Chlorpromazine Syrup

Pronunciation: klor-PROE-ma-zeen
Generic Name: Chlorpromazine
Brand Name: Generic only. No brands available.

Chlorpromazine Syrup is an antipsychotic. It may increase the risk of death when used to treat mental problems caused by dementia in elderly patients. Most of the deaths were linked to heart problems or infection. Chlorpromazine Syrup is not approved to treat mental problems caused by dementia. Discuss any questions or concerns with your doctor.

Chlorpromazine Syrup is used for:

Treating certain mental or mood disorders (eg, schizophrenia), the manic phase of manic-depressive disorder, anxiety and restlessness before surgery, the blood disease porphyria, severe behavioral and conduct disorders in children, nausea and vomiting, and severe hiccups. It is also used with other medicines to treat symptoms associated with tetanus. It may also be used for other conditions as determined by your doctor.

Chlorpromazine Syrup is a phenothiazine. It is not known exactly how it works

Do NOT use Chlorpromazine Syrup if:

• you are allergic to any ingredient in Chlorpromazine Syrup or to other phenothiazines (eg, thioridazine)


• you have severe drowsiness


• you have recently taken large amounts of alcohol or medicines that may cause drowsiness, such as barbiturates (eg, phenobarbital) or narcotic pain medicines (eg, codeine)


• you are taking certain antiarrhythmic medicines (eg, amiodarone, dofetilide, dronedarone, quinidine, sotalol), cisapride, pergolide, pimozide, quetiapine, or ziprasidone

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

Before using Chlorpromazine Syrup:

Some medical conditions may interact with Chlorpromazine Syrup. 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 a history of heart problems, low blood pressure, blood problems, bone marrow problems, low white blood cell count, diabetes, liver problems (eg, cirrhosis), kidney problems, neuroleptic malignant syndrome (NMS), enlarged prostate gland, seizures or epilepsy, or an adrenal gland tumor (pheochromocytoma)


• if you have asthma, lung infection, or other lung problems (eg, emphysema); increased pressure in the eyes; glaucoma; or if you are at risk for glaucoma


• if you have Alzheimer disease, dementia, Parkinson disease, or Reye syndrome


• if you have had high blood prolactin levels or a history of certain types of cancer (eg, breast, pancreas, pituitary, brain), or if you are at risk of breast cancer


• if you are regularly exposed to extreme heat or organophosphate insecticides


• if you have a history of alcohol abuse or if you consume more than 3 alcoholic drinks per day

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

• Lithium because the risk of a severe and sometimes permanent nervous system problem (encephalopathic syndrome) characterized by weakness, lethargy, fever, tremor, confusion, or uncontrolled muscle movements may be increased


• Certain antiarrhythmic medicines (eg, amiodarone, dofetilide, dronedarone, quinidine, sotalol), cisapride, pergolide, pimozide, quetiapine, or ziprasidone because the risk of side effects, such as racing heartbeat, dizziness, fainting, and life-threatening irregular heartbeat leading to unconsciousness, may be increased by Chlorpromazine Syrup


• Many prescription and nonprescription medicines (eg, used for allergies, blood clotting problems, cancer, infections, inflammation, aches and pains, heart problems, high blood pressure, high cholesterol, mental or mood problems, nausea or vomiting, Parkinson disease, seizures, stomach problems), multivitamin products, and herbal or dietary supplements (eg, herbal teas, coenzyme Q10, garlic, ginseng, gingko, St. John's wort) may interact with Chlorpromazine Syrup, increasing the risk of side effects

This may not be a complete list of all interactions that may occur. Ask your health care provider if Chlorpromazine Syrup 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 Chlorpromazine Syrup:

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

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


• Use a measuring device marked for medicine dosing. Ask your pharmacist for help if you are unsure of how to measure your dose.


• If you miss a dose of Chlorpromazine Syrup, 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 Chlorpromazine Syrup.

Important safety information:

• Chlorpromazine Syrup may cause drowsiness, dizziness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Chlorpromazine Syrup with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do not drink alcohol while you are using Chlorpromazine Syrup.


• Check with your doctor before you use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Chlorpromazine Syrup; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• Chlorpromazine Syrup may cause dizziness, light-headedness, or fainting; alcohol, hot weather, exercise, or fever may increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of any of these effects.


• Do not become overheated in hot weather or while you are being active; heatstroke may occur.


• Chlorpromazine Syrup may cause you to become sunburned more easily. Avoid the sun, sunlamps, or tanning booths until you know how you react to Chlorpromazine Syrup. Use a sunscreen or wear protective clothing if you must be outside for more than a short time.


• Chlorpromazine Syrup may lower the ability of your body to fight infection. Avoid contact with people who have colds or infections. Tell your doctor if you notice signs of infection like fever, sore throat, rash, or chills.


• Some patients who take Chlorpromazine Syrup may develop muscle movements that they cannot control. This is more likely to happen in elderly patients, especially women. The chance that this will happen or that it will become permanent is greater in those who take Chlorpromazine Syrup in higher doses or for a long time. Muscle problems may also occur after short-term treatment with low doses. Tell your doctor at once if you have muscle problems with your arms; legs; or your tongue, face, mouth, or jaw (eg, tongue sticking out, puffing of cheeks, mouth puckering, chewing movements) while taking Chlorpromazine Syrup.


• Neuroleptic malignant syndrome (NMS) is a possibly fatal syndrome that can be caused by Chlorpromazine Syrup. Symptoms may include fever; stiff muscles; confusion; abnormal thinking; fast or irregular heartbeat; and sweating. Contact your doctor at once if you have any of these symptoms.


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


• Chlorpromazine Syrup may increase the amount of a certain hormone (prolactin) in your blood. Symptoms may include enlarged breasts, missed menstrual period, decreased sexual ability, or nipple discharge. Contact your doctor right away if you experience any of these symptoms.


• Chlorpromazine Syrup may raise or lower your blood sugar. High blood sugar may make you feel confused, drowsy, or thirsty. It can also make you flush, breathe faster, or have a fruit-like breath odor. Low blood sugar may make you anxious, sweaty, weak, dizzy, drowsy, or faint. It may also make your vision change; give you a headache, chills, or tremors; or make you hungrier. If these symptoms occur, tell your doctor right away.


• Diabetes patients - Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Chlorpromazine Syrup may cause the results of some pregnancy tests to be wrong. Check with your doctor if you have questions or concerns about your pregnancy test results.


• Chlorpromazine Syrup may interfere with certain lab tests, including phenylketonuria (PKU) tests. Be sure your doctor and lab personnel know you are taking Chlorpromazine Syrup.


• Lab tests, including liver function, complete blood cell counts, and eye exams, may be performed while you use Chlorpromazine Syrup. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Chlorpromazine Syrup with caution in the ELDERLY; they may be more sensitive to its effects, especially dizziness, light-headedness (especially upon standing), rapid heartbeat, breathing problems, urinary retention, and constipation.


• Chlorpromazine Syrup should not be used in CHILDREN younger than 6 months old; safety and effectiveness in these 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 Chlorpromazine Syrup while you are pregnant. Using Chlorpromazine Syrup during the third trimester may result in uncontrolled muscle movements or withdrawal symptoms in the newborn. Discuss any questions or concerns with your doctor. Chlorpromazine Syrup is found in breast milk. Do not breast-feed while taking Chlorpromazine Syrup.

If you stop taking Chlorpromazine Syrup suddenly, you may have WITHDRAWAL symptoms. These may include nausea, vomiting, dizziness, and tremors.

Possible side effects of Chlorpromazine Syrup:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Agitation; constipation; dizziness; drowsiness; dry mouth; enlarged pupils; jitteriness; nausea; stuffy nose.

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); changes in menstrual period; changes in sexual ability; confusion; dark urine; difficulty swallowing; drooling; fainting; fast or irregular heartbeat; fever, chills, or sore throat; involuntary movements or spasms of the arms and legs, tongue, face, mouth, or jaw; mask-like face; muscle restlessness; prolonged or painful erection; restlessness; seizures; severe constipation; severe or persistent dizziness; shuffling walk; sleeplessness; stiff or rigid muscles; stomach pain; sweating; tremor; trouble urinating; unusual bruising or bleeding; unusual eye movements or inability to move your eyes; unusual mood or mental changes, including lack of response to your surroundings; unusual tiredness or weakness; unusually pale skin; vision changes; yellowing of the skin or eyes.

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. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Chlorpromazine 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 agitation; fainting; involuntary movements or muscle spasms; irregular heartbeat; light-headedness; loss of consciousness; restlessness; seizures; severe drowsiness or dizziness; tremors; twitching.

Proper storage of Chlorpromazine Syrup:

Store Chlorpromazine Syrup at room temperature, below 77 degrees F (25 degrees C), in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Chlorpromazine Syrup out of the reach of children and away from pets.

General information:

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


• Chlorpromazine Syrup 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.


• If using Chlorpromazine Syrup for an extended period of time, obtain refills before your supply runs out.


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

This information is a summary only. It does not contain all information about Chlorpromazine Syrup. 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 Chlorpromazine resources

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

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Idarubicin

Dosage Form: injection
Idarubicin

Hydrochloride Injection

Rxonly

FOR INTRAVENOUS USE ONLY

1. Idarubicin hydrochloride injection should be given slowly into a freely flowing intravenous infusion. It must never be given intramuscularly or subcutaneously. Severe local tissue necrosis can occur if there is extravasation during administration.


2. As is the case with other anthracyclines the use of Idarubicin hydrochloride injection can cause myocardial toxicity leading to congestive heart failure. Cardiac toxicity is more common in patients who have received prior anthracyclines or who have pre-existing cardiac disease.


3. As is usual with antileukemic agents, severe myelosuppression occurs when Idarubicin hydrochloride injection is used at effective therapeutic doses.


4. It is recommended that Idarubicin hydrochloride injection be administered only under the supervision of a physician who is experienced in leukemia chemotherapy and in facilities with laboratory and supportive resources adequate to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. The physician and institution must be capable of responding rapidly and completely to severe hemorrhagic conditions and/or overwhelming infection.


5. Dosage should be reduced in patients with impaired hepatic or renal function. (See DOSAGE AND ADMINISTRATION.)

Idarubicin Description

Idarubicin hydrochloride injection contains Idarubicin hydrochloride and is a sterile, semi-synthetic, preservative-free solution (PFS) antineoplastic anthracycline for intravenous use. Chemically, Idarubicin hydrochloride is 5, 12-Naphthacenedione, 9 - acetyl - 7 - [(3 - amino - 2,3,6 - trideoxy - α - L - lyxo - hexopyranosyl)oxy] - 7,8,9,10 - tetrahydro - 6,9,11 - trihydroxyhydrochloride, (7S-cis). The structural formula is as follows:

C26H27NO9•HCl          M.W. 533.96

Idarubicin hydrochloride injection is a sterile, clear, orange-red, isotonic parenteral preservative-free solution, available in 5 mL (5 mg), 10 mL (10 mg) and 20 mL (20 mg) single-use-only vials.

Each mL contains Idarubicin hydrochloride, USP 1 mg and the following inactive ingredients: glycerin, USP 25 mg and water for injection, USP q.s. Hydrochloric acid, NF and/or sodium hydroxide, NF is used to adjust pH to a target of 3.5.

Idarubicin - Clinical Pharmacology

Mechanism of Action

Idarubicin hydrochloride is a DNA-intercalating analog of daunorubicin which has an inhibitory effect on nucleic acid synthesis and interacts with the enzyme topoisomerase II. The absence of a methoxy group at position 4 of the anthracycline structure gives the compound a high lipophilicity which results in an increased rate of cellular uptake compared with other anthracyclines.

Pharmacokinetics

General Pharmacokinetics

Pharmacokinetic studies have been performed in adult leukemia patients with normal renal and hepatic function following intravenous administration of 10 to 12 mg/m2 of Idarubicin daily for 3 to 4 days as a single agent or combined with cytarabine. The plasma concentrations of Idarubicin are best described by a two or three compartment open model. The elimination rate of Idarubicin from plasma is slow with an estimated mean terminal half-life of 22 hours (range, 4 to 48 hours) when used as a single agent and 20 hours (range, 7 to 38 hours) when used in combination with cytarabine. The elimination of the primary active metabolite, Idarubicinol, is considerably slower than that of the parent drug with an estimated mean terminal half-life that exceeds 45 hours; hence, its plasma levels are sustained for a period greater than 8 days.

Distribution

The disposition profile shows a rapid distributive phase with a very high volume of distribution presumably reflecting extensive tissue binding. Studies of cellular (nucleated blood and bone marrow cells) drug concentrations in leukemia patients have shown that peak cellular Idarubicin concentrations are reached a few minutes after injection. Concentrations of Idarubicin and Idarubicinol in nucleated blood and bone marrow cells are more than a hundred times the plasma concentrations. Idarubicin disappearance rates in plasma and cells were comparable with a terminal half-life of about 15 hours. The terminal half-life of Idarubicinol in cells was about 72 hours. The extent of drug and metabolite accumulation predicted in leukemia patients for Days 2 and 3 of dosing, based on the mean plasma levels and half-life obtained after the first dose, is 1.7- and 2.3-fold, respectively, and suggests no change in kinetics following a daily × 3 regimen. The percentages of Idarubicin and Idarubicinol bound to human plasma proteins averaged 97% and 94%, respectively, at concentrations similar to maximum plasma levels obtained in the pharmacokinetic studies. The binding is concentration independent. The plasma clearance is twice the expected hepatic plasma flow indicating extensive extra hepatic metabolism.

Metabolism

The primary active metabolite formed is Idarubicinol. As Idarubicinol has cytotoxic activity, it presumably contributes to the effects of Idarubicin.

Elimination

The drug is eliminated predominately by biliary and to a lesser extent by renal excretion, mostly in the form of Idarubicinol.

Pharmacokinetics in Special Populations

Pediatric Patients

Idarubicin studies in pediatric leukemia patients, at doses of 4.2 to 13.3 mg/m2/day × 3, suggest dose independent kinetics. There is no difference between the half-lives of the drug following daily × 3 or weekly × 3 administration. Cerebrospinal fluid (CSF) levels of Idarubicin and Idarubicinol were measured in pediatric leukemia patients treated intravenously. Idarubicin was detected in 2 of 21 CSF samples (0.14 and 1.57 ng/mL), while Idarubicinol was detected in 20 of these 21 CSF samples obtained 18 to 30 hours after dosing (mean = 0.51 ng/mL; range, 0.22 to 1.05 ng/mL). The clinical relevance of these findings is unknown.

Hepatic and Renal Impairment

The pharmacokinetics of Idarubicin have not been evaluated in leukemia patients with hepatic impairment. It is expected that in patients with moderate or severe hepatic dysfunction, the metabolism of Idarubicin may be impaired and lead to higher systemic drug levels. The disposition of Idarubicin may be also affected by renal impairment. Therefore, a dose reduction should be considered in patients with hepatic and/or renal impairment (see DOSAGE AND ADMINISTRATION).

Drug-Drug Interactions

No formal drug interaction studies have been performed.

Clinical Studies

Four prospective randomized studies, three U.S. and one Italian, have been conducted to compare the efficacy and safety of Idarubicin (IDR) to that of daunorubicin (DNR), each in combination with cytarabine as induction therapy in previously untreated adult patients with acute myeloid leukemia (AML). These data are summarized in the following table and demonstrate significantly greater complete remission rates for the IDR regimen in two of the three U.S. studies and significantly longer overall survival for the IDR regimen in two of the three U.S. studies.

* Patients who had persistent leukemia after the first induction course received a second course † Memorial Sloan Kettering Cancer Center ‡ Cytarabine 25 mg/m2 bolus IV followed by 200 mg/m2 daily × 5 days by continuous infusion § Overall p < 0.05, unadjusted for prognostic factors or multiple endpoints ¶ Southeastern Cancer Study Group # Cytarabine 100 mg/m2 daily × 7 days by continuous infusion Þ Gruppo Italiano Malattie Ematologiche Maligne dell' Adulto
	Induction* Regimen Dose in mg/m2 – Daily x 3 Days		Complete Remission Rate, All Pts Randomized		Median Survival (days) All Pts Randomized
	IDR	DNR	IDR	DNR	IDR	DNR
U.S. (IND Studies)
1. MSKCC†	12‡	50‡	51/65§	38/65	508§	435
(Age ≤ 60 years)			(78%)	(58%)
2. SEG¶	12#	45#	76/111§	65/119	328	277
(Age ≥ 15 years)			(69%)	(55%)
3. U.S. Multicenter	13#	45#	68/101	66/113	393§	281
(Age ≥ 18 years)			(67%)	(58%)
Foreign (non-IND study)
GIMEMAÞ	12#	45#	49/124	49/125	87	169
(Age ≥ 55 years)			(40%)	(39%)

There is no consensus regarding optional regimens to be used for consolidation; however, the following consolidation regimens were used in U.S. controlled trials. Patients received the same anthracycline for consolidation as was used for induction.

Studies 1 and 3 utilized 2 courses of consolidation therapy consisting of Idarubicin 12 or 13 mg/m2 daily for 2 days, respectively (or DNR 50 or 45 mg/m2 daily for 2 days), and cytarabine, either 25 mg/m2 by IV bolus followed by 200 mg/m2 daily by continuous infusion for 4 days (Study 1), or 100 mg/m2 daily for 5 days by continuous infusion (Study 3). A rest period of 4 to 6 weeks is recommended prior to initiation of consolidation and between the courses. Hematologic recovery is mandatory prior to initiation of each consolidation course.

Study 2 utilized 3 consolidation courses, administered at intervals of 21 days or upon hematologic recovery. Each course consisted of Idarubicin 15 mg/m2 IV for 1 dose (or DNR 50 mg/m2 IV for 1 dose), cytarabine 100 mg/m2 every 12 hours for 10 doses and 6-thioguanine 100 mg/m2 orally for 10 doses. If severe myelosuppression occurred, subsequent courses were given with 25% reduction in the doses of all drugs. In addition, this study included 4 courses of maintenance therapy (2 days of the same anthracycline as was used in induction and 5 days of cytarabine).

Toxicities and duration of aplasia were similar during induction on the 2 arms in the U.S. studies except for an increase in mucositis on the IDR arm in one study. During consolidation, duration of aplasia on the IDR arm was longer in all three studies and mucositis was more frequent in two studies. During consolidation, transfusion requirements were higher on the IDR arm in the two studies in which they were tabulated, and patients on the IDR arm in Study 3 spent more days on IV antibiotics (Study 3 used a higher dose of Idarubicin).

The benefit of consolidation and maintenance therapy in prolonging the duration of remission and survival is not proven.

Intensive maintenance with Idarubicin is not recommended in view of the considerable toxicity (including deaths in remission) experienced by patients during the maintenance phase of Study 2.

A higher induction death rate was noted in patients on the IDR arm in the Italian trial. Since this was not noted in patients of similar age in the U.S. trials, one may speculate that it was due to a difference in the level of supportive care.

Indications and Usage for Idarubicin

Idarubicin hydrochloride injection in combination with other approved antileukemic drugs is indicated for the treatment of acute myeloid leukemia (AML) in adults. This includes French-American-British (FAB) classifications M1 through M7.

Warnings

Idarubicin is intended for administration under the supervision of a physician who is experienced in leukemia chemotherapy.

Idarubicin is a potent bone marrow suppressant. Idarubicin should not be given to patients with pre-existing bone marrow suppression induced by previous drug therapy or radiotherapy unless the benefit warrants the risk.

Severe myelosuppression will occur in all patients given a therapeutic dose of this agent for induction, consolidation or maintenance. Careful hematologic monitoring is required. Deaths due to infection and/or bleeding have been reported during the period of severe myelosuppression. Facilities with laboratory and supportive resources adequate to monitor drug tolerability and protect and maintain a patient compromised by drug toxicity should be available. It must be possible to treat rapidly and completely a severe hemorrhagic condition and/or a severe infection.

Pre-existing heart disease and previous therapy with anthracyclines at high cumulative doses or other potentially cardiotoxic agents are co-factors for increased risk of Idarubicin-induced cardiac toxicity and the benefit to risk ratio of Idarubicin therapy in such patients should be weighed before starting treatment with Idarubicin.

Myocardial toxicity as manifested by potentially fatal congestive heart failure, acute life-threatening arrhythmias or other cardiomyopathies may occur following therapy with Idarubicin. Appropriate therapeutic measures for the management of congestive heart failure and/or arrhythmias are indicated.

Cardiac function should be carefully monitored during treatment in order to minimize the risk of cardiac toxicity of the type described for other anthracycline compounds. The risk of such myocardial toxicity may be higher following concomitant or previous radiation to the mediastinal-pericardial area or in patients with anemia, bone marrow depression, infections, leukemic pericarditis and/or myocarditis. While there are no reliable means for predicting congestive heart failure, cardiomyopathy induced by anthracyclines is usually associated with a decrease of the left ventricular ejection fraction (LVEF) from pretreatment baseline values.

Since hepatic and/or renal function impairment can affect the disposition of Idarubicin, liver and kidney function should be evaluated with conventional clinical laboratory tests (using serum bilirubin and serum creatinine as indicators) prior to and during treatment. In a number of Phase III clinical trials, treatment was not given if bilirubin and/or creatinine serum levels exceeded 2 mg%. However, in one Phase III trial, patients with bilirubin levels between 2.6 and 5 mg% received the anthracycline with a 50% reduction in dose. Dose reduction of Idarubicin should be considered if the bilirubin and/or creatinine levels are above the normal range. (See DOSAGE AND ADMINISTRATION.)

Pregnancy Category D - Idarubicin was embryotoxic and teratogenic in the rat at a dose of 1.2 mg/m2/day or one tenth the human dose, which was nontoxic to dams. Idarubicin was embryotoxic but not teratogenic in the rabbit even at a dose of 2.4 mg/m2/day or two tenths the human dose, which was toxic to dams. There is no conclusive information about Idarubicin adversely affecting human fertility or causing teratogenesis. There has been one report of a fetal fatality after maternal exposure to Idarubicin during the second trimester.

There are no adequate and well-controlled studies in pregnant women. If Idarubicin is to be used during pregnancy, or if the patient becomes pregnant during therapy, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid pregnancy.

Precautions

General

Therapy with Idarubicin requires close observation of the patient and careful laboratory monitoring. Hyperuricemia secondary to rapid lysis of leukemic cells may be induced. Appropriate measures must be taken to prevent hyperuricemia and to control any systemic infection before beginning therapy.

Extravasation of Idarubicin can cause severe local tissue necrosis. Extravasation may occur with or without an accompanying stinging or burning sensation even if blood returns well on aspiration of the infusion needle. If signs or symptoms of extravasation occur the injection or infusion should be terminated immediately and restarted in another vein. (See DOSAGE AND ADMINISTRATION.)

Laboratory Tests

Frequent complete blood counts and monitoring of hepatic and renal function tests are recommended.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Formal long-term carcinogenicity studies have not been conducted with Idarubicin. Idarubicin and related compounds have been shown to have mutagenic and carcinogenic properties when tested in experimental models (including bacterial systems, mammalian cells in culture and female Sprague-Dawley rats).

In male dogs given 1.8 mg/m2/day 3 times/week (about one seventh the weekly human dose on a mg/m2 basis) for 13 weeks, or 3 times the human dose, testicular atrophy was observed with inhibition of spermatogenesis and sperm maturation with few or no mature sperm. These effects were not readily reversed after a recovery of 8 weeks.

Pregnancy Category D

(See WARNINGS.)

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Idarubicin, mothers should discontinue nursing prior to taking this drug.

Pediatric Use

Safety and effectiveness in children have not been established.

Geriatric Use

Patients over 60 years of age who were undergoing induction therapy experienced congestive heart failure, serious arrythmias, chest pain, myocardial infarction, and asymptomatic declines in LVEF more frequently than younger patients (see ADVERSE REACTIONS).

Adverse Reactions

Approximately 550 patients with AML have received Idarubicin in combination with cytarabine in controlled clinical trials worldwide. In addition, over 550 patients with acute leukemia have been treated in uncontrolled trials utilizing Idarubicin as a single agent or in combination. The table below lists the adverse experiences reported in U.S. Study 2 (see CLINICAL STUDIES) and is representative of the experiences in other studies. These adverse experiences constitute all reported or observed experiences, including those not considered to be drug related. Patients undergoing induction therapy for AML are seriously ill due to their disease, are receiving multiple transfusions, and concomitant medications including potentially toxic antibiotics and antifungal agents. The contribution of the study drug to the adverse experience profile is difficult to establish.

Induction Phase	Percentage of Patients
Adverse Experiences	IDR (N=110)	DNR (N=118)
Infection	95%	97%
Nausea & Vomiting	82%	80%
Hair Loss	77%	72%
Abdominal Cramps/Diarrhea	73%	68%
Hemorrhage	63%	65%
Mucositis	50%	55%
Dermatologic	46%	40%
Mental Status	41%	34%
Pulmonary-Clinical	39%	39%
Fever (not elsewhere classified)	26%	28%
Headache	20%	24%
Cardiac-Clinical	16%	24%
Neurologic-Peripheral Nerves	7%	9%
Pulmonary Allergy	2%	4%
Seizure	4%	5%
Cerebellar	4%	4%

The duration of aplasia and incidence of mucositis were greater on the IDR arm than the DNR arm, especially during consolidation in some U.S. controlled trials (see CLINICAL STUDIES).

The following information reflects experience based on U.S. controlled clinical trials.

Myelosuppression

Severe myelosuppression is the major toxicity associated with Idarubicin therapy, but this effect of the drug is required in order to eradicate the leukemic clone. During the period of myelosuppression, patients are at risk of developing infection and bleeding which may be life-threatening or fatal.

Gastrointestinal

Nausea and/or vomiting, mucositis, abdominal pain and diarrhea were reported frequently, but were severe (equivalent to WHO Grade 4) in less than 5% of patients. Severe enterocolitis with perforation has been reported rarely. The risk of perforation may be increased by instrumental intervention. The possibility of perforation should be considered in patients who develop severe abdominal pain and appropriate steps for diagnosis and management should be taken.

Dermatologic

Alopecia was reported frequently and dermatologic reactions including generalized rash, urticaria and a bullous erythrodermatous rash of the palms and soles have occurred. The dermatologic reactions were usually attributed to concomitant antibiotic therapy. Local reactions including hives at the injection site have been reported. Recall of skin reaction due to prior radiotherapy has occurred with Idarubicin administration.

Hepatic and Renal

Changes in hepatic and renal function tests have been observed. These changes were usually transient and occurred in the setting of sepsis and while patients were receiving potentially hepatotoxic and nephrotoxic antibiotics and antifungal agents. Severe changes in renal function (equivalent to WHO Grade 4) occurred in no more than 1% of patients, while severe changes in hepatic function (equivalent to WHO Grade 4) occurred in less than 5% of patients.

Cardiac

Congestive heart failure (frequently attributed to fluid overload), serious arrhythmias including atrial fibrillation, chest pain, myocardial infarction and asymptomatic declines in LVEF have been reported in patients undergoing induction therapy for AML. Myocardial insufficiency and arrhythmias were usually reversible and occurred in the setting of sepsis, anemia and aggressive intravenous fluid administration. The events were reported more frequently in patients over age 60 years and in those with pre-existing cardiac disease.

Overdosage

There is no known antidote to Idarubicin. Two cases of fatal overdosage in patients receiving therapy for AML have been reported. The doses were 135 mg/m2 over 3 days and 45 mg/m2 of Idarubicin and 90 mg/m2 of daunorubicin over a three day period.

It is anticipated that overdosage with Idarubicin will result in severe and prolonged myelosuppression and possibly in increased severity of gastrointestinal toxicity. Adequate supportive care including platelet transfusions, antibiotics and symptomatic treatment of mucositis is required. The effect of acute overdose on cardiac function is not fully known, but severe arrhythmia occurred in 1 of the 2 patients exposed. It is anticipated that very high doses of Idarubicin may cause acute cardiac toxicity and may be associated with a higher incidence of delayed cardiac failure.

Disposition studies with Idarubicin in patients undergoing dialysis have not been carried out. The profound multicompartment behavior, extensive extravascular distribution and tissue binding, coupled with the low unbound fraction available in the plasma pool make it unlikely that therapeutic efficacy or toxicity would be altered by conventional peritoneal or hemodialysis.

Idarubicin Dosage and Administration

(SeeWARNINGS)

For induction therapy in adult patients with AML the following dose schedule is recommended:

Idarubicin hydrochloride injection 12 mg/m2 daily for 3 days by slow (10 to 15 min) intravenous injection in combination with cytarabine. The cytarabine may be given as 100 mg/m2 daily by continuous infusion for 7 days or as cytarabine 25 mg/m2 intravenous bolus followed by cytarabine 200 mg/m2 daily for 5 days continuous infusion. In patients with unequivocal evidence of leukemia after the first induction course, a second course may be administered. Administration of the second course should be delayed in patients who experience severe mucositis, until recovery from this toxicity has occurred, and a dose reduction of 25% is recommended. In patients with hepatic and/or renal impairment, a dose reduction of Idarubicin hydrochloride injection should be considered. Idarubicin hydrochloride injection should not be administered if the bilirubin level exceeds 5 mg%. (See WARNINGS.)

The benefit of consolidation in prolonging the duration of remissions and survival is not proven. There is no consensus regarding optional regimens to be used for consolidation. (See CLINICAL STUDIES for doses used in U.S. Clinical studies.)

Preparation and Administration Precautions

Caution in handling the solution must be exercised as skin reactions associated with Idarubicin hydrochloride injection may occur. Skin accidentally exposed to Idarubicin hydrochloride injection should be washed thoroughly with soap and water and if the eyes are involved, standard irrigation techniques should be used immediately. The use of goggles, gloves, and protective gowns is recommended during preparation and administration of the drug.

Care in the administration of Idarubicin hydrochloride injection will reduce the chance of perivenous infiltration. It may also decrease the chance of local reactions such as urticaria and erythematous streaking. During intravenous administration of Idarubicin hydrochloride injection extravasation may occur with or without an accompanying stinging or burning sensation even if blood returns well on aspiration of the infusion needle. If any signs or symptoms of extravasation have occurred, the injection or infusion should be immediately terminated and restarted in another vein. If it is known or suspected that subcutaneous extravasation has occurred, it is recommended that intermittent ice packs (1/2 hour immediately, then 1/2 hour 4 times per day for 3 days) be placed over the area of extravasation and that the affected extremity be elevated. Because of the progressive nature of extravasation reactions, the area of injection should be frequently examined and plastic surgery consultation obtained early if there is any sign of a local reaction such as pain, erythema, edema or vesication. If ulceration begins or there is severe persistent pain at the site of extravasation, early wide excision of the involved area should be considered.

Idarubicin hydrochloride injection should be administered slowly (over 10 to 15 minutes) into the tubing of a freely running intravenous infusion of Sodium Chloride Injection, USP (0.9%) or 5% Dextrose Injection, USP. The tubing should be attached to a Butterfly needle or other suitable device and inserted preferably into a large vein.

Incompatibility

Unless specific compatibility data are available, Idarubicin hydrochloride injection should not be mixed with other drugs. Precipitation occurs with heparin. Prolonged contact with any solution of an alkaline pH will result in degradation of the drug.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and containers permit.

Handling and Disposal

Procedures for handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1–8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

How is Idarubicin Supplied

Each mL contains Idarubicin Hydrochloride 1 mg.

NDC Number	Idarubicin Hydrochloride Injection
0703-4154-11	5 mg single dose vial (1 mg/mL) packaged individually
0703-4155-11	10 mg single dose vial (1 mg/mL) packaged individually
0703-4156-11	20 mg single dose vial (1 mg/mL) packaged individually

Sterile single use only, contains no preservative.

Store under refrigeration 2° to 8°C (36° to 46°F), and protect from light. Retain in carton until time of use.

REFERENCES

1. ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society. 1999: 32-41.


2. Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. Washington, DC; Division of Safety, Clinical Center Pharmacy Department and Cancer Nursing Services, National Institutes of Health; 1992. US Department of Health and Human Services, Public Health Service Publication NIH 92-2621.


3. AMA Council on Scientific Affairs. Guidelines for Handling Parenteral Antineoplastics. JAMA. 1985; 253: 1590-1591.


4. National Study Commission on Cytotoxic Exposure - Recommendations for Handling Cytotoxic Agents. 1987. Available from Louis P. Jeffrey, Sc.D., Chairman, National Study Commission on Cytotoxic Exposure, Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115.


5. Clinical Oncological Society of Australia: Guidelines and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia. 1983; 1:426-428.


6. Jones RB, Frank R, Mass T. Safe Handling of Chemotherapeutic Agents: A Report from the Mount Sinai Medical Center. CA Cancer J Clin. 1983; 33: 258-263.


7. American Society of Hospital Pharmacists. ASHP Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs. Am J Hosp Pharm. 1990; 47:1033-1049.


8. Controlling Occupational Exposure to Hazardous Drugs (OSHA Work-Practice Guidelines). Am J Health-Syst Pharm. 1996; 53: 1669-1685.

Rev. A 9/2011

Teva Parenteral Medicines, Inc.

Irvine, CA 92618

PRINCIPAL DISPLAY PANEL

Idarubicin Hydrochloride Injection 5 mg/5 mL Vial Label Text

NDC 0703-4154-11

Rx only

Idarubicin

Hydrochloride Injection

5 mg/5 mL (1 mg/mL)

5 mL Single Dose Vial

FOR INTRAVENOUS USE ONLY

Sterile, Isotonic Solution

TEVA

PRINCIPAL DISPLAY PANEL

Idarubicin Hydrochloride Injection 10 mg/10 mL Vial Label Text

NDC 0703-4155-11

Rx only

Idarubicin

Hydrochloride Injection

10 mg/10 mL

(1 mg/mL)

10 mL Single Dose Vial

FOR INTRAVENOUS USE ONLY

Sterile, Isotonic Solution

TEVA

PRINCIPAL DISPLAY PANEL

Idarubicin Hydrochloride Injection 20 mg/20 mL Vial Label Text

NDC 0703-4156-11

Rx only

Idarubicin

Hydrochloride Injection

20 mg/20 mL

(1 mg/mL)

20 mL Single Dose Vial

FOR INTRAVENOUS USE ONLY

Sterile, Isotonic Solution

TEVA

Idarubicin HYDROCHLORIDE  Idarubicin hydrochloride  injection

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0703-4154 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Idarubicin HYDROCHLORIDE (Idarubicin) Idarubicin HYDROCHLORIDE 1 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength GLYCERIN   WATER   HYDROCHLORIC ACID   SODIUM HYDROXIDE

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0703-4154-11 1 VIAL In 1 CARTON contains a VIAL, SINGLE-DOSE 1 5 mL In 1 VIAL, SINGLE-DOSE This package is contained within the CARTON (0703-4154-11)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA065036	10/11/2011

Idarubicin HYDROCHLORIDE  Idarubicin hydrochloride  injection

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0703-4155 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Idarubicin HYDROCHLORIDE (Idarubicin) Idarubici

Fluvirin injectable

Generic Name: influenza virus vaccine (injectable) (in floo ENZ a VYE rus VAK seen)

Brand Names: Afluria, Fluarix, FluLaval, Fluvirin, Fluvirin Preservative-Free, Fluzone, Fluzone Preservative-Free, Fluzone Preservative-Free Pediatric

What is influenza virus injectable vaccine?

Influenza virus (commonly known as "the flu") is a serious disease caused by a virus. Influenza virus can spread from one person to another through small droplets of saliva that are expelled into the air when an infected person coughs or sneezes. The virus can also be passed through contact with objects the infected person has touched, such as a door handle or other surfaces.

Influenza virus vaccine is used to prevent infection caused by influenza virus. The vaccine is redeveloped each year to contain specific strains of inactivated (killed) flu virus that are recommended by public health officials for that year.

The injectable influenza virus vaccine (flu shot) is a "killed virus" vaccine. Influenza virus vaccine is also available in a nasal spray form, which is a "live virus" vaccine.

Influenza virus vaccine works by exposing you to a small dose of the virus, which helps your body to develop immunity to the disease. Influenza virus vaccine will not treat an active infection that has already developed in the body.

Influenza virus vaccine is for use in adults and children who are at least 6 months old.

Becoming infected with influenza (commonly known as "the flu") is much more dangerous to your health than receiving the vaccine to protect against it. Influenza causes thousands of deaths each year, and hundreds of thousands of hospitalizations. Like any medicine, this vaccine can cause side effects, but the risk of serious side effects is extremely low.

Like any vaccine, influenza virus vaccine may not provide protection from disease in every person. This vaccine will not prevent illness caused by avian flu ("bird flu").

What is the most important information I should know about this vaccine?

The injectable influenza virus vaccine (flu shot) is a "killed virus" vaccine. Influenza virus vaccine is also available in a nasal spray form, which is a "live virus" vaccine. This medication guide addresses only the injectable form of this vaccine.

You can still receive a vaccine if you have a cold or fever. In the case of a more severe illness with a fever or any type of infection, wait until you get better before receiving this vaccine.

Keep track of any and all side effects you have after receiving this vaccine. If you ever have to receive another influenza virus vaccine in the future, you will need to tell the doctor if the first shot caused any side effects.

Like any vaccine, influenza virus vaccine may not provide protection from disease in every person. This vaccine will not prevent illness caused by avian flu ("bird flu").

Becoming infected with influenza (commonly known as "the flu") is much more dangerous to your health than receiving the vaccine to protect against it. Influenza causes thousands of deaths each year, and hundreds of thousands of hospitalizations. Like any medicine, this vaccine can cause side effects, but the risk of serious side effects is extremely low.

What should I discuss with my healthcare provider before receiving this vaccine?

Do not receive this vaccine if you have ever had an allergic reaction to a flu vaccine, or if you have:

• 
  

  an active or uncontrolled neurologic disorder (such as Parkinson's disease, Alzheimer's disease, or epilepsy);

  
  


• 
  

  a history of Guillain-Barré syndrome (especially if you had it within 6 weeks after having a flu vaccine); or

  
  


• 
  

  if you are allergic to chicken or egg products.

  
  

Before receiving influenza virus vaccine, tell your doctor if you are allergic to any drugs, or if you have:

• 
  

  a bleeding or blood clotting disorder such as hemophilia or easy bruising;

  
  


• 
  

  a neurologic disorder or disease affecting the brain (or if this was a reaction to a previous vaccine);

  
  


• 
  

  an allergy to latex rubber;

  
  


• 
  

  a weak immune system caused by disease, bone marrow transplant, or by using certain medicines or receiving cancer treatments; or

  
  


• 
  

  if you are taking a blood thinner such as warfarin (Coumadin).

  
  

You can still receive a vaccine if you have a cold or fever. In the case of a more severe illness with a fever or any type of infection, wait until you get better before receiving this vaccine.

Vaccines may be harmful to an unborn baby and generally should not be given to a pregnant woman. However, not vaccinating the mother could be more harmful to the baby if the mother becomes infected with a disease that this vaccine could prevent. Your doctor will decide whether you should receive this vaccine, especially if you have a high risk of infection with influenza. It is not known whether influenza virus vaccine 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. This vaccine should not be given to a child younger than 6 months old.

How is this given?

Some brands of this vaccine are made for use in adults and not in children. Your child's doctor can recommend the best influenza virus vaccine for your child.

This vaccine is given as an injection (shot) into a muscle. You will receive this injection in a doctor's office or other clinic setting.

You should receive a flu vaccine every year. Your immunity will gradually decrease over the 12 months after you receive the influenza virus vaccine. Children receiving this vaccine may need a booster shot one month after receiving the first vaccine.

The influenza virus vaccine is usually given in October or November. Some people may need to have their vaccines earlier or later. Follow your doctor's instructions.

Your doctor may recommend treating fever and pain with an aspirin-free pain reliever such as acetaminophen (Tylenol) or ibuprofen (Motrin, Advil, and others) when the shot is given and for the next 24 hours. Follow the label directions or your doctor's instructions about how much of this medicine to take.

It is especially important to prevent fever from occurring if you have a seizure disorder such as epilepsy.

What happens if I miss a dose?

Since flu shots are usually given only one time per year, you will most likely not be on a dosing schedule. Call your doctor if you forget to receive your yearly flu shot in October or November.

If your child misses a booster dose of this vaccine, call your doctor for instructions.

What happens if I overdose?

An overdose of this vaccine is unlikely to occur.

What should I avoid before or after receiving this vaccine?

Follow your doctor's instructions about any restrictions on food, beverages, or activity after you receive this vaccine.

Influenza virus injectable vaccine side effects

Influenza virus injectable (killed virus) vaccine will not cause you to become ill with the flu virus that it contains. However, you may have flu-like symptoms at any time during flu season that may be caused by other strains of influenza virus.

You should not receive a booster vaccine if you had a life-threatening allergic reaction after the first shot. Keep track of any and all side effects you have after receiving this vaccine. If you ever have to receive another influenza virus vaccine in the future, you will need to tell the doctor if the first shot caused any 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:

• 
  

  severe weakness or unusual feeling in your arms and legs (may occur 2 to 4 weeks after you receive the vaccine);

  
  


• 
  

  high fever; or

  
  


• 
  

  unusual bleeding.

  
  

Less serious side effects may include:

• 
  

  low fever, chills;

  
  


• 
  

  redness, bruising, pain, swelling, or a lump where the vaccine was injected;

  
  


• 
  

  headache, tired feeling; or

  
  


• 
  

  joint or muscle pain.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect influenza virus injectable vaccine?

Before receiving this vaccine, tell your doctor if you are using phenytoin (Dilantin), theophylline (Respbid, Slo-Bid, Theodur, Uniphyl), or a blood thinner (warfarin, Coumadin).

Also tell the doctor if you have recently received drugs or treatments that can weaken the immune system, including:

• 
  

  an oral, nasal, inhaled, or injectable steroid medicine;

  
  


• 
  

  medications to treat psoriasis, rheumatoid arthritis, or other autoimmune disorders, such as azathioprine (Imuran), efalizumab (Raptiva), etanercept (Enbrel), leflunomide (Arava), and others; or

  
  


• 
  

  medicines to treat or prevent organ transplant rejection, such as basiliximab (Simulect), cyclosporine (Sandimmune, Neoral, Gengraf), muromonab-CD3 (Orthoclone), mycophenolate mofetil (CellCept), sirolimus (Rapamune), or tacrolimus (Prograf).

  
  

This list is not complete and there may be other drugs that can interact with this vaccine. Tell your doctor about all the prescription and over-the-counter medications you have received. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Fluvirin resources

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

Compare Fluvirin with other medications

• Influenza Prophylaxis

Where can I get more information?

• Your doctor or pharmacist may have information about influenza virus vaccine written for health professionals that you may read. You may also find additional information from your local health department or the Centers for Disease Control and Prevention.

See also: Fluvirin side effects (in more detail)

Miostat Ocular

Pronunciation: KAR-ba-kol
Generic Name: Carbachol
Brand Name: Miostat

Miostat Ocular is used for:

Contracting the pupil during and immediately following surgery. It is also reduces eye pressure in the first 24 hours after cataract surgery.

Miostat Ocular is a cholinergic agent/miotic. The exact way Miostat Ocular works is not fully understood. It works by constricting the iris and other parts of the eye, resulting in reduction of eye pressure.

Do NOT use Miostat Ocular if:

• you are allergic to any ingredient in Miostat Ocular


• you have acute swelling of the iris

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

Before using Miostat Ocular:

Some medical conditions may interact with Miostat Ocular. 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, chronic obstructive pulmonary disease (COPD), asthma, stomach or intestinal ulcers or spasm, or urinary tract blockage


• if you have an overactive thyroid or Parkinson disease

Some MEDICINES MAY INTERACT with Miostat Ocular. However, no specific interactions with Miostat Ocular are known at this time.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Miostat Ocular 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 Miostat Ocular:

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

• Miostat Ocular is usually administered as an injection at your doctor's office, hospital, or clinic. Ask your doctor any questions you may have about Miostat Ocular.


• If Miostat Ocular contains particles or if the vial is cracked or damaged in any way, do not use it.


• If you miss a dose of Miostat Ocular, contact your doctor right away.

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

Important safety information:

• Miostat Ocular may cause blurred vision. Make sure your vision is clear before driving or performing any task that requires good vision.


• Miostat Ocular is not recommended for use in CHILDREN; safety and effectiveness have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you plan on becoming pregnant, discuss your doctor the benefits and risks of using Miostat Ocular during pregnancy. It is unknown if Miostat Ocular is excreted in breast milk. If you are or will be breast-feeding while you are using Miostat Ocular, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Miostat Ocular:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Bladder tightness; change in vision; flushing; headache; indigestion; stomach cramps; stomach upset; sweating; urge to urinate.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blisters on the eye; blurred or decreased vision; cloudy vision; eye or eyelid swelling; eye pain or redness; increased tearing; sensitivity to light.

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. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Miostat 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; fainting; increased saliva; increased sweating; irregular heartbeat; nausea; vomiting.

Proper storage of Miostat Ocular:

Store Miostat Ocular at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Miostat Ocular out of the reach of children and away from pets.

General information:

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


• Miostat Ocular 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 Miostat Ocular. 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 Miostat resources

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

Compare Miostat with other medications

• Glaucoma
• Intraocular Hypertension
• Production of Miosis

Phenylephrine and Chlorpheniramine Tablets

Dosage Form: tablet
Phenylephrine Hydrochloride 20 mg /Chlorpherniramine Maleate 4 mg

DESCRIPTION:

Nasal Decongestant/Antihistamine sustained-release tablets for oral administration.

Each Phenylephrine Hydrochloride 20 mg / Chlorpheniramine Maleate 4 mg tablet contains:

Phenylephrine Hydrochloride .................................. 20 mg

Chlorpheniramine Maleate ........................................ 4 mg

In addition, this product contains the following as inactive ingredients: Croscarmellose sodium, Dicalcium phosphate dihydrate, Hydroxypropyl methylcellulose, Microcrystalline cellulose, Silicon dioxide, Stearic Acid, Talc.

CLINICAL PHARMACOLOGY:

Phenylephrine Hydrochloride is a sympathomimetic amine, which acts predominately by a direct action on alpha adrenergic receptors. In therapeutic doses, the drug has no effect on the beta adrenergic receptors of the heart. Clinically, Phenylephrine Hydrochloride shrinks swollen mucus membranes, reduces tissue hyperemia, edema, and nasal congestion; and increases nasal airway patency. In therapeutic doses, the drug causes little, if any, central nervous system (CNS) stimulation.

Chlorpheniramine Maleate competitively antagonizes most of the smooth muscle stimulating actions of histamine on the H1receptors of the GI tract, uterus, large blood vessels, and bronchial muscle. It also antagonizes the action of histamine which results in increased capillary permeability and the formation of edema. Chlorpheniramine Maleate is an alkylamine type of antihistamine. This group of antihistamines is among the most active histamine antagonists and is generally effective in relatively low doses. They thereby prevent, but do not reverse, responses mediated by histamine alone. The anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa. Chlorpheniramine Maleate is not so prone to produce drowsiness and is among the most suitable agents for daytime use, but a significant proportion of patients do experience this effect.

INDICATIONS & USAGE:

This product is indicated for the temporary relief of nasal congestion due to the common cold, hay fever, or other respiratory allergies and associated sinusitis.

CONTRAINDICATIONS:

This product is contraindicated in patients with hypersensitivity to antihistamines and/or sympathomimetics.

Antihistamines are contraindicated in patients receiving antihypertensive or antidepressant drugs containing monoamine oxidase (MAO) inhibitors since these agents may prolong and intensify anticholinergic and CNS depressant effects of antihistamines (see Drug Interactions section). Antihistamines should not be used to treat lower respiratory tract symptoms or be given to premature or newborn infants. This product is contraindicated in patients with severe hypertension or severe coronary artery disease.

Risk-benefit should be considered when the following medical problems exist: hyperthyroidism, diabetes mellitus, glaucoma, prostatic hypertrophy, urinary retention and asthma (although antihistamines may decrease allergen induced bronchoconstriction, their anticholinergic drying effects may cause thickening of secretions and impair expectoration during an acute episode of asthma).

WARNINGS:

Especially in infants and small children, antihistamines in overdosage may cause hallucinations, convulsions and death.

Antihistamines may diminish mental alertness. In young children, they may produce excitation.

PRECAUTIONS:

General: Because of its antihistamine component, this product should be used with caution in patients with a history of bronchial asthma, narrow-angle glaucoma, gastrointestinal obstruction, or urinary bladder neck obstruction. Because of its sympathomimetic component, this product should be used with caution in patients with diabetes, hypertension, heart disease, or thyroid disease.

Information for Patients

Patient consultation should include the following information regarding proper use of this medication:

• Do not take more medicine than the amount recommended.

• Do not drive or operate machinery if drowsiness or dizziness occurs.

• Avoid alcoholic beverages while taking this medication.

• If a dose is missed, the medication should be taken as soon as possible, unless it is almost time for the next dose, not doubling doses.

• This medication should be stored in a tight, light-resistant container at temperatures between 15º-30ºC (59º-86ºF).

Caution patients about the signs of potential side effects.

Drug/Laboratory Test Interactions

Combinations containing any of the following medications, depending on the amount present, may interact with this product.


• Anesthetics, hydrocarbon inhalation

• Tricyclic antidepressants

• Antihypertensives

• Alpha-adrenergic blocking agents

• Beta-adrenergic blocking agents

• CNS stimulating/depression producing medications

• MOA inhibitors


Antihistamines may interfere with skin tests using allergen extracts, producing false-negative results. It is recommended that antihistamines be discontinued at least 72 hours before such testing.

Carcinogenesis, Mutagenesis and Impairment of Fertility

No studies have been performed to evaluate the carcinogenic or mutagenic potential of this product.

Pregnancy

Pregnancy category C. It is not known whether this product can cause fetal harm when administered to a pregnant woman. This product should be given to pregnant woman only if clearly needed.

Labor and Delivery

Use of sympathomimetic amines during late pregnancy or during labor may cause fetal anoxia and bradycardia by increasing contractibility of the uterus and decreasing uterine blood flow.

Nursing Mothers

Because of the higher risk of intolerance of antihistamines in infants in general, and in newborns in particular, this product is contraindicated in nursing mothers.

Pediatrics

The use of antihistamines is not recommended in young children (newborns and infants). This age group may be at a higher risk than others because of an increased susceptibility to anticholinergic effects such as CNS excitation, and an increased tendency toward convulsion. In older children, antihistamines may cause a paradoxical reaction characterized by hyperexcitability. Very young children may be more sensitive to the effects of sympathomimetics.

Geriatrics

The elderly (60 years or older) may be more susceptible to the vasopressor effects of sympathomimetics. Confusion, hallucinations, seizures and CNS depression may be more likely to occur in geriatric patients taking sympathomimetics. Antihistamines may cause confusion, dizziness, sedation, hypotension, hyperexcitability, and anticholinergic side effects such as dryness of the mouth and urinary retention in geriatric patients. If these symptoms occur and continue, or are severe, medication should probably be discontinued.

ADVERSE REACTIONS:

The most frequent reactions include drowsiness, lightheadedness, nausea, and dryness of mouth. Less frequently restlessness, nervousness, trembling, or weakness may occur. These side effects need medical attention only if they continue or are bothersome. Those indicating need for immediate medical attention include: CNS depression (severe drowsiness), CNS stimulation (hallucinations, seizures), anticholinergic effects (clumsiness, flushing of the face, shortness of breath, troubled breathing), severe headache, hypertension, or hypotension.

DRUG ABUSE AND DEPENDENCE:

Central nervous system stimulants such as sympathomimetic amines have been abused. At high doses, subjects commonly experience an elevation of mood, a sense of increased energy and alertness and decreased appetite. Some individuals become anxious, irritable, and loquacious. In addition to the marked euphoria, the user experiences a sense of markedly enhanced physical strength and mental capacity. With continued use, tolerance develops, the user increases the dose, and toxic signs and symptoms appear. Depression may follow rapid withdrawal.

Nasal decongestants such as Phenylephrine Hydrochloride have been banned and tested by the U.S. Olympic Committee (USOC) and the National Collegiate Athletic Association (NCAA).

OVERDOSAGE:

Signs and symptoms: This product is comprised of pharmacologically different products. Therefore, it is difficult to predict the exact manifestation of symptoms in a given individual. A description of symptoms, which are likely to appear after ingestion of an excess of the individual components, follows: Overdosage with antihistamines may cause hallucinations, convulsions or possibly death, especially in infants and children. Antihistamines are more likely to cause dizziness, sedation, and hypotension in elderly patients. Overdosage with sympathomimetic amines can cause cardiac arrhythmias, cerebral hemorrhage and pulmonary edema. It can also cause palpitations, tremor, dizziness, vomiting, fear, labored breathing, headache, pallor, weakness, hallucinations, and delirium.


Recommended treatment: In the event of overdose, emergency treatment should be started immediately. Since the action of sustained release products may continue for as long as 12 hours, treatment should be directed toward reducing further absorption and supporting the patient for at least that length of time.


Since there is no specific antidote for overdose with this product, treatment is symptomatic and supportive with possible utilization of the following:

• If the amount ingested is considered dangerous or excessive induce vomiting with ipecac syrup unless the patient is convulsing, comatose, or has lost the gag reflex, in which case perform gastric lavage.

• Gastric lavage (isotonic or 0.45% sodium chloride solution) if patient is unable to vomit within 3 hours of ingestion.

• Saline cathartics (milk of magnesia) are sometimes used.

• Vasopressors to treat hypotension, however, epinephrine should not be used since it may further lower blood pressure.

• Oxygen and intravenous fluids

• Precaution against use of stimulants (analeptic agents) because they may cause seizures.

• For reflex bradycardia accompanying the pressor response to phenylephrine atropine may be used to block the effect.

• For excessive hypertensive effects, an alpha-adrenergic blocker, such as phentolamine, may be administered.

DOSAGE AND ADMINISTRATION:

Adults and adolescents 12 years of age and older: 1 or 2 tablets every 12 hours as directed by a physician.

Children 6 to 12 years: 1 tablet every 12 hours, as directed by a physician.

Not recommended for children under 6 years.

Tablets should not be crushed or chewed.

Do not exceed recommended doses in a 24-hour period.

HOW SUPPLIED:

Phenylephrine Hydrochloride 20 mg / Chlorpheniramine Maleate 4 mg are supplied as white, round shaped tablets imprinted upper “RE 330” with lower plain w/bisect. Bottles of 100 tablets, NDC 68032-330-10.

KEEP THIS AND ALL MEDICATION OUT OF THE REACH OF CHILDREN. IN CASE OF ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL ASSISTANCE OR CONTACT A POISON CONTROL CENTER IMMEDIATELY.

Dispense in a tight, light-resistant container as defined in the USP/NF with child resistant closures.

Store at controlled room temperature, 15°-30°C (59°-86°F); see USP Controlled Room Temperature. Avoid exposure to heat.

Manufactured for:

Rivers Edge Pharmaceuticals, LLC

Suwanee, GA 30024

PI 284 Rev. 06/08

330-11

PACKAGING:

NDC 68032-330-10 100 Tablets

PHENYLEPHRINE HCl 20 mg/CHLORPHENIRAMINE MALEATE 4 mg

TABLETS

Rx ONLY

Nasal Decongestant/Antihistamine


Each Extended-Release Tablet Contains:

Phenylephrine Hydrochloride ........... 20 mg

Chlorpheniramine Maleate ................. 4 mg


68032 330-10


DOSAGE AND AMINISTRATION

Adults and adolescents 12 years of age and older: 1 or 2 tablets every 12 hours as directed by a physician.

Children 6 to 12 years: 1 tablet every 12 hours, as directed by a physician.

Not recommended for children under 6 years.

See product literature for full prescribing information.


KEEP THIS AND ALL MEDICATION OUT OF THE REACH OF CHILDREN. IN CASE OF ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL ASSISTANCE OR CONTACT A POISON CONTROL CENTER IMMEDIATELY.


Dispense in a tight, light-resistant container as defined in the USP/NF with child resistant closures.


Store at controlled room temperature, 15°-30°C (59°-86°F); see USP Controlled Room Temperature. Avoid exposure to heat.


Manufactured for:

Rivers Edge Pharmaceuticals, LLC

Suwanee, GA 30024

PL 284 Rev. 06/08

PHENYLEPHRINE HYDROCHLORIDE, CHLORPHENIRAMINE MALEATE  phenylephrine hydrochloride, chlorpheniramine maleate  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 68032-330 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PHENYLEPHRINE HYDROCHLORIDE (PHENYLEPHRINE) PHENYLEPHRINE HYDROCHLORIDE 20 mg CHLORPHENIRAMINE MALEATE (CHLORPHENIRAMINE) CHLORPHENIRAMINE MALEATE 4 mg

Inactive Ingredients Ingredient Name Strength CROSCARMELLOSE SODIUM   DIBASIC CALCIUM PHOSPHATE DIHYDRATE   HYPROMELLOSE 2208 (100 MPA.S)   CELLULOSE, MICROCRYSTALLINE   SILICON DIOXIDE   STEARIC ACID   TALC

Product Characteristics Color white Score 2 pieces Shape ROUND Size 12mm Flavor Imprint Code RE;330 Contains

Packaging # NDC Package Description Multilevel Packaging 1 68032-330-10 100 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
unapproved drug other		09/03/2008	03/31/2011

Labeler - River's Edge Pharmaceuticals, LLC (133879135)

Revised: 12/2010River's Edge Pharmaceuticals, LLC

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