CIS-MDP
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CIS-MDP (CIS-MDP).
CIS-MDP (cisplatin) is a platinum-containing antineoplastic agent that forms intrastrand and interstrand DNA crosslinks, inhibiting DNA replication and transcription through binding to purine bases.
| Metabolism | Cisplatin undergoes nonenzymatic conversion to inactive metabolites via hydrolysis and complexation with proteins. It is not significantly metabolized by cytochrome P450 enzymes. The primary route of elimination is renal excretion of unchanged drug and metabolites. |
| Excretion | Renal: 85-95% of administered dose excreted unchanged in urine within 24 hours; biliary/fecal: <5% eliminated via feces. |
| Half-life | Terminal elimination half-life: 6-8 hours; clinically relevant for imaging timing and clearance from blood pool. |
| Protein binding | Approximately 25-30% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.2-0.3 L/kg; reflects distribution into extracellular fluid and bone matrix. |
| Bioavailability | Intravenous: 100% (only route of administration). |
| Onset of Action | Intravenous: Radiolabel uptake in bone begins within minutes; optimal imaging at 2-4 hours post-injection. |
| Duration of Action | Bone uptake persists for 24-48 hours, allowing delayed imaging; soft tissue clearance occurs within 4-6 hours. |
20 mCi (740 MBq) intravenous injection for bone scintigraphy; imaging performed 2-4 hours post-injection.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment; however, image quality may be compromised in severe renal failure due to reduced skeletal uptake and increased soft tissue retention. |
| Liver impairment | No dose adjustment required for hepatic impairment; not hepatically metabolized. |
| Pediatric use | 0.20-0.25 mCi/kg (7.4-9.25 MBq/kg) intravenous injection; minimum dose 2 mCi (74 MBq). |
| Geriatric use | No specific dose adjustment required; use standard adult dose unless significant renal impairment present. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CIS-MDP (CIS-MDP).
| Breastfeeding | Technetium Tc-99m medronate is excreted in human breast milk. The M/P ratio is not established. Interruption of breastfeeding is recommended for at least 24-48 hours after administration to minimize radiation exposure to the infant. Specific advice should be sought from nuclear medicine physician. |
| Teratogenic Risk | Technetium Tc-99m medronate (CIS-MDP) is a radioactive diagnostic agent. There are no adequate studies in pregnant women. The risk of fetal harm is related to radiation exposure. The US Nuclear Regulatory Commission recommends a fetal dose limit of 5 mSv during pregnancy. Potential fetal effects include increased risk of childhood cancer, and possible teratogenic effects at high doses. Risk is highest during first trimester. |
■ FDA Black Box Warning
CIS-MDP is a highly emetogenic chemotherapeutic agent. It must be administered under the supervision of a qualified physician experienced in cancer chemotherapy. Cumulative renal toxicity is dose-limiting; assess renal function before and during therapy. Severe myelosuppression, including thrombocytopenia and leukopenia, may occur. Anaphylactic-like reactions have been reported. Ototoxicity, especially high-frequency hearing loss, is cumulative and may be worse in children. Cisplatin is contraindicated in patients with preexisting renal impairment, hearing impairment, or myelosuppression unless the benefit outweighs the risk.
| Serious Effects |
Absolute: history of allergic reaction to cisplatin or other platinum-containing compounds, preexisting severe renal impairment (CrCl < 30 mL/min), hearing impairment, severely myelosuppressed patients, pregnancy. Relative: patients with preexisting peripheral neuropathy, history of significant ototoxicity, dehydration, active infection, or concurrent nephrotoxic drugs.
| Precautions | Renal toxicity: monitor serum creatinine, BUN, creatinine clearance, and electrolytes; maintain adequate hydration and diuresis. Neurotoxicity: peripheral neuropathy may be dose-limiting; monitor for paresthesias. Ototoxicity: audiometry recommended at baseline and periodically. Myelosuppression: monitor complete blood counts regularly. Electrolyte disturbances: hypomagnesemia, hypocalcemia, hypokalemia, and hypophosphatemia common; replace as needed. Hypersensitivity reactions: may occur, treat appropriately. Nausea/vomiting: use antiemetics aggressively. Hemolytic-uremic syndrome has been reported. Use caution in patients with prior platinum-based therapy. |
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| Fetal Monitoring | No specific monitoring required other than verifying pregnancy status prior to administration. Inadvertent exposure should be evaluated by a radiation safety officer and fetal dose estimated. |
| Fertility Effects | No known effects on fertility. Animal studies have not been conducted. Radiation exposure may theoretically affect gonadal tissues at very high doses, but diagnostic doses are unlikely to cause permanent impairment. |