Saturday, June 16, 2012

Learn a Drug a Day - Naproxen




Today's drug is naproxen.
Naproxen sodium has been developed as a more rapid absorbed formulation of naproxen for use as an analgesic.
What is naproxen indicated for?
INDICATIONS : 
  • It is known as a nonsteroidal anti-inflammatory drug (NSAID)
  • It is used to relieve pain and swelling (inflammation) from various conditions. 
  • It is used to treat acute migraine attacks, muscle aches, backaches, tendonitis, dental pain, and dysmenorrhoea (menstrual pain or menstrual cramps). 
  • It also reduces pain, swelling, and joint stiffness caused by arthritis, bursitis, and gout attacks. 




How does naproxen work?
MECHANISMS OF ACTION : 
  • Naproxen has anti-inflammatory, analgesic, antipyretic actions. It reduces prostaglandin synthesis by inhibiting the enzyme cyclooxygenase. 
  • It also inhibits platelet aggregation.
  • Onset: Analgesic: 1 hr; anti-inflammatory: Approx 2 wk.
  • Duration: Analgesic: ≤7 hr; anti-inflammatory: ≤12 hr.
  • Absorption: Readily absorbed from the GI tract (oral); peak plasma concentrations after 2-4 hr. Well absorbed rectally.
  • Distribution: Diffuses into synovial fluid; crosses the placenta; enters breast milk. Protein-binding: 99%.
  • Excretion: Via urine (as unchanged drug and metabolites), faeces; 13 hr (elimination half-life).




How is naproxen being used?
ROUTE OF ADMINISTRATION : 
  • It is taken orally as tablets.
  • Take this medication by mouth with a full glass of water. 
  • Do not lie down for at least 30 minutes after taking this drug. 
  • To prevent stomach upset, take this medication with food, milk, or an antacid. 
  • To minimize side effect risks (e.g., stomach bleeding), use this medication at the lowest effective dose for the shortest possible length of time. 
  • For ongoing conditions such as arthritis, it may take up to 2 weeks of regular use before the full benefits of this drug take effect. 
  • If patient is taking this drug on an "as needed" basis (not on a regular schedule), remember that pain medications work best if they are used as the first signs of pain occur. If you wait until the pain has significantly worsened, the medicine may not work as well. 
  • If patient uses this medication for migraine headache, and the pain is not relieved or worsens after the first dose, patient should tell doctor immediately and inform doctor if their condition worsens.




Is there any contraindication?
CONTRAINDICATIONS : 
  • It is contraindicated in patients with known hypersensitivity to naproxen.
  • It also should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients.
  • It is also contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery. 




Are there any possible side effects?
SIDE EFFECTS : 


(i) Common possible side effects : 
  • Upset stomach, nausea, heartburn, diarrhea, constipation, headache, tiredness, drowsiness, and dizziness may occur.
  • Many people using this medication do not have serious side effects. Serious side effects occur: stomach pain, difficult/painful swallowing, swelling of the hands/feet, sudden/unexplained weight gain, vision changes, hearing changes (e.g., ringing in the ears), mental/mood changes (e.g., depression), fast/pounding heartbeat, persistent/severe headache, fainting. 

(ii) Rare possible side effects : 
  • Change in the amount of urine, easy bruising/bleeding, signs of infection (e.g., fever, persistent sore throat), unexplained stiff neck. 
  • This drug may rarely cause serious (possibly fatal) liver disease. 
  • Yellowing eyes/skin, dark urine, unusual/extreme tiredness, severe stomach/abdominal pain, persistent nausea/vomiting. 
  • A very serious allergic reaction to this drug is unlikely. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing. 



What precautions are necessary?
PRECAUTIONS : 

General
  • Naproxen cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids and the patient should be observed closely for any evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis.
  • Patients with initial hemoglobin values of 10 g or less who are to receive long-term therapy should have hemoglobin values determined periodically.
  • The pharmacological activity of naproxen in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, noninflammatory painful conditions.
  • Because of adverse eye findings in animal studies with drugs of this class, it is recommended that ophthalmic studies be carried out if any change or disturbance in vision occurs.

Hepatic Effects

  • Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including napoxen. Hepatic abnormalities may be the result of hypersensitivity rather than direct toxicity. These laboratory abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy. The SGPT (ALT) test is probably the most sensitive indicator of liver dysfunction. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.
  • A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of more severe hepatic reaction while on therapy with naproxen.
  • If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, etc.), naproxen should be discontinued.
  • Chronic alcoholic liver disease and probably other diseases with decreased or abnormal plasma proteins (albumin) reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased. Caution is advised when high doses are required and some adjustment of dosage may be required in these patients. It is prudent to use the lowest effective dose.

Hematological Effects
  • Anemia is sometimes seen in patients receiving NSAIDs, including naproxen. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including naproxen, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
  • NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving naproxen who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.

Preexisting Asthma

  • Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bron-chospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, naproxen should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

Laboratory Tests

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (eg, eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, naproxen should be discontinued.

DRUG INTERACTIONS : 

(i) ACE-inhibitors
  • Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors.


    (ii) Antacids and Sucralfate
    • Concomitant administration of some antacids (magnesium oxide or aluminum hydroxide) and sucralfate can delay the absorption of naproxen.


      (iii) Aspirin
      • When naproxen is administered with aspirin, its protein binding is reduced, although the clearance of free naproxen is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of naproxen and naproxen sodium and aspirin is not generally recommended because of the potential of increased adverse effects.


        (iv) Cholestyramine
        • As with other NSAIDs, concomitant administration of cholestyramine can delay the absorption of naproxen.


          (v) Diuretics
          • Clinical studies, as well as postmarketing observations, have shown that naproxen can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure, as well as to assure diuretic efficacy.

            (vi) Lithium
            • NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.


              (vii) Methotrexate
              • NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. Naproxen, naproxen sodium and other nonsteroidal anti-inflammatory drugs have been reported to reduce the tubular secretion of methotrexate in an animal model. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.


                (viii) Warfarin
                • The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone. No significant interactions have been observed in clinical studies with naproxen and coumarin-type anticoagulants. However, caution is advised since interactions have been seen with other nonsteroidal agents of this class. The free fraction of warfarin may increase substantially in some subjects and naproxen interferes with platelet function.


                  (ix) Selective Serotonin Reuptake Inhibitors (SSRIs)
                  • There is an increased risk of gastrointestinal bleeding when selective serotonin reuptake inhibitors (SSRIs) are combined with NSAIDs. Caution should be used when NSAIDs are administed concomintantly with SSRIs.


                    (x) Other Information Concerning Drug Interactions
                    • Naproxen is highly bound to plasma albumin; it thus has a theoretical potential for interaction with other albumin-bound drugs such as coumarintype anticoagulants, sulphonylureas, hydantoins, other NSAIDs, and aspirin. Patients simultaneously receiving naproxen and a hydantoin, sulphonamide or sulphonylurea should be observed for adjustment of dose if required.
                    • Naproxen and other nonsteroidal anti-inflammatory drugs can reduce the antihypertensive effect of propranolol and other beta-blockers.
                    • Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly.
                    • Due to the gastric pH elevating effects of H2-blockers, sucralfate and intensive antacid therapy, concomitant administration of naproxen is not recommended.

                    Pregnancy and breastfeeding:  
                    • There are no adequate and well-controlled studies in pregnant women. naproxen should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.
                    • The naproxen has been found in the milk of lactating women. Because of the possible adverse effects of prostaglandin-inhibiting drugs on neonates, use in nursing mothers should be avoided.



                    References : 




                    1 comments:

                    tomcruse said...

                    Nice blog, Thanks for share such important information about Naproxen sodium. This is very useful for us..keep sharing.

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