Presentation and Status in Health Basket
Film Coated Tablets
60 X 250 mg
Film Coated Tablets
30 X 500 mg
One tablet of Remotiv 250 mg morning and evening.
One tablet of Remotiv 500 mg morning or evening. The tablets should be swallowed, without chewing, with a little liquid, preferably during or after a meal. Remotiv 500 mg tablet is not easily split.
The product should be taken for at least 14 days, since onset of action may be deferred until then. A minimum length of therapy of 4-6 weeks is recommended. The treatment period is up to 12 weeks.
Remotiv may be prescribed for more than 12 weeks following the physician’s assessment of the benefit-safety profile in long-term use.
For the treatment of symptoms of mild to moderate depression including dejected mood, mood lability, anxiety, inner restlessness, states of tension, difficulty in falling asleep and sleeping through the night which is associated with these conditions.
Hypersensitivity. Known photosensitivity. Concurrent use of immunosuppressants (systemic), medicdbines for HIV and chemotherapeutic drugs.
Although extracts of St. John’s wort have been used for many years without evidence of an adverse effect on the liver or kidney, there are no controlled clinical studies available in patients with impaired hepatic or renal function. Therefore, in such patients Remotiv should be used with caution and under medical supervision. In patients concurrently taking other drugs, especially drugs with a narrow therapeutic window, extracts of St. John’s wort should be taken only after careful consideration due to the possibility of potential drug interactions (see Drug Interactions). Plasma levels and/or the effect of the interactive drug should be monitored closely at the beginning of Remotiv therapy, when any change in dosage occurs and after Remotiv therapy is discontinued. Very rarely and especially in fair-skinned persons, unwanted reactions of the skin (sunburn- like redness) or eyes may occur after ingestion of St. John’s wort preparations and subsequent exposure to sun light. If such symptoms occur, the treatment must be discontinued. During treatment with Remotiv, the skin and eyes should therefore be protected from extensive sun exposure. It has been demonstrated that Remotiv does not affect driving ability or ability to use machinery safely. However, in isolated patients the underlying mood disorder or the medicine’s side effects may adversely affect the patient’s ability to drive or use machinery and these patients should be cautioned.
The most common adverse effects are gastrointestinal disturbances (4-6%), followed by headache, sweating, and asthenia (1-2%). Dizziness (<1%) and restlessness may also occasionally occur. If redness of the skin appears, therapy should be discontinued and the cutaneous symptoms should be followed-up. As for other anti-depressants, isolated cases of mania associated with the use of St. John’s wort have been reported.
Current data indicates that St. John’s wort preparations may induce hepatic cytochrome P450 enzymes, specifically CYP3A4, and transport proteins, specifically P-glycoprotein. This can result in drug interactions. Specifically, starting therapy with a St. John’s wort preparation can lead to a reduction in plasma levels of a concomitant medicine, and, conversely, stopping therapy with a St. John’s wort preparation can lead to an increase in plasma levels of a concomitant medicine. In case of an accidental intake of St. John’s wort preparations together with interactively acting substances, the St. John’s wort preparation should, generally, be discontinued gradually. Hyperforin (one of the constituents in St John’s wort) has been demonstrated to be responsible for many of the observed drug interactions. Therefore, due to its low hyperforin content, Remotiv may have less potential for drug interactions than other St. John’s wort preparations. Immunosuppressants (Cyclosporin and Tacrolimus and Sirolimus) Patients with a suppressed immune system from cyclosporine, tacrolimus or sirolimus must not be treated with St. John’s wort at the same time. St. John’s wort leads to a rapid and marked decrease in plasma levels and loss of the immunosuppressive effect with potentially severe consequences (transplant rejection). Anti-retroviral HIV-drugs from the group of non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) and proteinase inhibitors (e.g. indinavir) When treated with non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) and proteinase inhibitors (e.g. indinavir), the intake of St. John’s wort preparations is contra-indicated since St. John’s wort can lead to a decrease in plasma levels.
Cytostatics (Irinotecan/Imatinib): During treatment with irinotecan and imatinib, Remotiv is contraindicated. Interactions with other chemotherapy agents metabolized by CYP enzymes or P-glycoprotein are possible and should be avoided. Anticoagulants of the coumarin type (e.g. warfarin acenocoumarol, phenprocoumon) Patients taking oral anticoagulants must not be treated with St. John’s wort, since it influences their coagulation inhibiting effect (and increases the risk of thromboembolism). Antidepressives and other serotonergic substances (such as buspirone, amitriptyline, nortriptyline, citalopram, escitalopram, fluoxetine, paroxetine, sertraline, and others) Simultaneous use of St John’s wort and other anti-depressants such as selective serotonin re-uptake inhibitors (SSRIs) may lead to excessive serotonin stimulation and possible toxicity (serotonin syndrome) with autonomic dysfunction (such as perspiration, tachycardia, diarrhoea, fever), mental alterations (such as agitation, disorientation), and motor alterations (such as tremor, myoclonias). Concomitant use is not generally recommended and a sufficient washout period in-between Remotiv and other anti-depressants should be allowed in order to avoid serotonin syndrome. Similar precautions should be exercised for other serotonergic drugs such as buspirone. Selective serotonin 5-HT1 agonists used to treat migraine may theoretically also cause serotonin syndrome in concomitant use. Should the prescriber nevertheless decide to concomitantly prescribe Remotiv with an SSRI/SNRI or other serotonergic drug after a careful individual risk/benefit assessment, caution should be exercised and the patient should be closely monitored.
Methadone: Other preparations of St. John’s wort (not Remotiv) have been documented to cause a significant reduction in the plasma levels of methadone.
Digoxin: Prescribers should be aware that St. John’s wort preparations may interact with digoxin. Apparently due to Remotiv’s low hyperforin content, there is no evidence for a pharmacokinetic interaction between Remotiv and digoxin. A pharmacokinetic study showed that Remotiv (250 mg bid) had no effect on serum levels of digoxin. Drug interaction studies cannot predict with 100% certainty the response of an individual patient.
Hormonal Contraceptives: St. John’s wort can lead to reduced efficacy of hormonal contraceptives (e.g. oral products, injected depot preparations, sub cutaneous implants, transdermal, intrauterine, and vaginally applied products with hormone release). Several cases of interim bleeding with so-called low-dose micro pills (ethinylestradiol content 30 μg or lower) were reported internationally. Even individual cases of undesired pregnancies with hormonal contraceptives and concomitant intake of St. John’s wort were reported. Apparently due to Remotiv’s low hyperforin content, there is no evidence for a pharmacokinetic interaction between Remotiv and oral contraceptives. A pharmacokinetic study with a combined low-dose oral contraceptive (Lovelle=Mercilon=Feminet) showed that Remotiv (250 mg bid) did not affect the serum levels of the estrogenic or progesterone components of the oral contraceptive, and did not lead to spotting. Drug interaction studies cannot predict with 100% certainty the response of an individual patient.
Benzodiazepines: Other preparations of St. John’s wort (not Remotiv) have been documented to cause a significant reduction in the plasma levels of benzodiazepines that are metabolized via CYP3A4 such as alprazolam and midazolam. St. John’s wort should only be given with caution together with benzodiazepines
Anticonvulsants: There is also a theoretical possibility of an interaction between St. John’s wort and antiepileptics such as carbamazepine, phenobarbital and phenytoin. Stopping St. John’s wort abruptly may result in increased and possibly toxic, concentrations of the interacting drug.
Steroid hormones: It cannot be excluded that St. John’s wort preparations also influence the metabolisms of orally or intravenously applied steroid hormones. St. John’s wort should only be given with caution together with steroid hormones.
Statins: Other preparations of St. John’s wort (not Remotiv) have been documented to cause a significant reduction in the plasma levels or effects of simvastatin and atorvastatin, but not pravastatin.
Agents used for photodiagnostic procedures or for phototherapy: There is a possibility that concurrent use of Remotiv with agents used for photodiagnostic procedures or for phototherapy, eg porfimer, could lead to an increased risk of photosensitivity.
General: Surgeons/anesthesiologists should discuss with patients scheduled for surgery the need to initiate changes in dosing and administration of Remotiv during the peri-operative period. Remotiv must be discontinued at least 5 days before any surgery and started again only after consultation of a physician The amount of active ingredient may vary widely between different preparations containing St John’s wort. Switching from Remotiv to an alternative St. John’s wort preparation may therefore alter the degree of enzyme induction of other drugs taken concurrently.
Pregnancy and Lactation
Pregnancy & Lactation: Reproduction studies in animals have indicated no risks to the fetus. However, scientific evidence documenting the safe use of Remotiv during pregnancy and lactation in humans is not available. Therefore, the use of Remotiv in pregnant and nursing women should be avoided.
No acute or chronic toxic manifestations have been reported in humans but those side effects listed above could manifest with greater intensity. In addition, photosensitivity is also possible. In this case skin and eye exposure to sun or other UV irradiation (e.g. as found in solariums or tanning salons) should be avoided for about 1-2 weeks.