Interacting drugs - summary

 Allopurinol +

  + Ampicillin

 Rate of ampicillin-induced skin rashes much higher with allopurinol coadmin.on than with either drug alone

 + Anticoagulants

 Increased anticoagulant action of some agents enhanced, but probably not that of warfarin 

 + Cyclophosphamide

 Myelosuppressive effects of cyclophosphamide enhanced, possibly increasing the risk of bleeding or infection

 + Thiopurines

Clinically significant increases in pharmacologic and toxic effects of oral thiopurines have occured

 Theophylline clearance decreased with large allopurinol doses (600mg/day) leading to increased plasma theophylline levels and toxicity

+ Allopurinol

ACE inhibitors incr possibly higher risk of hypersensivity reaction when these agents are coadministered than when each drug is administered alone

 Aluminium  salts +

Pharmacologic effects of allopurinol decreased

Thiazide diuretics +

Coadministration increase the incidence of hypersensitivity reactions of Allopurinol.

Uricosuric agents +

Uricosuric agents which increase the excretion of urate are also likely to increase the excretion of oxipurinol and lower degree of inhibition of xanthine oxidase

Gout

Dermatologic- skin rash, usually maculopaular, sometimes scaly or exfoliative is most common. incidence of rash may be increased in presence of renal disorder. Skin reactions can be severe and fatal.

Severe reactions- fever, chills, arthalgias, cholestatic jaundice, eosinophilia, mild leukocytosis, leukopenia

GI- nausea, vomiting, diarrhea, intermittent abdominal pain, gastritis, dyspepsia

Hepatic- increased alkaline phosphatase, AST and ALT, hepatomegaly, cholestatic jaundice, granulomatous hepatitis hepatic necrosis.

Hematogic- leukopenia, leukocytosis, eosinophilia, thrombocytopenia

CNS- headache, peripheral neuropathy, neuritis, paresthesia, somnolence

Miscellaneous- arthalgia, acute atacks of gout, ecchymosis, fever, myopathy,epistaxis, taste loss or perversion, renal failure,uremia, alopecia, hypersentivity vasculitis, necrotizing angitis.

Intolerance to the drug,lactation.

Special precautions:

Acute gouty attack may be precipated in early Zyloric treatment. Propyhlactically with an antinflammatory or colchicine for at least 1 month. Withdraw immediately when sentivity (skin rash etc) appears. Asymptomatic hyperuricaemia per-se is not an indication for Zyloric. Pregnancy. Hepatic and renal impairment.

Monitoring- periodically determine liver and kidney function during the first few months of therapy. Perform BUN serum creatinine or creatinine clearance and ressess the patients dosage.

Acute attacks of gout- have increased during early stages of allopurinol administration even when normal or subnormal serum uric acid levels have been attained. In general, give doses of colchicine prophylactically when allopurinol is begun.

Fluid intake- sufficient to yield urinary output of atleast 2 L and the maintenance of aneutral or slightly alkaline urine are desirable to avoid theoritical posibilty of formation of xanthine calculi under the influence of allopurinol therapy and to help prevent precipiation of urates in patients receiving concomittant uricosurics.

Drowsiness- has occured occassionally. Patients should observe caution while driving or performing other tasks requiring alertness, cordination and physical dexterity. Bone marrow depression- has occured in patients receiving allopurinol, most of whom received concomittant drugs with the potential for causing reaction.

Warnings-

Asyptomatic hyperuricemia- the drug is not innocuous. Do not use to treat asympatomatic hyperuremia

Hepatotoxicity- a few cases of reversible clinical hepatotoxicity have occured insome patients asymptomatic rises in serum alkaline phosphatase or serum transaminase levels have been observed.

Renal function impairment- Patients with impaired renal function require less drug and careful observation during early stages of treatment, reduce dosage or discontinue therapy if increased abnormalities in renal function appear and persist.

Pregnancy- use only when clearly needed.

Lactation- excercise caution whennadministering toa nursing woman.

Children- allopurinol is rarely indicated for use in children.

Indications:

Gout, Leukemia, Lymphoma and other malignancies causing elevation of serum and urinary uric acid. Recurrent Calcium oxalate calculli.

Dosage:

Average dosage is 200 to 300mg/day for mild gout and 400 to 600mg/day for moderately severe gout. Max recommended dose is 800mg/day.

Overdosage- Symptoms/ Treatment Both alliopurinol and oxipurinol are dialyzable, however, the usefulness of hemodialysis or peritoneal dialysis in the management of allopurinol ovedose is unknown.

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.

For Availability/supplies 

Toxic epidermal necrolysis ( bullous )

 Bullous impetigo is the more severe form of of this disease. Characteristically local pyoderma precedes the sudden onset of generalized erythema, fever, and leukocytoses. Several days later large faccid bullae form and then burst, resulting in red denuded skin resembiling a burn.

The syndrome may be localised or generalized ( toxic epidermal necrolysis). Ritters syndrome , Leyelts disease or scaled skin syndrome ) .In the localised form, staphylococci can usually be recovered from the bullous lesions, while in the generalised form they usually cannot be.

Drugs causing adverse reactions- 

1. Barbiturates

2. Phenylbutazone

3. Sulfonamides

4. Phenophhthlein

5. Penicillins

6. Allopurinol

7. Iodides

8. Bromides

9. Nalidixic acid

1.Allopurinol is generally better tolerated if taken with food or milk. A fluid intake sufficient to yield of a daily output of at least 2 litres and the mainenance of a neutral or slightly alkaline urine are desirable. Drink at least 10 to 12 glasses of fluids per day.

2. May produce drowsiness, observe caution while driving or performing other tasks requiring alertness, coordination or physical dexterity.

3. Remind patients to continue drug therapy prescribed for gouty attacks since optimal benefit may be delayed for 2 to 6 weeks

4. Urinary acidification with large doses of Vitamin C may increase the possibility of kidney stone formation.

5. Tell your doctor if you have ever had any unusual allergic reaction to allupurinol given doses

6. Pregnancy- Allopurinol did not cause or birth defects in rats or rabbits given doses up to 20 times the amount given to humans.

7. Breast feeding- Mothers who are taking this medicine should discuss this with their doctor.

8. Children- This medicine has been tested in children and in efective doses , has not shown to cause different side effects or problems than it does inadults. 9. Elderly- There is no specific information copmparing use of allopurinol in the elderly with use in other age groups.

9. Other medicines- When you are taking Allopurinol, tell your doctor if you are taking anticoagulants or mercaptopurine. Some of the drugs are known to interact with allopurinol. Anticoagulants- (blood thinners) allopurinol may increase the chance of bleeding,changes in the dose of anticoagulants may be needed.

10. Other medical problems- Presence of other medical problems may affect the use of allopurinol. Make sure that you tell your doctor if you have other medical problems eg. Congestive heart disease or Diabetes mellitus or High blood pressure or Kidney disease- There is an increased risk of severe allergic reactions or other serious effects. A change of dose may be needed.

11.Take the medicine as ordered by the doctor. Dosing may be different for different patients. Follow your doctors instructions

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

13. Storage- Keep out of reach of children. Do not store in the bathroom or near the kitchen sink.Heat or moisture may cause the medicine to break down. Do not keep outdated medicines or medicines no longer needed. Make sure that the discarded medicine is out of reach of children

Pharmacology:

Allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. allopurinol is metabolised to oxipurinol (alloxanthine) which is also an inhibitor of xanthine oxidase.

Pharmacokinetics:

Allopurinol is approximately 90% absorbed from the GI tract. Peak plasma levels occur at 1.5 and 4.5 hours for allopurinol and oxipurinol respy. Allopurinol has a plasma half life of about 15 hours. Allopurinol is cleared by glomerular filtration; oxipurinol is reabsorbed in kidney tubules. Approx 20% is excreted in the feces.

Take immediately after meals

Pregnancy:

Use only when required

Lactation:

Excercise caution while administering to a nursing woman,

Children- Allopurinol is rarely indicated for use in children.