Megefel may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Megestrol 17α-acetate (a derivative of Megestrol) is reported as an ingredient of Megefel in the following countries:
International Drug Name Search
Generic Name: levobunolol ophthalmic (lee voe BYOO noe lole)
Brand Names: Akbeta, Betagan, Levobunolol
Levobunolol is a beta-blocker that reduces pressure inside the eye.
Levobunolol ophthalmic may also be used for other purposes not listed in this medication guide.
Before using this medication, tell your doctor if you have breathing problems such as bronchitis or emphysema, a history of heart disease or congestive heart failure, diabetes, history of stroke, blood clot, or circulation problems, a thyroid disorder, or a muscle disorder such as myasthenia gravis.
Levobunolol ophthalmic is sometimes given together with other eye medications. Do not use any other eye medication unless your doctor has prescribed it for you. If you use another eye medication, use it at least 10 minutes before or after using levobunolol ophthalmic. Do not use the medications at the same time.
asthma, or severe chronic obstructive pulmonary disease (COPD);
slow heartbeats; or
a heart condition called "AV block."
If you have any of these other conditions, you may need a dose adjustment or special tests to safely use this medication:
breathing problems such as bronchitis or emphysema;
a history of heart disease or congestive heart failure;
diabetes;
history of stroke, blood clot, or circulation problems;
a thyroid disorder; or
a muscle disorder such as myasthenia gravis.
Use levobunolol ophthalmic exactly as it was prescribed for you. Do not use the medication in larger amounts, or use it for longer than recommended by your doctor. Follow the instructions on your prescription label.
To apply the eye drops:
Tilt your head back slightly and pull down your lower eyelid. Hold the dropper above the eye with the dropper tip down. Look up and away from the dropper as you squeeze out a drop, then close your eye.
Gently press your finger to the inside corner of the eye (near your nose) for about 1 minute to keep the liquid from draining into your tear duct. If you use more than one drop in the same eye, wait about 5 minutes before putting in the next drop.
Do not allow the dropper tip to touch any surface, including the eyes or hands. If the dropper becomes contaminated it could cause an infection in your eye, which can lead to vision loss or serious damage to the eye.
Do not use the eye drops if the liquid has changed colors or has particles in it. Call your doctor for a new prescription.
Use the medication as soon as you remember. If it is almost time for the next dose, skip the missed dose and use the medicine at the next regularly scheduled time. Do not use extra medicine to make up the missed dose.
Overdose symptoms may include slow heart rate, feeling short of breath, swelling, rapid weight gain, or fainting.
Levobunolol ophthalmic is sometimes given together with other eye medications. Do not use any other eye medication unless your doctor has prescribed it for you. If you use another eye medication, use it at least 10 minutes before or after using levobunolol ophthalmic. Do not use the medications at the same time.
severe swelling, itching, burning, redness, pain, or discomfort in or around your eye;
drainage, crusting, or oozing of your eyes or eyelids;
bronchospasm (wheezing, chest tightness, trouble breathing);
slow heart rate, weak pulse, fainting, slow breathing (breathing may stop);
feeling short of breath, even with mild exertion;
swelling, rapid weight gain; or
severe blistering, peeling, and red skin rash.
Less serious side effects may include:
mild burning, stinging, itching, or discomfort of your eyes;
blurred vision;
mildly swollen or puffy eyes;
headache, dizziness, spinning sensation;
depression, confusion, tired feeling;
muscle weakness;
mild skin rash or itching; or
nausea, diarrhea.
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.
Before using levobunolol ophthalmic, tell your doctor if you are using any of the following drugs:
digoxin (digitalis, Lanoxin);
reserpine;
insulin or diabetes medications you take by mouth;
any other beta-blocker such as atenolol (Tenormin), bisoprolol (Zebeta), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), timolol (Blocadren), and others;
a calcium channel blocker such as amlodipine (Norvasc), diltiazem (Tiazac, Cartia, Cardizem), felodipine (Plendil), nifedipine (Nifedical, Procardia, Adalat), verapamil (Calan, Covera, Isoptin, Verelan); or
medicines to treat psychiatric disorders, such as chlorpromazine (Thorazine), haloperidol (Haldol), mesoridazine (Serentil), or thioridazine (Mellaril).
This list is not complete and there may be other drugs that can interact with levobunolol ophthalmic. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.
See also: Betagan side effects (in more detail)
Viscoteina may be available in the countries listed below.
Carbocisteine is reported as an ingredient of Viscoteina in the following countries:
International Drug Name Search
Generic Name: rho(d) immune globulin (Injection route, Intramuscular route, Intravenous route)
roe-dee i-MUNE GLOB-ue-lin
Intravascular hemolysis (IVH) leading to death has been reported in patients treated for immune thrombocytopenic purpura (ITP) with Rho(D) immune globulin. IVH can lead to clinically compromising anemia and multi-system organ failure, including acute respiratory distress syndrome (ARDS), acute renal insufficiency, renal failure, and disseminated intravascular coagulation (DIC). Alert patients and closely monitor for the signs and symptoms of IVH in a health care setting for at least eight hours after administration for ITP. Perform a dipstick urinalysis at baseline, 2 hours, 4 hours after administration, and prior to the end of the monitoring period. If signs and/or symptoms of IVH are present or suspected, post-treatment laboratory tests should be performed, including plasma hemoglobin, haptoglobin, LDH, and plasma bilirubin (direct and indirect) .
In the U.S.
In Canada
Available Dosage Forms:
Therapeutic Class: Immune Serum
Rho(D) immune globulin is used to treat immune thrombocytopenic purpura (ITP) in patients with Rh-positive blood. ITP is a type of blood disorder where the person has a very low number of platelets. Platelets help to clot the blood. Rho(D) immune globulin is also used to prevent antibodies from forming after a person with Rh-negative blood receives a transfusion with Rh-positive blood, or during pregnancy when a mother has Rh-negative blood and the baby is Rh-positive. It belongs to a group of medicines called immunizing agents. Rho(D) immune globulin works to boost the immune system and prevent excessive bleeding.
The Rh factor is one part of the red blood cell. A person has either Rh-positive or Rh-negative blood. If you receive the opposite type of blood, your body will create antibodies that can destroy the red blood cells. When a pregnant woman is Rh-negative and her baby is Rh-positive, the baby's blood can get into her system and cause her to make antibodies. When the same woman has a second baby with Rh-positive blood, the antibodies will destroy the red blood cells in the baby. Rho(D) immune globulin is given to these women during pregnancy or after delivery to prevent them from making antibodies.
This medicine is to be administered only by or under the supervision of your doctor.
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:
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.
Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of Rho(D) immune globulin in children. It is not recommended for an infant with Rh-positive blood whose mother is Rh-negative.
Although appropriate studies on the relationship of age to the effects of Rho(D) immune globulin have not been performed in the geriatric population, geriatric-specific problems are not expected to limit the usefulness of Rho(D) immune globulin in the elderly. However, elderly patients are more likely to have age-related heart, kidney, or liver problems, and might have conditions that require an adjustment in the dose for patients receiving Rho(D) immune globulin.
| 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. |
Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.
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 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.
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.
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:
This section provides information on the proper use of a number of products that contain rho(d) immune globulin. It may not be specific to BayRho-D. Please read with care.
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 or as a shot into one of your muscles.
It is very important that your doctor check the progress of you or your child at regular visits for any problems or unwanted effects that may be caused by this medicine. Blood and urine tests may be needed to check for unwanted effects.
Check with your doctor right away if you or your child have back pain; shaking chills; a fever; dark urine; a decreased amount of urine; a sudden weight gain; swelling of the hands or feet; or shortness of breath after receiving this medicine. These may be symptoms of a serious blood problem called intravascular hemolysis (IVH).
This medicine is made from donated human blood. Some human blood products have transmitted certain viruses to people who have received them. The risk of getting a virus from medicines made from human blood has been greatly reduced in recent years. This is the result of required testing of human donors for certain viruses, and testing during the making of these medicines. Although the risk is low, talk with your doctor if you have concerns.
This medicine may cause serious types of allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Tell your doctor right away if you or your child have itching, a rash, hives, chest pain, dizziness or lightheadedness, trouble breathing, or any swelling of your hands, face, or mouth after you receive this medicine.
This medicine may cause blood clots, especially in patients with a history of blood clotting problems, heart disease, and atherosclerosis (hardening of the arteries) or circulation problems. Patients who stay in bed for a long time because of surgery or illness may also have blood clots. Check with your doctor right away if you or your child suddenly have chest pain, shortness of breath, a severe headache, leg pain, or problems with vision, speech, or walking.
This medicine may cause a rare and serious lung problem a few hours after it is given. Tell your doctor right away if you or your child have any breathing problems with or without a fever after you receive the medicine.
While you are being treated with Rho(D) immune globulin, do not have any immunizations (vaccines) without your doctor's approval. Live virus vaccines should not be given for 3 months after receiving Rho(D) immune globulin.
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:
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:
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: BayRho-D side effects (in more detail)
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Zela may be available in the countries listed below.
Albendazole is reported as an ingredient of Zela in the following countries:
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Mirtazapine Teva may be available in the countries listed below.
Mirtazapine is reported as an ingredient of Mirtazapine Teva in the following countries:
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Fedral may be available in the countries listed below.
Ondansetron hydrochloride dihydrate (a derivative of Ondansetron) is reported as an ingredient of Fedral in the following countries:
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It is recommended that Bleomycin for Injection, USP be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available.
Pulmonary fibrosis is the most severe toxicity associated with Bleomycin. The most frequent presentation is pneumonitis occasionally progressing to pulmonary fibrosis. Its occurrence is higher in elderly patients and in those receiving greater than 400 units total dose, but pulmonary toxicity has been observed in young patients and those treated with low doses.
A severe idiosyncratic reaction consisting of hypotension, mental confusion, fever, chills, and wheezing has been reported in approximately 1% of lymphoma patients treated with Bleomycin.
Bleomycin for Injection, USP is a mixture of cytotoxic glycopeptide antibiotics isolated from a strain of Streptomyces verticillus. It is freely soluble in water. Bleomycin for Injection, USP contains sterile Bleomycin sulfate equivalent to 15 units or 30 units of Bleomycin. Sulfuric acid or sodium hydroxide can be used, if necessary, to adjust pH.
Bleomycin for Injection, USP may be given by the intramuscular, intravenous or subcutaneous routes.
Its chemical name is N’-[3-(dimethylsul-phonio)propyl]Bleomycin-amide (Bleomycin A2) and N’-[4-(guaniodobutyl)]Bleomycin-amide (Bleomycin B2). (Main component: Bleomycin A2, in which R is [CH3]2S+CH2CH2CH2-)
The molecular formula of Bleomycin A2 is C55H84N17O21S3 and a calculated molecular weight of 1414. The molecular formula of Bleomycin B2 is C55H84N20O21S2 and a calculated molecular weight of 1425. The structural formula of Bleomycins A2 and B2 are shown below.
Note: A unit of Bleomycin is equal to the formerly used milligram activity. The term milligram activity is a misnomer and was changed to units to be more precise.
Although the exact mechanism of action of Bleomycin is unknown, available evidence indicates that the main mode of action is the inhibition of DNA synthesis with some evidence of lesser inhibition of RNA and protein synthesis.
Bleomycin is known to cause single, and to a lesser extent, double-stranded breaks in DNA. In in vitro and in vivo experiments, Bleomycin has been shown to cause cell cycle arrest in G2 and in mitosis.
When administered into the pleural cavity in the treatment of malignant pleural effusion, Bleomycin acts as a sclerosing agent.
Absorption
Bleomycin is rapidly absorbed following either intramuscular, subcutaneous, intraperitoneal, or intrapleural administration reaching peak plasma concentrations in 30 to 60 minutes. Systemic bioavailability of Bleomycin is 100% and 70% following intramuscular and subcutaneous administrations, respectively, and 45% following both intraperitoneal and intrapleural administrations, compared to intravenous and bolus administration.
Following intramuscular doses of 1 to 10 units/m2, both peak plasma concentration and AUC increased in proportion with the increase of dose.
Following intravenous bolus administration of 30 units of Bleomycin to one patient with a primary germ cell tumor of the brain, a peak CSF level was 40% of the simultaneously-obtained plasma level and was attained in 2 hours after drug administration. The area under the Bleomycin CSF concentration x time curve was 25% of the area of the Bleomycin plasma concentration x time curve.
Distribution
Bleomycin is widely distributed throughout the body with a mean volume of distribution of 17.5 L/m2 in patients following a 15 units/m2 intravenous bolus dose. Protein binding of Bleomycin has not been studied.
Metabolism
Bleomycin is inactivated by a cytosolic cysteine proteinase enzyme, Bleomycin hydrolase. The enzyme is widely distributed in normal tissues with the exception of the skin and lungs, both targets of Bleomycin toxicity. Systemic elimination of the drug by enzymatic degradation is probably only important in patients with severely compromised renal function.
Excretion
The primary route of elimination is via the kidneys. About 65% of the administered intravenous dose is excreted in urine within 24 hours. In patients with normal renal function, plasma concentrations of Bleomycin decline biexponentially with a mean terminal half-life of 2 hours following intravenous bolus administration. Total body clearance and renal clearance averaged 51 mL/min/m2 and 23 mL/min/m2, respectively.
Following intrapleural administration to patients with normal renal function, a lower percentage of drug (40%) is recovered in the urine, as compared to that found in the urine after intravenous administration.
Age, Gender, and Race
The effects of age, gender, and race on the pharmacokinetics of Bleomycin have not been evaluated.
Pediatric
Children of less than 3 years of age have higher total body clearance than in adults, 71 mL/min/m2 versus 51 mL/min/m2, respectively, following intravenous bolus administration. Children of more than 8 years of age have comparable clearance as in adults.
In children with normal renal function, plasma concentrations of Bleomycin decline biexponentially as in adults. The volume of distribution and terminal half-life of Bleomycin in children appears comparable to that in adults.
Renal Insufficiency
Renal insufficiency markedly alters Bleomycin elimination. The terminal elimination half-life increases exponentially as the creatinine clearance decreases. Dosing reductions were proposed for patients with creatinine clearance values of < 50 mL/min (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Hepatic Insufficiency
The effect of hepatic insufficiency on the pharmacokinetics of Bleomycin has not been evaluated.
Drugs that Can Affect Renal Clearance
Because Bleomycin is eliminated predominantly through renal excretion, the administration of nephrotoxic drugs with Bleomycin may affect its renal clearance. Specifically, in one report of 2 children receiving concomitant cisplatin with Bleomycin, total body clearance of Bleomycin decreased from 39 to 18 mL/min/m2 as the cumulative dose of cisplatin exceeded 300 mg/m2. Terminal half-life of Bleomycin also increased from 4.4 to 6 hours. Fatal Bleomycin pulmonary toxicity has been reported in a patient with unrecognized cisplatin-induced oliguric renal failure.
Malignant Pleural Effusion
The safety and efficacy of Bleomycin 60 units and tetracycline (1 g) as treatment for malignant pleural effusion were evaluated in a multicenter, randomized trial. Patients were required to have cytologically positive pleural effusion, good performance status (0,1,2), lung re-expansion following tube thoracostomy with drainage rates of 100 mL/24 hours or less, no prior intrapleural therapy, no prior systemic Bleomycin therapy, no chest irradiation and no recent change in systemic therapy. Overall survival did not differ between the Bleomycin (n = 44) and tetracycline treatment (n = 41) groups. Of patients evaluated within 30 days of instillation, the recurrence rate was 36% (10/28) with Bleomycin and 67% (18/27) with tetracycline (p = 0.023). Toxicity was similar between groups.
Bleomycin for injection should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agents.
Head and neck (including mouth, tongue, tonsil, nasopharynx, oropharynx, sinus, palate, lip, buccal mucosa, gingivae, epiglottis, skin, larynx), penis, cervix, and vulva. The response to Bleomycin is poorer in patients with previously irradiated head and neck cancer.
Hodgkin's Disease, non-Hodgkin's lymphoma.
Embryonal cell, choriocarcinoma, and teratocarcinoma.
Bleomycin is effective as a sclerosing agent for the treatment of malignant pleural effusion and prevention of recurrent pleural effusions.
Bleomycin is contraindicated in patients who have demonstrated a hypersensitive or an idiosyncratic reaction to it.
Patients receiving Bleomycin must be observed carefully and frequently during and after therapy. It should be used with extreme caution in patients with significant impairment of renal function or compromised pulmonary function.
Pulmonary toxicities occur in 10% of treated patients. In approximately 1%, the nonspecific pneumonitis induced by Bleomycin progresses to pulmonary fibrosis, and death. Although this is age and dose related, the toxicity is unpredictable. Frequent roentgenograms are recommended. (See ADVERSE REACTIONS-Pulmonary.)
A severe idiosyncratic reaction (similar to anaphylaxis) consisting of hypotension, mental confusion, fever, chills, and wheezing has been reported in approximately 1% of lymphoma patients treated with Bleomycin. Since these reactions usually occur after the first or second dose, careful monitoring is essential after these doses. (See ADVERSE REACTIONS-Idiosyncratic Reactions.)
Renal or hepatic toxicity, beginning as a deterioration in renal or liver function tests, have been reported. These toxicities may occur at any time after initiation of therapy.
Bleomycin can cause fetal harm when administered to a pregnant woman. It has been shown to be teratogenic in rats. Administration of intraperitoneal doses of 1.5 mg/kg/day to rats (about 1.6 times the recommended human dose on a unit/m2 basis) on days 6 to 15 of gestation caused skeletal malformations, shortened innominate artery and hydroureter. Bleomycin is abortifacient but not teratogenic in rabbits, at intravenous doses of 1.2 mg/kg/day (about 2.4 times the recommended human dose on a unit/m2 basis) given on gestation days 6 to 18.
There have been no studies in pregnant women. If Bleomycin is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Bleomycin.
Patients with creatinine clearance values of less than 50 mL/min should be treated with caution and their renal function should be carefully monitored during the administration of Bleomycin. Lower doses of Bleomycin may be required in these patients than those with normal renal function (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).
The carcinogenic potential of Bleomycin in humans is unknown. A study in F344-type male rats demonstrated an increased incidence of nodular hyperplasia after induced lung carcinogenesis by nitrosamines, followed by treatment with Bleomycin. In another study where the drug was administered to rats by subcutaneous injection at 0.35 mg/kg weekly (3.82 units/m2 weekly or about 30% at the recommended human dose), necropsy findings included dose related injection site fibrosarcomas as well as various renal tumors. Bleomycin has been shown to be mutagenic both in vitro and in vivo. The effects of Bleomycin on fertility have not been studied.
Pregnancy Category D
(See WARNINGS section.)
It is not known whether the 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, it is recommended that nursing be discontinued by women receiving Bleomycin therapy.
Safety and effectiveness of Bleomycin in pediatric patients have not been established.
In clinical trials, pulmonary toxicity was more common in patients older than 70 years than in younger patients (see BOXED WARNING, WARNINGS, and ADVERSE REACTIONS, Pulmonary). Other reported clinical experience has not identified other differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Bleomycin is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
The most serious side effects are pulmonary adverse reactions, occurring in approximately 10% of treated patients. The most frequent presentation is pneumonitis occasionally progressing to pulmonary fibrosis. Approximately 1% of patients treated have died of pulmonary fibrosis. Pulmonary toxicity is both dose and age related, being more common in patients over 70 years of age and in those receiving over 400 units total dose. This toxicity, however, is unpredictable and has been seen in young patients receiving low doses.
Some published reports have suggested that the risk of pulmonary toxicity may be increased when Bleomycin is used in combination with G-CSF (filgrastim) or other cytokines. However, randomized clinical studies completed to date have not demonstrated an increased risk of pulmonary complications in patients treated with Bleomycin and G-CSF.
Because of lack of specificity of the clinical syndrome, the identification of patients with pulmonary toxicity due to Bleomycin has been extremely difficult. The earliest symptom associated with Bleomycin pulmonary toxicity is dyspnea. The earliest sign is fine rales.
Radiographically, Bleomycin-induced pneumonitis produces nonspecific patchy opacities, usually of the lower lung fields. The most common changes in pulmonary function tests are a decrease in total lung volume and a decrease in vital capacity. However, these changes are not predictive of the development of pulmonary fibrosis.
The microscopic tissue changes due to Bleomycin toxicity include bronchiolar squamous metaplasia, reactive macrophages, atypical alveolar epithelial cells, fibrinous edema, and interstitial fibrosis. The acute stage may involve capillary changes and subsequent fibrinous exudation into alveoli producing a change similar to hyaline membrane formation and progressing to a diffuse interstitial fibrosis resembling the Hamman-Rich syndrome. These microscopic findings are nonspecific; e.g., similar changes are seen in radiation pneumonitis and pneumocystic pneumonitis.
To monitor the onset of pulmonary toxicity, roentgenograms of the chest should be taken every 1 to 2 weeks (see WARNINGS). If pulmonary changes are noted, treatment should be discontinued until it can be determined if they are drug related. Recent studies have suggested that sequential measurement of the pulmonary diffusion capacity for carbon monoxide (DLCO) during treatment with Bleomycin may be an indicator of subclinical pulmonary toxicity. It is recommended that the DLCO be monitored monthly if it is to be employed to detect pulmonary toxicities, and thus the drug should be discontinued when the DLCO falls below 30% to 35% of the pretreatment value.
Because of Bleomycin's sensitization of lung tissue, patients who have received Bleomycin are at greater risk of developing pulmonary toxicity when oxygen is administered in surgery. While long exposure to very high oxygen concentrations is a known cause of lung damage, after Bleomycin administration, lung damage can occur at lower concentrations that are usually considered safe. Suggested preventive measures are:
Sudden onset of an acute chest pain syndrome suggestive of pleuropericarditis has been reported during Bleomycin infusions. Although each patient must be individually evaluated, further courses of Bleomycin do not appear to be contraindicated.
Pulmonary adverse events which may be related to the intrapleural administration of Bleomycin have been reported.
In approximately 1% of the lymphoma patients treated with Bleomycin, an idiosyncratic reaction, similar to anaphylaxis clinically, has been reported. The reaction may be immediate or delayed for several hours, and usually occurs after the first or second dose (see WARNINGS). It consists of hypotension, mental confusion, fever, chills, and wheezing. Treatment is symptomatic including volume expansion, pressor agents, antihistamines, and corticosteroids.
These adverse reactions have been reported in approximately 50% of treated patients. They consist of erythema, rash, striae, vesiculation, hyperpigmentation, and tenderness of the skin. Hyperkeratosis, nail changes, alopecia, pruritus, and stomatitis have also been reported. It was necessary to discontinue Bleomycin therapy in 2% of treated patients because of these toxicities.
Scleroderma-like skin changes have been reported.
Skin toxicity is a relatively late manifestation usually developing in the second and third week of treatment after 150 to 200 units of Bleomycin have been administered and appears to be related to the cumulative dose.
Intrapleural administration of Bleomycin has been associated with local pain. Hypotension possibly requiring symptomatic treatment has been reported. Death has been reported in association with Bleomycin pleurodesis in seriously ill patients.
Vascular toxicities coincident with the use of Bleomycin in combination with other antineoplastic agents have been reported. The events are clinically heterogeneous and may include myocardial infarction, cerebrovascular accident, thrombotic microangiopathy (HUS) or cerebral arteritis. Various mechanisms have been proposed for these vascular complications. There are also reports of Raynaud's phenomenon occurring in patients treated with Bleomycin in combination with vinblastine with or without cisplatin or, in a few cases, with Bleomycin as a single agent. It is currently unknown if the cause of Raynaud's phenomenon in these cases is the disease, underlying vascular compromise, Bleomycin, vinblastine, hypomagnesemia, or a combination of any of these factors.
Fever, chills, and vomiting have been reported. Anorexia and weight loss have been reported and may persist long after termination of this medication. Pain at tumor site, phlebitis, and other local reactions have been reported.
Malaise has been reported.
BECAUSE OF THE POSSIBILITY OF AN ANAPHYLACTOID REACTION, LYMPHOMA PATIENTS SHOULD BE TREATED WITH 2 UNITS OR LESS FOR THE FIRST TWO DOSES. IF NO ACUTE REACTION OCCURS, THEN THE REGULAR DOSAGE SCHEDULE MAY BE FOLLOWED.
The following dose schedule is recommended:
Squamous cell carcinoma, non-Hodgkin's lymphoma, testicular carcinoma- 0.25 to 0.50 units/kg (10 to 20 units/m2) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly.
Hodgkin's Disease - 0.25 to 0.50 units/kg (10 to 20 units/m2) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly. After a 50% response, a maintenance dose of 1 unit daily or 5 units weekly intravenously or intramuscularly should be given.
Pulmonary toxicity of Bleomycin appears to be dose related with a striking increase when the total dose is over 400 units. Total doses over 400 units should be given with great caution.
Note: When Bleomycin for injection is used in combination with other antineoplastic agents, pulmonary toxicities may occur at lower doses.
Improvement of Hodgkin's Disease and testicular tumors is prompt and noted within 2 weeks. If no improvement is seen by this time, improvement is unlikely. Squamous cell cancers respond more slowly, sometimes requiring as long as 3 weeks before any improvement is noted.
Malignant Pleural Effusion - 60 units administered as a single dose bolus intrapleural injection (see Administration, Intrapleural).
The following dosing reductions are proposed for patients with creatinine clearance (CrCL) values of less than 50 mL/min:
Patient CrCL (mL/min) | Bleomycin for Injection, USP Dose (%) |
| 50 and above | 100 |
| 40 to 50 | 70 |
| 30 to 40 | 60 |
| 20 to 30 | 55 |
| 10 to 20 | 45 |
| 5 to 10 | 40 |
CrCL can be estimated from the individual patient’s measured serum creatinine (Scr) values using the Cockcroft and Gault formula:
Males CrCL = [weight x (140 – Age)]/(72 x Scr)
Females CrCL = 0.85 x [weight x (140 – Age)]/(72 x Scr)
Where CrCL in mL/min/1.73m2, weight in kg, age in years, and Scr in mg/dL.
Bleomycin for injection may be given by the intramuscular, intravenous, subcutaneous, or intrapleural routes.
Administration Precautions
Caution should be exercised when handling Bleomycin for injection. Procedures for proper handling and disposal of anticancer drugs should be utilized. Several guidelines on this subject have been published.1-4 To minimize the risk of dermal exposure, always wear impervious gloves when handling vials containing Bleomycin for injection. If Bleomycin for injection contacts the skin, immediately wash the skin thoroughly with soap and water. If contact with mucous membranes occurs, the membranes should be flushed immediately and thoroughly with water. More information is available in the references listed below.
Intramuscular or Subcutaneous
The Bleomycin for injection, USP 15 units vial should be reconstituted and dissolved with 1 to 5 mL of sterile water for injection, USP, sodium chloride injection, 0.9%, USP, or bacteriostatic water for injection, USP. The Bleomycin for injection, USP 30 units vial should be reconstituted and dissolved with 2 to 10 mL of the above diluents.
Intravenous
The contents of the 15 units or 30 units vial should be dissolved in 5 mL or 10 mL, respectively, of Sodium Chloride for Injection, 0.9%, USP, and administered slowly over a period of 10 minutes.
Intrapleural
60 units of Bleomycin are dissolved in 50 to 100 mL Sodium Chloride for Injection, 0.9%, USP and administered through a thoracostomy tube following drainage of excess pleural fluid and confirmation of complete lung expansion. The literature suggests that successful pleurodesis is, in part, dependent upon complete drainage of the pleural fluid and reestablishment of negative intrapleural pressure prior to instillation of a sclerosing agent. Therefore, the amount of drainage from the chest tube should be as minimal as possible prior to instillation of Bleomycin. Although there is no conclusive evidence to support this contention, it is generally accepted that chest tube drainage should be less than 100 mL in a 24-hour period prior to sclerosis. However, Bleomycin instillation may be appropriate when drainage is between 100 to 300 mL under clinical conditions that necessitate sclerosis therapy. The thoracostomy tube is clamped after Bleomycin instillation. The patient is moved from the supine to the left and right lateral positions several times during the next four hours. The clamp is then removed and suction reestablished. The amount of time the chest tube remains in place following sclerosis is dictated by the clinical situation.
The intrapleural injection of topical anesthetics or systemic narcotic analgesia is generally not required.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Bleomycin for Injection, USP contains sterile Bleomycin sulfate equivalent to 15 units or 30 units of Bleomycin. Bleomycin for Injection, USP is supplied as follows:
| NDC Number | ||
| 0703 3154-01 | 15 Units per Vial | Individually packaged |
| 0703 3155-01 | 30 Units per Vial | Individually packaged |
Stability
The sterile powder is stable under refrigeration 2° to 8°C (36° to 46°F) and should not be used after the expiration date is reached.
Bleomycin for Injection, USP should not be reconstituted or diluted with 5% dextrose injection or other dextrose containing diluents. When reconstituted in 5% dextrose injection and analyzed by HPLC, Bleomycin for Injection, USP demonstrates a loss of A2 and B2 potency that does not occur when Bleomycin for Injection, USP is reconstituted in 0.9% sodium chloride for injection, 0.9%, USP.
Bleomycin for Injection, USP is stable for 24 hours at room temperature in 0.9 % sodium chloride injection.
Vial stoppers do not contain natural rubber latex.
1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.
2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling occupational exposure to hazardous drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/ot m_vi_2.html
3. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. 2006;63:1172-1193.
4. Polovich M, White JM, Kelleher LO, eds. 2005. Chemotherapy and biotherapy guidelines and recommendations for practice. 2nd ed. Pittsburgh, PA: Oncology Nursing Society.
Manufactured By:
Teva Parenteral Medicines, Inc.,
Irvine, CA 92618
Iss. 9/2011
NDC 0703-3154-01
Rx only
Bleomycin
for Injection, USP
equivalent to
15 Units Bleomycin
Caution: Cytotoxic Agent
Single Use Vial
For IV, IM, SC or
Intrapleural Use
TEVA
NDC 0703-3155-01
Rx only
Bleomycin
for Injection, USP
equivalent to
30 Units Bleomycin
Caution: Cytotoxic Agent
Single Use Vial
For IV, IM, SC or
Intrapleural Use
TEVA
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| ANDA | ANDA065033 | 09/27/2011 | |
| Bleomycin Bleomycin injection | ||||||||||||||||||||
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| ANDA | ANDA065033 | 09/27/2011 | |
| Labeler - Teva Parenteral Medicines, Inc (794362533) |
Hibideks may be available in the countries listed below.
Chlorhexidine digluconate (a derivative of Chlorhexidine) is reported as an ingredient of Hibideks in the following countries:
International Drug Name Search
Rinosal may be available in the countries listed below.
Fluticasone is reported as an ingredient of Rinosal in the following countries:
International Drug Name Search
