Voltaren gel istället för Solaraze. kost tillskott , Ashwaganda

Fråga: Jag har 2 frågor.

En hudläkare berättade för mig att man kan använda diklofenak gel, 3% för att behandla aktinisk keratos. Solaraze heter produkten men patienten kom åter och sa att det blev för dyrt. Kan man använda vanlig voltaren gel istället? Finns det studier som kan vägleda?

Den andra frågan gäller ett kost tillskott , Ashwaganda , som en patient åt och hade frågor omkring. Finns det utöver reklamens information någon vetenskaplig bedömning av produktens verkningar och ev effekter?

Svar: Sammanfattning Solaraze is formulated in hyaluronic acid and Indicated specifically for the treatment of actinic keratosis (AK). Other topical diclofenac preparations (such as Voltaren gel) are approved for other therapeutic indications than AK. Solaraze and e.g., Voltaren gel are not interchangeable drugs and the two products are not bioequivalent.

There is limited clinical data to support the traditional uses of ashwagandha. However, limited results suggest that ashwaghanda may reduce anxiety and improve semen quality and female sexual function. Large, confirmative trials are lacking.

Ashwagandha has been reported to be generally well tolerated in recommended doses, although case reports of toxicity have been published. Large doses of ashwagandha have also produced gastrointestinal disturbances and consequently it is contra-indicated in patients with stomach ulcers. Svar Solaraze Solaraze is formulated in hyaluronic acid (HA) in the form sodium hyaluronate and is indicated specifically for the treatment of actinic keratosis (AK) (1). Solaraze, in HA vehicle is designed to keep the drug in the epidermis and superficial dermis in order to optimize it for treatment of AK (2). HA has the potential to enhance delivery of diclofenac to sites of inflammation and/or neoplasia and retards the passage of diclofenac through skin resulting in depot formation in the epidermis (3).

Other topical diclofenac preparations (e.g., Voltaren gel) are approved for other therapeutic indications and are not approved for the treatment of AK (1). We have not found any studies that evaluated the use of of these preparations for AK, however, according to Jarvis B (3) other topical diclofenac preparations have not been shown to be effective in AK.

Solaraze and e.g., Voltaren gel are not interchangeable drugs according to the Summary of Product Characteristics (1) and the two products are not bioequivalent (2).

Ashwagandha Herbal Medicines, via Medicines Complete (4), published an evidence-based guide to the traditional uses, pharmacological properties, side effects and toxicity of Ashwagandha (Publication last updated on15 Jan 2019), which we summarize as follows:

Ashwagandha Withania somnifera is also known as Indian ginseng. The major constituents of interest are steroidal lactones and alkaloids however local species show considerable morphological and chemotypical variations. Reviews of in vitro and animal pharmacological studies investigating the properties of ashwaganda have reported it to have adaptogenic (antistress), anti-inflammatory, antioxidant, antitumour, cardioprotective, endocrine, haematopoetic, immunomodulatory, and neuroprotective effects. However, extrapolation of these results to clinical use in humans is difficult.

There are a limited number of clinical studies published on ashwagandha. Confirmation of all proposed clinical effects are required through further large-scale randomized controlled trials (4).

Anxiety disorders In a randomized, double-blind, placebo-controlled study in 39?patients with anxiety disorders the treatment group received an ethanolic extract of ashwagandha given orally in tablet form in an initial dose of 500?mg twice daily for 2 weeks, which was then adjusted at weekly intervals according to response or tolerability to a maximum dose of 2.5?g daily or a minimum dose of 500?mg daily. Results available for 33?patients at week?6 (the end of the study period) showed that ashwagandha extract had a greater anxiolytic effect than placebo (5). Results from another randomized, double-blind, placebo-controlled study in 61?patients with a history of chronic stress showed that ashwagandha root extract given orally in capsule form in a dose of 300?mg twice daily for 60?days produced a greater reduction in scores on all stress-assessment scales and lower serum-cortisol concentrations than placebo (6).

Cardiorespiratory performance The effects of ashwagandha on physical and cardiovascular performance during exercise have been investigated. In a randomized, single-blind, placebo-controlled study ashwagandha aqueous root extract given orally in capsule form in a dose of 500?mg daily to 10?healthy young adults for 8?weeks increased maximum velocity and average absolute and relative power (representing short-term aerobic activity), and increased maximum oxygen consumption (VO2 max, representing long-term aerobic and cardiovascular endurance) compared with placebo given to an equivalent group of participants (7). Another randomized, placebo-controlled study was conducted in 40 elite cyclists who were given either ashwagandha aqueous root extract in a dose of 500?mg twice daily for 8?weeks or placebo. Results from the treatment group showed a significant improvement in aerobic capacity as measured by VO2 max, metabolic equivalent, and total time to reach exhaustion stage compared with placebo (8).

Fertility Ashwagandha has been used traditionally in Ayurvedic medicine as an aphrodisiac, and more widely to treat infertility. A systematic review investigated the effects of ashwagandha on the male and female reproductive system (9). Eight clinical studies were included; two double-blind randomized placebo-controlled trial, including one on sexual function in 50 women, four prospective studies investigating infertility, and two reporting on a randomized placebo-controlled study of psychogenic erectile dysfunction. Root preparations were administered orally and over 60–90?days in all studies. The review concluded that ashwagandha significantly improved female sexual function but had no effect on erectile dysfunction. Improvements in semen quality were consistently reported post-treatment relative to baseline (9). Another review (10) focused on male infertility and the potential mechanisms of action of ashwagandha in more detail. Considering both the clinical and animal literature, it proposed that ashwagandha may exert its effects indirectly on hormone regulation through a GABA-mimetic pathway, and directly through its antioxidant mechanisms (10). Ashwagandha was compared with pentoxifylline and placebo in a triple-blind randomized clinical trial of idiopathic male infertility (11). Oral administration of 5?g daily of ashwagandha for 90?days has a statistically significant effect on sperm count (12.5% increase), motility (21.42%), and morphology (25.56%) relative to baseline, but not on semen volume or number of round cells. There were also no statistically significant differences in changes to sperm parameters between the ashwagandha and pentoxifylline arms (11).

Side-effects and toxicity There is a lack of preclinical safety data available. However, increased triiodothyronine (T3) and thyroxine (T4) concentrations were seen in mice given an ashwagandha dry root powder extract orally in a dose of 1.4?g/kg daily for 20?days.

There is a lack of clinical safety and toxicity data for ashwagandha. The American Herbal Pharmacopoeia states that ashwagandha appears to be well tolerated when used within recommended dosage. An aqueous extract of ashwagandha was generally well tolerated by 18 healthy volunteers in an open-label study over 30?days without any adverse effects or significant changes in hematological and biological organ function tests (12). An incremental dosing regimen was used, starting with an initial dose of 750?mg of aqueous ashwagandha extract daily, increased at 10-day intervals to 1?g daily and then to 1.25?g daily for the final 10?days (the equivalent dosage of crude pulverized ashwagandha roots ranging from 6–10?g daily).

One volunteer, in the study by Raut AA (12), reported increased appetite, libido and hallucinogenic effects with vertigo, and withdrew from the study on day 6. Gastrointestinal disturbances, including vomiting and diarrhea have resulted from large doses (undefined) due to irritation of mucous and serous membranes according to American Herbal Pharmacopoeia. A 32-year-old woman taking the recommended dose (500?mg daily) of a commercial preparation of ashwagandha extract [length of time used not specified] for the treatment of fatigue developed symptoms of thyrotoxicosis (confirmed by thyroid function tests) that resolved spontaneously on stopping treatment (13). A 28-year-old man developed a fixed-drug eruption on his penis while taking ashwagandha in a dose of 5?g daily for 10?days, for the treatment of reduced libido and he reported having had a similar reaction when taking ashwagandha 6 months previously. Following successful treatment with a corticosteroid and a histamine H1-antagonist, he was rechallenged with an oral dose of 1?g of ashwagandha powder and developed a flare-up at the same site within 12?hours (14). In a clinical trial, one participant experienced nausea and epigastric pain after oral administration of ashwagandha. These were not considered major adverse effects (11).

Contra-indications and warnings The American Herbal Pharmacopoeia states that ashwagandha should not be used in patients with gastric ulcers.

Drug interactions Ashwagandha might have mild blood-glucose-lowering effects, which might be additive with conventional antidiabetic drugs. Ashwagandha can affect the reliability of some digoxin assays, and might affect thyroid hormone concentrations, interfering with the control of hypo- and hyperthyroidism.

Pregnancy and lactation Although ashwagandha has been used in traditional medicine to prevent miscarriage, the American Herbal Pharmacopoeia states that abortifacient effects have been reported from large doses (undefined). Therefore, due to lack of conclusive clinical safety data, use of ashwagandha is not recommended during pregnancy. Pharmacological and toxicity data for use of ashwagandha during lactation are also lacking.

1. Produktresuméer. www.FASS.se
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3. Jarvis B, Figgitt DP. Topical 3% diclofenac in 2.5% hyaluronic acid gel: a review of its use in patients with actinic keratoses. Am J Clin Dermatol. 2003;4(3):203-13.
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12. Raut AA et al. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera) in healthy volunteers. J Ayurveda Integr Med (2012); 3: 111-114
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