Controlip: Indications, Dosage, Interactions, Side Effects and Contraindications

It is in a group of drugs called HMG CoA reductase inhibitors, or ‘statins’.

This medicine increases the levels of high-density lipoprotein ( good cholesterol ) and lowers the levels of low-density lipoprotein (bad cholesterol) and triglycerides in the blood.

Controlip is also used to reduce the risk of stroke , heart complications, or even heart attack in people with coronary artery disease, type 2 diabetes, or other risk factors.

Controlip can be used to treat other conditions not mentioned in the article. This medicine is only given to people over 10 years of age.

Indications

Lipid-altering agent therapy should be only one component of the multi-risk factor intervention in individuals at significantly increased risk of atherosclerotic vascular disease due to hypercholesterolemia.

Pharmacological therapy is recommended as an adjunct to the diet when the response to a diet restricted in saturated fat and cholesterol and other non-pharmacological measures alone have been inadequate.

In patients with CHD or multiple risk factors for CHD, Controlip calcium tablets can be started simultaneously with the diet.

Cardiovascular disease prevention

In adult patients without clinically evident coronary heart disease, but with multiple risk factors for coronary artery disease, such as age, smoking, hypertension, low HDL-C, or a family history of early coronary artery disease, Controlip calcium tablets are indicated for :

  • Reduce the risk of myocardial infarction.
  • Reduces the risk of stroke.
  • Reduce the risk of revascularization procedures and angina.

In patients with type 2 diabetes and without clinically evident coronary heart disease, but with multiple risk factors for coronary disease such as retinopathy, albuminuria, smoking, or hypertension, Controlip calcium tablets are indicated for:

  • Reduce the risk of myocardial infarction.
  • Reduces the risk of stroke.

In patients with clinically evident coronary artery disease, Controlip calcium tablets are indicated for:

  • Reduce the risk of angina.
  • Reduces the risk of non-fatal myocardial infarction.
  • Reduce the risk of fatal and non-fatal stroke.
  • Reduce the risk of revascularization procedures.
  • Reduce the risk of hospitalization by CHF.

Hyperlipidemia

Controlip calcium tablets are indicated:

  • As a dietary supplement to reduce elevated total C, LDL-C, apo B, and TG levels and to increase HDL-C in patients with primary hypercholesterolemia (familial and non-familial heterozygous) and mixed dyslipidemia (Types IIa and IIb of Fredrickson).
  • As a dietary supplement for the treatment of patients with elevated serum TG levels (Fredrickson Type IV).
  • For the treatment of patients with primary dysbetalipoproteinemia (Fredrickson Type III) who do not respond correctly to diet.
  • Reduce total C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or if such treatments are not available.
  • As a dietary supplement to reduce total C, LDL-C, and apo B levels in post-menarchal boys and girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia if after adequate dietary testing, the following findings are present:
    • LDL-C permanece ≥ 190 mg / dL.
    • LDL-C permanece ≥ 160 mg / dL.
    • There is a positive family history of premature cardiovascular disease or two or more CVD risk factors are present in the pediatric patient.

Limitations of use

Controlip calcium tablets have not been studied in conditions where the main lipoprotein abnormality is elevation of chylomicrons (Fredrickson Types I and V).

How should the Controlip be used?

Use Controlip as directed by your doctor. Check the drug label for exact dosing instructions.

  • An additional leaflet is available for patients with Controlip. Talk to your pharmacist if you have questions about this information.
  • Take Controlip by mouth with or without food.
  • Swallow Controlip whole. Do not break, crush, or chew before swallowing.
  • Taking Controlip at the same time each day will help you remember to take it.
  • Eating grapefruit or drinking grapefruit juice can increase the amount of Controlip in your blood, which can increase your risk of serious side effects.
  • Keep taking Controlip even if you feel better. Don’t miss any doses.
  • If you miss a dose of Controlip, take it as soon as possible if you remember within 12 hours of the missed dose. If it has been more than 12 hours since the missed dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at the same time.

Ask your healthcare provider any questions you may have about how to use the Controlip.

Controlip uses in details

Controlip is used to treat patients with high levels of cholesterol, triglycerides, or lipoproteins in the blood and to reduce the risk of heart disease, even when blood cholesterol is normal.

Description

  • Controlip 10 mg: each tablet contains calcium control equivalent to 10 mg of Controlip.
  • Controlip 20 mg: each tablet contains Controlip calcium equivalent to 20 mg of Controlip.
  • Controlip 40 mg: each tablet contains Controlip calcium equivalent to 40 mg of Controlip.
  • Controlip 80 mg: each tablet contains atorvastine calcium equivalent to 80 mg of Controlip.

Controlip is a white elliptical film-coated tablet containing Controlip calcium. Controlip calcium is a synthetic lipid-lowering agent, which is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor.

This enzyme catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting stage in cholesterol biosynthesis.

The empirical formula of Controlip calcium is (C  33  H  34  FN  2  O  5  )  2  Ca · 3H  2  O and its molecular weight is 1209.42.

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

Dosage

Hyperlipidemia

Hyperlipidemia (familial and non-familial heterozygous) and mixed dyslipidemia (Fredrickson Types IIa and IIb)

The recommended starting dose of Controlip calcium tablets is 10 or 20 mg once a day. Patients who require a large reduction in LDL-C (more than 45%) can start with 40 mg once a day. The dosage range for Controlip calcium tablets is 10 to 80 mg once a day.

Controlip calcium tablets can be administered as a single dose at any time of the day, with or without food. The initial dose and maintenance doses of Controlip calcium tablets should be individualized based on the characteristics of the patient, such as the goal of therapy and response.

After initiation and / or after titration of Controlip calcium tablets, lipid levels should be analyzed within 2 to 4 weeks and the dose adjusted accordingly.

Heterozygous Familial Hypercholesterolemia in Pediatric Patients

Heterozygous familial hypercholesterolaemia in pediatric patients (10 to 17 years of age) The recommended starting dose of Controlip calcium tablets is 10 mg / day; the maximum recommended dose is 20 mg / day (doses greater than 20 mg have not been studied in this patient population).

Doses should be individualized according to the recommended goal of therapy. Adjustments should be made at intervals of 4 weeks or more.

Homozygous familial hypercholesterolemia

The dose of Controlip calcium tablets in patients with homozygous HF is 10 to 80 mg daily. Controlip calcium tablets should be used as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) in these patients or if such treatments are not available.

Concomitant therapy to lower lipids

Controlip calcium tablets can be used with bile acid resins. The combination of HMG-CoA reductase inhibitors (statins) and fibrates should generally be used with caution.

Dosage in patients with renal impairment

Kidney disease does not affect plasma concentrations or LDL-C reduction of Controlip calcium tablets; therefore, no dose adjustment is necessary in patients with renal dysfunction.

Dosage in patients taking cyclosporine, clarithromycin, itraconazole, or certain protease inhibitors:

In patients taking cyclosporine or the HIV protease inhibitors (tipranavir plus ritonavir) or the hepatitis C protease inhibitor (telaprevir), treatment with Controlip calcium tablets should be avoided.

In HIV patients taking lopinavir plus ritonavir, caution should be exercised when prescribing Controlip calcium tablets and the lowest necessary dose.

In patients taking clarithromycin, itraconazole, or in HIV patients taking a combination of saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir.

Treatment with Controlip calcium tablets should be limited to 20 mg, and appropriate clinical evaluation is recommended to ensure that the lowest necessary dose of Controlip calcium is used.

In patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir.

Control interactions

The risk of myopathy during statin therapy increases with the concomitant administration of fibric acid derivatives, doses of niacin, cyclosporine, or strong CYP 3A4 inhibitors (eg clarithromycin, HIV protease inhibitors, and itraconazole).

Strong CYP 3A4 inhibitors

Controlip is metabolized by cytochrome P450 3A4. Concomitant administration of Controlip with strong CYP 3A4 inhibitors may lead to increases in plasma concentrations of Controlip. The degree of interaction and potentiation of effects depends on the variability of the effect in CYP 3A4.

Clarithromycin

Control of AUC was significantly increased by concomitant administration of Controlip 80 mg with clarithromycin (500 mg twice daily) compared to Controlip alone.

Therefore, in patients taking clarithromycin, caution should be exercised when the dose of Controlip exceeds 20 mg.

Protease inhibitor combination

AUC control increased significantly with concomitant administration of Controlip 40 mg with ritonavir plus saquinavir (400 mg twice daily) or Controlip 20 mg with lopinavir plus ritonavir (400 mg + 100 mg twice daily) compared to Controlip alone. .

Therefore, in patients taking HIV protease inhibitors, caution should be exercised when the dose of Controlip exceeds 20 mg.

Itraconazole

Control of AUC increased significantly with concomitant administration of Controlip 40 mg and itraconazole 200 mg. Therefore, in patients taking itraconazole, caution should be exercised when the dose of Controlip exceeds 20 mg.

Grape juice

It contains one or more components that inhibit CYP 3A4 and may increase Controlip plasma concentrations, especially with excessive consumption of grapefruit juice (> 1.2 liters per day).

Cyclosporine

The control metabolites and atorvastatin are substrates of the OATP1B1 transporter. OATP1B1 inhibitors (eg, Cyclosporine) can increase the bioavailability of Controlip.

Control of AUC was significantly increased with concomitant administration of Controlip 10 mg and cyclosporine 5.2 mg / kg / day compared to Controlip alone.

In cases where co-administration of Controlip with cyclosporine is necessary, the dose of Controlip should not exceed 10 mg.

Rifampin or other inducers of cytochrome P450 3A4

Concomitant administration of Controlip with inducers of cytochrome P450 3A4 (eg, Efavirenz, rifampin) can lead to variable reductions in plasma concentrations of Controlip.

Due to the dual interaction mechanism of rifampin, the simultaneous simultaneous administration of Controlip with rifampin is recommended, as delayed administration of Controlip after administration of rifampin has been associated with a significant reduction in plasma concentrations of Controlip.

Digoxin

When multiple doses of Controlip and digoxin were co-administered, stable plasma concentrations of digoxin increased by approximately 20%. Patients taking digoxin must be monitored appropriately.

Oral contraceptives

Concomitant administration of Controlip and an oral contraceptive increased AUC values ​​for norethindrone and ethinyl estradiol. These increases should be considered when selecting an oral contraceptive for a woman taking Controlip.

Warfarin

Controlip had no clinically significant effect on prothrombin time when administered to patients receiving chronic warfarin therapy.

Controlip side effects

The following serious adverse reactions are discussed in more detail in other sections of the label:

  • Rhabdomyolysis and myopathy.
  • Liver enzyme abnormalities.

Adverse experiences in clinical trials

Because clinical trials are conducted under widely varying conditions, the rates of adverse reactions seen in clinical studies of one drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates seen in the drug. clinical practice.

In the placebo-controlled Controlip calcium clinical trial database of 16,066 patients (8755 Controlip calcium vs 7311 placebo, age range 10 to 93 years, 39% female, 91% Caucasian, 3% Black, 2% Asian, 4% others).

With a median duration of treatment of 53 weeks, 9.7% of Controlip calcium patients and 9.5% of placebo patients discontinued due to adverse reactions regardless of causality.

The five most common adverse reactions in Controlip calcium-treated patients that led to treatment discontinuation and occurred at a higher rate than placebo were: myalgia (0.7%), diarrhea (0.5%), nausea (0.4%), increased alanine aminotransferase (0.4%) and increased liver enzyme (0.4%).

The most frequent adverse reactions (incidence> 2% and greater than placebo) regardless of causality, in patients treated with Controlip calcium in placebo-controlled trials were: nasopharyngitis (8.3%), arthralgia (6.9%) , diarrhea (6.8%), pain in the extremities (6.0%) and urinary tract infection (5.7%).

Other adverse reactions reported in placebo-controlled studies include:

  • Body in general: malaise, pyrexia.
  • Digestive system: abdominal discomfort, belching, flatulence, hepatitis, cholestasis.
  • Musculoskeletal system: musculoskeletal pain, muscle fatigue, neck pain, joint swelling.
  • Metabolic and nutritional system: transaminases increased, liver function test abnormal, blood alkaline phosphatase increased, creatine phosphokinase increased, hyperglycemia.
  • Nervous system: nightmare.
  • Respiratory system: epistaxis.
  • Skin and appendages: urticaria .
  • Special senses: blurred vision, tinnitus.
  • Urogenital system: positive urine white blood cells.

Anglo-Scandinavian Heart Results Test (ASCOT)

In ASCOT with 10,305 participants (age range 40 to 80 years, 19% female, 94.6% Caucasian, 2.6% African, 1.5% South Asian, 1.3% mixed / other) treated with Controlip calcium 10 mg daily (n = 5,168) or placebo (n = 5,137).

The safety and tolerability profile of the Controlip calcium group was comparable to that of the placebo group during a median of 3.3 years of follow-up.

Collaborative Diabetes Controlip Study (CARDS)

In CARDS with 2,838 subjects (age range 39 to 77 years, 32% women, 94.3% Caucasian, 2.4% South Asian, 2.3% Afro-Caribbean, 1.0% other) with type 2 diabetes treated with Controlip calcium 10 mg per day (n = 1,428) or placebo (n = 1,410).

There was no difference in the overall frequency of adverse reactions or serious adverse reactions between the treatment groups during a median follow-up of 3.9 years. No cases of rhabdomyolysis were reported.

Post-filing reports

The following adverse reactions have been identified during post approval use of Controlip calcium.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship with drug exposure.

Adverse reactions associated with Controlip calcium therapy reported since market introduction, which are not listed above, regardless of causation assessment, include the following:

  • Anaphylaxis.
  • Angioneurotic edema.
  • Bullous eruptions (including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis).
  • Rhabdomyolysis.
  • Miositis.
  • Fatigue.
  • Tendon rupture.
  • Fatal and non-fatal liver failure.
  • Dizziness
  • Depression.
  • Peripheral neuropathy.
  • Pancreatitis.

There have been rare reports of immune-mediated necrotizing myopathy associated with statin use.

There have been rare reports of post-marketing cognitive impairment (eg, amnesia, memory impairment and / or loss, confusion) that are associated with statin use.

These cognitive problems have been reported for all statins. Reports are generally not serious, and are reversible after statin discontinuation, with variable times to onset of symptoms (1 day to years) and resolution of symptoms (median 3 weeks).

Pediatric patients (10 to 17 years old)

In a 26-week controlled study in post-menarchal boys and girls (n = 140, 31% female, 92% Caucasian, 1.6% Black, 1.6% Asian, 4.8% other), the safety and tolerability profile of Controlip Calcium 10 to 20 mg daily was generally similar to placebo.

Controlip contraindications

  • Active liver disease, which may include unexplained persistent elevations in liver transaminase levels.
  • Hypersensitivity to any component of this drug.

The pregnancy

Women who are pregnant or may become pregnant. When Controlip is administered to a pregnant woman, there is a risk of fetal harm to the baby.

Serum cholesterol and triglycerides increase during normal pregnancy, and derivatives of cholesterol or cholesterol are essential for fetal development.

Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term treatment of primary hypercholesterolemia.

There are no adequate and well-controlled studies on the use of Controlip calcium during pregnancy; however, in rare reports, birth defects were observed after intrauterine statin exposure.

In rat and rabbit animal reproduction studies, Controlip did not reveal evidence of teratogenicity.

If the patient becomes pregnant while taking this medicine, Controlip calcium should be discontinued immediately and the patient should be informed of the potential hazard to the fetus.

Nursing mothers

It is not known whether Controlip is excreted in human milk; however, a small amount of another drug in this class passes into breast milk.

Because statins have the potential to cause serious adverse reactions in nursing infants, women requiring Controlip calcium treatment should not breastfeed their babies.