Hyperuricemia, or elevated blood levels of uric acid, is treated with allopurinol. Either primary or secondary gout can be treated with it. In severe asymptomatic hyperuricemia, it is also used. Due to a genetic enzyme deficiency, primary gout occurs. As xanthine oxidase is inhibited by allopurinol, uric acid is not produced. Chemotherapy and malignancies are the causes of secondary gout. Chemotherapeutic medicines promote cell lysis, which causes nucleic acids to break down and produce uric acid. Secondary gout is typically linked to cancers with significant cell burden, such as leukemias and lymphomas. It is also used to treat calcium oxalate calculi that come back repeatedly (when men excrete more than 800 mg of uric acid per day and women excrete more than 750 mg). Hyperuricemia brought on by the cancer treatment for leukaemia, lymphoma, or solid tumour malignancies is managed with allopurinol injection.
Allopurinol and Febuxostat:
Febuxostat |
Allopurinol |
|
General observation |
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| Mode of intake | Oral | Oral and intravenous |
| How to consume? | Intake without any regard to meals |
Consume with plenty of water after meals. Give the infusion over the course of 30 minutes. |
| Mechanism | Selective inhibitor of xanthine oxidase (both reduced and oxidized forms) | Non-selective inhibitor of xanthine oxidase inhibitor |
| Maximum daily dose | 120 mg | 800 mg |
| Adverse incident frequency | Same in both | Same in both |
Advantages of Febuxostat over Allopurinol |
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| Interaction with food | None | Better be taken after meals with water |
| Safety in kidney disease | Safe for ESRD and hemodialysis | Rrenal impairment require dose adjustments |
| Efficacy | Very effective in reducing serum uric acid levels | Less effective |
| Effect on Tophi reduction | Tophi reduced in patients receiving 80 mg of febuxostat (83%) followed by 120 mg (66%) | Only 50% of the patients on allopurinol had a reduction in tophi |
Advantages of Allopurinol over Febuxostat |
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| Uses and indications | Not recommended for treating secondary hyperuricemia | Indicates treatment for secondary hyperuricemia |
| Cardiovascular safety | Not safe in patients with cardiovascular diseases history (BOXED Warning) | Safe for patients with cardiovascular disease history |
| Gout flares [Ref] | Increase during the first year (9 – 49 weeks) | Gout flares were least obsereved during first year of the treatment. |
| Safety in liver disease | Hepatotoxicity is more common | Hepatotoxicity is less common |
| Price of one tablet in the US |
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Allopurinol Contraindications
Allopurinol should not be used in following conditions:
- Serious rash
- Renal disease
- Liver disease
- Anticoagulant therapy and bone-marrow suppression
- Driving or operating machinery
- Pregnancy
- Breast-feeding
Interactions with allopurinol
- The risk of experiencing hypersensitivity may be greater in those using ACE inhibitors.
- Patients using amoxicillin or ampicillin may be more susceptible to developing a skin rash.
- Patients receiving mercaptopurine or azathioprine should use with caution and dosage adjustment is required.
- Patients should use with caution if they are also using diuretics.
- Thiazide-treated patients may have a higher chance of developing hypersensitivity.
Allopurinol dose for Adults:
Allopurinol in acute Gout:
Note: The mobilisation of uric acid from the tissues after the start of allopurinol may result in Gout flare-ups. If flares happen, don't stop the treatment. Utilize NSAIDs and steroids and manage the flares appropriately.
Allopurinol for the chronic treatment of Gout:
-
Mildly symptomatic patient should take 200-300 mg per day
-
Severely symptomatic patients:should take 400-600 mg per day;
- To prevent acute gouty attacks, start dose at 100 mg per day and increase the dose on weekly basis
The maximum daily dose should not exceed 800 mg per day.
Alternative dosing recommendations:
- Start with taking 100 mg per day
- Dose can be increased gradually after 4 weeks while plasma uric acid levels must be monitored.
- Maximum dose of 600 to 900 mg/day may be required.
Allopurinol with chemotherapy:
- 600-800 mg per day oral tablets should be taken in 2-3 divided doses
Alternative dosing recommendations for tumor lysis syndrome:
- 10 mg/kg/day in 3 divided doses
- Start in 1-2 days before initiation of induction chemotherapy
- The dose can be continued for 3-7 days after chemotherapy
Allopurinol injection:
- Start within 1-2 days before chemotherapy with 200-400 mg/m 2/day dose (maximum: 600 mg/day)
Allopurinol dose with recurrent calcium oxalate stones:
- 200-300 mg/day orally
Allopurinol dosage in Children:
Allopurinol dose with chemotherapy:
-
For children <6 years 150 mg per day
-
For children 6-10 years 300 mg per day
-
For children >10 years must be refered to adult dosing.
Allopurinol dose for tumor lysis syndrome:
-
10 mg/kg/day in 3 divided doses
-
50-100 mg/m 2 every 8 hours
- Start the therapy 1-2 days before the induction chemotherapy.
- Treatment can be continued for 3-7 days after chemotherapy.
Allopurinol injection for Intravenous administration:
-
Starting dose: 200 mg/m 2 /day (before chemotherapy)
-
200-400 mg/m 2 /day in 1-3 divided doses
- Treatment continued for 3-7 days after chemotherapy
Allopurinol dose in Renal disease:
Lower doses are required because of the possibility of accumulation of allopurinol and metabolites.
-
200 mg per day for CrCl of 10-20 mL/minute
-
Less than 100 mg per day for CrCl of 3 - 10 mL/minut
-
100 mg per dose for CrCl of 10-20 mL/minute at extended intervals
Allopurinol dose in Gout:
Start the therapy with 50-100 mg daily, increase the dose slowly to achieve a serum uric acid level of ≤6 mg/dL
Allopurinol dose in patients with Hemodialysis:
- On post-dialysis alternate days start with 100mg intake
- Increase the dose gradually by 300 mg accordingly to the response.
- In case of daily dialysis, an additional 50% of the dose is required
Dose in Liver disease:
- Take initial dose of 100 mg once daily and gradually increase the dose.
- Liver function tests must be monitored frequently
How to administer Allopurinol?
- Consume after meals.
- Take plenty of water
- Avoid treatment during the acute flares of gouty arthritis.
Allopurinol Injection:
- Infuse a maximum of 600 mg per day over a period of 30 minutes or longer.
- The commencement of therapy should occur 24 to 48 hours prior to the beginning of chemotherapy that triggers tumour lysis.
Pregnancy Risk Factor C
- Allopurinol should only be used during pregnancy.
- Breastfeeding mothers should use it with caution
Side effects of Allopurinol:
- Gastrointestinal disorders
- Blood disorders
- Alopecia
- Stevens-Johnson syndrome & toxic epidermal necrolysis,
- Aplastic anemia
- Thrombocytopenia
- Rashes
- Visual disturbances
- Seizures.
- Arthralgia
- Drowsiness
- Vertigo
- Eosinophilia
- Taste disturbances
- Fever
- Headache
- Vasculitis
- Gynaecomastia
- Exfoliation
- Renal impairment
- Hypertension
- Malaise
- Hepatitis
- Neuropathy
- Paraesthesia
- Hemolytic anemia
- Lymphadenopathy
- Hepatotoxicity
- Leucopenia
- Hypersensitivity reactions
Monitoring Parameters:
- CBC
- Hypersensitivity
- Serum uric acid levels
- Renal function
- Hepatic function
- Input and output
Allopurinol mechanism of action:
- Allopurinol inhibits xanthine oxide, which is responsible for the conversion from hypoxanthine into xanthine and uric acids.
- This reduces the production of uric Acid without disrupting the biosynthesis vital purines.
The Peak effect of the drug is seen in 1-2 weeks About 80% of the drug is absorbed when taken via the oral route. Less than 1% of the drug is bound to proteins.
It is metabolized to active metabolites (75%), chiefly oxypurinol.
Bioavailability is 49% to 53%
Half-life elimination of the drug:
- Normal renal function:
- Parent drug: 1-3 hours;
- Oxypurinol: 18-30 hours
- End-stage renal disease:
- Prolonged
The time to reach the peak plasma concentration after oral administration is 30-120 minutes.
Excretion is primarily via Urine (76% as oxypurinol, 12% as unchanged drug)
Allopurinol and oxypurinol are dialyzable
Allopurinol brand names (International):
- Adenock
- AL
- Alinol
- Allo
- Allo-Puren
- Allogut
- Allohexal
- Allopin
- Alloprim
- Allopur
- Allopurinol-ratiopharm
- Alloric
- Alloril
- Allosig
- Allozym
- Allpargin
- Allurase
- Allurit
- Alopron
- Alopurinol
- Alositol
- Alpurase
- Alpuric
- Alpurin
- Alurin
- Aluron
- Anoprolin
- Anzief
- Aprinol
- Apronal
- Apurin
- Atisuril
- Benoxuric
- Bleminal
- Caplenal
- Cellidrin
- Clint
- Etindrax
- Foligan
- Genozyl
- Gichtex
- Goutilex
- Hamarin
- Hexanurat
- Huma-Purol
- Isoric
- Ketanrift
- Ketobun-A
- Litinol
- Llanol
- Masaton
- Mephanol
- Milurit
- Miniplanor
- Neufan
- Nilapur
- Nipurol
- No-Uric
- Nor-Purinol
- Pritanol
- Progout
- Proxuric
- Puribel 300
- Puricemia
- Puricos
- Purinol
- Remid
- Riball
- Ridonra
- Rinolic
- Ripunin
- Salterprim
- Sinoric
- Takanarumin
- Tylonic
- Unizuric 300
- Uric
- Uricad
- Uriconorm
- Urinol
- Urocuad
- Urogquad
- Uroquad
- Urosin
- Valeric
- Xandase
- Xanol
- Xanurace
- Zylapour
- Zyloprim
- Zyloric
- Zyngot
- Zyroric
Allopurinol Brands in Pakistan:
ZYLORIC (GLAXOSMITHKLINE)
Tablets : 300 mg :
30 tablets pack : Rs. 139.00
Tablets : 100 mg :
50 tablets pack : Rs. 80.72
ZYRIN (HELICON PHARMACEUTEK PAKISTAN (PVT) LTD)
Tablets : 100 mg :
50 tablets pack : Rs. 66
AGOUT (MEGA PHARMACEUTICALS (PVT) LTD)
Tablets : 300 mg :
20 tablets pack : Rs. 70.00
ALLOPURE (ZEB LABORATORIES)
Tablets : 300 mg :
20 tablets pack : Rs. 70.00
URIK (RAAZEE THERAPUTICS (PVT) LTD)
Tablets : 300 mg :
30 tablets pack : Rs. 98.00
ZYLOR (HELICON PHARMACEUTEK PAKISTAN (PVT) LTD)
Tablets : 300 mg :
20 tablets pack : Rs. 70.00
ZYNOL (PHARMEDIC (PVT) LTD)
Tablets : 300 mg :
20 tablets pack : Rs. 77.00
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