Schisandra has been used as a tonic and restorative, and as a treatment for respiratory and GI disorders. Schisandra has also demonstrated liver protectant, nervous system stimulant, and adaptogenic effects. However, clinical trials to support these uses are limited.
Schisandra fruit is used as an adaptogen at dosages of 1.5 to 6 g/day of powdered product. In a clinical study, schizandra tablets containing 91.1 mg of extract per tablet (extract standardized for schizandrin and gamma-schizandrin at a level of 3.1 mg/tablet) was used to improve athletic performance. Examples of various doses of schizandra preparations used in official medicine in Russia include the following: Tinctura Fructum Schizandrae prepared with air-dried fruits and 95% ethanol given as 20 to 30 drops twice daily. Tinctura Seminum Schizandrae prepared with dried seeds and 95% ethanol, given as 20 to 30 drops twice daily. Infusion Fructum Schizandrae prepared with air-dried fruits and water (1:20 w/v), given as 150 mL twice daily. Fructum Schizandrae contains air-dried fruits, given at a dose of 0.5 to 1.5 g twice daily. Schizandra seed powder 0.5 to 1.5 g administered twice daily before lunch and the evening meal for 20 to 30 days. Schizandra seed extract prepared by extracting air-dried seeds with 95% ethanol, given as a single dose of 0.05 or 0.2 mL/kg.
Contraindications have not been identified.
Information regarding safety and efficacy in pregnancy and lactation is lacking. Various compounds from the stem of Schisandra propinqua were cytotoxic against rat luteal cells and human decidual cells in vitro.
Because of its documented effects on hepatic and gastric enzyme activity, particularly cytochrome P450 (CYP-450) 3A, it is possible that schisandra may interfere with the metabolism of coadministered drugs (eg, midazolam). Findings from a study of healthy volunteers suggest that dosage adjustment may be needed in individuals concomitantly taking P-glycoprotein (P-gp) substrates (eg, tacrolimus).
Research reveals little information regarding adverse reactions with use of schisandra.
No data.
Schisandra spp. are climbing, aromatic, woody vines with white, pink, yellow, or reddish male or female flowers. The fruits are globular and red with several kidney-shaped seeds. The fruit is harvested in autumn when fully ripened.Chevalier 1996 S. chinensis is native to northeastern and north central China and is found in eastern Russia. Synonyms are Kansura chinensis, Sphaerostemma japonica, Sphaerostemma japonicum, Maximoviczia chinensis, and Maximoviczia amurensis.
Schisandra is one of many traditional Chinese herbs recommended for treating cough and various nonspecific pulmonary diseases.Hikino 1984 It has been studied extensively in Chinese and Japanese literature. Schisandra has been used for healing purposes in traditional medicine for more than 2,000 years, often as an ethanolic tincture. The Chinese name for the plant, "wu-wei-zu," means "5 taste fruit" because schisandra is associated with sweet, sour, bitter, and salty flavors and an astringent effect. Salty and sour tastes were believed to have effects on the liver and testicles, while the bitter and astringent properties were thought to be beneficial to the heart and lungs. The sweet component was believed to have effects on the stomach.Panossian 2008 The plant has also been traditionally used to manage stress, balance fluid levels, improve sexual stamina, treat rash, stimulate uterine contractions, and improve failing senses. Schisandra has also been used for treatment of diarrhea and dysentery.Chevalier 1996
The chemistry of schisandra has been studied extensively. The fruit contains reducing sugars and up to 10% organic acids (carboxylic, malic, citric, tartaric). The seeds contain reducing sugars, alkaloids, and fatty esters; however, no flavones, glycosides, or tannins are found in the seeds or fruit.Ma 1968 Approximately 2% of the fruit (by weight) is composed of lignans with a dibenzocyclooctane skeleton (eg, schizandrin, deoxyschizandrin, and related compounds such as schizandrol and schizanderer). In some specimens, the lignan content can approach 19% in the seeds and 10% in the stems.Song 1983 More than 30 lignans have been identified in the seed,Hikino 1984 including gomisins A, B, C, D, F, and GIkeya 1979; tigloylgomisin P; and angeloylgomisin.Ikeya 1980 Other plant constituents include phytosterols, volatile oil, and vitamins C and E.Chevalier 1996 Analytical methods have been devised for processing and standardization purposes.Rao 1986, Suprunov 1975, Zhu 1988 Metabolism of schisandra components has been reported.Cui 1992, Cui 1993, Hendrich 1986
Schisandra has been used as a tonic and restorative, and as a treatment for respiratory and GI disorders. Schisandra has also demonstrated liver protectant, nervous system stimulant, and adaptogenic effects. However, clinical trials to support these uses are limited.
In one report, alcohol and acetone extracts of S. chinensis fruit demonstrated antibacterial activity.(Ma 1968)
In one study, 3 lignans (gomisin N, gomisin J, and schisandran C) suppressed proinflammatory cytokine secretion in murine macrophages, suggesting potential anti-inflammatory activity.(Oh 2010)
In an in vitro study, several components isolated from Schisandra propinqua were found to exert antioxidant effects.(Huang 2009)
It has been suggested that Schisandra fructus exerts antioxidant effects through inhibition of lipid peroxidation, induction of the antioxidant system, and scavenging of reactive oxygen species. S. fructus has been investigated for its cytoprotective effects against doxorubicin-induced cardiotoxicity caused by the production of free radicals.(Choi 2008)
In a study of H9c2 cardiomyocytes, treatment with 150 mcg/mL and 300 mcg/mL of an S. fructus extract increased cell survival time by 15% and 25%, respectively, compared with doxorubicin controls (P<0.05). The extract also inhibited lipid peroxidation caused by doxorubicin and inhibited the production of reactive oxygen species.(Choi 2008)
In a study evaluating the effects of an ethanol extract and active components of the fruit of S. chinensis in rabbits, the lignans schisandrol A and schisandrol B enhanced the corpora cavernosae relaxation induced by sildenafil by 2-fold. Schisandrol A exerted the greatest relaxant effect and may have a synergistic role for patients with erectile dysfunction who do not adequately respond to sildenafil monotherapy.(Kim 2011)
Schisandra extract reduces benzo[a]pyrene (BaP) metabolism in the rat intestine but has an opposite effect in the liver. Experimental studies show that it increases the activity of glutathione S-transferase. In the intestine, schisandra shifts BaP metabolism in favor of diols and 3-hydroxybenzo[a]pyrene and away from BaP-4,5-epoxide and the mutagenic BaP quinones. Schisandra does not increase intestinal CYP activity.(Salbe 1985) In one report, schisandra extract had no effects on gastric secretory volume, gastric pH, or acid output,(Hernandez 1988) while another study showed schisandra had inhibitory effects on gastric contraction and stress-induced gastric ulceration when administered intravenously and orally in rats.(Maeda 1981)
In a study in mice, schisandra extract resulted in a decrease in glycogen content in the liver and muscles and an increase in glucose level in the liver and blood, suggesting the adaptogen stimulates glycogenolysis.(Panossian 2008)
In mice, topical administration of an ethanolic extract of Schisandra nigra was found to promote hair growth through down-regulation of the transforming growth factor–beta-2 pathway and proliferation of dermal papilla.(Kang 2009)
In a safety and efficacy study, treatment with a combination product containing schisandra was not found to improve quality-of-life parameters, viral load, or CD4 counts in asymptomatic HIV patients.(Maek-a-nantawat 2009)
The lignan components of schisandra possess pronounced liver protectant effects. The active principles appear to be the lignans wu-wei-zu C, shisantherin D, deoxygomisin A, gomisin N, and gomisin C. The presence of 1 or 2 methylenedioxy groups appears to be important in hepatoprotection.(Hikino 1984, Maeda 1982)
Animal studies of gomisin A offer evidence of liver protection, including protective actions against halothane-induced hepatitis(Jiaxiang 1993); carbon tetrachloride, d-galactosamine, and dl-ethionine toxicities(Ko 1995, Takeda 1986); hepatic failure induced by bacteria(Mizoguchi 1991); and preneoplastic hepatic lesions.(Miyamoto 1995, Nomura 1994, Nomura 1994, Ohtaki 1994) Gomisin A's mechanism for tumor inhibition may be a result of its ability to improve bile acid metabolism.(Ohtaki 1996) Gomisin A increased hepatic blood flow and accelerated hepatic cell proliferation and liver function recovery following partial hepatectomy in rats.(Takeda 1986) These effects were caused by protection of the hepatocyte plasma membrane.(Nagai 1989) Ethanol extracts of schisandra have been found to increase liver weight in rats and mice, an action attributed to schizandrin B and schizandrol B. In another murine study, schisandrin B reduced total cholesterol and triglyceride levels in a manner similar to fenofibrate, and also increased liver weights.(Pan 2008)
In a mouse study, a schisandra ethanol extract added to a semipurified basal diet over a 14-day period increased the enzymatic metabolism of the mutagens BaP and aflatoxin B (AFB), and increased CYP-450 activity. Despite this increased level of metabolism, schisandra extract increased in vitro mutagenicity of AFB. However, chemicals inducing similar patterns of enzymes have been found to reduce the in vivo binding of AFB to DNA.(Hendrich 1986) Schizandrins and approximately 6 related compounds may temporarily inhibit or lower the activity of hepatic ALT, as observed in animals pretreated with hepatotoxins.(Bao 1980, Maeda 1985, Pao 1974)
In a randomized, placebo-controlled trial, a commercially available mixture of schisandra with sesamin (2,064 mg/day) was administered for 5 months to 40 patients with borderline liver dysfunction. Compared with placebo, the mixture reduced ALT and AST in a time-dependent manner and improved fatty liver disease. Overall antioxidant capacity was increased, and measurements of oxidative stress, including total free radicals, superoxide anion radicals, and thiobarbituric acid reactive substances, were decreased.(Chiu 2013)
In a study of pre- and postmenopausal women, treatment with a combination product containing S. chinensis was found to increase urinary 2-OHE concentrations, suggesting a potential role in reducing the risk of breast cancer.(Laidlaw 2010)
In a double-blind, randomized, placebo-controlled trial in 36 postmenopausal women, schisandra extract (392 mg twice daily for 12 weeks) demonstrated a positive effect on the severity of menopausal symptoms. No significant difference was observed between groups for mean total Kupperman Index scores at 6 or 12 weeks. However, when evaluated with respect to group and time, schisandra extract led to lower total symptom scores over time, with significantly greater improvement specifically for hot flushes (P=0.018), sweating (P=0.009), and heart palpitations (P=0.015).(Park 2016)
Schisandra is a nervous system stimulant that reportedly increases reflex responses and improves mental alertness. In China, the berries are used to treat mental illnesses such as depression. Schisandra is also used to treat irritability and memory loss. Schisandra has also been evaluated for its inhibitory effects on the CNS. Although a stimulant, it is used as a sedative for insomnia in Chinese medicine.(Chevalier 1996) A phenolic-rich component from S. chinensis may be beneficial in the prevention and treatment of neurodegenerative conditions such as Alzheimer disease, Parkinson disease, and Huntington disease, as noted by a dose-dependent reduction in H2O2-induced cell death in SH-SY5Y cells.(Jung 2007)
In a study of mice, schisandra in combination with other herbs improved memory retention disorder and facilitated memory retention deficit, suggesting a possible role in treating age-related memory deficits in humans.(Nishiyama 1996) Schisandra in combination with Zizyphus spinosa and Angelica sinensis has accelerated neurocyte growth and may prevent atrophy of neurocyte process branches.(Hu 1994)
Schisandra's mechanism of CNS inhibition has been evaluated and may be related to an effect on dopaminergic receptors.(Zhang 1991) Gomisin A has also inhibited spontaneous and methamphetamine-induced motor activity in animals.(Maeda 1981)
In a murine model, schisandrin B conferred dose-dependent protection against brain infarction caused by cerebral ischemia/reperfusion, with protection ranging from 10% to 33%.(Chen 2008)
In a systematic review of medicinal plants and their impact on the microbiome-gut-brain axis (MGBA), results from 3 clinical studies provide support for the beneficial effects of S. chinensis in anxiety and depression via the MGBA. The fruit extract, particularly the lignans, were found to be the most effective in the relief of anxiety and depressive disorders, whereas a polysaccharide-rich extract was able to regulate intestinal homeostasis and reduce potentially harmful bacteria.(Pferschy-Wenzig 2022)
Administration of 1 g S. chinensis extract for 12 weeks has been shown to significantly increase muscle strength compared to placebo in healthy post-menopausal women (P=0.001)(Park 2020) as well as in healthy adults at least 50 years of age (P=0.003)(Cho 2021) in double-blind, randomized, controlled trials that enrolled 65 and 67 participants, respectively. Additionally, lactate levels (indicative of fatigue, P=0.038) as well as fasting glucose (−5.7 mg/dL, P=0.015) were significantly reduced in the extract group compared to placebo. However, no significant effects were found in insulin concentrations, muscle mass, serum creatinine, creatinine kinase, malondialdehyde, TNF-alpha, IL-6 or quality-of-life scores.(Cho 2021, Park 2020)
Schisandra has traditionally been used to treat respiratory ailments such as shortness of breath, wheezing, and cough.(Chevalier 1996)
In rat basophilic leukemia cells, schizandrins, schisandrols, gomisins, fargesin, eudesmin, and lirioresinol B dimethyl ether inhibited leukotriene production by 5-lipoxygenase, with the most potent inhibitory activity noted with schisandrol A and gomisins. Therefore, these compounds have the potential to be developed as antiallergic agents.(Lim 2009)
In humans, nonspecific resistance to stress involves the nervous, endocrine, and immune systems. A systematic review of adaptogens (plant extracts shown to enhance these responses) was conducted to determine efficacy in stress-induced fatigue and mental performance, using 2 grading scales (European Medicines Agency Assessment Scale and Natural Standards Evidence-Based Validated Grading Rationale). Use of schisandra for mental fatigue was assigned a grade B recommendation (according to both scales), based on nonrandomized clinical trials that showed an improvement in endurance and mental performance with a single dose (7 trials [N=1,712]) and with repeated administration (1 trial [n=665]). Schisandra use for symptoms of asthenia (fatigue and weakness) received a grade B/C recommendation (5 trials [N=406]). Evidence levels ranged from IIa to III, reflecting the availability of well-conducted studies but also a lack of randomized trials.(Panossian 2009)
In China, schisandra and tacrolimus are often coadministered when drug-induced hepatitis occurs in transplant recipients. A tacrolimus-sparing effect was reported in a study of 64 renal transplant patients treated with a prednisone, mycophenolate, and tacrolimus regimen with or without schisandra. After 6 months, a 34% reduction in tacrolimus dosage was observed in the group receiving schisandra compared with the schisandra-free group (14.3%), resulting in an estimated savings per day per patient day of $6.15.(Xin 2011)
Schisandra fruit is used as an adaptogen at dosages of 1.5 to 6 g/day of powdered product. In a clinical study, schizandra tablets containing 91.1 mg of extract per tablet (extract standardized for schizandrin and gamma-schizandrin at a level of 3.1 mg/tablet) was used to improve athletic performance.Panossian 1999, Panossian 2008, Schisandra 1999 Examples of various doses of schizandra preparations used in official medicine in Russia include the followingPanossian 2008:
Information regarding safety and efficacy in pregnancy and lactation is limited. Various compounds from the stem of S. propinqua were found to be cytotoxic in rat luteal cells and human decidual cells in vitro.Chen 2001 Schisandra use was ruled out as a probable cause in a case of congenital syngnathism (maxilla and mandible fusion) that led to the early death of an infant born to consanguineous parents.Villanueva-García 2009
Because of its documented effects on hepatic and gastric enzyme activity, particularly CYP3A, it is possible that schisandra may interfere with the metabolism of coadministered drugs (eg, midazolam).(Gurley 2012, Jiang 2010, Lai 2009, Xin 2009) Additionally, in a study of healthy volunteers, a 14-day treatment course with S. chinensis 300 mg twice daily was found to inhibit P-gp, based on increased oral bioavailability of the P-gp substrate talinolol; dosage adjustment may be needed in individuals concomitantly taking P-gp substrates (eg, tacrolimus).(Fan 2009, Xin 2007) In clinical trials, schisandra administration resulted in a 1.5-, 2.1-, and 2-fold increase in area under the curve (AUC) of talinolol, tacrolimus, and midazolam, respectively.(Gurley 2012) In rats, the administration of schisandrol extracts increased the oral bioavailability of paclitaxel by approximately 3-fold and more than doubled the AUCs of midazolam, nifedipine, paclitaxel, and tacrolimus.(Gurley 2012, Jin 2010) Schisandra may induce the metabolism of warfarin.(Koncic 2013)
Abemaciclib: CYP3A4 inhibitors (moderate) may increase the serum concentration of abemaciclib. Monitor therapy.(Verzenio August 2018)
Acalabrutinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of Acalabrutinib. Consder therapy modification.(Calquence October 2017)
Aprepitant: CYP3A4 inhibitors (moderate) may increase the serum concentration of aprepitant. Avoid combination.(Emend August 2014)
Aripiprazole: CYP3A4 inhibitors (moderate) may increase the serum concentration of ARIPiprazole. Monitor therapy. Aripiprazole dose reductions may be recommended with concomitant use of a CYP2D6 inhibitor. Aripiprazole dose reductions may be recommended in CYP2D6 "poor metabolizers." See full product monograph for genotype-based dosing information. Aripiprazole dose reduction is not recommended when used as adjunctive therapy for major depressive disorder.(Abilify February 2011, Abilify Maintena February 2013, Aung 2010, Azuma 2012, Kubo 2005)
Asunaprevir: CYP3A4 inhibitors (moderate) may increase the serum concentration of asunaprevir. Avoid combination.(Sunvepra March 2016)
Avanafil: CYP3A4 inhibitors (moderate) may increase the serum concentration of avanafil. Consider therapy modification.(Stendra April 2012)
Avapritinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of avapritinib. Consider therapy modification.(Ayvakit January 2020)
Axitinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of axitinib. Monitor therapy.(Inlyta 2020, Pithavala 2012)
Benzhydrocodone: CYP3A4 inhibitors (moderate) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Monitor therapy.(Apadaz February 2018, Viekira Pak June 2016)
Blonanserin: CYP3A4 inhibitors (moderate) may increase the serum concentration of blonanserin. Monitor therapy.(Lonasen September 2014, Shang 2017)
Brexpiprazole: CYP3A4 Inhibitors (moderate) may increase the serum concentration of brexpiprazole. Monitor therapy. Brexpiprazole dose reductions are recommended with concomitant use of both a CYP3A4 inhibitor and a moderate or strong CYP2D6 inhibitor. If brexpiprazole is used with a moderate CYP3A4 inhibitor in a patient who is a CYP2D6 poor metabolizer (ie, deficient CYP2D6 activity), the brexpiprazole dose should be reduced to 25% of the usual dose.(Rexulti July 2015)
Brigatinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of brigatinib. Consider therapy modification.(Alunbrig December 2018)
Budesonide (topical): CYP3A4 inhibitors (moderate) may increase the serum concentration of budesonide (topical). Avoid combination. US prescribing information recommends avoiding the use of topical (rectal) budesonide and CYP3A4 inhibitors. Canadian product labeling warns of increased budesonide exposure with concomitant use but does not recommend avoidance of the combination.(Entocort March 2009, Uceris October 2014)
Cannabis: CYP3A4 inhibitors (moderate) may increase the serum concentration of cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Monitor therapy. This interaction is mainly expected when physiologically significant amounts of tetrahydrocannabinol (THC, the major known psychoactive component of cannabis) are introduced systemically. While this encompasses the vast majority of medical and recreational cannabis use, some cannabis strains, products, and routes of administration specifically (and often intentionally) minimize systemic THC exposure. While cannabidiol concentrations are also likely increased by CYP3A4 inhibition, the clinical significance of this increase is less clear.(Sativex February 2014, Watanabe 2007)
Cilostazol: CYP3A4 inhibitors (moderate) may increase the serum concentration of cilostazol. Consider therapy modification.(Pletal July 2015, Suri 1999, Taniguchi 2007)
Cobimetinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of cobimetinib. Avoid combination.(Cotellic November 2015)
Colchicine: CYP3A4 inhibitors (moderate) may increase the serum concentration of colchicine. Consider therapy modification. Recommendations for management of this interaction differs between the Colcrys and Mitigare or Gloperba branded products. In patients with impaired hepatic function receiving the Mitigare or Gloperba branded products, use in combination with drugs that inhibit both CYP3A4 and P-glycoprotein is contraindicated. Management of this interaction and specific dose reductions vary according to indication for colchicine use. In patients with impaired renal function receiving the Mitigare or Gloperba branded products, use in combination with drugs that inhibit both CYP3A4 and P-glycoprotein is contraindicated.(Caraco 1992, Colcrys July 2009, Dupont 2002, Eleftheriou 2008, Gloperba January 2019, Gruberg 1999, Menta 1987, Mitigare September 2014, Noppen 1987, Rieger 1990, Rumpf 1990, Troger 2005, Yussim 1994)
CYP3A4 substrates (high-risk with inhibitors): CYP3A4 inhibitors (moderate) may decrease the metabolism of CYP3A4 substrates (high risk with inhibitors). Monitor therapy.(Bjornsson 2003)
Darafenacin: CYP3A4 inhibitors (moderate) may increase the serum concentration of darifenacin. Monitor therapy.(Enablex March 2012)
Deflazacort: CYP3A4 inhibitors (moderate) may increase serum concentrations of the active metabolite(s) of deflazacort. Consider therapy modification.(Emflaza February 2017)
Dronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy.(Sativex February 2014, Watanabe 2007)
Eletriptan: CYP3A4 inhibitors (moderate) may increase the serum concentration of eletriptan. Consider therapy modification.(Relpax November 2013)
Elexacaftor, tezacaftor, and ivacaftor: CYP3A4 inhibitors (moderate) may increase the serum concentration of elexacaftor, tezacaftor, and ivacaftor. Consider therapy modification.(Kalydeco March 2015, Trikafta October 2019)
Eliglustat: CYP3A4 inhibitors (moderate) may increase the serum concentration of eliglustat. Consider therapy modification. This combination should be avoided in patients also receiving a moderate or strong CYP2D6 inhibitor. This combination should be avoided in patients considered intermediate or poor CYP2D6 metabolizers. Eliglustat dose reduction is needed in patients who are a CYP2D6 extensive metabolizer with mild hepatic impairment (Child-Pugh class A). Eliglustat is contraindicated in CYP2D6 intermediate and poor metabolizers with any degree of hepatic impairment and in all patients with moderate or severe hepatic impairment.(Cerdelga August 2018, Terbinafine April 2012)
Encorafenib: CYP3A4 inhibitors (moderate) may increase the serum concentration of encorafenib. Consider therapy modification. Management of this interaction varies based on the encorafenib dose.(Braftovi June 2019)
Entrectinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of entrectinib. Consider therapy modification.(Rozlytrek August 2019)
Eplerenone: CYP3A4 inhibitors (moderate) may increase the serum concentration of eplerenone. Consider therapy modification. Dosing recommendations may vary depending on indication. Dosing recommendations may vary depending on international labeling.(Inspra May 2016, Inspra June 2014)
Everolimus: CYP3A4 inhibitors (moderate) may increase the serum concentration of everolimus. Consider therapy modification. Recommendations regarding optimal management of this interaction vary according to specific indication and product used. Consult specific prescribing information for precise recommendations regarding dose adjustment and monitoring.(Afinitor April 2018, Brandhorst 2008, Kovarik 2005, Kovarik 2005, Kovarik 2006, Kovarik 2002, Kovarik 2003, Zortress January 2018)
Flibanserin: CYP3A4 inhibitors (moderate) may increase the serum concentration of flibanserin. Avoid combination.(Addyi August 2015)
Fosaprepitant: CYP3A4 inhibitors (moderate) may increase the serum concentration of fosaprepitant. Avoid combination.(Emend April 2018)
Gilteritinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of gilteritinib. Monitor therapy.(Xospata May 2019)
Guanfacine: CYP3A4 inhibitors (moderate) may increase the serum concentration of guanFACINE. Consider therapy modification.(Intuniv April 2019, Li 2018)
Hydrocodone: CYP3A4 inhibitors (moderate) may increase the serum concentration of HYDROcodone. Monitor therapy. The significance of this interaction may be greater in patients who are also receiving a CYP2D6 inhibitor or with use of a CYP3A4 inhibitor that also inhibits CYP2D6, as CYP2D6 is partially responsible for hydrocodone metabolism. Some non-US labels recommend avoiding this combination when possible.(pdp-Hydrocodone December 2019, Zyhydro August 2014)
Ibrutinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of Ibrutinib. Consider therapy modification. The management of this interaction differs when ibrutinib is used for the treatment of B-cell malignancies versus when ibrutinib is used for the treatment of graft versus host disease.(de Jong 2015, Imbruvica August 2018)
Imatinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of imatinib. Monitor therapy.(Dutriex 2004)
Ivabridine: CYP3A4 inhibitors (moderate) may increase the serum concentration of Ivabradine. Avoid combination. European labeling allows for potential use of this combination with dose reduction in patients with adequate heart rates (except for verapamil or diltiazem, both of which are contraindicated). US labeling recommends avoiding this combination.(Corlanor April 2015, Procoralan January 2015)
Ivacaftor: CYP3A4 inhibitors (moderate) may increase the serum concentration of ivacaftor. Consider therapy modification.(Kalydeco March 2015)
Ivosidenib: CYP3A4 inhibitors (moderate) may increase the serum concentration of ivosidenib. Consider therapy modification.(Tibsovo July 2018)
Lefamulin: CYP3A4 inhibitors (moderate) may increase the serum concentration of lefamulin. Monitor therapy. This monograph is specific for the oral formulation of lefamulin. No clinical action is likely needed for coadministration of IV lefamulin and moderate CYP3A4 inhibitors.(Xelenta August 2019)
Lemborexant: CYP3A4 inhibitors (moderate) may increase the serum concentration of lemborexant. Avoid combination.(Dayvigo December 2019)
Lomitapide: CYP3A4 inhibitors (moderate) may increase the serum concentration of lomitapide. Avoid combination.(Juxtapid December 2012)
Lorlatinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of lorlatinib. Monitor therapy.(Lorbrena November 2018, Patel 2020)
Lumateperone: CYP3A4 inhibitors (moderate) may increase the serum concentration of lumateperone. Avoid combination.(Caplyta December 2019)
Lurasidone: CYP3A4 inhibitors (moderate) may increase the serum concentration of lurasidone. Consider therapy modification. Dosing recommendations may differ depending on international labeling.(Chiu 2014, Latuda July 2013, Latuda April 2016)
Manidipine: CYP3A4 inhibitors (moderate) may increase the serum concentration of manidipine. Monitor therapy.(Uno 2006)
Mirodenafil: CYP3A4 inhibitors (moderate) may increase the serum concentration of mirodenafil. Monitor therapy.(Shin 2009)
Naldemedine: CYP3A4 inhibitors (moderate) may increase the serum concentration of naldemedine. Monitor therapy.(Symproic March 2017)
Nalfurafine: CYP3A4 inhibitors (moderate) may increase the serum concentration of nalfurafine. Monitor therapy.(Ando 2012, Ramitch May 2017)
Naloxegol: CYP3A4 inhibitors (moderate) may increase the serum concentration of naloxegol. Avoid combination.(Bui 2016, Movantik September 2014)
Neratinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of neratinib. Avoid combination.(Abbas 2011, Nerlynx July 2017)
Nimodipine: CYP3A4 inhibitors (moderate) may increase the serum concentration of niMODipine. Monitor therapy.(Nimodipine Ascend 2015)
Pexidartinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of pexidartinib. Monitor therapy.(Turalio August 2019)
Pimecrolimus: CYP3A4 inhibitors (moderate) may decrease the metabolism of pimecrolimus. Monitor therapy.(Elidel March 2014)
Propafenone: CYP3A4 inhibitors (moderate) may increase the serum concentration of propafenone. Monitor therapy. Concurrent use of a CYP2D6 inhibitor should be avoided in patients receiving propafenone and a CYP3A4 inhibitor. Patients with genetically deficient CYP2D6 activity should avoid this combination.(Rythmol SR November 2011)
Ruxolitinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of ruxolitinib. Monitor therapy.(Jakafi 2017, Shi 2012)
Salmeterol: CYP3A4 inhibitors (moderate) may increase the serum concentration of salmeterol. Monitor therapy.(Manchee 1996, Serevent March 2008)
Saxagliptin: CYP3A4 inhibitors (moderate) may increase the serum concentration of SAXagliptin. Monitor therapy.(Onglyza July 2009, Patel 2011)
Sildenafil: CYP3A4 inhibitors (moderate) may increase the serum concentration of sildenafil. Monitor therapy. Management of this interaction differs according to whether sildenafil is being used for treatment of pulmonary arterial hypertension or for treatment of erectile dysfunction. Recommendations regarding management of this interaction differs between US and Canadian labeling.(Revatio December 2015, Revatio January 2014)
Silodosin: CYP3A4 inhibitors (moderate) may increase the serum concentration of silodosin. Monitor therapy.(Rapaflo January 2013)
Simeprevir: CYP3A4 inhibitors (moderate) may increase the serum concentration of simeprevir. Avoid combination.(Olysio November 2013)
Sonidegib: CYP3A4 inhibitors (moderate) may increase the serum concentration of sonidegib. Consider therapy modification.(Odomzo July 2015)
Tazemetostat: CYP3A4 inhibitors (moderate) may increase the serum concentration of tazemetostat. Consider therapy modification.(Tazverik January 2020)
Telithromycin: CYP3A4 inhibitors (moderate) may increase the serum concentration of telithromycin. Monitor therapy.(Ketek October 2015, Shi 2005)
Tetrahydrocannabinol: CYP3A4 inhibitors (moderate) may increase the serum concentration of tetrahydrocannabinol. Monitor therapy.(Stott 2013, Watanabe 2007)
Tezacaftor and ivacaftor: CYP3A4 inhibitors (moderate) may increase the serum concentration of tezacaftor and ivacaftor. Consider therapy modification.(Symdeko June 2019)
Tofacitinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of tofacitinib. Monitor therapy. The clinical significance of this interaction is increased with concomitant use of strong CYP2C19 inhibitors.(Gupta 2014, Xeljanz December 2019)
Tolvaptan: CYP3A4 inhibitors (moderate) may increase the serum concentration of tolvaptan. Consider therapy modification. The significance and management of this interaction varies between tolvaptan brand names.(Jynarque April 2018, Samsca April 2018)
Trabectedin: CYP3A4 Inhibitors (moderate) may increase the serum concentration of trabectedin. Monitor therapy.(Machiels 2014, Yondelis 2017)
Ubrogepant: CYP3A4 inhibitors (moderate) may increase the serum concentration of ubrogepant. Consider therapy modification.(Ubrelvy December 2019)
Udenafil: CYP3A4 inhibitors (moderate) may increase the serum concentration of udenafil. Monitor therapy.(Shin 2010, Udenafil September 2014)
Ulipristal: CYP3A4 inhibitors (moderate) may increase the serum concentration of ulipristal. Avoid combination. Significance of this interaction is greater when ulipristal is used for treatment of uterine fibroid signs/symptoms (Canadian indication).(ella August 2010, Fibristal June 2013, Pohl 2013)
Venetoclax: CYP3A4 inhibitors (moderate) may increase the serum concentration of venetoclax. Consider therapy modification.(Venclexta April 2016)
Vilazodone: CYP3A4 inhibitors (moderate) may increase the serum concentration of vilazodone. Monitor therapy.(Boinpally 2014, Viibryd January 2017)
Vindesine: CYP3A4 inhibitors (moderate) may increase the serum concentration of vindesine. Monitor therapy.(Chen 2007, Eldisine June 2014, Zhou 1993)
Zanubrutinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of zanubrutinib. Consider therapy modification.(Burkinsa November 2019)
Zuclopenthixol: CYP3A4 inhibitors (moderate) may increase the serum concentration of zuclopenthixol. Monitor therapy. Interaction most likely applies to poor CYP2D6 metabolizers or with use of strong CYP2D6 inhibitors.(Clopixol January 2011, Davies 2010)
Research reveals little information regarding adverse reactions with use of schisandra.
The minimum toxic dose of schisandra when given orally to mice was 3.6 g/kg. In a study of acute toxicity in mice, no effects on blood pressure, breath, or motility were noted following intraperitoneal administration; however, high doses caused convulsions (median effective dose [ED50]=175 mg/kg) and paresis (ED50=370 mg/kg).Panossian 2008 Symptoms of overdose (restlessness, insomnia, or dyspnea) have been reported.Koncic 2013
This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.
This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.
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