|
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.
Pronunciation
(GA ba pen tin)
Generic Available (U.S.)
Yes
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Neurontin®: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM229208.pdf
Gralise™: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM245196.pdf
REMS Components
Neurontin® capsules, oral solution. tablets: Released from REMS requirement 8/10/2011
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Adjunct for treatment of partial seizures with and without secondary generalized seizures in patients >12 years of age with epilepsy; adjunct for treatment of partial seizures in pediatric patients 3-12 years of age; management of postherpetic neuralgia (PHN) in adults
Use: Dental
Neuropathic pain (consult with physician)
Use: Unlabeled
Neuropathic pain, diabetic peripheral neuropathy, fibromyalgia, postoperative pain, restless legs syndrome (RLS), vasomotor symptoms
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal studies have documented teratogenic effects. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus.Patients exposed to gabapentin during pregnancy are encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Gabapentin is excreted in human breast milk. A nursed infant could be exposed to ~1 mg/kg/day of gabapentin; the effect on the child is not known. Use in breast-feeding women only if the benefits to the mother outweigh the potential risk to the infant.
Contraindications
Hypersensitivity to gabapentin or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Multiorgan hypersensitivity: Potentially serious, sometimes fatal multiorgan hypersensitivity (also known as drug reaction with eosinophilia and systemic symptoms [DRESS]) has been reported with some antiepileptic drugs, including gabapentin. Monitor for signs and symptoms of possible disparate manifestations associated with lymphatic, hepatic, renal, cardiac, and/or hematologic systems; fever, rash, and eosinophilia may also be present. Discontinue immediately if suspected.
• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur.
Disease-related concerns:
• Renal impairment: Use with caution in patients with severe renal impairment; dose adjustment required.
• Seizure disorder: The safety and efficacy of extended release gabapentin (Gralise™) has not been studied in patients with epilepsy.
Concurrent drug therapy issues:
• Sedatives: Effects with other sedative drugs or ethanol may be potentiated.
Dosage form specific issues:
• Product interchangeability: Gabapentin immediate release and extended release (Gralise™) products are not interchangeable with each other or with gabapentin encarbil (Horizant™) due to differences in formulations, indications, and pharmacokinetics.
Other warnings/precautions:
• Tumorigenic potential: Male rat studies demonstrated an association with pancreatic adenocarcinoma (clinical implication in humans is unknown).
• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal. Gralise™ should be withdrawn over ≥1 week.
Adverse Reactions
As reported for immediate release (IR) formulations in patients >12 years of age, unless otherwise noted in children (3-12 years) or with use of extended release (ER) formulation
>10%:
Central nervous system: Dizziness (IR: 17% to 28%; children 3%; ER: 11%), somnolence (IR: 19% to 21%; children 8%; ER: 5%), ataxia (3% to 13%), fatigue (11%; children 3%)
Miscellaneous: Viral infection (children 11%)
1% to 10%:
Cardiovascular: Peripheral edema (2% to 8%), vasodilatation (1%)
Central nervous system: Fever (children 10%), hostility (children 5% to 8%), emotional lability (children 4% to 6%), headache (IR: 3%; ER: 4%), abnormal thinking (2% to 3%; children 2%), amnesia (2%), depression (2%), nervousness (2%), abnormal coordination (1% to 2%), pain (ER: 1% to 2%), hyperesthesia (1%), lethargy (ER: 1%), twitching (1%), vertigo (ER: 1%)
Dermatologic: Pruritus (1%), rash (1%)
Endocrine & metabolic: Hyperglycemia (1%)
Gastrointestinal: Diarrhea (IR: 6%; ER: 3%), nausea/vomiting (3% to 4%; children 8%), abdominal pain (3%), xerostomia (2% to 5%), constipation (1% to 4%), weight gain (adults and children 2% to 3%), dyspepsia (IR: 2%; ER: 1%), flatulence (2%), dry throat (2%), dental abnormalities (2%), appetite stimulation (1%)
Genitourinary: Impotence (2%), urinary tract infection (ER: 2%)
Hematologic: Decreased WBC (1%), leukopenia (1%)
Neuromuscular & skeletal: Tremor (7%), weakness (6%), hyperkinesia (children 3% to 5%), abnormal gait (2%), back pain (2%), dysarthria (2%), myalgia (2%), fracture (1%)
Ocular: Nystagmus (8%), diplopia (1% to 6%), blurred vision (3% to 4%), conjunctivitis (1%)
Otic: Otitis media (1%)
Respiratory: Rhinitis (4%), bronchitis (children 3%), respiratory infection (children 3%), pharyngitis (1% to 3%), cough (2%)
Miscellaneous: Infection (5%)
Postmarketing and additional clinical reports (limited to important or life-threatening): Acute renal failure, anemia, angina, angioedema, aphasia, arrhythmias (various), aspiration pneumonia, blindness, blood glucose fluctuation, bradycardia, breast enlargement, bronchospasm, cerebrovascular accident, CNS tumors, coagulation defect, colitis, confusional state, Cushingoid appearance, dyspnea, encephalopathy, erythema multiforme, facial paralysis, fecal incontinence, gastroenteritis, glaucoma, glycosuria, hearing loss, heart block, heart failure, hematemesis, hematuria, hemiplegia, hemorrhage, hepatitis, hepatomegaly, hyperlipidemia, hyper-/hypotension, hyper-/hypothyroidism, hyper-/hypoventilation, hyponatremia, jaundice, joint swelling, leukocytosis, liver function tests increased, local myoclonus, lymphadenopathy, lymphocytosis, memory impairment, meningismus, MI, migraine, movement disorder, nephrosis, nerve palsy, non-Hodgkin's lymphoma, ovarian failure, palpitation, pancreatitis, paresthesia, peptic ulcer, pericardial effusion, pericardial rub, pericarditis, peripheral vascular disorder, pneumonia, psychosis, pulmonary embolus, pulmonary thrombosis, purpura, renal stone, retinopathy, seasonal allergy, skin necrosis, status epilepticus, Stevens-Johnson syndrome, subdural hematoma, suicidal behavior/ideation, syncope, tachycardia, thrombocytopenia, thrombophlebitis
Metabolism/Transport Effects
None known.
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Antacids: May decrease the serum concentration of Gabapentin. Management: Administer gabapentin at least 2 hours after antacid administration. Monitor patients closely for evidence of reduced response to gabapentin therapy when both of these drugs are being used. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ketorolac: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
Ketorolac (Nasal): May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
Ketorolac (Systemic): May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Food: Tablet, solution (immediate release): No significant effect on rate or extent of absorption; tablet (extended release): Increases rate and extent of absorption.
Herb/Nutraceutical: Avoid evening primrose (seizure threshold decreased). Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Storage
Capsules and tablets: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Oral solution: Store refrigerated at 2°C to 8°C (36°F to 46°F).
Mechanism of Action
Gabapentin is structurally related to GABA. However, it does not bind to GABAA or GABAB receptors, and it does not appear to influence synthesis or uptake of GABA. High affinity gabapentin binding sites have been located throughout the brain; these sites correspond to the presence of voltage-gated calcium channels specifically possessing the alpha-2-delta-1 subunit. This channel appears to be located presynaptically, and may modulate the release of excitatory neurotransmitters which participate in epileptogenesis and nociception.
Pharmacodynamics/Kinetics
Absorption: Variable, from proximal small bowel by L-amino transport system
Distribution: Vd: 58 ± 6 L
Protein binding: <3%
Bioavailability: Inversely proportional to dose due to saturable absorption:
Immediate release:
900 mg/day: 60%
1200 mg/day: 47%
2400 mg/day: 34%
3600 mg/day: 33%
4800 mg/day: 27%
Extended release: Variable; increased with higher fat content meal
Half-life elimination: 5-7 hours; anuria 132 hours; during dialysis 3.8 hours
Time to peak: Immediate release: 2-4 hours; extended release: 8 hours
Excretion: Proportional to renal function; urine (as unchanged drug)
Dosage
Oral:
Children: Immediate release: Anticonvulsant:
3-12 years: Initial: 10-15 mg/kg/day in 3 divided doses; titrate to effective dose over ~3 days; dosages of up to 50 mg/kg/day have been tolerated in clinical studies
3-4 years: Usual dose: 40 mg/kg/day in 3 divided doses
≥5-12 years: Usual dose: 25-35 mg/kg/day in 3 divided doses
See “Note” in adult dosing.
Children >12 years and Adults: Immediate release: Anticonvulsant: Initial: 300 mg 3 times/day; if necessary the dose may be increased up to 1800 mg/day; Maintenance: 900-1800 mg/day administered in 3 divided doses; doses of up to 2400 mg/day have been tolerated in long-term clinical studies; up to 3600 mg/day has been tolerated in short-term studies.
Note: If gabapentin is discontinued or if another anticonvulsant is added to therapy, it should be done slowly over a minimum of 1 week
Adults:
Immediate release:
Diabetic neuropathy (unlabeled use): 900-3600 mg/day (Bril, 2011)
Neuropathic pain (unlabeled use): 300-3600 mg/day (Attal, 2010; Dworkin, 2010)
Postherpetic neuralgia: Day 1: 300 mg, Day 2: 300 mg twice daily, Day 3: 300 mg 3 times/day; dose may be titrated as needed for pain relief (range: 1800-3600 mg/day in divided doses, daily doses >1800 mg do not generally show greater benefit)
Postoperative pain (unlabeled use): Usual dose: 300-1200 mg given 1-2 hours prior to surgery (Dauri, 2009)
Restless legs syndrome (RLS) (unlabeled use): Initial: 300 mg once daily 2 hours before bedtime. Doses ≥600 mg/day have been given in 2 divided doses (late afternoon and 2 hours before bedtime). Dose may be titrated every 2 weeks until symptom relief achieved (range: 300-1800 mg/day). Suggested maintenance dosing schedule: One-third of total daily dose given at 12 pm, remaining two-thirds total daily dose given at 8 pm. (Garcia-Borreguero, 2002; Happe, 2003; Saletu, 2010; Vignatelli, 2006)
Vasomotor symptoms associated with menopause (unlabeled use): Day 1: 300 mg at bedtime, Day 2: 300 mg twice daily, followed by 300 mg 3 times/day for 4 weeks and then tapered off (Butt, 2008)
Extended release (Gralise™): Postherpetic neuralgia: Day 1: 300 mg, Day 2: 600 mg, Days 3-6: 900 mg once daily, Days 7-10: 1200 mg once daily, Days 11-14: 1500 mg once daily, Days ≥15: 1800 mg once daily
Elderly: Studies in elderly patients have shown a decrease in clearance as age increases. This is most likely due to age-related decreases in renal function; dose reductions may be needed.
Dosing adjustment in renal impairment: Children ≥12 years and Adults: Note: Renal function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes.
Immediate release:
Clcr ≥60 mL/minute: 300-1200 mg 3 times/day
Clcr >30-59 mL/minute: 200-700 mg twice daily
Clcr >15-29 mL/minute: 200-700 mg once daily
Clcr 15 mL/minute: 100-300 mg once daily
Clcr <15 mL/minute: Reduce daily dose in proportion to creatinine clearance based on dose for creatinine clearance of 15 mL/minute (eg, reduce dose by one-half [range: 50-150 mg/day] for Clcr 7.5 mL/minute)
ESRD requiring hemodialysis: Dose for Clcr <15 mL/minute plus single supplemental dose of 125-350 mg (given after each 4 hours of hemodialysis)
Extended release: Note: Follow initial dose titration schedule if treatment-naive.
Clcr ≥60 mL/minute: 1800 mg once daily
Clcr >30-59 mL/minute: 600-1800 mg once daily; dependent on tolerability and clinical response
Clcr <30 mL/minute: Use is not recommended.
ESRD requiring hemodialysis: Use is not recommended.
Dosing adjustment in hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, gabapentin is not hepatically metabolized.
Dental Usual Dosing
Pain (unlabeled use): Children >12 years and Adults: Oral: 300-1800 mg/day given in 3 divided doses has been the most common dosage range
Postherpetic neuralgia or neuropathic pain: Adults: Oral: Day 1: 300 mg, Day 2: 300 mg twice daily, Day 3: 300 mg 3 times/day; dose may be titrated as needed for pain relief (range: 1800-3600 mg/day, daily doses >1800 mg do not generally show greater benefit)
Administration: Oral
Tablet, solution (immediate release): Administer first dose on first day at bedtime to avoid somnolence and dizziness. Dosage must be adjusted for renal function; when given 3 times daily, the maximum time between doses should not exceed 12 hours.
Tablet (extended release): Take with evening meal. Swallow whole; do not chew, crush, or split.
Monitoring Parameters
Monitor serum levels of concomitant anticonvulsant therapy; suicidality (eg, suicidal thoughts, depression, behavioral changes)
Test Interactions
False positives have been reported with the Ames N-Multistix SG® dipstick test for urine protein
Dietary Considerations
Immediate release tablet and solution may be taken without regard to meals; extended release tablet should be taken with food.
Patient Education
Avoid alcohol. You may experience drowsiness, lightheadedness, impaired coordination, dizziness, blurred vision, nausea, vomiting, anorexia, constipation, diarrhea, postural hypotension, or decreased sexual function or libido (reversible). Notify prescriber of persistent CNS effects (nervousness, restlessness, insomnia, anxiety, excitation, headache, sedation, worsening seizures or change in quality, mania, abnormal thinking), severe dizziness or passing out, suicide ideation or depression, rash or skin irritation, change in gait, bruising or bleeding, or worsening of condition.
Geriatric Considerations
Studies in the elderly have shown a decrease in clearance as age increases. This is most likely due to age-related decreases in renal function; calculations of Clcr recommended since dose reductions may be needed.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation), dry throat, and dental abnormalities.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Comment
Double-blind studies have failed to differentiate this drug from placebo when used as an adjunctive treatment for bipolar disorder. Gabapentin may be useful for some of the anxiety disorders.
Nursing: Physical Assessment/Monitoring
Assess for CNS depression. Taper dosage slowly when discontinuing. If treating seizures, teach patient safety and seizure precautions.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral: 100 mg, 300 mg, 400 mg
Neurontin®: 100 mg, 300 mg, 400 mg
Solution, oral: 250 mg/5 mL (470 mL)
Neurontin®: 250 mg/5 mL (470 mL) [cool strawberry-anise flavor]
Tablet, oral: 600 mg, 800 mg
Gralise™: 300 mg [contains soybean lecithin]
Gralise™: 600 mg
Neurontin®: 600 mg, 800 mg [scored]
Tablet, oral [combination package (each unit-dose starter kit contains)]:
Gralise™: 300 mg (9s) [white tablets; contains soybean lecithin] and 600 mg (69s) [beige tablets]
Pricing: U.S. (www.drugstore.com)
Capsules (Gabapentin)
100 mg (90): $43.99
300 mg (90): $18.99
400 mg (90): $74.99
Capsules (Neurontin)
100 mg (100): $93.99
300 mg (30): $69.99
400 mg (30): $83.99
Solution (Gabapentin)
250 mg/5 mL (470): $139.99
Solution (Neurontin)
250 mg/5 mL (470): $172.99
Tablets (Gabapentin)
600 mg (90): $98.99
800 mg (90): $99.99
Tablets (Neurontin)
600 mg (90): $396.98
800 mg (90): $481.00
Extemporaneously Prepared
Note: Commercial oral solution is available (50 mg/mL)
A 100 mg/mL suspension may be made with tablets (immediate release) and either a 1:1 mixture of Ora-Sweet® (100 mL) and Ora-Plus® (100 mL) or 1:1 mixture of methylcellulose 1% (100 mL) and Simple Syrup N.F. (100 mL). Crush sixty-seven 300 mg tablets in a mortar and reduce to a fine powder. Add small portions of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 200 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add sufficient quantity of vehicle to make 200 mL. Label "shake well" and "refrigerate". Stable for 91 days refrigerated (preferred) or 56 days at room temperature.
Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
References
Adler CH, “Treatment of Restless Legs Syndrome With Gabapentin,” Clin Neuropharmacol, 1997, 20(2):148-51.
Andrews CO and Fischer JH, “Gabapentin: A New Agent for the Management of Epilepsy,” Ann Pharmacother, 1994, 28(10):1188-96.
Attal N, Cruccu G, Baron R, et al, "EFNS Guidelines on the Pharmacological Treatment of Neuropathic Pain: 2010 Revision," Eur J Neurol, 2010, 17(9):1113-e88.
Bourgeois BF, “Antiepileptic Drugs in Pediatric Practice,” Epilepsia, 1995, 36(Suppl 2):34-45.
Bril V, England J, Franklin GM, et al, "Evidence-Based Guideline: Treatment of Painful Diabetic Neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation," Neurology, 2011, 76(20):1758-65.
Brown JT and Randall A, “Gabapentin Fails to Alter P/Q-Type Ca2+ Channel-Mediated Synaptic Transmission in the Hippocampus in vitro,” Synapse, 2005, 55(4):262-9.
Butt DA, Lock M, Lewis JE, et al, “Gabapentin for the Treatment of Menopausal Hot Flashes: A Randomized Controlled Trial,” Menopause, 2008, 15(2):310-8.
Dauri M, Faria S, Gatti A, et al, "Gabapentin and Pregabalin for the Acute Post-operative Pain Management. A Systematic-Narrative Review of the Recent Clinical Evidences," Curr Drug Targets, 2009, 10(8):716-33.
Dworkin RH, O'Connor AB, Audette J, et al, "Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update," Mayo Clin Proc, 2010, 85(3 Suppl):3-14.
Fischer JH, Barr AN, Rogers SL, et al, “Lack of Serious Toxicity Following Gabapentin Overdose,” Neurology, 1994, 44(5):982-3.
Garcia-Borreguero D, Larrosa O, de la Llave Y, et al, ”Treatment of Restless Legs Syndrome With Gabapentin: A Double-Blind, Cross-Over Study,” Neurology, 2002, 59(10):1573-9.
Goa KL and Sorkin EM, “Gabapentin: A Review of Its Pharmacological Properties and Clinical Potential in Epilepsy,” Drugs, 1993, 46(3):409-27.
Happe S, Sauter C, Klosch G, et al, “Gabapentin Versus Ropinirole in the Treatment of Idiopathic Restless Legs Syndrome,” Neuropsychobiology, 2003, 48(2):82-6.
Khurana DS, Riviello J, Helmers S, et al, “Efficacy of Gabapentin Therapy in Children With Refractory Partial Seizures,” J Pediatr, 1996, 128(6):829-33.
Lee DO, Steingard RJ, Cesena M, et al, “Behavioral Side Effects of Gabapentin in Children,” Epilepsia, 1996, 37(1):87-90.
Leiderman D, Garofalo E, and LaMoreaux L, “Gabapentin Patients With Absence Seizures: Two Double-Blind, Placebo Controlled Studies,” Epilepsia, 1993, 34(Suppl 6):45.
Mellick LB and Mellick GA, “Successful Treatment of Reflex Sympathetic Dystrophy With Gabapentin,” Am J Emerg Med, 1995, 13(1):96.
Saletu M, Anderer P, Saletu-Zyhlarz GM, et al, “Comparative Placebo-Controlled Polysomnographic and Psychometric Studies on the Acute Effects of Gabapentin Versus Ropinirole in Restless Legs Syndrome,”J Neural Transm, 2010, 117(4):463-73.
Short C and Cooke L, “Hypomania Induced by Gabapentin,” Br J Psychiatry, 1995, 166(5):679-80.
Sills GJ, “The Mechanisms of Action of Gabapentin and Pregabalin,” Curr Opin Pharmacol, 2006, 6(1):108-13.
Vignatelli L, Billiard M, Clarenbach P, et al, “EFNS Guidelines on Management of Restless Leg Syndrome and Periodic Limb Movement Disorder in Sleep,” Eur J Neurol, 2006, 13(10):1049-65.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
| 
