Dtic-Dome

See also Warning section.Nausea, vomiting, and loss of appetite commonly occur. Vomiting may last up to 12 hours. Your doctor may prescribe medication to prevent or relieve nausea and vomiting. Eating several small meals, not eating for 4 to 6 hours before treatment, or limiting activity may help lessen these effects. These symptoms usually decrease after 1 to 2 days. Diarrhea, flu-like symptoms (e.g., discomfort, uneasiness, body aches, headache), blurred vision, or flushing/numbness/tingling of the face may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Temporary hair loss may occur. Normal hair growth should return after treatment has ended.Many people using this medication have serious side effects. However, your doctor has prescribed this drug because he or she has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.If this medication leaks out of the vein into the tissue under the skin, it may cause serious tissue damage. Tell your doctor immediately if you experience pain, burning, redness, or swelling at the injection site.Tell your doctor right away if you have any serious side effects, including: mouth sores, confusion, seizures, sunburn (sun sensitivity).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

After intravenous administration of DTlC-Dome, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. Its disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours.1 In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours.1 The average cumulative excretion of unchanged DTlC in the urine is 40% of the injected dose in 6 hours.1 DTlC is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations DTIC is not appreciably bound to human plasma protein.

In man, DTlC is extensively degraded. Besides unchanged DTlC, 5-aminoimidazole -4 carboxamide (AlC) is a major metabolite of DTlC excreted in the urine. AlC is not derived endogenously but from the injected DTlC, because the administration of radioactive DTlC labeled with 14C in the imidazole portion of the molecule (DTlC-2-14C) gives rise to AIC-2-14C1.

Although the exact mechanism of action of DTIC-Dome (dacarbazine) is not known, three hypotheses have been offered:

1. inhibition of DNA synthesis by acting as a purine analog
2. action as an alkylating agent
3. interaction with SH groups

REFERENCES

1. Loo, T.J., et al.: Mechanism of action and pharmacology studies with DTlC (NSC-45388). Cancer Treatment Reports 60: 149–152, 1976.

Mechanism of Action

Non-cell cycle specific; alkylates DNA & RNA; causes DNA double strand breaks and apoptosis

Pharmacokinetics

Half-Life: 5 hr (terminal)

Peak Plasma: 8 mcg/mL (4.5 mg/kg dose)

Protein Bound: ~5%

Vd: 0.6 L/kg

Metabolism: Liver

Metabolites: 5-(3-monomethyl-1-triazenyl)-1H-imidazole-4-carboxamide (MIC)

Excretion: Urine (~40%)

No dacarbazine drug interactions have been identified. However, you should tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Not all drug interactions are known or reported and new drug interactions are continually being reported.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

You should not use dacarbazine if you are allergic to it.

FDA pregnancy category C. It is not known whether dacarbazine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether dacarbazine passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are being treated with dacarbazine.

Absorption

Bioavailability

Poorly absorbed from the GI tract.b

Distribution

Extent

Volume of distribution exceeds total body water content, suggesting localization in a body tissue, probably the liver.100

Crosses blood-brain barrier to a limited extent; CSF concentrations approximately 14% of plasma concentrations.100

Not known whether dacarbazine crosses the placenta or is distributed into milk.100

Plasma Protein Binding

Slightly bound.100

Elimination

Metabolism

Extensively metabolized; hepatic microsomal enzymes are involved.100 b Some metabolites may contribute to the antineoplastic effect of the drug.b

Elimination Route

Excreted in urine by tubular secretion; about 46% of an administered dose is excreted in urine within 6 hours (about 50% as unchanged drug and 50% as 5-amino-1H-imidazole-4-carboxamide [AIC]). (See Actions.)100 b

Half-life

Biphasic; initial-phase half-life averages 19 minutes; terminal half-life averages 5 hours.100

Storage

Parenteral

Powder for Injection

2–8°C; protect from light.100

Use reconstituted solutions containing 10 mg/mL in sterile water for injection within 8 hours if stored at room temperature or 72 hours if stored at 4°C.100 d

Use solutions further diluted with ≤500 mL of 5% dextrose or 0.9% sodium chloride injection within 8 hours if stored at room temperature or 24 hours if stored at 4°C.100 b d

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Variable
Dextrose 5% in waterHID
Sodium chloride 0.9%b

Drug Compatibility Admixture CompatibilityHID

Compatible
Ondansetron HCl
Variable
Ondansetron HCl with doxorubicin HCl
Incompatible
Hydrocortisone sodium succinateb

Y-Site CompatibilityHID

Compatible
Amifostine
Aztreonam
Doxorubicin HCl liposome injection
Etoposide phosphate
Filgrastim
Fludarabine phosphate
Granisetron HCl
Melphalan HCl
Ondansetron HCl
Paclitaxel
Palonosetron HCl
Sargramostim
Teniposide
Thiotepa
Vinorelbine tartrate
Incompatible
Allopurinol sodium
Hydrocortisone sodium succinate
Piperacillin sodium–tazobactam sodium
Variable
Heparin sodium

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.100

• Importance of informing patients of other important precautionary information. (See Cautions.)