A severe overdose can produce what looks like skin burns, and muscle spasms or even convulsions may occur. Case reports note that long-term use of glutethimide can decrease a person's calcium levels; one report tells of bones softening in a person who took the drug routinely for 10 years, and another report notes seizures occurring due to low calcium. The drug can also reduce a body's supply of vitamin D. After a dozen years of daily glutethimide ingestion, one person had lost so much muscle control that speech was difficult, unassisted walking was impossible, and control of urination and bowel movements was no longer possible. Similar case reports exist. Others, however, mention persons who took the drug for years without noticeable ill effect.
Abuse factors. Some illicit drug users take glutethimide with codeine. The combination supposedly produces a euphoria and stupor like heroin's. Users of the combination report increased sociability and feelings of intellectual insight in discussions that were actually about nothing. The drug mix can seriously impair breathing, and deaths are verified. Some of these deaths involve dosages of each drug that were theoretically safe, outcomes implying that glutethimide and codeine may boost each other's actions. Users of the combination have experienced typical unwanted actions of both drugs in addition to headaches, grouchiness, tremors, cramps, and trouble sleeping.
Glutethimide tolerance and dependence can develop. Withdrawal has symptoms similar to those seen with barbiturates. Seizures are noted in case reports. Among persons taking medical doses of glutethimide for months, a withdrawal syndrome can include hallucinations, fever, delirium, and convulsions. Case reports tell of withdrawal experiences that included catatonia. For addiction treatment, phenobarbital can be substituted for glutethimide, and a person can then be gradually weaned off the phenobarbital.
Drug interactions. The drug reduces effectiveness of warfarin, a medicine that fights heart attack and stroke by reducing blood clotting. Glutethimide is also supposed to be avoided if someone is taking the anti-blood-clotting substance coumarin. A U.S. Army aerospace test found that using alcohol with glutethimide did not harm breathing. That finding has rather narrow significance for most persons, but a more generally relevant finding came from an experiment showing that glutethimide raised blood alcohol levels of persons who had been drinking. Alcohol and glutethimide may be a mix to avoid. Antihistamines should be used cautiously with glutethimide. Animal experimentation shows that injection of marijuana's main active component THC (tetrahydrocannabinol) increases the potency of glutethimide, thereby increasing risk of overdose.
Cancer. Not enough scientific information to report.
Pregnancy. Glutethimide is related to thalidomide, perhaps the most notorious pharmaceutical cause of human birth defects. In experimentation with rats and rabbits glutethimide did not produce physically apparent birth defects. The death rate among rabbit offspring was 6%, however, compared to a 2% rate among offspring with no fetal drug exposure—a rate three times higher for the glutethimide group than for the nondrug group. One experiment found the death rate of rats with prenatal glutethimide exposure to be three times that of rats with no drug exposure. Surviving rats with fetal ex-
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