Psorigel Topical

Generic Name: coal tar (Topical route)

kole tar

Commonly used brand name(s)

In the U.S.

• Betatar Gel


• Cutar Emulsion


• Denorex


• DHS Tar


• Doak Tar


• Duplex T


• Fototar


• Ionil-T Plus


• Medotar


• MG 217


• Neutrogena T/Derm


• Neutrogena T/Gel

In Canada

• Estar


• Liquor Carbonis Detergens


• Psorigel


• Spectro Tar Skin Wash


• Tar Distillate

Available Dosage Forms:

• Liquid


• Shampoo


• Lotion


• Solution


• Cream


• Gel/Jelly


• Soap


• Kit


• Ointment


• Bar


• Foam


• Emulsion

Therapeutic Class: Keratolytic

Uses For Psorigel

Coal tar is used to treat eczema, psoriasis, seborrheic dermatitis, and other skin disorders.

Some of these preparations are available only with your doctor's prescription.

Before Using Psorigel

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

Coal tar products should not be used on infants, unless otherwise directed by your doctor. Studies on this medicine have been done only in adult patients, and there is no specific information comparing use of this medicine in children with use in other age groups.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of this medicine in the elderly with use in other age groups.

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

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. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

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.

Proper Use of coal tar

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

Use this medicine only as directed. Do not use more of it and do not use it more often than recommended on the label, unless otherwise directed by your doctor. To do so may increase the chance of side effects.

After applying coal tar, protect the treated area from direct sunlight and do not use a sunlamp for 72 hours, unless otherwise directed by your doctor, since a severe reaction may occur. Also, make sure you have removed all the coal tar medicine from your skin before you go back into direct sunlight or use a sunlamp.

Do not apply this medicine to infected, blistered, raw, or oozing areas of the skin.

Keep this medicine away from the eyes. If you should accidentally get some in your eyes, flush them thoroughly with water at once.

To use the cream or ointment form of this medicine:

• Apply enough medicine to cover the affected area, and rub in gently.

To use the gel form of this medicine:

• Apply enough gel to cover the affected area, and rub in gently. Allow the gel to remain on the affected area for 5 minutes, then remove excess gel by patting with a clean tissue.

To use the shampoo form of this medicine:

• Wet the scalp and hair with lukewarm water. Apply a generous amount of shampoo and rub into the scalp, then rinse. Apply the shampoo again, working up a rich lather, and allow to remain on the scalp for 5 minutes. Then rinse thoroughly.

To use the nonshampoo liquid form of this medicine:

• Some of these preparations are to be applied directly to dry or wet skin, some are to be added to lukewarm bath water, and some may be applied directly to dry or wet skin or added to lukewarm bath water. Make sure you know exactly how you should use this medicine. If you have any questions about this, check with your health care professional.


• If this medicine is to be applied directly to the skin, apply enough to cover the affected area, and rub in gently.


• Some of these preparations contain alcohol and are flammable. Do not use near heat, near open flame, or while smoking.

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 eczema, psoriasis, seborrheic dermatitis, and other skin disorders:
  
  • For cleansing bar dosage form:
    
    • Adults—Use one or two times a day, or as directed by your doctor.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For cream dosage form:
    
    • Adults—Apply to the affected area(s) of the skin up to four times a day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For gel dosage form:
    
    • Adults—Apply to the affected area(s) of the skin one or two times a day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For lotion dosage form:
    
    • Adults—Apply directly to the affected area(s) of the skin or use as a bath, hand or foot soak, or as a hair rinse, depending on the product.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For ointment dosage form:
    
    • Adults—Apply to the affected area(s) of the skin two or three times a day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For shampoo dosage form:
    
    • Adults—Use once a day to once a week or as directed by your doctor.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For topical solution dosage form:
    
    • Adults—Apply to wet the skin or scalp, or use as a bath, depending on the product.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For topical suspension dosage form:
    
    • Adults—Use as a bath.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, apply 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.

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.

Precautions While Using Psorigel

If this medicine is used on the scalp, it may temporarily discolor blond, bleached, or tinted hair.

Coal tar may stain the skin or clothing. Avoid getting it on your clothing. The stain on the skin will wear off after you stop using the medicine.

Psorigel Side Effects

In animal studies, coal tar has been shown to increase the chance of skin cancer.

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 as soon as possible if any of the following side effects occur:

Rare

• Skin irritation not present before use of this medicine


• skin rash

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

• Stinging (mild)—especially for gel and solution dosage forms

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.

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.

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More Psorigel Topical resources

• Psorigel Topical Use in Pregnancy & Breastfeeding
• Psorigel Topical Support Group
• 0 Reviews for Psorigel Topical - Add your own review/rating

Compare Psorigel Topical with other medications

• Dermatitis
• Psoriasis
• Seborrheic Dermatitis

Injectio Trimecainii Chlorati Ardeapharma

Injectio Trimecainii Chlorati Ardeapharma may be available in the countries listed below.

Ingredient matches for Injectio Trimecainii Chlorati Ardeapharma

Trimecaine

Trimecaine hydrochloride (a derivative of Trimecaine) is reported as an ingredient of Injectio Trimecainii Chlorati Ardeapharma in the following countries:

• Czech Republic

International Drug Name Search

Velban

Generic Name: Vinblastine Sulfate
Class: Antineoplastic Agents
VA Class: AN900
CAS Number: 143-67-9

• Administration Warnings


• 
  

  For IV use only.¹²⁷

  
  


• 
  

  Fatal if given intrathecally.¹²⁷ (See Intrathecal Administration under Cautions.)

  
  


• 
  

  Extremely important to properly place IV needle or catheter securely within vein before vinblastine is injected.¹²⁷

  
  


• 
  

  Leakage into surrounding tissues may cause considerable irritation.¹²⁷

  
  


• 
  

  Discontinue immediately if leakage occurs; administer remainder of the dose through another vein.^{127 b}

  
  


• 
  

  Local treatment of leakage area (e.g., with hyaluronidase injection, application of moderate heat) may help disperse vinblastine and minimize discomfort and possibility of cellulitis.¹²⁷

  
  

• Limit to Qualified Personnel


• 
  

  For administration only by individuals experienced in the administration of vinblastine sulfate.^{127 b}

  
  

Introduction

Antineoplastic agent; vinca alkaloid.^{134 139}

Uses for Velban

Hodgkin’s Disease

In combination chemotherapy as first- or second-line therapy for Hodgkin’s disease.^{127 135}

Often used with doxorubicin, bleomycin, and dacarbazine (known as the ABVD regimen) as first-line therapy for Hodgkin’s disease.^{135 138}

Under investigated in other combination regimens (e.g., Stanford V regimen: doxorubicin, bleomycin, vinblastine, vincristine, mechlorethamine, etoposide, and prednisone) for the treatment of advanced Hodgkin's disease.^{135 138}

Testicular Cancer

For the treatment of advanced nonseminomatous testicular carcinoma, combination chemotherapy regimens containing vinblastine, cisplatin, and bleomycin have been used;^{127 128 129 130} however, most clinicians recommend regimens containing cisplatin and bleomycin, in combination with etoposide rather than vinblastine, as first-line therapy, particularly because of the reduced risk of neuromuscular toxicity and evidence suggesting greater efficacy in poor-risk patients.^{128 129 130 135}

A regimen of cisplatin, ifosfamide, and either vinblastine or etoposide currently is considered by most clinicians to be the standard initial salvage (i.e., second-line) regimen in patients with recurrent testicular cancer.^{128 135}

AIDS-related Kaposi’s Sarcoma

Has been used alone^{135 140 141} or in combination^{140 142 143 144 145 146} chemotherapy for the palliative treatment of AIDS-related Kaposi’s sarcoma.

Single-agent therapy with vinblastine is considered an alternative regimen.¹³⁵

Combination chemotherapy with a vinca alkaloid (vinblastine or vincristine) also has been a preferred regimen,^{135 140 145 146} but many clinicians currently consider a liposomal anthracycline (doxorubicin or daunorubicin) the first-line therapy of choice for advanced AIDS-related Kaposi’s sarcoma.^{135 140 180 193 199}

Combination chemotherapy with conventional antineoplastic agents (e.g., bleomycin, conventional doxorubicin, etoposide, vinblastine, vincristine) has been used for more advanced disease (e.g., extensive mucocutaneous disease, lymphedema, symptomatic visceral disease).^{140 145 146 182 194}

A liposomal anthracycline for the treatment of advanced AIDS-related Kaposi’s sarcoma produces similar or higher response rates with a more favorable toxic effects profile than combination therapy with conventional chemotherapeutic agents.^{140 180 193 199}

Classic Kaposi’s Sarcoma

Single-agent vinblastine has been used for the treatment of classic Kaposi's sarcoma.^{127 140}

Bladder Cancer

In combination regimens with cisplatin and methotrexate, with or without doxorubicin, as first- or second-line therapy for invasive and advanced bladder cancer†.^{135 188 189 190 191}

Non-small Cell Lung Cancer

In combination with cisplatin and mitomycin (MVP)¹²⁶ as an alternative regimen for the treatment of non-small cell lung cancer†.^{135 192}

Currently preferred regimens for the treatment of advanced non-small cell lung cancer include the combination of cisplatin or carboplatin, with another agent, such as paclitaxel, docetaxel, vinorelbine, or gemcitabine.^{135 192}

Melanoma

Used in combination regimens (e.g., cisplatin, vinblastine, and dacarbazine, with or without interferon alfa and aldesleukin) for the treatment of metastatic melanoma†.^{135 216 218 219}

Superiority of combination regimens compared with dacarbazine alone not established,^{212 215 217} and dacarbazine monotherapy currently is a systemic treatment of choice for metastatic melanoma.^{135 213 214 215 217}

Brain Tumors

In combination with cisplatin and bleomycin or as monotherapy (second-line) for the treatment of intracranial germ cell tumors†.^{135 187}

Immune Thrombocytopenic Purpura

Has been used in the treatment of immune thrombocytopenic purpura†.²²⁴

Autoimmune Hemolytic Anemia

Slow IV infusions of vinblastine¹⁰⁶ or the use of vinblastine-loaded platelets^{107 108} has reportedly been effective in some cases for the treatment of autoimmune hemolytic anemia†.^{106 107 108}

Non-Hodgkin’s Lymphoma

Palliative treatment of non-Hodgkin’s lymphomas, including lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated), histiocytic lymphoma, and advanced stages of mycosis fungoides;¹²⁷ however, other agents currently are preferred.¹³⁵

Letterer-Siwe Disease

Treatment of Letterer-Siwe disease.¹²⁷

Velban Dosage and Administration

General

• 
  

  Consult specialized references for procedures for proper handling and disposal of antineoplastics.¹²⁷

  
  


• 
  

  Care must be taken to avoid contact with the eyes as severe irritation and possibly corneal ulceration (especially if administered under pressure) can result; if contact occurs, immediately wash eyes thoroughly.¹²⁷

  
  


• 
  

  Administration of antiemetics may easily control nausea and vomiting.^{127 b}

  
  

Administration

For solution and drug compatibility information, see Compatibility under Stability.

IV Administration

Administer IV only by individuals experienced in the administration of the drug.¹²⁷

Very irritating; must not be given IM, sub-Q, or intrathecally.¹²⁷ Intrathecal administration usually results in death.¹²⁷ (See Boxed Warning.)

Management of patients mistakenly receiving intrathecal vinblastine is a medical emergency.¹²⁷ If administered intrathecally, immediate neurosurgical intervention is required to prevent ascending paralysis leading to death.¹²⁷ (See Intrathecal Administration under Cautions.)

Administer appropriate quantity of commercially available or reconstituted solution by IV injection into the tubing of a running IV infusion or directly into a vein.^{127 b}

Because of the enhanced possibility of thrombosis, do not inject into an extremity with impaired or potentially impaired circulation caused by compression or invading neoplasm, phlebitis, or varicosity.^{127 b}

Because of possible leukopenic response, administer at intervals of at least 7 days;¹²⁷ however, even if 7 days have elapsed, do not give next dose until leukocyte count has returned to ≥4000/mm³.¹²⁷ Strict adherence to recommended dosage interval is important.^b

To ensure an adequate trial, therapy must be continued for at least 4–6 weeks.^b Some experts advocate a trial of at least 12 weeks, particularly in patients with carcinomas.^b

Extravasation

Extremely important to ensure that the needle or catheter is securely within the vein in order to avoid extravasation.¹²⁷

The manufacturers recommend rinsing the syringe and needle with venous blood after administration of the drug and before withdrawal of the needle to further minimize the possibility of extravasation.^{127 b}

If leakage occurs, discontinue injection immediately and administer remainder of the dose through another vein; local treatment of the area of leakage may minimize discomfort and the possibility of cellulitis.^b (See Boxed Warning and also see Local Effects under Cautions.)

Reconstitution

Reconstitute powder for injection by adding 10 mL of bacteriostatic sodium chloride injection containing benzyl alcohol as a preservative or 10 mL of sodium chloride injection (without preservatives) to a vial labeled as containing 10 mg of the drug to provide a solution containing 1 mg/mL.¹²⁷

Do not use other diluents; do not combine with any other chemical.¹²⁷

Dilution

To minimize the risk of extravasation and/or venous irritation, do not dilute in large volumes of IV solution (e.g., 100–250 mL).¹²⁷

Rate of Administration

Inject appropriate quantity of commercially available or reconstituted solution into the tubing of a running IV infusion or directly into a vein over about a 1-minute period.^b

To minimize risk of extravasation and/or venous irritation, do not infuse over long periods of time (i.e., from 30–60 minutes or longer).¹²⁷

Dispensing Precautions

When dispensing, must label syringe or container holding the individual dose with the statement: “Warning: Fatal if given intrathecally. For intravenous use only.”¹²⁷

Enclose container or syringe holding the individual dose in an overwrap (e.g., plastic bag or similar wrap with typed label) bearing the statements: “Do not remove covering until moment of injection. Fatal if given intrathecally. For intravenous use only.”¹²⁷ (See Intrathecal Administration under Cautions.)

Consider additional measures to prevent inadvertent intrathecal administration, including: administering diluted vinblastine solutions in minibags; preparing the medication at the time of administration; attaching a unique filter; dispensing separately from all other medications; dispensing directly to the individual who is administering the drug; conducting an independent check of the dose and route of administration for the drug both at the time of preparation and prior to administration; and administering vinblastine in a separate room from rooms where intrathecal medications are administered.²²⁵

Dosage

Available as vinblastine sulfate; dosage expressed in terms of the salt.¹²⁷

Dosage varies depending on the schedule used and whether vinblastine is administered as a single agent or incorporated within a particular chemotherapeutic regimen.¹²⁷ Consult published protocols for dosages in combination regimens.^b

Use of small daily doses for prolonged periods (even if equivalent to the total weekly dosage) is not recommended because it has produced severe toxicity with little or no added therapeutic benefit.^b

Pediatric Patients

General Dosage

Some evidence indicates that the usual initial pediatric dosage varies depending on the schedule used and whether vinblastine is administered as a single agent or incorporated within a particular chemotherapeutic regimen.¹²⁷

Hodgkin’s Disease

IV

In combination with other chemotherapeutic agents, an initial dosage of 6 mg/m² has been used.¹²⁷ Adjust dosage based on hematologic tolerance.¹²⁷ Consult published protocols for additional information on dosage.

Testicular Germ Cell Carcinoma

IV

An initial dosage of 3 mg/m² has been used in a combination regimen.¹²⁷ Adjust dosage based on hematologic tolerance.¹²⁷ Consult published protocols for additional information on dosage.

Letterer-Siwe Disease

IV

As monotherapy, an initial dosage of 6.5 mg/m² reportedly has been used.¹²⁷ Adjust dosage based on hematologic tolerance.¹²⁷ Consult published protocols for additional information on dosage.

Adults

General Dosage

Initial Dosage

IV

Initially, 3.7 mg/m² given as a single dose.¹²⁷

Dosage Modification

Determine subsequent dosage by clinical and hematologic response and patient tolerance to obtain optimum therapeutic results with minimum adverse effects.¹²⁷

Increase dosage at weekly intervals in increments of about 1.8–1.9 mg/m² until desired therapeutic response is obtained, the leukocyte count decreases to about 3000/mm³, or a maximum weekly dose of 18.5 mg/m² is reached.¹²⁷

In most adults, the optimum weekly dose will be 5.5–7.4 mg/m²; however, leukopenia (leukocyte count of 3000/mm³) may occur in some patients with 3.7 mg/m² per week, whereas other patients may tolerate 11.1–18.5 mg/m² per week.¹²⁷

Once the dose required to produce a leukocyte count of 3000/mm³ has been determined, administer a maintenance dose of one increment (1.8 mg/m²) less than this amount (e.g., the maximum dose that does not cause leukopenia) at weekly intervals.¹²⁷

Dosage generally is reduced in patients with recent exposure to radiation therapy or chemotherapy; single doses in these patients usually do not exceed 5.5 mg/m².^b

Maintenance Dosage

Duration of maintenance therapy varies according to disease being treated and combination of chemotherapeutic agents being used; there are differences of opinion regarding duration of maintenance therapy with the same protocol for a particular disease.¹²⁷

Prolonged chemotherapy for maintaining remissions involves several risks (i.e., life-threatening infectious diseases, sterility, possible appearance of other neoplasms resulting from immune system suppression).¹²⁷

In some disorders, survival following complete remission may not be as prolonged as that achieved with shorter periods of maintenance therapy; however, failure to provide maintenance therapy in some patients may lead to unnecessary relapse.¹²⁷

Prescribing Limits

Adults

IV

Maximum 18.5 mg/m² weekly.¹²⁷

Special Populations

Hepatic Impairment

In patients with a direct serum bilirubin >3 mg/dL, dosage reduction of 50% recommended.¹²⁷

Renal Impairment

No dosage reduction recommended.¹²⁷

Cautions for Velban

Contraindications

• 
  

  Substantial leukopenia (granulocytopenia).¹²⁷

  
  


• 
  

  Presence of bacterial infections; control infection prior to initiation of therapy.¹²⁷

  
  

Warnings/Precautions

Warnings

Intrathecal Administration

Fatal if administered intrathecally; immediate neurosurgical intervention required to prevent ascending paralysis leading to death.¹²⁷

Prognosis to date (principally with patients inadvertently administered vincristine intrathecally) generally has been poor despite immediate efforts to remove spinal fluid and flush with lactated Ringer's injection, with such efforts failing to prevent ascending paralysis and death in almost all cases.¹³³

In a very small number of patients, life-threatening paralysis and subsequent death have been averted, but devastating neurologic sequelae, with limited recovery afterwards, have resulted.¹²⁷

There are no published cases of survival following intrathecal administration of vinblastine to use as guidance for treatment.¹²⁷

According to published reports of survivors of inadvertent intrathecal administration of vincristine, treatment consists of immediate removal of as much CSF as safely possible via lumbar access, followed by insertion of an epidural catheter into the subarachnoid space via the intervertebral space above initial lumbar access and then CSF irrigation with lactated Ringer’s solution; add fresh frozen plasma (25 mL) to every L of lactated Ringer’s solution when available.¹²⁷

Insert intraventricular drain or catheter (by a neurosurgeon), continue CSF irrigation with fluid removal through the lumbar access connected to a closed drainage system.¹²⁷ Give lactated Ringer’s solution by continuous infusion at the rate of 150 mL/hour, or at a rate of 75 mL/hour when fresh frozen plasma has been added.¹²⁷ Adjust rate to maintain CSF protein concentration of 150 mg/dL.¹²⁷

Additional measures have been used but may not be essential, including glutamic acid (10 g IV over 24 hours, followed by 500 mg orally 3 times daily for 1 month), leucovorin (100-mg IV bolus followed by an infusion of 25 mg/hour for 24 hours, then 25 mg by IV bolus every 6 hours for 1 week), or pyridoxine hydrochloride (50 mg has been administered as an IV infusion over 30 minutes every 8 hours).^{127 133} The contribution of these additional therapies to reduction of neurotoxicity is unclear.¹²⁷

Hematologic Effects

Leukopenia occurs commonly and is usually the dose-limiting factor in therapy.^{127 b} Nadir in leukocyte count generally occurs 5–10 days after administration and recovery usually occurs within another 7–14 days;¹²⁷ however, following administration of high doses, recovery may take ≥21 days.^b

Perform blood counts weekly or at least before administration of each dose.^{127 b}

If leukopenia with <2000/mm³ occurs following a dose, carefully monitor patient for signs of infection.¹²⁷

More profound leukopenia possible in patients with cachexia or ulcerated areas of skin; avoid use in patients (especially geriatric patients) with these conditions.¹²⁷

In patients with malignant-cell infiltration of the bone marrow, an abrupt decrease in leukocyte and platelet counts may occur after moderate doses;¹²⁷ manufacturers recommend discontinuance in such patients,¹²⁷ but many clinicians consider it appropriate to continue therapy if the drug is clearly destroying tumor cells in the bone marrow.^b

Anemia also may occur.^b

Patients who receive myelosuppressive drugs experience an increased frequency of infections as well as possible hemorrhagic complications.^b

Nervous System Effects

Possible neurotoxicity, sometimes disabling;¹²⁷ occurs occasionally in patients receiving vinblastine, especially with high doses or prolonged therapy, but less frequently than with vincristine therapy.^b

When doses several times the recommended weekly dosage were administered daily for long periods, seizures, permanent CNS damage, and death occurred;¹²⁷ however, some clinicians believe that patients with rapidly progressing tumors with short generation times should receive large divided doses over several days, repeated as often as toxicity permits.^b

GI Effects

Possible stomatitis; although reversible, can be disabling.¹²⁷

GI symptoms, particularly constipation, abdominal pain, and adynamic ileus, may be related to neurotoxicity.^b

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity demonstrated in animals.¹²⁷ Avoid pregnancy during therapy.¹²⁷ If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.¹²⁷

Genitourinary Effects

Aspermia reported during therapy; reproductive studies in animals have revealed evidence of metaphase arrest and degenerative changes in germ cells.¹²⁷

General Precautions

Highly toxic drug with low therapeutic index; therapeutic response is not likely to occur without some evidence of toxicity.^b Administer only under constant supervision by clinicians experienced in therapy with cytotoxic agents.^b

Respiratory Effects

Acute shortness of breath and bronchospasm, which can be severe or life threatening, have occurred; reported most frequently when mitomycin was administered concomitantly.¹²⁷

Such reactions may occur a few minutes to several hours after administration of a vinca alkaloid, or up to 2 weeks after mitomycin dose.¹²⁷

Aggressive treatment may be required, particularly in patients with preexisting pulmonary dysfunction.¹²⁷

Progressive dyspnea, which may require chronic therapy, can occur in patients receiving vinblastine; do not readminister to these patients.¹²⁷

Patients with preexisting pulmonary dysfunction may be particularly susceptible to severe or life-threatening pulmonary effects.¹²⁷

Cardiovascular Effects

Caution is advised when using vinblastine in patients with ischemic cardiovascular disease, and care of this condition should be recommended.¹²⁷

Hypertension is the most common adverse cardiovascular effect of vinblastine.¹²⁷

Cases of unexpected MI and cerebrovascular accident reported in patients receiving vinblastine in combination with bleomycin and cisplatin.^{127 223}

Raynaud's phenomenon reported in patients receiving vinblastine and bleomycin, with or without cisplatin.¹²⁷

Local Effects

Tissue irritant; may cause phlebitis and necrosis.^{127 b} Extravasation can result in pain and cellulitis.^{127 b}

If extravasation of large amounts of the injection occurs, sloughing may result; local reactions may be severe and can persist for several weeks to months.^b

Manufacturers state that local injection of hyaluronidase and application of moderate heat may decrease local reactions resulting from extravasation;¹²⁷ however, some clinicians prefer to treat extravasation with cold compresses, dilution with 0.9% sodium chloride injection, and/or local injection of hydrocortisone.^b

Otic Effects

Eighth cranial nerve damage, which may be evident as vestibular manifestations (e.g., dizziness, nystagmus, vertigo) and by auditory manifestations (e.g., varying degrees of hearing impairment) that may be temporary or permanent, reported in patients receiving vinca alkaloids.¹²⁷

Use vinca alkaloids concomitantly with other potentially ototoxic drugs (e.g., platinum-containing antineoplastic agents) with extreme caution.¹²⁷ (See Specific Drugs under Interactions.)

Hyperuricemia

Hyperuricemia may result from extensive purine catabolism accompanying rapid cellular destruction in some patients receiving vinblastine, especially those with non-Hodgkin’s lymphomas or leukemia.^b

In some patients, uric acid nephropathy may result.^b

Minimize by adequate hydration, alkalinization of the urine, and/or administration of allopurinol.^b

Dermatologic Effects

Vinblastine-induced alopecia is common; other adverse dermatologic effects occur infrequently following vinblastine therapy and include dermatitis and vesiculation of the skin, phototoxicity, and epilation.^b

Epilation is partial and almost always reversible; in some cases, hair may regrow during maintenance therapy.^b

Specific Populations

Pregnancy

Category D.^{pdh 127} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether vinblastine is distributed in milk.¹²⁷ Discontinue nursing or the drug.¹²⁷

Geriatric Use

Avoid use in geriatric patients with cachexia or ulcerated areas of skin; more profound leukopenia is possible in such patients.¹²⁷

Hepatic Impairment

In patients with hepatic impairment, toxicity may be enhanced.¹²⁷ Caution advised.¹²⁷ (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Leukopenia, alopecia, constipation, nausea, vomiting, hypertension, malaise, bone pain, pain in tumor-containing tissue, jaw pain, paresthesia, peripheral neuropathy and neuritis, numbness, loss of deep tendon reflexes, muscle pain and weakness, ileus, anorexia, stomatitis, weight loss, anemia.^{127 b pdh}

Interactions for Velban

Metabolized by CYP3A.^{127 185}

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A: potential pharmacokinetic interaction (inhibition of vinblastine metabolism); earlier onset and/or increased severity of adverse effects of vinblastine may occur.¹²⁷ Use concomitantly with caution.^{127 185}

Ototoxic Drugs

Since varying degrees of permanent or temporary hearing impairment associated with eighth cranial nerve damage have been reported in patients receiving vinca alkaloids, use concomitantly with other potentially ototoxic drugs with extreme caution.¹²⁷ (See Specific Drugs under Interactions.)

Specific Drugs

Drug	Interaction	Comments
Antifungals, azoles	Itraconazole: Earlier onset and/or increased severity of neuromuscular effects reported with another vinca alkaloid (vincristine)184 185 Voriconazole: Possible neurotoxicity220	Monitor patients receiving a vinca alkaloid and an azole antifungal for increases in and/or prolongation of the effects of vinca alkaloids, including adverse effects (e.g., peripheral neuropathy, ileus); adjust dosage of the vinca alkaloid appropriately186 220
Aprepitant	Possible pharmacokinetic interaction221	Caution advised; monitor carefully221
Erythromycin	Increased vinblastine toxicity reported127
Ototoxic drugs (e.g., platinum-containing antineoplastic agents)	Potential additive ototoxic effect127	Varying degrees of permanent or temporary hearing impairment associated with eighth cranial nerve damage reported in patients receiving vinca alkaloids; use concomitantly with other potentially ototoxic drugs with extreme caution127
Phenytoin	Decreased serum concentrations of phenytoin and increased seizure activity reported127 131	Contribution of vinblastine to interaction is uncertain127 In patients receiving phenytoin and vinblastine concomitantly, monitor serum phenytoin concentrations and adjust dosage as necessary127 131
Tolterodine	Possible increased tolterodine concentrations222	Reduce tolterodine dosage to 50% of the recommended dosage222

Velban Pharmacokinetics

Absorption

Bioavailability

Unpredictably absorbed from the GI tract.^b

Distribution

Extent

Following IV administration, rapidly cleared from the blood and distributed into body tissues.^b Crosses the blood-brain barrier poorly and does not appear in the CSF in therapeutic concentrations.^b

Elimination

Metabolism

Reported to be extensively metabolized, mainly in the liver, to desacetylvinblastine, which is more active than the parent compound on a weight basis.^{b 127}

Mediated by CYP3A.¹²⁷

Elimination Route

Excreted slowly in urine and in feces via bile.^b

Special Populations

Metabolism via CYP isoenzymes may be impaired in patients with hepatic dysfunction.¹²⁷

Stability

Storage

Parenteral

Injection

2–8°C.^b Protect from light.^b

Powder for Injection

Store vials at 2–8°C to assure extended stability.¹²⁷ Protect from light.^b

After reconstitution with bacteriostatic sodium chloride injection (preserved with benzyl alcohol), solutions are stable for 28 days when refrigerated at 2–8°C.¹²⁷

When reconstituted with a diluent that does not contain a preservative, discard any unused portions immediately.¹²⁷

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Dextrose 5% in water
Ringer’s injection, lactated
Sodium chloride 0.9%

Drug Compatibility

Admixture CompatibilityHID

Compatible
Bleomycin sulfate
Variable
Doxorubicin HCl

Y-Site CompatibilityHID

Compatible
Allopurinol sodium
Amifostine
Amphotericin B cholesteryl sulfate complex
Aztreonam
Bleomycin sulfate
Cisplatin
Cyclophosphamide
Doxorubicin HCl
Doxorubicin HCl liposome injection
Droperidol
Etoposide phosphate
Filgrastim
Fludarabine phosphate
Fluorouracil
Gemcitabine HCl
Granisetron HCl
Heparin sodium
Leucovorin calcium
Melphalan HCl
Methotrexate sodium
Metoclopramide HCl
Mitomycin HCl
Ondansetron HCl
Paclitaxel
Pemetrexed disodium
Piperacillin sodium–tazobactam sodium
Sargramostim
Teniposide
Thiotepa
Vincristine sulfate
Vinorelbine tartrate
Incompatible
Cefepime HCl
Furosemide
Lansoprazole

ActionsActions

• 
  

  Mechanism of action not fully elucidated; vinblastine and other vinca alkaloids exert their cytotoxic effects by binding to tubulin, the protein subunit of the microtubules that form the mitotic spindle.^{134 139}

  
  


• 
  

  Formation of vinblastine-tubulin complexes prevents the polymerization of the tubulin subunits into microtubules and induces depolymerization of microtubules resulting in inhibition of microtubule assembly and cellular metaphase arrest.¹³⁴

  
  


• 
  

  In high concentrations, also exerts complex effects on nucleic acid and protein synthesis.^b

  
  


• 
  

  Also interferes with amino acid metabolism by blocking cellular utilization of glutamic acid and thus inhibits purine synthesis, the citric acid cycle, and the formation of urea.^b

  
  


• 
  

  Exerts some immunosuppressive activity.^b

  
  

Advice to Patients

• 
  

  Importance of notifying a clinician if fever, sore throat, unusual bleeding or bruising, or any other serious adverse event occurs.^{127 b}

  
  


• 
  

  Advise patients regarding avoidance of constipation.¹²⁷

  
  


• 
  

  Advise patients that alopecia may occur, but that scalp hair may regrow to its pretreatment extent even with continued therapy.¹²⁷

  
  


• 
  

  Advise patients that jaw pain and pain in the organs containing tumor tissue (possibly resulting from swelling of tumor tissue during treatment response) may occur.¹²⁷

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.^b

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^b

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹²⁷ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Vinblastine Sulfate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IV use only	1 mg/mL*	Vinblastine Sulfate Injection
	For injection, for IV use only	10 mg*	Vinblastine Sulfate for Injection

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions April 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Marmot AM, Damasio EE, Gori E. Vinblastine sulfate in idiopathic thrombocytopenic purpura. Lancet. 1971; 2:94. [IDIS 18500] [PubMed 4104002]

101. Sultan Y, Delobel J, Jeanneau C et al. Effect of periwinkle alkaloids in idiopathic thrombocytopenic purpura. Lancet. 1971; 1:496-7. [IDIS 19439] [PubMed 4100368]

102. Rodgers GM, Ries CA. Refractory idiopathic thrombocytopenic purpura. Ann Intern Med. 1980; 92:713-4.

103. Ahn YS, Harrington WJ, Mylvaganam R et al. Slow infusion of vinca alkaloids in the treatment of idiopathic thrombocytopenic purpura. Ann Intern Med. 1984; 100:192-6. [IDIS 181312] [PubMed 6537881]

104. Ahn YS, Byrnes JJ, Harrington WJ et al. The treatment of idiopathic thrombocytopenia with vinblastine-loaded platelets. N Engl J Med. 1978; 298:1101-7. [PubMed 565464]

105. Rosse WF. Whatever happened to vinca-loaded platelets? N Engl J Med. 1984; 310:1051-2. Editorial.

106. Medellin PL, Patten E, Weiss GB. Vinblastine for autoimmune hemolytic anemia. Ann Intern Med. 1982; 96:123. [IDIS 142633] [PubMed 7053689]

107. Gertz MA, Petitt RM, Pineda AA et al. Vinblastine-loaded platelets for autoimmune hemolytic anemia. Ann Intern Med. 1981; 95:325-6. [IDIS 137107] [PubMed 7271094]

108. Ahn YS, Harrington WJ, Byrnes JJ et al. Treatment of autoimmune hemolytic anemia with vinca-loaded platelets. JAMA. 1983; 249:2189-94. [PubMed 6834615]

109. Dyke RW. Acute bronchospasm after a vinca alkaloid in patients previously treated with mitomycin. N Engl J Med. 1984; 310:389. [IDIS 181096] [PubMed 6690968]

126. Veeder MH, Jett JR, Su JQ et al. A phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and cisplatin for metastatic squamous cell lung carcinoma. Cancer. 1992; 70:2281-7. [IDIS 304727] [PubMed 1394057]

127. Bedford Laboratories. Vinblastine sulfate for injection prescribing information. Bedford, OH; Dec 2001.

128. Testicular cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2007 May.

129. Williams SD, Birch R, Einhorn LH et al. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med. 1987; 316:1435-40. [IDIS 231286] [PubMed 2437455]

130. Loehrer PJ, Williams SD, Einhorn LH. Testicular cancer: the quest continues. J Natl Cancer Inst. 1988; 80:1373-83. [PubMed 3050140]

131. Hydantoins/antineoplastic agents. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St. Louis; JB Lippincott Co; 1991 Apr:373.

133. Dyke RW. Treatment of inadvertent intrathecal injection of vincristine. N Engl J Med. 1989; 321:1270-1. [IDIS 260603] [PubMed 2797094]

134. Zhou XJ, Rahmani R. Preclinical and clinical pharmacology of vinca alkaloids. Drugs. 1992; 44(Suppl 4):1-16. [PubMed 1283846]

135. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52. [PubMed 15529105]

136. Urba WJ, Longo DL. Hodgkin’s disease. N Engl J Med. 1992; 326:678-687. [IDIS 292239] [PubMed 1736106]

137. DeVita VT Jr, Hubbard SM. Hodgkin’s disease. N Engl J Med. 1993; 328:560-565. [IDIS 309839] [PubMed 8426624]

138. Adult Hodgkin’s lymphoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2007 May 3.

139. Rowinsky EK, Donehower RC. The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics. Pharmacol Ther. 1991; 52:35-84. [PubMed 1687171]

140. Kaposi’s sarcoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2006 Dec 13.

141. Volberding PA, Abrams DI, Conant M et al. Vinblastine therapy for Kaposi’s sarcoma in the acquired immunodeficiency syndrome. Ann Intern Med. 1985; 103:335-8. [IDIS 205816] [PubMed 4026082]

142. Kaplan L, Abrams D, Volberding P. Treatment of Kaposi’s sarcoma in acquired immunodeficiency syndrome with an alternating vincristine-vinblastine regimen. Cancer Treat Rep. 1986; 70:1121-2. [IDIS 222400] [PubMed 3742492]

143. Laubenstein LJ, Krigel RL, Odajnyk CM et al. Treatment of epidemic Kaposi’s sarcoma with etoposide or a combination of doxorubicin, bleomycin, and vinblastine. J Clin Oncol. 1984; 2:1115-20. [PubMed 6208343]

144. Gelmann EP, Longo D, Lane HC et al

Compro

prochlorperazine

Dosage Form: suppository
Compro®

PROCHLORPERAZINE

SUPPOSITORIES USP, 25mg

ANTIEMETIC - TRANQUILIZER

PRESCRIBING INFORMATION

WARNING

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Compro® Prochlorperazine Suppositories USP is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS).

Compro Description

Prochlorperazine is a clear, pale yellow, viscous liquid. It is sensitive to light, very slightly soluble in water, freely soluble in alcohol, in chloroform, and in ether.

Each suppository, for rectal administration, contains 25 mg of prochlorperazine; with glycerin, glyceryl monopalmitate, glyceryl monostearate, hydrogenated coconut oil fatty acids and hydrogenated palm kernel oil fatty acids.

Prochlorperazine has the molecular formula C20H24ClN3S. Its molecular weight is 373.95. The chemical name for prochlorperazine is 2-Chloro-10-[3-(4-methyl-1-piperazinyl)propyl] phenothiazine. The structural formula is:

Compro - Clinical Pharmacology

Prochlorperazine is a propylpiperazine derivative of phenothiazine. Like other phenothiazines, it exerts an antiemetic effect through a depressant action on the chemoreceptor trigger zone.

Indications and Usage for Compro

Prochlorperazine 25mg suppositories are indicated in the control of severe nausea and vomiting in adults.

Contraindications

Do not use in comatose states or in the presence of large amounts of central nervous system depressants (alcohol, barbiturates, narcotics, etc.).

Do not use in pediatric surgery.

Do not use in children under 2 years of age or under 20 lbs. Do not use in children for conditions for which dosage has not been established.

Warnings

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Compro® Prochlorperazine Suppositories USP is not approved for the treatment of patients with dementia-related psychosis (see BOXED WARNING).

The extrapyramidal symptoms which can occur secondary to prochlorperazine may be confused with the central nervous system signs of an undiagnosed primary disease responsible for the vomiting, e.g., Reye's Syndrome or other encephalopathy. The use of prochlorperazine and other potential hepatotoxins should be avoided in children and adolescents whose signs and symptoms suggest Reye's Syndrome.

Tardive Dyskinesia:

Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with neuroleptic (antipsychotic) drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of neuroleptic treatment, which patients are likely to develop the syndrome. Whether neuroleptic drug products differ in their potential to cause tardive dyskinesia is unknown.

Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of neuroleptic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.

There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if neuroleptic treatment is withdrawn. Neuroleptic treatment itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying disease process.

The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

Given these considerations, neuroleptics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic neuroleptic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to neuroleptic drugs, and 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient on neuroleptics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.

For further information about the description of tardive dyskinesia and its clinical detection, please refer to the sections on PRECAUTIONS and ADVERSE REACTIONS.

Neuroleptic Malignant Syndrome (NMS):

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association 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 antipsychotic drugs 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.

If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.

General:

Patients with bone marrow depression or who have previously demonstrated a hypersensitivity reaction (e.g., blood dyscrasias, jaundice) with a phenothiazine should not receive any phenothiazine, including prochlorperazine, unless in the judgement of the physician the potential benefits of treatment outweigh the possible hazards.

Prochlorperazine may impair mental and/or physical abilities, especially during the first few days of therapy. Therefore, caution patients about activities requiring alertness (e.g., operating vehicles or machinery).

Phenothiazines may intensify or prolong the action of central nervous system depressants (e.g., alcohol, anesthetics, narcotics).

Usage in Pregnancy:

Safety for the use of prochlorperazine during pregnancy has not been established. Therefore, prochlorperazine is not recommended for use in pregnant patients except in cases of severe nausea and vomiting that are so serious and intractable that, in the judgment of the physician, drug intervention is required and potential benefits outweigh possible hazards.

There have been reported instances of prolonged jaundice, extrapyramidal signs, hyperreflexia or hyporeflexia in newborn infants whose mothers received phenothiazines.

Nursing Mothers:

There is evidence that phenothiazines are excreted in the breast milk of nursing mothers.

Precautions

Leukopenia, Neutropenia and Agranulocytosis

In clinical trial and postmarketing experience, events of leukopenia/neutropenia and agranulocytosis have been reported temporally related to antipsychotic agents.

Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia. Patients with a pre-existing low WBC or a history of drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue Compro® at the first sign of a decline in WBC in the absence of other causative factors.

Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count <1000/mm3) should discontinue Compro® and have their WBC followed until recovery.

The antiemetic action of prochlorperazine may mask the signs and symptoms of overdosage of other drugs and may obscure the diagnosis and treatment of other conditions such as intestinal obstruction, brain tumor and Reye's Syndrome (see WARNINGS).

When prochlorperazine is used with cancer chemotherapeutic drugs, vomiting as a sign of the toxicity of these agents may be obscured by the antiemetic effect of prochlorperazine.

Because hypotension may occur, large doses and parenteral administration should be used cautiously in patients with impaired cardiovascular systems. If hypotension occurs after parenteral or oral dosing, place patient in head-low position with legs raised. If a vasoconstrictor is required, norepinephrine bitartrate and phenylephrine hydrochloride are suitable. Other pressor agents, including epinephrine, should not be used because they may cause a paradoxical further lowering of blood pressure.

Aspiration of vomitus has occurred in a few post-surgical patients who have received prochlorperazine as an antiemetic. Although no causal relationship has been established, this possibility should be borne in mind during surgical aftercare.

Deep sleep, from which patients can be aroused, and coma have been reported, usually with overdosage.

Neuroleptic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one third of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if the prescribing of these drugs is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of neuroleptic drugs. Neither clinical nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.

Chromosomal aberrations in spermatocytes and abnormal sperm have been demonstrated in rodents treated with certain neuroleptics.

As with all drugs which exert an anticholinergic effect, and/or cause mydriasis, prochlorperazine should be used with caution in patients with glaucoma.

Because phenothiazines may interfere with thermoregulatory mechanisms, use with caution in persons who will be exposed to extreme heat.

Phenothiazines can diminish the effect of oral anticoagulants.

Phenothiazines can produce alpha-adrenergic blockade.

Thiazide diuretics may accentuate the orthostatic hypotension that may occur with phenothiazines.

Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concomitantly.

Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs.

Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary. Potentiation of anticonvulsant effects does not occur. However, it has been reported that phenothiazines may interfere with the metabolism of phenytoin and thus precipitate phenytoin toxicity.

The presence of phenothiazines may produce false-positive phenylketonuria (PKU) test results.

Long-Term Therapy:

Given the likelihood that some patients exposed chronically to neuroleptics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided.

To lessen the likelihood of adverse reactions related to cumulative drug effect, patients with a history of long-term therapy with prochlorperazine and/or other neuroleptics should be evaluated periodically to decide whether the maintenance dosage could be lowered or drug therapy discontinued.

Children with acute illnesses (e.g., chicken pox, CNS infections, measles, gastroenteritis) or dehydration seem to be much more susceptible to neuromuscular reactions, particularly dystonias, than are adults. In such patients, the drug should be used only under close supervision.

Drugs which lower the seizure threshold, including phenothiazine derivatives, should not be used with metrizamide. As with other phenothiazine derivatives, prochlorperazine should be discontinued at least 48 hours before myelography, should not be resumed for at least 24 hours postprocedure, and should not be used for the control of nausea and vomiting occurring either prior to myelography with metrizamide, or postprocedure.

Geriatric Use:

Clinical studies of prochlorperazine did not include sufficient numbers of subjects aged 65 and over to determine whether elderly subjects respond differently from younger subjects. Geriatric patients are more sensitive to the side effects of antipsychotics, including prochlorperazine. These adverse events include hypotension, anticholinergic effects (such as urinary retention, constipation, and confusion), and neuromuscular reactions (such as parkinsonism and tardive dyskinesia) (see PRECAUTIONS and ADVERSE REACTIONS). Also, postmarketing safety experience suggests that the incidence of agranulocytosis may be higher in geriatric patients compared to younger individuals who received prochlorperazine. 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 (see DOSAGE AND ADMINISTRATION).

Pregnancy:

Non-teratogenic Effects

Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these infants. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases infants have required intensive care unit support and prolonged hospitalization.

Prochlorperazine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Adverse Reactions

Drowsiness, dizziness, amenorrhea, blurred vision, skin reactions and hypotension may occur.

Cholestatic jaundice has occurred. If fever with grippe-like symptoms occurs, appropriate liver studies should be conducted. If tests indicate an abnormality, stop treatment. There have been a few observations of fatty changes in the livers of patients who have died while receiving the drug. No causal relationship has been established.

Leukopenia and agranulocytosis have occurred. Warn patients to report the sudden appearance of sore throat or other signs of infection. If white blood cell and differential counts indicate leukocyte depression, stop treatment and start antibiotic and other suitable therapy.

Neuromuscular (Extrapyramidal) Reactions

These symptoms are seen in a significant number of hospitalized mental patients. They may be characterized by motor restlessness, be of the dystonic type, or they may resemble parkinsonism.

Depending on the severity of symptoms, dosage should be reduced or discontinued. If therapy is reinstituted, it should be at a lower dosage. Should these symptoms occur in children or pregnant patients, the drug should be stopped and not reinstituted. In most cases barbiturates by suitable route of administration will suffice. (Or, injectable diphenhydramine may be useful.) In more severe cases, the administration of an anti-parkinsonism agent, except levodopa (see PDR), usually produces rapid reversal of symptoms. Suitable supportive measures such as maintaining a clear airway and adequate hydration should be employed.

Motor Restlessness:

Symptoms may include agitation or jitteriness and sometimes insomnia. These symptoms often disappear spontaneously. At times these symptoms may be similar to the original neurotic or psychotic symptoms. Dosage should not be increased until these side effects have subsided.

If these symptoms become too troublesome, they can usually be controlled by a reduction of dosage or change of drug. Treatment with antiparkinsonian agents, benzodiazepines or propranolol may be helpful.

Dystonia:

Class effect:

Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

Pseudo-parkinsonism:

Symptoms may include: mask-like facies; drooling; tremors; pillrolling motion; cogwheel rigidity; and shuffling gait. Reassurance and sedation are important. In most cases these symptoms are readily controlled when an anti-parkinsonism agent is administered concomitantly. Anti-parkinsonism agents should be used only when required. Generally, therapy of a few weeks to 2 or 3 months will suffice. After this time patients should be evaluated to determine their need for continued treatment. (Note: Levodopa has not been found effective in pseudo-parkinsonism.) Occasionally it is necessary to lower the dosage of prochlorperazine or to discontinue the drug.

Tardive Dyskinesia:

As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may appear after drug therapy has been discontinued. The syndrome can also develop, although much less frequently, after relatively brief treatment periods at low doses. This syndrome appears in all age groups. Although its prevalence appears to be highest among elderly patients, especially elderly women, it is impossible to rely upon prevalence estimates to predict at the inception of neuroleptic treatment which patients are likely to develop the syndrome. The symptoms are persistent and in some patients appear to be irreversible. The syndrome is characterized by rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g., protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of extremities. In rare instances, these involuntary movements of the extremities are the only manifestations of tardive dyskinesia. A variant of tardive dyskinesia, tardive dystonia, has also been described.

There is no known effective treatment for tardive dyskinesia; anti-parkinsonism agents do not alleviate the symptoms of this syndrome. It is suggested that all antipsychotic agents be discontinued if these symptoms appear.

Should it be necessary to reinstitute treatment, or increase the dosage of the agent, or switch to a different antipsychotic agent, the syndrome may be masked.

It has been reported that fine vermicular movements of the tongue may be an early sign of the syndrome and if the medication is stopped at that time the syndrome may not develop.

Adverse Reactions Reported with Prochlorperazine or Other Phenothiazine Derivatives:

Adverse reactions with different phenothiazines vary in type, frequency and mechanism of occurrence, i.e., some are dose-related, while others involve individual patient sensitivity. Some adverse reactions may be more likely to occur, or occur with greater intensity, in patients with special medical problems, e.g., patients with mitral insufficiency or pheochromocytoma have experienced severe hypotension following recommended doses of certain phenothiazines.

Not all of the following adverse reactions have been observed with every phenothiazine derivative, but they have been reported with 1 or more and should be borne in mind when drugs of this class are administered: extrapyramidal symptoms (opisthotonos, oculogyric crisis, hyperreflexia, dystonia, akathisia, dyskinesia, parkinsonism) some of which have lasted months and even years- particularly in elderly patients with previous brain damage; grand mal and petit mal convulsions, particularly in patients with EEG abnormalities or history of such disorders; altered cerebrospinal fluid proteins; cerebral edema; intensification and prolongation of the action of central nervous system depressants (opiates, analgesics, antihistamines, barbiturates, alcohol), atropine, heat, organophosphorus insecticides; autonomic reactions (dryness of the mouth, nasal congestion, headache, nausea, constipation, obstipation, adynamic ileus, ejaculatory disorders/impotence, priapism, atonic colon, urinary retention, miosis and mydriasis); reactivation of psychotic processes, catatonic-like states; hypotension (sometimes fatal); cardiac arrest; blood dyscrasias (pancytopenia, thrombocytopenic purpura, leukopenia, agranulocytosis, eosinophilia, hemolytic anemia, aplastic anemia); liver damage (jaundice, biliary stasis); endocrine disturbances (hyperglycemia, hypoglycemia, glycosuria, lactation, galactorrhea, gynecomastia, menstrual irregularities, false-positive pregnancy tests); skin disorders (photosensitivity, itching, erythema, urticaria, eczema up to exfoliative dermatitis); other allergic reactions (asthma, laryngeal edema, angioneurotic edema, anaphylactoid reactions); peripheral edema; reversed epinephrine effect; hyperpyrexia; mild fever after large I.M. doses; increased appetite; increased weight; a systemic lupus erythematosus-like syndrome; pigmentary retinopathy; with prolonged administration of substantial doses, skin pigmentation, epithelial keratopathy, and lenticular and corneal deposits.

EKG changes-particularly nonspecific, usually reversible Q and T wave distortions-have been observed in some patients receiving phenothiazine tranquilizers.

Although phenothiazines cause neither psychic nor physical dependence, sudden discontinuance in long-term psychiatric patients may cause temporary symptoms, e.g., nausea and vomiting, dizziness, tremulousness.

Note: There have been occasional reports of sudden death in patients receiving phenothiazines. In some cases, the cause appeared to be cardiac arrest or asphyxia due to failure of the cough reflex.

Overdosage

(See also ADVERSE REACTIONS).

SYMPTOMS–Primarily involvement of the extrapyramidal mechanism producing some of the dystonic reactions described above.

Symptoms of central nervous system depression to the point of somnolence or coma. Agitation and restlessness may also occur. Other possible manifestations include convulsions, EKG changes and cardiac arrhythmias, fever and autonomic reactions such as hypotension, dry mouth and ileus.

TREATMENT–It is important to determine other medications taken by the patient since multiple-dose therapy is common in overdosage situations. Treatment is essentially symptomatic and supportive. Early gastric lavage is helpful. Keep patient under observation and maintain an open airway, since involvement of the extrapyramidal mechanism may produce dysphagia and respiratory difficulty in severe overdosage. Do not attempt to induce emesis because a dystonic reaction of the head or neck may develop that could result in aspiration of vomitus. Extrapyramidal symptoms may be treated with anti-parkinsonism drugs, barbiturates or diphenhydramine. See prescribing information for these products. Care should be taken to avoid increasing respiratory depression.

If administration of a stimulant is desirable, amphetamine, dextroamphetamine or caffeine with sodium benzoate is recommended.

Stimulants that may cause convulsions (e.g., picrotoxin or pentylenetetrazol) should be avoided.

If hypotension occurs, the standard measures for managing circulatory shock should be initiated. If it is desirable to administer a vasoconstrictor, norepinephrine bitartrate and phenylephrine hydrochloride are most suitable. Other pressor agents, including epinephrine, are not recommended because phenothiazine derivatives may reverse the usual elevating action of these agents and cause a further lowering of blood pressure.

Limited experience indicates that phenothiazines are not dialyzable.

Compro Dosage and Administration

Adults: Dosage should be increased more gradually in debilitated or emaciated patients.

Elderly Patients: In general, dosages in the lower range are sufficient for most elderly patients. Since they appear to be more susceptible to hypotension and neuromuscular reactions, such patients should be observed closely. Dosage should be tailored to the individual, response carefully monitored and dosage adjusted accordingly. Dosage should be increased more gradually in elderly patients.

To Control Severe Nausea and Vomiting: Adjust dosage to the response of the individual. Begin with the lowest recommended dosage.

Rectal Dosage: 25 mg twice daily.

How is Compro Supplied

Compro® Prochlorperazine Suppositories USP, 25 mg (for adults) are easy to open, and available in boxes of 12.

12's - NDC 0574-7226-12

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]

Do not remove from wrapper until ready to use.

Paddock Laboratories, Inc.

Minneapolis, MN 55427

(12-10)

PRINCIPAL DISPLAY PANEL - 25 mg Carton

NDC 0574-7226-12

Compro®

Prochlorperazine

Suppositories, USP

25mg

FOR RECTAL USE ONLY

Paddock

Laboratories, Inc.

Rx only

UNIT DOSE

12

ADULT

SUPPOSITORIES

Compro  prochlorperazine  suppository

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0574-7226 Route of Administration RECTAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PROCHLORPERAZINE (PROCHLORPERAZINE) PROCHLORPERAZINE 25 mg

Inactive Ingredients Ingredient Name Strength GLYCERIN   GLYCERYL MONOSTEARATE   HYDROGENATED COCONUT OIL   PALM KERNEL OIL

Product Characteristics Color YELLOW (Pale Yellow) Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0574-7226-12 12 PACKET In 1 CARTON contains a PACKET 1 1 SUPPOSITORY In 1 PACKET This package is contained within the CARTON (0574-7226-12)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA040246	09/01/2000

Labeler - Paddock Laboratories, Inc. (086116803)

Establishment
Name	Address	ID/FEI	Operations
Paddock Laboratories, Inc.		086116803	MANUFACTURE

Revised: 12/2010Paddock Laboratories, Inc.

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