Palocap

Dosage Form & Strength

For oral use, 2 mg once daily after a meal. The dose should not exceed 2 mg/day.If there is no therapeutic benefit at the recommended dose, administration of this drug should be discontinued and appropriate alternative treatment methods should be considered.

Indications

Indicated for the treatment of idiopathic (primary) osteoarthritis of hip/knee.

Contraindications

•Patients who have a history of hypersensitivity reactions or a history of this drug and its components •Patients with allergic reactions to sulfonamide •Patients with a history of asthma, acute rhinitis, nasal polyps, angioedema, urticaria, or allergic reactions to aspirin or other nonsteroidal anti-inflammatory drugs (including COX-2 inhibitors) •Patients with uncontrolled hypertension (systolic blood pressure above 140 mmHg or higher and/or diastolic blood pressure above 90 mmHg or higher) •Patients with edema or fluid retention •Patients with renal and hepatic impairment •Patients with active peptic ulcer or gastrointestinal bleeding •Patients with inflammatory bowel disease such as Crohn’s disease or ulcerative colitis •Patients with congestive heart failure (NYHA II – IV) •Established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease •Pregnant women or women who may be pregnant •Nursing mother •Treatment of pain before and after coronary artery bypass graft (CABG) •Patients with hyperkalemia •Patients with a blood clotting disorder or receiving anticoagulants

Adverse Effects

The most commonly reported TEAEs with the treatment of polmacoxib were associated with GI and general disorders

Special Warnings & Precautions

If a person who regularly drinks three or more drinks daily who needs to take this medicine or other antipyretic analgesics, they must consult a doctor or pharmacist. When these people take this drug, gastrointestinal bleeding can occur.

Drug Interactions

Since this drug is mainly metabolized by CYP3A4 in the liver, caution should be exercised when co-administered with drugs that inhibit CYP3A4.

Mechanism of Action

Distinct from other NSAIDs, polmacoxib has a dual mechanism of action that includes inhibition of COX-2 and inhibition of Carbonic Anhydrase-I/II.

Pharmacokinetics

Mean (SD) Tmax: 5.6 (1.0) hours; mean (SD) Cmax: 3.5 (0.9) ng/mL; mean (SD) t1/2:131 (19) hours; excretion: primarily via the fecal route.

Absorption, Distribution, Metabolism & Excretion

Absorption: A one compartment model with first order absorption and elimination described polmacoxib concentration‐time profiles well. Estimates (% relative SD) between plasma and whole blood were in agreement for the absorption rate constant, 1.54 (58.6) and 1.43 (28.0) hour_1, respectively. A whole blood concentration that is ~ 50 to 70 times higher than in plasma. Polmacoxib 2 mg resulted in an area under the time–concentration curve (AUC) (0–1,176 h post-dose) of 632.9 ± 162.1 ng/ml × h, whereas polmacoxib 8 mg achieved 2,366.8 ± 761.9 ng/ml × h, corresponding to 3.7 times that with the low dose. This was consistent with dose linearity in drug exposure. Cmax-plasma was 3.5 ± 0.9 and 14.1 ± 3.7 ng/ml for polmacoxib 2 mg and 8 mg, respectively. The tmax values were 5.6 ± 1.0 and 5.0 ±1.7 h for polmacoxib 2 mg and 8 mg, respectively. Metabolism: Following oral single doses of 2 or 8 mg polmacoxib to healthy volunteers the estimates (% relative SD) between plasma and whole blood for clearance were 3.29 (10.4) and 0.04 (7.7) L/h/70 kg, respectively. In plasma, a higher clearance, which was associated with a higher Vd, was found in men compared with women. Mean blood Vz/F values in male subjects increased with increasing dose. Relative to female subjects, male subjects had higher blood Vz/F. Excretion: Following oral administration of single doses of 2 or 8 mg polmacoxib to healthy volunteers the mean ± SD elimination half‐lives were 131±19 and 127±33 hours, respectively. In a multiple ascending oral dose study that was performed on 8 male and 8 female subjects per dose cohort (each subject was administered 1 of 3 sequential dose levels (8-mg loading dose þ2 mg/d, 10-mg loading dose þ 4 mg/d, or 12-mgloading dose þ 8 mg/d). Men tended to demonstrate a slightly longer t½ than women. Mean t½ β, ss values in the whole blood and plasma samples ranged between 123 and 205 hours and 101 and 169 hours, respectively. The variable t½β, ss was affected by sex. Male subjects tended to demonstrate a slightly longer t½ than female subjects

Drug Use in Pregnancy

Pregnancy: It has been reported that this drug does not delay delivery in rats. However, the effect of this drug on delivery and childbirth in pregnant women is unknown.

Drug Use in Renal Impairment

Renal Impairment: This drug should not be administered because there is no administration experience

Drug Use in Hepatic Impairment

Hepatic Impairment: This drug should not be administered because there is no administration experience

Drug Use in Pediatric Population

Pediatric: Safety and effectiveness of polmacoxib in paediatric patients under 18 years of age have not been established.

Drug Use in Geriatric Population

Elderly: Elderly people are likely to have decreased renal function, liver function, and especially heart function, so appropriate observation is required when administering polmacoxib to the elderly. In patients with arthritis age 70 or older, the blood drug concentration of is 1.4 times higher than that in arthritis patients aged 40 to 69 years, so it should be administered carefully.