Caduet

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Caduet

• By Davidson Pettit Garrick Purdie
• Lea Rahtu Ingrid Ramos
• Cierra Rogers Trenton Ross

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A Combination Drug

• The leading cause of death in the United States
  for both men and women is a heart attack.
• Two of the biggest risk factors for heart attack
  are high cholesterol and high blood pressure.
• For many of these people, treating these two
  issues meant taking Norvasc and Lipitor. Norvasc
  is the most prescribed medicine for high blood
  pressure, while Lipitor is one of the most
  successful cholesterol treatments available
  (Leibovitz et al, 2003).

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Discovery

• Caduet is the first pill which helps both high
  blood pressure and high cholesterol.
• The food and Drug Administration (FDA) approved
  Caduet in January 2004.
• It was released into market at June 23, 2004.
• Final human trials 2003
• FDA approved Atorvastatin in December of 1996.
• Norvasc was approved 12/5/1995.

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Physical Characteristics
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Structural Formula
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Strength Combinations
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Pharmacokinetics Absorption

• Amlodipine
• Plasma levels peak between 6 and 12 hours
• Bioavailability between 64-90
• Not affected by food

• Atorvastatin
• Plasma levels peak between 1 and 2 hours
• Bioavailability around 14
• Absorption goes down with food

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Pharmacokinetics Distribution

• Amlodipine
• 93 of drug in circulation bound to plasma
  proteins
• Plasma levels become steady after 7 8 days of
  taking drug

• Atorvastatin
• 98 of drug in circulation bound to plasma
  proteins
• It is thought that the Ca in drug is likely
  distributed in human milk

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Metabolism of ActionNorvasc Component of Caduet
AKA Amlodipine

• The purple channel in this picture represents the
  calcium channel which amlodipine blocks to
  inhibit the influx of Ca in vascular smooth
  muscle and cardiac muscle. This vasodilates the
  arteries and increases blood flow reducing blood
  pressure.

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Mechanism of Action

• The Lipitor component of Caduet competes with
  HMG-CoA reducatase substrate to inhibit the
  convertion of HMG-CoA into Mevalonatea precursor
  of Cholesterol and other Sterols.
• This prevents the production of more lipoproteins
  and increases the degradation of existing
  lipoproteins to prevent their accumulation and
  eventually blockage of arteriols.
• Amlodipine
• 90 of the drug is metabolized in the liver

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Excretion

• Amlodipine
• Half-life of 30-50 hours
• Excreted in the urine

• Atorvastatin
• Half-life of around 14 hours
• Excreted in the bile

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Adverse Reactions

• AMLODIPINE COMPONENT
• Most adverse reactions reported were considered
  mild to moderate in severity.
• Most common side effects were headache and edema
• There was a greater incidence of adverse
  reactions in women than men.
• Also a wide variety of rarely reported reactions
  including vertigo, high blood sugar, dry mouth,
  loss of appetite, diarrhea, muscle cramps, and
  vomiting

• ATORVASTATIN COMPONENT
• Most often well tolerated.
• Less than 2 of patients were discontinued due to
  adverse rxns.
• These rxns were mostly mild and temporary.
• The most frequent adverse reactions attributed to
  atorvastatin calcium drug therapy include
  constipation, flatulence, dyspepsia, and
  abdominal pain.
• Wide range of rare rxns include chest pain,
  nausea, bronchitis, rhinitis, insomnia,
  dizziness, arthritis, UTI, hematuria,
  albuminuria, peripheral edema, to increased
  urinary frequency.

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Drug InteractionsNo drug interaction studies
have been conducted with Caduet and other drugs,
although extensive studies have been conducted on
the individual components.

• Amlodipine has not indicated to have any negative
  effect on the protein binding of several drugs
  tested.
• Many drugs that are related to cardiovascular
  disease, including diuretics, beta-blockers,
  nitroglycerin, and angiotensin-converting enzyme
  inhibitors.
• NSAIDs, antibiotics and others were also
  administered safely in conjunction with
  amlodipine.

• Atorvastatin can increase the risk of myopathy
  during treatment with simultaneous administration
  of fibric acid derivatives, lipid-modifying doses
  of niacin or cytochrome P450 3A4 inhibitors
  (because atorvastatin is metabolized by this
  cytochrome.)
• Plasma concentrations increased 40 in healthy
  individuals when co-administered erythromycin, a
  known inhibitor of cytochrome P450 3A4.
• Digoxin, Maalox, and oral contraceptives can all
  alter the plasma concentrations of atorvastatin
  in differing ways

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Overdosage and Warnings

• Amlodipine
• Over dosage may cause excessive peripheral
  vasodilation (therefore leading to hypotension)
  and possibly reflex tachycardia. Very few
  experiences in humans with amlodipine over
  dosages have occurred.
• Atorvastatin
• There is no specific treatment for and overdose
  on atorvastatin. The patient should only be
  treated systematically. As atorvastatin binds
  extensively with plasma proteins, hemodialysis
  would not be expected to increase clearance of
  the drug.

• Beta blocker withdrawal
• The amlodipine component of Caduet is not a
  beta-blocker and therefore does not protect
  against the dangers of abrupt beta-blocker
  withdrawal. The withdrawal of beta-blockers
  should be gradual to prevent such withdrawal

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Conclusion

• In total, the role of Caduet and what it means
  to Pfizer has been debated since its
  introduction. Some regard it as a ploy by Pfizer
  to retain patents of very popular drugs whose
  original patents are running out. Others see it
  as a way for many among us who struggle with
  juggling many different medications at once to
  streamline their pill boxes. Still others hail it
  as a breakthrough in the coordination of drugs so
  that they will work in concert to allay disease.
  In truth, the motives may be more complicated
  than the explanations offered, but the result is
  an effective drug for the treatment of conditions
  that lead to the US greatest killer.