Drugs 3: Vinblastine

Vinblastine is the agent in the ABVD regimen I feel as though I know the least about.  The other three drugs at least have one easy thing about them:  doxorubicin = heart, bleomycin = lungs, and for me, dacarbazine = pain.  I honestly don't even remember reading about vinblastine once in pharmacy school.  The other name for vinblastine is Velban and it is a plant alkaloid.  It is generic.


This little factoid comes from the package insert:

It is the salt of an alkaloid extracted from Vinca rosea Linn., a common flowering herb known as the periwinkle.

An even more interesting piece of history comes from wikipedia:

Vinblastine was first isolated by Robert Noble and Charles Thomas Beer from the Madagascar periwinkle plant. Vinblastine's utility as a chemotherapeutic agent was first discovered when it was crushed into a tea. Consumption of the tea led to a decreased number of white blood cells; therefore, it was hypothesized that vinblastine might be effective against cancers of the white blood cells such as lymphoma. 

It has an interesting looking molecular structure.

Like the others, vinblastine is an IV product, given as a short infusion rather than slow push.  It is a moderate vesicant.  My dose is 13.44mg IV every other week, or 6mg/m2.  

How does it work?  The package insert is not as clear as Lexi-Comp.  Using the latter resource:

Vinblastine binds to tubulin and inhibits microtubule formation, therefore, arresting the cell at metaphase by disrupting the formation of the mitotic spindle; it is specific for the M and S phases. Vinblastine may also interfere with nucleic acid and protein synthesis by blocking glutamic acid utilization.

In other words, it inhibits cell division by binding to the parts of the cell that push and pull chromosomes apart as daughter cells are about to split.  For those of you interested in pharmacology, the package insert has other interesting information on effect reversal. 

Vinblastine has low emetic potential (<10%).  It is known for its myelosuppressive properties, causing leukopenia and granulocytopenia (nadir: 5-10 days; recovery: 7-14 days).  Incidentally, this seems like an appropriate spot for a pictorial.  Here is a graph of my WBCs.

Any guesses when the chemotherapy started?    Vinblastine is contraindicated in "significant granulocytopenia."    

Other side effects include constipation, alopecia, bone and jaw pain, malaise, and hypertension.   More rare things include a host of GI effects including mucositis and a metallic taste.   It can cause paresthesias, photosensitivity, and rash.  Other curious things include SIADH, Raynaud's, and nystagmus. 

Otic side effects are even more curious to me, and Lexi lists the following:  Auditory damage, deafness, vestibular damage.  I have had, almost daily for weeks, that sensation where your ears need to be popped.  They don't pop, though, and simply pressing on them seems to cure the weird sensation.  (So if I have my hands over my ears near you, I'm not trying to be rude.) However, I've not noticed any balance issues.

Vinblastine is an interesting drug from a pharmacokinetic perspective.  Per the package insert, it has a triphasic serum decay pattern.   The terminal half life is 25 hours, therefore, it is about 4-5 days until it is nearly all gone.  It has a very large volume of distribution (27L/kg) and is extensively bound (99%).  

Vinblastine is also interesting metabolically:  Per Lexi, it is a substrate of cytochrome P450 isozymes 2D6, 3A4, and P-glycoprotein.  Meanwhile, it inhibits 2D6 and 3A4 while inducing PGP.  It is a weak inhibitor, however.  This can obviously lead various drug-drug interactions, and so, I decided to look at the interaction profile of my ABVD regimen.  Aprepitant (Emend) can actually boost the concentrations of adriamycin and vinblastine mildly.  Adriamycin and vinblastine are also PGP players, but since the drugs are not given orally and we are not aiming for the CNS, the interaction is only theoretical.  Bleomycin and dacarbazine show no interactions.  What else?  These chemos can decrease my zyrtec and increase my flonase.  No big deal.

What else is vinblastine used for?

Hodgkin's and non-Hodgkin's lymphoma, testicular cancer, breast cancer, mycosis fungoides, Kaposi's sarcoma, histiocytosis (Letterer-Siwe disease), choriocarcinoma,

 bladder cancer, melanoma, nonsmall cell lung cancer (NSCLC), ovarian cancer, and soft tissue sarcoma (desmoid tumors).

What else to say about vinblastine?  Package insert is here.  Chemocare website is here.  Lymphomainfo.net website here.