Xeloda

Generic Name: Capecitabine
Class: Antineoplastic Agents
VA Class: AN300
Chemical Name: Pentyl ester [1-(5-deoxy-β-d-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinyl]-carbamic acid
Molecular Formula: C₁₅ H₂₂FN₃O₆
CAS Number: 154361-50-9

• Alterations in Anticoagulant Effects


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  Altered coagulation parameters (e.g., increased PT, increased INR) and/or bleeding, sometimes fatal, reported in patients, with or without liver metastases, receiving capecitabine concomitantly with coumarin-derivative anticoagulants.^{1 29 35} Generally occurs within several days to months following initiation of therapy, but has been reported within 1 month following discontinuance of therapy.^{1 29} (See Coagulopathy under Cautions and also see Specific Drugs under Interactions.)

  
  


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  Age >60 years and diagnosis of cancer may independently increase risk of coagulopathy.^{1 35}

  
  


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  Monitor anticoagulant response (PT or INR) frequently in patients receiving concomitant capecitabine and oral coumarin-derivative therapy; adjust anticoagulant dosage accordingly.¹

  
  

Introduction

Antineoplastic agent; prodrug of fluorouracil (an antimetabolite).^{1 2 3 5 6 7 14}

Uses for Xeloda

Breast Cancer

Treatment of metastatic breast cancer in combination with docetaxel in patients with disease that failed to respond to, or recurred or relapsed during or following, anthracycline-containing chemotherapy.^{1 33}

Synergistic effect with combination therapy; docetaxel increases the expression of an enzyme found at higher concentrations in many tumor cells that is involved in converting capecitabine to its active moiety, fluorouracil.^{10 37}

Palliative treatment of metastatic breast cancer, as monotherapy, in patients with disease resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or in patients with disease resistant to paclitaxel who are not candidates for further anthracycline therapy (e.g., cumulative doses of 400 mg/m² of doxorubicin or doxorubicin equivalents).^{1 18 33 34}

Colorectal Cancer

Used alone as adjuvant therapy following the complete resection of primary tumor in patients with stage III (Dukes’ C) colon cancer when treatment with fluoropyrimidine therapy alone is preferred.^{1 40 41} May be used as an alternative to fluorouracil/leucovorin when single-agent therapy is desired for convenience or lesser toxicity.^{40 41 43}

Initial (first-line) treatment of metastatic colorectal cancer when fluoropyrimidine therapy alone is preferred.^{1 34}

Gastric Cancer

Being investigated for use in combination regimens for advanced gastric cancer†.^{44 45}

Xeloda Dosage and Administration

Administration

Oral Administration

Administer orally with water twice daily within 30 minutes after the end of a meal, in the morning and evening.¹

If administered concomitantly with docetaxel, patients should be premedicated prior to docetaxel administration.¹ Consult docetaxel manufacturer's labeling for specific information.¹

Dosage

Adults

Breast Cancer

Combination Therapy

Oral

Initially, 1250 mg/m² twice daily (2500 mg/m² total daily dose) for 2 weeks followed by a 1-week rest period; courses of therapy are given in 3-week cycles.¹ (See Table 1.)

Treatment was continued for at least 6 weeks in a clinical trial.¹

Consult published protocols for dosages in combination regimens and methods and sequence of administration.¹

After the initial dose, modify subsequent doses as necessary based on individual patient tolerance with careful monitoring to obtain optimal therapeutic response with minimal toxicity.¹ (See Table 2.)

Monotherapy

Oral

Initially, 1250 mg/m² twice daily (2500 mg/m² total daily dose) for 2 weeks followed by a 1-week rest period; courses of therapy are given in 3-week cycles.¹ (See Table 1.)

Some experts suggest that a trial of 2 cycles (i.e., 6 weeks) of therapy is adequate to assess response.²⁶ During a clinical trial, onset of response typically occurred within 6–12 weeks.¹⁵

After the initial dose, modify subsequent doses as necessary based on individual patient tolerance with careful monitoring to obtain optimal therapeutic response with minimal toxicity.¹ (See Table 3.)

Colorectal Cancer

Adjuvant Therapy for Colon Cancer

Oral

Initially, 1250 mg/m² twice daily (2500 mg/m² total daily dose) for 2 weeks followed by a 1-week rest period; courses of therapy are given in 3-week cycles for a total of 8 cycles and a treatment period of 6 months.¹ (See Table 1.)

After the initial dose, modify subsequent doses as necessary based on individual patient tolerance with careful monitoring to obtain optimal therapeutic response with minimal toxicity.¹ (See Table 3.)

First-line Therapy for Metastatic Colorectal Cancer

Oral

Initially, 1250 mg/m² twice daily (2500 mg/m² total daily dose) for 2 weeks followed by a 1-week rest period; courses of therapy are given in 3-week cycles.¹ (See Table 1.)

After the initial dose, modify subsequent doses as necessary based on individual patient tolerance with careful monitoring to obtain optimal therapeutic response with minimal toxicity.¹ (See Table 3.)

Other Dosage Considerations

Recommended Initial Dosage

Divide into 2 equal doses given morning and evening.

Table 1. Recommended Initial Dosage of Capecitabine: 1250 mg/m2 twice daily

Body Surface Area (m2)	Total Daily Dose (mg)
≤1.25	3000
1.26–1.37	3300
1.38–1.51	3600
1.52–1.65	4000
1.66–1.77	4300
1.78–1.91	4600
1.92–2.05	5000
2.06–2.17	5300
≥2.18	5600

Dosage Modification for Toxicity

Adjust doses according to the severity and recurrence of the toxicity. (See Table 2 and Table 3.)¹

When therapy is interrupted because of toxicity, resume according to planned treatment cycles;¹ doses omitted because of toxicity should not be replaced.¹ Once a dosage has been reduced for toxicity, it should not be increased at a later time.¹

If a patient experiences either no toxicity or NCIC grade 1 toxicity within a course of treatment, maintain the current dose for subsequent courses of therapy until more serious toxicity occurs.¹

Prophylaxis for toxicity should be instituted whenever possible; all dosage modifications should be based on the worst preceding toxicity.

NCIC Common Toxicity Criteria except for hand-foot syndrome, which is defined according to a grading system incorporated by Roche and accepted by FDA.^{1 25}

Table 2. Recommended Dosage Modifications for Toxicity with Capecitabine and Docetaxel Therapy

NCIC Toxicity Grade	Number of Appearances	Comments
Grade 2	1st appearance	Interrupt therapy until resolved to grade 0–1, then resume at 100% of the original capecitabine dose; do not replace missed doses If toxicity persists when the next course of therapy is due, delay therapy until toxicity resolved to grade 0–1, then resume therapy at 100% of the original capecitabine and docetaxel doses
	2nd appearance	Interrupt therapy until resolved to grade 0–1, then resume at 75% of the original capecitabine dose; do not replace missed doses If toxicity persists when the next course of therapy is due, delay therapy until resolved to grade 0–1, then resume therapy at 75% of the original capecitabine dose and at 55 mg/m2 of docetaxel
	3rd appearance	Interrupt therapy until resolved to grade 0–1, then resume at 50% of the original capecitabine dose; do not replace missed doses If toxicity persists when the next course of therapy is due, delay therapy until resolved to grade 0–1, then resume therapy at 50% of the original capecitabine dose and discontinue docetaxel
	4th appearance	Discontinue therapy permanently
Grade 3	1st appearance	Interrupt therapy until resolved to grade 0–1, then resume at 75% of the original capecitabine dose; do not replace missed doses If toxicity persists when the next course of therapy is due, delay therapy until toxicity resolved to grade 0–1, then resume therapy at 75% of the original capecitabine dose and at 55 mg/m2 of docetaxel
	2nd appearance	Interrupt therapy until resolved to grade 0–1 and then resume at 50% of the original capecitabine dose; do not replace missed doses If toxicity persists when the next course of therapy is due, delay therapy until resolved to grade 0–1, then resume therapy at 50% of the original capecitabine dose and discontinue docetaxel
	3rd appearance	Discontinue therapy permanently
Grade 4	1st appearance	Discontinue therapy permanently Or If deemed in best interest of patient to continue therapy, interrupt therapy until resolved to grade 0–1, then resume therapy at 50% of the original dose of capecitabine
	2nd appearance	Discontinue therapy permanently

All dose modifications should be based on the worst preceding toxicity.

NCIC Common Toxicity Criteria except for hand-foot syndrome, which is defined according to a grading system incorporated by Roche and accepted by FDA.^{1 25}

Table 3. Recommended Dosage Modifications for Toxicity of Capecitabine Monotherapy

NCIC Grade of Toxicity	Number of Appearances	During a Course of Therapy	Dose Adjustment for Next Cycle (% of Initial Dose)
Grade 2	1st appearance	Interrupt therapy until resolved to grade 0–1	100%
	2nd appearance	Interrupt therapy until resolved to grade 0–1	75%
	3rd appearance	Interrupt therapy until resolved to grade 0–1	50%
	4th appearance	Discontinue therapy permanently
Grade 3	1st appearance	Interrupt therapy until resolved to grade 0–1	75%
	2nd appearance	Interrupt therapy until resolved to grade 0–1	50%
	3rd appearance	Discontinue therapy permanently
Grade 4	1st appearance	Discontinue therapy permanently
		or
		If deemed in best interest of patient to continue therapy, interrupt therapy until resolved to grade 0–1	50%

Special Populations

Hepatic Impairment

No initial dosage adjustment necessary in patients with mild to moderate hepatic dysfunction secondary to liver metastases.^{1 23} Use with caution; monitor patients carefully during therapy.^{1 23}

Renal Impairment

Contraindicated in patients with severe renal impairment (Cl_cr <30 mL/minute).^{1 36}

In patients with moderate renal impairment (Cl_cr 30–50 mL/minute), reduce dosage (as monotherapy or in combination with docetaxel) by 25% of the initial dose (i.e., from 1250 to 950 mg/m² twice daily).^{1 36}

No adjustment in starting dose recommended in patients with mild renal impairment.^{1 36}

Monitor carefully in patients with mild or moderate renal impairment because the frequency and/or severity of adverse effects may be increased.^{1 36} Discontinue treatment promptly if the patient develops a grade 2, 3, or 4 adverse effect; modify dosage for toxicity.^{1 36} (See Table 2 and Table 3.)

Geriatric Patients

Manufacturer states that insufficient data are available to recommend dosage adjustment for age in geriatric patients;¹ however, the greater frequency of decreased hepatic and/or renal function in the elderly should be considered.²⁶

Patients >80 years of age receiving monotherapy: Some experts recommend dosage reduction (e.g., reduce initial dosage by up to 20%).²⁶ (See Geriatric Use under Cautions.)

Patients >60 years of age receiving capecitabine/docetaxel combination: Some experts recommend dosage reduction (reduce initial dose by 25% [to 950 mg/m²]).³⁷ (See Geriatric Use under Cautions.)

Cautions for Xeloda

Contraindications

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  Severe renal impairment (Cl_cr <30 mL/minute).^{1 36}

  
  


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  Known dihydropyrimidine dehydrogenase (DPD) deficiency.¹

  
  


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  Known hypersensitivity to fluorouracil.¹

  
  


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  Known hypersensitivity to capecitabine or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Coagulopathy

Altered coagulation parameters and/or bleeding, sometimes fatal, reported in patients receiving capecitabine concomitantly with coumarin anticoagulants (e.g., warfarin, phenprocoumon [no longer commercially available in the US]).^{1 29 35} Generally occurs within several days to months following initiation of therapy; similar events reported in at least a few patients within 1 month following discontinuance of therapy.^{1 29}

Alterations in anticoagulant effect associated with capecitabine therapy reported in patients with or without liver metastases.^{1 29} Age >60 years and diagnosis of cancer are independent variables predisposing patients to an increased risk of coagulopathy.^{1 35}

Monitor anticoagulant response (PT or INR) frequently, and adjust the anticoagulant dose accordingly in patients receiving concomitant therapy.^{1 29 35} (See Specific Drugs under Interactions.)

GI Effects

Possible diarrhea, sometimes severe or life-threatening.¹

If grade 2, 3, or 4 diarrhea occurs, immediately discontinue administration until the diarrhea resolves or decreases in intensity to grade 1.¹ Decrease subsequent doses in patients who have experienced grade 3 or 4 diarrhea or recurring episodes of grade 2 diarrhea.^{1 25} (See Table 2 and Table 3.)

Median time to onset of grade 2 to 4 diarrhea was 34 days (range: 1–369 days) following initiation of therapy; median duration of grade 3 to 4 diarrhea was 5 days.¹

Diarrhea may respond to standard antidiarrheal therapy (e.g., loperamide).¹ Monitor patients with severe diarrhea closely and give fluid and electrolyte replacement for dehydration as indicated.¹

Severe adverse GI effects may occur more frequently in geriatric patients.¹ (See Geriatric Use under Cautions.)

Necrotizing enterocolitis (typhlitis) reported.¹

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; avoid pregnancy during therapy.¹ However, potential benefits from use of the drug may be acceptable in certain conditions despite the possible risks to the fetus.^{1 12 13}

Use during pregnancy only in life-threatening situations or severe disease for which safer drugs cannot be used or are ineffective.^{1 12} If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.¹

Embryotoxic and teratogenic in animals.¹

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions,¹ including bronchospasm,³⁸ reported.

General Precautions

Hand-foot Syndrome

Palmar-plantar erythrodysesthesia or chemotherapy-induced acral erythema (hand-foot syndrome) occurs in 54–63% of patients and is severe (grade 3) in 11–24% of patients.¹ Median time to onset is 79 days (range: 11–360 days).¹

If grade 2 or 3 hand-foot syndrome occurs, withhold administration of capecitabine until manifestations resolve or decrease in intensity to grade 1.¹ Decrease subsequent doses in patients experiencing grade 3 hand-foot syndrome or recurring episodes of grade 2 hand-foot syndrome.^{1 25} (See Table 2 and Table 3.)

Topical emollients (e.g., hand creams, udder balm)^{15 16 19} or oral pyridoxine therapy^{16 19 22} may ameliorate the manifestations of hand-foot syndrome.

Cardiotoxicity

Risk of MI/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, ECG changes, and cardiomyopathy.¹ Increased incidence in patients with a history of CAD.¹

Dihyropyrimidine Dehydrogenase Activity Deficiency

Rarely, severe, unexpected toxicity (e.g., stomatitis, diarrhea, neutropenia, neurotoxicity) associated with fluorouracil has been attributed to a deficiency of dihyropyrimidine dehydrogenase activity.¹ (See Contraindications under Cautions.)

Hyperbilirubinemia

Risk of severe, possibly life-threatening hyperbilirubinemia, occurring alone or in combination with docetaxel.¹

If grade 2, 3, or 4 elevations in serum bilirubin concentration occur, discontinue administration of capecitabine until the hyperbilirubinemia resolves or decreases in intensity to grade 1.¹

Severe or life-threatening hyperbilirubinemia associated with capecitabine therapy occurs more frequently in patients with hepatic metastases.¹ Monitor liver function carefully during therapy in patients with mild to moderate hepatic impairment secondary to liver metastases.¹

Hematologic Effects

Possible lymphopenia, neutropenia, thrombocytopenia, or anemia.¹

Specific Populations

Pregnancy

Category D.¹

Lactation

Distributed into milk in mice.¹ Discontinue nursing because of the potential risk to nursing infants.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹

Geriatric Use

Safety and efficacy in geriatric patients not specifically studied to date; however, geriatric individuals may experience increased frequency and severity of toxicity (e.g., grade 3 or 4 diarrhea, nausea, or vomiting; severe hand-foot syndrome).¹ (See GI Effects and also see Hand-foot Syndrome under Cautions.)

Possible increased risk of coagulopathy in patients >60 years receiving concomitant anticoagulant therapy.^{1 35} (See Coagulopathy under Cautions.)

Monitor geriatric patients closely for the occurrence of capecitabine-induced adverse effects.¹

Hepatic Impairment

Monitor carefully in patients with mild to moderate hepatic impairment due to liver metastases.¹ Safety and efficacy not studied in patients with severe hepatic impairment.¹

Renal Impairment

Contraindicated in patients with severe renal impairment (Cl_cr <30 mL/minute).^{1 36}

Frequency and/or severity of adverse effects may be increased in patients with mild or moderate renal impairment.^{1 36} Monitor carefully.^{1 36} Discontinue treatment promptly if the patient develops a grade 2, 3, or 4 adverse effect; modify dosage for toxicity.^{1 36} (See Table 2 and Table 3.)

Common Adverse Effects

Abdominal pain,¹ diarrhea,¹ nausea,¹ vomiting,¹ stomatitis,¹ constipation,¹ fatigue/weakness,¹ anemia,¹ lymphopenia,^{1 25} dermatitis,¹ hand-foot syndrome.¹

Interactions for Xeloda

Potential inhibition of CYP2C9.¹

Does not inhibit CYP isoenzymes 1A2, 2A6, 3A4, 2C9, 2C19, 2D6, or 2E1 in vitro.¹

Drugs Metabolized by Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (decreased warfarin metabolism) probably through inhibition of CYP2C9.^{1 35} (See Specific Drugs under Interactions.)

No formal drug interaction studies between capecitabine and CYP2C9 substrates other than warfarin have been performed.^{1 35}

Specific Drugs

Drug	Interaction	Comments
Antacids (aluminum and magnesium hydroxide)	Increased rate and extent of absorption of capecitabine.1 Increased plasma concentrations of 5′-deoxy-5-fluorocytidine (5′-DFCR).1 Concurrent administration had no effect on the other 3 major metabolites of capecitabine (i.e., 5′-deoxy-5-fluorouridine [5′-DFUR], fluorouracil, and α-fluoro-β-alanine [FBAL])1 17	Clinical effects of concomitant administration are uncertain17 Some clinicians advise delay of administration of antacids for ≥2 hours following induction of capecitabine therapy26
Anticoagulants	Altered coagulation parameters and/or bleeding, sometimes fatal, reported in patients receiving concomitant therapy1 29 35	Use concomitantly with great caution1 29 35 Monitor PT or INR frequently if used concomitantly; adjust anticoagulant dosage accordingly1 29 35
Leucovorin	Potential increased antineoplastic activity and toxicity of fluorouracil (the active moiety of capecitabine)1	Deaths from severe enterocolitis, diarrhea, and dehydration reported in geriatric patients receiving a weekly regimen of combination therapy1
Phenytoin	Potential increased serum phenytoin concentrations1	Use concomitantly with caution1 35 and monitor serum concentrations of phenytoin carefully; reduction in phenytoin dosage may be necessary1

Xeloda Pharmacokinetics

Absorption

Bioavailability

Readily absorbed from the GI tract; about 70% is absorbed.^{5 14 19 25}

Peak plasma concentrations of capecitabine occur in about 1.5 hours, and peak plasma concentrations of fluorouracil occur slightly later at 2 hours.¹

Onset

For treatment of breast cancer, onset of response to monotherapy typically occurred within 6–12 weeks.¹⁵

Food

Food decreases the rate and extent of absorption and, to a lesser extent, decreases the peak plasma concentration and AUC of its metabolites.^{1 5}

Special Populations

Reduced peak plasma concentration and AUC of capecitabine and its catabolite, α-fluoro-β-alanine (FBAL) reported in Japanese patients compared with white patients.¹ Clinical importance of these differences is not known.¹

Among patients 27–86 years of age, a 20% increase in age is associated with a 15% increase in the AUC of FBAL.¹

Distribution

Extent

Distributed into tumors, intestinal mucosa, plasma, liver, and other tissues.^{3 5 7} Not known whether distributed into CSF and brain tissue in humans; does not readily penetrate the blood-brain barrier in animal studies.^{24 25}

Studies have shown a higher concentration of fluorouracil, its active moiety, in tumor than in surrounding normal tissue, plasma, or muscle.^{1 3 9}

Not known whether capecitabine or its metabolites cross the placenta²⁵ or are distributed into milk.¹

Plasma Protein Binding

<60% (mainly albumin); not concentration dependent.¹

Elimination

Metabolism

Capecitabine is a prodrug of fluorouracil; metabolized to fluorouracil following oral administration.¹

Extensively metabolized in the liver and tumors to inactive, intermediate metabolites that are hydrolyzed mainly in tumor tissue to the active moiety fluorouracil.^{1 3 5 6 7 8}

Fluorouracil is anabolized to active metabolites, 5-fluoro-2′-deoxyuridine-5′-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP).^{1 4 8}

Fluorouracil is catabolized by dihydropyrimidine dehydrogenase to dihydrofluorouracil (FUH₂), a much less toxic metabolite.^{1 4 5 8}

Elimination Route

Excreted principally in urine (95.5%) as metabolites; fecal excretion is minimal (2.6%).¹

Half-life

About 45–60 minutes for capecitabine and its metabolites, except for FBAL, which has an initial half-life of about 3 hours.^{1 6 14}

Special Populations

Increased systemic exposure in patients with renal impairment;^{1 36} systemic exposure to capecitabine was about 25% greater in patients with moderate or severe renal impairment than in those with normal renal function.¹

Dialysis may reduce circulating concentrations of 5′-DFUR, a low molecular weight metabolite of the drug.¹

Stability

Storage

Oral

Tablets

Tight containers at 25°C (may be exposed to 15–30°C.)¹

ActionsActions

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  Prodrug; has little pharmacologic activity until it is converted to fluorouracil, an antimetabolite.^{1 5 6 7}

  
  


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  Converted to fluorouracil by enzymes that are expressed at higher concentrations in many tumors than in adjacent normal tissues or plasma; high tumor concentrations of the active drug may be achieved with less systemic toxicity.^{1 3 5 14}

  
  


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  Fluorouracil is metabolized in both normal and tumor cells to 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP).^{1 4} The main mechanism of action may be the binding of the deoxyribonucleotide of the drug (FdUMP) and the folate cofactor (N^5–10-methylenetetrahydrofolate) to thymidylate synthase (TS) to form a covalently bound ternary complex, which inhibits the formation of thymidylate from 2′-deoxyuridylate, thereby interfering with DNA synthesis.^{1 4} In addition, FUTP can be incorporated into RNA in place of uridine triphosphate (UTP), producing a fraudulent RNA and interfering with RNA processing and protein synthesis.^{1 4}

  
  


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  Active in xenograft tumors that are resistant to fluorouracil indicating incomplete cross-resistance between the drugs.^{2 8 9}

  
  

Advice to Patients

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  Importance of discontinuing the drug and contacting clinician if >4 bowel movements each day or any diarrhea at night occurs.¹

  
  


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  Importance of discontinuing the drug and contacting clinician if >1 episode of vomiting occurs in a 24-hour period.¹

  
  


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  Importance of discontinuing the drug and contacting clinician if loss of appetite occurs or if the amount of food consumed each day is much less than usual.¹

  
  


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  Importance of discontinuing the drug and contacting clinician if pain, redness, swelling, or sores in mouth occur.¹

  
  


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  Importance of discontinuing the drug and contacting clinician if pain and swelling or redness of hands or feet that prevents normal activity occur.¹

  
  


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  Importance of notifying clinician if fever (≥100.5°F) or other signs of infection occur.¹

  
  


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  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

  
  


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  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; necessity for clinicans to advise women to avoid pregnancy during therapy and to advise pregnant women of risk to the fetus.¹

  
  


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  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

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

Capecitabine

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	150 mg	Xeloda	Roche
		500 mg	Xeloda	Roche

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Xeloda 150MG Tablets (GENENTECH): 60/$521 or 180/$1481.98

Xeloda 500MG Tablets (GENENTECH): 120/$3440 or 240/$6779.78

Disclaimer

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

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

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

1. Roche Laboratories Inc. Xeloda (capecitabine) tablets prescribing information. Nutley, NJ; 2006 Jun 12.

2. Cao S, Lu K, Ishitsuka H et al. Antitumor efficacy of capecitabine against fluorouracil-sensitive and -resistant tumors. Proc Am Soc Clin Oncol. 1997; 16:A795.

3. Schüller J, Cassidy J, Dumont E et al. Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol. 2000; 45:291-7. [PubMed 10755317]

4. Pinedo HM, Peters GFJ. Fluorouracil: biochemistry and pharmacology. J Clin Oncol. 1988; 6:1653-64. [PubMed 3049954]

5. Reigner B, Verweij J, Dirix L et al. Effect of food on the pharmacokinetics of capecitabine and its metabolites following oral administration in cancer patients. Clin Cancer Res. 1998; 4:941-8. [IDIS 402744] [PubMed 9563888]

6. Budman DR, Meropol NJ, Reigner B et al. Preliminary studies of a novel oral fluoropyrimidine carbamate: capecitabine. J Clin Oncol. 1998; 16:1795-802. [IDIS 406120] [PubMed 9586893]

7. Miwa M, Ura M, Nishida M et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer. 1998; 34:1274-81. [PubMed 9849491]

8. Ishikawa T, Sekiguchi F, Fukase Y et al. Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts. Cancer Res. 1998; 58:685-90. [PubMed 9485021]

9. Ishikawa T, Utoh M, Sawada N et al. Tumor selective delivery of 5-fluorouracil by capecitabine, a new oral fluoropyrimidine carbamate, in human cancer xenografts. Biochem Pharmacol. 1998; 55:1091-7. [PubMed 9605432]

10. Sawada N, Ishikawa T, Fukase Y et al. Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by Taxol/Taxotere in human cancer xenografts. Clin Cancer Res. 1998; 4:1013-9. [PubMed 9563897]

11. Harris J, Morrow M, Norton L. Malignant tumors of the breast. In: DeVita VT Jr, Hellman S, Rosenberg SA eds. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven Publishers; 1997:1557-1616.

12. Food and Drug Administration. Labeling and prescription drug advertising: content and format for labeling for human prescription drugs. 21 CFR Parts 201 and 202. Final Rule. [Docket No. 75N-0066] Fed Regist. 1979; 44:37434-67.

13. Department of Health and Human Services, Food and Drug Administration. Subpart B—Labeling requirements for prescription drugs and/or insulin. (21 CFR Ch. 1 (4-1-87 Ed.)). 1987:18-24.

14. Mackean M, Planting A, Twelves C et al. Phase I and pharmacologic study of intermittent twice-daily oral therapy with capecitabine in patients with advanced and/or metastatic cancer. J Clin Oncol. 1998; 16:2977-85. [IDIS 414245] [PubMed 9738566]

15. Blum JL, Jones SE, Buzdar AU et al. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol. 1999; 17:485-93. [IDIS 422570] [PubMed 10080589]

16. Berg D. Managing the side effects of chemotherapy for colorectal cancer. Semin Oncol. 1998; 25(Suppl 11):53-9. [PubMed 9786317]

17. Reigner B, Clive S, Cassidy J et al. Influence of the antacid Maalox on the pharmacokinetics of capecitabine in cancer patients. Cancer Chemother Pharmacol. 1999; 43:309-15. [PubMed 10071982]

18. Anon. Trastuzumab and capecitabine for metastatic breast cancer. Med Lett Drugs Ther. 1998; 40:106-8. [PubMed 9814369]

19. Oncologic Drugs Advisory Committee Meeting. 56th meeting. Bethesda, MD: Food and Drug Administration; 1998 Mar 19.

20. Van Cutsem E, Findlay M, Osterwalder B et al. Capecitabine, an oral fluoropyrimidine carbamate with substantial activity in advanced colorectal cancer: results of a randomized phase II study. J Clin Oncol. 2000; 18:1337-45. [PubMed 10715306]

21. O’Shaughnessy JA, Blum J, Moiseyenko V et al. Randomized, open-label, phase II trial of oral capecitabine (Xeloda) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer. Ann Oncol. 2001; 12:1247-54. [PubMed 11697835]

22. Fabian CJ, Molina R, Slavik M et al. Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with continuous 5-fluorouracil infusion. Invest New Drugs. 1990; 8:57-63. [PubMed 2345070]

23. Twelves C, Glynne-Jones R, Cassidy J et al. Effect of hepatic dysfunction due to liver metastases on the pharmacokinetics of capecitabine and its metabolites. Clin Cancer Res. 1999; 5:1696-702. [IDIS 431263] [PubMed 10430071]

24. Roche Laboratories. Data on file. Clinical reference 111-005.

25. Roche Laboratories, Nutley, NJ: Personal communication.

26. Reviewers’ comments (personal observations).

27. Roche Laboratories. Data on file. Clinical reference 111-013.

28. Roche Laboratories. Data on file. Clinical reference 111-009.

29. Benedetti F. Dear doctor letter: Important prescribing information: potential Xeloda interaction with coumarin derivatives. Nutley, NJ: Roche Laboratories; 1999 Mar.

30. Roche Laboratories. Data on file. Clinical reference 111-012.

31. Van Cutsem E, Twelves C, Cassidy J et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001; 19:4097-106. [PubMed 11689577]

32. Hoff PM, Ansari R, Batist G et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001; 19:2282-92. [IDIS 463399] [PubMed 11304782]

33. Breast cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2006 Jul 11.

34. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; :1:41-52.

35. U.S. Food and Drug Administration. MedWatch safety information 2001. From FDA web site ().

36. Szatrowski TP. Dear doctor letter regarding safety information for use of Xeloda in patients with renal impairment at baseline. Nutley, NJ: Roche Laboratories; 2000 Nov.

37. O’Shaughnessy J, Miles D, Vukelja S et al. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol. 2002; 20:2812-23. [IDIS 482792] [PubMed 12065558]

38. Roche Laboratories Inc. Xeloda (capecitabine) tablets prescribing information. Nutley, NJ; 1999 Mar.

39. Mayer RJ. Oral versus intravenous fluoropyrimidines for advanced colorectal cancer: by either route, it's all the same. J Clin Oncol. 2001; 19:4093-6. [IDIS 479751] [PubMed 11689576]

40. Colon cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institu

Difusil

Difusil may be available in the countries listed below.

Ingredient matches for Difusil

Pentoxifylline

Pentoxifylline is reported as an ingredient of Difusil in the following countries:

• Peru

International Drug Name Search

Triptorelin Pamoate

Class: Antineoplastic Agents
VA Class: AN500
Chemical Name: 6-d-Tryptophan luteinizing hormone-releasing factor (pig)
Molecular Formula: C₆₄H₈₂N₁₈O₁₃
CAS Number: 57773-63-4
Brands: Trelstar

Special Alerts:

[Posted 10/20/2010] ISSUE: Gonadotropin-Releasing Hormone (GnRH) agonists will have new safety information added to the Warnings and Precautions section of the drug labels. This new information warns about increased risk of diabetes and certain cardiovascular diseases (heart attack, sudden cardiac death, stroke) in men receiving these medications for the treatment of prostate cancer.

BACKGROUND: GnRH agonists are approved to treat the symptoms (palliative treatment) of advanced prostate cancer. The benefits of GnRH agonist use for earlier stages of prostate cancer that have not spread (non-metastatic prostate cancer) have not been established. FDA’s notification to manufacturers of GnRH agonists to add this safety information is based on the Agency’s review of several published studies. Most of the studies reviewed by FDA reported small but statistically significant increased risks of diabetes and/or cardiovascular events in patients receiving GnRH agonists.

RECOMMENDATIONS: Healthcare professionals should evaluate patients for risk factors for these diseases and carefully weigh the benefits and risks of using GnRH agonists before determining appropriate treatment for prostate cancer. Patients who are receiving treatment with GnRH agonists should undergo periodic monitoring of blood glucose and/or glycosylated hemoglobin (HbA1c). Healthcare professionals should also monitor patients for signs and symptoms suggestive of development of cardiovascular disease and manage according to current clinical practice. For more information visit the FDA website at: and .

[Posted 05/03/2010] FDA notified healthcare professionals and patients of FDA’s preliminary and ongoing review which suggests an increase in the risk of diabetes and certain cardiovascular diseases in men treated with GnRH agonists, drugs that suppress the production of testosterone, a hormone that is involved in the growth of prostate cancer.

Most of the studies reviewed by FDA reported small, but statistically significant increased risks of diabetes and/or cardiovascular events in patients receiving GnRH agonists. FDA’s review is ongoing and the agency has not made any conclusions about GnRH agonists and whether they increase the risk of diabetes and cardiovascular disease in patients receiving these medications for prostate cancer.

Healthcare professionals and patients should be aware of these potential safety issues and carefully weigh the benefits and risks of GnRH agonists when determining treatment choices. FDA recommends that patients receiving GnRH agonists should be monitored for development of diabetes and cardiovascular disease. Patients should not stop their treatment with GnRH agonists unless told to do so by their healthcare professional.

Some GnRH agonists are also used in women and in children for other indications than those above. There are no known comparable studies that have evaluated the risk of diabetes and heart disease in women and children taking GnRH agonists. For more information visit the FDA website at: and .

Introduction

Antineoplastic agent; synthetic decapeptide analog of gonadotropin-releasing hormone (GnRH, luteinizing hormone-releasing hormone, gonadorelin);^{1 7} structurally related to leuprolide and goserelin.^{1 2 3 4 6 7}

Uses for Triptorelin Pamoate

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Prostate Cancer

Palliative treatment of advanced prostate cancer; considered alternative therapy when orchiectomy or estrogen therapy is not appropriate or is unacceptable to the patient.^{1 7}

Triptorelin Pamoate Dosage and Administration

Administration

IM Administration

Administer by IM injection once monthly (every 28 days) as a depot 1-month formulation or every 84 days (12 weeks) as a long-acting 3-month formulation.^{1 7}

Inject IM into buttock; rotate injection sites periodically.^{1 7}

Administer under the supervision of a qualified clinician.^{1 7}

Reconstitution

Reconstitute powder just prior to administration.^{1 7} Discard suspension if not used immediately after reconstitution.^{1 7}

Using a syringe with 20-gauge needle, add 2 mL of sterile water for injection to vial containing the powder (1- or 3-month formulation); do not reconstitute with other diluents.^{1 7} Shake well to disperse particles and obtain a uniform, milky suspension.^{1 7}

If using the single-dose delivery system, add contents of the prefilled syringe (2 mL of sterile water for injection) to vial containing the powder according to the manufacturer’s instructions.^{1 7} Mix well.^{1 7}

Withdraw entire contents of vial and use immediately.^{1 7}

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as triptorelin pamoate; dosage is expressed in terms of triptorelin.^{1 7}

Adults

Prostate Cancer

IM

3.75 mg every 28 days (monthly) as the 1-month formulation or 11.25 mg every 84 days (12 weeks) as the 3-month formulation.^{1 7}

Special Populations

Hepatic Impairment

Potential need for dosage adjustment not determined.¹

Renal Impairment

Potential need for dosage adjustment not determined.¹

Cautions for Triptorelin Pamoate

Contraindications

• 
  

  Known hypersensitivity to triptorelin or any other ingredient in the formulation, other GnRH agonists, or GnRH.^{1 7}

  
  


• 
  

  Known or suspected pregnancy.^{1 7}

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Endocrine Effects

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Possible worsening of signs and/or symptoms of prostate cancer and/or development of new manifestations (e.g., bone pain, neuropathy, hematuria, urethral or bladder outlet obstruction) due to increases in serum testosterone concentrations during initial weeks of therapy.^{1 2 3 5 7}

Possible spinal cord compression contributing to paralysis; possibly fatal.^{1 2 5 7}

Increased risk of neurologic and/or genitourinary complications during initial therapy in patients with prostate cancer and metastatic vertebral lesions and/or urinary tract obstruction.^{1 7} Observe such patients closely during initial weeks of therapy.^{1 5 7}

If spinal cord compression or renal impairment develops, institute standard treatment of these complications; consider immediate orchiectomy in extreme cases.^{1 7}

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactic shock and angioedema reported rarely.^{1 7} If such reactions occur, discontinue immediately and provide supportive and symptomatic care.^{1 7}

Major Toxicities

Pituitary Apoplexy

Pituitary apoplexy, a clinical syndrome resulting from infarction of the pituitary gland, reported rarely.^{1 7} Most cases occur within 2 weeks of the first dose, sometimes within the first hour.^{1 7} If manifestations occur (e.g., sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, sometimes cardiovascular collapse), immediate medical attention required.^{1 7} In most cases, pituitary adenoma diagnosed.¹

General Precautions

Laboratory Monitoring

Periodically determine serum testosterone and prostate-specific antigen concentrations to monitor therapeutic response.^{1 7}

Specific Populations

Pregnancy

Category X.^{1 7} (See Contraindications under Cautions.)

Lactation

Not known whether distributed into milk; not recommended for use in nursing women.^{1 7}

Pediatric Use

Safety and efficacy not established in children.^{1 7}

Geriatric Use

Studies conducted principally in patients ≥65 years of age, since prostate cancer occurs mainly in an older patient population.^{1 7}

Common Adverse Effects

Temporary worsening of disease manifestations, hot flushes (flashes), skeletal pain, impotence, headache, pain at injection site, leg pain and edema, dysuria, hypertension.^{1 7}

Also observed with 3-month formulation: decreased hemoglobin and erythrocyte counts, increased BUN, increased serum concentrations of glucose, AST, ALT, and alkaline phosphatase.⁷

Interactions for Triptorelin Pamoate

Metabolism unlikely to involve CYP enzymes; effect of triptorelin on other drug-metabolizing enzymes unknown.⁷

Drugs That Induce Hyperprolactinemia

Potential pharmacologic interaction (possible decrease in triptorelin efficacy due to decreased number of GnRH receptors) with drugs such as antipsychotic agents, methyldopa, metoclopramide, and reserpine.^{1 6 7}

Triptorelin Pamoate Pharmacokinetics

Absorption

Bioavailability

Not active when administered orally.^{1 7}

Following IM administration as Trelstar Depot or Trelstar LA, peak plasma concentrations usually are attained within 1 or 3 hours, respectively.^{1 7}

Duration

Following IM injection of Trelstar Depot or Trelstar LA in males, therapeutic plasma concentrations persist for 1 or 3 months, respectively.^{1 7}

Distribution

Extent

Not known whether triptorelin is distributed into milk.^{1 7}

Plasma Protein Binding

No evidence that triptorelin binds to plasma proteins.^{1 7}

Elimination

Metabolism

Metabolism is unknown; involvement of CYP enzymes is unlikely.^{1 7} No metabolites identified to date.^{1 7}

Elimination Route

Hepatic and renal elimination.^{1 7}

Half-life

Approximately 3 hours.^{1 7}

Special Populations

In males with hepatic impairment or moderate or severe renal impairment, AUC increased 2- to 4-fold compared with healthy males.^{1 7}

Stability

Storage

Parenteral

Powder for Injection

20–25°C (may be exposed to 15–30°C).^{1 7} Do not freeze.⁷

Discard suspension if not used immediately after reconstitution.^{1 7}

ActionsActions

• 
  

  Potent inhibitor of gonadotropin secretion when given continuously in therapeutic doses; greater activity than naturally occurring GnRH.^{1 7}

  
  


• 
  

  Transient surge in circulating levels of LH, FSH, testosterone, and estradiol observed after initial administration.^{1 7} Sustained decreases in LH and FSH secretion and reduced testicular and ovarian steroidogenesis observed following chronic, continuous administration (generally 2–4 weeks after initiation of therapy).^{1 4 7}

  
  


• 
  

  Reduction of serum testosterone in males comparable to effects achieved after surgical castration; results in inactivation of physiologic functions and tissues dependent on testosterone.^{1 2 4 7} These effects usually are reversible after cessation of therapy.^{1 7}

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Risk of worsening manifestations of prostate cancer during initial weeks of therapy.^{1 7}

  
  


• 
  

  Importance of promptly reporting weakness or paresthesia of lower limbs and/or worsening of urinary signs and symptoms to clinicians.⁶

  
  


• 
  

  Importance of promptly reporting sudden onset of headache, vomiting, or visual changes to clinicians.^{1 7}

  
  


• 
  

  Risk of anaphylactoid and other sensitivity reactions.^{1 7}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{1 7}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 7} If used during pregnancy, apprise of potential fetal hazard.⁷

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

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

Triptorelin Pamoate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IM use only	3.75 mg (of triptorelin)	Trelstar Depot	Watson
			Trelstar Depot Clip’n’Ject	Watson
		11.25 mg (of triptorelin)	Trelstar LA	Watson
			Trelstar LA Clip’n’Ject	Watson

Disclaimer

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

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

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions November 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Watson Pharma. Trelstar Depot 3.75 mg (triptorelin pamoate for injectable suspension) prescribing information. Corona, CA; 2006 Aug.

2. Parmar H, Phillips RH, Lightman SL et al. Randomised controlled study of orchidectomy vs long-acting D-Trp-6-LHRH microcapsules in advanced prostatic carcinoma. Lancet. 1985; 2:1201-5. [PubMed 2866289]

3. Mahler C. Is disease flare a problem? Cancer. 1993; 72:3799-802.

4. Rolandi E, Martorana G, Franceschini R et al. Treatment of prostatic cancer with a depot preparation of an LHRH analogue: endocrine effects. Curr Ther Res. 1985; 38:670-5.

5. Kahan A, Delrieu F, Amor B et al. Disease flare induced by D-Trp⁶-LHRH analogue in patients with metastatic prostatic cancer. Lancet. 1984; 1:971-2. [IDIS 184509] [PubMed 6143912]

6. Pharmacia & Upjohn, Kalomazoo, MI: Personal communication.

7. Watson Pharma. Trelstar LA 11.25 mg (triptorelin pamoate for injectable suspension) prescribing information. Corona, CA: 2006 Aug.

8. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52.

More Triptorelin Pamoate resources

• Triptorelin Pamoate Side Effects (in more detail)
• Triptorelin Pamoate Use in Pregnancy & Breastfeeding
• Triptorelin Pamoate Drug Interactions
• Triptorelin Pamoate Support Group
• 1 Review for Triptorelin Pamoate - Add your own review/rating

Compare Triptorelin Pamoate with other medications

• Prostate Cancer

Citrate Of Magnesia

Generic Name: magnesium supplement (Oral route, Parenteral route)

Commonly used brand name(s)

In the U.S.

• Almora


• Citrate Of Magnesia


• Dewee's Carminative


• Elite Magnesium


• Mag-Gel 600


• Maginex


• Mag-Tab SR


• Phillips Milk of Magnesia

In Canada

• Liquid Calcium-Magnesium Strawberry Flavor


• Mag 2


• Magnelium


• Magnesium


• Magnesium-Rougier

Available Dosage Forms:

• Capsule


• Powder for Suspension


• Liquid


• Capsule, Liquid Filled


• Tablet


• Tablet, Enteric Coated


• Tablet, Extended Release


• Packet


• Powder


• Syrup

Uses For Citrate Of Magnesia

Magnesium is used as a dietary supplement for individuals who are deficient in magnesium. Although a balanced diet usually supplies all the magnesium a person needs, magnesium supplements may be needed by patients who have lost magnesium because of illness or treatment with certain medicines.

Lack of magnesium may lead to irritability, muscle weakness, and irregular heartbeat.

Injectable magnesium is given only by or under the supervision of a health care professional. Some oral magnesium preparations are available only with a prescription. Others are available without a prescription.

Importance of Diet

For good health, it is important that you eat a balanced and varied diet. Follow carefully any diet program your health care professional may recommend. For your specific dietary vitamin and/or mineral needs, ask your health care professional for a list of appropriate foods. If you think that you are not getting enough vitamins and/or minerals in your diet, you may choose to take a dietary supplement.

The best dietary sources of magnesium include green leafy vegetables, nuts, peas, beans, and cereal grains in which the germ or outer layers have not been removed. Hard water has been found to contain more magnesium than soft water. A diet high in fat may cause less magnesium to be absorbed. Cooking may decrease the magnesium content of food.

The daily amount of magnesium needed is defined in several different ways.

• For U.S.—


• Recommended Dietary Allowances (RDAs) are the amount of vitamins and minerals needed to provide for adequate nutrition in most healthy persons. RDAs for a given nutrient may vary depending on a person's age, sex, and physical condition (e.g., pregnancy).


• Daily Values (DVs) are used on food and dietary supplement labels to indicate the percent of the recommended daily amount of each nutrient that a serving provides. DV replaces the previous designation of United States Recommended Daily Allowances (USRDAs).

• For Canada—


• Recommended Nutrient Intakes (RNIs) are used to determine the amounts of vitamins, minerals, and protein needed to provide adequate nutrition and lessen the risk of chronic disease.

Normal daily recommended intakes in milligrams (mg) for magnesium are generally defined as follows:

Persons	U.S. (mg)	Canada (mg)
Infants birth to 3 years of age	40 to 80	20–50
Children 4 to 6 years of age	120	65
Children 7 to 10 years of age	170	100–135
Adolescent and adult males	270–400	130–250
Adolescent and adult females	280–300	135–210
Pregnant females	320	195–245
Breast-feeding females	340–355	245–265

Before Using Citrate Of Magnesia

If you are taking a dietary supplement without a prescription, carefully read and follow any precautions on the label. For these supplements, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group 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

Problems in children have not been reported with intake of normal daily recommended amounts.

Geriatric

Problems in older adults have not been reported with intake of normal daily recommended amounts.

Studies have shown that older adults may have lower blood levels of magnesium than younger adults. Your health care professional may recommend that you take a magnesium supplement.

Pregnancy

It is especially important that you are receiving enough vitamins and minerals when you become pregnant and that you continue to receive the right amount of vitamins and minerals throughout your pregnancy. The healthy growth and development of the fetus depend on a steady supply of nutrients from the mother. However, taking large amounts of dietary supplements during pregnancy may be harmful to the mother and/or fetus and should be avoided.

Breast Feeding

It is especially important that you receive the right amount of vitamins and minerals so that your baby will also get the vitamins and minerals needed to grow properly. However, taking large amounts of a dietary supplement while breast-feeding may be harmful to the mother and/or baby and should be avoided.

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 any of these dietary supplements, 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 dietary supplements in this class 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.

• Digoxin


• Eltrombopag


• Levomethadyl


• Licorice


• Mycophenolate Mofetil


• Mycophenolic Acid


• Quinine


• Rilpivirine

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 dietary supplements in this class. Make sure you tell your doctor if you have any other medical problems, especially:

• Heart disease—Magnesium supplements may make this condition worse.

• Kidney problems—Magnesium supplements may increase the risk of hypermagnesemia (too much magnesium in the blood), which could cause serious side effects; your health care professional may need to change your dose.

Proper Use of magnesium supplement

This section provides information on the proper use of a number of products that contain magnesium supplement. It may not be specific to Citrate Of Magnesia. Please read with care.

Magnesium supplements should be taken with meals. Taking magnesium supplements on an empty stomach may cause diarrhea.

For individuals taking the extended-release form of this dietary supplement:

• Swallow the tablets whole. Do not chew or suck on the tablet.


• Some tablets may be broken or crushed and sprinkled on applesauce or other soft food. However, check with your health care professional first, since this should not be done for most tablets.

For individuals taking the powder form of this dietary supplement:

• Pour powder into a glass.


• Add water and stir.

Dosing

The dose medicines in this class 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 these medicines. 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 oral dosage form (capsules, chewable tablets, crystals for oral solution, extended-release tablets, enteric-coated tablets, powder for oral solution, tablets, oral solution):
  
  • To prevent deficiency, the amount taken by mouth is based on normal daily recommended intakes (Note that the normal daily recommended intakes are expressed as an actual amount of magnesium. The salt form [e.g., magnesium chloride, magnesium gluconate, etc.] has a different strength.):
    
    • For the U.S.
    
    
    • Adult and teenage males—270 to 400 milligrams (mg) per day.
    
    
    • Adult and teenage females—280 to 300 mg per day.
    
    
    • Pregnant females—320 mg per day.
    
    
    • Breast-feeding females—340 to 355 mg per day.
    
    
    • Children 7 to 10 years of age—170 mg per day.
    
    
    • Children 4 to 6 years of age—120 mg per day.
    
    
    • Children birth to 3 years of age—40 to 80 mg per day.
    
    
    • For Canada
    
    
    • Adult and teenage males—130 to 250 mg per day.
    
    
    • Adult and teenage females—135 to 210 mg per day.
    
    
    • Pregnant females—195 to 245 mg per day.
    
    
    • Breast-feeding females—245 to 265 mg per day.
    
    
    • Children 7 to 10 years of age—100 to 135 mg per day.
    
    
    • Children 4 to 6 years of age—65 mg per day.
    
    
    • Children birth to 3 years of age—20 to 50 mg per day.
    
    
  
  
  • To treat deficiency:
    
    • Adults, teenagers, and children—Treatment dose is determined by prescriber for each individual based on severity of deficiency.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, 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.

If you miss taking your magnesium supplement for one or more days there is no cause for concern, since it takes some time for your body to become seriously low in magnesium. However, if your health care professional has recommended that you take magnesium, try to remember to take it as directed every day.

Storage

Keep out of the reach of children.

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

Do not keep outdated medicine or medicine no longer needed.

Citrate Of Magnesia 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:

Rare

• Dizziness or fainting


• flushing


• irritation and pain at injection site—for intramuscular administration only


• muscle paralysis


• troubled breathing

Symptoms of overdose (rare in individuals with normal kidney function)

• Blurred or double vision


• coma


• dizziness or fainting


• drowsiness (severe)


• increased or decreased urination


• slow heartbeat


• troubled breathing

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:

Less common (with oral magnesium)

• Diarrhea

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.

Nitridazol

Nitridazol may be available in the countries listed below.

Ingredient matches for Nitridazol

Itraconazole

Itraconazole is reported as an ingredient of Nitridazol in the following countries:

• Argentina

International Drug Name Search

Xyralid RC Cream

Pronunciation: LYE-doe-kane/HYE-droe-KOR-ti-sone/SIL-ee-um
Generic Name: Lidocaine/Hydrocortisone
Brand Name: Xyralid RC

Xyralid RC Cream is used for:

Treating pain, itching, soreness, and discomfort caused by hemorrhoids or other anal conditions. It also helps to relieve constipation.

Xyralid RC Cream is a kit that contains an anesthetic and corticosteroid cream and a bulk-forming laxative. The anesthetic works by helping to decrease soreness and discomfort. The corticosteroid works by reducing swelling, redness, and itching. The bulk-forming laxative works by absorbing water in the intestines. This helps to soften and stool so it can be more easily passed.

Do NOT use Xyralid RC Cream if:

• you are allergic to any ingredient in Xyralid RC Cream or to similar medications (eg, dibucaine)


• you have a tuberculous or fungal skin infection, a herpes simplex skin infection, chickenpox, shingles, or a skin infection following smallpox vaccination

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

Before using Xyralid RC Cream:

Some medical conditions may interact with Xyralid RC Cream. 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 had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any anesthetic medicine


• if you have a history of thinning skin, skin infection, or other skin disorders


• if you have recently received a vaccination or if you have ever had a positive tuberculin (TB) skin test


• if you have stomach pain, nausea, vomiting, rectal bleeding, or trouble swallowing


• if you have liver problems, diabetes, high blood sugar levels, very poor health, stomach or bowel pain, nausea, or vomiting; or if you have had a sudden change in bowel habits persisting for more than 2 weeks

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

• Class IA antiarrhythmics (eg, disopyramide) because the risk of their side effects may be increased by Xyralid RC Cream

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

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

• To use the rectal cream: Clean the affected area with the cleansing wipe as directed before you apply the cream. Attach the applicator to the tube of rectal cream and squeeze gently until a small amount of cream shows. Lubricate the tip of the applicator with the cream and apply as directed by your doctor.


• To use the bulk-forming laxative: Mix the contents of the packet with fluid in the shaker cup provided. Take the laxative with plenty of fluid according to the directions provided or as directed by your doctor.


• If you miss a dose of Xyralid RC Cream, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Xyralid RC Cream.

Important safety information:

• Do not get Xyralid RC Cream in your eyes, ears, nose, or mouth. If you get it in any of these areas, rinse at once with cool tap water.


• If your symptoms do not get better within 7 days or if they get worse, check with your doctor.


• Do NOT use more than the recommended dose, use more often, or use for longer than prescribed without checking with your doctor.


• If you use topical products too often, your condition may become worse.


• Xyralid RC Cream may cause a numbing effect at the application site. Do not scratch, rub, or expose the area to extreme hot or cold temperature until the numbness is gone.


• Xyralid RC Cream has a corticosteroid in it. Before you start any new medicine, check the label to see if it has a corticosteroid in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• Do not take additional laxatives or stool softeners with Xyralid RC Cream unless directed by your doctor.


• Tell your doctor if you fail to have a bowel movement even after using Xyralid RC Cream.


• Taking the bulk-forming laxative without enough liquid may cause it to swell and block your throat or esophagus and may cause choking. If you experience chest pain, vomiting, or difficulty swallowing or breathing after taking the laxative, seek immediate medical attention.


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


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


• Xyralid RC Cream should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: It is not known if Xyralid RC Cream can cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Xyralid RC Cream while you are pregnant. It is not known if Xyralid RC Cream is found in breast milk after topical use. If you are or will be breast-feeding while you use Xyralid RC Cream, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Xyralid RC Cream:

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:

Abdominal fullness; mild stinging, burning, redness, or discoloration at the application site; minor bloating.

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); chest pain; difficulty swallowing; excessive irritation; rectal bleeding; skin infection (eg, redness, swelling, pus discharge); vomiting.

This is not a complete list of all side effects that may occur. If you have questions or need medical advice about side effects, contact your doctor or health care provider. You may report side effects to FDA at 1-800-FDA-1088 (1-800-332-1088) or at http://www.fda.gov/medwatch.

See also: Xyralid RC 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. Xyralid RC Cream may be harmful if swallowed.

Proper storage of Xyralid RC Cream:

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

General information:

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


• Xyralid RC Cream 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 Xyralid RC Cream. 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 Xyralid RC resources

• Xyralid RC Side Effects (in more detail)
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• Xyralid RC Drug Interactions
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