Source: Health Sciences Authority (SG) Revision Year: 2022 Publisher: Kowa Company, Ltd., 6-29, Nishiki 3-chome, Naka-ku, Nagoya, Aichi, JAPAN
PARMODIA is contraindicated:
Muscle toxicity, including very rare cases of rhabdomyolysis (with and without acute renal failure), has been reported with other lipid-lowering agents.
Muscle toxicity should be suspected in patients presenting diffuse myalgia, myositis, muscle cramps and weakness and/or marked increases in CK (>5 times the upper limit of normal range [ULN]). In such cases, treatment with PARMODIA should be stopped.
An increased risk of rhabdomyolysis has been reported with other fibrates when co-administered with an HMG-CoA reductase inhibitor (statin), especially in cases of pre-existing muscular disease. PARMODIA should be used with caution in patients receiving statins.
In common with other lipid-lowering agents, PARMODIA should be used with caution in patients with hepatic disorder or those with a history of hepatic disorder. Abnormal liver function tests may occur. The plasma concentration of PARMODIA may increase in patients with hepatic disorder (Child-Pugh grade A cirrhosis, etc.) (see section 5.2). Liver function should be monitored periodically during treatment.
In patients with renal impairment, renal function should be monitored periodically during treatment with PARMODIA. If eGFR is <30 mL/min/1.73 m², dose reduction or prolonged dosing intervals should be considered. The maximum dose is 0.2 mg daily.
Since cholelithiasis has been reported, PARMODIA should be used with caution in patients with a history of cholelithiasis.
The safety of PARMODIA in low birth weight infants, newborns, infants, and children has not been established. No data are available.
PARMODIA is metabolized mainly by cytochrome P450 (CYP) 2C8, CYP2C9, and CYP3A. PARMODIA is a substrate of organic anion transporting polypeptide (OATP) 1B1 and OATP1B3.
Contraindications for co-administration (Do not co-administer with the following drugs.):
| Drug | Clinical symptoms/Treatment | Mechanism/Risk factors |
|---|---|---|
| Cyclosporine | Concomitant administration of cyclosporine or rifampicin with PARMODIA resulted in an increase in the plasma concentration of pemafibrate (see section 5.2). | Presumably due to inhibition of OATP1B1, OATP1B3, CYP2C8, CYP2C9, and CYP3A by cyclosporine. |
| Rifampicin | Presumably due to inhibition of OATP1B1 and OATP1B3 by rifampicin. |
Precautions for co-administration (PARMODIA should be administered with caution when co-administered with the following drugs.):
| Drug | Clinical symptoms/Treatment | Mechanism/Risk factors |
|---|---|---|
| HMG-CoA reductase inhibitors Pravastatin sodium Simvastatin Fluvastatin sodium, etc. | Muscle toxicity should be suspected in patients presenting diffuse myalgia, myositis, muscle cramps and weakness and/or marked increases in CK (>5 times ULN). In such cases, treatment with PARMODIA should be stopped. | Risk factor: patients with pre- existing muscular disease |
| Clopidogrel sulfate | Concomitant administration of clopidogrel sulfate or clarithromycin with PARMODIA resulted in an increase in the plasma concentration of pemafibrate (see section 5.2). Dose reduction of PARMODIA should be considered as necessary when used concomitantly with PARMODIA. | Presumably due to inhibition of CYP2C8 and OATP1B1 by clopidogrel sulfate. |
| Clarithromycin HIV protease inhibitors Ritonavir, etc. | Presumably due to inhibition of CYP3A, OATP1B1 and OATP1B3 by clarithromycin (or HIV protease inhibitors). | |
| Fluconazole | Concomitant administration of fluconazole with PARMODIA resulted in an increase in the plasma concentration of pemafibrate (see section 5.2). | Presumably due to inhibition of CYP2C9 and CYP3A by fluconazole. |
| Anion exchange resins Cholestyramine Colestimide | PARMODIA should be administered with the longest interval possible after the intake of anion exchange resins because the plasma concentration of pemafibrate may be decreased. | PARMODIA may be absorbed onto anion exchange resins, and the absorption of pemafibrate may be reduced. |
| Strong CYP3A inducers Carbamazepine Phenobarbital Phenytoin Foods containing hypericum perforatum (St. John’s wort), etc. | The plasma concentration of pemafibrate may be decreased, which may reduce the efficacy of PARMODIA. | The strong induction of CYP3A by these drugs may accelerate the metabolism of pemafibrate. |
PARMODIA is contraindicated in pregnant or possibly pregnant women (see section 4.3). The safety of PARMODIA has not been established for use during pregnancy.
The use of PARMODIA should be avoided in breast-feeding women. If the administration of PARMODIA is unavoidable, breast-feeding should be discontinued. An animal study (rat) has shown that PARMODIA is excreted in rat milk.
No current data.
No studies of the effects of PARMODIA on a patient’s ability to drive, or to measure a reduced capacity to safely use machines have been performed.
In clinical studies conducted by the time of approval in Japan, adverse reactions were observed in 206 of 1,418 patients (14.5%). The most commonly reported adverse reactions included cholelithiasis observed in 20 patients (1.4%), diabetes mellitus in 20 patients (1.4%), and blood creatine phosphokinase increased in 12 patients (0.8%).
Adverse reactions and frequencies observed in clinical studies conducted by the time of approval in Japan are listed below. If any of the following adverse reactions or similar is observed, the patients should be treated appropriately according to the symptoms.
| ≥1% | ≥0.1% to <1% | |
|---|---|---|
| Liver | Cholelithiasis | Hepatic function abnormal, Aspartate aminotransferase increased, Alanine aminotransferase increased |
| Muscle | Blood creatine phosphokinase increased, Myoglobin blood increased, Myalgia | |
| Skin | Rash, Itching | |
| Others | Diabetes mellitus (including Diabetes mellitus aggravated) | Glycosylated haemoglobin increased, Low density lipoprotein increased, Blood uric acid increased |
Not applicable.
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