Parenteral products approved in the US.
The earliest product approved in the US was RIMSO-50 (recently acquired by BionichePharma USA, LLC). The product is indicated for the symptomatic relief of patients with interstitial cystitis, a condition involving inflammation
of the bladder wall (4). It is a sterile, nonpyrogenic aqueous DMSO formulation (50% w/w DMSO aqueous solution) supplied in
50-mL bottles. RIMSO-50 is instilled directly into a patient's bladder using an aseptic syringe or a catheter and is allowed
to remain in the bladder for 15 min before discharge.
Bayer Healthcare Pharmaceuticals(Leverkusen, Germany) has released Viadur, a subcutaneously implanted device that uses DMSO as a solubilizing excipient, for
the treatment of prostate cancer (5). The device is implanted in the upper arm and must be removed when a 12-month treatment
course has completed. Alza's Duros technology is used to administer leuprolide acetate in a sustained fashion over 12 months.
This device contains a solution of dimethyl sulfoxide USP (104 mg) and leuprolide acetate (72 mg) and represents an alternative
to other implanted depot delivery systems.
With regard to injectable products, there is currently one application listed in FDA's Center for Drug Evaluation and Research (CDER) inactive ingredient database (6). The product is intended for administration by intravenous infusion. The dosage
form of this product is described as "powder, for injection suspension, lyophilized." The amount of DMSO in this product is
not described.
There are two device applications referenced by FDA's Center for Devices and Radiological Health (CDRH). These applications are similar in that they use DMSO as a solubilizing excipient to deliver a medical polymer (ethyl
vinyl alcohol copolymer, EVOH) into the body to provide a structural benefit. The first of these device products (Onyx, EV3
Inc.) is a liquid embolic system intended for use in the brain as a treatment of brain arteriovenous malformations (7). The
medical polymer is injected as a DMSO solution, containing either 6 or 8% EVOH copolymer, at a controlled rate into the bloodstream.
As the DMSO dissolves in the bloodstream, a polymeric embolus forms that contains a micronized contrast agent. The other device
Tegress (C.R. Bard) serves as bulking agent in the urethra. The action is similar to the Onyx product by means of in situ precipitation of injected DMSO-EVOH copolymer solution in the body (8) .
One product referenced for topical application is listed in the CDER inactive ingredients database and is described as a topical
dressing (6). The maximum potency of DMSO is 16.5 mg. A number of other topical or transdermal products that include DMSO
are under FDA review for approval at the time of this writing.
Oral products approved in the US.
No approved applications have been developed in the US that incorporate DMSO as a component of an orally administered product.
DMSO is essentially nontoxic when ingested, having an oral single-dose LD-50 value of 17.4–28.3 g/kg (rat) (9). The low chronic
and acute oral toxicity may offer pharmaceutical formulators a delivery option for difficult-to-dissolve medications.
Products for animal health approved in the US.
Currently there are two products approved for veterinary use in the US. Domoso is indicated for use in horses for acute swelling
and is prepared both as a liquid and gel formulation (10). Domoso is 90% DMSO. Synotic contains 60% DMSO and 0.01% fluocinolone
acetonide and is approved for otic treatment in canines (10).
Cryopreservation.
Dimethyl sulfoxide USP, Ph Eur has long been appreciated as a media for the cryopreservation of bone marrow and blood components.
DMSO is an example of a substance "that would be generally acceptable" as a cryoprotectant for use in human cells, tissues,
and cellular and tissue-based products (HCT/Ps), as defined by FDA (11). HCT/Ps intended for use in human recipients are regulated
by the Center for Biologics Evaluation and Research (CBER). Among the applications referenced by CBER is an HIV test kit (Nuclisense HIV-1QT) (12). Dimethyl sulfoxide USP is widely
used in United States for the cryopreservation of hematopoietic stem cells supplied from umbilical cord blood at childbirth.
Cord blood can be used to treat certain genetic disorders (i.e., acute lymphoblastic leukemia) that affect the blood and immune
system by means of allogenetic or autologous injection.
DMSO-containing products marketed outside the US.
In Europe, there are several topical products in which DMSO acts as an excipient. One of these uses an antiviral (idoxuridine)
in the treatment of herpes zoster (13). A second product is approved for use in Canada and in the European Union for the topical
treatment of certain types of joint pain.
In Germany, DMSO was approved on an over-the-counter basis for sports-related injuries as Dolicur (Schering AG) and provisions
exist in the Russian republics that allow for DMSO self medication (14). DMSO is widely used in China for self-medicated topical
pain relief.
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