Melphalan

Dosage Form: injection
Melphalan Hydrochloride for Injection

WARNING

Melphalan should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Severe bone marrow suppression with resulting infection or bleeding may occur. Controlled trials comparing intravenous (IV) to oral Melphalan have shown more myelosuppression with the IV formulation. Hypersensitivity reactions, including anaphylaxis, have occured in approximately 2% of patients who received the IV formulation. Melphalan is leukemogenic in humans. Melphalan produces chromosomal aberrations in vitro and in vivo and, therefore, should be considered potentially mutagenic in humans.

Melphalan Description

Melphalan, also known as L-phenylalanine mustard, phenylalanine mustard, L-PAM, or L-sarcolysin, is a phenylalanine derivative of nitrogen mustard. Melphalan is a bifunctional alkylating agent that is active against selected human neoplastic diseases. It is known chemically as 4-[bis(2-chloroethyl)amino]-L-phenylalanine. The molecular formula is C13H18Cl2N2O2 and the molecular weight is 305.20. The structural formula is:

Melphalan is the active L-isomer of the compound and was first synthesized in 1953 by Bergel and Stock; the D-isomer, known as medphalan, is less active against certain animal tumors, and the dose needed to produce effects on chromosomes is larger than that required with the L-isomer. The racemic (DL-) form is known as merphalan or sarcolysin.

Melphalan is practically insoluble in water and has a pKa1 of~2.5.

Melphalan Hydrochloride for Injection is supplied as a sterile, nonpyrogenic, freeze-dried powder. Each single-use vial contains Melphalan hydrochloride equivalent to 50 mg Melphalan and the inactive ingredient povidone 20 mg. Melphalan Hydrochloride for Injection is reconstituted using the sterile diluent provided. Each vial of sterile diluent contains sodium citrate 0.2 g, propylene glycol 6.0 mL, ethanol (96%) 0.52 mL, and Water for Injection to a total of 10 mL. Melphalan Hydrochloride for Injection is administered intravenously.

Melphalan - Clinical Pharmacology

Melphalan is an alkylating agent of the bischloroethylamine type. As a result, its cytotoxicity appears to be related to the extent of its interstrand cross-linking with DNA, probably by binding at the N7 position of guanine. Like other bifunctional alkylating agents, it is active against both resting and rapidly dividing tumor cells.

Pharmacokinetics

The pharmacokinetics of Melphalan after IV administration has been extensively studied in adult patients. Following injection, drug plasma concentrations declined rapidly in a biexponential manner with distribution phase and terminal elimination phase half-lives of approximately 10 and 75 minutes, respectively. Estimates of average total body clearance varied among studies, but typical values of approximately 7 to 9 mL/min/kg (250 to 325 mL/min/m2) were observed. One study has reported that on repeat dosing of 0.5 mg/kg every 6 weeks, the clearance of Melphalan decreased from 8.1 mL/min/kg after the first course, to 5.5 mL/min/kg after the third course, but did not decrease appreciably after the third course. Mean (±SD) peak Melphalan plasma concentrations in myeloma patients given IV Melphalan at doses of 10 or 20 mg/m2 were 1.2 ± 0.4 and 2.8 ± 1.9 mcg/mL, respectively.

The steady-state volume of distribution of Melphalan is 0.5 L/kg. Penetration into cerebrospinal fluid (CSF) is low. The extent of Melphalan binding to plasma proteins ranges from 60% to 90%. Serum albumin is the major binding protein, while α 1-acid glycoprotein appears to account for about 20% of the plasma protein binding. Approximately 30% of the drug is (covalently) irreversibly bound to plasma proteins. Interactions with immunoglobulins have been found to be negligible.

Melphalan is eliminated from plasma primarily by chemical hydrolysis to monohydroxyMelphalan and dihydroxyMelphalan. Aside from these hydrolysis products, no other Melphalan metabolites have been observed in humans. Although the contribution of renal elimination to Melphalan clearance appears to be low, one study noted an increase in the occurrence of severe leukopenia in patients with elevated BUN after 10 weeks of therapy.

CLINICAL TRIAL

A randomized trial compared prednisone plus IV Melphalan to prednisone plus oral Melphalan in the treatment of myeloma. As discussed below, overall response rates at week 22 were comparable; however, because of changes in trial design, conclusions as to the relative activity of the 2 formulations after week 22 are impossible to make.

Both arms received oral prednisone starting at 0.8 mg/kg/day with doses tapered over 6 weeks. Melphalan doses in each arm were:

Arm 1 Oral Melphalan 0.15 mg/kg/day × 7 followed by 0.05 mg/kg/day when WBC began to rise.

Arm 2 IV Melphalan 16 mg/m2 q 2 weeks × 4 (over 6 weeks) followed by the same dose every 4 weeks.

Doses of Melphalan were adjusted according to the following criteria:

Table 1. Criteria for Dosage Adjustment in a Randomized Clinical Trial

WBC/mm3	Platelets	Percent of Full Dose
≥4,000	≥100,000	100
≥3,000	≥75,000	75
≥2,000	≥50,000	50
<2,000	<50,000	0

One hundred seven patients were randomized to the oral Melphalan arm and 203 patients to the IV Melphalan arm. More patients had a poor-risk classification (58% versus 44%) and high tumor load (51% versus 34%) on the oral compared to the IV arm (P<0.04).

Response rates at week 22 are shown in the following table:

Table 2. Response Rates at Week 22

Initial Arm	Evaluable Patients	Responders n (%)	P
Oral Melphalan	100	44 (44%)	P>0.2
IV Melphalan	195	74 (38%)

Because of changes in protocol design after week 22, other efficacy parameters such as response duration and survival cannot be compared.

Severe myelotoxicity (WBC ≤1,000 and/or platelets ≤25,000) was more common in the IV Melphalan arm (28%) than in the oral Melphalan arm (11%).

An association was noted between poor renal function and myelosuppression; consequently, an amendment to the protocol required a 50% reduction in IV Melphalan dose if the BUN was ≥30 mg/dL. The rate of severe leukopenia in the IV arm in the patients with BUN over 30 mg/dL decreased from 50% (8/16) before protocol amendment to 11% (3/28) (P = 0.01) after the amendment.

Before the dosing amendment, there was a 10% (8/77) incidence of drug-related death in the IV arm. After the dosing amendment, this incidence was 3% (3/108). This compares to an overall 1% (1/100) incidence of drug-related death in the oral arm.

Indications and Usage for Melphalan

Melphalan Hydrochloride for Injection is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.

Contraindications

Melphalan should not be used in patients whose disease has demonstrated prior resistance to this agent. Patients who have demonstrated hypersensitivity to Melphalan should not be given the drug.

Warnings

Melphalan Hydrochloride for Injection may cause local tissue damage should extravasation occur, and consequently it should not be administered by direct injection into a peripheral vein. It is recommended that Melphalan Hydrochloride for Injection be administered by injecting slowly into a fast-running IV infusion via an injection port, or via a central venous line (see DOSAGE AND ADMINISTRATION: Administration Precautions).

Melphalan should be administered in carefully adjusted dosage by or under the supervision of experienced physicians who are familiar with the drug's actions and the possible complications of its use.

As with other nitrogen mustard drugs, excessive dosage will produce marked bone marrow suppression. Bone marrow suppression is the most significant toxicity associated with Melphalan Hydrochloride for Injection in most patients. Therefore, the following tests should be performed at the start of therapy and prior to each subsequent dose of Melphalan Hydrochloride: platelet count, hemoglobin, white blood cell count, and differential. Thrombocytopenia and/or leukopenia are indications to withhold further therapy until the blood counts have sufficiently recovered. Frequent blood counts are essential to determine optimal dosage and to avoid toxicity. Dose adjustment on the basis of blood counts at the nadir and day of treatment should be considered.

Hypersensitivity reactions including anaphylaxis have occurred in approximately 2% of patients who received the IV formulation (see ADVERSE REACTIONS). These reactions usually occur after multiple courses of treatment. Treatment is symptomatic. The infusion should be terminated immediately, followed by the administration of volume expanders, pressor agents, corticosteroids, or antihistamines at the discretion of the physician. If a hypersensitivity reaction occurs, IV or oral Melphalan should not be readministered since hypersensitivity reactions have also been reported with oral Melphalan.

Carcinogenesis

Secondary malignancies, including acute nonlymphocytic leukemia, myeloproliferative syndrome, and carcinoma, have been reported in patients with cancer treated with alkylating agents (including Melphalan). Some patients also received other chemotherapeutic agents or radiation therapy. Precise quantitation of the risk of acute leukemia, myeloproliferative syndrome, or carcinoma is not possible. Published reports of leukemia in patients who have received Melphalan (and other alkylating agents) suggest that the risk of leukemogenesis increases with chronicity of treatment and with cumulative dose. In one study, the 10-year cumulative risk of developing acute leukemia or myeloproliferative syndrome after oral Melphalan therapy was 19.5% for cumulative doses ranging from 730 to 9,652 mg. In this same study, as well as in an additional study, the 10-year cumulative risk of developing acute leukemia or myeloproliferative syndrome after oral Melphalan therapy was less than 2% for cumulative doses under 600 mg. This does not mean that there is a cumulative dose below which there is no risk of the induction of secondary malignancy. The potential benefits from Melphalan therapy must be weighed on an individual basis against the possible risk of the induction of a second malignancy.

Adequate and well-controlled carcinogenicity studies have not been conducted in animals. However, intraperitoneal (IP) administration of Melphalan in rats (5.4 to 10.8 mg/m2) and in mice (2.25 to 4.5 mg/m2) 3 times per week for 6 months followed by 12 months post-dose observation produced peritoneal sarcoma and lung tumors, respectively.

Mutagenesis

Melphalan has been shown to cause chromatid or chromosome damage in humans. Intramuscular administration of Melphalan at 6 and 60 mg/m2 produced structural aberrations of the chromatid and chromosomes in bone marrow cells of Wistar rats.

Impairment of Fertility

Melphalan causes suppression of ovarian function in premenopausal women, resulting in amenorrhea in a significant number of patients. Reversible and irreversible testicular suppression have also been reported.

Pregnancy

Pregnancy Category D

Melphalan may cause fetal harm when administered to a pregnant woman. While adequate animal studies have not been conducted with IV Melphalan, oral (6 to 18 mg/m2/day for 10 days) and IP (18 mg/m2) administration in rats was embryolethal and teratogenic. Malformations resulting from Melphalan included alterations of the brain (underdevelopment, deformation, meningocele, and encephalocele) and eye (anophthalmia and microphthalmos), reduction of the mandible and tail, as well as hepatocele (exomphaly). There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.

Precautions

General

In all instances where the use of Melphalan Hydrochloride for Injection is considered for chemotherapy, the physician must evaluate the need and usefulness of the drug against the risk of adverse events. Melphalan should be used with extreme caution in patients whose bone marrow reserve may have been compromised by prior irradiation or chemotherapy or whose marrow function is recovering from previous cytotoxic therapy.

Dose reduction should be considered in patients with renal insufficiency receiving IV Melphalan. In one trial, increased bone marrow suppression was observed in patients with BUN levels ≥30 mg/dL. A 50% reduction in the IV Melphalan dose decreased the incidence of severe bone marrow suppression in the latter portion of this study.

Administration of live vaccines to immunocompromised patients should be avoided.

Information for Patients

Patients should be informed that the major acute toxicities of Melphalan are related to bone marrow suppression, hypersensitivity reactions, gastrointestinal toxicity, and pulmonary toxicity. The major long-term toxicities are related to infertility and secondary malignancies. Patients should never be allowed to take the drug without close medical supervision and should be advised to consult their physicians if they experience skin rash, signs or symptoms of vasculitis, bleeding, fever, persistent cough, nausea, vomiting, amenorrhea, weight loss, or unusual lumps/masses. Women of childbearing potential should be advised to avoid becoming pregnant.

Laboratory Tests

Periodic complete blood counts with differentials should be performed during the course of treatment with Melphalan. At least 1 determination should be obtained prior to each dose. Patients should be observed closely for consequences of bone marrow suppression, which include severe infections, bleeding, and symptomatic anemia (see WARNINGS).

Drug Interactions

The development of severe renal failure has been reported in patients treated with a single dose of IV Melphalan followed by standard oral doses of cyclosporine. Cisplatin may affect Melphalan kinetics by inducing renal dysfunction and subsequently altering Melphalan clearance. IV Melphalan may also reduce the threshold for BCNU lung toxicity. When nalidixic acid and IV Melphalan are given simultaneously, the incidence of severe hemorrhagic necrotic enterocolitis has been reported to increase in pediatric patients.

Carcinogenesis, Mutagenesis, Impairment of Fertility

See WARNINGS section.

Pregnancy

Teratogenic Effects

Pregnancy Category D

See WARNINGS section

Nursing Mothers

It is not known whether this drug is excreted in human milk. IV Melphalan should not be given to nursing mothers.

Pediatric Use

The safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Melphalan Hydrochloride for Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Adverse Reactions

(SEE OVERDOSAGE)

The following information on adverse reactions is based on data from both oral and IV administration of Melphalan as a single agent, using several different dose schedules for treatment of a wide variety of malignancies.

Hematologic

The most common side effect is bone marrow suppression leading to leukopenia, thrombocytopenia, and anemia. White blood cell count and platelet count nadirs usually occur 2 to 3 weeks after treatment, with recovery in 4 to 5 weeks after treatment. Irreversible bone marrow failure has been reported.

Gastrointestinal

Gastrointestinal disturbances such as nausea and vomiting, diarrhea, and oral ulceration occur infrequently. Hepatic disorders ranging from abnormal liver function tests to clinical manifestations such as hepatitis and jaundice have been reported. Hepatic veno-occlusive disease has been reported.

Hypersensitivity

Acute hypersensitivity reactions including anaphylaxis were reported in 2.4% of 425 patients receiving Melphalan Hydrochloride for Injection for myeloma (see WARNINGS). These reactions were characterized by urticaria, pruritus, edema, skin rashes, and in some patients, tachycardia, bronchospasm, dyspnea, and hypotension. These patients appeared to respond to antihistamine and corticosteroid therapy. If a hypersensitivity reaction occurs, IV or oral Melphalan should not be readministered since hypersensitivity reactions have also been reported with oral Melphalan. Cardiac arrest has also been reported rarely in association with such reports.

Miscellaneous

Other reported adverse reactions include skin hypersensitivity, skin ulceration at injection site, skin necrosis rarely requiring skin grafting, maculopapular rashes, vasculitis, alopecia, hemolytic anemia, allergic reaction, pulmonary fibrosis (including fatal outcomes), and interstitial pneumonitis. Temporary significant elevation of the blood urea has been seen in the early stages of therapy in patients with renal damage. Subjective and transient sensation of warmth and/or tingling.

Overdosage

Overdoses resulting in death have been reported. Overdoses, including doses up to 290 mg/m2, have produced the following symptoms: severe nausea and vomiting, decreased consciousness, convulsions, muscular paralysis, and cholinomimetic effects. Severe mucositis, stomatitis, colitis, diarrhea, and hemorrhage of the gastrointestinal tract occur at high doses (>100 mg/m2). Elevations in liver enzymes and veno-occlusive disease occur infrequently. Significant hyponatremia caused by an associated inappropriate secretion of ADH syndrome has been observed. Nephrotoxicity and adult respiratory distress syndrome have been reported rarely. The principal toxic effect is bone marrow suppression. Hematologic parameters should be closely followed for 3 to 6 weeks. An uncontrolled study suggests that administration of autologous bone marrow or hematopoietic growth factors (i.e., sargramostim, filgrastim) may shorten the period of pancytopenia. General supportive measures together with appropriate blood transfusions and antibiotics should be instituted as deemed necessary by the physician. This drug is not removed from plasma to any significant degree by hemodialysis or hemoperfusion. A pediatric patient survived a 254-mg/m2 overdose treated with standard supportive care.

Melphalan Dosage and Administration

The usual IV dose is 16 mg/m2. Dosage reduction of up to 50% should be considered in patients with renal insufficiency (BUN ≥30 mg/dL) (see PRECAUTIONS: General). The drug is administered as a single infusion over 15 to 20 minutes. Melphalan is administered at 2-week intervals for 4 doses, then, after adequate recovery from toxicity, at 4-week intervals. Available evidence suggests about one third to one half of the patients with multiple myeloma show a favorable response to the drug. Experience with oral Melphalan suggests that repeated courses should be given since improvement may continue slowly over many months, and the maximum benefit may be missed if treatment is abandoned prematurely. Dose adjustment on the basis of blood cell counts at the nadir and day of treatment should be considered.

Administration Precautions

As with other toxic compounds, caution should be exercised in handling and preparing the solution of Melphalan Hydrochloride. Skin reactions associated with accidental exposure may occur. The use of gloves is recommended. If the solution of Melphalan Hydrochloride contacts the skin or mucosa, immediately wash the skin or mucosa thoroughly with soap and water.

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. 1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration whenever solution and container permit. If either occurs, do not use this product.

Care should be taken to avoid possible extravasation of Melphalan and in cases of poor peripheral venous access, consideration should be given to use of a central venous line (see WARNINGS).

Preparation for Administration/Stability

1. Melphalan Hydrochloride for Injection must be reconstituted by rapidly injecting 10 mL of the supplied diluent directly into the vial of lyophilized powder using a sterile needle (20-gauge or larger needle diameter) and syringe. Immediately shake vial vigorously until a clear solution is obtained. This provides a 5-mg/mL solution of Melphalan. Rapid addition of the diluent followed by immediate vigorous shaking is important for proper dissolution.


2. Immediately dilute the dose to be administered in 0.9% Sodium Chloride Injection, USP, to a concentration not greater than 0.45 mg/mL.


3. Administer the diluted product over a minimum of 15 minutes.


4. Complete administration within 60 minutes of reconstitution.

The time between reconstitution/dilution and administration of Melphalan Hydrochloride for Injection should be kept to a minimum because reconstituted and diluted solutions of Melphalan Hydrochloride for Injection are unstable. Over as short a time as 30 minutes, a citrate derivative of Melphalan has been detected in reconstituted material from the reaction of Melphalan Hydrochloride with Sterile Diluent for Melphalan Hydrochloride for Injection. Upon further dilution with saline, nearly 1% label strength of Melphalan hydrolyzes every 10 minutes.

A precipitate forms if the reconstituted solution is stored at 5°C. DO NOT REFRIGERATE THE RECONSTITUTED PRODUCT.

How is Melphalan Supplied

Melphalan Hydrochloride for Injection is supplied in a carton containing one single-use clear glass vial of freeze-dried Melphalan hydrochloride equivalent to 50 mg Melphalan and one 10-mL clear glass vial of sterile diluent.

NDC 67457-195-01

NOVAPLUS® NDC 67457-215-01

Novation, the supply company of VHA and UHC, and NOVAPLUS are trademarks of Novation LLC.

Store between 20° to 25°C (68° - 77°F). [See USP for Controlled Room Temperature]. Protect from light.

REFERENCES

1. ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburg, PA: Oncology Nursing Society; 1999:32-41.


2. Recommendations for the safe handling of parenteral antineoplastic drugs. Washington, DC: Division of Safety, Clinical Center Pharmacy Department and Cancer Nursing Services, National Institutes of Health; 1992. US Dept of Health and Human Services. Public Health Service publication NIH 92-2621.


3. AMA Council on Scientific Affairs. Guidelines for handling parenteral antineoplastics. JAMA. 1985;253:1590-1591.


4. National Study Commission on Cytotoxic Exposure. Recommendations for handling cytotoxic agents. 1987. Available from Louis P. Jeffrey, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115.


5. Clinical Oncological Society of Australia. Guidelines and recommendations for safe handling of antineoplastic agents. Med J Australia. 1983;1:426-428.


6. Jones RB, Frank R, Mass T. Safe handling of chemotherapeutic agents: a report from the Mount Sinai Medical Center. CA-A Cancer J for Clin. 1983;33:258-263.


7. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm. 1990;47:1033-1049.


8. Controlling Occupational Exposure to Hazardous Drugs. (OSHA Work-Practice Guidelines.) Am J Health-Syst Pharm. 1996;53:1669-1685.

Melphalan for Injection manufactured for:

Bioniche Pharma USA LLC,

Lake Forest, IL 60045

Made in Italy

August 2008

P080815

PRINCIPAL DISPLAY PANEL - 50 mg Carton

SINGLE USE

NDC 67457-195-01

Rx Only

Melphalan

Hydrochloride

for Injection

50 mg*

Cytotoxic Agent

*Each vial of Melphalan for injection contains

Melphalan hydrochloride equivalent to 50 mg

Melphalan and 20 mg povidone.

One vial of sterile, nonpyrogenic diluent containing

0.2 g sodium citrate, 6.0 mL propylene glycol,

0.52 mL ethanol (95%), and Water for Injection

to a total of 10 mL.

For intravenous infusion

BIONICHEPHARMA

PRINCIPAL DISPLAY PANEL - 50 mg Carton

NDC 67457-215-01

Melphalan

Hydrochloride

for Injection

50 mg*

For intravenous infusion

Cytotoxic Agent – SINGLE USE

*Each vial of Melphalan for injection contains Melphalan

hydrochloride equivalent to 50 mg Melphalan and 20 mg

povidone.

One vial of sterile, nonpyrogenic diluent containing 0.2 g

sodium citrate, 6.0 mL propylene glycol, 0.52 mL ethanol

(95%), and Water for Injection to a total of 10 mL.

Rx Only

NOVAPLUS®

Melphalan HYDROCHLORIDE  Melphalan hydrochloride  kit

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 67457-195

Packaging # NDC Package Description Multilevel Packaging 1 67457-195-01 1 KIT In 1 CARTON None

QUANTITY OF PARTS Part # Package Quantity Total Product Quantity Part 1 1 VIAL, GLASS   10 mL Part 2 1 VIAL, GLASS   10 mL

Part 1 of 2 Melphalan HYDROCHLORIDE  Melphalan hydrochloride  injection, powder, for solution

Product Information NDC Product Code (Source) 67457-193     Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Melphalan Hydrochloride (Melphalan) Melphalan Hydrochloride 50 mg  in 10 mL

Inactive Ingredients Ingredient Name Strength povidone 20 mg  in 10 mL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 67457-193-50 10 mL In 1 VIAL, GLASS None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090270 10/06/2009

Part 2 of 2 STERILE DILUENT  sodium citrate, propylene glycol and water  injection, solution

Product Information NDC Product Code (Source) 67457-194     Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength No Active Ingredients Found

Inactive Ingredients Ingredient Name Strength Sodium Citrate 0.2 g  in 10 mL propylene glycol 0.52 mL  in 10 mL Water

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 67457-194-10 10 mL In 1 VIAL, GLASS None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090270 10/06/2009

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA090270	01/21/2011

Melphalan HYDROCHLORIDE  Melphalan hydrochloride  kit

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 67457-215

Packaging # NDC Package Description Multilevel Packaging 1 67457-215-01 1 KIT In 1 CARTON None

QUANTITY OF PARTS Part # Package Quantity Total Product Quantity Part 1 1 VIAL, GLASS   10 mL Part 2 1 VIAL, GLASS   10 mL

Part 1 of 2 Melphalan HYDROCHLORIDE  Melphalan hydrochloride  injection, powder, for solution

Product Information NDC Product Code (Source) 67457-213     Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Melphalan Hydrochloride (Melphalan) Melphalan Hydrochloride 50 mg  in 10 mL

Inactive Ingredients Ingredient Name Strength povidone 20 mg  in 10 mL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 67457-213-50 10 mL In 1 VIAL, GLASS None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090270 10/06/2009

Part 2 of 2 STERILE DILUENT  sodium citrate, propylene glycol and water  injection, solution

Product Information       Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength No Active Ingredients Found

Inactive Ingredients Ingredient Name Strength Sodium Citrate 0.2 g  in 10 mL propylene glycol 0.52 mL  in 10 mL Water

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging #

Melpaque HP

Generic Name: hydroquinone topical (HYE droe KWIN one)

Brand Names: Aclaro, Aclaro PD, Alera, Alphaquin HP, Alustra, Claripel, Eldopaque, Eldopaque Forte, Eldoquin, Eldoquin Forte, EpiQuin Micro, Esoterica, Esoterica with Sunscreen, Glyquin, Glyquin-XM, Hydroquinone and Sunscreen, Lustra, Lustra-AF, Lustra-Ultra, Melpaque HP, Melquin HP, Melquin-3, Nuquin HP, Solaquin, Solaquin Forte

What is Melpaque HP (hydroquinone topical)?

Hydroquinone decreases the formation of melanin in the skin. Melanin is the pigment in skin that gives it a brown color.

Hydroquinone topical is used to lighten areas of darkened skin such as freckles, age spots, chloasma, and melasma.

Hydroquinone topical may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Melpaque HP (hydroquinone topical)?

Before using hydroquinone topical, tell your doctor if you are allergic to any drugs, or if you have liver or kidney disease.

Do not use hydroquinone topical on skin that is sunburned, windburned, dry, chapped, or irritated, or on an open wound. It could make these conditions worse. Wait until these conditions have healed before applying hydroquinone topical. Avoid getting this medication in your mouth or eyes. If it does get into any of these areas, rinse with water.

Avoid using skin products that can cause irritation, such as harsh soaps, shampoos, or skin cleansers, hair coloring or permanent chemicals, hair removers or waxes, or skin products with alcohol, spices, astringents, or lime. Do not use other medicated skin products unless your doctor has told you to.

Avoid exposure to sunlight or artificial UV rays (sunlamps or tanning beds). Hydroquinone topical can make your skin more sensitive to sunlight and sunburn may result. Use a sunscreen (minimum SPF 15) and wear protective clothing if you must be out in the sun.

What should I discuss with my healthcare provider before using Melpaque HP (hydroquinone topical)?

Do not use hydroquinone topical on skin that is sunburned, windburned, dry, chapped, or irritated, or on an open wound. It could make these conditions worse. Wait until these conditions have healed before applying hydroquinone topical.

Before using hydroquinone topical, tell your doctor if you are allergic to any drugs, or if you have:

• 
  

  liver disease; or

  
  


• 
  

  kidney disease.

  
  

If you have any of these conditions, you may need a dose adjustment or special tests to safely use this medication.

This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether hydroquinone topical passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I use Melpaque HP (hydroquinone topical)?

Use this medication exactly as directed on the label, or as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended.

Hydroquinone topical is for external use only. Wash your hands before and after applying this medication, unless you are treating a skin area on your hand.

Apply the medication to clean, dry skin. Apply just enough medication to cover the affected area. Avoid applying to the unaffected surrounding skin. Rub in the medication gently and completely.

Avoid getting this medication on your lips or inside your nose or mouth. Hydroquinone may cause numbness of these areas. If the medication does get on any of these areas, rinse with water.

It is important to use hydroquinone topical regularly to get the most benefit.

Store hydroquinone topical at room temperature away from moisture and heat.

What happens if I miss a dose?

Use the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

An overdose of topically applied hydroquinone is not likely to cause life-threatening symptoms.

What should I avoid while using Melpaque HP (hydroquinone topical)?

Avoid getting this medication in your mouth or eyes. If it does get into any of these areas, rinse with water. Do not use hydroquinone topical on sunburned, windburned, dry, chapped, irritated, or broken skin.

Your skin may be more sensitive to weather extremes such as cold and wind. Protect your skin with clothing and use a moisturizing cream or lotion as needed.

Avoid using skin products that can cause irritation, such as harsh soaps, shampoos, or skin cleansers, hair coloring or permanent chemicals, hair removers or waxes, or skin products with alcohol, spices, astringents, or lime. Do not use other medicated skin products unless your doctor has told you to.

Using hydroquinone topical together with benzoyl peroxide, hydrogen peroxide, or other peroxide products may cause a temporary staining of your skin. This staining can usually be removed with soap and water. Avoid exposure to sunlight or artificial UV rays (sunlamps or tanning beds). Hydroquinone topical can make your skin more sensitive to sunlight and sunburn may result. Use a sunscreen (minimum SPF 15) and wear protective clothing if you must be out in the sun.

Melpaque HP (hydroquinone topical) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using hydroquinone topical and call your doctor if you have severe burning, stinging, or other irritation of your skin after apply the medication.

Less serious side effects may include mild burning, stinging, itching, redness, or irritation of treated skin.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Melpaque HP (hydroquinone topical)?

It is not likely that other drugs you take orally or inject will have an effect on topically applied hydroquinone. But many drugs can interact with each other. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Melpaque HP resources

• Melpaque HP Side Effects (in more detail)
• Melpaque HP Use in Pregnancy & Breastfeeding
• Melpaque HP Support Group
• 0 Reviews for Melpaque HP - Add your own review/rating

• Alustra MedFacts Consumer Leaflet (Wolters Kluwer)


• Epiquin Micro Prescribing Information (FDA)


• Esoterica Cream MedFacts Consumer Leaflet (Wolters Kluwer)


• Solaquin Forte Cream MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Melpaque HP with other medications

• Dermatological Disorders

Where can I get more information?

• Your pharmacist can provide more information about hydroquinone topical.

See also: Melpaque HP side effects (in more detail)

Melatonin/L-Tryptophan

Pronunciation: meh-lah-TOE-nin/L TRIP-toe-fan
Generic Name: Melatonin/L-Tryptophan
Brand Name: Restone

Melatonin/L-Tryptophan is used for:

Helping sleep problems, jet lag, and anxiety or depression, and boosting the immune system. It may also be used for other conditions as determined by your doctor. Check with your pharmacist for more details regarding the use of Melatonin/L-Tryptophan.

Melatonin/L-Tryptophan is an herbal product. It works by increasing certain substances in the brain.

Do NOT use Melatonin/L-Tryptophan if:

• you are allergic to any ingredient in Melatonin/L-Tryptophan

Contact your doctor or health care provider right away if any of these apply to you.

Before using Melatonin/L-Tryptophan:

Some medical conditions may interact with Melatonin/L-Tryptophan. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you are taking any medicine to suppress your immune system or medicines for depression or other mental or mood problems

Some MEDICINES MAY INTERACT with Melatonin/L-Tryptophan. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Anticoagulants (eg, warfarin), benzodiazepines (eg, alprazolam), beta-blockers (eg, metoprolol), calcium channel blockers (eg, diltiazem), corticosteroids (eg, prednisone), 5-HT₁ receptor agonists or triptans (eg, sumatriptan), interleukin-2, meperidine, monoamine oxidase inhibitors (MAOIs) (eg, phenelzine), nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, ibuprofen), phenothiazines (eg, thioridazine), St. John's wort, tamoxifen, or tramadol

This may not be a complete list of all interactions that may occur. Ask your health care provider if Melatonin/L-Tryptophan may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Melatonin/L-Tryptophan:

Use Melatonin/L-Tryptophan as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Use as directed on the package, unless instructed otherwise by your doctor.


• If you miss a dose of Melatonin/L-Tryptophan, take it as soon as possible. If it is almost for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Melatonin/L-Tryptophan.

Important safety information:

• Melatonin/L-Tryptophan may cause drowsiness or affect your thinking or reactions. These effects may be worse if you take it with alcohol or certain medicines. Use Melatonin/L-Tryptophan with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Check with your doctor before you use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Melatonin/L-Tryptophan; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• This product has not been approved by the Food and Drug Administration (FDA) as safe and effective for any medical condition. The long-term safety of herbal products is not known. Before using any alternative medicine, talk with your doctor or pharmacist.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Melatonin/L-Tryptophan while you are pregnant. It is not known if Melatonin/L-Tryptophan is found in breast milk. If you are or will be breast-feeding while you use Melatonin/L-Tryptophan, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Melatonin/L-Tryptophan:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Burping; diarrhea; drowsiness; dry mouth; gas; headache; heartburn; loss of appetite; nausea; stomach upset; vomiting; weakness.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, throat, or tongue); blurred vision; decreased coordination; light-headedness.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Melatonin/L-Tryptophan:

Store at room temperature away from heat, moisture, and light. Do not store in the bathroom. Melatonin/L-Tryptophan does not have a childproof container. Keep Melatonin/L-Tryptophan out of the reach of children and away from pets.

General information:

• If you have any questions about Melatonin/L-Tryptophan, please talk with your doctor, pharmacist, or other health care provider.


• Melatonin/L-Tryptophan is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Melatonin/L-Tryptophan. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

Menopur injectable

Generic Name: menotropins (injectable) (MEN oh troe pins)

Brand Names: Menopur, Repronex

What are menotropins?

Menotropins are an equal mixture of the naturally occurring follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH are important for the development of follicles (eggs) produced by the ovaries and for the development of sperm.

Menotropins are used to stimulate ovulation (the release of an egg) when a woman's ovaries can produce a follicle but hormonal stimulation is deficient. Menotropins are also used to stimulate the development of multiple eggs for in vitro fertilization. Likewise, menotropins are used to stimulate the production of sperm in men who have functioning testes but in whom hormonal stimulation is deficient.

Menotropins may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about menotropins?

Menotropins may increase the likelihood of multiple births. Multiple births may carry additional risk both for the mother and for the fetuses.

What should I discuss with my healthcare provider before using menotropins?

Menotropins will not induce ovulation or sperm production if your ovaries or testes are not functioning properly.

Do not use menotropins without first taking to your doctor if you

• 
  

  might be pregnant;

  
  


• 
  

  have a thyroid problem;

  
  


• 
  

  have cancer or a tumor of the breast, ovary, uterus, hypothalamus, or pituitary gland;

  
  


• 
  

  have undiagnosed vaginal bleeding;

  
  


• 
  

  have ovarian cysts or enlargement; or

  
  


• 
  

  have any other serious or chronic medical illness.

  
  

You may not be able to use menotropins, or you may require a dosage adjustment or special monitoring if you have any of the conditions listed above.

Do not use menotropins if you are pregnant. Menotropins are in the FDA pregnancy category X. This means that they are known to cause birth defects. It is not known whether menotropins pass into breast milk. Do not use menotropins without first talking to your doctor if you are breast-feeding a baby.

How should I use menotropins?

Use menotropins exactly as directed by your doctor. If you do not understand these directions, ask your doctor, nurse, or pharmacist to explain them to you.

Formulations of menotropins intended for intramuscular injection (an injection into muscle) must not be administered subcutaneously (under the skin), and vice versa. If you are administering this medication at home, your doctor will give you detailed instructions on how to mix the solution and give yourself the injection. Do not inject menotropins if you are not sure how.

Use the solution immediately after it is mixed. Throw away any medicine that is left over.

Never reuse a needle or syringe. Dispose of all needles and syringes in an appropriate, puncture-resistant disposal container.

Store menotropins at room temperature or in the refrigerator, away from direct light, moisture, and heat.

What happens if I miss a dose?

Contact your doctor if you miss a dose of menotropins. Do not use a double dose of this medication without first talking to your doctor.

What happens if I overdose?

An overdose of menotropins is unlikely to threaten life. Notify your doctor immediately or call an emergency room or poison control center for advice.

Symptoms of a menotropins overdose are not known. Ovarian hyperstimulation syndrome (OHSS) may result with an overdose of menotropins. Symptoms of OHSS include swelling of the hands or legs, abdominal pain and swelling, shortness of breath, weight gain, and nausea or vomiting. OHSS can be fatal.

What should I avoid while using menotropins?

There are no restrictions on food, beverages, or activity during therapy with menotropins unless your doctor directs otherwise.

Menotropins side effects

Stop using menotropins and seek emergency medical attention if you experience an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives).

Less than 2% of female patients treated with menotropins develop ovarian hyperstimulation syndrome (OHSS), especially after the first cycle of therapy. Symptoms of OHSS include swelling of the hands or legs, abdominal pain and swelling, shortness of breath, weight gain, and nausea or vomiting. OHSS can be fatal. Notify your doctor immediately or seek emergency medical attention if you develop any of these side effects.

Serious pulmonary (lung and breathing) conditions have been reported in patients using menotropins. Seek medical attention if you experience any sudden changes in your breathing.

Other side effects may also occur. Notify your doctor if you experience

• 
  

  ovarian enlargement presenting as abdominal or pelvic pain, tenderness, pressure, or swelling;

  
  


• 
  

  nausea, vomiting, or diarrhea;

  
  


• 
  

  shortness of breath;

  
  


• 
  

  pain, warmth, or tenderness centralized in an arm or leg;

  
  


• 
  

  fever or chills;

  
  


• 
  

  headache or drowsiness;

  
  


• 
  

  weakness or aching of muscles or joints;

  
  


• 
  

  breast enlargement or tenderness;

  
  


• 
  

  pain, swelling, or irritation at the injection site; or

  
  


• 
  

  rash.

  
  

Menotropins may increase the likelihood of multiple births. Multiple births may carry additional risk both for the mother and for the fetuses.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect menotropins?

It is not known whether other medications will interact with menotropins. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines including vitamins, minerals, and herbal products.

More Menopur resources

• Menopur Side Effects (in more detail)
• Menopur Use in Pregnancy & Breastfeeding
• Menopur Drug Interactions
• Menopur Support Group
• 0 Reviews for Menopur - Add your own review/rating

Compare Menopur with other medications

• Female Infertility
• Follicle Stimulation
• Ovulation Induction

Where can I get more information?

• Your pharmacist can provide more information about menotropins.

See also: Menopur side effects (in more detail)

Melquin HP

Generic Name: hydroquinone topical (HYE droe KWIN one)

Brand Names: Aclaro, Aclaro PD, Alera, Alphaquin HP, Alustra, Claripel, Eldopaque, Eldopaque Forte, Eldoquin, Eldoquin Forte, EpiQuin Micro, Esoterica, Esoterica with Sunscreen, Glyquin, Glyquin-XM, Hydroquinone and Sunscreen, Lustra, Lustra-AF, Lustra-Ultra, Melpaque HP, Melquin HP, Melquin-3, Nuquin HP, Solaquin, Solaquin Forte

What is Melquin HP (hydroquinone topical)?

Hydroquinone decreases the formation of melanin in the skin. Melanin is the pigment in skin that gives it a brown color.

Hydroquinone topical is used to lighten areas of darkened skin such as freckles, age spots, chloasma, and melasma.

Hydroquinone topical may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Melquin HP (hydroquinone topical)?

Before using hydroquinone topical, tell your doctor if you are allergic to any drugs, or if you have liver or kidney disease.

Do not use hydroquinone topical on skin that is sunburned, windburned, dry, chapped, or irritated, or on an open wound. It could make these conditions worse. Wait until these conditions have healed before applying hydroquinone topical. Avoid getting this medication in your mouth or eyes. If it does get into any of these areas, rinse with water.

Avoid using skin products that can cause irritation, such as harsh soaps, shampoos, or skin cleansers, hair coloring or permanent chemicals, hair removers or waxes, or skin products with alcohol, spices, astringents, or lime. Do not use other medicated skin products unless your doctor has told you to.

Avoid exposure to sunlight or artificial UV rays (sunlamps or tanning beds). Hydroquinone topical can make your skin more sensitive to sunlight and sunburn may result. Use a sunscreen (minimum SPF 15) and wear protective clothing if you must be out in the sun.

What should I discuss with my healthcare provider before using Melquin HP (hydroquinone topical)?

Do not use hydroquinone topical on skin that is sunburned, windburned, dry, chapped, or irritated, or on an open wound. It could make these conditions worse. Wait until these conditions have healed before applying hydroquinone topical.

Before using hydroquinone topical, tell your doctor if you are allergic to any drugs, or if you have:

• 
  

  liver disease; or

  
  


• 
  

  kidney disease.

  
  

If you have any of these conditions, you may need a dose adjustment or special tests to safely use this medication.

This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether hydroquinone topical passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I use Melquin HP (hydroquinone topical)?

Use this medication exactly as directed on the label, or as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended.

Hydroquinone topical is for external use only. Wash your hands before and after applying this medication, unless you are treating a skin area on your hand.

Apply the medication to clean, dry skin. Apply just enough medication to cover the affected area. Avoid applying to the unaffected surrounding skin. Rub in the medication gently and completely.

Avoid getting this medication on your lips or inside your nose or mouth. Hydroquinone may cause numbness of these areas. If the medication does get on any of these areas, rinse with water.

It is important to use hydroquinone topical regularly to get the most benefit.

Store hydroquinone topical at room temperature away from moisture and heat.

What happens if I miss a dose?

Use the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

An overdose of topically applied hydroquinone is not likely to cause life-threatening symptoms.

What should I avoid while using Melquin HP (hydroquinone topical)?

Avoid getting this medication in your mouth or eyes. If it does get into any of these areas, rinse with water. Do not use hydroquinone topical on sunburned, windburned, dry, chapped, irritated, or broken skin.

Your skin may be more sensitive to weather extremes such as cold and wind. Protect your skin with clothing and use a moisturizing cream or lotion as needed.

Avoid using skin products that can cause irritation, such as harsh soaps, shampoos, or skin cleansers, hair coloring or permanent chemicals, hair removers or waxes, or skin products with alcohol, spices, astringents, or lime. Do not use other medicated skin products unless your doctor has told you to.

Using hydroquinone topical together with benzoyl peroxide, hydrogen peroxide, or other peroxide products may cause a temporary staining of your skin. This staining can usually be removed with soap and water. Avoid exposure to sunlight or artificial UV rays (sunlamps or tanning beds). Hydroquinone topical can make your skin more sensitive to sunlight and sunburn may result. Use a sunscreen (minimum SPF 15) and wear protective clothing if you must be out in the sun.

Melquin HP (hydroquinone topical) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using hydroquinone topical and call your doctor if you have severe burning, stinging, or other irritation of your skin after apply the medication.

Less serious side effects may include mild burning, stinging, itching, redness, or irritation of treated skin.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Melquin HP (hydroquinone topical)?

It is not likely that other drugs you take orally or inject will have an effect on topically applied hydroquinone. But many drugs can interact with each other. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Melquin HP resources

• Melquin HP Side Effects (in more detail)
• Melquin HP Use in Pregnancy & Breastfeeding
• Melquin HP Support Group
• 0 Reviews for Melquin HP - Add your own review/rating

• Alustra MedFacts Consumer Leaflet (Wolters Kluwer)


• Epiquin Micro Prescribing Information (FDA)


• Esoterica Cream MedFacts Consumer Leaflet (Wolters Kluwer)


• Solaquin Forte Cream MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Melquin HP with other medications

• Dermatological Disorders

Where can I get more information?

• Your pharmacist can provide more information about hydroquinone topical.

See also: Melquin HP side effects (in more detail)

melphalan

Generic Name: melphalan (MEL fa lan)

Brand Names: Alkeran, Alkeran I.V.

What is melphalan?

Melphalan is a cancer medication. Melphalan interferes with the growth of cancer cells and slows their growth and spread in the body.

Melphalan is used to treat multiple myeloma (a type of blood cancer), cancer of the ovary, and breast cancer.

Melphalan may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about melphalan?

Do not use this medication if you are pregnant. It could cause harm to the unborn baby. Use an effective form of birth control, and tell your doctor if you become pregnant during treatment. Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Melphalan can cause serious side effects, including: decreased bone marrow function and blood problems (easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms, bloody or black stools, pale or yellowed skin, confusion or weakness); breathing problems; or liver damage (nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice [yellowing of the skin or eyes]). Call your doctor at once if you have any of these side effects.

In some cases, second cancers have been reported to occur during and after treatment with melphalan. Talk to your doctor about your individual risk and benefit of this medication.

What should I discuss with my healthcare provider before using melphalan?

Before using melphalan, tell your doctor if you have:

• kidney disease; or


• 
  

  decreased bone marrow (from other diseases or medications).

  
  

If you have any of these conditions, you may not be able to use melphalan, or you may need a dosage adjustment or special tests during treatment.

FDA pregnancy category D. This medication can cause harm to an unborn baby. Do not use melphalan if you are pregnant. Tell your doctor if you become pregnant during treatment. Use an effective form of birth control while you are using this medication.

This medication can affect fertility (your ability to have children), whether you are a man or a woman.

It is not known whether melphalan passes into breast milk or if it could harm a nursing baby. Do not take melphalan without telling your doctor if you are breast feeding a baby.

How should I take melphalan?

Take this medication exactly as it was prescribed for you. Do not take the medication in larger or smaller amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results from this medication.

Take the melphalan oral tablet with a large glass of water.

Melphalan injection is given through a needle placed into a vein. Your doctor, nurse, or other healthcare provider will give you this injection in a clinic or hospital setting.

Tell your doctor right away if any of the melphalan injection gets on your skin or if you feel pain, burning, or other skin irritation when the medicine is injected.

Melphalan is usually given for a few weeks at a time, followed by a 4-week period off the drug, during which your blood is tested to see how your body responded to the medication. Your doctor will determine how often you use melphalan and for how long. Follow your doctor's instructions carefully.

Melphalan can lower the blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. To be sure your blood cells do not get too low, your blood will need to be tested on a regular basis. It is important that you not miss any scheduled visits to your doctor.

Store melphalan tablets in the refrigerator and protect them from light. If you store melphalan injection at home, keep it at room temperature and protect it from heat, moisture, and light.

See also: Melphalan dosage (in more detail)

What happens if I miss a dose?

Call your doctor for instructions if you miss a dose of melphalan.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include severe nausea, vomiting, diarrhea, mouth sores, bloody or black stools, coughing up blood or vomit that looks like coffee grounds.

What should I avoid while taking melphalan?

Avoid contact with people who have colds, the flu, or other contagious illnesses. Contact your doctor immediately if you develop signs of infection.

Do not receive a "live" vaccine while you are being treated with melphalan, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you.

Melphalan side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have any of these serious side effects:

• 
  

  easy bruising or bleeding, unusual weakness;

  
  


• 
  

  fever, chills, body aches, flu symptoms;

  
  


• 
  

  nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

  
  


• 
  

  missed menstrual periods;

  
  


• 
  

  unusual lumps or masses;

  
  


• 
  

  red skin rash, rapid pulse, pain, weight loss;

  
  


• 
  

  breathing problems or a cough that won't go away; or

  
  


• 
  

  pale or yellowed skin, dark colored urine, confusion and weakness.

  
  

Less serious side effects may include:

• 
  

  mild nausea, vomiting, diarrhea;

  
  


• 
  

  white patches or sores inside your mouth or on your lips;

  
  


• 
  

  temporary hair loss; or

  
  


• 
  

  mild skin itching and rash.

  
  

In some cases, second cancers have been reported to occur during and after treatment with melphalan. Talk to your doctor about your individual risk and benefit in using this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Melphalan Dosing Information

Usual Adult Dose for Multiple Myeloma:

Usual Intravenous Dose: 16 mg/m2
The drug is administered as a single infusion over 15 to 20 minutes. Melphalan is administered at two week intervals for four doses, then, after adequate recovery from toxicity, at four week intervals.

Usual Oral Dose: 6 mg once a day. After 2 to 3 weeks of treatment, the drug should be discontinued for up to 4 weeks during which time the blood count should be followed carefully. When the white blood cell and platelet counts are rising, a maintenance dose of 2 mg daily may be instituted. Because of the patient to patient variation in melphalan plasma levels following oral administration of the drug, several investigators have recommended that the dosage of melphalan be cautiously escalated until some myelosuppression is observed in order to assure that potentially therapeutic levels of the drug have been reached.

Experience with oral melphalan suggests that repeated courses should be given since improvement may continue slowly over many months, and the maximum benefit may be missed if treatment is abandoned prematurely.

Other dosage regimens have been used by various investigators. Osserman and Takatsuki have used an initial course of 10 mg/day for 7 to 10 days. They report that maximal suppression of the leukocyte and platelet counts occurs within 3 to 5 weeks and recovery within 4 to 8 weeks. Continuous maintenance therapy with 2 mg/day is instituted when the white blood cell count is greater than 4000 cells/mcL and the platelet count is greater than 100,000 cells/mcL. Dosage is adjusted to between 1 and 3 mg/day depending upon the hematological response. It is desirable to try to maintain a significant degree of bone marrow depression so as to keep the leukocyte count in the range of 3000 to 3500 cells/mcL.

Hoogstraten et al have started treatment with 0.15 mg/kg per day for 7 days. This is followed by a rest period of at least 14 days, but it may be as long as 5 to 6 weeks. Maintenance therapy is started when the white blood cell and platelet counts are rising. The maintenance dose is 0.05 mg/kg per day or less and is adjusted according to the blood count.

One study by Alexanian et al has shown that the use of melphalan in combination with prednisone significantly improves the percentage of patients with multiple myeloma who achieve palliation. One regimen has been to administer courses of melphalan at 0.25 mg/kg per day for 4 consecutive days (or, 0.20 mg/kg per day for five consecutive days) for a total dose of 1 mg/kg per course. These four to five day courses are then repeated every 4 to 6 weeks if the granulocyte count and the platelet count have returned to normal levels.

Response may be very gradual over many months; it is important that repeated courses or continuous therapy be given since improvement may continue slowly over many months, and the maximum benefit may be missed if treatment is abandoned too soon.

Available evidence suggests about one third to one half of the patients with multiple myeloma show a favorable response to the drug.

Usual Adult Dose for Ovarian Cancer:

For use in the treatment of epithelial ovarian cancer:
Common regimen: 0.2 mg/kg orally daily for 5 days as a single course.
Courses are repeated every four to five weeks depending upon hematologic tolerance.

What other drugs will affect melphalan?

Before taking melphalan, tell your doctor if you are being treated with any other medicines that weaken your immune system, such as:

• 
  

  cyclosporine (Gengraf, Neoral, Sandimmune);

  
  


• 
  

  radiation therapy;

  
  


• 
  

  steroids (prednisone and others); or

  
  


• 
  

  another chemotherapy medicine.

  
  

This list is not complete and there may be other drugs that can interact with melphalan. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More melphalan resources

• Melphalan Side Effects (in more detail)
• Melphalan Dosage
• Melphalan Use in Pregnancy & Breastfeeding
• Melphalan Drug Interactions
• Melphalan Support Group
• 0 Reviews for Melphalan - Add your own review/rating

• melphalan Advanced Consumer (Micromedex) - Includes Dosage Information


• Melphalan Prescribing Information (FDA)


• Melphalan Professional Patient Advice (Wolters Kluwer)


• Melphalan Monograph (AHFS DI)


• Melphalan MedFacts Consumer Leaflet (Wolters Kluwer)


• Alkeran Prescribing Information (FDA)

Compare melphalan with other medications

• Multiple Myeloma
• Ovarian Cancer

Where can I get more information?

• Your pharmacist can provide more information about melphalan.

See also: melphalan side effects (in more detail)

Menthoderm Cream

Pronunciation: METH-il sa-LIS-i-late/MEN-thol
Generic Name: Methyl Salicylate/Menthol
Brand Name: Trade names include Menthoderm and Thera-Gesic Plus

Menthoderm Cream is used for:

Temporary relief of minor aches and pains caused by arthritis, simple backache, strains, sprains, and bruises. It may also be used for other conditions as determined by your doctor.

Menthoderm Cream is a topical analgesic. It works by temporarily relieving minor pain.

Do NOT use Menthoderm Cream if:

• you are allergic to any ingredient in Menthoderm Cream, including oil of wintergreen

Contact your doctor or health care provider right away if any of these apply to you.

Before using Menthoderm Cream:

Some medical conditions may interact with Menthoderm Cream. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have had an allergic reaction to aspirin or other salicylates


• if you have a wound at the affected area or your skin is broken or damaged in any way

Some MEDICINES MAY INTERACT with Menthoderm Cream. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Anticoagulants (eg, warfarin) because the risk of their side effects may be increased by Menthoderm Cream

Ask your health care provider if Menthoderm Cream may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Menthoderm Cream:

Use Menthoderm Cream as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Apply a thin layer of medicine to the painful or sore area. You may apply up to 3 thin layers of medicine depending on your pain level. Check with your doctor or the package label if you have questions about how to apply Menthoderm Cream.


• Wash your hands immediately after using Menthoderm Cream.


• You may wash the treated area once the medicine has been absorbed into the skin.


• Do not apply Menthoderm Cream to wounds or damaged skin.


• Do not use Menthoderm Cream right after you shower or take a bath.


• Do not bandage, wrap, or cover the affected area until after the medicine has been absorbed and you have washed the area.


• Do not use Menthoderm Cream more than 3 to 4 times per day.


• If you miss a dose of Menthoderm Cream, use it as soon as you remember. Continue to use it as directed by your doctor or on the package label.

Ask your health care provider any questions you may have about how to use Menthoderm Cream.

Important safety information:

• Menthoderm Cream is for external use only. Do not get it in your eyes, ears, lips, mouth, or genital area. If you get it in any of these areas, rinse right away with cool water.


• Do not use a heating pad after you apply Menthoderm Cream.


• Do NOT use more than the recommended dose or use more often than directed without checking with your doctor.


• Do not use Menthoderm Cream over large areas of the body without checking with your doctor.


• Do not allow Menthoderm Cream to come into contact with clothing or any surface other than skin.


• If your symptoms do not get better within 7 days, if they get worse, or if they clear up and then return, check with your doctor.


• Menthoderm Cream may cause harm if it is swallowed. If you may have taken it by mouth, contact your poison control center or emergency room right away.


• Menthoderm Cream should not be used in CHILDREN younger than 12 years old without first checking with the child's doctor; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Menthoderm Cream while you are pregnant. It is not known if Menthoderm Cream is found in breast milk after topical use. If you are or will be breast-feeding while you use Menthoderm Cream, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Menthoderm Cream:

All medicines may cause side effects, but many people have no, or minor, side effects. No COMMON side effects have been reported with Menthoderm Cream. Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); skin redness or irritation.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Menthoderm side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Menthoderm Cream:

Store Menthoderm Cream at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Menthoderm Cream out of the reach of children and away from pets.

General information:

• If you have any questions about Menthoderm Cream, please talk with your doctor, pharmacist, or other health care provider.


• Menthoderm Cream is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Menthoderm Cream. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Menthoderm resources

• Menthoderm Side Effects (in more detail)
• Menthoderm Use in Pregnancy & Breastfeeding
• Menthoderm Drug Interactions
• Menthoderm Support Group
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