Universal reference book for medicines
Product name: EVRA В® (EVRA В® )

Active substance: ethinylestradiol, norelgestromin

Type: Hormonal contraceptive for transdermal use

Manufacturer: JANSSEN-CILAG INTERNATIONAL (Belgium) manufactured by LTS LOHMANN THERAPIE-SYSTEME (Germany), which manufactures control JANSSEN PHARMACEUTICA (Belgium)
Composition, form of production and packaging
Transdermal therapeutic system (TTS) of
square form, with beige matte substrate, rounded corners, colorless glue (adhesive) layer and transparent protective film;The inscription "EVRA" is printed on the substrate.

1 TTS release within 24 h

noregestromine 6 mg 203 Ојg

ethinylestradiol 600 Ојg 33.9 Ојg

TTS base composition: outer layer of pigmented low density polyethylene and inner layer of polyester.

Composition of the middle layer of TTS: adhesive mixture of polyisobutylene-polybutene, crospovidone, non-woven material from polyester, lauryl lactate.

Composition of the removable protective layer of TTC: a film of polyethylene terephthalate, a coating of polydimethylsiloxane.

1 PC.
- bags made of laminated paper and aluminum foil (3) - bags of polymer film (1) - packs of cardboard.
1 PC.
- bags of laminated paper and aluminum foil (3) - bags made of polymer film (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the print edition of 2007.

PHARMACHOLOGIC EFFECT

Contraceptive for transdermal administration.
Oppresses the gonadotropic function of the pituitary gland, suppresses the development of the follicle and prevents the process of ovulation. The contraceptive effect is enhanced by increasing the viscosity of cervical mucus and reducing the susceptibility of the endometrium to the blastocyst. The Pearl Index is 0.90.
The frequency of pregnancy does not depend on such factors as age, race and is increased in women with a body weight of more than 90 kg.

PHARMACOKINETICS

Suction and distribution

C ss of noreglestromine and ethinyl estradiol in serum are reached 48 hours after the application of the TTS of Eur and are 0.8 ng / ml and 50 pg / ml, respectively.

With long-term use of TTS, Eur C ss and AUC increase somewhat.
Under different temperature regimes and physical activity, there were no significant changes in C ssand AUC of noreglestromine, and the ethinylestradiol AUC increased slightly with exercise, while C ss remained unchanged.
The target values ​​of C ss of noregestromine and ethinylestradiol are maintained for 10 days of TTS application, i.e.
the clinical efficacy of TTS may persist, even if a woman carries out another TTC replacement 2 full days after the scheduled seven-day period.
Norelgestromine and norgestrel (serum noreglestromine metabolite) have a high degree (more than 97%) of binding to serum proteins.
Norelgestromine binds to albumin, norgestrel binds primarily to sex hormone binding globulins. Ethinyl estradiol has a high degree of binding to serum albumin.
Metabolism

Norelgestromine is metabolized in the liver, with the formation of the metabolite norgestrel, as well as various hydroxylated and conjugated metabolites.
Ethinyl estradiol is metabolized to various hydroxylated compounds and their glucuronide and sulfate conjugates. Progestogens and estrogens inhibit many of the microsomal liver enzymes of the cytochrome P 450 system (including CYP3A4, CYP2C19).
Excretion

The mean T 1/2 of noreglestromine and ethinylestradiol is about 28 hours and 17 hours, respectively.
Metabolites of noregestromine and ethinylestradiol are excreted in urine and feces.
Pharmacokinetics in special clinical cases

The C ss and AUC values ​​of noreglestromine and ethinylestradiol slightly decrease with increasing age, body weight or body surface area.

INDICATIONS

- Contraception in women.

DOSING MODE

The patient should be informed that in order to achieve the maximum contraceptive effect, it is necessary to strictly follow the instructions for the application of the Eurasian TTC.
At the same time, only one TTC can be used.
Each used TTS is removed and immediately replaced with a new one on the same day of the week (the "day of replacement") on the 8th and 15th days of the menstrual cycle (2nd and 3rd week).
TTS can be changed at any time of day of replacement. During the 4th week, from the 22nd to the 28th day of the cycle, the TTC is not used. The new contraceptive cycle begins the day after the end of the 4th week; the next TTS should be glued, even if the menstruation was not or it did not end.
Under no circumstances should a break in the application of the TTC Eur should be more than 7 days, otherwise the risk of pregnancy increases.
In such situations for 7 days it is necessary to use the barrier method of contraception at the same time. the risk of ovulation increases every day exceeding the recommended duration of the period free from the use of TTS. In the case of sexual intercourse during such an increased period, the probability of conception is very high.
Beginning of the application of TTC Evra

If during the previous menstrual cycle the woman did not use the hormonal contraceptive

Contraception with the help of TTC Evra begins on the first day of menstruation.
Glue one TTS Evra to the skin and use it all week (7 days). The day of gluing the first TTC of Eur (1st day / day of the beginning) determines the subsequent days of replacement. Day replacement will occur on the same day each week (8th and 15th days of the cycle). On the 22nd day of the cycle, the TTS is removed, and from the 22nd to the 28th day of the cycle the woman does not use the TTC of Evra. The next day is considered the first day of a new contraceptive cycle. If a woman starts using the TTC of Eur on the first day of the cycle, then the barrier methods of contraception should be used simultaneously during the first 7 days of the first contraceptive cycle.
If a woman goes from using a combined oral contraceptive to using the TTC Evra

TTS Evra should be glued to the skin on the first day of menstruation, which began after the termination of taking a combined oral contraceptive.
If menstruation does not begin within 5 days after taking the contraceptive pill, then you must exclude pregnancy before starting the use of the TTC Eur.
If the application of Evra begins after the first day of menstruation, then within 7 days it is necessary to use barrier methods of contraception at the same time.

If, after taking the last contraceptive pill, more than 7 days have passed, a woman may have ovulation, and therefore she should consult a doctor before starting to use the TTC of Eur.
Sexual intercourse during this extended period, free from taking contraceptive pills, can lead to the onset of pregnancy.
If a woman passes from the use of drugs containing only progestogen, to use the TTC Evra

A woman can switch from using a progestogen only (on the day of removal of the implant, on the day the next injection is to be made), but within the first 7 days of using the TTS, a barrier method should be used to enhance the contraceptive effect.

After an abortion or miscarriage

After abortion or miscarriage before the 20th week of pregnancy, you can immediately begin using the TTC Evra.
If a woman begins to use the TTS Evra immediately after an abortion or a miscarriage, then additional methods of contraception are not required. A woman should know that ovulation can occur within 10 days after an abortion or a miscarriage. After an abortion or miscarriage at the 20th week of pregnancy or later, the use of the TTS of Eur can be started on the 21st day after the abortion or miscarriage, or on the 1st day of the first menstruation.
After childbirth

Women who are not breastfeeding should begin using the TTS of Eur not earlier than 4 weeks after giving birth.
If a woman starts to use the TTS of Eur later, then within the first 7 days she must additionally use the barrier method of contraception. If there was sexual intercourse, it is necessary to exclude pregnancy before starting the application of TTC Eur, or a woman should wait for the first menstruation.
When full or partial tapping of the TTC Evra

If the TTC Evra has completely or partially peeled off, then an insufficient amount of its active ingredients is supplied to the blood.

Even with a partial peeling off of the TTS Eur in less than a day (up to 24 hours): re-paste the TTC Eur on the same place or immediately replace it with a new TTC Eur.
No additional contraceptives are required. The next TTC Eur should be glued to the usual "replacement day".
At partial peeling more than a day (24 hours and longer), and also if a woman does not know exactly when the TTC Evra partially or completely peeled off - pregnancy may occur.
A woman should immediately begin a new cycle, pasting a new TTC of Eur and consider this day as the first day of the contraceptive cycle.Barrier methods of contraception should be applied simultaneously only in the first 7 days of a new cycle.
Do not try to re-glue the TTC of Eur, if it has lost its adhesive properties;
Instead, it is necessary to immediately glue a new TTS Evra. Do not use additional adhesive tapes or bandages to hold in place the TTC Eur.
If you missed the regular days of replacing the TTC Evra

At the beginning of any contraceptive cycle (week 1 / day 1): at an increased risk of pregnancy, a woman should glue the first TTS of the new cycle of Eur as soon as she remembers it.
This day is considered a new "1st day" and a new "day of replacement" is counted. Non-hormonal contraception should be applied simultaneously during the first 7 days of a new cycle. In the case of sexual intercourse during such an elongated period without the use of the TTS of Eur, conception may occur.
In the middle of the cycle (2nd week / 8th day or 3rd week / 15th day):

-If from the day of replacement, 1 or 2 days (up to 48 hours) have passed: a woman should immediately glue a new TTS.
The next TTC should be glued to the usual "replacement day". If the TTS application was correct within 7 days preceding the first missed TTS attachment day, additional contraception is not required;
-if if more than 2 days (48 hours or more) have passed since the day of replacement: there is an increased risk of pregnancy.
The woman should stop the current contraceptive cycle and immediately begin a new 4-week cycle, pasting the new TTC of Eur. This day is considered a new "1st day" and a new "day of replacement" is counted. Barrier contraception should be applied simultaneously during the first 7 days of the new cycle;
- At the end of the cycle (week 4 / day 22): if the TTC is not deleted at the beginning of the 4th week (day 22), then it should be removed as soon as possible.
The next contraceptive cycle should begin on the usual "replacement day", which is the next day after the 28th day. Additional contraception is not required.
Change day of replacement

In order to postpone menstruation for one cycle, a woman should glue a new TTS of Eur at the beginning of the 4th week (22nd day), thus missing a period free from the use of the TTC of Eur.
Intermenstrual bleeding or spotting may occur. After 6 consecutive weeks of TTS use, there should be a 7-day interval free from the use of TTS. After the end of this interval, regular use of the drug is resumed.
If, at the appointed day for a week, free from the application, the woman wants to change the day of replacement, she must complete the current cycle, removing the third TTC of Eur;
a woman can choose a new day of replacement, pasting the first TTC of the Eur of the next cycle on the selected day. A period free from the use of the TTC of Eur, in no case shall be more than 7 days. The shorter this period, the higher the probability that a woman will not have another menstrual period, and during the next contraceptive cycle, intermenstrual bleeding or spotting may occur.
Mode of application

TTS Evra should be applied to clean, dry, intact and healthy skin of the buttocks, abdomen, outer surface of the upper part of the shoulder or the upper part of the trunk with minimal hair, in areas where it will not come into contact with tight clothing.

In order to avoid possible irritation, every next TTS of the Eur should be glued to another area of ​​the skin, this can be done within the same anatomical area.

TTS Eur should be pressed tightly, so that its edges are in good contact with the skin.
To prevent the decrease in the adhesive properties of the TTC Eur, makeup, creams, lotions, powders and other local remedies can not be applied to those areas of the skin where it is glued or glued.
A woman should examine the TTC of Eur every day in order to be sure of her strong attachment.

Used TTS should be disposed of carefully in accordance with the instructions.

SIDE EFFECT

From the central nervous system and peripheral nervous system: dizziness, migraine, paresthesia, hypesthesia, convulsions, tremor, emotional lability, depression, anxiety, insomnia, drowsiness.

From the cardiovascular system: increased blood pressure, palpitation, edematous syndrome, varicose veins.

On the part of the digestive system: gingivitis, anorexia or increased appetite, gastritis, gastroenteritis, dyspepsia, abdominal pain, vomiting, diarrhea, flatulence, constipation, hemorrhoids.

On the part of the respiratory system: infections of the upper respiratory tract, shortness of breath, bronchial asthma.

On the part of the reproductive system: pain in sexual intercourse (dyspareunia), vaginitis, dysmenorrhea, decreased libido, mammary gland enlargement, menstrual irregularities (including intermenstrual bleeding, hypermenorrhea), changes in vaginal secretion, changes in cervical mucus, lactation not in connection with childbirth, abnormal ovarian function, mastitis, mammary fibroadenomas, ovarian cysts.

From the urinary system: infection of the urinary tract.

From the musculoskeletal system: muscle cramps, myalgia, arthralgia, ostalgia (including back pain, pain in the lower extremities), tendonosis (changes in tendons), muscle weakness.

Dermatological reactions: skin itching, urticaria, skin rash, contact dermatitis, bullous rash, acne, skin discoloration, eczema, increased sweating, alopecia, photosensitivity, dry skin.

From the side of the organ of vision: conjunctivitis, visual impairment.

From the side of metabolism: weight gain, hypertriglyceridemia, hypercholesterolemia.

Other: flu-like syndrome, fatigue, allergic reactions, chest pain, asthenic syndrome, syncope, anemia, abscesses, lymphadenopathy.

Rarely (with a frequency of> 0.01% to <0.1%): hypertension or hypotension of muscles, impaired coordination of movements, dysphonia, hemiplegia, neuralgia, stupor, increased libido, depersonalization, apathy, paranoia, benign breast tumors, cervical cancer in situ , pain in the perineum, ulceration of the genitals, atrophy of the mammary glands, decrease in blood pressure, enanthema, dry mouth or increased salivation, colitis, pain during urination, hyperprolactinaemia, melanosis, skin pigmentation disorders, chloasma, xerophthalmia, weight loss or obesity, inflammation
subcutaneous tissue, alcohol intolerance, cholecystitis, cholelithiasis, impaired liver function, purpura, blood flushes to the face, thrombosis (including deep vein thrombosis, pulmonary arterial thrombosis), superficial veins thrombophlebitis, vein pain, pulmonary embolism .
CONTRAINDICATIONS

- Venous thrombosis including.
in the anamnesis (including a deep vein thrombosis, pulmonary thromboembolism);
- arterial thrombosis, incl.
in the anamnesis (including acute disturbance of cerebral circulation, myocardial infarction, retinal artery thrombosis) or precursors of thrombosis (including angina pectoris or transient ischemia);
- the presence of serious or multiple risk factors for arterial thrombosis: severe arterial hypertension (more than 160/100 mm Hg), diabetes mellitus with vascular lesions;

- hereditary dyslipoproteinemia;

- hereditary predisposition to venous or arterial thrombosis (eg, resistance of activated protein C, deficiency of antithrombin III, deficiency of protein C, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies - antibodies against cardiolipin, lupus anticoagulant);

- Migraine with aura;

- confirmed or suspected breast cancer;

- endometrial cancer and confirmed or suspected estrogen-dependent tumors;

- adenoma and carcinoma of the liver;

- Genital bleeding;

- postmenopausal period;

- age up to 18 years;

- Postpartum period (4 weeks);

- lactation period;

- Hypersensitivity to the components of the drug.

It is inadmissible to apply the mammary glands to the area, as well as hyperemic, irritated or damaged skin areas.

Caution should be used when instructing in a family history of venous or arterial thromboembolism in the brothers, sisters or parents at a relatively young age;
with prolonged immobilization; obesity (body mass index more than 30 kg / m 2 , calculated as the ratio of body weight in kilograms to the square of growth in meters);thrombophlebitis of superficial veins and varicose veins; dyslipoproteinemia; arterial hypertension; damage to the valvular apparatus of the heart; atrial fibrillation;diabetes mellitus; systemic lupus erythematosus; hemolytic-uremic syndrome; Crohn's disease; ulcerative colitis; violations of liver function; hypertriglyceridemia (including in family history); acute liver dysfunction during a previous pregnancy or previous use of sex hormones; in the menstrual cycle; impaired renal function.
PREGNANCY AND LACTATION

Evra drug is contraindicated in pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER

With caution should be used with impaired renal function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

With caution should be used in human liver; acute liver dysfunction during a previous pregnancy or previous use of sex hormones.
APPLICATION FOR CHILDREN

The drug is contraindicated in children and adolescents under 18 years.

SPECIAL INSTRUCTIONS

There is no clinical evidence that transdermal contraceptive system on any aspect of the safety of oral contraceptives.
Before the start or resumption of the use of TTS Evra is necessary to collect a detailed medical history (including family history) and to exclude pregnancy. It should measure blood pressure and a physical examination with the warnings and contraindications.
If you suspect that a family history of venous thromboembolism (if venous thromboembolism occurred in a sibling or parent at a relatively young age), a woman should be referred to a specialist for consultation, before addressing the issue of the use of hormonal contraception.
The risk of cardiovascular complications is elevated in women with thrombophlebitis of superficial veins and varicose veins, as well as obesity (body mass index over 30 kg / m 2 ).
When prolonged immobilization, it is recommended to cease the use of hormonal contraceptives (if elective surgery is to be done for 4 weeks. To it) after major surgery in the lower extremities or severe trauma and resume hormonal contraception no sooner than 2 weeks. after complete remobilization.
Some epidemiological studies have shown an increased risk of cervical cancer in women who have long been used combined oral contraceptives.
In women taking combined oral contraceptives, may experience liver tumors that can cause life-threatening intra-abdominal haemorrhage. In case the women receiving transdermal Evra, severe pain in the upper abdomen, liver enlargement, or intra-abdominal bleeding symptoms should make a differential diagnosis to eliminate the possibility of liver tumor.
Women with hypertriglyceridemia, or this disease in family history may be at increased risk of pancreatitis when using combined hormonal contraceptives.
If you have any pharmacologically uncontrolled hypertension in women during use of combined hormonal contraceptive medication should be discontinued. Application TTC Evra can be resumed after the normalization of blood pressure.
It reported that the oral administration of combined hormonal contraceptives may occur or worsen the disease listed below, but convincing evidence of their connection with the use of combined oral contraceptives have. These include: jaundice and / or pruritus related to cholestasis; cholelithiasis; porphyria; systemic erythematosus; hemolytic-uremic syndrome; Sydenham's chorea; gestational herpes, otosclerosis-related hearing loss. Hormonal contraceptives may affect some endocrine indicators, markers of liver function and blood components are:
- increased concentrations of prothrombin and clotting factors VII, VIII, IX and X; reduced antithrombin III level; reduced level of protein S; enhanced platelet aggregation induced by noradrenaline;
- increasing the concentration of thyroxine binding globulin, which causes an increase in the concentration of total thyroid hormone, which is measured by the iodine content associated with a protein content of T 4 (determined by chromatography or radioimmunoassay); reduced binding of free T 3 ion exchange resin, as evidenced by increased concentration of thyroxine binding globulin concentration of free T 4 is not changed. It can be increased serum concentrations of other binding proteins;
- globulin increased concentration of sex hormone binding that results in increased concentrations of total circulating endogenous sex hormones. However, the concentration of free or biologically active sex steroids decreases or remains unchanged.
In women who use the TTC Evra may slightly increase the concentration of LDL-HDL cholesterol, total cholesterol, LDL-C and triglycerides, while the ratio of LDL-C / LDL-HDL may remain unchanged.
Hormonal contraceptives may cause a decrease in the concentrations of serum folate. This could have potentially clinically significant consequences if pregnancy occurs the woman shortly after the cancellation of hormonal contraceptives. Currently, all women should take folic acid during and after the end of hormonal contraception.
Combined hormonal contraceptives may affect the resistance of peripheral tissues to insulin and glucose tolerance, but there is no evidence of the need to change the mode of diabetes therapy during use of combined hormonal contraceptives. However, it should be carefully monitored condition of patients suffering from diabetes, especially in the early stages of use TTS Evra.
It reported a worsening of endogenous depression, of epilepsy, of Crohn's disease and ulcerative colitis in women taking combined oral contraceptives.
Women who have had a hyperpigmentation of the skin during pregnancy, should avoid exposure to sunlight or artificial ultraviolet light while wearing TTC Evra. Often, the pigmentation is not fully reversible.
Women should be informed that hormonal contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases through.
Women who take drugs that induce microsomal enzymes (hydantoins, barbiturates, primidone, carbamazepine, rifampicin, oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, modafinil, and phenylbutazone), and antibiotics (except tetracycline) should temporarily use a barrier method of contraception in addition to the use of Evra transdermal or choose another method of contraception. A barrier method should be used during the course of treatment the above drugs, as well as for 28 days after discontinuation of inducers of microsomal enzymes, and within 7 days after you stop taking antibiotics. If the period exceeds the receiving concomitant medications 3-week cycle using TTS Evra, the new contraceptive cycle should begin immediately after the previous one, ie. E. Without the usual period of free use of the TTS.Women receiving long-term therapy with drugs that induce hepatic enzymes, have to choose another method of contraception.
When assigning against application of transdermal Evra drugs that are metabolized isozymes CYP3A4, CYP2C19, especially those with a narrow therapeutic index (e.g., cyclosporin) should eliminate the possibility of clinically significant interaction.
Any use of combined oral contraceptives may be disturbed menstrual cycle (spotting or intermenstrual bleeding), especially in the first months of use of these funds. The duration of the adaptation period - about three cycles.
If while using the TTC Evra in accordance with the recommendations of the observed persistence of intermenstrual bleeding or a bleeding occurs after previous regular cycles, it is necessary to take into account other reasons, in addition to the use of the TTC. It should be borne in mind the possibility of non-hormonal causes of menstrual irregularities and, if necessary, to carry out adequate diagnostic testing to rule out organic disease or pregnancy.
Some women in the period of free use of TTS Evra menstruation may not occur. If a woman violated the instructions for use in the period preceding the first failed menstruation, or if she did not have two of menstruation after breaks use the TTC, it is necessary to exclude pregnancy before continuing the use of the TTC Evra.
In some women, the abolition of hormonal contraceptives may provoke the occurrence of amenorrhea or oligomenorrhea, especially when they are available before the start of hormonal contraception.
If Evra transdermal application causes skin irritation, it is possible to attach a new TTS to a different area of skin and wear it until the next day replacement.
Women with 90 kg of body weight or more contraceptive efficacy may be reduced.
In the event of liver dysfunction symptoms use of combined oral contraceptives should be discontinued until the normalization of liver function markers.
In case of recurrence associated with cholestasis itching that occurred during a previous pregnancy or previous use of sex hormones, combined hormonal contraceptives should be abolished.
Safety and efficacy of transdermal Evra set only for women aged 18 to 45 years.
Disposal
Immediately after removal of the TTS sachet should be tightly stuck to the skin. After removal of the TTS it still contains significant amounts of active ingredients.The residual hormones can harm the environment in the event of their falling into the water, and therefore should be carefully used by the TTC to recycle. For this purpose, special adhesive tape separated from the outside of the bag. Place the used TTS in a bag so that its adhesive side facing the painted area on the bag, and lightly pressed for sealing. A sealed bag discarded. Used TTS should not be thrown into the toilet or drain.
OVERDOSE

Symptoms: nausea, vomiting, vaginal bleeding.
Treatment: there is no specific antidote.
TTS must be removed and symptomatic therapy.
DRUG INTERACTION

Hydantoins, barbiturates, primidone, carbamazepine and rifampicin and oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, modafinil and phenylbutazone can cause accelerated metabolism of sex hormones which may cause intermenstrual bleeding or inefficiency of hormonal contraception, t. E. Of unintended pregnancy. The mechanism of interaction of these drugs and active ingredients TTC Evra based on the ability of these agents to induce liver enzymes, which are metabolised involving sex hormones. Maximal induction of enzyme is usually achieved not earlier than after 2-3 weeks, and may be stored at least 4 weeks after discontinuation of the corresponding drug.
Receiving vegetable preparations containing St. John's wort (Hypericum perforatum) simultaneously using TTS Evra can lead to loss of contraceptive effect. Women taking these herbal remedies may experience intermenstrual bleeding and unwanted pregnancies occur. This is due to the fact that St. John's wort induces the enzymes that metabolize hormones. Inducing effect can persist for 2 weeks. after withdrawal vegetable preparation containing St. John's wort.
Loss contraceptive effect may cause antibiotics (including ampicillin and tetracycline). Examination of pharmacokinetic interaction showed that oral administration of tetracycline hydrochloride for 3 days before and during the 7 days while using TTS Evra, has no significant effect on the pharmacokinetics norelgestromina or ethinyl estradiol.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

List B. The drug should be kept out of reach of children at a temperature of from 15 В° to 25 В° C.
Shelf life - 2 years.
Store in original container, store in the refrigerator and freezer.
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