Melphalan 2 mg, 5 mg Tabl ets SMPC, Taj Phar mace uticals

MELPHALA N Taj Phar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, MELP HALAN Dosage & Rx I nfo | MELPHA LAN Us es, Side E ffe ct s -: I ndi cations, Side Effects, Warnings , MELPHAL AN - Drug Infor mation - Taj Phar ma, MELP HALAN dose Taj pharma ceuti cals MELPHALAN i nteractions, Taj Pha rmace utical MELPHALAN contraindications, ME LPHALA N price, ME LPHA LAN Taj Phar ma Cancer, oncologyMelphalan 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on ME LPHA LAN Taj Phar maceuticals Taj pharma ceuti cals Hydera bad.

RX that potentially therapeutic levels have been

reached.
MELPHALAN TABLET
Multiple Myleloma:
2 MG, 5 MG
Numerous regimes have been used and the
1. NAME OF THE MEDICINAL scientific literature should be consulted for
PRODUCT details. The administration of Melphalan and
Melphalan 2 mg, 5 mg Tablets prednisone is more effective than Melphalan
alone. The combination is usually given on
2. QUALITATIVE AND an intermittent basis, although the
QUANTITATIVE COMPOSITION superiority of this technique over continuous
Each tablet contains 2 mg melphalan. therapy is not established. A typical oral
Each tablet contains 5 mg melphalan. dosage schedule is 0.15 mg/kg
3. PHARMACEUTICAL FORM bodyweight/day in divided doses for 4 days
Film-coated tablets repeated at intervals of six weeks.
Prolonging treatment beyond one year in
MELPHALAN are white to off-white film- responders does not appear to improve
coated, round, biconvex tablets. results.
4. CLINICAL PARTICULARS Ovarian adenocarcinoma:
4.1 Therapeutic indications A typical regimen is 0.2 mg/kg
Melphalan Tablets are indicated in the bodyweight/day orally for 5 days. This is
treatment of multiple myeloma and repeated every 4-8 weeks, or as soon as the
advanced ovarian adenocarcinoma. bone marrow has recovered. Melphalan has
Melphalan either alone or in combination also been used intravenously in the
with other drugs has a significant therapeutic treatment of ovarian carcinoma.
effect in a proportion of patients suffering Advanced carcinoma of the breast:
from advanced breast carcinoma.
Melphalan has been given orally at a dose of
Melphalan is effective in the treatment of a 0.15 mg/kg bodyweight or 6 mg/m2 body
proportion of patients suffering from surface area/day for 5 days and repeated
polycythaemia vera. every 6 weeks. The dose was decreased if
4.2 Posology and method of bone marrow toxicity was observed.
administration Polycythaemia vera:
Posology For remission induction the usual dose is 6-
Since Melphalan is myelosuppressive, 10 mg daily for 5-7 days, after which 2-4 mg
frequent blood counts are essential during daily is given until satisfactory disease
therapy and the dosage should be delayed or control is achieved. Therapy is maintained
adjusted if necessary (see Special Warnings with a dose of 2-6 mg per week. During
and Precautions for Use). maintenance therapy, careful haematological
Oral administration in Adults: The control is essential with dosage adjustment
absorption of Melphalan after oral according to the results of frequent blood
administration is variable. Dosage may need counts.
to be cautiously increased until Children:
myelosuppresion is seen, in order to ensure
Melphalan 2 mg, 5 mg Tabl ets SMPC, Taj Phar mace uticals
MELPHALA N Taj Phar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, MELP HALAN Dosage & Rx I nfo | MELPHA LAN Us es, Side E ffe ct s -: I ndi cations, Side Effects, Warnings , MELPHAL AN - Drug Infor mation - Taj Phar ma, MELP HALAN dose Taj pharma ceuti cals MELPHALAN i nteractions, Taj Pha rmace utical MELPHALAN contraindications, ME LPHALA N price, ME LPHA LAN Taj Phar ma Cancer, oncologyMelphalan 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on ME LPHA LAN Taj Phar maceuticals Taj pharma ceuti cals Hydera bad.

Melphalan is very rarely indicated in platelet counts, treatment should be

children and dosage guidelines cannot be temporarily interrupted. Melphalan should
stated. be used with caution in patients who have
undergone recent radiotherapy or
Use in the elderly:
chemotherapy in view of increased bone
There is no specific information available on marrow toxicity.
the use of Melphalan in elderly patients.
Renal impairment:
Dosage in renal impairment:
Patients with renal impairment should be
In patients with moderate to severe renal closely observed as they may have uraemic
impairment currently available marrow suppression. (See undesirable
pharmacokinetic data do not justify an effects for elevation of blood urea Section
absolute recommendation on dosage 4.8)
reduction when administering the oral
Mutagenicity:
preparation to these patients, but it may be
prudent to use a reduced dose initially. Melphalan is mutagenic in animals and
chromosome aberrations have been observed
in patients being treated with the drug.
4.3 Contraindications
Melphalan should not be given to patients Carcinogenicity:
who have suffered a previous
The evidence is growing that melphalan in
hypersensitivity reaction to melphalan.
common with other alkylating agents has
been reported to be leukaemogenic. There
4.4 Special Warnings and precautions for have been reports of acute leukaemia
use occurring after melphalan treatment for
diseases such as amyloid, malignant
Melphalan is an active cytotoxic agent for
melanoma, macroglobulinaemia, cold
use only under the direction of physicians
agglutinin syndrome and ovarian cancer.
experienced in the administration of such
agents. A comparison of patients with ovarian
cancer who received alkylating agents with
Immunisation using a live organism vaccine
those who did not, showed that the use of
has the potential to cause infection in
alkylating agents, including melphalan,
immunocompromised hosts. Therefore,
significantly increased the incidence of
immunisations with live organism vaccines
acute leukaemia. The leukaemogenic risk
are not recommended.
must be balanced against the potential
Monitoring: therapeutic benefit when considering the use
of melphalan.
Since Melphalan is a potent
myelosuppresive agent, it is essential that Melphalan causes suppression of ovarian
careful attention should be paid to the function in premenopausal women resulting
monitoring of blood counts to avoid the in amenorrhoea in a significant number of
possibility of excessive myelosuppression patients.
and the risk of irreversible bone marrow
aplasia. Blood counts may continue to fall
after treatment is stopped, so at the first sign
of an abnormally large fall in leucocyte or
Melphalan 2 mg, 5 mg Tabl ets SMPC, Taj Phar mace uticals
MELPHALA N Taj Phar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, MELP HALAN Dosage & Rx I nfo | MELPHA LAN Us es, Side E ffe ct s -: I ndi cations, Side Effects, Warnings , MELPHAL AN - Drug Infor mation - Taj Phar ma, MELP HALAN dose Taj pharma ceuti cals MELPHALAN i nteractions, Taj Pha rmace utical MELPHALAN contraindications, ME LPHALA N price, ME LPHA LAN Taj Phar ma Cancer, oncologyMelphalan 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on ME LPHA LAN Taj Phar maceuticals Taj pharma ceuti cals Hydera bad.

4.5 Interaction with other medicinal 4.7 Effects on ability to drive and use
products and other forms of interaction machines
Not known.
Vaccinations with live organism vaccines
are not recommended in 4.8 Undesirable Effects
immunocompromised individuals (see For this product there is no modern clinical
Warnings and Precautions). documentation which can be used as support
for determining the frequency of undesirable
Nalidixic acid together with high-dose
effects. Undesirable effects may vary in
intravenous melphalan has caused deaths in
their incidence depending on the indication
children due to haemorrhagic enterocolitis.
and dose received and also when given in
Impaired renal function has been described combination with other therapeutic agents.
in bone marrow transplant patients who
The following convention has been utilised
were pre-conditioned with high dose
for the classification of frequency:- Very
intravenous melphalan and who
common ≥1/10, common ≥1/100, <1/10,
subsequently received ciclosporin to prevent
uncommon ≥1/1000 and <1/100, rare
graft-versus-host disease.
≥1/10,000 and <1/1000, very rare
4.6 Pregnancy and lactation <1/10,000.
As with all cytotoxic chemotherapy,
adequate contraceptive precautions should Blood and Lymphatic System Disorders
be advised when either partner is receiving
Melphalan.
Very bone marrow depression leading to
Teratogenicity: common: leucopenia, thrombocytopenia and
anaemia
The teratogenic potential of Melphalan has
Rare: haemolytic anaemia
not been studied. In view of its mutagenic
properties and structural similarity to known
teratogenic compounds, it is possible that Immune System Disorders
melphalan could cause congenital defects in
the offspring of patients treated with the
Rare: allergic reactions (see Skin and
drug.
Subcutaneous Tissue Disorders)
Pregnancy:
The use of melphalan should be avoided Allergic reactions to melphalan such as
whenever possible during pregnancy, urticaria, oedema, skin rashes and
particularly during the first trimester. In any anaphylactic shock have been reported
individual case the potential hazard to the uncommonly following initial or subsequent
foetus must be balanced against the expected dosing, particularly after intravenous
benefit to the mother. administration. Cardiac arrest has also been
Lactation: reported rarely in association with such
events.
Mother receiving Melphalan should not
breast-feed.
Melphalan 2 mg, 5 mg Tabl ets SMPC, Taj Phar mace uticals
MELPHALA N Taj Phar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, MELP HALAN Dosage & Rx I nfo | MELPHA LAN Us es, Side E ffe ct s -: I ndi cations, Side Effects, Warnings , MELPHAL AN - Drug Infor mation - Taj Phar ma, MELP HALAN dose Taj pharma ceuti cals MELPHALAN i nteractions, Taj Pha rmace utical MELPHALAN contraindications, ME LPHALA N price, ME LPHA LAN Taj Phar ma Cancer, oncologyMelphalan 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on ME LPHA LAN Taj Phar maceuticals Taj pharma ceuti cals Hydera bad.

Respiratory, Thoracic and Mediastinal Disorders There is no specific antidote. The blood
picture should be closely monitored for at
Gastrointestinal Disorders least four weeks following overdosage until
Very nausea, vomiting and diarrhoea; there is evidence of recovery.
common: stomatitis at high dose General supportive measures, together with
Rare: stomatitis at conventional dose appropriate blood transfusion, should be
instituted if necessary.
Gastrointestinal effects such as nausea and
vomiting have been reported in up to 30% of 5. PHARMACOLOGICAL
patients receiving conventional oral doses of PROPERTIES
melphalan.
5.1 Pharmacodynamic properties
Hepatobiliary Disorders
Rare: hepatic disorders ranging from Melphalan is a bifunctional alkylating agent.
abnormal liver function tests to Formation of carbonium intermediates from
clinical manifestations such as each of the two bis-2-chlorethyl groups
hepatitis and jaundice enables alkylation through covalent binding
Skin and Subcutaneous Tissue Disorders with the 7-nitrogen of guanine on DNA,
cross-linking two DNA strands and thereby
Very alopecia at high dose preventing cell replication.
common:
Common: alopecia at conventional dose 5.2 Pharmacokinetic properties
Absorption
Rare: maculopapular rashes and pruritus
(see Immune System Disorders) The absorption of oral melphalan is highly
Renal and Urinary Disorders variable with respect to both the time to first
appearance of the drug in plasma and peak
Common: temporary significant elevation of the plasma concentration.
blood urea has been seen in the early
stages of melphalan therapy in In studies of the absolute bioavailability of
myeloma patients with renal damage melphalan the mean absolute bioavailability
ranged from 56 to 85%.
Intravenous administration can be used to
4.9 Overdose
avoid variability in absorption associated
with myeloablative treatment.
Symptoms and signs:
In a study of 18 patients administered
Gastro-intestinal effects, including nausea,
melphalan 0.2 to 0.25 mg/kg bodyweight
vomiting and diarrhoea are the most likely
orally, a maximum plasma concentration
signs of acute oral overdosage. Diarrhoea,
(range 87 to 350 nanograms/ml) was
sometimes haemorrhagic, has been reported
reached within 0.5 to 2.0 h.
after intravenous overdosage. The principal
toxic effect is bone marrow aplasia, leading The administration of melphalan tablets
to leucopoenia, thrombocytopenia and immediately after food delayed the time to
anaemia. achieving peak plasma concentrations and
reduced the area under the plasma
Treatment:
concentration-time curves by between 39
and 45%.
Melphalan 2 mg, 5 mg Tabl ets SMPC, Taj Phar mace uticals
MELPHALA N Taj Phar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, MELP HALAN Dosage & Rx I nfo | MELPHA LAN Us es, Side E ffe ct s -: I ndi cations, Side Effects, Warnings , MELPHAL AN - Drug Infor mation - Taj Phar ma, MELP HALAN dose Taj pharma ceuti cals MELPHALAN i nteractions, Taj Pha rmace utical MELPHALAN contraindications, ME LPHALA N price, ME LPHA LAN Taj Phar ma Cancer, oncologyMelphalan 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on ME LPHA LAN Taj Phar maceuticals Taj pharma ceuti cals Hydera bad.

Distribution Colloidal anhydrous silica

Magnesium stearate
Melphalan displays limited penetration of
the blood-brain barrier. Several investigators Tablet Film Coating:
have sampled cerebrospinal fluid and found Hypromellose
no measurable drug. Low concentrations Titanium dioxide
(~10% of that in plasma) were observed in a Macrogol
single high-dose study in children.
6.2 Incompatibilities
Elimination
None known
In 13 patients given oral melphalan at 0.6
mg/kg bodyweight, the plasma mean 6.3 Shelf life
terminal elimination half-life was 90 ± 57
min with 11% of the drug being recovered in 24 months
the urine over 24 h.
6.4 Special precautions for storage
In 18 patients administered melphalan 0.2 to
0.25 mg/kg bodyweight orally, the mean
Store at 2°C to 8°C.
elimination half-life was 1.12 ± 0.15 h.
6.5Nature and contents of container
Special Patient Populations
• Renal impairment Supplied in amber glass bottles with a child
resistant closure containing 25 or 50 tablets.
Melphalan clearance may be decreased in
renal impairment (see Dosage and
6.6 Special precautions for disposal and
Administration - Renal impairment and
other handling
Warnings and Precautions - Renal
impairment).
Safe handling of MELPHALAN tablets:
• Elderly
The handling of Melphalan tablets should
No correlation has been shown between age follow guidelines for the handling of
and melphalan clearance or with melphalan cytotoxic drugs according to prevailing local
terminal elimination half-life (see Dosage recommendations and/or regulations (for
and Administration). example Royal Pharmaceutical Society of
Great Britain Working Party on the
5.3 Preclinical safety data Handling of Cytotoxic Drugs).
There are no preclinical data of relevance to Provided the outer coating of the tablet is
the prescriber, which are additional to that in intact, there is no risk in handling Melphalan
other sections of the SmPC. tablets.
6. PHARMACEUTICAL Melphalan tablets should not be divided.
PARTICULARS
Disposal:
6.1 List of excipients Melphalan tablets should be destroyed in
accordance with relevant local regulatory
Tablet Core: requirements concerning the disposal of
Microcrystalline cellulose cytotoxic drugs.
Crospovidone
Melphalan 2 mg, 5 mg Tabl ets SMPC, Taj Phar mace uticals
MELPHALA N Taj Phar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, MELP HALAN Dosage & Rx I nfo | MELPHA LAN Us es, Side E ffe ct s -: I ndi cations, Side Effects, Warnings , MELPHAL AN - Drug Infor mation - Taj Phar ma, MELP HALAN dose Taj pharma ceuti cals MELPHALAN i nteractions, Taj Pha rmace utical MELPHALAN contraindications, ME LPHALA N price, ME LPHA LAN Taj Phar ma Cancer, oncologyMelphalan 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on ME LPHA LAN Taj Phar maceuticals Taj pharma ceuti cals Hydera bad.

7. MANUFACTURER:

Manufactured in India by:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Survey No.188/1 to 189/1,190/1 to 4,
Athiyawad, Dabhel,
Daman- 396210 (INDIA)