1 tab daily without any break, taken preferably at the same time each day with some liquid as needed. Tablets must be taken continuously without regard to vaginal bleeding. When a pack is finished the next one should be started without interruption.
Tablet-taking can be started on any day of the menstrual cycle.
There is no experience with Kalist treatment >15 months in patients with endometriosis.
The efficacy of Kalist may be reduced in the event of missed tablets, vomiting and/or diarrhea (if occurring within 3-4 hrs after tab taking). In the event of missed tablet(s), the woman should take 1 tab only, as soon as she remembers, and should then continue the next day to take the tab at her usual time. A tablet not absorbed due to vomiting or diarrhea should likewise be replaced by 1 tablet.
Renal Impairment: There are no data suggesting the need for a dosage adjustment in patients with renal impairment.
Hepatic Impairment: Kalist is contraindicated in patients with present or past severe hepatic disease.
Administration: For oral use.
Effects of Other Drugs on Kalist: Individual Enzyme-Inducers or Inhibitors (CYP3A4): Progestogens including Kalist are metabolized mainly by the cytochrome P-450 3A4 system (CYP3A4), located both in the intestinal mucosa and in the liver. Therefore, inducers or inhibitors of CYP3A4 may affect the progestogen drug metabolism.
An increased clearance of sex hormones due to enzyme induction may reduce the therapeutic effect of Kalist and may result in undesirable effects eg, changes in the uterine bleeding profile.
A reduced clearance of sex hormones due to enzyme inhibition may increase the exposure to Kalist and may result in undesirable effects.
Substances with Enzyme-Inducing Properties: Interactions can occur with drugs (eg, phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, nevirapine and products containing St. John’s wort) that induce microsomal enzymes (eg, cytochrome P-450 enzymes) which can result in increased clearance of sex hormones.
Maximum enzyme induction is generally not seen for 2-3 weeks but may then be sustained for at least 4 weeks after the cessation of therapy.
The effect of the CYP3A4 inducer rifampicin was studied in healthy postmenopausal women. Co-administration of rifampicin with estradiol valerate/Kalist tablets led to significant decreases in steady-state concentrations and systemic exposures of Kalist and estradiol. The systemic exposure of Kalist and estradiol at steady state, measured by AUC (0-24 hrs), were decreased by 83% and 44%, respectively.
Substances with Enzyme-Inhibiting Properties: Known CYP3A4 inhibitors like azole antifungals (eg, ketoconazole, itraconazole, fluconazole), cimetidine, verapamil, macrolides (eg, erythromycin, clarithromycin and roxithromycin), diltiazem, protease inhibitors (eg, ritonavir, saquinavir, indinavir, nelfinavir), antidepressants (eg, nefazodone, fluvoxamine, fluoxetine) and grapefruit juice may increase plasma levels of progestogens and result in undesirable efffects.
In a study investigating the effect of CYP3A4 inhibitors (ketoconazole, erythromycin) on the combination of estradiol valerate/Kalist, steady-state Kalist plasma levels were increased. Co-administration with the strong inhibitor ketoconazole resulted in a 186% increase of AUC (0-24 hrs) at steady state for Kalist. When co-administered with the moderate inhibitor erythromycin, the AUC (0-24 hrs) of Kalist at steady state were increased by 62%.
The clinical relevance of these interactions is unknown.
Effects of Kalist on Other Drugs: Based on in vitro inhibition studies, a clinically relevant interaction of Kalist with the cytochrome P-450 enzyme mediated metabolism of other drugs is unlikely.
Note: The prescribing information of concomitant medication should be consulted to identify potential interactions.
Drug-Food Interactions: A standardized high fat meal did not affect the bioavailability of Kalist.
Other Forms of Interactions: The use of progestogens may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of (carrier) proteins (eg, corticosteroid-binding globulin and lipid/lipoprotein fractions), parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Changes generally remain within the normal laboratory range.
Incompatibilities: Not applicable.
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Information checked by Dr. Sachin Kumar, MD Pharmacology