Drug Information

   


    










 


Pharmacokinetics

 


Absorption of melphalan from the gastrointestinal tract is
variable; the mean bioavailability is reported to be 56% but it
may range from 25 to 89%. Absorption is reduced by the presence of
food. Following absorption it is rapidly distributed throughout
body water with a volume of distribution of about 0.5 litres per
kg body-weight, and has been reported to be inactivated mainly by
spontaneous hydrolysis. The terminal plasma half-life of melphalan
has been reported to be of the order of 40 to 140 minutes.
Melphalan is excreted in the urine, about 10% as unchanged drug.
About 50 to 60% of an absorbed dose has been stated to be protein
bound initially, increasing to 80 to 90% after 12 hours.

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Indication
& Dosage


 


Oral

MULTIPLE MYELOMA:
Several regimens have been recommended.
One regimen is start 6mg/day as a single dose daily, adjusted
according to weekly blood counts. After 2-3 weeks discontinue for
4 weeks and start maintenance dose at 2mg/kg

ADVANCED OVARIAN CANCER: 0.2mg/kg
daily for 5 days. This course can be repeated every 4-5 weeks.



IV

MYELOMAS, SOLID TUMORS, LYMPHOMAS:
16mg/m2 as an IV
infusion over 15-20 mins. Repeat at 2 week intervals for 4 doses
followed by 4-week intervals.

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Action

 


An alkylating agent active against some malignancies. It is active
against both resting and rapidly dividing cells. 

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Interactions

 


Concomitant
administration of nalidixic acid with high-dose intravenous
melphalan in children has resulted in fatal haemorrhagic
enterocolitis.



With Food

The bioavailability of oral melphalan is significantly reduced, by
up to 45%, by concomitant administration with food. Some recommend
that melphalan should not be taken with food, and that if
administration is switched from after to before food patients
should be monitored for increased toxicity.

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Adverse
Effect & Precaution


 

The onset of
neutropenia and thrombocytopenia is variable; bone-marrow
depression has been reported 2 to 3 weeks after starting treatment
with melphalan, with a nadir at 3 to 5 weeks, but has also
occurred after only 5 days. Recovery may be prolonged.

Skin rashes
and hypersensitivity reactions, including anaphylaxis, may occur.
Cardiac arrest has been reported in association with such effects.
Gastrointestinal disturbances may sometimes occur, particularly at
high doses where diarrhoea, vomiting, and stomatitis may become
dose-limiting. Haemolytic anaemia, vasculitis, and pulmonary
fibrosis have been reported. Suppression of ovarian function is
common in premenopausal women; temporary or permanent sterility
may occur in male patients. As with other alkylating agents,
melphalan also has carcinogenic, mutagenic, and teratogenic
potential.



Care is required in patients with impaired renal function. The
dose of the intravenous preparation should be reduced by 50% in
patients with moderate to severe renal impairment and dosage
reduction should be considered when administering melphalan by
mouth. High dose regimens are not recommended in patients with
severe renal impairment.

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Drug Information
   

    

 
Pharmacokinetics
 

Absorption of melphalan from the gastrointestinal tract is variable; the mean bioavailability is reported to be 56% but it may range from 25 to 89%. Absorption is reduced by the presence of food. Following absorption it is rapidly distributed throughout body water with a volume of distribution of about 0.5 litres per kg body-weight, and has been reported to be inactivated mainly by spontaneous hydrolysis. The terminal plasma half-life of melphalan has been reported to be of the order of 40 to 140 minutes. Melphalan is excreted in the urine, about 10% as unchanged drug. About 50 to 60% of an absorbed dose has been stated to be protein bound initially, increasing to 80 to 90% after 12 hours.

TOP
  

Indication & Dosage
 

Oral
MULTIPLE MYELOMA:
Several regimens have been recommended. One regimen is start 6mg/day as a single dose daily, adjusted according to weekly blood counts. After 2-3 weeks discontinue for 4 weeks and start maintenance dose at 2mg/kg
ADVANCED OVARIAN CANCER: 0.2mg/kg daily for 5 days. This course can be repeated every 4-5 weeks.

IV
MYELOMAS, SOLID TUMORS, LYMPHOMAS:
16mg/m2 as an IV infusion over 15-20 mins. Repeat at 2 week intervals for 4 doses followed by 4-week intervals.

TOP
  

Action
 

An alkylating agent active against some malignancies. It is active against both resting and rapidly dividing cells. 

TOP
 

Interactions
 

Concomitant administration of nalidixic acid with high-dose intravenous melphalan in children has resulted in fatal haemorrhagic enterocolitis.

With Food
The bioavailability of oral melphalan is significantly reduced, by up to 45%, by concomitant administration with food. Some recommend that melphalan should not be taken with food, and that if administration is switched from after to before food patients should be monitored for increased toxicity.

TOP
    

Adverse Effect & Precaution
 
The onset of neutropenia and thrombocytopenia is variable; bone-marrow depression has been reported 2 to 3 weeks after starting treatment with melphalan, with a nadir at 3 to 5 weeks, but has also occurred after only 5 days. Recovery may be prolonged.
Skin rashes and hypersensitivity reactions, including anaphylaxis, may occur. Cardiac arrest has been reported in association with such effects. Gastrointestinal disturbances may sometimes occur, particularly at high doses where diarrhoea, vomiting, and stomatitis may become dose-limiting. Haemolytic anaemia, vasculitis, and pulmonary fibrosis have been reported. Suppression of ovarian function is common in premenopausal women; temporary or permanent sterility may occur in male patients. As with other alkylating agents, melphalan also has carcinogenic, mutagenic, and teratogenic potential.

Care is required in patients with impaired renal function. The dose of the intravenous preparation should be reduced by 50% in patients with moderate to severe renal impairment and dosage reduction should be considered when administering melphalan by mouth. High dose regimens are not recommended in patients with severe renal impairment.

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By |2022-07-20T16:41:41+00:00July 20, 2022|Uncategorized|Comments Off on Melphanlan

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