Cyklokapron

Generic Name: tranexamic acid (Intravenous route)

tran-ex-AM-ik AS-id

Commonly used brand name(s)

In the U.S.

• Cyklokapron

Available Dosage Forms:

• Solution

Therapeutic Class: Hemostatic

Uses For Cyklokapron

Tranexamic acid injection is used to control or prevent excessive or heavy bleeding during dental procedures in patients with hemophilia. This medicine is for short-term use only, usually 2 to 8 days.

Tranexamic acid injection is an antifibrinolytic agent. It works by blocking the breakdown of blood clots. It may also be used for other conditions as determined by your doctor.

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

Before Using Cyklokapron

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

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of tranexamic acid injection in children.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of tranexamic acid injection in the elderly. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving tranexamic acid injection.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	B	Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while 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. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Anti-Inhibitor Coagulant Complex


• Chlorpromazine


• Desogestrel


• Dienogest


• Drospirenone


• Estradiol Cypionate


• Estradiol Valerate


• Ethinyl Estradiol


• Ethynodiol Diacetate


• Etonogestrel


• Levonorgestrel


• Medroxyprogesterone Acetate


• Mestranol


• Norelgestromin


• Norethindrone


• Norgestimate


• Norgestrel


• Tretinoin

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Bleeding problems (bleeding in the brain) or


• Blood clots, active or history of or


• Head injury or


• Vision problems (problems seeing certain colors)—Should not be used in patients with these conditions.

• Blood vessel problems, history of or


• Hematuria (blood in the urine) caused by or


• Retinal artery or vein occlusion (blood clot in the eye) or


• Seizures, history of or


• Urinary tract problems (e.g., bleeding)—Use with caution. May make these conditions worse.

• Disseminated intravascular coagulation or DIC (blood clotting problem)—Should be treated under strict supervision of an experienced doctor in treating this disorder.

• Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper Use of Cyklokapron

A nurse or other trained health professional will give you this medicine in a hospital. This medicine is given through a needle placed in one of your veins.

Precautions While Using Cyklokapron

Your doctor will check the progress of you or your child closely while you are receiving this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to receive it. Blood tests will be needed to check for unwanted effects.

If you or your child will be receiving tranexamic acid injection for longer than several days, your doctor may want you to have your eyes checked regularly by an ophthalmologist (eye doctor). This will allow your doctor to check for unwanted effects that may be caused by this medicine.

Tranexamic acid injection should not be used together with factor IX complex (e.g., BeneFIX®, Proplex® T) or anti-inhibitor coagulant concentrates (e.g., Feiba VH®). Doing so, may increase the chance of having serious side effects.

This medicine may cause some people to become dizzy or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or are not alert.

Cyklokapron Side Effects

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

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

Rare

• Anxiety


• blurred vision


• changes in vision


• chest pain


• confusion


• cough


• dizziness or lightheadedness


• fainting


• fast heartbeat


• greatly increased or decreased frequency of urination or amount of urine


• increased thirst


• loss of appetite


• nausea or vomiting


• numbness of the hands


• pain, redness, or swelling in the arm or leg


• sudden shortness of breath or troubled breathing

Incidence not known

• Convulsions or seizures


• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position


• sweating


• trouble seeing


• unusual tiredness or weakness

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

• Diarrhea


• mental depression


• muscle twitching or jerking


• nightmares or unusually vivid dreams


• rash


• rhythmic movement of the muscles

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:

Incidence not known

• Giddiness


• hives, itching, or redness of the skin

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

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

See also: Cyklokapron side effects (in more detail)

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

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

More Cyklokapron resources

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

• Cyklokapron Prescribing Information (FDA)


• Cyklokapron MedFacts Consumer Leaflet (Wolters Kluwer)


• Tranexamic Acid Professional Patient Advice (Wolters Kluwer)


• Lysteda Prescribing Information (FDA)


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Compare Cyklokapron with other medications

• Bleeding Disorder
• Factor IX Deficiency
• Hemophilia A

Cytarabine

Cytarabine Injection

For Intravenous, Intrathecal and Subcutaneous Use Only

Rx only 

Warning

Only physicians experienced in cancer chemotherapy should use Cytarabine Injection.

For induction therapy patients should be treated in a facility with laboratory and supportive resources sufficient to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. The main toxic effect of Cytarabine injection is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Less serious toxicity includes nausea, vomiting, diarrhea and abdominal pain, oral ulceration, and hepatic dysfunction.

The physician must judge possible benefit to the patient against known toxic effects of this drug in considering the advisability of therapy with Cytarabine Injection. Before making this judgement or beginning treatment, the physician should be familiar with the following text.

Cytarabine Description

Cytarabine Injection, an antineoplastic, is a sterile solution of Cytarabine for intravenous, intrathecal or subcutaneous administration. Each mL contains 20 mg Cytarabine in 100 mg (20 mg/mL) single dose vial and 100 mg Cytarabine in 2 g (100 mg/mL) single dose vial.

Cytarabine Injection 100 mg/5 mL is a sterile solution for intravenous, intrathecal or subcutaneous administration. Each mL contains 20 mg Cytarabine, USP, and the following inactive ingredients: sodium chloride 6.8 mg and Water for Injection q.s. When necessary the pH is adjusted with hydrochloric acid and/or sodium hydroxide to a pH of 7.4. Each vial contains approximately 0.58 mEq sodium.

Cytarabine Injection 2 g/20 mL is a sterile solution for intravenous, intrathecal or subcutaneous administration. Each mL contains 100 mg Cytarabine, USP, and the following inactive ingredients: Water for Injection q.s. When necessary the pH is adjusted with hydrochloric acid and/or sodium hydroxide to a pH of 7.7.

Cytarabine is chemically 1-ß-D-Arabinofuranosylcytosine. The structural formula is:

Cytarabine is an odorless, white to off-white crystalline powder which is freely soluble in water and slightly soluble in alcohol and in chloroform.

Cytarabine - Clinical Pharmacology

Cell Culture Studies

Cytarabine is cytotoxic to a wide variety of proliferating mammalian cells in culture. It exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis (S-phase) and under certain conditions blocking the progression of cells from the G1 phase to the S-phase. Although the mechanism of action is not completely understood, it appears that Cytarabine acts through the inhibition of DNA polymerase. A limited, but significant, incorporation of Cytarabine into both DNA and RNA has also been reported. Extensive chromosomal damage, including chromatoid breaks, have been produced by Cytarabine and malignant transformation of rodent cells in culture has been reported. Deoxycytidine prevents or delays (but does not reverse) the cytotoxic activity.

Cellular Resistance and Sensitivity

Cytarabine is metabolized by deoxycytidine kinase and other nucleotide kinases to the nucleotide triphosphate, an effective inhibitor of DNA polymerase; it is inactivated by a pyrimidine nucleoside deaminase, which converts it to the non-toxic uracil derivative. It appears that the balance of kinase and deaminase levels may be an important factor in determining sensitivity or resistance of the cell to Cytarabine.

Human Pharmacology

Cytarabine is rapidly metabolized and is not effective orally; less than 20 percent of the orally administered dose is absorbed from the gastrointestinal tract.

Following rapid intravenous injection of Cytarabine labeled with tritium, the disappearance from plasma is biphasic. There is an initial distributive phase with a half-life of about 10 minutes, followed by a second elimination phase with a half-life of about 1 to 3 hours. After the distributive phase, more than 80 percent of plasma radioactivity can be accounted for by the inactive metabolite 1-ß-D-arabinofuranosyluracil (ara-U). Within 24 hours about 80 percent of the administered radioactivity can be recovered in the urine, approximately 90 percent of which is excreted as ara-U.

Relatively constant plasma levels can be achieved by continuous intravenous infusion.

After subcutaneous or intramuscular administration of Cytarabine labeled with tritium, peak-plasma levels of radioactivity are achieved about 20 to 60 minutes after injection and are considerably lower than those after intravenous administration.

Cerebrospinal fluid levels of Cytarabine are low in comparison to plasma levels after single intravenous injection. However, in one patient in whom cerebrospinal fluid levels are examined after 2 hours of constant intravenous infusion, levels approached 40 percent of the steady state plasma level. With intrathecal administration, levels of Cytarabine in the cerebrospinal fluid declined with a first order half-life of about 2 hours. Because cerebrospinal fluid levels of deaminase are low, little conversion to ara-U was observed.

Immunosuppressive Action

Cytarabine injection is capable of obliterating immune responses in man during administration with little or no accompanying toxicity. Suppression of antibody responses to E-coli-VI antigen and tetanus toxoid have been demonstrated. This suppression was obtained during both primary and secondary antibody responses.

Cytarabine injection also suppressed the development of cell-mediated immune responses such as delayed hypersensitivity skin reaction to dinitrochlorobenzene. However, it had no effect on already established delayed hypersensitivity reactions.

Following 5-day courses of intensive therapy with Cytarabine injection the immune response was suppressed, as indicated by the following parameters: macrophage ingress into skin windows; circulating antibody response following primary antigenic stimulation; lymphocyte blastogenesis with phytohemagglutinin. A few days after termination of therapy there was a rapid return to normal.

Indications and Usage for Cytarabine

Cytarabine Injection in combination with other approved anti-cancer drugs is indicated for remission induction in acute non-lymphocytic leukemia of adults and pediatric patients. It has also been found useful in the treatment of acute lymphocytic leukemia and the blast phase of chronic myelocytic leukemia. Intrathecal administration of Cytarabine Injection (preservative free preparations only) is indicated in the prophylaxis and treatment of meningeal leukemia.

Contraindications

Cytarabine Injection is contraindicated in those patients who are hypersensitive to the drug.

Warnings

(See boxed WARNING)

Cytarabine is a potent bone marrow suppressant. Therapy should be started cautiously in patients with pre-existing drug-induced bone marrow suppression. Patients receiving this drug must be under close medical supervision and, during induction therapy, should have leucocyte and platelet counts performed daily. Bone marrow examinations should be performed frequently after blasts have disappeared from the peripheral blood. Facilities should be available for management of complications, possibly fatal, of bone marrow suppression (infection resulting from granulocytopenia and other impaired body defenses, and hemorrhage secondary to thrombocytopenia). One case of anaphylaxis that resulted in acute cardiopulmonary arrest and required resuscitation has been reported. This occurred immediately after the intravenous administration of Cytarabine injection.

Severe and at times fatal CNS, GI and pulmonary toxicity (different from that seen with conventional therapy regimens of Cytarabine injection) has been reported following some experimental dose schedules for Cytarabine injection. These reactions include reversible corneal toxicity, and hemorrhagic conjunctivitis, which may be prevented or diminished by prophylaxis with a local corticosteroid eye drop; cerebral and cerebellar dysfunction, including personality changes, somnolence and coma, usually reversible; severe gastrointestinal ulceration, including pneumatosis cystoides intestinalis leading to peritonitis; sepsis and liver abscess; pulmonary edema, liver damage with increased hyperbilirubinemia; bowel necrosis; and necrotizing colitis. Rarely, severe skin rash, leading to desquamation has been reported. Complete alopecia is more commonly seen with experimental high dose therapy than with standard treatment programs using Cytarabine injection. If experimental high dose therapy is used, do not use a preparation containing benzyl alcohol.

Cases of cardiomyopathy with subsequent death have been reported following experimental high dose therapy with Cytarabine in combination with cyclophosphamide when used for bone marrow transplant preparation.

A syndrome of sudden respiratory distress, rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly has been reported following experimental high dose therapy with Cytarabine used for the treatment of relapsed leukemia from one institution in 16/72 patients. The outcome of this syndrome can be fatal.

Two patients with childhood acute myelogenous leukemia who received intrathecal and intravenous Cytarabine injection at conventional doses (in addition to a number of other concomitantly administered drugs) developed delayed progressive ascending paralysis resulting in death in one of the two patients.

Use in Pregnancy (Category D)

Cytarabine Injection can cause fetal harm when administered to a pregnant woman. Cytarabine causes abnormal cerebellar development in the neonatal hamster and is teratogenic to the rat fetus. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential should be advised to avoid becoming pregnant.

A review of the literature has shown 32 reported cases where Cytarabine injection was given during pregnancy, either alone or in combination with other cytotoxic agents:

Eighteen normal infants were delivered. Four of these had first trimester exposure. Five infants were premature or of low birth weight. Twelve of the 18 normal infants were followed up at ages ranging from six weeks to seven years, and showed no abnormalities. One apparently normal infant died at 90 days of gastroenteritis.

Two cases of congenital abnormalities have been reported, one with upper and lower distal limb defects, and the other with extremity and ear deformities. Both of these cases had first trimester exposure.

There were seven infants with various problems in the neonatal period, including pancytopenia, transient depression of WBC, hematocrit or platelets; electrolyte abnormalities; transient eosinophilia; and one case of increased lgM levels and hyperpyrexia possibly due to sepsis. Six of the seven infants were also premature. The child with pancytopenia died at 21 days of sepsis.

Therapeutic abortions were done in five cases. Four fetuses were grossly normal, but one had an enlarged spleen and another showed Trisomy C chromosome abnormality in the chorionic tissue.

Because of the potential for abnormalities with cytotoxic therapy, particularly during the first trimester, a patient who is or who may become pregnant while on Cytarabine should be apprised of the potential risk to the fetus and the advisability of pregnancy continuation. There is a definite, but considerably reduced risk if therapy is initiated during the second or third trimester. Although normal infants have been delivered to patients treated in all three trimesters of pregnancy, follow-up of such infants would be advisable.

Precautions

1. General Precautions

Patients receiving Cytarabine Injection must be monitored closely. Frequent platelet and leucocyte counts and bone marrow examinations are mandatory. Consider suspending or modifying therapy when drug-induced marrow depression has resulted in a platelet count under 50,000 or a polymorphonuclear granulocyte count under 1000/mm3. Counts of formed elements in the peripheral blood may continue to fall after the drug is stopped and reach lowest values after drug-free intervals of 12 to 24 days. When indicated, restart therapy when definite signs of marrow recovery appear (on successive bone marrow studies). Patients whose drug is withheld until “normal” peripheral blood values are attained may escape from control.

When large intravenous doses are given too quickly, patients are frequently nauseated and may vomit for several hours post-injection. This problem tends to be less severe when the drug is infused.

The human liver apparently detoxifies a substantial fraction of an administered dose. In particular, patients with renal or hepatic function impairment may have a higher likelihood of CNS toxicity after high-dose Cytarabine injection treatment. Use the drug with caution and possibly at reduced dose in patients whose liver or kidney function is poor.

Periodic checks of bone marrow, liver and kidney functions should be performed in patients receiving Cytarabine injection.

Like other cytotoxic drugs, Cytarabine Injection may induce hyperuricemia secondary to rapid lysis of neoplastic cells. The clinician should monitor the patient’s blood uric acid level and be prepared to use such supportive and pharmacologic measures as might be necessary to control this problem.

Acute pancreatitis has been reported to occur in a patient receiving Cytarabine Injection by continuous infusion and in patients being treated with Cytarabine Injection who have had prior treatment with L-asparaginase.

2. Information for patient

Not applicable.

3. Laboratory tests

See General Precautions.

4. Drug Interactions

Reversible decreases in steady-state plasma digoxin concentrations and renal glycoside excretion were observed in patients receiving beta-acetyldigoxin and chemotherapy regimens containing cyclophosphamide, vincristine and prednisone with or without Cytarabine injection or procarbazine.

Steady-state plasma digitoxin concentrations did not appear to change. Therefore, monitoring of plasma digoxin levels may be indicated in patients receiving similar combination chemotherapy regimens. The utilization of digitoxin for such patients may be considered as an alternative.

An in vitro interaction study between gentamicin and Cytarabine showed a Cytarabine related antagonism for the susceptibility of K. pneumoniae strains. This study suggests that in patients on Cytarabine being treated with gentamicin for a K. pneumoniae infection, the lack of a prompt therapeutic response may indicate the need for re-evaluation of antibacterial therapy.

Clinical evidence in one patient showed possible inhibition of fluorocytosine efficacy during therapy with Cytarabine injection. This may be due to potential competitive inhibition of its uptake.

5. Carcinogenesis, mutagenesis, impairment of fertility

Extensive chromosomal damage, including chromatoid breaks have been produced by Cytarabine and malignant transformation of rodent cells in culture has been reported.

6. Pregnancy

Pregnancy Category D. See WARNINGS.

7. Labor and delivery

Not applicable.

8. 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 Cytarabine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

9. Pediatric use

See INDICATIONS AND USAGE.

Adverse Reactions

Expected Reactions

Because Cytarabine is a bone marrow suppressant, anemia, leukopenia, thrombocytopenia, megaloblastosis and reduced reticulocytes can be expected as a result of administration with Cytarabine Injection. The severity of these reactions are dose and schedule dependent. Cellular changes in the morphology of bone marrow and peripheral smears can be expected.

Following 5-day constant infusions or acute injections of 50 mg/m2 to 600 mg/m2, white cell depression follows a biphasic course. Regardless of initial count, dosage level, or schedule, there is an initial fall starting the first 24 hours with a nadir at days 7-9. This is followed by a brief rise which peaks around the twelfth day. A second and deeper fall reaches nadir at days 15-24. Then there is a rapid rise to above baseline in the next 10 days. Platelet depression is noticeable at 5 days with a peak depression occurring between days 12-15. Thereupon, a rapid rise to above baseline occurs in the next 10 days.

Infectious Complications

Injection: Viral, bacterial, fungal, parasitic, or saprophytic infections, in any location in the body may be associated with the use of Cytarabine injection alone or in combination with other immunosuppressive agents following immunosuppressant doses that affect cellular or humoral immunity. These infections may be mild, but can be severe and at times fatal.

The Cytarabine (Ara-C) Syndrome

A Cytarabine syndrome has been described by Castleberry. It is characterized by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis and malaise. It usually occurs 6-12 hours following drug administration. Corticosteroids have been shown to be beneficial in treating or preventing this syndrome. If the symptoms of the syndrome are deemed treatable, corticosteroids should be contemplated as well as continuation of therapy with Cytarabine Injection.

Most Frequent Adverse Reactions

anorexia nausea vomiting diarrhea	oral and anal inflammation or ulceration hepatic dysfunction fever	rash thrombophlebitis bleeding (all sites)
Nausea and vomiting are most frequent following rapid intravenous injection.

Less Frequent Adverse Reactions

sepsis pneumonia cellulitis at injection site skin ulceration urinary retention renal dysfunction neuritis neural toxicity

sore throat esophageal ulceration esophagitis chest pain pericarditis bowel necrosis abdominal pain pancreatitis freckling jaundice

conjunctivitis (may occur with rash) dizziness alopecia anaphylaxis (see WARNINGS) allergic edema pruritis shortness of breath urticaria headache

Experimental Doses

Severe and at times fatal CNS, GI and pulmonary toxicity (different from that seen with conventional therapy regimens of Cytarabine injection) has been reported following some experimental dose schedules of Cytarabine injection. These reactions include reversible corneal toxicity and hemorrhagic conjunctivitis, which may be prevented or diminished by prophylaxis with a local corticosteroid eye drop; cerebral and cerebellar dysfunction, including personality changes, somnolence and coma, usually reversible; severe gastrointestinal ulceration, including pneumatosis cystoides intestinalis leading to peritonitis; sepsis and liver abscess; pulmonary edema, liver damage with increased hyperbilirubinemia; bowel necrosis; and necrotizing colitis. Rarely, severe skin rash, leading to desquamation has been reported. Complete alopecia is more commonly seen with experimental high dose therapy than with standard treatment programs using Cytarabine. If experimental high dose therapy is used, do not use a preparation containing benzyl alcohol.

Cases of cardiomyopathy with subsequent death have been reported following experimental high dose therapy with Cytarabine in combination with cyclophosphamide when used for bone marrow transplant preparation. This cardiac toxicity may be schedule dependent.

A syndrome of sudden respiratory distress, rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly has been reported following experimental high dose therapy with Cytarabine used for the treatment of relapsed leukemia from one institution in 16/72 patients. The outcome of this syndrome can be fatal.

Two patients with adult acute non-lymphocytic leukemia developed peripheral motor and sensory neuropathies after consolidation with high-dose Cytarabine, daunorubicin, and asparaginase. Patients treated with high-dose Cytarabine should be observed for neuropathy since dose schedule alterations may be needed to avoid irreversible neurologic disorders.

Ten patients treated with experimental intermediate doses of Cytarabine (1 g/m2) with and without other chemotherapeutic agents (meta-AMSA, daunorubicin, etoposide) at various dose regimes developed a diffuse interstitial pneumonitis without clear cause that may have been related to the Cytarabine.

Two cases of pancreatitis have been reported following experimental doses of Cytarabine injection and numerous other drugs. Cytarabine injection could have been the causative agent.

Overdosage

There is no antidote for overdosage of Cytarabine Injection. Doses of 4.5 g/m2 by intravenous infusion over 1 hour every 12 hours for 12 doses have caused an unacceptable increase in irreversible CNS toxicity and death.

Single doses as high as 3 g/m2 have been administered by rapid intravenous infusion without apparent toxicity.

Cytarabine Dosage and Administration

Cytarabine Injection is not active orally. The schedule and method of administration varies with the program of therapy to be used. Cytarabine Injection may be given by intravenous infusion or injection, subcutaneously, or intrathecally (preservative free preparation only).

Thrombophlebitis has occurred at the site of drug injection or infusion in some patients, and rarely patients have noted pain and inflammation at subcutaneous injection sites. In most instances, however, the drug has been well tolerated.

Patients can tolerate higher total doses when they receive the drug by rapid intravenous injection as compared with slow infusion. This phenomenon is related to the drug’s rapid inactivation and brief exposure of susceptible normal and neoplastic cells to significant levels after rapid injection. Normal and neoplastic cells seem to respond in somewhat parallel fashion to these different modes of administration and no clear-cut clinical advantage has been demonstrated for either.

In the induction therapy of acute non-lymphocytic leukemia, the usual Cytarabine dose in combination with other anti-cancer drugs is 100 mg/m2/day by continuous IV infusion (Days 1-7) or 100 mg/m2 IV every 12 hours (Days 1-7).

The literature should be consulted for the current recommendations for use in acute lymphocytic leukemia.

Intrathecal Use in Meningeal Leukemia

Cytarabine injection has been used intrathecally in acute leukemia in doses ranging from 5 mg/m2 to 75 mg/m2 of body surface area. The frequency of administration varied from once a day for 4 days to once every 4 days. The most frequently used dose was 30 mg/m2 every 4 days until cerebrospinal fluid findings were normal, followed by one additional treatment. The dosage schedule is usually governed by the type and severity of central nervous system manifestations and the response to previous therapy.

Cytarabine injection given intrathecally may cause systemic toxicity and careful monitoring of the hematopoietic system is indicated. Modification of other anti-leukemia therapy may be necessary. Major toxicity is rare. The most frequently reported reactions after intrathecal administration were nausea, vomiting and fever; these reactions are mild and self-limiting. Paraplegia has been reported. Necrotizing leukoencephalopathy occurred in 5 children; these patients had also been treated with intrathecal methotrexate and hydrocortisone, as well as by central nervous system radiation. Isolated neurotoxicity has been reported. Blindness occurred in two patients in remission whose treatment had consisted of combination systemic chemotherapy, prophylactic central nervous system radiation and intrathecal Cytarabine injection.

When Cytarabine injection is administered both intrathecally and intravenously within a few days, there is an increased risk of spinal cord toxicity, however, in serious life-threatening disease, concurrent use of intravenous and intrathecal Cytarabine Injection is left to the discretion of the treating physician.

Focal leukemic involvement of the central nervous system may not respond to intrathecal Cytarabine injection and may better be treated with radiotherapy.

Chemical Stability of Infusion Solutions

Chemical stability studies were performed by ultraviolet assay on Cytarabine Injection in infusion solutions. These studies showed that when Cytarabine Injection was added to Water for Injection, 5% Dextrose in Water or Sodium Chloride Injection, 94 to 96 percent of the Cytarabine was present after 192 hours storage at room temperature.

Parenteral drugs should be inspected visually for particulate matter and discoloration, prior to administration, whenever solution and container permit.

HANDLING AND DISPOSAL

Procedures for proper handling and disposal of anti-cancer drugs should be considered. Several guidelines on this subject have been published.1-7 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

How is Cytarabine Supplied

Cytarabine Injection is available as follows:

100 mg/5 mL in a single dose flip top vial (cool green cap) packaged in a carton of 5. NDC No.: 61703-305-38

2 g/20 mL in a single dose flip top vial (green cap) packaged individually. NDC No.: 61703-319-22

STORAGE CONDITIONS

Protect from light. Retain in carton until time of use.

Store the product at controlled room temperature 15° to 30°C (59° to 86°F).

REFERENCES

1. Recommendations for the Safe Handling of Parenteral Antinoeplastic Drugs, NIH Publications No. 83-2621. For sale by the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C.  20402.


2. AMA Council Report, Guidelines for Handling Parenteral Antineoplastics, JAMA, 1985; 2.53 (11): 1590-1592.


3. National Study Commission on Cytotoxic Exposure – Recommendations for Handling Cytotoxic Agents. Available from Louis P. Jeffrey, ScD., Chairman, National Study Commission on Cytotoxic Exposure, Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, Massachusetts 02115.


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


5. Jones RB, et al: Safe Handling of Chemotherapeutic Agents: A Report from the Mount Sinai  Medical  Center. CA-A Cancer Journal of Clinicians, 1983; (Sept/Oct) 258-263.


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


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

Hospira, Inc.

Lake Forest, IL 60045

Product of Australia

Revision August 2007

483176

432333

483178

Cytarabine  Cytarabine  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 61703-305 Route of Administration INTRAVENOUS, INTRATHECAL, SUBCUTANEOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Cytarabine (Cytarabine) Cytarabine 20 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE   WATER   HYDROCHLORIC ACID   SODIUM HYDROXIDE

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 61703-305-38 5 VIAL In 1 CARTON contains a VIAL, SINGLE-DOSE 1 5 mL In 1 VIAL, SINGLE-DOSE This package is contained within the CARTON (61703-305-38)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA071868	04/25/2011

Cytarabine  Cytarabine  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 61703-319 Route of Administration INTRAVENOUS, INTRATHECAL, SUBCUTANEOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Cytarabine (Cytarabine) Cytarabine 100 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength WATER   HYDROCHLORIC ACID   SODIUM HYDROXIDE

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 61703-319-22 1 VIAL In 1 CARTON contains a VIAL, SINGLE-DOSE 1 20 mL In 1 VIAL, SINGLE-DOSE This package is contained within the CARTON (61703-319-22)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA075383	04/25/2011

Labeler - Hospira Worldwide, Inc. (141588017)

Revised: 05/2011Hospira Worldwide, Inc.

More Cytarabine resources

• Cytarabine Use in Pregnancy & Breastfeeding
• Cytarabine Drug Interactions
• Cytarabine Support Group
• 0 Reviews for Cytarabine - Add your own review/rating

• Cytarabine Professional Patient Advice (Wolters Kluwer)


• Cytarabine MedFacts Consumer Leaflet (Wolters Kluwer)


• Cytarabine Monograph (AHFS DI)


• cytarabine Advanced Consumer (Micromedex) - Includes Dosage Information


• cytarabine Concise Consumer Information (Cerner Multum)

Compare Cytarabine with other medications

• Acute Myeloid Leukemia
• Acute Nonlymphocytic Leukemia
• Chronic Myelogenous Leukemia
• Leukemia
• Meningeal Leukemia
• Non-Hodgkin's Lymphoma

budesonide Nasal

bue-DES-oh-nide

Commonly used brand name(s)

In the U.S.

• Rhinocort


• Rhinocort Aqua

In Canada

• Gen-Budesonide Aq

Available Dosage Forms:

• Aerosol Powder


• Spray

Therapeutic Class: Anti-Inflammatory

Pharmacologic Class: Adrenal Glucocorticoid

Uses For budesonide

Budesonide nasal spray is used to treat an itchy or runny nose, sneezing, or other symptoms caused by hay fever (allergic rhinitis). It is a steroid (cortisone-like medicine) that works by preventing the inflammation that occurs with allergic reactions.

budesonide is available only with your doctor's prescription.

Before Using budesonide

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 budesonide, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to budesonide 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

Appropriate studies have not been performed on the relationship of age to the effects of budesonide nasal spray in children younger than 6 years of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of budesonide nasal spray in the elderly.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while 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. When you are taking budesonide, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using budesonide with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Boceprevir


• Bupropion


• Telaprevir

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

• Erythromycin


• Itraconazole


• Ketoconazole

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Cataracts, history of or


• Glaucoma, history of—Use with caution. May make these conditions worse.

• Chicken pox (includes recent exposure) or


• Herpes simplex infection of the eye or


• Infections (virus, bacteria, fungus, or parasite), any type and untreated or


• Measles (includes recent exposure) or


• Tuberculosis, active or history of—Can reduce the body's ability to fight off these infections.

• Injury to the nose, recent or


• Nose surgery, recent or


• Sores or ulcers in the nose, recent—budesonide may prevent proper healing of these conditions.

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

Proper Use of budesonide

Use budesonide only as directed by your doctor. Do not use more of it and do not use it more often than your doctor ordered. To do so may increase the amount that is absorbed from the nose and the chance of unwanted effects. Do not change your dose or stop using budesonide without checking with your doctor first.

budesonide comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

budesonide is only used in the nose. Do not get it in your eyes. If it does get in the eyes, rinse them with water right away and call your doctor.

In order for budesonide to help you, it must be used on a regular basis as ordered by your doctor. budesonide usually begins to work in about 2 days, but up to 2 weeks may pass before you feel its full effects.

Do not use budesonide for any other nose problem without checking with your doctor first.

To use the spray:

• Shake the bottle gently before each use.


• When you use the spray for the first time, you must prime the bottle. Pump the bottle 8 times or until a fine spray comes out.


• Gently blow your nose before using the spray. Insert the tip of the bottle into your nostril.


• Close the opposite nostril with a finger and lean your head slightly forward.


• Spray into your nostril and breathe gently inward. Lean your head backward for a few seconds.


• If a second dose is needed in the same nostril, lean the head slightly forward and repeat the same steps.


• Spray the opposite nostril using the same steps.


• Do not blow your nose for 15 minutes after using the spray.


• Wipe the tip of the bottle with a clean tissue and put the cap back on.


• If you do not use the bottle for 2 days, prime it again by releasing one spray.


• If you do not use the bottle for more than 14 days, clean the spray tip and prime it again by releasing two sprays.


• After you prime the bottle, there will only be 120 doses or sprays. Keep track of the number of sprays you use. Throw the bottle away after you use 120 sprays even if some liquid remains in the bottle.

Dosing

The dose of budesonide 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 budesonide. 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 nasal dosage form (spray):
  
  • For treatment of allergic rhinitis:
    
    • Adults, teenagers, and children 12 years of age and older—At first, one spray in each nostril once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 4 sprays in each nostril per day.
    
    
    • Children 6 to 11 years of age—At first, one spray in each nostril once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 2 sprays in each nostril per day.
    
    
    • Children younger than 6 years of age—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

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

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

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

After you prime the bottle, there will only be 120 doses or sprays. Keep track of the number of sprays you use. Throw the bottle away after you use 120 sprays even if some liquid remains in the bottle.

Precautions While Using budesonide

It is very important that your doctor check the progress of you or your child at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

If you or your child feel that your symptoms do not improve within a few days or if they become worse, check with your doctor.

budesonide may increase your risk of having some unwanted effects in the nose. Check with your doctor right away if you or your child have bloody mucus; sores inside the nose; unexplained nosebleeds; or a whistling sound when you breathe while you are using budesonide.

budesonide may cause thrush (a type of fungus infection) in the nose or throat. Tell your doctor right away if you or your child have white patches in the throat, or pain when you eat or swallow.

budesonide may cause a serious type of allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you or your child have a rash; itching; hoarseness; trouble breathing; trouble swallowing; or any swelling of your hands, face, or mouth while you are using budesonide.

You may get infections more easily while you are using budesonide. Avoid close contact with anyone who has chickenpox or measles if you have never had these infections. This is especially important for children. Tell your doctor right away if you think you have been exposed to chickenpox or measles.

Using too much of budesonide or using it for a long time may increase your risk of having adrenal gland problems. Talk to your doctor if you or your child have more than one of these symptoms while you are using budesonide: darkening of the skin; diarrhea; dizziness; fainting; loss of appetite; mental depression; nausea; skin rash; unusual tiredness or weakness; or weight loss.

budesonide may slow down a child's growth if it is used for a long time. Talk to your child's doctor if you think your child is not growing properly or if you have any questions about this.

Check with your doctor right away if blurred vision, difficulty in reading, or any other change in vision occurs during or after treatment. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

budesonide Side Effects

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

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

More common

• Bloody nose

Less common

• Body aches or pain


• congestion


• cough


• difficulty with breathing


• dryness or soreness of the throat


• fever


• hoarseness


• noisy breathing


• runny nose


• shortness of breath


• tender, swollen glands in the neck


• tightness in the chest


• trouble with swallowing


• voice changes


• wheezing

Incidence not known

• Backache


• blistering, crusting, irritation, itching, or reddening of the skin


• bloody mucus


• blurred vision


• cracked, dry, or scaly skin


• darkening of the skin


• decreased vision


• diarrhea


• difficulty with swallowing


• dizziness


• eye pain


• facial hair growth in females


• fainting


• fast, irregular, pounding, or racing heartbeat or pulse


• full or round face, neck, or trunk


• headache


• hives or welts


• increased thirst or urination


• irritability


• itching


• lack or slowing of normal growth in children


• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs


• loss of appetite


• loss of sexual desire or ability


• menstrual irregularities


• mental depression


• muscle wasting


• nausea or vomiting


• nosebleeds


• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue


• skin rash


• swelling


• tearing


• unusual tiredness or weakness

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:

Incidence not known

• Burning, itching, swollen, or sore throat


• loss of sense of smell

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.

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

More budesonide Nasal resources

• Budesonide Nasal Use in Pregnancy & Breastfeeding
• Budesonide Nasal Drug Interactions
• Budesonide Nasal Support Group
• 3 Reviews for Budesonide Nasal - Add your own review/rating

• Rhinocort Aqua Prescribing Information (FDA)


• Rhinocort Aqua eent Monograph (AHFS DI)


• Rhinocort Aqua Spray MedFacts Consumer Leaflet (Wolters Kluwer)


• Rhinocort Aqua Consumer Overview

Compare budesonide Nasal with other medications

• Hay Fever

Cytoxan Tablets

Pronunciation: SYE-kloe-FOS-fa-mide
Generic Name: Cyclophosphamide
Brand Name: Cytoxan

Cytoxan is used for:

Treating certain types of the following cancers: lymphoma, multiple myeloma, leukemia, mycosis fungoides, neuroblastoma, ovarian cancer, eye cancer, and breast cancer. It is usually used in combination with other medicines. It may also be used to treat certain kidney problems (nephrotic syndrome) in children or for other conditions as determined by your doctor.

Cytoxan is an antineoplastic. It works by stopping or slowing the growth or spread of certain cancer cells.

Do NOT use Cytoxan if:

• you are allergic to any ingredient in Cytoxan or to other similar medicines


• you have severely suppressed bone marrow function


• you are in the first 3 months of pregnancy or you are breast-feeding


• you are taking a tumor necrosis factor (TNF)-blocking medicine (eg, etanercept)

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

Before using Cytoxan:

Some medical conditions may interact with Cytoxan. 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 an infection, chickenpox, a suppressed immune system, bone marrow suppression or other bone marrow problems, low levels of white blood cells or platelets, or liver or kidney problems


• if you are receiving or have received cytotoxic therapy or x-ray or radiation therapy


• if you have had an adrenal gland removed (adrenalectomy)


• if you are receiving or have received chemotherapy or radiation therapy

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

• TNF-blocking medicines (eg, etanercept) because the risk of certain types of cancer may be increased


• Doxorubicin or trastuzumab because the risk of heart-related side effects and toxicity may be increased


• Imidazoles (eg, ketoconazole) or phenobarbital because they may increase the risk of Cytoxan's side effects


• Ondansetron because it may decrease Cytoxan's effectiveness


• Succinylcholine because its actions and the risk of its side effects may be increased by Cytoxan


• Indomethacin because the risk of its side effects may be increased by Cytoxan


• Digoxin because its effectiveness may be decreased by Cytoxan

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

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

• Take Cytoxan by mouth with or without food. Check with your doctor about how you should take Cytoxan with regard to food.


• If you experience nausea, vomiting, diarrhea, or loss of appetite, contact your doctor to discuss ways to reduce these side effects.


• Drinking extra fluids and emptying your bladder regularly while you are taking Cytoxan is recommended. Check with your doctor for instructions.


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

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

Important safety information:

• Cytoxan may reduce the number of clot-forming cells (platelets) in your blood. Avoid activities that may cause bruising or injury. Tell your doctor if you have unusual bruising or bleeding. Tell your doctor if you have dark, tarry, or bloody stools.


• Cytoxan 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.


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


• Cytoxan may decrease your body's ability to heal wounds. Discuss any questions or concerns with your doctor.


• Cytoxan may increase your chance of developing a second cancer, sometimes even years after stopping treatment with Cytoxan. Discuss any questions or concerns with your doctor.


• Cytoxan may cause infertility that is sometimes permanent. Discuss any questions or concerns with your doctor.


• Talk with your doctor before you receive any vaccines while you are using Cytoxan.


• The use of birth control is recommended while using Cytoxan.


• Lab tests, including complete blood cell counts, platelet counts, and urine tests, may be performed while you use Cytoxan. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Cytoxan with caution in the ELDERLY; they may be more sensitive to its effects.


• PREGNANCY and BREAST-FEEDING: Cytoxan has been shown to cause harm to the fetus. Do not become pregnant while you are using it. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of using Cytoxan while you are pregnant. Cytoxan is found in breast milk. Do not breast-feed while taking Cytoxan.

Possible side effects of Cytoxan:

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:

Appetite loss; absence of menstrual periods; color change in skin; diarrhea; general unwell feeling; hair loss; nausea; skin rash; stomach discomfort or pain; texture change in nails; vomiting; weakness.

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); blood in urine; bloody or black tarry stools; chest pain; chills; fever; hallucinations; increased or decreased urination; infection; lower back or abdominal pain; painful urination; persistent cough; pneumonia; red, swollen, or blistered skin; seizures; severe stomach pain; shortness of breath; sore throat; sores in the mouth; swelling of the hands or feet; unusual bruising or bleeding; unusual or severe tiredness or weakness; 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: Cytoxan 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 back or stomach pain; fast heartbeat; red or bloody urine; weakness.

Proper storage of Cytoxan:

Store Cytoxan at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Cytoxan out of the reach of children and away from pets.

General information:

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


• Cytoxan 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 Cytoxan. 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 Cytoxan resources

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

Compare Cytoxan with other medications

• Acute Lymphocytic Leukemia
• Acute Nonlymphocytic Leukemia
• Bladder Cancer
• Brain Tumor
• Breast Cancer
• Bullous Pemphigoid
• Cancer
• Cervical Cancer
• Chronic Lymphocytic Leukemia
• Chronic Myelogenous Leukemia
• Cogan's Syndrome
• Dermatomyositis
• Endometrial Cancer
• Ewing's Sarcoma
• Histiocytosis
• Hodgkin's Lymphoma
• IgA Nephropathy
• Multiple Myeloma
• Multiple Sclerosis
• Mycosis Fungoides
• Nephrotic Syndrome
• Neuroblastoma
• Non-Hodgkin's Lymphoma
• Non-Small Cell Lung Cancer
• Organ Transplant, Rejection Prophylaxis
• Osteosarcoma
• Ovarian Cancer
• Pemphigoid
• Pemphigus
• Prostate Cancer
• Rheumatoid Arthritis
• Small Cell Lung Cancer
• Systemic Lupus Erythematosus
• Systemic Sclerosis
• Testicular Cancer
• Wegener's Granulomatosus
• Wilms' Tumor

Pretir

Pretir may be available in the countries listed below.

Ingredient matches for Pretir

Azithromycin

Azithromycin is reported as an ingredient of Pretir in the following countries:

• Colombia

International Drug Name Search

Cytovene

Generic Name: Ganciclovir Sodium
Class: Nucleosides and Nucleotides
VA Class: AM800
Chemical Name: 2-Amino-1,9-dihydro-9-[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]-6H-purin-6-one sodium salt
CAS Number: 84245-13-6

• 
  

  Clinical toxicity of oral and IV ganciclovir includes granulocytopenia, anemia, and thrombocytopenia.¹

  
  


• 
  

  In animal studies, ganciclovir was carcinogenic, teratogenic, and caused aspermatogenesis.¹

  
  


• 
  

  The only FDA-approved indications for IV ganciclovir are treatment of CMV retinitis in immunocompromised patients and prevention of CMV disease in transplant recipients at risk.¹

  
  


• 
  

  The only FDA-approved indications for oral ganciclovir are prevention of CMV disease in patients with advanced HIV infection, maintenance treatment of CMV retinitis in immunocompromised patients, and prevention of CMV disease in solid organ transplant recipients.¹

  
  


• 
  

  Because oral ganciclovir is associated with a risk of more rapid progression of CMV retinitis, it should be used as maintenance treatment only in those for whom this risk is balanced by the benefits associated with avoiding daily IV infusions.¹

  
  

Introduction

Antiviral; purine nucleoside analog of guanine.^{1 2 3 8 9 10 11 12}

Uses for Cytovene

Cytomegalovirus (CMV) Infections

Treatment of CMV retinitis in immunocompromised patients, including HIV-infected patients.^{1 5 11 21 28 100 103 104 105 117 118 126 127 139 164 174 175 187 207 225 243 268} ganciclovir is not curative; stabilization or improvement of ocular manifestations may occur, but progression of retinitis is possible during or following treatment.^{1 4 5 8 9 11 13 21 27 28 63 65 77 94 100 120 126 128 139 167 168}

Drugs of choice for initial induction and maintenance therapy of CMV retinitis are IV ganciclovir, IV foscarnet, IV cidofovir, oral valganciclovir, or intravitreal fomivirsen.^{268 319 322 331} A regimen of both ganciclovir and foscarnet is used for treatment of CMV retinitis in patients who have relapsed following monotherapy with either drug.^{268 319 322 331}

Primary prevention (primary prophylaxis) of CMV disease in HIV-infected patients at risk for the disease, including adults, adolescents, and children who are positive for CMV antibody and have CD4⁺ T-cell counts <50/mm³.^{317 320 321 322} USPHS/IDSA recommends oral ganciclovir as the drug of choice for primary CMV prophylaxis in these patients.³¹⁷

Long-term suppressive or maintenance therapy (secondary prophylaxis) of recurrent CMV disease in HIV-infected adults, adolescents, or children.³¹⁷ USPHS/IDSA recommends IV ganciclovir or IV foscarnet as drugs of choice for such prophylaxis.³¹⁷

Prevention of CMV disease in solid organ transplant recipients and bone marrow transplant (BMT) recipients at risk for the disease.^{1 268 271 283 284 286 287 304 305 307 313 324}

Has been used in immunocompromised patients for parenteral treatment of extraocular CMV infections, including GI infections†,^{3 4 5 6 8 11 16 20 21 26 68 69 70 76 77 92 102 108 110 122 134 146 166 193 194 207} pneumonitis†,^{3 4 5 8 10 11 15 16 17 18 19 20 21 33 43 64 72 73 74 106 107 108 109 110 111 121 122 137 140 145 146 147 149 151 154 159 180 188 193 198 199 200 201 202 207 219 220 225} nervous system†,^{4 5 8 11 21 110 165 207 231} hepatobiliary†,^{4 5 8 20 21 68 106 108 146 166 219} or cardiac†^{110 171 220} CMV infections.^{3 5 8 15 19 108 140} Safety and efficacy have not been established for extraocular CMV infections;^{1 2} use in these infections should be limited to severe and/or potentially life-threatening infections when potential benefits outweigh risks.^{3 6 15 16 72 106 107 110 134 146 219 262}

Safety and efficacy not established for treatment of congenital or neonatal CMV disease or for treatment of CMV infections in immunocompetent patients.¹

Cytovene Dosage and Administration

General

• 
  

  Frequent monitoring of neutrophil and platelet counts is necessary during ganciclovir induction and maintenance therapy.^{1 2 20 191}

  
  


• 
  

  Dosage adjustment and/or interruption of ganciclovir therapy may be necessary if hematologic abnormalities occur.^{1 2}

  
  


• 
  

  Ganciclovir should be withheld if the ANC declines to <500/mm³ or the platelet count declines to <25,000/mm³ and should not be resumed until there is evidence of bone marrow recovery.^{1 2}

  
  

Administration

Administer orally or by slow IV infusion.^{1 2}

Do not administer by rapid IV infusion or direct IV injection since potentially toxic plasma ganciclovir concentrations may result.^{1 2} In addition, do not administer by IM or sub-Q injection.^{1 2}

Can be administered via a commercially available intravitreal implant for treatment of CMV retinitis.^{323 340} Although ganciclovir has been administered by intravitreal injection† for the treatment of ocular infections,^{4 5 8 67 84 117 129 135 170 209} safety and efficacy of intravitreal injection of solutions made from the powder for IV infusion have not been established.^{4 5 8 67 170}

Oral Administration

Administer orally with food.¹

Oral ganciclovir should be used only for prevention of CMV disease in HIV-infected patients or transplant recipients at risk for the disease or for maintenance treatment of CMV retinitis in patients in whom the disease is stable following initial IV induction therapy.¹

IV Infusion

For solution and drug compatibility information see Compatibility under Stability.

Handle the powder and reconstituted and diluted solutions cautiously because of the high pH of the solutions and because of the mutagenic and/or carcinogenic potential of the drug.^{1 2} Use protective equipment (e.g., latex gloves, protective eyewear).^{1 2}

Since ganciclovir shares some of the properties of cytotoxic drugs, consider consulting specialized references for procedures for proper handling and disposal of antineoplastics, although there is no general agreement that all of the procedures recommended in such guidelines are necessary or appropriate.^{1 2}

Because of the high pH of ganciclovir solutions, a vein with adequate blood flow should be used to allow for rapid dilution and distribution of the drug, which may minimize risk of phlebitis.^{1 2}

Reconstitution and Dilution

For intermittent IV infusion, reconstitute 500-mg vial by adding 10 mL of sterile water for injection to provide a solution containing 50 mg/mL.^{1 2} Bacteriostatic water for injection containing parabens should not be used.^{1 2} Shake vial well to ensure complete dissolution of the drug.^{1 2}

The appropriate dose of reconstituted solution should then be withdrawn from the vial and diluted in 50–250 (usually 100) mL of a compatible IV infusion solution.^{1 2 8} For use in fluid-restricted patients, the appropriate dose of reconstituted solution may be diluted to a concentration ≤10 mg/mL; use of more concentrated solutions is not recommended.^{1 2 8 191}

Rate of Administration

Administer by slow IV infusion over 1 hour, either via a large peripheral or central vein,^{4 190} at a constant rate of administration.^{1 2}

For highly concentrated solutions (e.g., 5–10 mg/mL), a controlled-infusion device (e.g., pump) is recommended.^{8 262}

Dosage

Available as ganciclovir and ganciclovir sodium; dosage expressed in terms of ganciclovir.^{1 2}

Because the risk of toxicity may be increased with higher doses and/or more rapid infusion,^{1 2} recommended doses, frequencies of administration, and rate of IV infusion should not be exceeded.^{1 2}

Pediatric Patients

Cytomegalovirus (CMV) Infections

Treatment of CMV Retinitis

Oral

Maintenance therapy in children >3 months of age†: after an initial IV induction regimen, 1 g 3 times daily.^{1 191} Alternatively, 500 mg 6 times daily (every 3 hours while awake).^{1 191}

IV

Initial induction therapy in children >3 months of age†: 5 mg/kg every 12 hours for 14–21 days.^{1 191}

Maintenance treatment in children >3 months of age†: 5 mg/kg once daily.^{1 2 5 20 191 216 268} Alternatively, 6 mg/kg once daily 5 days weekly.^{1 2 71 106 191 262 268}

Primary Prevention (Primary Prophylaxis) of CMV in HIV-infected Children and Adolescents

Oral

Infants and children†: 30 mg/kg 3 times daily.³¹⁷

Adolescents: 1 g 3 times daily.³¹⁷

Prevention of Recurrence (Secondary Prophylaxis) of CMV in HIV-infected Children and Adolescents

Oral

1 g 3 times daily.³¹⁷ Initiate secondary prophylaxis after initial induction treatment.³¹⁷

IV

Infants and children†: 5 mg/kg daily.³¹⁷

Adolescents: 5–6 mg/kg once daily 5–7 days each week.³¹⁷

Consideration can be given to discontinuing secondary CMV prophylaxis in adolescents with sustained (e.g., for ≥6 months) increase in CD4⁺ T-cell counts to >100–150/mm³ in response to potent antiretroviral therapy.³¹⁷ This decision should be made in consultation with an ophthalmologist and factors such as the magnitude and duration of CD4⁺ T-cell increase, anatomic location of the retinal lesion, vision in the contralateral eye, and feasibility of regular ophthalmic monitoring should be considered.³¹⁷ Relapse of CMV retinitis could occur following discontinuance of secondary prophylaxis, especially in those whose CD4⁺ T-cell count decreases to <50/mm³; relapse has been reported rarely in those with CD4⁺ T-cell counts >100/mm³.³¹⁷

Reinitiate secondary CMV prophylaxis if CD4⁺ T-cell count decreases to <100–150/mm³.³¹⁷

Adults

Cytomegalovirus (CMV) Infections

Treatment of CMV Retinitis

Oral

Maintenance therapy after an initial IV induction regimen: 1 g 3 times daily.¹ Alternatively, 500 mg 6 times daily (every 3 hours while awake).¹

IV

Initial induction therapy: 5 mg/kg every 12 hours for 14–21 days.^{1 191}

Maintenance therapy: 5 mg/kg once daily.^{1 2 5 20 191 216 268} Alternatively, 6 mg/kg once daily 5 days weekly.^{1 2 71 106 191 262 268}

Primary Prevention (Primary Prophylaxis) of CMV in HIV-infected Adults

Oral

1 g 3 times daily.^{1 317}

Prevention of Recurrence (Secondary Prophylaxis) of CMV in HIV-infected Adults

Oral

1 g 3 times daily.³¹⁷ Initiate secondary prophylaxis after initial induction treatment.³¹⁷

IV

5–6 mg/kg once daily 5–7 days each week.³¹⁷

Consideration can be given to discontinuing secondary CMV prophylaxis in adults with sustained (e.g., for ≥6 months) increase in CD4⁺ T-cell counts to >100–150/mm³ in response to potent antiretroviral therapy.³¹⁷ This decision should be made in consultation with an ophthalmologist and factors such as the magnitude and duration of CD4⁺ T-cell increase, anatomic location of the retinal lesion, vision in the contralateral eye, and feasibility of regular ophthalmic monitoring should be considered.³¹⁷ Relapse of CMV retinitis could occur following discontinuance of secondary prophylaxis, especially in those whose CD4⁺ T-cell count decreases to <50/mm³; relapse has been reported rarely in those with CD4⁺ T-cell counts >100/mm³.³¹⁷

Reinitiate secondary CMV prophylaxis if CD4⁺ T-cell count decreases to <100–150/mm³.³¹⁷

Prevention of CMV Disease in Transplant Recipients

Oral

1 g 3 times daily.¹

IV

Initially, 5 mg/kg every 12 hours for 7–14 days, then 5 mg/kg once daily 7 days per week or 6 mg/kg once daily 5 days per week.¹

Duration of ganciclovir maintenance in organ transplant recipients depends on several factors including the duration and degree of immunosuppression.^{1 283 302 303} Bone marrow allograft recipients have received IV ganciclovir for up to 100–120 days following transplantation.^{1 271 284} In cardiac allograft recipients, ganciclovir should be continued for >28 days in patients to prevent late development of CMV disease.^{1 283} Liver transplant recipients have received oral ganciclovir for up to 98 days following transplantation.^{1 325}

Special Populations

Renal Impairment

In patients with impaired renal function, doses and/or frequency of administration of oral or IV ganciclovir must be modified in response to the degree of impairment.^{1 2 5 6 9 11 28 33 191 346} Dosage should be based on the patient’s measured or estimated Cl_cr.^{1 2}

IV Dosage for Adults with Renal Impairment1

Clcr (mL/min)	Induction Dosage	Maintenance Dosage
50–69	2.5 mg/kg every 12 h	2.5 mg/kg every 24 h
25–49	2.5 mg/kg every 24 h	1.25 mg/kg every 24 h
10–24	1.25 mg/kg every 24 h	0.625 mg/kg every 24
<10	1.25 mg/kg 3 times weekly, following hemodialysis	0.625 mg/kg 3 times weekly, following hemodialysis

Oral Dosage for Adults with Renal Impairment1

Clcr (mL/min)	Dosage
50–69	1.5 g once daily or 500 mg 3 times daily
25–49	1 g once daily or 500 mg 2 times daily
10–24	500 mg once daily
<10	500 mg 3 times weekly, following hemodialysis

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function.^{1 2} (See Renal Impairment under Dosage and Administration.)

Cautions for Cytovene

Contraindications

• 
  

  Known hypersensitivity to ganciclovir or acyclovir.^{1 2}

  
  

Warnings/Precautions

Warnings

Hematologic Effects

Hematologic toxicity, principally neutropenia (ANC <1000/mm³) and/or thrombocytopenia (platelet count <50,000/mm³) frequently occurs.^{1 2 3 4 8 11 21 33 75 109 110 122 133 149 172 215 248 264 265} Anemia also reported.¹

Neutropenia usually develops early in treatment (e.g., during the first or second week of induction therapy),^{1 2 3 5 20 23 74 122} but can occur at any time.^{1 2 5 20 23 74}

In most cases, interruption of ganciclovir therapy^{1 2 3 4 8 23 74 92 122 149 190 248} or a decrease in dosage^{2 4 6 8 140 149 190 248} will result in increased neutrophil counts, usually evident within 3–7 days; however, prolonged or irreversible neutropenia has occurred.^{1 2 3 4 74 92 122 174} Bacterial or fungal sepsis and subsequent death have been reported occasionally in patients with ganciclovir-induced neutropenia.^{1 2 3 4 74 122 174} In addition, neutropenia has recurred following reinitiation of ganciclovir therapy,^{1 2 3 33} occasionally even at reduced dosage.³

CBCs should be monitored frequently.^{1 2 20 191 279} Neutrophil and platelet counts should be performed several times weekly (every other day or 2 or 3 times weekly) during IV induction therapy and at least weekly thereafter during maintenance therapy.^{1 2 279} More frequent monitoring is recommended for patients who have previously experienced leukopenia with ganciclovir or another nucleoside analog or in whom neutrophil counts are <1000/mm³ prior to initiating therapy with the drug.^{1 2} Manufacturer suggests that daily monitoring of neutrophil counts be considered in such patients;² others suggest that less frequent monitoring (e.g., twice weekly) may be sufficient during maintenance therapy.²⁶² Manufacturer also recommended that neutrophil and platelet counts be monitored daily in patients undergoing hemodialysis.^{1 2}

If neutropenia and/or thrombocytopenia occur, dosage adjustment and/or interruption of ganciclovir therapy may be necessary.^{1 2 3 4 5 6 8 100 102 104 105 106 122 140 149 164 189 190 191 248}

Do not use if ANC is <500/mm³ or if platelet count is <25,000/mm³.¹

Use with caution in patients with preexisting cytopenias or a history of cytopenic reactions to other drugs, chemicals, or radiation therapy.^{1 2}

Mutagenic, Carcinogenic, and Teratogenic Potential

Ganciclovir has mutagenic and teratogenic potential that should be considered when weighing the benefits and risks of therapy.¹

Women of childbearing potential should use effective contraception during treatment.¹ In addition, men should practice barrier contraception during and for ≥90 days after treatment.¹

Potential carcinogen in humans.¹

Effects on Fertility

Animal studies indicate ganciclovir causes inhibition of spermatogenesis and subsequent infertility; effects were reversible at lower doses and irreversible at higher doses.¹ Suppression of fertility in female animals also noted.¹

Human data not available; possibility that ganciclovir at recommended doses may cause temporary or permanent inhibition of spermatogenesis.¹

General Precautions

Local Reactions

Initially reconstituted ganciclovir solutions have a high pH (pH 11).¹ Despite further dilution in IV fluids, phlebitis and/or pain may occur at site of IV infusion.¹

To avoid local irritation, care must be taken to infuse only into veins with adequate blood flow to permit rapid dilution and distribution of the drug.¹

Sodium Content

Ganciclovir sodium contains approximately 4 mEq of sodium per gram of ganciclovir.^{1 2 191}

Specific Populations

Pregnancy

Category C.¹ (See Mutagenic, Carcinogenic, and Teratogenic Potential under Cautions.)

Lactation

Distributed into milk in animals;^{1 3} not known whether distributed into milk in humans.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy of oral or IV ganciclovir not established in children.¹

Only limited experience with IV ganciclovir in children younger than 12 years of age.^{1 2 157 217} Safety and efficacy in treatment of congenital or neonatal CMV infections, including retinitis, not established.^{1 2}

Because of the drug’s potential for long-term carcinogenic and adverse reproductive effects, manufacturer warns that oral or IV ganciclovir should be used in children with extreme caution and only when potential benefits outweigh possible risks.^{1 2}

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.¹

Renal Impairment

Use with caution in patients with impaired renal function.¹

Dosage adjustments necessary based on degree of renal impairment.¹

Common Adverse Effects

Hematologic effects (neutropenia, thrombocytopenia, anemia);^{1 2 5 75 131 172 174} nervous system effects (headache, confusion);^{1 2 3 8} injection site reactions (inflammation, phlebitis, pain.^{1 2 21 122 133 215}

Interactions for Cytovene

Nephrotoxic Drugs

Possible increased risk of adverse effects; use concomitantly with caution and closely monitor renal function.¹

Specific Drugs

Drug	Interaction	Comments
Amphotericin B	Possible additive toxicity, including nephrotoxicity1	Use concomitantly only if potential benefits outweigh risks.1 Consider risk of nephrotoxicity in renal transplant patients.1
Antineoplastic agents (adriamycin, vinblastine, vincristine)	Possible additive toxicity1	Use concomitantly only if potential benefits outweigh risks1
Co-trimoxazole	Possible additive toxicity1	Use concomitantly only if potential benefits outweigh risks1
Dapsone	Possible additive toxicity1	Use concomitantly only if potential benefits outweigh risks1
Didanosine	Increased AUC of didanosine; no effect on ganciclovir pharmacokinetics1 347 b	Appropriate dosages for concomitant use with respect to safety and efficacy not established.b If used concomitantly, monitor closely for didanosine toxicity.347
Flucytosine	Possible additive toxicity1	Use concomitantly only if potential benefits outweigh risks1
Foscarnet	In vitro evidence of additive or synergistic antiviral activity against CMV and HSV-2274 275 276 277 278
Imipenem	Seizures reported with concomitant use1 2 3 258	Use concomitantly only when potential benefits outweigh possible risks1 2 258
Immunosuppressive agents (azathioprine, corticosteroids, cyclosporine)	Possible increased risk of bone marrow suppression or increased risk of nephrotoxicity. No effect on cyclosporine clearance.15 19 140 188 193 202 219 262	Consider need for decreased dosage or temporary withdrawal of the immunosuppressive agent15 19 140 188 193 202 219 262
Interferons	In vitro evidence of synergistic antiviral effects against CMV, HSV-1 or -2, and varicella-zoster virus with interferons alfa and beta and, to a lesser extent, interferon gamma180 181 182 183 184 221
Pentamidine	Possible additive toxicity1	Use concomitantly only if potential benefits outweigh risks1
Probenecid	Possible increase in AUC and decrease in renal clearance of ganciclovir 1
Zidovudine	Possible pharmacokinetic interaction.1 Increased risk of hematologic toxicity.1 2 83 84 295	Concomitant use not recommended1 18 83 84 87 96 126 129 133 135 170 187 191 293 295

Cytovene Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from GI tract;^{3 4 8 26 58 235} peak plasma concentrations attained within 1 hour after a dose.⁵⁸

Absolute bioavailability of oral ganciclovir is only 5 or 6–9% under fasting or nonfasting conditions, respectively.¹

Distribution

Extent

Distribution into human body tissues and fluids has not been fully elucidated.^{5 9 64 262} Autopsy findings in patients who received IV ganciclovir suggest that the drug concentrates in the kidney, with substantially lower concentrations occurring in lung, liver, brain, and testes.^{5 9 64}

Appears to have good ocular distribution following IV administration;^{2 5 93 104 117} distributed into aqueous and vitreous humor.^{3 104}

Distributed into CSF following IV administration.^{1 2 3 4 5 9 28 59 64 68}

Crosses the placenta in animals.³ Distributed into milk in animals;^{1 3} not known whether distributed into milk in humans.¹

Plasma Protein Binding

1–2%.¹

Elimination

Metabolism

With the exception of intracellular phosphorylation of the drug, ganciclovir does not appear to be metabolized appreciably in humans.^{1 2 4 5 11 28 59 61 64 124}

Elimination Route

Following oral administration, 86% of the dose is recovered in feces and 5% is recovered in urine.¹

Following IV administration, approximately 90–99% of the dose is excreted unchanged in urine.^{1 2 3 4 5 11 28 59 61 64 124} Renal excretion appears to occur principally via glomerular filtration,^{1 2 3 5 11 59 124} although limited renal tubular secretion also may occur.^{1 2 5 59}

Removed by hemodialysis.^{1 2 3 5 60 108 124 151}

Half-life

In adults with normal renal function: half-life in the initial distribution phase averages 0.23–0.76 hours and half-life in the terminal elimination phase averages 2.53–3.6 hours.^{1 2 3 4 5 8 9 11 59 61 64 124 132 205} Half-life following oral administration is 4.8 hours.¹

Special Populations

Plasma concentrations may be higher and elimination half-life prolonged in patients with impaired renal function.^{1 2 3 5}