You are on page 1of 13

Generic Name: Isoxsuprine Brand Name: Vasodilan

DESCRIPTION Each tablet taken orally contains Isoxsuprine Hydrochloride, USP with the following chemical structure: C H NO – HCl p-Hydroxy-a[1-[(methyl-2-phenoxyethyl)amino]ethyl]benzyl alcohol hydrochloride.

rash. If rash appears, the drug should be discontinued. Although available evidence suggests a temporal association of these reactions with Isoxsuprine Hydrochloride, a causal relationship can be neither confirmed nor refuted. Beta Adrenergic receptor stimulants such as Isoxsuprine Hydrocholoride have been used to inhibit pre-term labor. Maternal and fetal tachycardia may occur under such

INDICATIONS Based on a review of this drug by the National Academy of Sciences-National Research and/or other information, the FDA has classified the indications as follows: Possibly Effective 1. For the relief of symptoms associated with cerebrovascular insufficiency. 2. In peripheral vascular disease of arteriosclerosis obliterans, thromboangitis obliterans (Buerger's disease) and Raynaud's disease. Final classification of the less-than-effective indications requires further investigation.

use. Hypocalcemia, hypoglycemia, hypotension and ileus have been reported to occur in infants whose mothers received Isoxsuprine Hydrochloride. Pulmonary edema has been reported in mothers treated with beta stimulants. Isoxsuprine Hydrochloride is neither approved nor recommended for use in the treatment of premature labor.

DOSAGE AND ADMINISTRATION Oral: 10 to 20 mg, three or four times daily.

HOW SUPPLIED Isoxsuprine HCl tablets, USP 10 mg Bottles of 100 NDC 42582-100-10 CONTRAINDICATIONS PRINCIPAL DISPLAY PANEL - 10 mg Bottle Label There are no known contraindications to oral use when administered in recommended doses. Isoxsuprine Hydrochloride, USP should not be given immediately postpartum or in the presence of arterial bleeding. Bi-Coastal Pharmaceutical Corp.® NDC 42582-100-10 Isoxsuprine Hydrochloride ADVERSE REACTIONS On rare occasion oral administration of the drug has been associated in time with the occurrence of hypotension, tachycardia, chest pain, nausea, vomiting, dizziness, abdominal distress, and severe Tablets, USP 10 mg Rx only 100 Tablets

and cardiac function as measured by left ventricular ejection function (LVEF). acute myeloblastic leukemia. and creatinine. Patients should be carefully monitored during treatment for possible clinical complications due to myelosuppression. (See WARNINGS andDOSAGE AND ADMINISTRATION. transitional cell bladder carcinoma. or other anthracyclines or anthracenediones. or hypersensitivity to doxorubicin. Supportive care may be necessary for the treatment of severe neutropenia and severe infectious complications. and/or other . Hodgkin's disease. anthracyclines and anthracenediones. severe hepatic impairment. especially with greater cumulative CONTRAINDICATIONS Patients should not be treated with doxorubicin if they have any of the following conditions: baseline neutrophil count <1500 cells/mm3. Doxorubicin is also indicated for use as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer. severe arrhythmias.Generic Name: Doxorubicin Brand Name: Adriamycin INDICATIONS AND USAGE Doxorubicin has been used successfully to produce regression in disseminated neoplastic conditions such as acute lymphoblastic leukemia. any of its excipients. Also. recent myocardial infarction. daunorubicin. Patients should recover from acute toxicities of prior cytotoxic treatment (such as stomatitis. and generalized infections) before beginning treatment with doxorubicin. previous treatment with complete cumulative doses of doxorubicin. gastric carcinoma. malignant lymphoma and bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types. severe myocardial insufficiency. idarubicin. soft tissue and bone sarcomas. ovarian carcinoma. Wilms' tumor. breast carcinoma. thrombocytopenia.) WARNINGS General Doxorubicin should be administered only under the supervision of qualified physicians experienced in the use of cytotoxic therapy. thyroid carcinoma. neutropenia. neuroblastoma. AST. serum levels of total bilirubin. initial treatment with doxorubicin should be preceded by a careful baseline assessment of blood counts. Monitoring for potential cardiotoxicity is also important.

including premature ventricular contractions and ventricular tachycardia. subsequently leading to possible development of congestive heart failure during early adulthood. The risk of developing CHF increases rapidly with increasing total cumulative doses of doxorubicin in excess of 400 mg/m2. and advanced age. ascites. Monitoring Cardiac Function The risk of serious cardiac impairment may be decreased through regular monitoring of LVEF during the course of treatment with prompt discontinuation of doxorubicin at the first sign of impaired function. Repeated MUGA or ECHO determinations of LVEF should be performed. cardiomegaly and hepatomegaly. dyspnea. and 3/14 (21%) at 728 mg/m2. have also been reported. pulmonary edema. it is probable that the toxicity of doxorubicin and other anthracyclines or anthracenediones is additive.exposure to doxorubicin. Anthracycline-induced cardiotoxicity may be manifested by early (or acute) or late (delayed) events. based on a combined index of signs. are rarely of clinical importance.9% at 400 mg/m2. cumulative anthracycline doses. The probability of developing impaired myocardial function. and gallop rhythm. This late cardiac toxicity may be related to the dose of doxorubicin. The preferred method for assessment of cardiac function is evaluation of LVEF measured by multigated radionuclide angiography (MUGA) or echocardiography (ECHO). Tachyarrhythmias. Doxorubicin may potentiate the toxicity of other anticancer therapies. 3 to 5% at a dose of 400 mg/m2. particularly with higher. concomitant use of other cardiotoxic drugs. Life-threatening CHF is the most severe form of anthracycline-induced cardiomyopathy and represents the cumulative dose-limiting toxicity of the drug. idarubicin and mitoxantrone. In a prospective study of doxorubicin in combination with cyclophosphamide. the probability of CHF at various cumulative doses of doxorubicin was 1. Such intervention may relieve symptoms and improve the functional status of the patient.) Cardiac Function Cardiotoxicity is a known risk of anthracycline treatment. Cardiotoxicity may occur at lower doses in patients with prior mediastinal/pericardial irradiation. An ECG may also be done. Although not formally tested. after load reducers such as angiotensin I converting enzyme (ACE) inhibitors. Delayed cardiomyopathy is manifested by a reduction in LVEF and/or signs and symptoms of congestive heart failure (CHF) such as tachycardia. 5 to 8% at a dose of 450 mg/m2 and 6 to 20% at a dose of 500 mg/m2 given in a schedule of a bolus injection once every 3 weeks. dependent edema. symptoms and decline in left ventricular ejection fraction (LVEF) is estimated to be 1 to 2% at a total cumulative dose of 300 mg/m2 of doxorubicin. Cardiomyopathy and/or congestive heart failure may be encountered several months or years after discontinuation of doxorubicin therapy. cardiac toxicity may occur at doses lower than the recommended cumulative dose of doxorubicin. Drug Interactions. Delayed cardiotoxicity usually develops late in the course of therapy with doxorubicin or within 2 to 3 months after treatment termination. Pediatric patients appear to be at particular risk for developing delayed cardiac toxicity in that doxorubicin-induced cardiomyopathy impairs myocardial growth as pediatric patients mature. In a retrospective review. The total dose of doxorubicin administered to the individual patient should also take into account previous or concomitant therapy with related compounds such as daunorubicin.5% at 500 mg/m2. Early cardiotoxicity of doxorubicin consists mainly of sinus tachycardia and/or electrocardiogram (ECG) abnormalities such as non-specific ST-T wave changes. Data also suggest that pre-existing heart disease is a cofactor for increased risk of doxorubicin cardiotoxicity. low salt diet. 7. bradycardia. fluorouracil and/or vincristine in patients with breast cancer or small cell lung cancer. doxorubicin exposure at an early age. 8/110 (7%) at 575 mg/m2. A baseline cardiac evaluation with a MUGA scan or an ECHO is recommended. The risk of acute manifestations of doxorubicin cardiotoxicity in pediatric patients may be as much or lower than in adults. The longer the length of follow-up. as well as atrioventricular and bundlebranch block have also been reported. oliguria.5% at 300 mg/m2. Subacute effects such as pericarditis/myocarditis have also been reported. As many as 40% of pediatric patients may have subclinical cardiac dysfunction and 5 to 10% of pediatric patients may develop congestive heart failure on long term follow-up. (See PRECAUTIONS. and bed rest. the probability of developing congestive heart failure was reported to be 5/168 (3%) at a cumulative dose of 430 mg/m2 of doxorubicin. Treatment of doxorubicin-induced congestive heart failure includes the use of digitalis. pleural effusion. 4. diuretics. especially in patients with risk factors for increased cardiac toxicity. Studies have suggested that concomitant administration of doxorubicin and calcium channel entry blockers may increase the risk of doxorubicin cardiotoxicity. In such cases. These effects do not usually predict subsequent development of delayed cardiotoxicity. The technique used for . several months to years after completion of treatment. the greater the increase in the detection rate. but later events.7% at 450 mg/m2 and 20. and are generally not considered an indication for the suspension of doxorubicin treatment.

the incidence was estimated at 1. this invasive examination is not practically performed on a routine basis. Pediatric patients are at increased risk for developing delayed cardiotoxicity following doxorubicin administration and therefore a follow-up cardiac evaluation is recommended periodically to monitor for this delayed cardiotoxicity. if test results indicate deterioration in cardiac function associated with doxorubicin. (See DOSAGE AND ADMINISTRATION. A dose-dependent. even if blood returns well on aspiration of the infusion needle. infections. Thrombocytopenia and anemia may also occur.) Extravasation On intravenous administration of doxorubicin. in combination with radiotherapy. In both experiences. or when doses of anthracyclines have been escalated. extravasation may occur with or without an accompanying stinging or burning sensation. The rate of developing secondary AML or MDS has been estimated in an analysis of 8563 patients with early breast cancer treated in 6 studies conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP). the monitoring of cardiac function must be particularly strict and the risk-benefit of continuing treatment with doxorubicin in patients with impaired cardiac function must be carefully evaluated. who received radiotherapy. In general. deterioration in cardiac function during or after the completion of therapy with doxorubicin is indicated by a drop in fractional shortening (FS) by an absolute value of ≥10 percentile units or below 29%.11–0. ECG changes such as dysrhythmias. In another analysis of 1474 patients with breast cancer who received adjuvant treatment with doxorubicin-containing regimens in clinical trials conducted at University of Texas M. Endomyocardial biopsy is recognized as the most sensitive diagnostic tool to detect anthracyclineinduced cardiomyopathy. however. Instruction for Use/Handling.5% at 10 years. Clinical consequences of severe myelosuppression include fever. particularly prior anthracycline or anthracenedione use. reaching its nadir 10 to 14 days after treatment with recovery usually occurring by the 21st day. but ECG is not a sensitive or specific method for following anthracycline-related cardiotoxicity. a 10% decline in LVEF to below the lower limit of normal or an absolute LVEF of 45%. Myelosuppression requires careful monitoring. for an incidence of 0. Among 4483 such patients who received conventional doses of AC. or a prolongation beyond normal limits of the systolic time interval may be indicative of anthracycline-induced cardiomyopathy. sepsis/septicemia. patients who received regimens with higher cyclophosphamide dosages. tissue hypoxia.810 patient years.41%).) Hepatic Impairment . Secondary Leukemia The occurrence of secondary AML or MDS has been reported most commonly in patients treated with chemotherapy regimens containing anthracyclines (including doxorubicin) and DNA-damaging antineoplastic agents. the benefit of continued therapy should be carefully evaluated against the risk of producing irreversible cardiac damage. Total and differential WBC.32 cases per 1000 patient years (95% CI 0. and a decline in LVEF of 10 percentile units or an LVEF below 55%. and platelet counts should be assessed before and during each cycle of therapy with doxorubicin. Effects at Site of Injection Phlebosclerosis may result from an injection into a small vessel or from repeated injections into the same vein. Acute lifethreatening arrhythmias have been reported to occur during or within a few hours after doxorubicin administration.16–0. or who were aged 50 or older had an increased risk of secondary AML or MDS. If any signs or symptoms of extravasation have occurred. (See DOSAGE AND ADMINISTRATION. red blood cell (RBC).57) and a cumulative incidence at 5 years of 0. or death. 11 cases of AML or MDS were identified. Such cases generally have a 1–3 year latency period. including NSABP B-15. hemorrhage. Pediatric patients are also at risk of developing secondary AML.assessment should be consistent through follow-up. Anderson Cancer Center. or a 20% decline in LVEF at any level is indicative of deterioration in cardiac function. the injection or infusion should be immediately terminated and restarted in another vein. a reduction of the QRS voltage. In adults. reversible leukopenia and/or granulocytopenia (neutropenia) are the predominant manifestations of doxorubicin hematologic toxicity and is the most common acute dose-limiting toxicity of this drug. In pediatric patients.D. when patients have been heavily pretreated with cytotoxic drugs.21% (95% CI 0. In patients with risk factors. leukopenia is usually transient. Following the recommended administration procedures may minimize the risk of phlebitis/thrombophlebitis at the injection site. doxorubicin may produce myelosuppression. With the recommended dose schedule. septic shock. Hematologic Toxicity As with other cytotoxic agents. Patients in these studies received standard doses of doxorubicin and standard or escalated doses of cyclophosphamide (AC) adjuvant chemotherapy and were followed for 61.

therefore. symptoms of CHF. Paclitaxel There have been a number of reports in the literature that describe an increase in cardiotoxicity when doxorubicin is co-administered with paclitaxel. alkaline phosphatase. If doxorubicin is to be used during pregnancy. Literature reports suggest that adding cyclosporine to doxorubicin results in more profound and prolonged hematologic toxicity than doxorubicin alone. hypoplasia of the urinary bladder and cardiovascular anomalies. Enhanced doxorubicin-induced neutropenia and thrombocytopenia were observed.4 mg/kg/day (about 1/14 the recommended human dose on a body surface area basis) in rabbits when administered during the period of organogenesis. and bilirubin. evidence of infection. Toxicities associated with doxorubicin. the patient should be apprised of the potential hazard to the fetus. Drug Interactions Doxorubicin is extensively metabolized by the liver. prior to individual dosing. Verapamil A study of the effects of verapamil on the acute toxicity of doxorubicin in mice revealed higher initial peak concentrations of doxorubicin in the heart with a higher incidence and severity of degenerative changes in cardiac tissue resulting in a shorter survival. as well as a risk of treatment-related leukemia. Patients should be advised that their urine may appear red for 1 to 2 days after administration of doxorubicin and that they should not be alarmed. PRECAUTIONS General Doxorubicin is not an anti-microbial agent. toxicity of recommended doses of doxorubicin can be enhanced by hepatic impairment. Doxorubicin was embryotoxic (increase in embryofetal deaths) and abortifacient at 0. or if the patient becomes pregnant during therapy. Coma and/or seizures have also been described. dehydration. Doxorubicin was teratogenic and embryotoxic at doses of 0. tracheoesophageal fistula. may be increased when doxorubicin is used in combination with other cytotoxic drugs. Progesterone In a published study. (See DOSAGE AND ADMINISTRATION. Information for Patients Patients should be informed of the expected adverse effects of doxorubicin. pharmacokinetics. Women treated with doxorubicin may develop irreversible amenorrhea. therapeutic efficacy. particularly when given in conjunction with other emetigenic drugs. diarrhea. Two published studies report that initial administration of paclitaxel infused over 24 hours followed by doxorubicin administered over 48 hours resulted in a significant decrease in doxorubicin clearance with more profound neutropenic and stomatitis episodes than the reverse sequence of administration. Teratogenicity and embryotoxicity were also seen using discrete periods of treatment.Since metabolism and excretion of doxorubicin occurs predominantly by the hepatobiliary route. especially hematologic and gastrointestinal events. and stomatitis) and potential neutropenic complications. Patients should consult their physician if vomiting. Changes in hepatic function induced by concomitant therapies may affect doxorubicin metabolism. vomiting. or injection-site pain occurs following therapy with doxorubicin. understand that there is a risk of irreversible myocardial damage associated with treatment with doxorubicin. men undergoing treatment with doxorubicin should use effective contraceptive methods. prophylactic use of antiemetics should be considered before administration of doxorubicin. Antiemetics may reduce nausea and 9day gestation period at doses of 1. Patients should be informed that they will almost certainly develop alopecia. evaluation of hepatic function is recommended using conventional laboratory tests such as SGOT.) Pregnancy Category D Doxorubicin can cause fetal harm when administered to a pregnant woman.8 mg/kg/day (about 1/13 the recommended human dose on a body surface area basis) when administered during the period of organogenesis in rats. Because doxorubicin may induce chromosomal damage in sperm. Cyclosporine The addition of cyclosporine to doxorubicin may result in increases in AUC for both doxorubicin and doxorubicinol possibly due to a decrease in clearance of parent drug and a decrease in metabolism of doxorubicinol.25 mg/kg/day and greater. Patients should . and/or toxicity. Women of childbearing age should be advised to avoid becoming pregnant. including gastrointestinal symptoms (nausea. progesterone was given intravenously to patients with advanced malignancies (ECOG PS<2) at high doses (up to 10 g over 24 hours) concomitantly with a fixed doxorubicin dose (60 mg/m2) via bolus injection. or premature menopause. There are no adequate and wellcontrolled studies in pregnant women. Characteristic malformations included esophageal and intestinal atresia. fever. SGPT. Doxorubicin is emetigenic. The most susceptible was the 6.

Concurrent treatment with doxorubicin has been reported to exacerbate cyclophosphamide-induced hemorrhagic cystitis. and SCE assays) and the in vivo mouse micronucleus assay.2 mg/kg/day (about 1/200 and 1/50 the recommended human dose on a body surface area basis) when administered from 14 days before mating through late gestation period. Oligospermia or azoospermia were evidenced in men treated with doxorubicin. Doxorubicin is mutagenic as it induces DNA damage in rabbit spermatozoa and dominant lethal mutations in mice. Carcinogenesis.) Pediatric patients treated with doxorubicin or other topoisomerase II inhibitors are at risk for developing acute myelogenous leukemia and other neoplasms. This effect may be permanent. doxorubicin. urine alkalinization.Dexrazoxane In a clinical study of women with metastatic breast cancer. . Men undergoing doxorubicin treatment should use effective contraceptive methods. diffuse degeneration of the seminiferous tubules. Laboratory Tests Initial treatment with doxorubicin requires observation of the patient and periodic monitoring of complete blood counts. and left ventricular ejection fraction.) Abnormalities of hepatic function tests may occur.1 mg/kg (about 1/100 the recommended human dose on a body surface area basis) was toxic to male reproductive organs producing testicular atrophy and oligospermia in rats. Cytarabine Necrotizing colitis manifested by typhlitis (cecal inflammation). V79 hamster cell. doxorubicin can potentially induce chromosomal damage in human spermatozoa. Oligospermia or azoospermia were evidenced in men treated with doxorubicin. Therefore. Doxorubicin is mutagenic as it induced DNA damage in rabbit spermatozoa and dominant lethal mutations in mice. producing testicular atrophy. Doxorubicin was toxic to male reproductive organs in animal studies. Doxorubicin was mutagenic in the in vitro Ames assay. Doxorubicin decreased fertility in female rats at the doses of 0. with the initiation of a regimen of fluorouracil. human lymphoblast. (See WARNINGS. In women. (See WARNINGS. Cyclophosphamide The addition of cyclophosphamide to doxorubicin treatment does not affect exposure to doxorubicin. Blood uric acid levels. Like other cytotoxic drugs. the concurrent use of the cardioprotectant. mainly in combination therapies. dexrazoxane. Acute myeloid leukemia has been reported as a second malignancy after treatment with doxorubicin and cyclophosphamide. hepatic function tests. Dexrazoxane is only indicated for use in women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300 mg/m2 and are continuing with doxorubicin therapy. but may result in an increase in exposure to doxorubicinol. doxorubicin may induce "tumor lysis syndrome" and hyperuricemia in patients with rapidly growing tumors. This may occur several years after the end of the therapy. Mutagenesis. and cyclophosphamide (FAC) was associated with a lower tumor response rate. and creatinine should be evaluated after initial treatment. and hypospermia. doxorubicin may cause infertility during the time of drug administration. potassium. Men undergoing doxorubicin treatment should use effective contraceptive methods. Later initiation of dexrazoxane (after administration of a cumulative doxorubicin dose of 300 mg/m2 of doxorubicin had been given as a component of FAC) was not associated with a reduction in chemotherapy activity. a metabolite. and administration of live vaccines to immunosuppressed patients including those undergoing cytotoxic chemotherapy may be hazardous. and Impairment of Fertility Carcinogenicity studies have not been conducted with doxorubicin. and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor-lysis syndrome. A single IV dose of doxorubicin at 0. Hydration. saquinavir in combination with cyclophosphamide. mainly in combination therapies. Doxorubicin may . doxorubicin. calcium. bloody stools and severe and sometimes fatal infections have been associated with a combination of doxorubicin given by intravenous push daily for 3 days and cytarabine given by continuous infusion daily for 7 or more days. and clastogenic in multiple in vitro assays (CHO cell. and etoposide increased mucosal toxicity in patients with HIV-associated non-Hodgkin's lymphoma. Secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) have been reported in patients treated with doxorubicin-containing combination chemotherapy regimens. doxorubicin may potentially induce chromosomal damage in human spermatozoa. phosphate. However. Literature reports have also described the following drug interactions Phenobarbital increases the elimination of doxorubicin. Doxorubicinol only has 5% of the cytotoxic activity of doxorubicin. phenytoin levels may be decreased by doxorubicin. streptozocin (Zanosar®) may inhibit hepatic metabolism of doxorubicin. sperm counts have been reported to return to normal levels in some instances.05 and 0. Therefore.

Mucositis (stomatitis and esophagitis) may occur within 5 to 10 of beginning therapy. Hyperpigmentation of nailbeds and dermal creases. Anorexia. Other reactions reported are: Ocular Conjunctivitis. Anaphylaxis may occur. or photosensitivity may occur. although premature menopause can occur. doxorubicinol have been detected in the milk of at least one lactating patient.) Doxorubicin. diarrhea.cause amenorrhea. and hyperpigmentation of the oral mucosa have been occasionally reported. Follow-up cardiac evaluations are recommended periodically to monitor for this delayed cardiotoxicity. The decision to use doxorubicin in the treatment of older patients should be based upon a consideration of overall performance status and concurrent illnesses. Geriatric Use An estimated 4600 patients who were 65 and over were included in the reported clinical experience of doxorubicin use for various indications.) Because of the potential for serious adverse reactions in nursing infants from doxorubicin. Pediatric patients treated with doxorubicin or other topoisomerase II inhibitors are at a risk for developing acute myelogenous leukemia and other neoplasms. (See WARNINGS. Hematologic. . which is usually temporary. Neurological Peripheral neurotoxicity in the form of local-regional sensory and/or motor disturbances have been reported in patients treated intra-arterially with doxorubicin. This may be alleviated by antiemetic therapy. Cardiotoxicity (See WARNINGS. keratitis. No overall differences in safety and effectiveness were observed between these patients and younger patients. Radiation recall reaction has occurred with doxorubicin administration. Other Malaise/asthenia have been reported. may occur leading to bleeding or severe infections which can be fatal. and onycholysis have been reported in a few cases. itching. in addition to age of the individual patient. The effect may be severe leading to ulceration and represents a site of origin for severe infections. chills and urticaria have been reported occasionally. ADVERSE REACTIONS Dose limiting toxicities of therapy are myelosuppression and cardiotoxicity.) Pregnancy Category D (See WARNINGS. Ulceration and necrosis of the colon. It may also contribute to gonadal impairment. Rash. Seizures and coma have been reported in patients treated with doxorubicin in combination with cisplatin or vincristine. This reaction has been reported in patients with acute nonlymphocytic leukemia treated with a 3-day course of doxorubicin combined with cytarabine. mothers should be advised to discontinue nursing during doxorubicin therapy. dehydration. The dosage regimen consisting of administration of doxorubicin on three successive days results in greater incidence and severity of mucositis. Pediatric Use Pediatric patients are at increased risk for developing delayed cardiotoxicity. and lacrimation occur rarely. Recovery of menses is related to age at treatment. Hematologic (See WARNINGS.) Cutaneous Reversible complete alopecia occurs in most cases. mostly in combination with cisplatin. Ovulation and menstruation may return after termination of therapy. (See CLINICAL PHARMACOLOGY. especially the cecum. abdominal pain. Secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) have been reported in patients treated with anthracycline-containing adjuvant combination chemotherapy regimens. Pharmacokinetics.) Nursing Mothers Doxorubicin and its major metabolite. and most patients recover from this adverse event within another 5 to 10 days. may contribute to prepubertal growth failure. A case of apparent cross sensitivity to lincomycin has been reported.) Hypersensitivity Fever. Animal studies have demonstrated seizures and coma in rodents and dogs treated with intra-carotid doxorubicin. (SeeWARNINGS. primarily in pediatric patients. Pediatric patients receiving concomitant doxorubicin and actinomycinD have manifested acute "recall" pneumonitis at variable times after local radiation therapy. Gastrointestinal Acute nausea and vomiting occurs frequently and may be severe. but greater sensitivity of some older individuals cannot be ruled out. as a component of intensive chemotherapy regimens administered to pediatric patients.

film-coated tablet is debossed with “250” on one side and “K” on the other side and contains Tranylcypromine sulfate equivalent to 10 mg of Tranylcypromine. and serotonin in storage sites throughout the nervous system and. although the drug is excreted in 24 hours. this increased concentration of monoamines in the brain stem is the basis for its antidepressant activity. INDICATIONS For the treatment of Major Depressive Episode Without Melancholia. . and Opadry® II pink 85F14289. It increases the concentration of epinephrine. croscarmellose sodium. norepinephrine. dark pink. When Tranylcypromine is withdrawn. dibasic calcium phosphate anhydrous. and titanium dioxide. Inactive ingredients consist of colloidal silicon dioxide. microcrystalline cellulose.Tranylcypromine Description Chemically. Tranylcypromine sulfate is (±)-trans-2-phenylcyclopropylamine sulfate (2:1). magnesium stearate. polyvinyl alcohol. Opadry pink is used for purposes of coating and contains the following: FD&C Red # 40. ACTION Tranylcypromine is a non-hydrazine monoamine oxidase inhibitor with a rapid onset of activity. in theory. talc. polyethylene glycol 3350. talc. monoamine oxidase activity is recovered in 3 to 5 days. Each round.

Tranylcypromine sulfate should be used in adult patients who can be closely supervised. The effectiveness of Tranylcypromine sulfate has been established in adult outpatients. In the presence of pheochromocytoma Tranylcypromine sulfate should not be used in the presence of pheochromocytoma since such tumors secrete pressor substances. 3. As described in the American Psychiatric Association's Diagnostic and Statistical Manual. In patients with cerebrovascular defects or cardiovascular disorders Tranylcypromine sulfate should not be administered to any patient with a confirmed or suspected cerebrovascular defect or to any patient with cardiovascular disease or hypertension. and suicidal ideation or attempts. allow a medication-free interval of at least a week. third edition (DSM III). It should rarely be the first antidepressant drug given. Similarly. 2. then initiate Tranylcypromine sulfate using half the normal starting dosage for at least the first week of therapy. The effectiveness of Tranylcypromine sulfate in patients who meet the criteria for Major Depressive Episode with Melancholia (endogenous features) has not been established. most of whom had a depressive illness which would correspond to a diagnosis of Major Depressive Episode Without Melancholia. feelings of guilt or worthlessness. . increased fatigability. Major Depressive Episode implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning and includes at least 4 of the following 8 symptoms: change in appetite. Contraindications Tranylcypromine sulfate is contraindicated: 1. slowed thinking or impaired concentration. psychomotor agitation or retardation. the drug is suited for patients who have failed to respond to the drugs more commonly administered for depression. at least a week should elapse between the discontinuance of Tranylcypromine sulfate and the administration of another MAO inhibitor or a dibenzazepinerelated entity. loss of interest in usual activities or decrease in sexual drive. In combination with MAO inhibitors or with dibenzazepine-related entities Tranylcypromine sulfate should not be administered together or in rapid succession with other MAO inhibitors or with dibenzazepine-related entities. Rather. or the readministration of Tranylcypromine sulfate. In patients being transferred to Tranylcypromine sulfate from another MAO inhibitor or from a dibenzazepinerelated entity. Hypertensive crises or severe convulsive seizures may occur in patients receiving such combinations. change in sleep.

Amlodipine side effects Get emergency medical help if you have any of these signs of an allergic reaction to amlodipine: hives. swelling in your hands. This medication is for use in adults and children who are at least 6 years old. In clinical studies.Generic Name: amlodipine Brand Names: Norvasc What is amlodipine? Amlodipine is in a group of drugs called calcium channel blockers. or feet. or angiographically documented coronary artery disease in patients without heart failure or an ejection fraction less than 40%: 5 to 10 mg orally once a day • • • • feeling like you might pass out. lips. sweating. Amlodipine is used to treat high blood pressure (hypertension) or chest pain (angina) and other conditions caused by coronary artery disease. Less serious amlodipine side effects may include: • • • • • headache. drowsiness. ankles. redness. Usual Adult Amlodipine Dose for Angina Pectoris: Chronic stable or vasospastic angina. dizziness. Most patients with chronic stable or vasospastic angina require 10 mg for adequate effect. or chest pain or heavy feeling. most patients with coronary artery disease Amlodipine Dosing Information * required 10 mg. Amlodipine may also be used for other purposes not listed in this medication guide. or tingly feeling). Call your doctor at once if you have a serious side effect such as: Usual Adult Amlodipine Dose for Hypertension: Initial dose: 5 mg orally once a day Maintenance dose: 5 to 10 mg orally once a day Small or fragile patients may be started on 2. pounding heartbeats or fluttering in your chest.5 mg orally once a day. difficulty breathing. nausea. swelling of your face. stomach pain. or flushing (warmth. . or throat. general ill feeling. tired feeling. tongue. Amlodipine relaxes (widens) blood vessels and improves blood flow. pain spreading to the arm or shoulder.

Do not start a new medication without telling your doctor. Tell your doctor about all medications you use. Usual Pediatric Dose for Hypertension: 6 to 17 years: 2.5 mg to 5 mg orally once a day Most patients with chronic stable or vasospastic angina require 10 mg for adequate effect. and herbal products. This includes prescription. most patients with coronary artery disease required 10 mg. There may be other drugs that can interact with amlodipine. What other drugs will affect amlodipine? Tell your doctor about all other heart or blood pressure medications you are taking.5 mg orally once a day Maintenance dose: 2. most patients require 10 mg for adequate effect. Usual Geriatric Amlodipine Dose for Hypertension: Initial dose: 2. In clinical studies. or angiographically documented coronary artery disease in patients without heart failure or an ejection fraction less than 40%: 5 to 10 mg orally once a day Chronic stable or vasospastic angina: 5 to 10 mg orally once a day The lower dose is recommended in the elderly.5 to 10 mg orally once a day Usual Geriatric Dose for Angina Pectoris: Doses in excess of 5 mg daily have not been studied in pediatric patients. over-the-counter.Usual Adult Amlodipine Dose for Coronary Artery Disease: Chronic stable or vasospastic angina. however. . vitamin.

vomiting. upset stomach. Maintenance dose: 5 to 20 mg orally once a day. • • • • • • feeling like you might pass out. Usual Adult Dose for Congestive Heart Failure: Initial dose: 5 mg orally once a day (If on diuretic. depressed mood. Maintenance dose: 20 to 40 mg orally once a day. the diuretic dose should be reduced). drowsiness. tongue.Generic Name: lisinopril Brand Names: Prinivil. and to improve survival after a heart attack. but experience with this dose is limited. or mild skin itching or rash. severe stomach pain. in patients not receiving a diuretic. rapid weight gain. Lisinopril side effects Get emergency medical help if you have any of these signs of an allergic reaction to lisinopril: hives. diarrhea. muscle weakness. Lisinopril is used to treat high blood pressure (hypertension). urinating more or less than usual. dizziness. swelling of your face. lips. headache. fever. Usual Adult Dose for Myocardial Infarction: . Lisinopril may also be used for purposes not listed in this medication guide. chills. Zestril What is lisinopril? Lisinopril is in a group of drugs called ACE inhibitors. ACE stands for angiotensin converting enzyme. Lisinopril Dosing Information Usual Adult Dose for Hypertension: Call your doctor at once if you have a serious side effect such as: Initial dose: 10 mg orally once a day. tired feeling. body aches. • • nausea. and pounding or uneven heartbeats. chest pain. flu symptoms. Some patients appear to have a further response to 80 mg. congestive heart failure. difficult breathing. or swelling. Less serious lisinopril side effects may include: • • • cough. or not at all. or throat.

celecoxib (Celebrex). or • a diuretic (water pill). Motrin). If hypotension occurs (systolic blood pressure <=100 mm Hg) a daily maintenance dose of 5 mg may be given with temporary reductions to 2. If prolonged hypotension occurs (systolic blood pressure <90 mm Hg for more than 1 hour). Usual Geriatric Dose for Hypertension: Initial dose: 2. Maximum dose: 40 mg/day. What other drugs will affect lisinopril? Tell your doctor about all other medicines you use.61 mg/kg or greater than 40 mg have not been studied in pediatric patients. Cambia. meloxicam (Mobic). lithium (Lithobid. Naprelan. salt substitutes that contain potassium. and others. especially: • • • • • • gold injections to treat arthritis. lisinopril should be withdrawn. Maintenance dose: Dosages should be increased at 2. indomethacin (Indocin).5 to 5 mg/day increments at 1 to 2 week intervals. Maintenance dose: 10 mg orally once a day.5 mg oral dose of lisinopril. Coronary Artery Disease Medications . Subsequent doses: 5 mg orally after 24 hours. Maximum dose: Doses above 0. Solareze).Initial dose: 5 mg orally (within 24 hours of the onset of acute myocardial infarction).5 mg if needed. Treximet). Eskalith).07 mg/kg once daily (Maximum initial dose is 5 mg once daily) Maintenance dose: Dosage should be adjusted according to blood pressure response at 1 to 2 week intervals. Patients with a low systolic blood pressure (<=120 mm Hg) when treatment is started or during the first 3 days after the infarct should be given a lower 2. Naprosyn. Klor-Con. a potassium supplement such as K-Dur. diclofenac (Arthrotec. Pennsaid. Voltaren. naproxen (Aleve. Cataflam. 10 mg orally after 48 hours. Usual Adult Dose for Diabetic Nephropathy: Initial dose: 10 to 20 mg orally once a day. insulin or diabetes medication you take by mouth. Dosage may be titrated upward every 3 days.5 to 5 mg orally once a day. Maintenance dose: 20 to 40 mg orally once a day. aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Advil. Usual Pediatric Dose for Hypertension: Pediatric patients greater than or equal to 6 years of age: Initial dose: 0. Flector Patch. Dosing should continue for six weeks.