Vinblastine

Common side effects of vinblastine include:

• hair loss
• nausea
• vomiting
• diarrhea
• a decrease in white blood cells and platelet counts.
• constipation
• cramping
• weight loss
• changes in taste and appetite
• mouth sores
• anemia

The side effects listed below are serious and need to be told to your doctor about within 24 hours of noticing them:

• vomiting more than four to five times in a day
• diarrhea more than four to five times in a day
• constipation
• strange bleeding or bruising
• bone pain
• severe stomach pain
• sores on the lips or mouth
• blood in the urine or stool (this can look like black or tarry stools) 

This is not a complete list of this medication’s side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Vinblastine is usually administered by a healthcare provider in a medical setting making it unlikely for an overdose to occur. However, if overdose is suspected, seek emergency medical attention.

Vinblastine is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Vinblastine is used to treat Hodgkin's disease, certain types of lymphoma, testicular cancer, breast cancer, choriocarcinoma (a type of uterine cancer), Kaposi's sarcoma, and Letterer-Siwe disease.

Vinblastine is often used in combination with other cancer medications.

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

Prior to the use of the drug, patients should be advised of the possibility of untoward symptoms.

In general, the incidence of adverse reactions attending the use of Vinblastine sulfate appears to be related to the size of the dose employed.  With the exception of epilation, leukopenia and neurologic side effects, adverse reactions generally have not persisted for longer than 24 hours.  Neurologic side effects are not common; but when they do occur, they often last for more than 24 hours.  Leukopenia, the most common adverse reaction, is usually the dose-limiting factor.

The following are manifestations that have been reported as adverse reactions, in decreasing order of frequency.  The most common adverse reactions are underlined:

HematologicLeukopenia (granulocytopenia), anemia, thrombocytopenia (myelosuppression).

DermatologicAlopecia is common.   A single case of light sensitivity associated with this product has been reported.

GastrointestinalConstipation, anorexia, nausea, vomiting, abdominal pain, ileus, vesiculation of the mouth, pharyngitis, diarrhea, hemorrhagic enterocolitis, bleeding from an old peptic ulcer and rectal bleeding.

NeurologicNumbness of digits (paresthesias), loss of deep tendon reflexes, peripheral neuritis, mental depression, headache, convulsions.

Treatment with vinca alkaloids has resulted rarely in both vestibular and auditory damage to the eighth cranial nerve.  Manifestations include partial or total deafness which may be temporary or permanent, and difficulties with balance including dizziness, nystagmus and vertigo.  Particular caution is warranted when Vinblastine sulfate is used in combination with other agents known to be ototoxic such as the platinum-containing oncolytics.

CardiovascularHypertensionCardiac effects such as myocardial infarction, angina pectoris and transient abnormalities of ECG related to coronary ischemia have been reported very rarely.  Cases of unexpected myocardial infarction and cerebrovascular accidents have occurred in patients undergoing combination chemotherapy with Vinblastine, bleomycin and cisplatin. Raynaud’s phenomenon has also been reported with this combination.

PulmonarySee PRECAUTIONS.

MiscellaneousMalaise, bone pain, weakness, pain in tumor-containing tissue, dizziness, jaw pain, skin vesiculation, hypertension, Raynaud’s phenomenon when patients are being treated with Vinblastine sulfate in combination with bleomycin and cis-platinum for testicular cancer.  The syndrome of inappropriate secretion of antidiuretic hormone has occurred with higher than recommended doses.

Nausea and vomiting usually may be controlled with ease by antiemetic agents.  When epilation develops, it frequently is not total; and, in some cases, hair regrows while maintenance therapy continues.

Extravasation during intravenous injection may lead to cellulitis and phlebitis.  If the amount of extravasation is great, sloughing may occur.

Signs and Symptoms

Side effects following the use of Vinblastine sulfate are dose related.  Therefore, following administration of more than the recommended dose, patients can be expected to experience these effects in an exaggerated fashion.  (See CLINICAL PHARMACOLOGY, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS.)  There is no specific antidote.  In addition, neurotoxicity similar to that with vincristine sulfate may be observed.  Since the major route of excretion may be through the biliary system, toxicity from this drug may be increased when there is hepatic insufficiency.

Treatment

To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center.  Telephone numbers of certified poison control centers are listed in the Physicians’ Desk Reference (PDR).  In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs and unusual drug kinetics in your patient.  Overdoses of Vinblastine sulfate have been reported rarely.  The following is provided to serve as a guide should such an overdose be encountered.

Supportive care should include the following: (1) prevention of side effects that result from the syndrome of inappropriate secretion of antidiuretic hormone (this would include restriction of the volume of daily fluid intake to that of the urine output plus insensible loss and perhaps the administration of a diuretic affecting the function of the loop of Henle and the distal tubule); (2) administration of an anticonvulsant; (3) prevention of ileus: (4) monitoring the cardiovascular system; and (5) determining daily blood counts for guidance in transfusion requirements and assessing the risk of infection.  The major effect of excessive doses of Vinblastine sulfate will be myelosuppression, which may be life-threatening.  There is no information regarding the effectiveness of dialysis nor of cholestyramine for the treatment of overdosage.

Vinblastine sulfate in the dry state is irregularly and unpredictably absorbed from the gastrointestinal tract following oral administration.  Absorption of the solution has not been studied.  If Vinblastine is swallowed, activated charcoal in a water slurry may be given by mouth along with a cathartic.  The use of cholestyramine in this situation has not been reported.

Symptoms of overdose will appear when greater-than-recommended doses are given.  Any dose of Vinblastine sulfate that results in elimination of platelets and neutrophils from blood and marrow and their precursors from marrow should be considered life-threatening.  The exact dose that will do this in all patients is unknown.  Overdoses occurring during prolonged consecutive-day infusions may be more toxic than the same total dose given by rapid intravenous injection.  The intravenous median lethal dose in mice is 10 mg/kg body weight; in rats, it is 2.9 mg/kg.  The oral median lethal dose in rats is 7 mg/kg.

Protect the patient’s airway and support ventilation and perfusion.  Meticulously monitor and maintain, within acceptable limits, the patient’s vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying if the drug has been swallowed.  Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed.  Safeguard the patient’s airway when employing gastric emptying or charcoal.

(vin BLAS teen)

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous, as sulfate:

Generic: 1 mg/mL (10 mL)

Solution Reconstituted, Intravenous, as sulfate:

Generic: 10 mg (1 ea [DSC])

Treatment of Hodgkin lymphoma; lymphocytic lymphoma; histiocytic lymphoma; mycosis fungoides; testicular cancer; Kaposi sarcoma; histiocytosis X (Letterer-Siwe disease); has also been used for the treatment of refractory/resistant breast cancer and choriocarcinoma

No dosage adjustment necessary.

In order to prevent inadvertent intrathecal administration, the Institute for Safe Medication Practices (ISMP) strongly recommends dispensing vinblastine in a minibag (NOT in a syringe). For IV administration only. Fatal if given intrathecally. The preferred administration is as a short infusion in a 25 to 50 mL minibag. If administration via a minibag is not possible, may also be administered as an undiluted 1-minute infusion into a free flowing IV line to prevent venous irritation/extravasation. Prolonged administration times (≥30 to 60 minutes) and/or increased administration volumes may increase the risk of vein irritation and extravasation.

Vesicant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote; remove needle/cannula; apply dry warm compresses for 20 minutes 4 times a day for 1 to 2 days; elevate extremity (Perez Fidalgo 2012). Remaining portion of the vinblastine dose should be infused through a separate vein.

Hyaluronidase: If needle/cannula still in place, administer 1 to 6 mL hyaluronidase (150 units/mL) into the existing IV line; the usual dose is 1 mL hyaluronidase for each 1 mL of extravasated drug (Perez Fidalgo 2012; Schulmeister 2011). If needle/cannula was removed, inject 1 to 6 mL (150 units/mL) subcutaneously in a clockwise manner using 1 mL for each 1 mL of drug extravasated (Schulmeister 2011) or administer 1 mL (150 units/mL) as 5 separate 0.2 mL injections (using a 25-gauge needle) subcutaneously into the extravasation site (Polovich 2009).

Concerns related to adverse effects:

• Bone marrow suppression: Leukopenia commonly occurs; granulocytopenia may be severe with higher doses. The leukocyte nadir generally occurs 5 to 10 days after administration; recovery typically occurs 7 to 14 days later. Monitor for infections if WBC <2,000/mm3. Leukopenia may be more pronounced in cachectic patients and patients with skin ulceration and may be less pronounced with lower doses used for maintenance therapy. Leukocytes and platelets may fall considerably with moderate doses when marrow is infiltrated with malignant cells (further use in this situation is not recommended). Thrombocytopenia and anemia may occur rarely.

• Extravasation: [US Boxed Warning]: Vinblastine is a vesicant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation. Extravasation may cause significant irritation. Individuals administering should be experienced in vinblastine administration. If extravasation occurs, discontinue immediately and initiate appropriate extravasation management, including local injection of hyaluronidase and moderate heat application to the affected area. Use a separate vein to complete administration.

• Gastrointestinal toxicity: Stomatitis may occur (rare); may be disabling, but is usually reversible.

• Neurotoxicity: May rarely cause disabling neurotoxicity; usually reversible. Seizures and severe and permanent CNS damage has occurred with higher then recommended doses and/or when administered more frequently than recommended.

• Pulmonary toxicity: Acute shortness of breath and severe bronchospasm have been reported, most often in association with concurrent administration of mitomycin; may occur within minutes to several hours following vinblastine administration or up to 14 days following mitomycin administration; use caution in patients with preexisting pulmonary disease.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; toxicity may be increased; may require dosage modification.

• Ischemic heart disease: Use with caution in patients with ischemic heart disease.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Special handling:

• Hazardous agent: Avoid eye contamination (exposure may cause severe irritation).

Other warnings/precautions:

• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.

• NOT for intrathecal use: [US Boxed Warning]: For IV use only. Intrathecal administration may result in death. To prevent administration errors, the Institute for Safe Medication Practices (ISMP) Targeted Medication Safety Best Practices for Hospitals initiative strongly recommends dispensing vinblastine diluted in a minibag (ISMP, 2014). If not dispensed in a minibag, affix an auxiliary label stating "For intravenous use only - fatal if given by other routes" and also place in an overwrap labeled "Do not remove covering until moment of injection." Vinblastine should NOT be prepared during the preparation of any intrathecal medications. After preparation, keep vinblastine in a location away from the separate storage location recommended for intrathecal medications. Vinblastine should NOT be delivered to the patient at the same time with any medications intended for central nervous system administration.

CBC with differential and platelet count, serum uric acid, hepatic function tests