Dosage guidance:
Dosing: Pitavastatin 1 to 4 mg/day is considered a moderate-intensity statin (generally reduces low-density lipoprotein cholesterol [LDL-C] by ~30% to 49%). If LDL-C must be lowered ≥50%, select a high-intensity statin (atorvastatin or rosuvastatin). Assess response ~1 to 3 months after therapy initiation or dose adjustment and every 3 to 12 months thereafter (Ref).
Clinical considerations: Use in conjunction with lifestyle modification (eg, diet, exercise). When initiating therapy and selecting dose intensity, consider age, baseline LDL-C, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, risk-enhancing factors, potential adverse effects, and drug interactions (Ref).
Heterozygous familial hypercholesterolemia:
Note: Use of pitavastatin should be limited to patients unable to tolerate a high-intensity statin (atorvastatin or rosuvastatin). Multiple lipid-lowering therapies may be needed if statin monotherapy is not effective. Referral to a lipid specialist should be considered if treatment goals are not met (Ref).
Patients unable to tolerate high-intensity therapy:
Moderate-intensity therapy: Oral: 1 to 4 mg once daily (Ref).
Prevention of atherosclerotic cardiovascular disease (off-label use):
Note: If LDL-C goal (eg, percent reduction or absolute goal) is not met with the initial dose, may consider up-titration to a maximum of 4 mg/day based on estimated 10-year ASCVD risk (see ACC/AHA ASCVD Risk Estimator Plus online), LDL-C response, and tolerability. If LDL-C goal is not met with maximally tolerated dose, consider switching to a high-intensity statin (atorvastatin or rosuvastatin); additional lipid-lowering therapy may be warranted (Ref).
Primary prevention:
Patients without diabetes, age 40 to 75 years, and LDL-C 70 to 189 mg/dL:
ASCVD 10-year risk 5% to <7.5%:
Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest shared decision-making if ASCVD 10-year risk is 5% to 10%; however, in patients with a baseline LDL-C ≥160 mg/dL, statin therapy is usually recommended (Ref).
Moderate-intensity therapy: Oral: 1 to 4 mg once daily to reduce LDL-C by 30% to 49% (Ref).
ASCVD 10-year risk ≥7.5% to <20%:
Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest initiating moderate-intensity statin therapy in most patients if ASCVD 10-year risk is >10% to <20% and LDL-C is >100 mg/dL (Ref).
Moderate-intensity therapy: Oral: 1 to 4 mg once daily to reduce LDL-C by 30% to 49%; higher risk patients with multiple risk-enhancing factors may benefit from high-intensity statin therapy (ie, with atorvastatin or rosuvastatin) to reduce LDL-C by ≥50% (Ref).
ASCVD 10-year risk ≥20% (alternative agent):
Note: Use of pitavastatin should be limited to patients unable to tolerate a high-intensity statin (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral: 1 to 4 mg once daily (Ref).
Patients with diabetes:
Age 40 to 75 years without additional ASCVD risk factors :
Moderate-intensity therapy: Oral: 1 to 4 mg once daily to reduce LDL-C by 30% to 49% (Ref).
ASCVD 10-year risk ≥7.5% or multiple ASCVD risk factors (alternative agent) :
Note: Use of pitavastatin should be limited to patients unable to tolerate a high-intensity statin (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral: 1 to 4 mg once daily (Ref).
Patients with LDL-C ≥190 mg/dL and age 20 to 75 years (regardless of ASCVD risk estimate or coexisting diabetes mellitus) (alternative agent):
Note: Use of pitavastatin should be limited to patients unable to tolerate a high-intensity statin (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral: 1 to 4 mg once daily (Ref).
Secondary prevention in patients with established ASCVD (eg, coronary heart disease, cerebrovascular disease [ischemic stroke or transient ischemic attack], peripheral arterial disease) (alternative agent):
Note: Use of pitavastatin should be limited to patients unable to tolerate a high-intensity statin (Ref). Patients with high-risk ASCVD may require additional therapies to achieve LDL-C goal (eg, <70 mg/dL or <50 mg/dL if very high risk) (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate doses of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral: 1 to 4 mg once daily (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
GFR ≥60 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling.
GFR 15 to 59 mL/minute/1.73 m2 (not receiving hemodialysis): Initial: 1 mg once daily; maximum: 2 mg/day
ESRD receiving hemodialysis: Initial: 1 mg once daily; maximum: 2 mg/day
Contraindicated in active liver disease or decompensated cirrhosis.
Severe muscle symptoms or fatigue: Promptly discontinue use; evaluate CPK, creatinine, and urinalysis for myoglobinuria (Ref).
Mild to moderate muscle symptoms: Discontinue use until symptoms can be evaluated; evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases). Upon resolution, resume the original or lower dose of pitavastatin. If muscle symptoms recur, discontinue pitavastatin use. After muscle symptom resolution, may then use a low dose of a different statin; gradually increase if tolerated. In the absence of continued statin use, if muscle symptoms or elevated CPK continues after 2 months, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (Ref).
Refer to adult dosing.
(For additional information see "Pitavastatin: Pediatric drug information")
Dosage guidance:
Dosing: Dosage should be individualized according to the baseline LDL-C level, the recommended goal of therapy, and patient response; adjustments should be made at intervals of 4 weeks.
Clinical considerations: Lifestyle changes are recommended to be implemented for at least 6 to 12 months before beginning pharmacotherapy (Ref).
Heterozygous familial hypercholesterolemia (HeFH): Children ≥8 years and Adolescents: Livalo (pitavastatin calcium): Oral: Initial: 2 mg once daily; evaluate lipids after 4 weeks and titrate dose accordingly; maximum daily dose: 4 mg/day; lipid levels should be evaluated 4 weeks after any dose adjustment.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Muscle symptoms (potential myopathy): Children ≥8 years and Adolescents: Discontinue use until symptoms can be evaluated; check CPK level; based on experience in adult patients, also evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism; reduced renal or hepatic function; rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases). Upon resolution (symptoms and any associated CPK abnormalities), resume the original dose or consider a lower dose of pitavastatin and retitrate. If muscle symptoms recur, discontinue pitavastatin use. After muscle symptom resolution, may then reinitiate a different statin at an initial low dose; gradually increase if tolerated. Based on experience in adult patients, if muscle symptoms or elevated CPK persists for 2 months in the absence of continued statin use, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (Ref).
Children ≥8 years and Adolescents: Livalo: There are no pediatric-specific recommendations (has not been established); based on experience in adult patients, dosage reductions should be considered.
Children ≥8 years and Adolescents: Livalo: Contraindicated in active liver disease or in patients with unexplained persistent elevations of serum transaminases.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
1% to 10%:
Gastrointestinal: Constipation (4%), diarrhea (3%)
Neuromuscular & skeletal: Back pain (4%), myalgia (2% to 3%)
Frequency not defined:
Infection: Influenza
Nervous system: Headache
Neuromuscular & skeletal: Arthralgia
Respiratory: Nasopharyngitis
Postmarketing:
Cardiovascular: Chest pain (AlZahrani 2019)
Dermatologic: Acute generalized exanthematous pustulosis (Saito-Sasaki 2016), lichen planus
Endocrine & metabolic: Elevated glycosylated hemoglobin, increased serum glucose
Gastrointestinal: Abdominal distress, abdominal pain, dyspepsia, nausea
Genitourinary: Erectile dysfunction
Hepatic: Hepatic failure, hepatitis, increased serum alkaline phosphatase, increased serum bilirubin, increased serum transaminases, jaundice
Hypersensitivity: Angioedema (Naz 2018), hypersensitivity reaction
Nervous system: Asthenia, depression, dizziness, fatigue, hypoesthesia, insomnia, malaise, myasthenia gravis (including exacerbation of myasthenia gravis, ocular myasthenia), peripheral neuropathy
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen, muscle spasm, myopathy, rhabdomyolysis
Respiratory: Interstitial lung disease
Hypersensitivity to pitavastatin or any component of the formulation; active liver disease or decompensated cirrhosis; coadministration with cyclosporine.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Diabetes mellitus: Increases in HbA1c and fasting blood glucose have been reported; however, the benefits of statin therapy far outweigh the risk of dysglycemia. Optimize lifestyle measures including exercise, maintaining a healthy body weight, and making healthy food choices.
• Hepatotoxicity: Elevations in serum transaminases have been reported; elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy in most cases. Postmarketing reports of fatal and nonfatal hepatic failure have been reported and are rare. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy promptly. Consider baseline and periodic liver enzyme tests, as clinically indicated. Ethanol may enhance the potential of adverse hepatic effects; instruct patients to avoid excessive ethanol consumption.
• Hypersensitivity: Hypersensitivity reactions, including angioedema, rash, pruritus, and urticaria, have been reported.
• Myopathy/Rhabdomyolysis: Myopathy with CPK >10 times the ULN and rhabdomyolysis (sometimes fatal) with or without acute renal failure secondary to myoglobinuria have been reported; patients should be monitored closely. This risk is dose-related (doses >4 mg) and is increased with concurrent use of colchicine, erythromycin, fibrates, niacin (doses ≥1 g/day), or rifampin. If concurrent use is warranted, consider lower starting and maintenance doses of pitavastatin; use is contraindicated with cyclosporine and not recommended with gemfibrozil. Use caution in patients ≥65 years of age, uncontrolled hypothyroidism, and renal impairment; these patients are predisposed to myopathy. Immune-mediated necrotizing myopathy (IMNM) associated with HMG-CoA reductase inhibitors use has also been reported rarely; discontinue therapy if IMNM is suspected. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine, particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing pitavastatin. Temporarily withhold therapy in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (eg, sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, electrolyte disorders; uncontrolled epilepsy). Discontinue therapy if markedly elevated CPK levels occur or myopathy is diagnosed/suspected; consider treatment with immunosuppressants and additional neuromuscular and serologic testing.
Disease-related concerns:
• Hepatic impairment: Use is contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases; use with caution in patients who consume large amounts of ethanol or have a history of liver disease.
• Myasthenia gravis: May rarely worsen or precipitate myasthenia gravis (MG); monitor for worsening MG if treatment is initiated (AAN [Narayanaswami 2021]).
• Renal impairment: Use with caution in patients with renal impairment; these patients are predisposed to myopathy and rhabdomyolysis. Dosage adjustment required in patients with GFR <60 mL/minute/1.73 m2 including end-stage renal disease receiving hemodialysis.
Special Populations:
• Older adult: Use with caution in patients ≥65 years of age; these patients are predisposed to myopathy and rhabdomyolysis.
• Surgical patients: The manufacturer recommends temporary discontinuation for elective major surgery, acute medical or surgical conditions, or in any patient experiencing an acute or serious condition predisposing to renal failure (eg, sepsis; shock; severe hypovolemia; trauma; severe metabolic, endocrine, electrolyte disorders; uncontrolled epilepsy). Based on current research and clinical guidelines, HMG-CoA reductase inhibitors should be continued in the perioperative period for noncardiac and cardiac surgery (ACC/AHA [Fleisher 2014]; ACC/AHA [Hillis 2011]). Perioperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality.
Other warnings/precautions:
• Appropriate use: The effect on cardiovascular morbidity and mortality has not been determined.
• Hyperlipidemia: Secondary causes of hyperlipidemia should be ruled out prior to therapy.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral, as calcium:
Livalo: 1 mg, 2 mg, 4 mg
Generic: 1 mg, 2 mg, 4 mg
Tablet, Oral, as magnesium [strength expressed as base]:
Zypitamag: 1 mg [DSC], 2 mg, 4 mg
Yes
Tablets (Livalo Oral)
1 mg (per each): $12.79
2 mg (per each): $12.79
4 mg (per each): $12.79
Tablets (Pitavastatin Calcium Oral)
1 mg (per each): $11.50 - $12.15
2 mg (per each): $11.50 - $12.15
4 mg (per each): $11.50 - $12.15
Tablets (Zypitamag Oral)
2 mg (per each): $9.30
4 mg (per each): $9.30
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: Administer with or without food; may take without regard to time of day.
Oral: Administer without regard to food or time of day; take at the same time each day.
Heterozygous familial hypercholesterolemia (Livalo [pitavastatin calcium] only): As an adjunctive therapy to diet to reduce elevated total cholesterol, LDL-C, and apo B in children and adolescents ≥8 years of age.
Heterozygous familial hypercholesterolemia: As an adjunctive therapy to diet to reduce elevated total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B), and triglycerides, and to increase high-density lipoprotein cholesterol in adults with primary hyperlipidemia.
Primary and secondary prevention of atherosclerotic cardiovascular disease
HMG-CoA reductase inhibitors (when referred to as "statins") may be confused with nystatin.
Pitavastatin may be confused with atorvastatin, fluvastatin, lovastatin, nystatin, pravastatin, rosuvastatin, simvastatin
Substrate of CYP2C8 (minor), CYP2C9 (minor), OATP1B1/1B3 (SLCO1B1/1B3), UGT1A3, UGT2B7; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abiraterone Acetate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Asciminib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Belumosudil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid coadministration of belumosudil with these substrates of OATP1B1/1B3 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the OATP1B1/1B3 substrate may be required. Risk D: Consider therapy modification
Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). More specifically, bezafibrate may increase the serum concentration of fluvastatin Management: Avoid use of bezafibrate and HMG-CoA reductase inhibitors (statins) unless strictly indicated due to the increased of muscle toxicity (including rhabdomyolysis). In patients who may be predisposed to myopathy, concomitant use is contraindicated. Risk D: Consider therapy modification
Bulevirtide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Coadministration of bulevirtide with OATP1B1/1B3 (also known as SLCO1B1/1B3) substrates should be avoided when possible. If used together, close clinical monitoring is recommended. Risk D: Consider therapy modification
Bulevirtide: May increase the serum concentration of NTCP Substrates. Management: Coadministration of bulevirtide with sodium taurocholate co-transporting polypeptide (NTCP) substrate should be avoided when possible. If used together, close clinical monitoring is recommended. Risk D: Consider therapy modification
Ceftobiprole Medocaril: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Ciprofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Management: Avoid the use of HMG-CoA reductase inhibitors and ciprofibrate if possible. If concomitant therapy is considered, benefits should be carefully weighed against the risks, and patients should be monitored closely for signs/symptoms of muscle toxicity. Risk D: Consider therapy modification
Cobicistat: May increase the serum concentration of Pitavastatin. Risk C: Monitor therapy
Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). HMG-CoA Reductase Inhibitors (Statins) may increase the serum concentration of Colchicine. Risk C: Monitor therapy
CycloSPORINE (Systemic): May increase the serum concentration of Pitavastatin. Risk X: Avoid combination
Daclatasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
DAPTOmycin: HMG-CoA Reductase Inhibitors (Statins) may enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping statin (HMG-CoA reductase inhibitor) therapy prior to daptomycin. If daptomycin is used with a statin, creatine phosphokinase (CPK) monitoring could be considered. Risk D: Consider therapy modification
Darolutamide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Encorafenib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Erythromycin (Systemic): May increase the serum concentration of Pitavastatin. Management: Limit pitavastatin to a maximum of 1 mg/day when used in combination with erythromycin. If this combination is used, monitor patients more closely for evidence of pitavastatin toxicity. Risk D: Consider therapy modification
Etravirine: May increase the serum concentration of Pitavastatin. Risk C: Monitor therapy
Fenofibrate and Derivatives: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Fostemsavir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest possible starting statin dose and monitor patients closely for statin-related adverse effects (eg, muscle aches and pains) during coadministration with fostemsavir. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Specifically, the risk for muscle toxicities, including rhabdomyolysis may be significantly increased. Management: Avoid concurrent use whenever possible. Use is listed as contraindicated in product characteristic summaries in several countries, although UK labeling suggests that use could be considered under exceptional circumstances and with close supervision. Risk X: Avoid combination
Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk X: Avoid combination
Glecaprevir and Pibrentasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest statin dose possible if combined with glecaprevir/pibrentasvir and monitor for increased statin effects/toxicities. Avoid concomitant use with atorva-, simva-, or lovastatin. Limit rosuvastatin to 10 mg daily and reduce pravastatin dose 50% Risk D: Consider therapy modification
Lanthanum: May decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Administer HMG-CoA reductase inhibitors (eg, statins) at least two hours before or after lanthanum. Risk D: Consider therapy modification
Leflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Leniolisib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Letermovir: May increase the serum concentration of Pitavastatin. Risk X: Avoid combination
Niacin: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of Pitavastatin. Management: Canadian product labeling recommends use of the lowest pitavastatin dose with this combination. Risk C: Monitor therapy
Pretomanid: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk X: Avoid combination
Repaglinide: HMG-CoA Reductase Inhibitors (Statins) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
RifAMPin: May increase the serum concentration of Pitavastatin. Management: Limit pitavastatin dose to a maximum of 2 mg/day with concurrent rifampin. Risk D: Consider therapy modification
Roxadustat: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Rupatadine: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Specifically, the risk for increased CPK and/or other muscle toxicities may be increased. Risk C: Monitor therapy
Simeprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Trabectedin: HMG-CoA Reductase Inhibitors (Statins) may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Risk C: Monitor therapy
Trofinetide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider therapy modification
Vadadustat: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Voxilaprevir: May increase the serum concentration of Pitavastatin. Risk X: Avoid combination
Adequate contraception is recommended if an HMG-CoA reductase inhibitor (statin) is required in patients who may become pregnant (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]). Patients planning to become pregnant should discuss their lifetime risk of cardiovascular disease, as well as risks and benefits of statin therapy with their health care team (CCS [Pearson 2021]). When appropriate, statins can be discontinued 1 to 2 months prior to conception (AHA/ACC [Grundy 2019]).
When a statin is needed in a patient of reproductive potential, a more hydrophilic option (eg, pravastatin, rosuvastatin) may be preferred to limit placental transfer (CCS [Pearson 2021]).
In healthy pregnancies, changes in lipid synthesis occur that are required for normal placental and fetal growth. Low-density lipoprotein cholesterol and triglycerides increase as pregnancy progresses and decline postpartum. HMG-CoA reductase inhibitors (statins) decrease the synthesis of cholesterol and substances derived from cholesterol. Therefore, based on the mechanism of action, in utero exposure may cause fetal harm (Lecarpentier 2012); however, data from available studies have not shown an increased risk of major congenital anomalies following first trimester exposure (Bateman 2015; Chang 2021; Vahedian-Azimi 2021a). Additional data are needed to evaluate other pregnancy outcomes, such as miscarriage (Vahedian-Azimi 2021b).
Because there is potential for fetal harm, statins should be discontinued once pregnancy is recognized (AHA/ACC [Grundy 2019]; Brunham 2018). If lipid-lowering therapy during pregnancy is required, it should be individualized based on the therapeutic needs of the patient, considering the lifetime risk of untreated disease, use of nonstatin therapies, as well as the known risks and benefits of statins. Based on limited data, when a statin is needed in a pregnant patient, a more hydrophilic option (eg, pravastatin, rosuvastatin) may be preferred. Lipophilic statins (eg, atorvastatin, fluvastatin, lovastatin, simvastatin, pitavastatin) may be more likely to cross the placenta and increase the risk of congenital malformations (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]; Lecarpentier 2012).
Additional data are needed to clarify the role of statins for the prevention of atherosclerotic cardiovascular disease in at-risk pregnant patients (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]; Parikh 2021).
It is not known if pitavastatin is present in breast milk.
HMG-CoA reductase inhibitors (statins) decrease the synthesis of cholesterol and substances derived from cholesterol. Normal concentrations of cholesterol in breast milk are required for infant development (Holmsen 2017; Lecarpentier 2012). Due to the potential for adverse events in the breastfed infant, breastfeeding is not recommended by the manufacturer. Available guidelines recommend resuming statin therapy once breastfeeding is completed (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]).
Red yeast rice contains variable amounts of several compounds that are structurally similar to HMG-CoA reductase inhibitors, primarily monacolin K (or mevinolin) which is structurally identical to lovastatin; concurrent use of red yeast rice with HMG-CoA reductase inhibitors may increase the incidence of adverse and toxic effects (Lapi 2008; Smith 2003).
ACC/AHA Blood Cholesterol Guideline recommendations ( ACC/AHA [Grundy 2019]):
Lipid panel (total cholesterol, HDL, LDL, triglycerides): Lipid profile (fasting or nonfasting) before initiating treatment. Fasting lipid profile should be rechecked 4 to 12 weeks after starting therapy and every 3 to 12 months thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.
Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (AST and ALT); measure AST, ALT, total bilirubin, and alkaline phosphatase if symptoms suggest hepatotoxicity (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine or yellowing of skin or sclera) during therapy.
CPK: CPK should not be routinely measured. Baseline CPK measurement is reasonable for some individuals (eg, family history of statin intolerance or muscle disease, clinical presentation, concomitant drug therapy that may increase risk of myopathy). May measure CPK in any patient with symptoms suggestive of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).
Evaluate for new-onset diabetes mellitus during therapy; if diabetes develops, continue statin therapy and encourage adherence to a heart-healthy diet, physical activity, a healthy body weight, and tobacco cessation.
If patient develops a confusional state or memory impairment, may evaluate patient for nonstatin causes (eg, exposure to other drugs), systemic and neuropsychiatric causes, and the possibility of adverse effects associated with statin therapy.
Manufacturer's labeling: Consider neuromuscular and serologic testing if immune-mediated necrotizing myopathy is suspected.
Inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis (reduces the production of mevalonic acid from HMG-CoA); this then results in a compensatory increase in the expression of LDL receptors on hepatocyte membranes and a stimulation of LDL catabolism. In addition to the ability of HMG-CoA reductase inhibitors to decrease levels of high-sensitivity C-reactive protein (hsCRP), they also possess pleiotropic properties including improved endothelial function, reduced inflammation at the site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects (de Denus 2002; Ray 2005).
Distribution: Vd: ~148 L
Protein binding: >99%, primarily to albumin and alpha 1-acid glycoprotein
Metabolism: Hepatic, via UGT1A3 and UGT2B7; minimal metabolism via CYP2C9 and CYP2C8
Bioavailability: 51%
Half-life elimination: ~12 hours
Time to peak, plasma: ~1 hour
Excretion: Feces (79%); urine (15%)
Altered kidney function: Cmax and AUC were 60% and 102% higher in patients with GFR 30 to 59 mL/minute/1.73 m2 and 40% and 86% higher in patients with ESRD on hemodialysis, respectively.
Hepatic function impairment: Half-life was 15 and 10 hours for patients with moderate and mild impairment, respectively.
Older adult: Cmax and AUC were 10% and 30% higher, respectively, in elderly patients compared with younger patients.
Sex: Cmax and AUC were 60% and 54% higher, respectively, in women compared with men.
Race/ethnicity: Cmax and AUC were 21% and 5% lower, respectively, in black patients compared with white patients.
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