Pitavastatin; Uses, Dosage, Side Effects, Drug Interactions

Pitavastatin (usually as a calcium salt) is a member of the blood cholesterol lowering or a lipid-lowering agent that belongs to the statin class of medications for treatment of dyslipidemia. It is also used for primary and secondary prevention of cardiovascular disease.

Mechanism of Action of Pitavastatin

Pitavastatin is lipid-lowering agent that works to control the synthesis of cholesterol via competitive inhibition of the liver enzyme, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. As a result, a compensatory increase in LDL-receptor expression can be observed which facilitates an increase LDL catabolism.

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Hepatic ATP-binding cassette transporter A1 (ABCA1) plays a key role in high-density lipoprotein (HDL) production by apolipoprotein A-I (ApoA-I) lipidation. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, increase ABCA1 mRNA levels in hepatoma cell lines . We investigated how statins increase ABCA1 in rat hepatoma McARH7777 cells. Pitavastatin, atorvastatin, and simvastatin increased total ABCA1 mRNA levels, whereas pravastatin had no effect. Pitavastatin also increased ABCA1 protein. Hepatic ABCA1 expression in rats is regulated by both liver X receptor (LXR) and sterol regulatory element-binding protein (SREBP2) pathways. Pitavastatin repressed peripheral type ABCA1 mRNA levels and its LXR-driven promoter, but activated the liver-type SREBP-driven promoter, and eventually increased total ABCA1 mRNA expression. Furthermore, pitavastatin increased peroxisome proliferator-activated receptor a (PPARa) and its downstream gene expression. Knockdown of PPARa attenuated the increase in ABCA1 protein, indicating that pitavastatin increased ABCA1 protein via PPARa activation, although it repressed LXR activation. Furthermore, the degradation of ABCA1 protein was retarded in pitavastatin-treated cells. These data suggest that pitavastatin increases ABCA1 protein expression by dual mechanisms: SREBP2-mediated mRNA transcription and PPARa-mediated ABCA1 protein stabilization, but not by the PPAR-LXR-ABCA1 pathway.

Indications of Pitavastatin

• Dyslipidemia
• High Cholesterol
• Fredrickson type IIb hyperlipidemia?
• Mixed hypercholesterolemia
• Hyperlipoproteinemia
• Prevention of cardiovascular disease
• High cholesterol, familial heterozygous
• Lower LDL (bad) cholesterol and triglyceride levels
• Increase HDL (good) cholesterol levels
• Pitavastatin is used along with a proper diet to help lower “bad” cholesterol and fats (such as LDL, triglycerides) and raise “good” cholesterol (HDL) in the blood. It belongs to a group of drugs known as “statins.” It works by reducing the amount of cholesterol made by the liver. Lowering “bad” cholesterol and triglycerides and raising “good” cholesterol decreases the risk of heart disease and helps prevent strokes and heart attacks.
• It is indicated as an adjunctive therapy to diet to reduce elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia.
• American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guideline recommends statins as first-line therapy for the prevention of atherosclerotic cardiovascular disease (ASCVD) in adults. Pitavastatin may be used for primary or secondary prevention in adults when moderate?-intensity statin therapy is indicated.

It has neutral or possibly beneficial effects on glucose control. As a consequence, pitavastatin is likely to be appropriate for patients with metabolic syndrome? plus high LDL, low HDL and diabetes mellitus?.

Contra-Indications of Pitavastatin

• Alcoholism
• Uncontrolled Epilepsy?
• hemorrhage in the brain
• Severely Low Blood Pressure
• Liver Failure
• Liver problems
• Kidney? disease with the reduction in kidney function
• Rhabdomyolysis
• Recent operation
• Loss of Memory
• High Blood Sugar?
• Abnormal liver function tests
• Trauma?
• Pregnancy
• A mother who is producing milk and breastfeeding
• Muscle Pain? or Tenderness? with Increase Creatine Kinase
• Metabolic Syndrome? X
• Muscle Damage Due to Auotimmunity

Dosage? of Pitavastatin

Strengths: 1 mg; 2 mg; 4 mg

Hyperlipidemia

• Initial dose: 2 mg orally once a day
• Maintenance dose: 1 mg to 4 mg orally once a day
• Maximum dose: 4 mg/day

Dyslipidemia

• Initial dose: 2 mg orally once a day
• Maintenance dose: 1 mg to 4 mg orally once a day
• Maximum dose: 4 mg/day

Side Effects of Pitavastatin

The most common

• back pain
• constipation
• muscle aches
• Nausea and vomiting
• Severe? stomach ache
• diarrhoea,
• anorexia,
• flatulence,
• headache,
• dizziness,
• heartburn
• joint pain

 Common

• Nausea and vomiting
• Severe stomach ache
• Severe diarrhea
• Mouth sores
• Vaginal thrush
• Skin rash
• Headache

Less common

• Difficulty with moving
• joint pain
• muscle aching or cramping
• muscle pains or stiffness
• pain in the arms and legs
• swollen joints
• Back pain
• difficulty having a bowel movement
• Burning, numbness, tingling, or painful sensations
• decreased interest in sexual intercourse
•  discouragement

Drug Interactions of Pitavastatin

Atovastatin may interact with following drugs, suppliments & may change the efficasy of drug

Other medications can affect the removal of pitavastatin from your body, which may affect how pitavastatin works. Examples include cyclosporine, macrolide antibiotics (such as erythromycin), rifamycins (such as rifampin), sofosbuvir/velpatasvir/voxilaprevir, among others.

• colchicine,
• gemfibrozil
• cyclosporine
• desipramine
• dexamethasone
• dronedarone
• haloperidol
• loperamide
• macrolide antibiotics (e.g., azithromycin, erythromycin, clarithromycin)
• metronidazole
• midazolam
• mifepristone
• norfloxacin
• ondansetron
• paliperidone
• phenobarbital

Do not take any red yeast rice products while you are taking pitavastatin because some red yeast rice products may also contain a statin called lovastatin. Taking pitavastatin and red yeast rice products together can increase your risk of serious muscle and liver problems.

Pregnancy & Lactation of Pitavastatin

FDA Pregnancy Catagory X

Pregnancy 

Pitavastatin is a category X pregnancy drug. Category X drugs should never be used during pregnancy. Call your doctor right away if you become pregnant while taking this drug.

Lactation

Pitavastatin may pass into breast milk and may cause side effects in a child who is breastfed. You should not breastfeed while taking pitavastatin. Talk to your doctor if you breastfeed your child. You need to decide whether to stop breastfeeding or stop taking this medication.

References