Vaniqa (Eflornithine)
Ornidyl®, Vaniqa, Vaniqa Cream(Cream 13.9 %)
Classification:
Dermatological Agents
Description: Eflornithine (or DFMO), is used topically to reduce unwanted facial hair in women, and parenterally to treat protozoal infections. In the US, the drug is only commercially available as the topical cream. The intravenous formulation of eflornithine has been used to treat African sleeping sickness as well as Pneumocystis carinii pneumonia (PCP). Systemic eflornithine has a serious side effect profile, but is considered less toxic than the arsenical melarsoprol. An oral dosage form of eflornithine is under investigation for trypanosomiasis as well as for cancer treatment or chemoprevention (Ilex Oncology, San Antonio, TX). Investigational studies have included superficial bladder cancer, Barrett’s esophagus, non-melanoma skin cancer, recurrent colon polyps and prostate cancer. In January 2004, a phase III trial of eflornithine in superficial bladder cancer was discontinued; the findings of an independent monitoring board indicated that eflornithine did not prevent the recurrence of bladder cancer any more than placebo. Other investigational uses of eflornithine include the treatment of intestinal cryptosporidium, gliomas, breast cancer prophylaxis or adjuvant treatment and the topical treatment of pseudofolliculitis barbae. The topical formulation of eflornithine was approved by the FDA on July 31, 2000. The FDA approved the IV formulation, which is designated as an orphan drug, in November 1990. Parenteral eflornithine is only available from the World Health Organization.
Mechanism of Action: Eflornithine is a specific irreversible inhibitor of the enzyme ornithine decarboxylase (ODC). In all mammalian and many non-mammalian cells, decarboxylation of ornithine by ODC is a mandatory step in the production of polyamines (i.e., putrescine, spermine, and spermidine). Polyamines are ubiquitous in living cells and are thought to play important roles in nucleic acid synthesis, cell division and differentiation. In sleeping sickness, eflornithine deprives the trypanosomes of ODC and polyamine synthesis for a prolonged period compared with mammalian cells, leading to cessation of replication and growth of the parasite. Eflornithine exerts trypanostatic action. Eflornithine is not considered universally effective against the Trypanosoma class of organisms; the drug does not appear to adequately treat sleeping sickness caused by Trypanosoma rhodesiense.
Similarly, ODC activity has been detected in P. carinii and accounts for eflornithine activity in PCP. The onset of action may take one to two weeks using the IV formulation for trypanosomiasis and PCP.
There are no studies evaluating the mechanism of action of topical eflornithine in the reduction of unwanted facial hair. However, it is postulated that topical eflornithine irreversibly inhibits skin ODC activity, resulting in a reduction in the rate of hair growth. The onset of action may take 4-8 weeks using the topical cream for facial hirsutism.
Since ODC is elevated in most tumors and pre-malignant lesions, oral eflornithine (DFMO) is being investigated as a cancer treatment and chemopreventative. DFMO inhibits the growth of rapidly dividing cells that have an obligatory need for polyamine synthesis, i.e., tumor cells.
Pharmacokinetics: Eflornithine is administered orally, parenterally and topically. When applied topically, percutaneous absorption is < 1%. Following oral administration, bioavailability is 55% and peak serum levels occur within approximately 5 hours. Bioequivalence has been demonstrated between the investigational oral liquid and tablet formulations of eflornithine. Eflornithine does not bind significantly to human plasma proteins. Eflornithine crosses the blood-brain barrier and produces cerebrospinal fluid to blood ratios between 0.13 and 0.51. One study suggests that CSF levels need to remain above 50 nmol/ml for a trypanosomiasis cure, but the amount of time concentrations need to remain above this level is unknown. The terminal elimination half-life is roughly 3 hours for the IV formulation and 8 hours for the topical cream. Eflornithine is not known to be metabolized; 80% of the drug is excreted unchanged in the urine within 24 hours.
Special Populations: Systemic eflornithine requires dosage adjustment in renal impairment, although specific guidelines are not available. Higher failure rates of eflornithine in children versus adults are attributed to different pharmacokinetics in children, resulting in lower CSF concentrations at similar weight-adjusted doses.
Related entries
Syndicate
|
