made from human plasma (part of the blood) and may contain viruses and other infectious agents that can cause disease. Although donated human plasma is screened, tested, and treated to reduce the risk of it containing anything that could cause disease, there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

Some viruses, such as parovovirus B19 and hepatitis A, may be more difficult to identify or remove from antihemophilic factor (factor VIII). Parovovirus can seriously affect pregnant women and people with weak immune systems. Symptoms of parovovirus B19 infection include fever, chills, runny nose, and drowsiness followed about 2 weeks later by a rash and joint pain. Symptoms of hepatitis A may include several days to weeks of poor appetite, tiredness, and low-grade fever followed by nausea, vomiting, and stomach pain. Dark-colored urine and jaundice (yellowing of the skin or eyes) may also occur. Contact your doctor if you develop any of these symptoms after treatment with antihemophilic factor (factor VIII).

Carry an ID card or wear a medical alert bracelet stating that you have hemophilia, in case of emergency. Any doctor, dentist, or emergency medical care provider who treats you should know that you have a bleeding disorder.

Your body may develop antibodies to this medication, making it less effective. Contact your doctor if this medicine does not seem to be working as well as before in controlling your bleeding.

If you need to have any type of surgery, tell the surgeon ahead of time that you are using antihemophilic factor (factor VIII). You may need to stop using the medicine for a short time.

What should I discuss with my healthcare provider before using antihemophilic factor (factor VIII)?

This medication comes in many different strengths. Be sure the strength printed on the medicine bottle label is correct for the dose your doctor has prescribed for you.

Do not use this medication if you have:

• 
  

  a history of allergy to antihemophilic factor; or

  
  


• 
  

  a history of allergy to products made with human or animal proteins, especially mouse proteins.

  
  

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether this medication passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Some forms of this medication are made from human plasma (part of the blood) and may contain viruses and other infectious agents that can cause disease. Although donated human plasma is screened, tested, and treated to reduce the risk of it containing anything that could cause disease, there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

Some viruses, such as parovovirus B19 and hepatitis A, may be more difficult to identify or remove from antihemophilic factor (factor VIII). Parovovirus can seriously affect pregnant women and people with weak immune systems. Symptoms of parovovirus B19 infection include fever, chills, runny nose, and drowsiness followed about 2 weeks later by a rash and joint pain. Symptoms of hepatitis A may include several days to weeks of poor appetite, tiredness, and low-grade fever followed by nausea, vomiting, and stomach pain. Dark-colored urine and jaundice (yellowing of the skin or eyes) may also occur. Contact your doctor if you develop any of these symptoms after treatment with antihemophilic factor (factor VIII).

How should I use antihemophilic factor (factor VIII)?

This medication is given as an injection through a needle placed into a vein. Your doctor, nurse, or other healthcare provider will give your first injection. Then you will be given instructions on how to use your injections at home. Do not use this medicine at home if you do not fully understand how to give the injection and properly dispose of needles and other items used in giving the medicine.

To be sure this medication is helping your condition, your blood will need to be tested on a regular basis. Do not miss any scheduled visits to your doctor.

Carry an ID card or wear a medical alert bracelet stating that you have hemophilia, in case of emergency. Any doctor, dentist, or emergency medical care provider who treats you should know that you have a bleeding disorder.

Your body may develop antibodies to this medication, making it less effective. Contact your doctor if this medicine does not seem to be working as well as before in controlling your bleeding.

If you need to have any type of surgery, tell the surgeon ahead of time that you are using antihemophilic factor (factor VIII). You may need to stop using the medicine for a short time.

Store the powder medicine in the refrigerator. Do not freeze. Do not mix this medicine with the liquid diluent until you are ready to give the injection. Once the medicine has been mixed, you must use it within 3 hours. Do not refrigerate the mixed medicine. Keep it at room temperature. You may also store the powder at room temperature for up to 6 months or until the expiration date printed on the label (whichever comes first). Do not put the medicine back into the refrigerator once you have kept it at room temperature.

What happens if I miss a dose?

Contact your doctor for instructions if you miss a dose of this medication.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

What should I avoid while using antihemophilic factor (factor VIII)?

There are no restrictions on food, beverages, or activity while using this medication unless your doctor has told you otherwise.

Antihemophilic factor (factor VIII) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have any of these serious side effects:

• 
  

  nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

  
  


• 
  

  fever, chills, runny nose, and drowsiness followed about 2 weeks later by a rash and joint pain;

  
  


• 
  

  fast heart rate, chest pain, trouble breathing;

  
  


• 
  

  feeling light-headed, fainting; or

  
  


• 
  

  pain, redness, swelling, or oozing where the medicine was injected.

  
  

Other, less serious side effects may be more likely to occur, such as:

• 
  

  unusual taste in your mouth;

  
  


• 
  

  cough, runny or stuffy nose;

  
  


• 
  

  mild itching;

  
  


• 
  

  swelling in your hands, ankles, or feet;

  
  


• 
  

  headache or dizziness;

  
  


• 
  

  mild nausea, diarrhea, stomach pain;

  
  


• 
  

  sweating;

  
  


• 
  

  joint pain; or

  
  


• 
  

  chills or flushing (warmth or tingly feeling).

  
  

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect antihemophilic factor (factor VIII)?

Other drugs that affect bleeding or blood-clotting may interact with antihemophilic factor (factor VIII) and cause dangerous side effects or make the medicine less effective.

There may be other drugs that can affect antihemophilic factor (factor VIII). Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?

• Your pharmacist has additional information about antihemophilic factor (factor VIII) written for health professionals that you may read.

What does my medication look like?

Antihemophilic factor (factor VIII) is available with a prescription under several brand names. Generic formulations may also be available. Ask your pharmacist any questions you have about this medication, especially if it is new to you.

Ambenonium

Pronunciation: AM-be-NOE-nee-um
Generic Name: Ambenonium
Brand Name: Mytelase

Ambenonium is used for:

Treating myasthenia gravis. It may also be used for other conditions as determined by your doctor.

Ambenonium is a cholinesterase inhibitor. It works by improving nerve impulses in muscles so that the muscles are better able to work.

Do NOT use Ambenonium if:

• you are allergic to any ingredient in Ambenonium


• you are taking quinine, quinidine, atropine, belladonna, ganglionic blocking agents (eg, mecamylamine), or cholinergic agents (eg, guanidine)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Ambenonium:

Some medical conditions may interact with Ambenonium. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have heart problems (eg, heart block, slow heartbeat); Parkinson disease; a urinary tract infection; asthma; kidney problems; or a blockage of your stomach, bowel, or bladder

Some MEDICINES MAY INTERACT with Ambenonium. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Atropine, belladonna, ganglionic blocking agents (eg, mecamylamine), quinine, or quinidine because effectiveness of Ambenonium may be decreased


• Cholinergic agents (eg, guanidine) because the risk of side effects may be increased

This may not be a complete list of all interactions that may occur. Ask your health care provider if Ambenonium may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Ambenonium:

Use Ambenonium as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Ambenonium by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.


• If you miss a dose of Ambenonium, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Ambenonium.

Important safety information:

• Tell your doctor or dentist that you take Ambenonium before you receive any medical or dental care, emergency care, or surgery.


• Do not change your dose without checking with your doctor.


• Ambenonium should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Ambenonium while you are pregnant. It is not known if Ambenonium is found in breast milk. Do not breast-feed while taking Ambenonium.

Possible side effects of Ambenonium:

All medicines may cause side effects, but many people have no, or minor, side effects. When used in small doses, no COMMON side effects have been reported with this product. Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); diarrhea; fainting; increased production of saliva or tears; increased sweating; muscle cramps, twitching, or weakness; nausea; small pupils; stomach cramps; tremor; trouble speaking or swallowing; unusual tiredness with anxiety and dizziness or light-headedness; urgent urination; vision changes; vomiting; weakness.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch .

See also: Ambenonium side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include diarrhea; dizziness or light-headedness; fainting; frequent or urgent urination; increased production of saliva; increased sweating; muscle twitching, weakness, or paralysis; nausea; pale skin; panic; severe anxiety; severe headache; slow heartbeat; small pupils; stomach cramps; tremor; trouble breathing; trouble speaking or swallowing; unusual tiredness; vision changes (eg, blurred vision); vomiting; weakness.

Proper storage of Ambenonium:

Store Ambenonium at room temperatures up to 77 degrees F (25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Ambenonium out of the reach of children and away from pets.

General information:

• If you have any questions about Ambenonium, please talk with your doctor, pharmacist, or other health care provider.


• Ambenonium is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Ambenonium. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Ambenonium resources

• Ambenonium Side Effects (in more detail)
• Ambenonium Use in Pregnancy & Breastfeeding
• Ambenonium Drug Interactions
• Ambenonium Support Group
• 0 Reviews for Ambenonium - Add your own review/rating

• ambenonium Concise Consumer Information (Cerner Multum)

Compare Ambenonium with other medications

• Myasthenia Gravis

Visionblue

trypan blue

Dosage Form: injection, solution

Description

Visionblue™ (trypan blue ophthalmic solution) 0.06% is a sterile solution of trypan blue (an acid di-azo group dye). Visionblue™ is a selective tissue staining agent for use as a medical aid in ophthalmic surgery.

Each mL of Visionblue™ 0.06% contains: 0.6 mg trypan blue; 1.9 mg sodium mono-hydrogen orthophosphate (Na2HPO4.2H2O); 0.3 mg sodium di-hydrogen orthophosphate (NaH2PO4.2H2O); 8.2 mg sodium chloride (NaCl); and water for injection. The pH is 7.3 - 7.6. The osmolality is 257-314 mOsm/kg.


The drug substance trypan blue has the chemical name 3,3’-[(3,3’-dimethyl-4,4’-biphenylylene) bis (azo)] bis(5-amino-4-hydroxy-2,7-naphthalenedisulfonic acid) tetra sodium salt, a molecular weight of 960.8, a molecular formula of C34H24N6Na4O14S4, and has the following chemical structure:

Clinical Pharmacology

Visionblue™ selectively stains connective tissue structures in the human eye such as the anterior lens capsule of the human crystalline lens.


Visionblue™ is intended to be applied directly on the anterior lens capsule, staining any portion of the capsule which comes in contact with the dye. Excess dye is washed out of the anterior chamber. The dye does not penetrate the capsule, permitting visualization of the anterior capsule in contrast to the non‑stained lens cortex and inner lens material.

Indications and Usage

Visionblue™ is indicated for use as an aid in ophthalmic surgery by staining the anterior capsule of the lens.

Contraindications

Visionblue™ is contraindicated when a non-hydrated (dry state), hydrophilic acrylic intraocular lens (IOL) is planned to be inserted into the eye because the dye may be absorbed by the IOL and stain the IOL.

Precautions

General

It is recommended that after injection all excess Visionblue™ be immediately removed from the eye by thorough irrigation of the anterior chamber.

Carcinogenesis, mutagenesis, impairment of fertility

Trypan blue is carcinogenic in rats. Wister/Lewis rats developed lymphomas after receiving subcutaneous injections of 1% trypan blue dosed at 50 mg/kg every other week for 52 weeks (total dose approximately 1,250,000-fold the maximum recommended human dose of 0.06 mg per injection in a 60 kg person, assuming total absorption).


Trypan blue was mutagenic in the Ames test and caused DNA strand breaks in vitro.

Pregnancy

Teratogenic Effects: Pregnancy Category C.

Trypan blue is teratogenic in rats, mice, rabbits, hamsters, dogs, guinea pigs, pigs, and chickens. The majority of teratogenicity studies performed involve intravenous, intraperitoneal, or subcutaneous administration in the rat. The teratogenic dose is 50 mg/kg as a single dose or 25 mg/kg/day during embryogenesis in the rat. These doses are approximately 50,000- and 25,000-fold the maximum recommended human dose of 0.06 mg per injection based in a 60 kg person, assuming that the whole dose is completely absorbed. Characteristic anomalies included neural tube, cardiovascular, vertebral, tail, and eye defects. Trypan blue also caused an increase in post-implantation mortality, and decreased fetal weight. In the monkey, trypan blue caused abortions with single or two daily doses of 50 mg/kg between 20th to 25th days of pregnancy, but no apparent increase in birth defects (approximately 50,000-fold maximum recommended human dose of 0.06 mg per injection, assuming total absorption). There are no adequate and well-controlled studies in pregnant women. Trypan blue should be given to a pregnant woman only if the potential benefit justifies the potential risk to the fetus.

Nursing mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when trypan blue is administered to a nursing woman.

Pediatric use

The safety and effectiveness of trypan blue have been established in pediatric patients. Use of trypan blue is supported by evidence from an adequate and well-controlled study in pediatric patients.

Geriatric use

No overall differences in safety and effectiveness have been observed between elderly and younger patients.

Adverse Reactions

Adverse reactions reported following use of Visionblue™ include discoloration of high water content hydrogen intraocular lenses (see Contraindications) and inadvertent staining of the posterior lens capsule and vitreous face.  Staining of the posterior lens capsule or staining of the vitreous face is generally self limited, lasting up to one week.

Dosage and Administration

Cataract surgery

Visionblue™ is packaged in a 2.25 mL syringe to which a blunt cannula has to be attached.


After opening the eye, an air bubble is injected into the anterior chamber of the eye in order to minimize dilution of Visionblue™ by the aqueous. Visionblue™ is carefully applied onto the anterior lens capsule using a blunt cannula. Sufficient staining is achieved as soon as the dye has contacted the capsule. The anterior chamber is then irrigated with balanced salt solution to remove all excess dye. An anterior capsulotomy can then be performed.

How Supplied

Visionblue™ 0.06% is supplied as follows:


0.5 mL of Visionblue™ in a sterile single-use Luer Lok, 2.25 mL glass syringe, grey rubber plunger stopper and tip cap with polypropylene plunger rod in a peel pouch. 

Storage and Handling

Visionblue™ is stored at 15-25ºC (59-77ºF). Protect from direct sunlight.

Rx ONLY


Manufactured by                                       Distributed in the United States by

D.O.R.C. International b.v.                        Dutch Ophthalmic, USA

Scheijdelveweg 2                                       One Little River Road

3214 VN Zuidland                                      P.O. Box 968

The Netherlands                                        Kingston, NH-03848, U.S.A.

                                                                    Phone: 800-75-DUTCH or 603-642-8468.


Revision date: March 22, 2006                Copyright ©, 2006 Dutch Ophthalmic Research Center

US Patents 6,367,480 and 6,720,314

Visionblue  trypan blue  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 68803-612 (14202-612-10) Route of Administration OPHTHALMIC, INTRAOCULAR DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TRYPAN BLUE (TRYPAN BLUE) TRYPAN BLUE 0.3 mg  in 0.5 mL

Inactive Ingredients Ingredient Name Strength SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE 0.15 mg  in 0.5 mL SODIUM PHOSPHATE, DIBASIC, DIHYDRATE 0.85 mg  in 0.5 mL SODIUM CHLORIDE 4.1 mg  in 0.5 mL WATER 0.5 mL  in 0.5 mL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 68803-612-10 10 POUCH In 1 CARTON contains a POUCH 1 1 SYRINGE In 1 POUCH This package is contained within the CARTON (68803-612-10) and contains a SYRINGE, GLASS 1 0.5 mL In 1 SYRINGE, GLASS This package is contained within a POUCH and a CARTON (68803-612-10)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA021670	12/16/2004

Labeler - Dutch Ophthalmic Research Center International B.V. (407522184)

Establishment
Name	Address	ID/FEI	Operations
Pharmpur GmbH		340805167	manufacture

Revised: 02/2010Dutch Ophthalmic Research Center International B.V.

More Visionblue resources

• Visionblue Side Effects (in more detail)
• Visionblue Use in Pregnancy & Breastfeeding
• Visionblue Support Group
• 0 Reviews for Visionblue - Add your own review/rating

• VisionBlue Advanced Consumer (Micromedex) - Includes Dosage Information

Compare Visionblue with other medications

• Ophthalmic Surgical Staining

Adcortyl Intra-Articular / Intradermal Injection 10mg / ml

The wording of leaflets is regularly updated. This electronic text is the most up-to-date version and may differ from the leaflet in your pack. If you have any questions about the information provided, please ask your doctor or pharmacist.

ADCORTYL

INTRA-ARTICULAR/INTRADERMAL INJECTION 10 mg/ml

Triamcinolone acetonide

• Adcortyl IA/ID Injection is a steroid medicine, prescribed for many different conditions, including serious illnesses.



• You need to take it regularly to get the maximum benefit.



• Don’t stop taking this medicine without talking to your doctor – you may need to reduce the dose gradually.



• Adcortyl IA/ID Injection can cause side effects in some people (read section 4 below). Some problems such as mood changes (feeling depressed or ‘high’), or stomach problems can happen straight away. If you feel unwell in any
  way, keep taking your tablets, but see your doctor straight away.



• Some side effects only happen after weeks or months. These include weakness of arms and legs, or developing a rounder face (read section 4 for more information).



• If you take it for more than 3 weeks, you will get a blue ‘steroid card’: always keep it with you and show it to any doctor or nurse treating you.



• Keep away from people who have chicken pox or shingles, if you have never had them. They could affect you
  severely. If you do come into contact with chicken pox or shingles, see your doctor straight away.

Now read the rest of this leaflet. It includes other important information on the safe and effective use of this medicine that might be especially important for you.

Your doctor has prescribed Adcortyl injection for you. This leaflet gives a summary of information about your medicine. If you want to know more, or are not sure about anything, ask your doctor or pharmacist.

REMEMBER: This medicine is for YOU. Only a doctor can prescribe it. Never give it to anyone else. It may harm them
even if they have the same symptoms as you.

Q. What Is In Adcortyl Intra-Articular / Intradermal (Ia/Id) Injection?

A. Adcortyl IA/ID Injection belongs to a group of medicines called steroids. Their full name is corticosteroids. These corticosteroids occur naturally in the body, and help to maintain health and well-being. Boosting your body with extra corticosteroid (such as Adcortyl IA/ID Injection) is an effective way to treat various illnesses involving inflammation in the body. Adcortyl IA/ID Injection reduces this inflammation, which could otherwise go on making your condition worse. You must take this medicine regularly to get maximum benefit from it.

The injection contains triamcinolone acetonide 10mg/ml and is supplied in packs of 5 x 1.0ml glass ampoules or a single 5ml glass vial. The other ingredients are benzyl alcohol, polysorbate 80, carmellose, sodium chloride and water for injection.

UK PRODUCT LICENCE

Held by:

E. R. Squibb & Sons Limited

Uxbridge

UB8 1DH

England

Tel.:0800 7311736

IRISH PRODUCT AUTHORISATION

Held by:

Bristol-Myers Squibb Pharmaceuticals Ltd.

Swords

County Dublin

Tel.:1-800-749-749

MANUFACTURER

Bristol-Myers Squibb S.r.l.

Contrada Fontana del Ceraso

03012 Anagni (FR)

Italy

Q. What Is This Medicine For?

A. Adcortyl IA/ID Injection is for the treatment of joint pain, swelling and stiffness in inflammatory disorders such as rheumatoid arthritis. It is also used to treat various forms of allergic dermatitis, skin overgrowths such as
thickened scar tissue, and patchy baldness, which is usually reversible.

Before Receiving Your Medicine

Q. Should I be receiving Adcortyl IA/ID injection?

A. You should not receive this medicine if you have ever had an allergic reaction to similar medicines or to any of the ingredients in Adcortyl IA/ID injection. You should not receive this medicine if you are suffering from an infection
unless your doctor has also prescribed a treatment for the infection.

Q. Is there anything else I should discuss with my doctor before receiving Adcortyl IA/ID injection?

A. Check with your doctor before receiving Adcortyl IA/ID injection if you have had any recent infection, tuberculosis (TB), bowel disorders, an ulcer, blood clots, cancer, thin (brittle) bones, high blood pressure or heart failure, mental disorders, epilepsy, myasthenia gravis or glaucoma (increased pressure in your eyes).

Check with your doctor first:

• If you have ever had severe depression or manic-depression (bipolar disorder). This includes having had depression before while taking steroid medicines like Adcortyl IA/ID Injection.



• If any of your close family has had these illnesses.

If either of these applies to you, talk to a doctor before taking Adcortyl IA/ID Injection.

Q. What if I have been in contact with someone who has an infectious disease such as Chickenpox, Shingles or Measles?

A. Steroid medicines suppress your body's natural immune response. Therefore, if you come into contact with anyone who has an infectious disease such as chickenpox, shingles or measles, consult your doctor promptly, especially if you have not had the disease before. You should take particular care to avoid these diseases.

Q. Can I be immunised (vaccinated)?

A. While you are being treated with this medicine (or if you have recently stopped a course of treatment) do not have any immunisation without consulting your doctor.

Q. What if I am pregnant or think I may be pregnant? What if I am planning to become pregnant? What if I am breast-feeding?

A. You should make sure you discuss this with your doctor as soon as possible before receiving Adcortyl IA/ID injection.

Q. What if I have had problems with my kidneys, liver or thyroid?

A. Remind your doctor as the dose of Adcortyl may need to be adjusted.

Q. Can I take other medicines?

A. Corticosteroids can increase the chance of bleeding from the gut caused by aspirin, ibuprofen or other non-steroidal anti-inflammatory drugs (NSAIDs). If you have hypothrombinaemia (a tendency to bleed), your doctor will be
more careful about giving you Adcortyl IA/ID injection if you are taking ibuprofen or another NSAID. Always tell your doctor about all other medicines you are taking, even those you have bought at a pharmacy or other places, e.g. supermarket. Some medicines used to treat epilepsy, tuberculosis or breast cancer can reduce the effectiveness of Adcortyl. On the other hand, Adcortyl can affect the action of some medicines used to treat diabetes, high blood pressure or to thin the blood.

Always tell your doctor if you are taking oral contraceptives, hormone replacement therapy (HRT), growth hormone, thyroid drugs, cyclosporin, or medicines for treating fungal infections, or if you are to be vaccinated or to be given an anaesthetic.

Q. Is it all right to take exercise?

A. You must take care not to over-use a joint which feels better after you receive Adcortyl IA/ID injection as the joint will still need to recover from the inflammation which caused your symptoms.

Q. Is it all right to drive?

A. This medicine does not usually affect your ability to drive but it can affect your eyesight. Tell your doctor immediately if you have any pain in the eyes or visual disturbances.

Q. Is it all right to drink alcohol?

A. There is no known interaction between Adcortyl and alcohol.

Q. What if I am diabetic?

A. Remind your doctor as your insulin dose may need to be changed.

Q. Who should I tell that I have received this injection?

A. Your doctor or pharmacist will have given you a Steroid Treatment Card with your prescription or medicine. YOU SHOULD ALWAYS CARRY THIS CARD WITH YOU as it must be shown to any of the following persons:

• Doctor or Nurse - before having any surgery or emergency treatment or if any new treatment is prescribed.



• Dentist - before having any dental surgery



• Pharmacist - before buying any medicine



• Optician - it is advisable to have regular eye tests

Q. Is there any important information about the ingredients of Adcortyl that I need to know?

A. Adcortyl IA/ID Injection contains 15mg/ml benzyl alcohol which may cause harmful or allergic reactions in infants and children. Adcortyl IA/ID injection must not be given to premature or newly born babies.

Administraton Of Your Medicine

Q. How will Adcortyl IA/ID injection be given and how often?

A. The effect of the injection will vary from patient to patient and further injections may be given when symptoms return and not at regular intervals.

Use in inflammatory joint disorders:

The dose of injection to be given into a joint or into a tendon sheath depends upon the size of the joint to be treated and the severity of the condition. Doses of 2.5 - 5mg (0.25-0.5ml) for smaller joints and 5-15mg (0.5-1.5ml) for larger joints usually give relief of symptoms. This medicine should not be used for injection into the Achilles tendon.

Use in allergic dermatitis:

The dose is usually 2-3mg (0.2-0.3ml) depending on the size of the problem area of the skin but no more than 5mg (0.5ml) should be injected at any one site. If several sites are injected the total dose given should not exceed 30mg (3ml). Further doses may be given if necessary at one or two week intervals.

Children: Adcortyl IA/ID is not recommended for children under 6 years of age. It may be given to older children but the dose is adjusted according to their size and weight and is always kept as low as possible for the shortest possible time.

During times of illness or stress, patients on long-term treatment may require the addition of oral steroid tablets or, if they have recently finished a course of Adcortyl IA/ID injections, may need to start taking oral steroid tablets for
a while.

Q. How long should I continue receiving Adcortyl IA/ID injection?

A. Your doctor will advise you whether it is wise for you to have further injections.

Treatment with steroids is usually kept as short as possible and must not be stopped abruptly. Joints may become permanently damaged by repeated injections over a long period of time.

When the treatment is stopped you may notice flu-like symptoms, runny nose or itchy eyes or skin.

Mental problems while taking Adcortyl IA/ID injection

Mental health problems can happen while taking steroids like Adcortyl IA/ID Injection (see also section 4 Possible Side Effects).

• These illnesses can be serious.



• Usually they start within a few days or weeks of starting the medicine.



• They are more likely to happen at high doses.



• Most of these problems go away if the dose is lowered or the medicine is stopped. However, if problems do happen they might need treatment.

Talk to a doctor if you (or someone taking this medicine), shows any signs of mental problems. This is particularly important if you are depressed, or might be thinking about suicide. In a few cases, mental problems have happened when doses are being lowered or stopped.

Undesirable Effects

Q. Are there any unwanted effects of Adcortyl IA/ID injection?

A. All medicines may cause some unwanted or “side” effects. Some which can occur with steroid treatment are as follows. Tell your doctor immediately if you get ulcer pains in your stomach or severe pain in your abdomen, facial swelling or an unexpected rash. Patients have reported increased appetite, weight gain, indigestion, sickness, feeling tired or weak. Steroid treatment may cause increased risk of infection, thinning of bones or tendons causing fractures or torn muscles, water retention, irregular heart beat, high blood pressure or blood clots. Skin disorders or eye problems, including glaucoma and cataracts, may occur and wounds or broken bones may be slow to heal. Treatment with steroids can stop the body from producing some hormones and may slow or stop children’s growth rate. If you are female, your periods may become irregular. Elevation or depression of mood, sleeplessness and severe headaches have been reported. Very rare instances of blindness have been reported following injection to the face.

In particular, when Adcortyl IA/ID is injected into a joint you may notice some indentation appearing after a while in the surrounding area. There may also be some temporary worsening of the pain and discomfort after the injection. Similarly, injections given under the skin may cause slight changes in skin colour around the site of injection. These changes should disappear in time.

Serious effects: tell a doctor straight away

Steroids including Adcortyl IA/ID injection can cause serious mental health problems. These are common in both adults and children. They can affect about 5 in every 100 people taking medicines like Adcortyl IA/ID injection.

• Feeling depressed, including thinking about suicide.



• Feeling high (mania) or moods that go up and down.



• Feeling anxious, having problems sleeping, difficulty in thinking or being confused and losing your memory.



• Feeling, seeing or hearing things which do not exist. Having strange and frightening thoughts, changing how you act or having feelings of being alone.

If you notice any of these problems talk to a doctor straight away.

Tell your doctor or pharmacist if you notice any other troublesome side effects.

Looking After Your Medicine

Adcortyl IA/ID injection will be kept in the pharmacy until it is given to you by your doctor or nurse. It should be stored upright, at a temperature not exceeding 25°C and should not be allowed to freeze. After first opening, the
5ml multidose vial may be stored for 28 days below 25°C. It should not be used after the expiry date shown on the outer packaging. Keep out of reach and sight of children.

DATE OF LAST REVISION April 2008

1041116A7