Summary of the product

Name of the Drug: Lipitor Tablets

Non-proprietary name: Atorvastatin Calcium

Pharmacological Category: Lipid modifier. HMG-CoA reductase inhibitor/

Antihyperlipoproteinemic agent.

Atorvastatin, commonly known by its brand name Lipitor, is a member of the statin drug class. It
is prescribed primarily to reduce cholesterol levels in the bloodstream and lower the risk of
heart-related conditions like heart attacks and strokes. It's important to note that the specific
brand names and formulations of this medication may vary depending on the country. For
accurate information, it's best to consult with a healthcare provider or refer to the medication
packaging.

Chemical Name and Structure

Atorvastatin calcium is [R-(R*, R*)]-2-(4-fluorophenyl)-ß, δ-dihydroxy-5- (1-methylethyl)-3-

phenyl-4-[(phenylamino) carbonyl]-1H-pyrrole-1-heptanoic acid, calcium salt (2:1) trihydrate.
The empirical formula of atorvastatin calcium is (C33H34 FN2O5)2Ca•3H2O and its molecular
weight is 1209.42.

Introduction
Atorvastatin calcium is a white to off-white crystalline powder that is insoluble in aqueous
solutions of pH 4 and below. Atorvastatin calcium is very slightly soluble in distilled water, pH
7.4 phosphate buffer, and acetonitrile, slightly soluble in ethanol, and freely soluble in methanol.

Lipitor tablets for oral administration contain 10, 20, 40, or 80 mg atorvastatin and the following
inactive ingredients: calcium carbonate, USP; candelilla wax, FCC; croscarmellose sodium, NF;
hydroxypropyl cellulose, NF; lactose monohydrate, NF; magnesium stearate, NF;
microcrystalline cellulose, NF; Opadry White YS-1-7040 (hydroxypropylmethylcellulose,
polyethylene glycol, talc, titanium dioxide); polysorbate 80, NF; simethicone emulsion.

Lipitor, developed by Pfizer and FDA-approved in 1996, has been a transformative medication in
cardiovascular medicine. Marketed under the generic name atorvastatin, it has revolutionized the
management of high cholesterol levels and the prevention of heart-related issues. Lipitor's
efficacy, safety, and widespread acceptance have made it a cornerstone in cholesterol treatment,
impacting preventive cardiology as well. By competitively inhibiting HMG-CoA reductase, an
enzyme crucial in cholesterol production, Lipitor significantly reduces LDL cholesterol,
lowering the risk of atherosclerosis and cardiovascular diseases. Its enduring impact and
widespread use highlight its pivotal role in cardiovascular medicine.

Lipitor, a commonly prescribed medication, is used to treat adult patients with hyperlipidemia
and dyslipidemia, alongside lifestyle modifications. It is effective in lowering LDL-C,
triglycerides, apo B, total cholesterol, and the Total-C to HDL-C ratio and can raise HDL-C in
various lipid disorders. Lipitor is used to treat specific diseases such as primary
hypercholesterolemia, mixed hyperlipidemia, dysbetalipoproteinemia, hypertriglyceridemia, and
familial hypercholesterolemia. It is also employed in preventing cardiovascular disease in at-risk
populations, such as those with hypertension, type 2 diabetes mellitus, and hypertension.

In the pediatric field, Lipitor is used for males and postmenarchal girls with heterozygous
familial hypercholesterolemia. Specific criteria, including measuring LDL-C levels after a
dietary trial, must be met for pediatric use. However, caution is advised for children under ten
due to the lack of proven safety and efficacy. Lipitor is approved for use in all indications,
including the elderly, though some differences in safety and efficacy may be observed.

Mechanism of Action
Atorvastatin's mechanism of action is intricately linked to its role as an HMG-CoA reductase
inhibitor. By selectively targeting this enzyme, atorvastatin reduces the conversion of HMG-CoA
to mevalonate, a critical step in cholesterol synthesis. This competitive inhibition leads to
decreased intracellular cholesterol levels, triggering a compensatory upregulation of LDL
receptors. Beyond its lipid-lowering effects, atorvastatin exhibits anti-inflammatory and
antioxidant properties, contributing to its comprehensive cardiovascular benefits. The drug's
multifaceted approach addresses not only elevated cholesterol levels, but also inflammatory
processes implicated in atherosclerosis. The intricate interplay of molecular events underscores
the precision of atorvastatin's mechanism, showcasing a targeted, evidence-based approach that
has reshaped the landscape of cardiovascular medicine.

Pharmacokinetics

The way atorvastatin is processed in the body is critical for its effectiveness and safety. After
being taken orally, the drug is quickly absorbed, reaching peak plasma concentrations within a
few hours. Atorvastatin is mainly metabolized in the liver, primarily through the cytochrome
P450 3A4 pathway. While the metabolites are not active pharmacologically, they play a role in
how atorvastatin is processed and eliminated from the body. The drug's extended half-life of
about 14 hours allows for once-daily dosing, which is convenient for patients. Variability in how
the body processes atorvastatin, influenced by both genetics and the environment, underscores
the need for personalized dosing plans. Studies on the drug's pharmacokinetics have provided
valuable insights into how it is absorbed, distributed, metabolized, and excreted. Atorvastatin's
consistent pharmacokinetic profile across different patient groups is due to its predictable
behavior in the body. The drug's interactions with other medications that affect the cytochrome
P450 system highlight the importance of considering potential interactions when prescribing it
with other drugs. Ongoing research on atorvastatin's pharmacokinetics aims to further refine our
understanding of how the drug is processed in the body and optimize its use in clinical practice.

Pharmacodynamics

Atorvastatin primarily works by reducing LDL cholesterol levels in the bloodstream. It also has
beneficial effects on triglycerides and can modestly increase levels of HDL cholesterol. The
response to atorvastatin varies depending on the dosage, highlighting the need to customize
treatment for optimal lipid control. Its effects on various lipid parameters contribute to its
comprehensive approach to managing abnormal lipid levels. Besides its effects on lipids,
atorvastatin also has other beneficial effects, such as reducing inflammation and oxidative stress
associated with atherosclerosis. These effects extend its benefits beyond just lowering
cholesterol. The response to atorvastatin can vary from person to person, emphasizing the
importance of tailoring treatment to individual needs. Advances in our understanding of lipid
metabolism and atherosclerosis continue to shape our knowledge of how atorvastatin works. Its
inclusion in treatment guidelines reflects its established role not only in managing lipids but also
in addressing other factors that contribute to cardiovascular risk. Ongoing research aims to
uncover more about how atorvastatin affects the cardiovascular system, paving the way for more
personalized and targeted treatments.

Warnings and Precautions

It is crucial to understand the proper usage of a drug, including LIPITOR. LIPITOR is

contraindicated in patients with active liver disease, hypersensitivity to atorvastatin or any of its
components, or unexplained increases in serum transaminases exceeding three times the upper
limit. Contraindications also include breastfeeding, pregnancy, and concurrent use of certain
medications. Patients must adhere to a conventional cholesterol-lowering diet to receive the
recommended dosage and administration of LIPITOR. Initiating therapy involves assessing lipid
profiles and addressing secondary causes of elevated cholesterol levels. Starting doses vary
based on the indication and may require adjustments during treatment. Therapeutic lifestyle
modifications are essential to the management of LIPITOR.

The warnings and precautions for LIPITOR encompass a wide range of potential risks. These
include possible effects on CoQ10 levels, an increased risk of hemorrhagic stroke with higher
doses, and the potential for interactions with the synthesis of gonadal and adrenal steroids.
Special attention is given to pregnant women, nursing mothers, and specific groups such as
pediatric and geriatric populations. The primary goal is to ensure patient safety by providing
healthcare professionals with a comprehensive understanding of potential risks and safety
measures.

Safety and Tolerability

Atorvastatin, marketed as Lipitor, is generally well-tolerated, with common side effects including
myalgia, arthralgia, and mild gastrointestinal symptoms that are often transient and manageable.
However, rare but severe adverse effects such as myopathy and an increased risk of
rhabdomyolysis may occur, especially when atorvastatin is used concurrently with specific
medications or in predisposed individuals. Regular monitoring of liver function tests is
recommended to ensure safety due to infrequent reports of elevated transaminases. This
highlights the importance of ongoing communication between patients and healthcare providers
to address any emerging symptoms or concerns related to Lipitor's use promptly.

A review of Lipitor's adverse reactions reveals a wide range of potential risks, from serious
conditions like rhabdomyolysis to commonly reported reactions like arthralgia and
nasopharyngitis. The drug interaction section emphasizes the complexity of using Lipitor with
other medications. Specific contraindications, such as cyclosporine and hepatitis C antivirals, are
highlighted, along with a comprehensive list of potential interactions, side effects, and clinical
observations. This level of detail is essential for healthcare providers to monitor patients
effectively and make informed decisions about co-prescribing.

Lipitor's mechanism of action is explained in clinical pharmacology, with a focus on its selective
inhibition of HMG-CoA reductase, a key enzyme in cholesterol synthesis. The drug's
effectiveness in treating various hypercholesterolemia and dyslipidemia disorders is
demonstrated through its pharmacodynamics. A thorough understanding of the complex
interactions between Lipitor and the body is ensured by discussing its pharmacokinetics,
including absorption, metabolism, and excretion, across different demographic groups.

Atorvastatin's metabolism by CYP3A4 makes it susceptible to interactions with strong inhibitors

or inducers of this enzyme, potentially affecting its plasma concentration. Close monitoring is
required when atorvastatin is used concomitantly with drugs like warfarin, as it may impact the
efficacy of the anticoagulant, necessitating dosage adjustments. Understanding atorvastatin's
metabolic pathways and potential interactions underscores the importance of conducting a
comprehensive medication review when initiating or adjusting therapy to achieve optimal patient
outcomes.

Rhabdomyolysis, a rare but serious condition involving muscle breakdown, is a potential concern
with atorvastatin, especially when combined with medications that increase this risk. Patients
with active liver disease or unexplained, persistent elevations in liver transaminases should not
take atorvastatin, highlighting the importance of thorough pre-treatment evaluations. Caution is
advised in patients with a history of myopathy or predisposing factors, requiring careful
assessment of the risks and benefits before starting atorvastatin therapy. Increased awareness of
these warnings and precautions is essential to ensure the safe and appropriate use of atorvastatin
in a variety of patient populations.

Clinical trials involving Lipitor have demonstrated its efficacy in improving lipid profiles and
reducing cardiovascular risk across different patient groups. These trials showcase the drug's
broad applicability. The summary of toxicology studies provides healthcare providers with
reassurance about the drug's safety, as it has shown minimal acute toxicity and few long-term
side effects. The patient medication information section is a valuable resource that educates
patients on how to use the product, precautions to take, warnings, and when to seek medical
advice.

This comprehensive three-page overview provides a detailed analysis of Lipitor's indications,

contraindications, dosage and administration, warnings, adverse reactions, medication
interactions, clinical pharmacology, and safety profile, including insights from toxicology studies
and clinical trials. For healthcare providers, it serves as an invaluable resource for navigating the
complexities of prescribing Lipitor and ensuring patient safety and efficacy.

Clinical Efficacy

Clinical trials, including the pivotal "Treating to New Targets" study, have unequivocally
demonstrated the clinical efficacy of atorvastatin. The reduction in LDL cholesterol achieved
with atorvastatin has led to significant improvements in cardiovascular outcomes. Long-term
trials involving diverse patient populations provide robust evidence of atorvastatin's effectiveness
in preventing atherosclerotic events. Key efficacy endpoints, such as major cardiovascular events
and changes in lipid profiles, are crucial measures in evaluating atorvastatin's impact.
Atorvastatin's efficacy extends beyond lipid modification to address a broader range of
cardiovascular risk factors. Whether used in individuals with familial hypercholesterolemia or
those at moderate risk, atorvastatin consistently demonstrates its clinical utility. Health economic
analyses support the cost-effectiveness of atorvastatin in achieving long-term cardiovascular risk
reduction. The inclusion of atorvastatin in treatment guidelines is based on strong evidence
supporting its efficacy and safety. The consistent demonstration of efficacy across diverse patient
groups reinforces atorvastatin's status as a cornerstone in evidence-based cardiovascular
medicine. Ongoing research, including real-world evidence studies, continues to enhance our
understanding of atorvastatin's clinical efficacy and its impact on cardiovascular outcomes.

Patient Information

Patient education is crucial for ensuring the optimal effectiveness of atorvastatin. Patients should
be informed about the importance of adhering to prescribed doses and attending regular follow-
up appointments. It is also essential to educate patients about potential side effects, particularly
muscle-related symptoms, so they can promptly recognize and report any unusual symptoms.
This emphasis on patient education fosters an active partnership between healthcare providers
and patients, promoting comprehensive care.

When using atorvastatin in special populations, caution is warranted due to limited data,
especially in pediatric populations where long-term effects on growth and development are not
fully understood. Dose adjustments may be necessary for patients with hepatic impairment,
highlighting the need for personalized treatment. The safety of atorvastatin during pregnancy or
lactation is not well-established, so its use in these populations should be approached cautiously,
weighing potential risks and benefits.

Atorvastatin is commonly available in blister packs or bottles, allowing for flexible dosing and
easy administration. Proper storage instructions, such as storing at controlled room temperature
and protecting from moisture and heat, are crucial for maintaining the stability and efficacy of
the medication. Attention to packaging and storage details ensures the overall quality and
integrity of atorvastatin, ensuring its potency throughout the treatment course.

Manufacturer Information

Lipitor is manufactured by Pfizer Inc., a leading pharmaceutical company recognized for its
dedication to research, development, and quality standards. Contact information for Pfizer is
readily available on the official packaging and the company's websites, ensuring transparency
and accessibility for patient inquiries or concerns. Familiarity with the manufacturer enhances
patient confidence and underscores the importance of obtaining medications from reputable
sources.
Regulatory Approval

Lipitor, also known as atorvastatin, obtained regulatory approval following comprehensive

evaluation of its efficacy and safety in extensive clinical trials involving diverse patient
populations. Regulatory agencies conduct continuous monitoring to promptly update safety
information based on ongoing post-marketing surveillance. The regulatory approval process
reflects a commitment to patient safety and the thorough assessment of a drug's risk-benefit
profile.

Post-Marketing Surveillance

Continuous monitoring of atorvastatin's long-term safety profile is crucial for post-marketing

surveillance. Vigilant surveillance mechanisms promptly address any emerging safety concerns,
leading to the continuous refinement of atorvastatin's risk-benefit profile. Updates to prescribing
information demonstrate the dynamic nature of post-marketing surveillance and the commitment
to providing healthcare professionals with the most up-to-date safety information.

Post-market Adverse reactions

The following adverse events have been reported in post-marketing experience with Lipitor,
irrespective of causality assessment:

Rare reports include severe myopathy with or without rhabdomyolysis, as detailed in the
warnings and precautions section regarding muscle effects, renal issues, and drug interactions.
Additionally, there have been rare reports of immune-mediated necrotizing myopathy associated
with statins, as outlined in the muscle effects warnings and precautions.

Isolated reports include gynecomastia, thrombocytopenia, arthralgia, and allergic reactions such
as urticaria, angioedema, anaphylaxis, and bullous rashes (including erythema multiforme,
Stevens-Johnson syndrome, and toxic epidermal necrolysis). Other isolated reports involve
fatigue, myositis, back pain, chest pain, malaise, dizziness, amnesia, peripheral edema, weight
gain, abdominal pain, insomnia, hypoesthesia, tinnitus, tendon rupture, pancreatitis, dysgeusia,
and Ewing's sarcoma in pediatric patients.

The following adverse events have been reported with some statins:

- Sleep disturbances, including insomnia and nightmares.

 - Mood-related disorders, including depression.
- Very rare cases of interstitial lung disease, especially with long-term therapy.

Rare post-marketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia,
memory impairment, confusion) associated with statin use have been noted. These cognitive
issues are generally non-serious and reversible upon statin discontinuation, with varying times to
symptom onset (ranging from 1 day to years) and symptom resolution (median of 3 weeks).

Safety and Efficacy

LIPITOR® is a lipid metabolism regulator indicated as an adjunct to diet for the reduction of
elevated total cholesterol, LDL-cholesterol, triglycerides, and for increasing HDL-cholesterol in
various hyperlipidemic and dyslipidemic conditions. This includes primary
hypercholesterolemia, combined hyperlipidemia, dysbetalipoproteinemia, hypertriglyceridemia,
and familial hypercholesterolemia. For homozygous familial hypercholesterolemia, LIPITOR®
should be used when other treatments are not available or as an adjunct to such treatments. It is
also indicated to reduce the risk of myocardial infarction in patients without clinically evident
coronary heart disease but with multiple risk factors for coronary heart disease, patients with
type 2 diabetes mellitus and other risk factors, and patients with clinically evident coronary heart
disease.

Clinical trials have shown significant therapeutic responses within 2 weeks, with the maximum
response usually achieved within 2-4 weeks, maintained during chronic therapy. Dosage
adjustments, if necessary, should be made at intervals of 2 to 4 weeks.

Efficacy

Clinical Trials

Lipitor has been extensively evaluated in a wide range of clinical trials, demonstrating significant
reductions in LDL-C (low-density lipoprotein cholesterol), total cholesterol, triglycerides, and an
increase in HDL-C (high-density lipoprotein cholesterol) across various patient populations,
including those with primary hypercholesterolemia, mixed dyslipidemia, and familial
hypercholesterolemia.
In pediatric patients (10-17 years) with heterozygous familial hypercholesterolemia, Lipitor
significantly reduced LDL-C and apo B levels, with a safety and tolerability profile similar to
that observed in adults.

Safety

Common Adverse Reactions

Most common adverse reactions include nasopharyngitis, arthralgia, diarrhea, pain in extremity,
and hyperglycemia. These effects were generally mild and transient.

Serious Adverse Reactions

Rhabdomyolysis with acute renal failure secondary to myoglobinuria, myalgia, myositis, and
myopathy have been reported but are rare. Monitoring for muscle symptoms is advised.

Increases in serum transaminases were observed in less than 1% of patients, typically transient
and resolved or improved with dose adjustment or discontinuation.

Post-market adverse reactions include immune-mediated necrotizing myopathy (IMNM),

gynecomastia, thrombocytopenia, and allergic reactions such as anaphylaxis and angioedema.

Drug Interactions

Significant interactions may occur with cyclosporine, certain antiviral agents, and other
medications that can alter the pharmacokinetics of atorvastatin or increase the risk for myopathy.

Co-administration with drugs that inhibit CYP3A4 or other hepatic transporters can lead to
increased plasma concentrations of atorvastatin, necessitating caution and potential dose
adjustments.

Special Populations
In pediatric patients with familial hypercholesterolemia, Lipitor was effective in reducing LDL-C
levels, with a safety profile consistent with that in adults. However, doses greater than 20 mg/day
have not been studied in this population.

In geriatric patients, efficacy and safety profiles are similar to those in younger adults, but
increased systemic exposure in some elderly individuals may necessitate careful dose selection
and monitoring.

Warnings and Precautions

Muscle effects, liver enzyme abnormalities, and the potential for serious liver injury are
highlighted. Monitoring for signs of muscle pain, weakness, or tenderness, and conducting liver
function tests before and during treatment, are recommended.

Lipitor should be used with caution in patients with a history of liver disease, significant alcohol
consumption, or in situations where an increase in plasma levels may occur.

Therefore, Lipitor (atorvastatin calcium) has demonstrated considerable efficacy in lowering

elevated lipid levels across diverse patient populations, including those with primary
hypercholesterolemia, mixed dyslipidemia, familial hypercholesterolemia, and in the prevention
of cardiovascular disease. Clinical trials have consistently shown that Lipitor effectively reduces
LDL-C ("bad" cholesterol), total cholesterol, triglycerides, while also increasing HDL-C ("good"
cholesterol). These effects contribute to a reduced risk of cardiovascular events such as
myocardial infarction and stroke. Notably, its efficacy extends to pediatric patients (ages 10-17)
with heterozygous familial hypercholesterolemia, showcasing significant reductions in LDL-C
and apo B levels. The therapeutic benefits of Lipitor underscore its role as a cornerstone in the
management of dyslipidemia and cardiovascular disease prevention.

The safety profile of Lipitor has been thoroughly evaluated, with most adverse reactions being
mild and transient, such as nasopharyngitis, arthralgia, diarrhea, pain in extremity, and
hyperglycemia. Serious adverse reactions, although rare, include myopathy, rhabdomyolysis with
acute renal failure, and liver enzyme abnormalities. Post-market surveillance has identified
additional adverse reactions like immune-mediated necrotizing myopathy (IMNM),
gynecomastia, and thrombocytopenia. Lipitor's interactions with other drugs, particularly those
affecting the CYP3A4 enzyme system, necessitate careful monitoring and dose adjustments to
mitigate the risk of increased plasma concentrations and associated adverse effects. Special
consideration is given to pediatric and geriatric populations to ensure a balance between efficacy
and safety, with dose adjustments based on individual response and potential for increased
systemic exposure.

Overall, Lipitor offers significant benefits in lipid management and cardiovascular risk reduction,
with a well-characterized safety profile. Healthcare providers must consider individual patient
factors, potential drug interactions, and the rare but serious risks of muscle and liver-related
adverse effects when prescribing Lipitor. Monitoring and patient education on recognizing
symptoms of adverse reactions are essential components of Lipitor therapy to optimize patient
outcomes and maintain a favorable risk-benefit profile.