Etoricoxib / Paracetamol

Brands of Etoricoxib / Paracetamol in Kenya

Ecofree Plus, Medisel Kenya Ltd

MODE OF ACTION

Paracetamol
Paracetamol has a central analgesic effect that is mediated through activation of descending serotonergic pathways. Debate exists about its primary site of action, which may be inhibition of prostaglandin (PG) synthesis or through an active metabolite influencing cannabinoid receptors.

Etoricoxib

Like any other selective COX-2 inhibitor (“coxib”), etoricoxib selectively inhibits isoform 2 of the enzyme cyclooxygenase (COX-2). It has approximately 106-fold selectivity for COX-2 inhibition over COX-1. This reduces the generation of prostaglandins (PGs) from arachidonic acid.

INDICATIONS

This drug is indicated in adults and adolescents 16 years of age and older for the symptomatic relief of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, and the pain and signs of inflammation associated with acute gouty arthritis.

This drug is indicated in adults and adolescents 16 years of age and older for the short-term treatment of moderate pain associated with dental surgery.

The decision to prescribe this drug should be based on an assessment of the individual patient’s overall risks

CONTRAINDICATIONS

  • Hypersensitivity to the active substance or to any of the excipients.
  • Active peptic ulceration or active gastro-intestinal (GI) bleeding.
  • Patients who, after taking acetylsalicylic acid or NSAIDs including COX-2 (cyclooxygenase-2) inhibitors, experience bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions.
  • Pregnancy and lactation
  • Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score ≥10).
  • Estimated renal creatinine clearance <30 ml/min.
  • Children and adolescents under 16 years of age.
  • Inflammatory bowel disease.
  • Congestive heart failure (NYHA II-IV).
  • Patients with hypertension whose blood pressure is persistently elevated above 140/90 mmHg and has not been adequately controlled.
  • Established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease.
  • Hypersensitivity to paracetamol.

DRUG INTERACTION

Paracetamol

Cholestyramine: The speed of absorption of paracetamol is reduced by cholestyramine. Therefore, the cholestyramine should not be taken within one hour if maximal analgesia is required.

Metoclopramide and Domperidone: The absorption of paracetamol is increased by metoclopramide and domperidone. However, concurrent use need not be avoided.

Warfarin: The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

Chloramphenicol: Increased plasma concentration of chloramphenicol.

Etoricoxib

Oral anticoagulants:
Patients receiving oral anticoagulants should be closely monitored for their prothrombin time INR, particularly in the first few days when therapy with etoricoxib is initiated or the dose of etoricoxib is changed

Diuretics, ACE inhibitors and Angiotensin II Antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible.

Acetylsalicylic Acid:

Concomitant administration of low-dose acetylsalicylic acid with etoricoxib may result in an increased rate of GI ulceration or other complications compared to use of Etoricoxib alone. Concomitant administration of etoricoxib with doses of acetylsalicylic acid above those for cardiovascular prophylaxis or with other NSAIDs is not recommended

Cyclosporin and tacrolimus: Although this interaction has not been studied with etoricoxib, coadministration of cyclosporin or tacrolimus with any NSAID may increase the nephrotoxic effect of cyclosporin or tacrolimus. Renal function should be monitored when etoricoxib and either of these drugs is used in combination.

Pharmacokinetic interactions

The effect of etoricoxib on the pharmacokinetics of other drugs

Lithium:
NSAIDs decrease lithium renal excretion and therefore increase lithium plasma levels. If necessary, monitor blood lithium closely and adjust the lithium dosage while the combination is being taken and when the NSAID is withdrawn.

Methotrexate:
Adequate monitoring for methotrexate-related toxicity is recommended when etoricoxib and methotrexate are administered concomitantly.

Oral contraceptives:
An increase in ethinyl estradiol (EE) exposure can increase the incidence of adverse events associated with oral contraceptives (e.g., venous thrombo-embolic events in women at risk).

Hormone Replacement Therapy (HRT):
Increases in estrogenic concentration should be taken into consideration when selecting post-menopausal hormone therapy for use with etoricoxib because the increase in oestrogen exposure might increase the risk of adverse events associated with HRT.

Prednisone/prednisolone:
In drug-interaction studies, etoricoxib did not have clinically important effects on the pharmacokinetics of prednisone/prednisolone.

Digoxin:
Patients at high risk of digoxin toxicity should be monitored when etoricoxib and digoxin are administered concomitantly.

Effect of etoricoxib on drugs metabolised by sulfotransferases

Etoricoxib is an inhibitor of human sulfotransferase activity, particularly SULT1E1, and has been shown to increase the serum concentrations of ethinyl estradiol. While knowledge about effects of multiple sulfotransferases is presently limited and the clinical consequences for many drugs are still being examined, it may be prudent to exercise care when administering etoricoxib concurrently with other drugs primarily metabolised by human sulfotransferases (e.g., oral salbutamol and minoxidil).

Effect of etoricoxib on drugs metabolised by CYP isoenzymes

Based on in vitro studies, etoricoxib is not expected to inhibit cytochromes P450 (CYP) 1A2, 2C9, 2C19, 2D6, 2E1 or 3A4. In a study in healthy subjects, daily administration of etoricoxib 120 mg did not alter hepatic CYP3A4 activity as assessed by the erythromycin breath test.

Effects of other drugs on the pharmacokinetics of etoricoxib

The main pathway of etoricoxib metabolism is dependent on CYP enzymes. CYP3A4 appears to contribute to the metabolism of etoricoxib in vivo. In vitro studies indicate that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 also can catalyse the main metabolic pathway, but their quantitative roles have not been studied in vivo.

Ketoconazole:
Ketoconazole, a potent inhibitor of CYP3A4, dosed at 400 mg once a day for 11 days to healthy volunteers, did not have any clinically important effect on the single-dose pharmacokinetics of 60 mg etoricoxib (43% increase in AUC).

Voriconazole and Miconazole:
Co-administration of either oral voriconazole or topical miconazole oral gel, strong CYP3A4 inhibitors, with etoricoxib caused a slight increase in exposure to etoricoxib, but is not considered to be clinically meaningful based on published data.

Rifampicin:
Coadministration of etoricoxib with rifampicin, a potent inducer of CYP enzymes, produced a 65% decrease in etoricoxib plasma concentrations. This interaction may result in recurrence of symptoms when etoricoxib is coadministered with rifampicin. While this information may suggest an increase in dose, doses of etoricoxib greater than those listed for each indication have not been studied in combination with rifampicin and are therefore not recommended.

Antacids:
Antacids do not affect the pharmacokinetics of etoricoxib to a clinically relevant extent.

ADVERSE EFFECTS

Paracetamol

Blood and lymphatic system disorders

Not known: Blood dyscrasias including thrombocytopenia, agranulocytosis.

Immune system disorders

Not known: Hypersensitivity reactions (including skin rashes)

Skin and subcutaneous tissue disorders

Very rare cases of serious skin reactions have been reported.

Infections and infestations
alveolar osteitis
Common
gastroenteritis, upper respiratory infection, urinary tract infection
Uncommon
Blood and lymphatic system disorders
anaemia (primarily associated with gastrointestinal bleeding), leukopenia, thrombocytopenia
Uncommon
Immune system disorders
hypersensitivity‡ ß
Uncommon
angioedema/anaphylactic /anaphylactoid reactions including shock‡
Rare
Metabolism and nutrition disorders
oedema/fluid retention
Common
appetite increase or decrease, weight gain
Uncommon
Psychiatric disorders
anxiety, depression, mental acuity decreased, hallucinations‡
Uncommon
confusion‡, restlessness‡
Rare
Nervous system disorders
dizziness, headache
Common
dysgeusia, insomnia, paresthaesia/hypaesthesia, somnolence
Uncommon
Eye disorders
blurred vision, conjunctivitis
Uncommon
Ear and labyrinth disorders
tinnitus, vertigo
Uncommon
Cardiac disorders
palpitations, arrhythmia‡
Common
atrial fibrillation, tachycardia‡, congestive heart failure, non-specific ECG changes, angina pectoris‡, myocardial infarction§
Uncommon
Vascular disorders
hypertension
Common
flushing, cerebrovascular accident§, transient ischaemic attack, hypertensive crisis‡, vasculitis‡
Uncommon
Respiratory, thoracic and mediastinal disorders
bronchospasm‡
Common
cough, dyspnoea, epistaxis
Uncommon
Gastrointestinal disorders
abdominal pain
Very common
Constipation, flatulence, gastritis, heartburn/acid reflux, diarrhea, dyspepsia/epigastric discomfort, nausea, vomiting, oesophagitis, oral ulcer
Common
abdominal distention, bowel movement pattern change, dry mouth, gastroduodenal ulcer, peptic ulcers including gastrointestinal perforation and bleeding, irritable bowel syndrome, pancreatitis‡
Uncommon
Hepatobiliary disorders
ALT increased, AST increased
Common
hepatitis‡
Rare
hepatic failure‡, jaundice‡
Rare†
Skin and subcutaneous tissue disorders
ecchymosis
Common
facial oedema, pruritus, rash, erythema‡, urticaria‡
Uncommon
Stevens-Johnson syndrome‡, toxic epidermal necrolysis‡, fixed drug eruption‡
Rare†
Musculoskeletal and connective tissue disorders
muscular cramp/spasm, musculoskeletal pain/stiffness
Uncommon
Renal and urinary disorders
proteinuria, serum creatinine increased, renal failure/renal insufficiency‡(see section 4.4)
Uncommon
General disorders and administration site conditions
asthenia/fatigue, flu-like disease
Common
chest pain
Uncommon
Investigations
blood urea nitrogen increased, creatine phosphokinase increased, hyperkalaemia, uric acid increased
Uncommon
blood sodium decreased

Reporting of suspected adverse reactions:

The PPB Department of Pharmacovigilance was set up with a vision to develop, implement and continuously upgrade an appropriate system for detecting, reporting, and monitoring adverse drug reactions (ADRs) and other relevant problems with medicines in Kenya. The department strives to ensure the safety and efficacy of pharmaceutical products in Kenya.
Reporting suspected adverse reactions after authorization of the medicinal product are important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals/ Patients are encouraged to report any suspected adverse reactions via Pharmacovigilance Yellow Form, pv@pharmacyboardkenya.org or clicking below button:


Etoricoxib / Paracetamol in Kenya
Etoricoxib / Paracetamol in Kenya
Etoricoxib / Paracetamol in Kenya
Etoricoxib / Paracetamol in Kenya
Etoricoxib / Paracetamol in Kenya
Etoricoxib / Paracetamol in Kenya

Clinical | Pharmacokinetic data


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