Does St. John's wort interfere with the antiandrogenic effect of oral contraceptive pills?

BACKGROUND: St. John's wort (SJW), a commonly used herbal remedy, has been shown to compromise the efficacy of drugs, including oral contraceptive pills (OCPs), by inducing cytochrome P-450. We investigated whether the simultaneous use of SJW with OCPs resulted in elevated serum androgen levels with implications of impaired OCP treatment of hirsutism and acne. MATERIALS AND METHODS: Fifteen healthy women were treated with the low-dose OC Loestrin 1/20trade mark for 2 months and then additionally with SJW for 2 months. Androgen and sex hormone-binding globulin (SHBG) levels were measured in serum by immunoassay methods; free testosterone (fT) was calculated. Results were analyzed using the Wilcoxon signed-rank test. RESULTS: There were no statistically significant differences in androgen levels after the addition of SJW in women using Loestrin 1/20trade mark. However, there were decreases in total testosterone and fT levels (10.7% and 15.8%, respectively) along with a small increase in SHBG levels (7.0%). CONCLUSIONS: In women using OCPs and SJW simultaneously, it appears that SJW does not interfere with the antiandrogenic properties of OCPs.

Oral contraceptive steroid induced platelet coagulant hyperactivity: dissociation of in vivo and in vitro effects.

The use of oral contraceptives (OC) has been associated with an increased risk of thromboembolic events in a subset of women. Factors predisposing to this problem are still not clearly defined although an increased platelet coagulant activity (CA) has been reported. This study was designed to evaluate the CA of platelets from asymptomatic current OC users compared with control subjects. The asymptomatic OC users were found to have evidence of hypercoagulability in the form of increased availability of platelet CA. These findings were present in both collagen stimulated and unstimulated platelets. In order to understand the mechanism we examined the in vitro effects of estradiol and/or progesterone on platelets. Platelets from normal males were incubated for one hour with estrogen and/or progesterone. There was no significant difference in CA of hormone treated platelets compared with control platelets from the same donor. CA was analyzed in platelets exposed to epinephrine, adenosine diphosphate, and collagen in the platelet aggregometer. Although a dose dependent effect was observed on CA of platelets exposed to the range of aggregating agents, the results show no significant difference between CA of the hormone treated and control platelets (p greater than 0.05). Likewise, platelet aggregation and release of nucleotide were not different between hormone treated and control platelets. Thus a direct effect of the hormones on platelets is an unlikely mechanism causing the increased CA seen in OC users.

Adverse drug interactions in dental practice: interactions involving antibiotics. Part II of a series.

BACKGROUND: The prudent use of antibiotics is an integral part of dental practice. While these agents generally are considered safe in the dental setting, their use can result in interactions that can lead to serious morbidity in dental patients. METHODS: The faculty of a symposium entitled "Adverse Drug Interactions in Dentistry: Separating the Myths From the Facts" did an extensive literature review on drug interactions. Through this, they were able to establish a significance rating of alleged adverse drug interactions as they relate to dentistry, based on their scientific documentation and severity of effect. The author of this article focused on antibiotics. RESULTS: Most of the reported drug interactions discussed in this article are well-documented by clinical studies. It is particularly important that dentists be aware of the potentially serious and life-threatening interactions of the antibiotics erythromycin, clarithromycin and metronidazole, and of the antifungal agents ketoconazole and itraconazole, with a host of other drugs whose metabolism is impaired by these antimicrobial agents. In contrast, the alleged ability of commonly employed antibiotics to reduce the effectiveness of oral contraceptive agents is not adequately supported by clinical research. It still is recommended, however, that clinicians discuss this possible interaction with their patients, as it might represent a relatively rare event that cannot be discerned in clinical trials. CONCLUSIONS: Potentially serious adverse drug interactions can occur between antimicrobial agents used in dental practice and other drugs patients are taking for a variety of medical conditions. CLINICAL IMPLICATIONS: It is important that dentists stay abreast of potential drug interactions involving antibiotics to avoid serious morbidity among their patients.

Antibiotics and oral contraceptives.

With the exception of rifampin-like drugs, there is a lack of scientific evidence supporting the ability of commonly prescribed antibiotics, including all those routinely employed in outpatient dentistry, to either reduce blood levels and/or the effectiveness of oral contraceptives. To date, all clinical trials studying the effects of concomitant antibiotic therapy (with the exception of rifampin and rifabutin) have failed to demonstrate an interaction. Like all drugs, oral contraceptives are not 100% effective with the failure rate in the typical United States population reported to be as high as 3%. It is thus possible that the case reports of unintended pregnancies during antibiotic therapy may simply represent the normal failure rate of these drugs. Considering that both drug classes are prescribed frequently to women of childbearing potential, one would expect a much higher rate of oral contraceptive failure in this group of patients if a true drug:drug interaction existed. On the other hand, if the interaction does exist but is a relatively rare event, occurring in, say, 1 in 5000 women, clinical studies such as those described in this article would not detect the interaction. The pharmacokinetic studies of simultaneous antibiotic and oral contraceptive ingestion, and the retrospective studies of pregnancy rates among oral contraceptive users exposed to antibiotics, all suffer from one potential common weakness, i.e., their relatively small sample size. Sample sizes in the pharmacokinetic trials ranged from 7 to 24 participants, whereas the largest retrospective study of pregnancy rates still evaluated less than 800 total contraceptive users. Still, the incidence of such a rare interaction would not differ from the accepted normal failure rate of oral contraceptive therapy. The medico-legal ramifications of what looks like at best a rare interaction remains somewhat "murky." On one hand, we have medico-legal experts advising the profession to exercise caution and warn all oral contraceptive users of a potential reduction in efficacy during antibiotic therapy. These opinions are not evidence-based and rely heavily on one or two legal proceedings that cannot even be substantiated. On the other hand, there is one recently published legal proceeding in which the outcome was in favor of the oral surgeon. There is clearly a need for additional scientific research in oral contraceptive users that incorporates larger sample sizes, different time courses (prophylactic use versus standard 7-10 day use versus extended use), and different delivery systems (systemic administration versus local-controlled delivery) of antibiotic therapy. Though experts on this topic still recommend informing oral contraceptive users of the potential for a rare interaction, and for clinicians to advise them to employ additional barrier techniques of birth control during antibiotic therapy and for at least 1 week beyond the last dose [40], it is hoped that a set of guidelines regarding this controversy will eventually be published that is evidence-based, and not solely the results of anecdotal reports, expert opinions, and legal proceedings.

[Retinoids: drug interactions]. / Rétinoïdes: interactions médicamenteuses.

PIP: There is little available literature on possible drug interactions involving retinoids despite their widespread use. Unlike some other molecules, the retinoids regardless of their generation do not entail a high risk of interference with other medications. A current study found that concomitant administration of etretinate did not significantly modify the timing or value of the peak serum level of 8 methoxy sporalene. Isotretinoin seems to have an inhibiting effect on certain microsomal hepatic and cutaneous oxydases. An isolated observation has been reported of reduced serum concentration of the antiepileptic Carbamazepine in a patient treated with isotretinoin for severe acne. The report, through unconfirmed, should prompt intensified monitoring of patients receiving antiepileptics and retinoids. Among potential pharmacodynamic interactions, studies with the most evident practical importance have assessed possible interference of orally administered retinoids with the efficacy of oral contraceptives (OCs). 1 study of isotretinoin and OCs concluded on the basis of serum levels of progesterone on the 21st or 22nd cycle day that there was no interference. Another study using the same evaluation criteria concluded that there is no interaction between the aromatic retinoids etretinate or acitretin and OCs. The use of low-dose progestins is however not recommended. A recent study on healthy volunteers demonstrated the absence of influence of acitretin on the efficacy of the antivitamin K agent phenprocoumon. The combination of cyclines with isotretinoin can cause intracranial hypertension and is formally contraindicated. Intracranial hypertension has also been reported with aromatic retinoids, which are not recommended. The combination of lithium and retinoids should also be avoided. Because of the additive effect of undesirable side effects, the combination of retinoids and potentially hepatotoxic molecules especially methotrexate and of isotretinoin and potentially photosensitizing molecules should be avoided.^ieng

Antibiotic interference with oral contraceptive steroid efficacy.

PIP: Dentists prescribing antibiotics to women of childbearing age should be aware that current lower dosage oral contraceptives may fail and cause pregnancy, putting the practitioner at risk for damage claims. The most common antibiotics used in dental practice that may compromise oral contraceptive efficacy are penicillins, such as penicillin V, penicillin G, ampicillin, flucloxacillin, tolampicillin, amoxycillin and cloxacillin, and tetracyclines, such as tetracycline, oxytetracycline, doxycycline and chlortetracycline. Other common antibiotics include sulfonamides, erythromycin, metronidazole, griseofulvin and cephalosporins. The physiological basis for failure of the combined pill is loss of gut bacteria, and decreased enteric recycling of estrogen metabolites. The reason why progesterone-only pills may fail is unknown, and probably not related to drug interaction. Studies on blood levels of estrogens are conflicting; furthermore, it is impossible to predict which woman is at risk. Dentists should inform all women of childbearing age of possible failure of oral contraceptives. They should attempt to get an accurate drug history from female patients, and insert a signed copy in patients' record. It would be helpful to remind the pharmacist to label oral contraceptive prescription bottles with warnings about concurrent antibiotic usage.^ieng

Cicloxilic acid and the bile lipids in oral contraceptive users.

Cholesterol supersaturation of gallbladder bile induced by oral contraceptives is significantly reduced by the administration of cis-2-hydroxy-2-phenyl-cyclohexane-carboxilic acid (cicloxilic acid), a choleretic substance which has been demonstrated to exert an antilithogenic effect in the rat and in man.

[New aspects of tuberculosis therapy]. / Neuere Gesichtspunkte zur Tuberkulosetherapie

The introduction of ethambutol and rifampicin has modified the therapy of tuberculosis. Therapy in hospitals or sanatoria can be shortened, and intermittent regimens (once or twice weekly under supervision) are possible. Better knowledge of the side effects of particular drugs, particularly rifampicin, (such as allergic reactions in intermittent administration and reduced effect of oral contraceptives) has been gained. Instead of mere supervision, preventive chemotherapy is given in many cases such as in recently discovered fibrotic lesions and in high risk cases (silicosis, treatment with corticosteroids and immunosuppressive agents)minadequate treatment may lead to functional impairment such as fibrosis and cor pulmonale. These aspects are discussed and the resultant guidelines for the treatment of tuberculosis are presented.

PIP: The introduction of ethambutol and rifampicin has changed tuberculos is treatment, rendering possible ambulatory treatment with intermittent regimens. The steroid metabolic effects of Rifampicin, however, pose problems when tuberculostatic and contraceptive therapies are concurrent. It has been reported that metabolism of ethinyl estradiol is intensified by a factor of 4 during rifampicin therapy, explaining the cases of pregnancy occurring during simultaneous rifampicin and contraceptive therapy. Menstrual cycle disturbances have also been observed in patients treated only with Rifampicin. The author recommends that oral contraceptives and rifampicin not to be taken together; which course of therapy should be preferred depends on the ind ividual situation.

Anticonvulsants in pregnancy.

OBJECTIVE: To review the potential problems and their management associated with the use of anticonvulsant drugs during pregnancy. DATA SOURCES: Studies published between 1968 and 1990 assessing the effect of pregnancy on the pharmacokinetics of anticonvulsant drugs, the teratogenicity of anticonvulsants, breast feeding and anticonvulsants and use of the oral contraceptive pill in patients taking anticonvulsant medication, were reviewed. RESULTS OF DATA SYNTHESIS: In general, plasma levels fall during pregnancy and rise during the puerperium. A number of factors including possible reduced absorption, increased volume of distribution, reduced protein binding, increased clearance and noncompliance, contribute to this fall in plasma concentration. All anticonvulsants are potentially teratogenic. The incidence of fetal malformations is higher in patients treated with multiple anticonvulsant drugs and on higher dosages with higher plasma levels. Anticonvulsants are excreted in low concentrations in breast milk. All anticonvulsants except valproic acid have been associated with failure of the oral contraceptive pill. This is due to liver enzyme induction of these drugs. CONCLUSION: As plasma levels of anticonvulsants fall during pregnancy, concentrations should be monitored regularly. Due to the fall in protein binding, marginally low total plasma levels of highly protein bound drugs may not reflect reduced unbound levels, and hence an increase in dosage may not be required. In order to reduce teratogenicity, one should aim to use a single anticonvulsant drug and the lowest dosage able to achieve seizure control. In general, breast feeding is not contraindicated.

PIP: The objective of this study was to review the potential problems and their management associated with the use of anticonvulsants in pregnancy. Studies published between 1968-90 assessing the effect of pregnancy on the pharmacokinetics of anticonvulsant drugs, the teratogenicity of anticonvulsants, breastfeeding, and anticonvulsants and the use of oral contraceptives (OCs) in patients taking anticonvulsant medication were reviewed. In general, plasma levels fall during pregnancy and rise during the puerperium. A number of factors including possible reduced absorption, increased volume of distribution, reduced protein binding, increased clearance, and noncompliance all contribute to this fall in plasma concentration. All such drugs are potentially teratogenic. The incidence of fetal malformations is higher in those patients treated with multiple anticonvulsant drugs and on higher dosages with higher plasma levels. Anticonvulsants are excreted i low concentrations in breastmilk. All except valproic acid have been associated with the failure of OCs, this due to liver enzyme induction of these drugs. As plasma levels of anticonvulsants fall during pregnancy, concentrations should be monitored regularly. Due to the fall in protein binding, marginally low total plasma levels of highly protein bound drugs may not reflect reduced unbound levels, and thus an increase in dosage may not be required. In order to reduce teratogenicity, one should aim to use a single anticonvulsant drug and the lowest dosage able to receive seizure control. In general, breastfeeding is not contraindicated.