QUINACRINE STERILIZATION (QS)
SAFETY AND EFFICACY

by Jack Lippes, MD

Professor of Obstetrics and Gynecology, School of Medicine, State University of New York, Buffalo, 1975-present; President, Association of Planned Parenthood Physicians, 1977-1978; National Medical Advisory Committee, Planned Parenthood – World Population, 1969-1962, 1974-1977; Consultant, Population Council, 1960-1992; Vice-President for Research and Medical Affairs, Family Health International, 1984-1985; Inventor of the Lippes Loop IUD, 1959.

Workshop presentation at the American Public Health Association Annual Meeting, Chicago, IL, November 8, 1999

Is the drug “Quinacrine” (Q) safe?  More than one hundred million people in the world have taken Q over the past 50 years to prevent or treat malaria, children and pregnant women among them.  After 50 years of follow-up, no clusters of cancer have been reported.  No abnormalities of newborns have been observed.  During World War II, three million American soldiers took this drug while serving in the south Pacific.  Fifty-four years later there were no clusters of cancer in these veterans.  From this vast experience we have learned that ingesting Q on a daily basis for long periods of time has minimal toxicity.  There are very few drugs which have been used so extensively for so long a time, studied so thoroughly and whose safety remains unquestioned.

“But wait a minute,” say the doubters.  It is a different drug when put in the uterus.  Quinacrine inserted in the uterus is rapidly absorbed into the blood stream, as is also the case for absorption from the gut for oral administration.  Observing plasma levels after transcervical insertion, it is noted that these levels rapidly fall after 3 hours.  Where is the drug going?  Q is redistributed to all tissues of the body depending on circulation to these tissues.  During the brief 3 hours of high plasma concentration, the level of Q in the uterus is high as the Q pellets dissolve and the drug is absorbed.  This brief period is enough to produce scarring of the proximal fallopian tube leading to occlusion.

In the prevention of malaria and treatment of lupus, 100 mg of Q daily is prescribed, a yearly dose of 36,500 mg, often continuing for years.  The two doses for QS of 252 mg each, given a month apart, for a total dose of 504 mg, is minuscule by comparison.  Repeated daily doses are also necessary for treatment of malaria and giardiasis and produce far higher tissue concentrations of Q than the one or two insertions required for QS.  The distinguished doctor, Jaime Zipper, who discovered quinacrine sterilization, has records of 1500 QS cases performed in his clinic in Chile and then followed for 20 years.  No increase in the incidence of cancers and no serious problems were observed.  Isn’t this a completed phase I or phase II study?

American women are sterilized by tubal ligation.  This is usually done by laparoscopy, popularly known as “band aid surgery.”  The incision or incisions are only 4 or 5 millimeters, and can be covered by a band aid.  Other than opening the abdomen, this is the only sterilization method available to American women.  Examine laparoscopic sterilization for mortality.  Two deaths can be expected in 100,000 cases.  Zero with QS.  How about complications with the surgical method?

• General anesthesia has its own specific complications.  On rare occasions, the endotracheal tube may be placed in the esophagus instead of the trachea.  Curare-like drugs paralyze the patient’s ability to breathe.  With the endotracheal tube in the esophagus, the anesthesiologist pushes gas, including oxygen, into the stomach not into the lungs.  That error leads to anoxia and in a few minutes brain damage, and if the error is not detected, death.
• The Verres needle is important for laparoscopy.  It is used to produce a pneumoperitoneum, so there is space in the abdominal cavity enabling the surgeon to see the organs in the abdomen and to move the laparoscopic instruments.  That needle can perforate a blood vessel and a huge quantity of carbon dioxide may be injected into the bloodstream, creating a gas embolus.  Furthermore, a gas embolus can also occur if the abdomen is over-distended with carbon dioxide.  Now, a seriously ill patient is in the intensive care unit, and she may die.
• A 4 to 5 millimeter incision is made just beneath the umbilicus to facilitate a laparoscopic trocar puncturing the gas-distended abdomen.  Such a sharp instrument can and has punctured the bowel.  This usually is seen through the scope, but now the surgeon must make a large incision in the abdomen to repair that rent in the bowel.  This patient is not going home the same day.
• Cautery frequently is used for laparoscopic sterilization.  The fallopian tube must be interrupted.  One way to accomplish this through the laparoscope is to burn the tube and cut it through the burned area.  It is an effective method.  Unfortunately, there are times when a spark or something else happens that results in a burn of the intestine.  The patient has had her tubal ligation and goes home.  About 3 to 5 days later, that burned area ruptures and intestinal contents spill into the peritoneal cavity.  This patient is in acute pain as a result of this catastrophic event.  She returns to the hospital where the treatment is usually a bowel resection and the management of a severe peritonitis with all that this entails.

NONE of these serious accidents has ever happened with QS!!

Why should American women be compelled to take the risks of laparoscopy?  Why are American women denied the option of Quinacrine Sterilization?  Why hasn’t there been a clinical trial of QS in the United States?  Why?

Are there complications with QS?  Yes.  The most serious occur when the inserter perforates the uterus and quinacrine is deposited in the peritoneal cavity.  It is an uncommon accident, unique to QS.   It is painful, but once the Q is absorbed, pain diminishes and nothing else happens.  This is not life threatening.

Is the failure rate higher with QS than with laparoscopic sterilization?  Newer protocols for QS show a pregnancy failure rate of approximately two per 100 women after two years of use, about twice that reported for surgical sterilization.  But the risk of ectopic pregnancy following failures of surgical sterilization is much higher than for QS.  Using older QS data with a higher failure rate than the present, the QS risk of ectopic pregnancy in Vietnam per 1000 woman-years was found to be the same as that of surgical sterilization in the US:  0.89 vs. 0.7 to 0.8, respectively.

We should discuss costs.  This is a “no brainer.”  QS in the United States would be the charge for two office visits plus the cost of the pellets, perhaps $300 to $400.  Laparoscopic sterilization can run $3000 to $4000 and maybe more depending on where you are.

Some physicians think the IUD is the answer.  The method of inserting Q and an IUD is the same.  Why take on a new and untried method here in the US when we have the Copper T?  A word is needed about continuation rates.  As recorded in the 1999 edition of the Physician’s Desk Reference, combined data from the Population Council and WHO reveal that the Copper T 380A is discontinued by patients for a variety of reasons such as  expulsions, pain, backache, personal reasons and, most often, because of bleeding.  At the end of 3 years, only 23% of women who started with the  Copper T were still using it.  At the 10-year mark that continuation rate dropped to 5%.  Sterilization is the only method of family limitation where the continuation rate approaches 100%.  Why can’t we have a clinical trial of QS in the US directed by outstanding investigators working in our academic institutions perhaps under the supervision of the National Institutes of Health and/or the FDA?  Why can’t American women have Quinacrine Sterilization as an option?