This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or standards of non-Merck sources.

ALERT: U.S. Boxed Warning

The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.

Pronunciation

(ka pe SITE a been)

Generic Available (U.S.)

No

Index Terms

• CAPE

U.S. Brand Names

• Xeloda®

Canadian Brand Names

• Xeloda®

Pharmacologic Category

• Antineoplastic Agent, Antimetabolite
• Antineoplastic Agent, Antimetabolite (Pyrimidine Analog)

Pharmacologic Category Synonyms

• Antimetabolite Antineoplastic
• Chemotherapy Agent, Antimetabolite

Use: Labeled Indications

Treatment of metastatic colorectal cancer; adjuvant therapy of Dukes' C colon cancer; treatment of metastatic breast cancer

Use: Unlabeled/Investigational

Treatment of gastric cancer, pancreatic cancer, esophageal cancer, ovarian cancer, metastatic renal cell cancer, neuroendocrine tumors, metastatic CNS lesions

Pregnancy Risk Factor

D

Pregnancy Considerations

Animal studies have demonstrated teratogenicity and fetal loss. There are no adequate and well-controlled studies in pregnant women; however, fetal harm may occur. Women of childbearing potential should avoid pregnancy.

Lactation

Excretion in breast milk unknown/not recommended

Breast-Feeding Considerations

It is not known if the drug is excreted in breast milk. Because of the potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued when receiving capecitabine therapy.

Contraindications

Hypersensitivity to capecitabine, fluorouracil, or any component of the formulation; known deficiency of dihydropyrimidine dehydrogenase (DPD); severe renal impairment (Cl_cr <30 mL/minute)

Warnings/Precautions

Boxed warnings:

• Warfarin: See “Concurrent drug therapy issues” below.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal.

Concerns related to adverse effects:

• Cardiotoxicity: There has been cardiotoxicity associated with fluorinated pyrimidine therapy, including myocardial infarction, angina, dysrhythmias, cardiogenic shock, sudden death, ECG changes, and cardiomyopathy. These adverse events may be more common in patients with a history of coronary artery disease.

• Diarrhea: Can cause severe diarrhea; median time to first occurrence is 34 days; subsequent doses should be reduced after grade 3 or 4 diarrhea or recurrence of grade 2 diarrhea. Dehydration may occur rapidly in patients with diarrhea, nausea, vomiting, anorexia, and/or weakness; adequately hydrate prior to treatment initiation. Elderly patients may be a higher risk for dehydration. Note: The Canadian labeling recommends treatment interruption for dehydration requiring I.V. hydration lasting <24 hours or dosage reduction if I.V hydration required for ≥24 hours; correct precipitating factors and ensure rehydration prior to resuming therapy.

• Hand-and-foot syndrome: May cause hand-and-foot syndrome (palmar-plantar erythrodysesthesia or chemotherapy-induced acral erythema) is characterized by numbness, dysesthesia/paresthesia, tingling, painless or painful swelling, erythema, desquamation, blistering, and severe pain. If grade 2 or 3 hand-and-foot syndrome occurs, interrupt administration of capecitabine until the event resolves or decreases in intensity to grade 1. Following grade 3 hand-and-foot syndrome, decrease subsequent doses of therapy.

• Necrotizing enterocolitis (typhlitis): Has been reported.

Disease-related concerns:

• Bone marrow suppression: Bone marrow suppression may occur, hematologic toxicity is more common when used in combination therapy; use with caution; dosage adjustments may be required. Canadian labeling recommends that patients with baseline platelets <100,000/mm³ and/or neutrophils <1500/mm³ not receive capecitabine therapy and also to withhold therapy for grade 3 or 4 hematologic toxicity during treatment.

• Dihydropyrimidine dehydrogenase (DPD) deficiency: Rare and unexpected severe toxicity (stomatitis, diarrhea, neutropenia, neurotoxicity) may be attributed to dihydropyrimidine dehydrogenase (DPD) deficiency.

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Renal impairment: Use with caution in patients with renal impairment; reduce dose with moderate impairment and carefully monitor and reduce subsequent dose (with any grade 2 or higher adverse effect) with mild-to-moderate impairment.

Concurrent drug therapy issues:

• Alkylating therapy: Use with caution in patients who have received alkylating therapy.

• Fluorouracil/leucovorin (FU/LV): In patients with colorectal cancer, treatment with capecitabine immediately following 6 weeks of FU/LV therapy has been associated with an increased incidence of grade ≥3 toxicity, when compared to patients receiving the reverse sequence, capecitabine (two 3-week courses) followed by FU/LV (Hennig, 2008).

• Warfarin: [U.S. Boxed Warning]: Capecitabine may increase the anticoagulant effects of warfarin; monitor closely.

Special populations:

• Elderly: Use with caution in patients ≥80 years of age.

• Pediatrics: Safety and efficacy have not been established in children.

• Pelvic radiation therapy recipients: Use with caution in patients who have received extensive pelvic radiation.

Adverse Reactions

Frequency listed derived from monotherapy trials.

>10%:

Cardiovascular: Edema (9% to 15%)

Central nervous system: Fatigue (16% to 42%), fever (7% to 18%), pain (12%)

Dermatologic: Palmar-plantar erythrodysesthesia (hand-and-foot syndrome) (54% to 60%; grade 3: 11% to 17%; may be dose limiting), dermatitis (27% to 37%)

Gastrointestinal: Diarrhea (47% to 57%; may be dose limiting; grade 3: 12% to 13%; grade 4: 2% to 3%), nausea (34% to 53%), vomiting (15% to 37%), abdominal pain (7% to 35%), stomatitis (22% to 25%), appetite decreased (26%), anorexia (9% to 23%), constipation (9% to 15%)

Hematologic: Lymphopenia (94%; grade 4: 14%), anemia (72% to 80%; grade 4: <1% to 1%), neutropenia (2% to 26%; grade 4: 2%), thrombocytopenia (24%; grade 4: 1%)

Hepatic: Bilirubin increased (22% to 48%; grades 3/4: 11% to 23%)

Neuromuscular & skeletal: Paresthesia (21%)

Ocular: Eye irritation (13% to 15%)

Respiratory: Dyspnea (14%)

5% to 10%:

Cardiovascular: Venous thrombosis (8%), chest pain (6%)

Central nervous system: Headache (5% to 10%), lethargy (10%), dizziness (6% to 8%), insomnia (7% to 8%), mood alteration (5%), depression (5%)

Dermatologic: Nail disorder (7%), rash (7%), skin discoloration (7%), alopecia (6%), erythema (6%)

Endocrine & metabolic: Dehydration (7%)

Gastrointestinal: Motility disorder (10%), oral discomfort (10%), dyspepsia (6% to 8%), upper GI inflammatory disorders (colorectal cancer: 8%), hemorrhage (6%), ileus (6%), taste perversion (colorectal cancer: 6%)

Neuromuscular & skeletal: Back pain (10%), weakness (10%), neuropathy (10%), myalgia (9%), arthralgia (8%), limb pain (6%)

Ocular: Abnormal vision (colorectal cancer: 5%), conjunctivitis (5%)

Respiratory: Cough (7%)

Miscellaneous: Viral infection (colorectal cancer: 5%)

<5%, postmarketing, and/or case reports: Abdominal distension, angina, appetite increased, arthritis, ascites, asthma, ataxia, atrial fibrillation, bone pain, bradycardia, bronchitis, bronchopneumonia, bronchospasm, cachexia, cardiac arrest, cardiac failure, cardiomyopathy, cerebral vascular accident, cholestatic hepatitis, coagulation disorder, colitis, confusion, deep vein thrombosis, diaphoresis, duodenitis, dysarthria, dysphagia, dysrhythmia, ecchymoses, ECG changes, encephalopathy, epistaxis, esophagitis, fibrosis, fingerprint distortion (secondary to hand-and-foot syndrome), fungal infection, gastric ulcer, gastritis, gastroenteritis, gastrointestinal perforation, hematemesis, hemoptysis, hepatic failure, hepatic fibrosis, hepatitis, hoarseness, hot flushes, hypokalemia, hypomagnesemia, hyper-/hypotension, hypersensitivity, hypertriglyceridemia, idiopathic thrombocytopenia purpura, ileus, impaired balance, infection, influenza-like illness, intestinal obstruction (~1%), irritability, joint stiffness, keratoconjunctivitis, lacrimal duct stenosis, laryngitis, leukopenia, loss of consciousness, lymphedema, MI, multifocal leukoencephalopathy, myocardial ischemia, myocarditis, necrotizing enterocolitis (typhlitis), nocturia, oral candidiasis, pericardial effusion, thrombocytopenic purpura, pancytopenia, photosensitivity reaction, pneumonia, proctalgia, pruritus, pulmonary embolism, radiation recall syndrome, renal impairment, respiratory distress, sedation, sepsis, skin ulceration, sore throat, Stevens-Johnson syndrome, tachycardia, thirst, thrombophlebitis, toxic epidermal necrolysis, toxic megacolon, tremor, ventricular extrasystoles, vertigo, weight gain

Metabolism/Transport Effects

Inhibits CYP2C9 (strong)

Drug Interactions

BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination

Carvedilol: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Risk C: Monitor therapy

CYP2C9 Substrates (High risk): CYP2C9 Inhibitors (Strong) may decrease the metabolism of CYP2C9 Substrates (High risk). Risk D: Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification

Fosphenytoin: Capecitabine may increase the serum concentration of Fosphenytoin. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification

Leucovorin Calcium-Levoleucovorin: May enhance the adverse/toxic effect of Capecitabine. Risk C: Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination

Phenytoin: Capecitabine may increase the serum concentration of Phenytoin. Risk D: Consider therapy modification

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination

Vitamin K Antagonists (eg, warfarin): Capecitabine may increase the serum concentration of Vitamin K Antagonists. Risk D: Consider therapy modification

Ethanol/Nutrition/Herb Interactions

Food: Food reduced the rate and extent of absorption of capecitabine.

Storage

Store at room temperature of 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).

Mechanism of Action

Capecitabine is a prodrug of fluorouracil. It undergoes hydrolysis in the liver and tissues to form fluorouracil which is the active moiety. Fluorouracil is a fluorinated pyrimidine antimetabolite that inhibits thymidylate synthetase, blocking the methylation of deoxyuridylic acid to thymidylic acid, interfering with DNA, and to a lesser degree, RNA synthesis. Fluorouracil appears to be phase specific for the G₁ and S phases of the cell cycle.

Pharmacodynamics/Kinetics

Absorption: Rapid and extensive

Protein binding: <60%; ~35% to albumin

Metabolism:

Hepatic: Inactive metabolites: 5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine

Tissue: Active metabolite: Fluorouracil

Half-life elimination: 0.5-1 hour

Time to peak: 1.5 hours; Fluorouracil: 2 hours

Excretion: Urine (96%, 57% as α-fluoro-β-alanine); feces (<3%)

Dosage

Oral:

Adults: Note: Details concerning dosing in combination regimens should also be consulted. Capecitabine toxicities, particularly hand-foot syndrome, may be higher in North American populations (for the treatment of colorectal cancer); therapy initiation at doses of 1000 mg/m² twice daily (for 2 weeks every 21 days) may be considered (Haller, 2008; NCCN Colon Cancer Guidelines)

Metastatic breast cancer, metastatic colorectal cancer: 1250 mg/m² twice daily (morning and evening) for 2 weeks, every 21 days

Adjuvant therapy of Dukes' C colon cancer: Recommended for a total of 24 weeks (8 cycles of 2 weeks of drug administration and 1 week rest period).

Pancreatic cancer (unlabeled use): 1000 mg/m² twice daily for 2 weeks, every 21 days (NCCN pancreatic Cancer Guidelines v.1.2009) or 1250 mg/m² twice daily for 2 weeks, every 21 days (Cartwright , 2002)

Elderly: The elderly may be more sensitive to the toxic effects of fluorouracil. Insufficient data are available to provide dosage modifications.

Dosing adjustment in renal impairment:

Cl_cr 51-80 mL/minute: No adjustment of initial dose

Cl_cr 30-50 mL/minute: Administer 75% of normal dose

Cl_cr <30 mL/minute: Use is contraindicated

Dosing adjustment in hepatic impairment:

Mild-to-moderate impairment: No starting dose adjustment is necessary; however, carefully monitor patients

Severe hepatic impairment: Patients have not been studied

Dosage modification guidelines: See table.

Refer to package labeling for modifications when administered in combination with docetaxel.

Dosage adjustments for hematologic toxicity in combination therapy with ixabepilone:

Neutrophils <500/mm³ for ≥7 days or neutropenic fever: Hold for concurrent diarrhea or stomatitis until neutrophils recover to >1000/mm³, then continue at same dose

Platelets <25,000/mm³ (or <50,000/mm³ with bleeding): Hold for concurrent diarrhea or stomatitis until platelets recover to >50,000/mm³, then continue at same dose

Dosage: Combination Regimens

Biliary adenocarcinoma: Gemcitabine-Capecitabine (Biliary Cancer)

Breast cancer:

Bevacizumab-Capecitabine (Breast Cancer)

Capecitabine + Docetaxel (Breast Cancer)

Capecitabine + Lapatinib (Breast Cancer)

Capecitabine-Trastuzumab

Ixabepilone-Capecitabine

Colorectal cancer: CAPOX (Colorectal Cancer)

Esophageal cancer:

Cisplatin-Capecitabine (Esophageal Cancer)

Epirubicin-Cisplatin-Capecitabine (Esophageal Cancer)

Epirubicin-Oxaliplatin-Capecitabine

Irinotecan-Capecitabine (Esophageal Cancer)

Gastric cancer:

Capecitabine-Docetaxel (Gastric Cancer)

Cisplatin-Capecitabine (Gastric Cancer)

Epirubicin-Oxaliplatin-Capecitabine

Irinotecan-Capecitabine (Gastric Cancer)

Trastuzumab-Cisplatin-Capecitabine (Gastric Cancer)

Gastrointestinal cancer: CAPOX (Biliary Cancer)

Lung cancer (nonsmall cell): Capecitabine + Docetaxel (NSCLC)

Pancreatic cancer:

CAPOX (Pancreatic Cancer)

Gemcitabine-Capecitabine (Pancreatic Cancer)

Renal cell cancer: Gemcitabine-Capecitabine (RCC)

Administration: Oral

Usually administered in 2 divided doses taken 12 hours apart. Doses should be taken with water within 30 minutes after a meal.

Monitoring Parameters

Renal function should be estimated at baseline to determine initial dose. During therapy, CBC with differential, hepatic function, and renal function should be monitored.

Dietary Considerations

Because current safety and efficacy data are based upon administration with food, it is recommended that capecitabine be administered with food. In all clinical trials, patients were instructed to take with water within 30 minutes after a meal.

Patient Education

Take within 30 minutes after a meal. Maintain adequate hydration, unless instructed to restrict fluid intake. You may be more susceptible to infection. May cause lethargy; dizziness; visual changes; confusion; anxiety; nausea; vomiting; loss of appetite; dry mouth; loss of hair (will grow back when treatment is discontinued); photosensitivity; dry, itchy skin; and dry or irritated eyes (avoid contact lenses). Report persistent or severe diarrhea, vomiting, or abdominal pain; skin rash, redness, tenderness, or peeling (especially hands and feet); respiratory difficulty; chest pain or palpitations; unusual bleeding or bruising; or vision changes.

Geriatric Considerations

Patients ≥80 years of age may experience a greater incidence of grade 3 or 4 adverse events (diarrhea, hand-and-foot syndrome, nausea/vomiting).

Additional Information

Oncology Comment: An investigational uridine prodrug, uridine triacetate (formerly called vistonuridine), has been studied in a limited number of cases of fluorouracil overdose. Of 17 patients receiving uridine triacetate beginning within 8-96 hours after fluorouracil overdose, all patients fully recovered (von Borstel, 2009). Updated data has described a total of 28 patients treated with uridine triacetate for fluorouracil overdose (including overdoses related to continuous infusions delivering fluorouracil at rates faster than prescribed), all of whom recovered fully (Bamat, 2010). Rrefer to Uridine Triacetate monograph.

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Stomatitis, abnormal taste, and taste disturbance.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Sedation is common; may cause dizziness or insomnia

Mental Health: Effects on Psychiatric Treatment

Neutropenia is common; use caution with clozapine and carbamazepine

Nursing: Physical Assessment/Monitoring

Evaluate renal and hepatic function and CBC with differential at baseline and regularly during therapy. Assess all adverse reactions on a regular basis during therapy; dosage adjustments may be necessary. Teach sexually active female patients the necessity for contraception.

Oncology: Emetic Potential

Low (10% to 30%)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, oral:

Xeloda®: 150 mg, 500 mg

Pricing: U.S. (www.drugstore.com)

Tablets (Xeloda)

150 mg (60): $521.00

500 mg (120): $3440.00

Extemporaneously Prepared

Hazardous agent: Use appropriate precautions for handling and disposal.

A 10 mg/mL oral solution may be made with tablets. Crush four 500 mg tablets in a mortar and reduce to a fine powder; add to 200 mL water. Capecitabine tablets are water soluble (data on file from Roche). Administer immediately after preparation, 30 minutes after a meal.

Judson IR, Beale PJ, Trigo JM, et al, “A Human Capecitabine Excretion Balance and Pharmacokinetic Study After Administration of a Single Oral Dose of ¹⁴C-Labelled Drug,” Invest New Drugs, 1999, 17(1):49-56.

References

Bamat MK, Tremmel R, O'Neil JD, et al, “Uridine Triacetate: An Orally Administered Life-Saving Antidote for 5-FU Overdose,” J Clin Oncol, 28(15s):9084 [abstract 9084 from 2010 ASCO Annual Meeting].

Cartwright TH, Cohn A, Varkey JA, et al, “Phase II Study of Oral Capecitabine in Patients With Advanced or Metastatic Pancreatic Cancer,” J Clin Oncol, 2002, 20(1):160-4.

Cassidy J, Tabernero J, Twelves C, et al, "XELOX (Capecitabine Plus Oxaliplatin): Active First-Line Therapy for Patients With Metastatic Colorectal Cancer," J Clin Oncol, 2004, 22(11):2084-91.

Haller DG, Cassidy J, Clarke S, et al, “Potential Regional Differences for the Tolerability Profiles of Fluoropyrimidines,” J Clin Oncol, 2008, 26(13):2118-23.

Hennig IM, Naik JD, Brrown S, et al, “Severe Sequence-Specific Toxicity When Capecitabine Is Given After Fluorouracil and Leucovorin,” J Clin Oncol, 2008, 26(20):3411-7.

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(8):2282-92.

Ishitsuka H, “Capecitabine: Preclinical Pharmacology Studies,” Invest New Drugs, 2000, 18(4):343-54.

Johnston PG and Kaye S, “Capecitabine: A Novel Agent for the Treatment of Solid Tumors,” Anticancer Drugs, 2001, 12(8):639-46.

Judson IR, Beale PJ, Trigo JM, et al, “A Human Capecitabine Excretion Balance and Pharmacokinetic Study After Administration of a Single Oral Dose of ¹⁴C-Labelled Drug,” Invest New Drugs, 1999, 17(1):49-56.

McGavin JK and Goa KL, “Capecitabine: A Review of Its Use in the Treatment of Advanced or Metastatic Colorectal Cancer,” Drugs, 2001, 61(15):2309-26.

Morgan C, Tillett T, Braybrooke J, et al, “Management of Uncommon Chemotherapy-Induced Emergencies,” Lancet Oncol, 2011 [epub ahead of print].

National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Prevention and Treatment of Colon Cancer,” Version 2.2010. Available at http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf

National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Prevention and Treatment of Pancreatic Adenocarcinoma,” Version 1.2009. Available at http://www.nccn.org/professionals/physician_gls/PDF/pancreatic.pdf

Schilsky RL, “Pharmacology and Clinical Status of Capecitabine,” Oncology, 2000, 14(9):1297-306.

Twelves C, Wong A, Nowacki MP, et al, “Capecitabine as Adjuvant Treatment for Stage III Colon Cancer,” N Engl J Med, 2005, 352(26):2696-704.

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(21):4097-106.

Videnovic A, Semenov I Chua-Adajar R, et al, “Capecitabine-Induced Multifocal Leukoencephalopathy: A Report of Five Cases,” Neurology, 2005, 65(11):1792-4.

von Borstel R, O'Neil J, and Bamat M, “Vistonuridine: An Orally Administered, Life-Saving Antidote for 5-Fluorouracil (5FU) Overdose,” J Clin Oncol, 2009, 27(15S):9616 [abstract from 2009 ASCO Annual Meeting].

Wong M, Choo SP, and Tan EH, “Travel Warning With Capecitabine,” Ann Oncol, 2009, 20(7):2081.

International Brand Names

• Apecitab (AR)
• Capecitabina (PE)
• Capibine (IN)
• Xeloda (AR, AT, AU, BB, BE, BF, BG, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CO, CZ, DE, DK, EC, ES, ET, FI, FR, GB, GH, GM, GN, GR, GY, HK, HN, ID, IE, IL, IS, IT, JM, KE, KP, LR, LU, MA, ML, MR, MU, MW, MX, NE, NG, NL, NO, PH, PK, PL, PT, PY, RU, SC, SD, SE, SG, SL, SN, SR, TH, TN, TR, TT, TZ, UG, UY, VE, ZA, ZM, ZW)

Lexi-Comp.com

Last full review/revision May 2011

Content last modified May 2011