<p>An increased clearance of sex hormones due to hepatic enzyme induction may reduce the clinical efficacy of the drug and eventually cause irregular bleeding. Such hepatic enzyme-inducing properties have been established for hydantoins, barbiturates, primidone, carbamazepine, and rifampicin and are also suspected for oxcarbazepine, topiramate, felbamate and griseofulvin. The mechanism of this interaction appears to be based on the hepatic enzyme-inducing properties of these drugs. Maximal enzyme induction is generally not seen for 2-3 weeks but may then be sustained for at least 4 weeks after the cessation of drug therapy. In rare cases reduced E2 levels have been observed under the simultaneous use of certain antibiotics (e.g. penicillins and tetracycline).<br />
The main metabolites of DRSP are generated without involvement of the cytochrome P450 system. Inhibitors of this enzyme system are therefore unlikely to influence the metabolism of DRSP. Nevertheless, inhibitors of&#39;CYP3A4, like cimetidine, ketoconazole and others, may inhibit the metabolism of E2.</p>

<ul>
	<li>Interaction with alcohol</li>
	<li>Acute alcohol ingestion during use of HRT may lead to elevations</li>
	<li>Known or suspected premalignant conditions or malignancies, if sex steroid-influenced</li>
	<li>Presence or history of liver tumors (benign or malignant)</li>
	<li>Severe hepatic disease</li>
	<li>Presence or history of severe renal disease as long as renal function values have not returned to normal</li>
	<li>Acute arterial thromboembolism (e.g. myocardialinfarction, stroke)</li>
	<li>Active deep venous thrombosis,thromboembolic disorders,or a documented history of these conditions</li>
	<li>A high risk of venous or arterial thrombosis</li>
	<li>Severe hypertriglyceridemia</li>
	<li>Pregnancy or lactation (see section 4.6 Pregnancy and lactation)</li>
	<li>Hypersensitivity to the active substances or to any of the excipients</li>
</ul>