a. African Plum Tree

.

II. Scientific/Common Names

a. Prunus Africana

b. Pygeum Africanum

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III. Family

a. Rosaceae

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IV. Active Ingredients

a. The active ingredients are extracted from the bark of the herb

b. 14% triterpenes (urolic acids, oleanolic acid, crataegolic acid)

c. 0.5% n-docosanol

d. Phytosterol (?-sitosterol, ?-sitosterone, Campesterol)

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V. Mechanism Of Action

a. Extracts have anti-proliferative effects on fibroblasts and inhibits

bladder hyper-reactivity, which are over produced in BPH.

b. Phytosterols competes with androgen precursors and inhibit

prostaglandin biosynthesis to reduce prostatic cholesterol levels.

c. Triterpenes have anti-inflammatory activity by inhibiting enzymes

involved in the depolymerization of proteoglycans in prostate

connective tissue.

d. Improves symptoms of BPH and prostatic adenoma (esp. nocturia,

flow rate, voided volume, and/or residual volume) by increasing

prostatic secretions and improves seminal fluid composition.

.

VI. Indications

a. Common use

.....i. Benign prostatic hypertrophy (BPH) and prostatic

.....adenoma (nocturia, dysuria, pollakiuria, micturitional

.....disorders, and/or bladder fullness)

b. Other use:

.....i. Fertility disorder

.....ii. Urinary tract infections (UTI) (inflammation and/or difficult urination)

.....iii. Inflammation

.....iv. Kidney disease

.....v. Malaria

.....vi. Stomachache

.....vii. Fever

.....viii. Madness

.....ix. Aphrodisiac

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Original author Nina Dinh

Reviewed 5/12/03 Susan Paulsen Pharm D

.

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VII. Efficacy

a. Breza J, et al, performed an open-label uncontrolled study in

patients suffering from mild to moderate benign prostatic

hyperplasia (BPH) symptoms (urinary frequency (day and/or at

night), urgency, straining in order to commence urination, weak

urinary stream or dribbling, and/or sensation of incomplete

emptying of bladder). Eligible patients were entered into the

treatment phase: P. africanum extract, Tadenan®, 50mg twice daily

(AM & PM dosing) for two months.

.....i. Inclusion criteria included male patients aged 50 to 75

.....years old, mentally alert with good physical health, and

.....with a diagnosed of moderate symptomatic BPH via

.....questionnaire (micturitional problems ? 6 months (e.g.

.....nocturnal frequency), a score at the inclusion visit V1 of ?

.....12 on the IPSS scale, and a QOL score at visit V1 of ? 3

.....on the QOL scale of Mebust), digital rectal examination

.....(prostatic hyperplasia characteristic of “adenomatous”

.....lesion), uroflowmetry (max urinary flow rate ? 15ml/s and

.....voiding volume or urine volume ? 150ml), transabdominal

.....ultrasonography (residual urinary volume < 100ml and

.....prostate volume < 100ml), and biochemical criteria (SrCr <

.....160µmol/L, Serum prostate specific antigen (PSA) ?

.....4ng/ml or PSA density < 0.15, and urine bacterial count <

.....10^5/ml).

ii. Exclusion criteria included patients suffering from any

.....disease or history of surgical intervention on the prostate or

.....bladder, micturitional problems due to identified bladder

.....pathology (e.g. neurogenic bladder, bladder neck stenosis,

.....lithiasis, bladder cancer, etc), known urethral stricture,

.....diagnosed prostatic cancer, recurrent urinary infections,

.....BPH judged by investigator (urologist) to need surgical

.....treatment, known renal, hepatic, or cardiac insufficiency, or

.....hypersensitive to P. africanum extract. Plus, patients

.....unable to understand or follow the study protocol or is/are

.....involved in another clinical trial within the past 3 months.

.....iii. Methods, 85 patients from 3 different centers (Warsaw,

.....Bratislava, and Prague) with an overall mean age of 63.35

.....± 6.28 years were evaluated at the first visit (V1), then a 2

.....weeks wash-out period without treatment (V2) to check for

.....condition stability, thereafter patients were entered into the

.....treatment phase: P. africanum extract, Tadenan®, 50mg

.....twice daily (AM & PM dosing) for two months (V3-1st month

.....and V4-2nd month), plus reassessment after 1 month of

.....completing the treatment phase (V5) (at this time patient is

.....no longer on medication).

.

Original author Nina Dinh

Reviewed 5/12/03 Susan Paulsen Pharm D

.

.

iv. Primary outcome measured was the mean change in IPSS

.....score (scale 0-35) from baseline visit V2 to V4 after 2

.....months of active treatment. Results showed, average total

.....IPSS for all 3 centers at visit V1 = 16.29 ± 3.79 and visit V2

.....= 16.17 ± 3.38. When the mean of V1 and V2 were

.....compared this showed that during the 2 weeks washout

.....period the patients’ conditions were stable. At V3 IPSS

.....was relatively reduced by 31% when compared to V2 and

.....was 40% at V4 and V5 (P < 0.001).

v. Secondary outcomes measured were changes from

.....baseline of V2 to V4 for nocturnal urinary frequency (IPSS

.....question 7), QOL, max urinary flow rate, average urinary

.....flow rate, urinary volume, and changes in post-micturitional

.....residual volume and prostatic volume. Results showed,

.....QOL scores in all 3 centers were similar in terms of mean

.....value at visit V1 = 3.66 ± 0.76 and at visit V2 = 3.60 ± 0.74,

.....the mean change after 2 weeks washout period was not

.....statistically significant. However, QOL was statistically

.....significant at V4 = 31% and V5 = 34% improvement from

.....baseline (P < 0.001). Nocturia, according to the IPSS

.....questionnaire the mean at visit V2 for all centers was

.....around 2.6 times/night, the change between V1 and V2

.....lacked statistical significant. However, at V3 = 1.95

.....times/night and V4 = 1.66 times/night, the changes

.....between V2 and V4 gave a 32% reduction (P < 0.001). At

.....the beginning of the study, more than half of the patients

.....getting up to urinate at night ? 3 times but by the end of the

.....2 months treatment phase (V4) it was reduced to 16

.....patients. The mean maximal urinary flow and average

.....urinary flow increased from baseline at V3 (10.97 to

.....13.07ml/s and 5.94 to 6.93ml/s) and with additional

.....improvement at V4 (P < 0.001). Urinary volume at V4

.....increased from baseline of 218.63ml to 264.04ml (P <

.....0.01). There was no statistically significant change in post-

.....micturitional residual volume from baseline to V4 (32.60ml

.....to 29.62ml).

vi. Safety assessment, at each of the 5 visits investigator

.....assessed biochemical and haematological safety by

.....patient reports and conventional laboratory tests

.....(differential blood count, platelets, creatinine, ASAT, ALAT,

.....?-GT, and alkaline phosphatase). In addition, at V2 and V4

.....patients were asked to complete a simplified sexual life

.....questionnaire (e.g. improved, remained unchanged, or got

.....worse). Results showed, at V2 = 89% (76/85) of patients

.....were satisfied with their sexual life, of these patients 7

.....claimed improvement at V4. However, 3 patients went

.

Original author Nina Dinh

Reviewed 5/12/03 Susan Paulsen Pharm D

.

.

.....from “satisfactory” to “got worse” at V4 and 1 patient had

.....been impotent for several years remained impotent.

.....Furthermore, no adverse events or clinically relevant

.....changes in biochemical parameters were observed (there

.....was 3 increased PSA in the Warsaw group but was not

.....associated with the development of prostatic carcinoma).

vii. Conclusion, according to this study and others P.

.....africanum is effective and safe under the open-label

.....conditions because beneficial effects can be seen after one

.....month of treatment with a tendency to further improved by

.....the second month.

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b. Chatelain C, et al, preformed a randomized, parallel, double blind,

with a long-term open label study comparing once daily dosing to

twice daily dosing of pygeum africanum extract in patients with

benign prostatic hyperplasia.

.....i. Inclusion criteria included age ? 50, showed clinical

.....symptoms of BPH (urinary symptoms, International

.....Prostate Symptom Score (IPSS) ? 10, and quality of life

.....(QOL) ? 3), prostate volume ? 30 cm confirmed by digital

.....rectal examination and transrectal ultrasound, voided

.....volume ? 140mL, residual volume ? 150mL, prostate-

.....specific antigen (PSA) < 10ng/mL, and SrCr < 160µmol/L.

ii. Exclusion criteria included candidates for or had previous

.....prostate or bladder surgery, prostate and/or bladder

.....cancer, urinary symptoms due to other causes, and

.....treatment during the 3 months preceding inclusion with

.....finasteride, P. africanum, Serenoa repens, or with any ?-

.....blocker during 1 month before inclusion.

iii. Primary outcome was to achieve ? 40% reduction in the

.....mean IPSS from baseline and the main efficacy end point

.....was the % of patients reaching this goal.

iv. Secondary outcome measures were global IPSS, nocturia,

.....QOL, voided volume, residual volume, and prostate

.....volume. Safety was assessed on drug side effects, vital

.....signs, clinical biology, serum PSA at 12 months, and

.....satisfaction of the patients’ sexual function.

v. Methods, 101 patients were randomized to group A (50mg

.....twice daily) and 108 patients to group B (100mg once

.....daily) for duration of 2 months. In addition, the first 174

.....patients that completed the comparative phase were

.....enrolled in the open-label extension phase (an additional

.....10 months of treatment with 100mg once daily regimen).

vi. Comparative phase results, for efficacy the % of patients

.....achieving therapeutic goal for group A was 42.6% (95% CI

.....33% to 53%) and group B was 40.7% (95% CI 31% to

.

Original author Nina Dinh

Reviewed 5/12/03 Susan Paulsen Pharm D

.

.

.....51%). IPSS decreased similarly in both groups. The mean

.....IPSS was reduced from 17.2 (group A) and 16.7 (group B)

.....to 10.7 (-37.6%) and 10.9 (-34.6%). Nocturia improved

.....equally in both groups, from 2.3 to 1.5 in both groups.

.....QOL improved in both groups, from 4.3 (group A) and 4.1

.....(group B) to 3.1 and 3.0. Voided volume increased by

.....1.63mL/s (16%) in group A and 2.02mL/s (18.6%) in group

.....B. Residual volume did not vary significantly.

vii. Open-label extension phase results, the % of patients

.....reaching the therapeutic goal increased with time: 20.1% at

.....1 month, 42.0% at 2 months, 57.1% at 5 months, 65.4% at

.....8 months, and 62.8% at 12 months. The mean IPSS

.....decreased from 16.2 (baseline) to 8.7 (-46.3%). Nocturia

.....after 12 months decreased from 2.3 to 1.4. QOL improved

.....from 4.1 (baseline) to 2.4 (-41.5%) and after 12 months

.....58.1% of patients had a score ? 2. Prostate volume at the

.....end of the study was reduced from 42.0 to 39.9 cm.

.....Voided volume and other urinary parameters improved

.....after 2 months of the study and maintained improvement

.....even after 12 months.

viii. Safety assessment results, no significant changes in blood

.....or urinalyses in either group or during the study. At 12

.....months there was no significant variation of the PSA level.

.....After 2 months, sexual activity was not significantly

.....affected. The most common side effects reported were

.....gastrointestinal (constipation, dyspepsia, nausea), but

.....most were not related to treatment. In the comparative

.....phase, 2.6% of patients experienced drug related side

.....effects and 2.9% in the open-label extended phase (refer

.....to table IV). Furthermore, in the comparative phase 1.3%

.....of patients experienced serious side effects (muscular and

.....joint pain, dysuria, urinary retention, hematuria, meningeal

.....carcinoma, and/or subdural hematoma) and 4.0% in the

.....open-label extended phase. All together 23 patients

.....dropped out from the study: 8 (4.6%) due to adverse

.....events and 15 (8.6%) for non-medical reasons.

ix. Conclusion, P. africanum is considered as an alternative

.....treatment for patients with mild to moderate symptoms of

.....BPH. The recommended regimen is with P. africanum

.....extract 100mg daily or 50mg twice daily for 12 months are

.....both safe and efficacious for the treatment of mild to

.....moderate BPH. Currently there is no reporting or

.....mentioning of the long-term effects (? 12 months) on

.....efficacy or safety issues with the usage of this herb.

.

Original author Nina Dinh

Reviewed 5/12/03 Susan Paulsen Pharm D

.

.

c. Lucchetta G, et al, performed a study focused on men with reduced

prostatic secretion in the ejaculate at 2 successive examinations.

The thought is that P. africanum bark extract is known to stimulate

prostatic secretion therefore can this extract increase the amount of

prostatic secretion of a normal physiological composition which

would enable the spermatozoa to mature under optimum

conditions. The authors hypothesized that P. africanum extract’s

effects would be more apparent in cases where the initial reduction

was greater.

.....i. Methods, 22 males with reduced prostatic secretion

.....combined with reduced fertility got their ejaculate analyzed

.....as follows: 1) spermatozoa and round-cell count

.....(million/cm ) 2) motility at 1 and 6 hours 3) % of ‘normal’

.....shaped cells 4) determination of volume and pH 5)

.....determination of protein concentration (followed Lowry’s

.....method but modified by Eggstein) 6) determination of

.....fructose (resorcinol technique) 7) determination of acid

.....phosphatase activity (p-nitrophenyl phosphate technique)

.....8) detection of IgA by antiserum anti-IgA (produced by

.....Behring, batch #1000834 with Ouchterlony technique).

.....Patients were given two tablets of P. africanum to be taken

.....three times daily for 3 months (no documentation of

.....strength). At the end of treatment phase, 2 sperm counts

.....will be collected and examined followed the treatment at

.....1week interval.

ii. Inclusion criteria included males from the sterility clinic with

.....prostatic secretion insufficiency at 2 sperm counts carried

.....out at 1week interval (prostatic phosphatase activity <

.....400IU/ml).

iii. No mention of exclusion criteria

iv. Results, the effects of treatment on semen parameters

.....(number of round cells (million/cm ), % of motility at 1 hour,

.....and fructose (g/l) showed no statistically significant when

.....comparing the treatment. However, the semen

.....parameters that showed statistically significant results were

.....the number of spermatozoa (million/cm ) (P = 0.01),

.....proteins (g/l) (P = 0.05), and acid phosphatase activity

.....(IU/cm) (P = 0.05) (Table 1). Effects of treatment on the

.....various protein groups indicated a reduction in serous

.....proteins. Quantitative analysis shows in 4 cases the

.....prealbumins present before treatment completely

.....disappeared after treatment (Table II). Treatment in

.....patients with or without IgA in the seminal fluid showed that

.....the presence of IgA in the seminal fluid causes a reduction

.....in the efficiency of the treatment (P = 0.05) (Table III).

.

Original author Nina Dinh

Reviewed 5/12/03 Susan Paulsen Pharm D

.

.

v. Conclusion, P. africanum extract does produce an increase

.....in prostatic secretion in patients with reduced fertility and

.....diminished prostatic secretion. In patients without

.....infectious state the increase was more significant,

.....therefore improvement of seminal fluid composition should

.....lead to a better maturation of spermatozoa.

.

VIII. Contraindications & Allergies

a. Pregnancy

b. Lactation

c. Children

d. Hypersensitive to pygeum

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IX. Dosage forms

a. Powder

b. Capsule

c. Tablet

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X. Recommended Doses & Duration

a. Orally take 100mg daily or 50mg twice daily (max dose of

200mg/day) of standardized lipophilic extract (unknown component

partials), it is safe and effective for functional symptoms of BPH for

6-8 week cycles.

b. Orally take 2 tablets three times a day for 3 months for fertility

disorders (unknown strength).

c. Currently there is insufficient reliable information available about

the usage of pygeum for its other indications

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XI. Drug Interaction and Drug-Disease Interactions

a. Unknown due to no reporting and/or lack of human data available.

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XII. Adverse Reactions/Side Effects

a. GI: Nausea, vomiting, diarrhea, abdominal pain, anorexia, and/or

irritation

b. Skin: Hypersensitivity reactions

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XIII. Safety Issues

a. The safety and efficacy of pygeum extract has been demonstrated

in numerous short-term (approximately 8 week duration) open label

studies and several controlled studies in men to reduce fertility

problems and diminish benign prostatic hyperplasia. However, no

studies have been performed in pregnancy, lactating women, or

children. Therefore, it is contraindicated in these populations due

to unavailable or unreliable findings.

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