Naproxen/ Esomeprazole

Registered South African indications:

• Rheumatic conditions
• Gastric/duodenal ulcer

Contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Hypersensitivity to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs
• Third trimester of pregnancy 
• Severe renal impairment
• Severe hepatic impairment
• Severe cardiac failure
• Active peptic ulceration
• Gastrointestinal bleeding
• Cerebrovascular bleeding
• Bleeding disorders
• Coadministration with Atazanavir
• Coadministration with Nelfinavir

Cautions

• First and second trimesters of pregnancy 
• Breastfeeding
• Mild to moderate renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Systemic lupus erythematosus
• Mixed connective tissue disease
• Prolonged use
• Gastrointestinal disease
• Hypertension
• Mild to moderate cardiac failure
• Ischaemic heart disease
• Peripheral arterial disease
• Cerebrovascular disease
• Asthma
• Female patients intending to conceive
• Risk of osteoporosis

Forms avail. in SA and covered in this monograph: tab

Rheumatoid arthritis
Osteoarthritis
Anklosing spondylitis
Patients requiring proton pump inhibitors to reduce the risk of nonsteroidal anti-inflammatory associated gastric or duodenal ulcers 

Naproxen/ Esomeprazole
500/20 (mg)

• Oral (tab): 1 tab, 12hrly

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Do not cut/crush/chew

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Take 30mins prior to food intake

Not established for use in children below 18 years 

Pregnancy

• First and second trimester: Caution
• Third trimester: Contraindicated
• Naproxen: Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre-and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period 
• In women attempting to conceive or during the first and second trimester of pregnancy, naproxen/esomeprazole should not be given unless the potential benefit to the patient outweighs the potential risk to the foetus. If naproxen/esomeprazole is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the duration of treatment should be kept as short as possible
• During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:
  - cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
  - renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;
• During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the mother and the neonate at the end of pregnancy, to:
  - possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses
  - inhibition of uterine contractions resulting in delayed or prolonged labour
• Consequently, naproxen/esomeprazole is contraindicated during the third trimester of pregnancy
• Esomeprazole: There are limited amount of data from the use of esomeprazole in pregnant women. With the racemic mixture omeprazole, data on a larger number of exposed pregnancies stemming from epidemiological studies indicate no malformative nor foetotoxic effects. Animal studies with esomeprazole do not indicate direct or indirect harmful effects with respect to embryonal/foetal development. Animal studies with the racemic mixture do not indicate direct or indirect harmful effects with respect to pregnancy, parturition or postnatal development

Breastfeeding

• Caution; not recommended
• Naproxen is excreted in low quantities in human milk. It is unknown whether esomeprazole is excreted in human milk. A published case report on the racemic mixture omeprazole indicated excretion of low quantities in the human breast milk (weight-adjusted dose < 7%). naproxen/esomeprazole should not be used during breastfeeding

Renal Impairment

• CrCl ≥30ml/min: Caution; dose adjustment recommended
  A reduction in the total daily naproxen dose should be considered 
  When total daily dose of 1000 mg of naproxen is not considered appropriate, alternative treatment with lower strength of naproxen or of other NSAIDs as non-fixed combination should be utilised
• CrCl <30ml/min: Contraindicated

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended
  A reduction in the total daily naproxen dose should be considered
  When total daily dose of 1000 mg of naproxen is not considered appropriate, alternative treatment with lower strength of naproxen or of other NSAIDs as non-fixed combination should be utilised
  Avoid use in moderate renal impairment
• Severe: Contraindicated

Elderly

• Caution; dose adjustment recommended
  Use lowest effective dose
  When total daily dose of 1000 mg of naproxen is not considered appropriate, alternative treatment with lower strength of naproxen or of other NSAIDs as non-fixed combination should be utilised

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Headache
• Paraesthesia
• Syncope
• Tremor
• Somnolence
• Anxiety
• Depression
• Insomnia
• Confusion
• Dream abnormalities
• Fatigue

Cardiovascular Disorders

• Arrhythmia
• Palpitations
• Myocardial infarction
• Tachycardia
• Hypertension

Respiratory Disorders

• Asthma
• Bronchospasm
• Dyspnoea

Gastrointestinal Disorders

• Dyspepsia
• Abdominal pain
• Constipation
• Diarrhoea
• Oesophagitis
• Nausea and vomiting
• Flatulence
• Gastric or duodenal ulcers
• Gastritis
• Dry mouth
• Gastrointestinal bleeding
• Stomatitis
• Eructation
• Glossitis
• Diverticulitis

Hepatobiliary Disorders

• Abnormal liver function tests

Genitourinary Disorders

• Proteinuria
• Renal impairment

Endocrine and Metabolic Disorders

• Fluid retention
• Hyperkalaemia
• Hyperuricaemia
• Hypomagnesaemia
• Menstrual disorders

Musculoskeletal Disorders

• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Rashes 
• Dermatitis
• Pruritis
• Urticaria
• Alopecia
• Hyperhidrosis

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
• Ecchymoses
• Eosinophilia
• Leukopenia
• Fever

Sensory Disorders

• Taste disturbance

• Antiretroviral agents
• Analgesics
• Acetylsalicylic acid
• Cyclosporin
• Tacrolimus
• Diuretics
• Selective serotonin reuptake inhibitors
• Corticosteroids
• Angiotensin-converting enzyme inhibitors
• Angiotensin II antagonists
• Digoxin
• Lithium
• Methotrexate
• Sulphonylureas
• Hydantoins
• Clopidogrel
• Anticoagulants
• Platelet inhibitors
• Beta blockers
• Probenecid
• Proton pump inhibitors
• Cholestyramine
• CYP2C19 substrates
• CYP2C19 inhibitors
• CYP2C19 inducers
• CYP3A4 inhibitors

None routine. Specific cases may require

• Renal function 
• Hepatic function 
• Serum magnesium levels 

Naproxen
Naproxen inhibits prostaglandin synthesis by inhibition of cyclooxygenase.

Esomeprazole
Esomeprazole is a proton pump inhibitor which suppresses gastric acid secretion by inhibition of the H⁺/K⁺-ATPase in the gastric parietal cell, thereby blocking the final step in acid production and reducing gastric acidity. 

COMBINATION PREPARATIONS

Naproxen/ Esomeprazole

Tablet 500mg/20mg

• Vimovo (AstraZeneca) originator