CFB

Approved Indications:

• Hyperlipidemia (Type IIb, III, IV, and V):
  Treatment of mixed dyslipidemia, particularly elevated triglycerides (hypertriglyceridemia), low HDL cholesterol, and elevated VLDL cholesterol.
• Primary Hypercholesterolemia (Type IIa):
  When statins are contraindicated, not tolerated, or insufficient alone.
• Familial Combined Hyperlipidemia:
  In patients with persistent lipid abnormalities despite dietary control.
• Secondary Hyperlipoproteinemia:
  Including that associated with diabetes mellitus, when not adequately controlled by diet or other non-pharmacologic means.

Off-label/Clinically Accepted Uses:

• Adjunctive therapy in metabolic syndrome or non-alcoholic fatty liver disease (NAFLD) with coexisting dyslipidemia.
• Prevention of pancreatitis in severe hypertriglyceridemia.

Adults:

• Standard Dose:
  100 mg once daily, preferably in the evening, after a meal.
• Treatment Duration:
  Long-term, based on lipid profile monitoring and cardiovascular risk. Periodic reassessment every 3–6 months.

Elderly:

• No specific dose adjustment required.
  However, renal function should be evaluated regularly due to age-related decline.

Renal Impairment:

• Mild to Moderate (eGFR 30–60 mL/min):
  Caution advised; consider dose reduction or alternative therapy.
• Severe Renal Impairment (eGFR <30 mL/min):
  Contraindicated due to risk of accumulation and toxicity.

Hepatic Impairment:

• Use with caution.
  Avoid in active liver disease or significant hepatic dysfunction.

Pediatrics:

• Not recommended in children and adolescents under 18 years due to limited safety data.

Administration Route:
Oral. Take whole with water after food to enhance bioavailability and minimize GI side effects.

Ciprofibrate is a fibric acid derivative (fibrate) that acts as an agonist of the peroxisome proliferator-activated receptor alpha (PPAR-α). Activation of PPAR-α leads to increased transcription of genes involved in fatty acid oxidation and lipoprotein metabolism. This results in:

• Enhanced lipolysis and clearance of triglyceride-rich particles (e.g., VLDL)
• Increased hepatic uptake of LDL
• Elevation of HDL cholesterol due to increased synthesis of apolipoproteins A-I and A-II
  Overall, ciprofibrate reduces serum triglycerides and LDL-C levels and raises HDL-C, thereby improving the lipid profile and reducing cardiovascular risk in dyslipidemic patients.

• Absorption:
  Rapidly absorbed after oral administration; peak plasma concentration reached in 1–4 hours.
• Bioavailability:
  Enhanced when taken with food.
• Distribution:
  High plasma protein binding (>95%). Widely distributed in tissues, especially the liver.
• Metabolism:
  Undergoes hepatic metabolism via conjugation pathways; no significant CYP450 involvement.
• Half-life:
  Approximately 35–86 hours, allowing once-daily dosing.
• Excretion:
  Primarily eliminated via the urine (~70–80%), both as parent compound and metabolites; minor fecal excretion.

• Pregnancy:
  Not assigned a specific FDA category.
  Use contraindicated during pregnancy due to potential teratogenic effects observed in animal studies.
• Lactation:
  Excretion into human breast milk is unknown, but due to potential for adverse effects in infants, use is not recommended while breastfeeding.

• Primary Class: Antihyperlipidemic agent
• Subclass: Fibrate (Fibric Acid Derivative)
• Mechanistic Class: PPAR-α agonist

• Hypersensitivity to ciprofibrate or any component of the formulation
• Active liver disease, including persistent elevations of liver enzymes
• Severe renal impairment (eGFR <30 mL/min)
• Pre-existing gallbladder disease
• Pregnancy and lactation
• History of photoallergic or phototoxic reactions to fibrates

• Myopathy and Rhabdomyolysis:
  Risk increases when used with statins or in renal impairment; monitor for muscle pain or weakness.
• Liver Function:
  Periodic monitoring of ALT, AST, and bilirubin required. Discontinue if elevations persist.
• Gallstones (Cholelithiasis):
  Fibrates increase cholesterol excretion into bile; monitor for biliary symptoms.
• Renal Monitoring:
  Regular evaluation of serum creatinine, especially in elderly or those with borderline renal function.
• Photosensitivity:
  Advise patients to avoid excessive sunlight and use sun protection.
• Discontinuation Criteria:
  If no adequate response after 3 months of use, therapy should be reassessed or discontinued.

Common:

• Gastrointestinal disturbances (nausea, abdominal pain, diarrhea)
• Fatigue
• Headache
• Increased liver enzymes

Less Common:

• Muscle pain, myalgia
• Skin rash or eczema
• Photosensitivity reactions

Serious / Rare:

• Myopathy or rhabdomyolysis (particularly when combined with statins)
• Gallstones
• Hepatotoxicity (rare but serious)
• Pancreatitis (rare)

Onset:
Gastrointestinal effects may occur early in treatment; muscle-related effects often appear after weeks to months of therapy.

• Statins (e.g., Simvastatin, Atorvastatin):
  Increased risk of myopathy or rhabdomyolysis; avoid or use with caution.
• Oral Anticoagulants (e.g., Warfarin):
  Potentiation of anticoagulant effect; frequent INR monitoring required.
• Cyclosporine:
  Risk of nephrotoxicity may be increased; monitor renal function.
• Bile Acid Sequestrants:
  May reduce absorption of ciprofibrate; administer ciprofibrate at least 1–4 hours before or after.
• Oral Hypoglycemics (e.g., Sulfonylureas):
  Enhanced hypoglycemic effect in some cases; monitor blood glucose levels closely.

• EMA and other health authorities recommend avoiding fibrate–statin combinations unless absolutely necessary and under strict monitoring.
• Periodic re-evaluation of fibrate use is encouraged in the absence of clinical benefit after 3 months.
• No new safety warnings or changes in indication as of the latest international lipid guidelines (e.g., ESC/EAS).

• Temperature: Store below 25°C (77°F)
• Humidity: Keep container tightly closed to protect from moisture
• Light Protection: Store in original packaging, protected from direct sunlight
• Handling Precautions: Keep out of reach of children
• Reconstitution/Refrigeration: Not required (oral solid formulation)