Neuroxicam® Capsules x 20, x 100 (Piroxicam 20 mg)

NEUROXICAM (PIROXICAM 20mg) Capsule and Injections

DESCRIPTION
Neuroxicam® brand of Piroxicam is a member of the chemical class of nonsteroidal anti-inflammatory agents, N-heterocyclic carboxamides of 1,2-benzothiazine-1,1-dioxide. Piroxicam is an amphoteric compound. It exhibits a weakly acidic 4-hydroxy proton (pka 5.1) and a weakly basic pyridinyl nitrogen (pka 1.8) as determined by ultraviolent absorption spectrophotometry in methanol-water (2.5 - 97.5 v/v) solvent medium. It occurs as a white to off-white crystalline solid, poorly soluble in water, dilute acid and most organic solvents. It is slightly soluble in alcohols and in aqueous alkaline solution.

Neuroxicam Chemical formula

ACTIONS
Neuroxicam® is a nonsteroidal anti-inflammatory agent which also possesses analgestic and antipyretic properties. It is effective regardless of the etiology of the inflammation. While its mode of action is not fully understood, independent studies in-vitro as well as in-vivo have shown that Neuroxicam® interact at several steps in the immune and inflammation responses through:
• Inhibition of prostanoid synthesis, including prostaglandins, through a reversible inhibition of the cyclooxygenase enzyme.
• Inhibition of neutrophil aggregation • Inhibition of polymorphonuclear cell and monocyte migration to the area of inflammation
• Inhibition of lysosomal enzymes release from stimulated leucocytes
• Inhibition of superoxide anion generation by the neutrophil.
• Reduction of both systemic and synovial fluid rheumatoid factor production in patients with rheumatic arthritis

In clinical studies Neuroxicam® has been found effective as an analgesic in pain of various etiologies (post traumatic pain, post episiotomy pain and post operative pain). The onset of analgesia is prompt. Drug plasma concentrations generally peak within three to five hours after medication. A single 20mg dose generally produces peak Piroxicam plasma levels of 1.5 to 2mcg/ml while maximum drug plasma concentrations, after repeated daily ingestions of 20mg Piroxicam, usually stabilise at 3 to 8mcg/ml. Most patients approximate steady plasma levels with 7-12 days. Treatment with a loading dose of regimen of 40mg daily for the first two days followed by 20mg daily thereafter allows a high percentage (approximately 76%) of steady state levels to be achieved immediately following the second dose. Steady state levels, area under the curves and eliminated half- life are similar to that following a 20mg daily dose regimen. Neuroxicam® is extensively metabolized and less than 5% of the daily dose is excreted unchanged in urine and feaces. One important metabolic pathway is hydroxylation of the pyridyl ring of the NeuroXicam® chain, followed by conjugation with glucuronic acid and urinary elimination.

INDICATIONS
Neuroxicam® is indicated for a variety of conditions requiring anti-inflammatory and/or analgesic activity, such as rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis (arthrosis, degenerative joint disease), ankylosing spondylitis, acute musculoskeletal disorders, acute gout, pain after operative intervention and following acute trauma. Neuroxicam® is indicated for the treatment of primary dysmenorrheal in patients 12 years of age or older. Neuroxicam® is indicated for the relief of fever and pain associated with acute upper respiratory tract inflammation.

DOSAGE AND ADMINISTRATION
Rheumatoid Arthritis Osteoarthritis (Arthrosis, Degenerative Joint Disease), Ankylosing, spondylitis. The recommended starting dose is 20mg given as a single daily dose. The majority of patients will be maintained on 20mg daily dose. Acute Musculoskeletal Disorders Therapy should be initiated with 40mg daily for the first two days given in single or divided does. For the remainder of 7-14 day treatment period, the dose should be reduced to 20mg daily.
Acute Gout: The therapy should be initiated by a single dose of 40mg followed by the next 4-6 days by 40mg given in a single divided daily dosage. Neuroxicam® is not indicated for the long-term management of gout.
Post-operative and post traumatic Pain: The recommended starting dose is 20mg, given as a single dose. In case where a more rapid onset of action is desired, therapy should be initiated with 40mg daily for the first two days, given in single or divide doses. For the reminder of the treatment period, the dose should be reduced to 20mg daily.
Dysmenorrhoea: The treatment of primary dysmenorrhoea is initiated at the earliest onset of symptoms with a recommended starting dose of 40mg given as a single daily dose for the first two days. Treatment may be continued thereafter with a single daily dose of 20mg for the next three days as necessary.
Upper Respiratory Tract Inflammation: The usual adult dosage is 20mg orally once daily. In cases where a more rapid onset of action is desired, therapy should be initiated with 40mg once daily for the first two days, followed by 20mg daily for the first three to five days.

CONTRA-INDICATIONS
1. Active peptic ulceration
2. Neuroxicam® should not be used in those patients who have previously shown hypersensitivity to the drug. The potential exists for cross sensitivity to aspirin and other non-steroid anti-inflammatory drugs. Neuroxicam® should not be given to patients in whom aspirin or other non-steroidal anti-inflammatory drugs induce the symptoms of asthma, nasal polyps, angioedema or urticaria.

PRECUATIONS
Infrequent incidences of peptic ulceration, perforation and gastrointestinal bleeding

WARNINGS
Pregnancy: Although no teratogenic effects were seen in animal testing, the safety of Neuroxicam® use during pregnancy or during lactation has not been established. Neuroxicam® inhibits prostaglandin synthesis and release through a reversible inhibition of the cycloxygenase enzyme. This effect, as with other non-steroidal anti-inflammatory agents has been associated with an increased incidence of dystocia and delayed parturition in pregnant animals when drug administration was continued into late pregnancy. Non steroidal anti-inflammatory drugs are also known to induce closure of the ductus arteriosus in infants. The presence of Piroxicam has been determined during initial and long term dosing conditions (52 days). Piroxicam appeared in breast milk at about 1%-3% of the maternal plasma concentration. No accumulation of Piroxicam occurred in milk relative to that in plasma during treatment. Neuroxicam® is therefore not recommended for use in nursing mothers as the clinical safety has not been established.

"KEEP ALL MEDICINES AWAY FROM CHILDREN"

ADVERSE REACTIONS
Neuroxicam® is generally well tolerated. Gastrointestinal symptoms are most commonly encountered side effects but in most instances do not interfere with the course of therapy. These adverse reactions include stomatitis, anorexia, epigastric distress, nausea, constipation, abdominal discomfort, flatulence, diarrhoea, abdominal pain, indigestion, gastro-intestinal bleeding, perforation and ulceration have been reported with Neuroxicam®. Objective evaluations of gastric mucosal appearances and intestinal blood loss show that 20mg/day of Neuroxicam® administered either in single or divided daily doses is significantly less irritating to the gastrointestinal tract than acetylsalicylic acid. Long-term administration of doses higher than 20mg increase risk of gastrointestinal side effects. Other than gastrointestinal symptoms, eodema, mainly ankle eodema, has been reported in a small percentage of patients. CNS effects such as dizziness, headache, somnolence, insomnia, depression, nervousness, hallucinations, mood alterations, dream abnormalities, mental confusion, paresthesias and vertigo have been reported rarely. Swollen eyes, blurred vision and eye irritations has been reported. Routine ophthalmoscopy and slit-lamp examination have revealed no evidence of ocular changes. Malaise and tinnitus may occur. Dermal hypersensitivity reactions, usually in the form of skin rash and pruritus have been reported. Onycholysis and alopecia have rarely been reported. Photo-allergic reactions have infrequently been associated with therapy. As with other non-steroidal anti-inflammatory drugs, toxic epidermal necrolysis (Lyell's disease), and Stevens-Johnson syndrome may develop in rare cases. Vesiculo bullous reactions have been reported rarely. Hypersensitivity reactions such as anaphylaxis, dionchospasm, urticaria/ angioedema, vasculitis, and "serum sickness" have been reported rarely. Decreases in haemoglobin and hematocrit, unassociated with obvious gastrointestinal bleeding have occurred. Anaemia has been reported. Thrombocytopenia and non-thrombocytopanic purpura (Henoch-Scholein) Leucopenia and eosinophillia have been reported. Rare cases of asplatic anaemia and hemolytic anemia are also reported. Epistaxis has rarely been reported. Changes in different liver function parameters has been observed. As with other nonsteroidal anti-inflammatory agents, some patients may develop increased serum transaminase levels during treatment with Neuroxicam® severe hepatic eactions including jaundice and cases of fatal hepatitis have been reported with Neuroxicam®. Although such reactions are rare, if abnormal liver functions tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestation occur (e.g. eosinophiia, rash e.t.c.), Neuroxicam® should be discontinued. Palpitations and dyspnea have been reported rarely. Anecdotal cases of positive ANA and of hearing impairment have been reported rarely in patients receiving Neuroxicam®. Metabolic abnormalities such as hypoglycemia, weight increase or decrease have been reported rarely.

OVERDOSAGE
In the event of overdosage, Neuroxicam® supportive and symptomatic therapy is indicated. Studies indicate that administration of activated charcoal may result in reduced absorption and re-absorption of Piroxicam thus reducing the total amount of active drug available.

PRESENTATION
Neuroxicam® 20mg Capsules: - Box of 10x10 capsules in Blister pack.
Neuroxicam® 20mg/ml injection- 1ml Ampoule packed by 100's

NAFDAC REGISTRATION NUMBER: 04-4512

Manufactured by:
DRUGFIELD PHAMACEUTICAL LIMITED
Lynson Chemical Avenue,
Km 38, Lagos-Abeokuta Expressway,
Sango-Otta, Nigeria.