Danilo120 mg

Danilo is a selective COX-2 inhibitor (coxib-class) NSAID used for the relief of pain and inflammation in the following established indications:

• Osteoarthritis (OA) — for relief of joint pain and stiffness.
• Rheumatoid arthritis (RA) — for relief of joint pain, swelling, and inflammation.
• Ankylosing spondylitis — for relief of spinal and joint pain and inflammation.
• Acute gouty arthritis — for short-term relief of pain and inflammation during an acute gout flare.
• Acute pain, including short-term moderate pain following dental surgery.

Danilo provides symptomatic relief of pain and inflammation; it does not alter the underlying course of the disease and is not a cure. It should be used at the lowest effective dose for the shortest duration consistent with the individual patient's treatment goals, because of a dose- and duration-related cardiovascular thrombotic risk (see Precautions and Warnings).

Each tablet contains Etoricoxib as the active pharmaceutical ingredient, commonly available in Bangladesh as:

• Etoricoxib 30 mg tablet
• Etoricoxib 60 mg tablet
• Etoricoxib 90 mg tablet
• Etoricoxib 120 mg tablet

Tablets also contain standard pharmaceutical excipients (binders, fillers, coating/coloring agents) that do not have independent therapeutic activity.

Danilo is a selective cyclooxygenase-2 (COX-2) inhibitor NSAID (a "coxib") used to relieve pain, swelling, and stiffness caused by inflammatory and degenerative joint conditions and acute pain states. By preferentially sparing the COX-1 enzyme, Danilo is associated with a lower incidence of upper gastrointestinal ulceration and bleeding compared with non-selective NSAIDs, though this risk is not eliminated. Danilo carries an established cardiovascular thrombotic risk that increases with dose and duration of use, which shapes its contraindications and precautions more strictly than for many other NSAIDs.

Danilo is not approved by the US FDA; the FDA declined approval in 2007 over cardiovascular safety concerns. However, Danilo is approved and widely marketed in the European Union, United Kingdom, and many other countries including Bangladesh, where it is available as 30 mg, 60 mg, 90 mg, and 120 mg tablets under various brand names.

Danilo belongs to the class of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), specifically the selective cyclooxygenase-2 (COX-2) inhibitor subgroup, commonly referred to as "coxibs." It has analgesic, anti-inflammatory, and antipyretic properties.

Etoricoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, which is induced at sites of inflammation and is chiefly responsible for the synthesis of prostaglandins that mediate pain, inflammation, fever, and swelling. At therapeutic doses, Etoricoxib has minimal effect on the constitutively expressed COX-1 enzyme, which is involved in maintaining gastric mucosal protection and normal platelet function — this selectivity underlies its comparatively lower rate of upper gastrointestinal ulceration versus non-selective NSAIDs, although the risk is not eliminated. Because COX-2 also contributes to vascular prostacyclin production, COX-2-selective inhibition can shift the thromboxane–prostacyclin balance toward a prothrombotic state, which is the basis for the cardiovascular risk associated with this class.

Pharmacokinetics: Etoricoxib is well absorbed after oral administration, with peak plasma concentrations reached in about 1 hour; oral bioavailability is approximately 100%. It is highly protein bound (~92%) and is extensively metabolized in the liver, primarily via cytochrome P450 (CYP3A4 and, to a lesser extent, CYP2C9, CYP2C19, CYP1A2), to inactive or minimally active metabolites. The elimination half-life is approximately 22 hours, supporting once-daily dosing, and metabolites are excreted mainly in the urine.

Danilo tablets should be swallowed whole with a glass of water and may be taken with or without food. Do not crush or chew the tablet unless directed by your physician. Take Danilo exactly as prescribed; do not increase the dose or take it more often or for longer than recommended.

Danilo has the following well-recognized, clinically significant drug interactions:

• Warfarin/oral anticoagulants: Danilo (particularly at 90–120 mg) can significantly increase prothrombin time (INR) in patients on warfarin, raising bleeding risk; INR should be monitored closely, especially when starting or stopping Danilo.
• ACE inhibitors, angiotensin receptor blockers (ARBs), and diuretics: Danilo may reduce their antihypertensive effect and increase the risk of acute renal impairment, particularly in volume-depleted or elderly patients (the "triple whammy" effect of NSAID plus ACE inhibitor/ARB plus diuretic).
• Lithium: Danilo reduces renal clearance of lithium, increasing plasma lithium levels and risk of toxicity; monitor lithium levels when starting, adjusting, or stopping Danilo.
• Methotrexate: Danilo, especially at higher doses, can reduce renal clearance of methotrexate and increase methotrexate levels, raising the risk of toxicity; monitoring is advised.
• Low-dose aspirin: Concurrent use increases the rate of gastrointestinal ulceration compared with Danilo alone; Danilo is not a substitute for low-dose aspirin used for cardiovascular protection.
• Oral contraceptives and hormone replacement therapy: Danilo can increase plasma ethinyl estradiol concentrations, which may increase the frequency and severity of estrogen-related adverse effects; this should be considered when selecting contraception.
• Rifampicin: This strong hepatic enzyme inducer substantially reduces plasma concentrations of Danilo, which may reduce its effectiveness.
• Cyclosporine and tacrolimus: NSAIDs including Danilo may potentiate the nephrotoxicity of these agents; renal function should be monitored with concurrent use.

Most side effects of Danilo are mild and reversible on discontinuation. Commonly reported effects include:

• Cardiovascular: Hypertension (new-onset or worsening), palpitations, edema/fluid retention.
• Gastrointestinal: Dyspepsia, abdominal pain, heartburn, nausea, diarrhea, flatulence; less commonly, peptic ulcer or gastrointestinal bleeding (lower incidence than with non-selective NSAIDs, but not absent — see Precautions).
• Nervous system: Headache, dizziness.
• Hepatic: Elevated liver enzymes (ALT/AST).
• General: Fatigue/asthenia, flu-like symptoms.

Serious but less common or rare reactions include gastrointestinal ulceration/bleeding/perforation, hepatotoxicity (including rare hepatitis), acute kidney injury, hyperkalemia, severe hypersensitivity reactions (angioedema, anaphylaxis, severe skin reactions such as Stevens-Johnson syndrome), atrial fibrillation, and cardiovascular thrombotic events (myocardial infarction, stroke), consistent with the class-wide and drug-specific cardiovascular risk of Danilo. Very rarely, confusion or hallucinations have been reported. Patients should seek prompt medical attention for signs of GI bleeding (black stools, vomiting blood), unexplained rash, jaundice, marked swelling, or chest pain/shortness of breath.

Danilo is contraindicated during pregnancy and in women attempting to conceive. Like other NSAIDs, drugs that inhibit prostaglandin synthesis may cause premature closure of the fetal ductus arteriosus, oligohydramnios, and other complications, particularly with use in the second and third trimesters; NSAID exposure in early pregnancy has also been associated with increased risk of miscarriage in some studies. Women of childbearing potential who require pain relief should discuss safer alternatives with their physician if pregnancy is suspected, confirmed, or planned.

Danilo is contraindicated during breastfeeding. It is not known with certainty whether Danilo is excreted in human breast milk, but related coxibs are excreted in animal milk, and a risk to the nursing infant cannot be excluded. Women who need Danilo should not breastfeed; consult a physician about alternative analgesics compatible with lactation.

Cardiovascular thrombotic risk: Danilo carries a dose- and duration-related risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal; this risk is a defining feature of the drug and underlies several of its contraindications (established cardiovascular disease, uncontrolled hypertension, heart failure). Danilo should be used at the lowest effective dose for the shortest duration necessary, and should not be used in patients with pre-existing cardiovascular disease or uncontrolled risk factors.

Blood pressure: Danilo can cause new-onset hypertension or worsen existing hypertension more than some other NSAIDs; blood pressure should be monitored, particularly during the first weeks of treatment and after dose increases, and treatment should be discontinued if hypertension cannot be adequately controlled.

Fluid retention and edema: Fluid retention, edema, and heart failure exacerbation have been reported; use with caution in patients with a history of cardiac decompensation, and monitor for signs of fluid overload.

Gastrointestinal risk: Although the risk is lower than with non-selective NSAIDs, serious gastrointestinal adverse events including bleeding, ulceration, and perforation can still occur, sometimes without warning symptoms, especially in elderly patients or those with a prior history of peptic ulcer disease or concurrent aspirin/anticoagulant use.

Hepatic effects: Elevations in liver enzymes and, rarely, serious hepatic reactions (including hepatitis) have been reported; discontinue Danilo if signs or symptoms of liver dysfunction develop or if abnormal liver test results persist or worsen.

Renal effects: Danilo can reduce renal blood flow and precipitate renal impairment, particularly in patients with pre-existing renal impairment, heart failure, hepatic impairment, or volume depletion (e.g. from diuretic use), and in the elderly. Renal function should be assessed before and periodically during treatment in at-risk patients.

Skin reactions: Serious skin reactions, some fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported very rarely; discontinue Danilo at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Masking of fever/inflammation: As with other anti-inflammatory drugs, Danilo may mask fever and other signs of inflammation or infection.

Danilo should be used with particular caution in elderly patients, who are more susceptible to cardiovascular, renal, gastrointestinal, and hepatic adverse effects (see Use in Special Populations).

Limited clinical experience with Danilo overdose exists. Reported symptoms following overdose have included nausea, vomiting, abdominal pain, dizziness, and, potentially in more severe cases, hypertension, acute renal impairment, or gastrointestinal bleeding. There is no specific antidote for Danilo overdose.

In case of suspected overdose, seek immediate medical attention or contact a poison control center/emergency services right away. Management is supportive and symptomatic, guided by the treating physician; this may include standard supportive measures and monitoring of cardiovascular, renal, and gastrointestinal status. Do not attempt to manage an overdose at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pregnant Women

Danilo is contraindicated during pregnancy and in women attempting to conceive (see Pregnancy and Lactation).

Breastfeeding Mothers

Danilo is contraindicated during breastfeeding (see Pregnancy and Lactation).

Pediatric Patients

Danilo is contraindicated in children and adolescents under 16 years of age; safety and efficacy have not been established in this population.

Elderly Patients

No dose adjustment is generally required based on age alone, but elderly patients are at increased risk of cardiovascular, renal, gastrointestinal, and hepatic adverse effects associated with Danilo and should be monitored closely, using the lowest effective dose for the shortest duration necessary.

Renal Impairment

No dose adjustment is needed for creatinine clearance ≥30 mL/min. Danilo is contraindicated in severe renal impairment (creatinine clearance <30 mL/min).

Hepatic Impairment

Reduced maximum doses apply in mild and moderate hepatic impairment (see Dosage and Administration). Danilo is contraindicated in severe hepatic impairment.

Danilo should be used at the lowest effective dose for the shortest duration consistent with individual treatment goals, because its cardiovascular thrombotic risk increases with dose and duration of use. For acute gouty arthritis, treatment is limited to a maximum of 8 days; for acute pain following dental surgery, treatment is limited to a maximum of 3 days. For chronic conditions such as osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis, longer-term use may be appropriate but requires regular medical review to reassess the need for continued therapy and to monitor for cardiovascular, renal, hepatic, and gastrointestinal adverse effects.

Non-Steroidal Anti-Inflammatory Drug (NSAID) – Selective COX-2 Inhibitor (Coxib)

Etoricoxib selectively inhibits cyclooxygenase-2 (COX-2), the enzyme induced at sites of tissue injury and inflammation that converts arachidonic acid into prostaglandins responsible for pain, swelling, and fever. At therapeutic doses, Etoricoxib has little effect on cyclooxygenase-1 (COX-1), which is constitutively expressed and helps maintain gastric mucosal integrity and normal platelet aggregation; this selectivity accounts for its relatively lower gastrointestinal toxicity compared with non-selective NSAIDs. Because COX-2 also contributes to endothelial prostacyclin production, selective COX-2 inhibition can tip the balance toward platelet thromboxane A2 activity, which underlies the drug's cardiovascular thrombotic risk.

The safety and efficacy of Danilo have not been established in children and adolescents under 16 years of age, and its use is contraindicated in this age group. Alternative, better-studied analgesic/anti-inflammatory options appropriate for pediatric patients should be used instead, under physician guidance.