HMG-COA reductase inhibitors include- Fluvastatin, Lovastatin, Pravastatin, Simvastatin
Refer - Lovastatin

 Drug interactions -Summary

HMG -COA reductase inhibitors +

Warfarin   
    anticoagulant effect of warfarin may be increased. Monitor
    prothrombin time

Bile salts +   Pravastatin  
     a 40%  decrease in pravastatin bioavailability may occur. Take
     Pravastatin  1 hour before and 4 hour after bile acid sequestrant

Cyclosporine + Lovastatin 
     severe myopathy or rhabdomyolysis may occur with concurrent
      administration

Erythromycin +  Lovastatin 
     severe myopathy or rhabdomyolysis may occur with concurrent
      administration

Gemfibrozil +  HMG -CoAInhibitors    
     severe myopathy or rhabdomyolysis may occur. This has been
     reported with lovastatin. The urinary excretion and and protein
     binding of pravastin may be decreased by gemfibrozil.
      Avoid this concurrent use

Niacin +   Lovastatin 
   severe myopathy or rhabdomyolysis may occur with concurrent
     administration

Rhabdomylosis and acute renal failure with gemfiboz, nicotin  acid, immunosupressants,
erythromycin.
Coumarin anticoagulants- bleeding or increased prothrombin  time.
May increase the anticoagulant
effect of warfarin or anisindione due to inhibition of anticoagulants hepatic metabolism. Risk of
bleeding may be increased

 Antihyperlipidemic agent

Approved by FDA in 1989

LIST OF DRUGS DURING 2004

HMG-COA reductase inhibitors include- Fluvastatin, Lovastatin, Pravastatin, Simvastatin
Refer - Lovastatin

INFORMATION UPDATE-

STATINS-   ADVERSE EFFECTS

Recent data suggests a number of additional side effects, namely-

-Treatment of any statin may be associated with depression. sleep disturbances,memory  loss,
 and sexual dysfunction

-Statin therapy is associted with a slightly increased risk of development of diabetes

- Statins may rarely be associated with  intestinal lung disease . Patients should be adviced
  to seek medical attention if symptoms such as dyspnoea, non-productive cough or
  deterioration of general health eg fatigue, weight loss and fever, occur

Simavastatin Dose-
-Due to increased risk of serious life threatening myopathy, no patient should be initially
  started on 80mg dose
- Use other treatments if patients LDL targets are not met with 40mg daily dose
- Patients concurrently on amiodarone , verapramil, or diltiazem should not be prescribed
  more than 10mg daily
- Patients concurrently on amlodipine or ranolazine must not receive more than 20mg daily
- Concurrent use of itraconazole , ketoconazole, posaconazole, erythromycin, clarithromycin,

Musculoskeletal-

Rhabdomylosis, myopathy, arthakgia CNS- Dysfunction of certain cranial nerves (including alteration of tasts), impairement of extra-ocular movement, facial paralysis), tremor, vertigo, memory loss, paresthesia, peripheral neuropathy, perihpheralnerve palsy, anxiety, insomnia, depression GU- gynaecomastia, loss of libido, erectile dysfunction

Opthalmic- progression of cataracts(lens opacities) opthalmoplegia

Miscellaneous- alopecia, edema Hypersensitivity- anaphlaxis, angioedema, lupus-syndrome like syndrome, polymayalgia, rheumatica, vasculitis, purpura thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESRincrease, eosinophillia, arthritis, arthalgia, urticaria, asthenia, photosentivity, fever, chiils, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme including Stenens Johnson sdyndrome.

GI- pancreatitis, hepatitis, including chronic active hepatitis,cholestatic jaundice,fatty changes in the liver, cirrhosis, fulimant hepatic necrosis, hepatoma, anorexia, vomiting. Dermatogic- alopecia, pruritus, various skin changes, (eg nodules, discoloration dryness of skin/mucous membranes, change to hair/nails Lab test abnormalities- increased serum transaminase (AST, ALT, CRK ) 11% with lovastatin, levels at least normal), alkaline phosphatase and bilirubin, thyroid function test abnormalities.

Hypersensitivity, acute liver disease, unexplained persistent elevation of serum transaminase, pregnancy, lactation.

Special precautions:

Long term use, history of liver disease,concomittant use with gemfibrozil, nicotinic acid (1g or more/day), immunosupressants erythromycin.

Renal impairment, severe acute infections, major surgery or trauma, severe metabolic, endocrine or electrolyte disorders and patients with uncontrolled seizures. Diet- before instituting therapy, attempt to control hypercholesterolemia with diet, excercise and weight reduction in obese patients. Treat underlying medical problems.

Ophthamologic chages- there were no clinically significant differences between lovastatin and placebo groups in the incidence, type or lenticular opacities.

Homogenous hypercholesterolemia- lovastatin and simavastatin are less effective in patients with a rare familial hypercholesterolemia, possibly because these patients have no functional LDL receptors. Pravastatin may be useful in these patients who are not completely devoid of LDL receptors but have a reduced level of LDL recptor activity. Sleep disturbances- lovastatin and simavastatin may interfere with sleep,causing insomnia, whereas provastatin does not apperar to disturb sleep.

Photosentivity- photosentization may occur, therfore caution patients to take protective measures against exposure to ultraviolet or sunlight.

Warnings- Liver dysfunction- use with caution in patients who consume substantial quantities of alcohol or who have ahistory of liver disease.

Skeletal muscle effects- Rhbdomylosis with renal dysfunction secondary to myoglobinuria has occured with some drugs in this class.Myalgia has occured with Lovastatin.Consider myopathy in any patient with diffuse myalgia , muscle tenderness or weakness or marked elevation of CPK.

Endocrine effects-excercise caution when administering HMG-CoA reductase inhibitors with drugs that affect steroid levels of activity. CNS- in animals , CNS vascular lesions characterized by perivascular hemorrhage and edema and mononulclear cell infiltration of perivasscular spaces and other similar CNS vascular lesions have been observed with other drugs in this class.

Morbidity/Mortality- the efect of HMG-CoA reductase inhibitor-induced changes in lipoprotein levels, including reduction of serum cholesterol on cardiovasscular morbidity ormortality has not been established. Hyperlipoproteinemia- although lovastatin, may be useful in reducing elevated LDL cholesterol levels in patients with combined hypercholesterolemia and hypertriglyceridemia whre hypercholesterolemia is the major abnormality, it has not been studied in conditions where the major abnormality is elevation of chylomicrons, VLDL or intermediate density lipoprotein (LDL) ie hyperlipoproteinemia types I,III, IV or V.

Hypercholesterolemia secondary causes- prior to initiating therapy, exclude secondary causes of hypercholesterrolemia (eg poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, disproteinemias, obsructive liver disease, other drug therapy, alcoholism ) and measures , total HDL-C and trioglycerides

Hypersentivity- an aparent hypersentivity syndrome has occured.

Renal function impairment- closely monitor patients with renal impairment who are receving pravastatin.

Elderly- elderlty patients > 65 years old, demonstrated a greater treatment response in respect of LDL-C, total C and LDL/HDL ration than < 65 years old.

Pregnancy- if a patient becomes pregnant while on the drug, discontinue the drug and appraise her of the potential hazard to the fetus.

Lactation- because of the potential for serious adverse reactions in nursing infants, caution women taking these drugs not to nurse their infants. Children- safey and efficacy in individuals < 18 years old have not been established, treatment of this age group is not recommended. at this time.

Approved by FDA in 1989

Antihyperlipidemic agent Dosage: Indidualise dose. Initial 2mg/day with the evening meal.

Dose range from 20 to 80mg/day in single or divided doses. Maximum dose 80mg/day.

Overdosage

Symptoms Lovasstatin- A few cases of accidental overdosage has been reported. , no patients had any specific symptoms and all recovered without sequelae.

Maximum dosage taken was fifty-two 20mg tablets (1.04g)

Treatment

1.Vomiting was induced by ipecac. in both children and no capsules were noted in their emesis.

2. Neither child experienced any adverse symptoms and both recovered from the incident without problems.

Fluvastatin- The maximum amount that could have been igested was 80mg.

Pravastatin- Two cases reported of pravastatin overdodse, both of which were symptomatic and not associated with clinical lab abnormaities.

Simavastatin- A few cases of overdosage was reported, no patient had any specific symptoms, all receoverd with sequalae. The maximum dose taken was 450mg.

Treatment

1. Treat symptomaticaaly and institurte supportive measures.

2. The dialyzability of these agents and their metabolites is not known.

Missed dose

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

1. May cause photosentivity (sensitivity to sunlight) . Avoid prolonged exposure to the sun and other ultraviolet light.

2. Use sunscreens and wear protective clothing until tolerance is determined

3. Promptly report unexplained muscle pain, tenderness or weakness, especially if accompanied by fever or malaise

4. Follow dietary recommendations.

5. Take lovastatin with meals, fluvastatin and simvastatin may be taken without regrads to meals.

6.Allergies- tell your doctor if you have ever had any unusual or allergic reaction to HMG-CoA reductase iinhibitors Also tell your doctor if youare allergic to any other substances, such as foods, presrvatives or dyes.

7.Diet- before prescribing medicines to lower your cholesterol your doctor will probably try to control your condition by prescribing a personal diet for you.Such a diet will be low in tatal fat. However, check with your doctor before going on any diet.

8.Pregnancy - should not be used during pregnancy.

9.Breast feeding- are not recommended during breast feeding 9 Children - early information seems to show that these medicines may be effective in children, but their long term safety has not been studied

10. Elderly- this medicine has been tested in a limited number of patients 65 years of age or older, and has not been shown to cause different side effects or problems in older people than it does in younger adults.

11. Other medicines - Let your doctor know what other medicines you are taking, so that he can advice you accordingly. Cyclosporine or Gemifibrozil or Niacin - use of these medicines with an HMG-CoA reductase inhibitors may increase the risk of developing muscle problems and kidney failure

12. Other medical problems - Tell your doctor if you have any other medical problems especially - Alcohol abuse or Liver disease - use of this medicine may make liver problems worse Convulsions not well controlled or Organ transplant with therapy to prevent transplant or if you had recently had any major surgery - patients with these conditions may be at risk of developing problems that may lead to kidney failure

13. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

14. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

15. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

Lovastatin

when given underfasting conditions plasm aconcentrations are about two0third of those found when it is administered immediately after meals.

Provastatin

presence of food reduces systemic bioavailability of pravastatin. However pravastatin may be taken withour regards to meals

Simvastatin

may be taken without regard to meals. Fluvastatin- may be taken without regard to meals.

Pregnancy

If a patient becomes pregnant while on the drug, discontinue the drug and appraise her of the potential hazard to the fetus.

Lactation

Because of the potential for serious adverse reactions innnursing infants, caution women taking these drugs not to nurse their infants.

Children

Safey and efficacy in individuals < 18 years old have not been established, treatment of this age group is not recommended. at this time.