Iodopengha may be available in the countries listed below.
Eugenol is reported as an ingredient of Iodopengha in the following countries:
Lidocaine is reported as an ingredient of Iodopengha in the following countries:
International Drug Name Search
Acide ascorbique may be available in the countries listed below.
Acide ascorbique (DCF) is known as Ascorbic Acid in the US.
International Drug Name Search
Glossary
| DCF | Dénomination Commune Française |
Treating bacterial infections of the skin, including dandruff. It may also be used for other conditions as determined by your doctor.
Ovace Foam is a sulfonamide. It works by restricting the production of folic acid, which bacteria need for growth. This kills the bacteria.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Ovace Foam. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Ovace Foam. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Ovace Foam may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Ovace Foam as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Ovace Foam.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Mild irritation.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody diarrhea; fever; joint pain; red, swollen, or blistered skin; severe diarrhea; severe or persistent irritation; sores in the mouth; stomach cramps/pain.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Ovace side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Ovace Foam may be harmful if swallowed. Symptoms of ingestion may include change in the amount of urine; nausea; vomiting.
Store Ovace Foam at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Avoid temperatures above 104 degrees F (40 degrees C). Store away from heat and direct sunlight. Do not puncture, break, or burn the canister even if it appears to be empty. Store away from moisture and light. Do not freeze. Keep Ovace Foam out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Ovace Foam. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Abdine Cold Relief Powder
Bell's Hot Lemon Cold Relief Powders
Abdine Hot Lemon Cold Relief Powders
Cold & Flu Relief Powders Lemon Flavour
Cold Relief Powders Lemon Flavour
Paracetamol BP 650 mg
Powder for oral solution
To give effective relief from the symptoms of cold and flu.
Adults, the elderly and children over 12 years: one sachet every four hours to a maximum of 4 sachets in any 24 hour period.
If symptoms persist for more than 3 days, consult your doctor.
Hypersensitivity to paracetamol or any of the other constituents.
Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazard of overdose is greater in those with non-cirrhotic, alcoholic liver disease.
Do not exceed the recommended dose.
Patients should be advised not to take other paracetamol-containing products concurrently.
If symptoms persist, consult your doctor.
Keep out of the reach of children.
On the label:
'Do not take with any other paracetamol-containing products'.
'Immediate medical advice should be sought in the event of an overdose, even if you feel well.'
On the leaflet (or label if no leaflet exists):
'Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed, serious liver damage'.
The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular daily use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.
Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage, but patients should follow the advice of their doctor regarding its use.
Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding.
None.
Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur.
There have been a few reports of blood dyscrasias including thrombocytopenia and agranulocytosis but these were not necessarily causally related to paracetamol.
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion.
Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported. Liver damage is possible in adults who have taken 10 g or more of paracetamol. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.
Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention and any patient who has ingested around 7.5 g or more of paracetamol in the preceding 4 hours should undergo gastric lavage. Administration of oral methionine or intravenous N-acetylcysteine which may have a beneficial effect up to at least 48 hours after the overdose, may be required. General supportive measures must be available.
This product is a mixture of active ingredients and excipients in powder form. When the contents of a sachet are passed through a disintegration unit (BP method) none of the granules are left on the wire mesh.
Sources: Martindale, The Extra Pharmacopoeia, 29th Edition.
Paracetamol is readily absorbed from the gastro-intestinal tract with peak plasma concentrations occurring about 30 minutes to two hours after ingestion. It is metabolised in the liver and excreted in the urine mainly as the gluconoride and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol.
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
Ascorbic Acid, Sucrose, Sodium Citrate BP, Citric Acid BP, Tartaric Acid BP, Sodium Cyclamate, Spray Dried Lemon Juice, Lemon Aroma, Starch (modified, edible) and Natural
Colour E100.
None known.
As packaged for sale: Three years
Do not store above 25°C
A trifoil laminated sachet containing 5 g of powder.
Pack size: 5, 8 or 10 sachets per carton.
Empty the contents of one sachet into a tumbler and fill with hot water. Stir till dissolved.
Bell Sons & Co (Druggists) Ltd
Gifford House
Slaidburn Crescent
Southport
Merseyside PR9 9AL
PL 03105/0069
01 March 1999
February 2010
(IF APPLICABLE)
(IF APPLICABLE)
Boots Rehydration Treatment
This medicine is available without prescription to treat minor conditions. However, you still need to take it carefully to get the best results from it.
This medicine contains Glucose and various salts which belong to a group of medicines called oral electrolytes which act to replace lost fluids and salts.
It can be used to relieve short term (acute) diarrhoea and replace lost salts and fluids, in order to prevent dehydration.
This medicine can be taken by adults and children over 1 year old. However, some people should not take this medicine or should seek the advice of their pharmacist or doctor first.
Do not give this medicine to infants under 1 year old, unless your doctor tells you to.
You can take this medicine if you are pregnant and breastfeeding.
Talk to a doctor straight away if an infant under the age of 1 year has diarrhoea.
Diarrhoea is a common symptom of a number of serious stomach and bowel conditions. If your diarrhoea continues for more than 24 to 48 hours or keeps coming back talk to your doctor.
This medicine is not expected to affect any other medicines that you may be taking.
If you are unsure about interactions with any medicines, talk to your pharmacist. This includes medicines prescribed by your doctor and medicine you have bought for yourself, including herbal and homeopathic remedies.
Check the sachet is not broken before use. If it is, do not take the sachet.
Drink the solution.
Adults and children of 12 years and over: Take 1 or 2 sachets dissolved in water, after each loose bowel movement.
Children of 1 to 11 years: Take 1 sachet dissolved in water, after each loose bowel movement
Infants under 1 year: Do not give this medicine unless your doctor tells you to. Follow your doctors instructions and ask your pharmacist if you need more information. If needed stop all solid and liquid feeds. Over the first 24 hours give one to one and a half times the normal feed volume that your baby takes at each feed.
Breastfed infants: Give this medicine at normal feed times only. Then breastfeed until the infant is no longer hungry.
Bottle fed infants: Stop all feeds. Give this medicine at normal feed times only.
As diarrhoea improves re-introduce normal diet.
Do not take or give more than the amount recommended.
Do not take this medicine for more than 24 to 48 hours. If your diarrhoea does not go away within 24 to 48 hours talk to your doctor.
If you take too many sachets: Talk to your pharmacist or doctor.
This medicine is not expected to cause side effects. If you notice any side effects talk to your pharmacist or doctor.
Store below 25°C. Store in a dry place.
Keep this medicine in a safe place out of the sight and reach of children, preferably in a locked cupboard.
Use by the date on the end flap of the carton.
Each sachet contains Citric Acid Anhydrous 0.128 g, Glucose Monohydrate 3.58 g, Potassium Chloride 0.3 g, Sodium Chloride 0.47 g, Sodium Citrate Dihydrate 0.39 g which are the active ingredients.
As well as the active ingredients the sachets also contain aspartame (E951,a source of phenylalanine), colloidal silicon dioxide, blackcurrant flavourings.
The pack contains 6 sachets containing granules.
Manufactured for
by the Marketing Authorisation Holder
Leaflet prepared August 2008
If you would like any further information about this medicine, please contact
Other formats
To request a copy of this leaflet in Braille, large print or audio please call, free of charge:
0800 198 5000 (UK only)
Please be ready to give the following information:
Product name: Boots Rehydration Treatment
Reference number: 12063/0046
This is a service provided by the Royal National Institute of the Blind.
3656eMC
Somazina may be available in the countries listed below.
Citicoline is reported as an ingredient of Somazina in the following countries:
Citicoline sodium salt (a derivative of Citicoline) is reported as an ingredient of Somazina in the following countries:
International Drug Name Search
Bedol
17-β estradiol 2 mg
Film Coated Tablet
Hormone replacement therapy (HRT) for oestrogen deficiency symptoms in peri- and post-menopausal hysterectomised women. Second line therapy for prevention of postmenopausal osteoporosis in women at high risk of future fractures where other therapies are ineffective or inappropriate (2mg).
Administration: Oral
Bedol is an oestrogen-only product. The calendar pack consists of 28 tablets each containing 2 mg of 17- β estradiol. One tablet is taken on each day of the 28 day treatment cycle.
For initiation and continuation of treatment of postmenopausal symptoms, the lowest effective dose for the shortest duration (see also Section +4.4) should be used.
Starting Bedol
Treatment of hysterectomised women and postmenopausal women may be started on any convenient day. If the patient is menstruating, treatment is started up to day 5 of bleeding. Patients changing from a cyclic or continuous sequential preparation should complete the cycle and then start Bedol without a break in therapy. Patients changing from a continuous combined preparation may start therapy at any time if amenorrhoea is established, or otherwise start on the first day of bleeding.
Progestogen administration (where indicated)
Women with intact uteri should normally use a standard dose of a progestogen in either a cyclic or continuous sequential or continuous combined regimen. Where a progestogen is necessary, it should be added for at least 12 – 14 days every 28 day cycle to reduce the risk to the endometrium (see Section 4.4). It should be started on the recommended day of the cycle, considering the day of the first Bedol tablet to be day 1. If a progestogen has been prescribed as continuous combined therapy it should be started at the same time as Bedol. A menstrual type vaginal bleed occurs at the end of the treatment cycle when progestogens are given as sequential regimens.
Unless there is a previous diagnosis of endometriosis, it is not recommended to add a progestogen in hysterectomised women.
Missed doses
If a dose is forgotten the patient should be advised to take it as soon as they remember. However, if a whole day has passed, patients should be advised not to take the missed tablet but to continue to take one tablet daily. A missed dose may increase the likelihood of break-through bleeding and spotting.
Children or males: Bedol is not intended for children or males.
Use in the elderly: There are no special dosage requirements.
Known, past or suspected breast cancer;
Known or suspected oestrogen dependent malignant tumours (e.g. endometrial cancer);
Undiagnosed genital bleeding;
Untreated endometrial hyperplasia;
Previous idiopathic or current venous thromboembolism (deep venous thrombosis, pulmonary embolism);
Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction);
Acute liver disease or a history of liver disease as long as liver function tests has failed to return to normal;
Known hypersensitivity to the active substances or to any of the excipients;
Porphyria;
For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be undertaken at least annually and HRT should only be continued as long as the benefit outweighs the risk
Medical examination/follow-up
Before initiating or reinstituting HRT, a complete personal and family medical history should be taken. Physical (including pelvic and breast) examination should be guided by this and by the contraindications (section 4.3) and warnings (section 4.4) for use. During treatment, periodic check-ups are recommended of a frequency and nature adapted to the individual woman. Women should be advised what changes in their breasts should be reported to their doctor or nurse (see 'Breast cancer' below). Investigations, including mammography, should be carried out in accordance with currently accepted screening practices, modified to the clinical needs of the individual.
Conditions which need supervision
If any of the following conditions are present, have occurred previously, and/or have been aggravated during pregnancy or previous hormone treatment, the patient should be closely supervised. It should be taken into account that these conditions may recur or be aggravated during treatment with Bedol, in particular:
- Leiomyoma (uterine fibroids) or endometriosis;
- A history of, or risk factors for, thromboembolic disorders (see below);
- Risk factors for oestrogen dependent tumours, e.g. 1st degree heredity for breast cancer;
- Hypertension;
- Liver disorders (e.g. liver adenoma);
- Diabetes mellitus with or without vascular involvement;
- Cholelithiasis;
- Migraine or severe headache;
- Systemic lupus erythematosus;
- A history of endometrial hyperplasia (see below);
- Epilepsy;
- Asthma;
- Otosclerosis.
Reasons for immediate withdrawal of therapy
Therapy should be discontinued when a contra-indication is discovered and in the following situations:
- Jaundice or deterioration in liver function;
- Significant increase in blood pressure;
- New onset of migraine-type headache;
- Pregnancy.
Endometrial hyperplasia
The risk of endometrial hyperplasia and carcinoma is increased when oestrogens are administered alone for prolonged periods (see section 4.8). The addition of a progestogen for at least 12 days per cycle in non-hysterectomised women greatly reduces this risk.
Break-through bleeding and spotting may occur during the first months of treatment. If break-through bleeding or spotting appears after some time on therapy, or continues after treatment has been discontinued, the reason should be investigated, which may include endometrial biopsy to exclude endometrial malignancy.
Unopposed oestrogen stimulation may lead to premalignant or malignant transformation in the residual foci of endometriosis. Therefore, the addition of progestogens to oestrogen replacement therapy should be considered in women who have undergone hysterectomy because of endometriosis, if they are known to have residual endometriosis.
Breast cancer
A randomised placebo-controlled trial, the Women's Health Initiative study (WHI), and epidemiological studies including the Million Women Study (MWS) have reported an increased risk of breast cancer in women taking oestrogens, oestrogen-progestogen combinations or tibolone for HRT for several years (see Section 4.8). For all HRT, an excess risk becomes apparent within a few years of use and increases with duration of intake but returns to baseline within a few (at most five) years after stopping treatment.
In the MWS, the relative risk of breast cancer with conjugated equine oestrogens (CEE) or estradiol (E2) was greater when a progestogen was added, either sequentially or continuously, and regardless of type of progestogen. There was no evidence of a difference in risk between the different routes of administration.
In the WHI study, the continuous combined conjugated equine oestrogen and medroxyprogesterone acetate (CEE + MPA) product used was associated with breast cancers that were slightly larger in size and more frequently had local lymph node metastases compared to placebo.
HRT, especially oestrogen-progestogen combined treatment, increases the density of mammographic images which may adversely affect the radiological detection of breast cancer.
Venous thromboembolism
HRT is associated with a higher relative risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. One randomised controlled trial and epidemiological studies found a two to threefold higher risk for users compared with non-users. For non-users, it is estimated that the number of cases of VTE that will occur over a 5 year period is about 3 per 1000 women aged 50-59 years and 8 per 1000 women aged between 60-69 years. It is estimated that in healthy women who use HRT for 5 years, the number of additional cases of VTE over a 5 year period will be between 2 and 6 (best estimate = 4) per 1000 women aged 50-59 years and between 5 and 15 (best estimate = 9) per 1000 women aged 60-69 years. The occurrence of such an event is more likely in the first year of HRT than later.
Generally recognised risk factors for VTE include a personal history or family history, severe obesity (Body Mass Index> 30 kg/m2) and systemic lupus erythematosis (SLE). There is no consensus about the role of varicose veins in VTE.
Patients with a history of VTE or known thrombophilic states have an increased risk of VTE. HRT may add to this risk. Personal or strong family history of thromboembolism or recurrent spontaneous abortion should be investigated in order to exclude a thrombophilic predisposition. Until a thorough evaluation of thrombophilic factors has been made or anticoagulant treatment initiated, use of HRT in such patients should be viewed as contraindicated. Those women already on anticoagulant treatment require careful consideration of the benefit-risk of use of HRT.
The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or major surgery. As in all post-operative patients, scrupulous attention should be given to prophylactic measures to prevent VTE following surgery. Where prolonged immobilisation is liable to follow elective surgery, particularly abdominal or orthopaedic surgery to the lower limbs, consideration should be given to temporarily stopping HRT four to six weeks earlier, if possible. Treatment should not be started until the woman is completely mobilised.
If VTE develops after initiating therapy, the drug should be discontinued. Patients should be told to contact their doctors immediately when they are aware of a potential thromboembolic symptom (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).
Coronary artery disease (CAD)
There is no evidence from randomised controlled trials of cardiovascular benefit with continuous combined conjugated oestrogens and medroxyprogesterone acetate (MPA). Two large clinical trials (WHI and HERS i.e. Heart and Estrogen/progestin Replacement Study) showed a possible increased risk of cardiovascular morbidity in the first year of use and no overall benefit. For other HRT products there are only limited data from randomised controlled trials examining effects in cardiovascular morbidity or mortality. Therefore it is uncertain whether these findings also extend to other HRT products.
Stroke
One large randomised clinical trial (WHI-trial) found, as a secondary outcome, an increased risk of ischaemic stroke in healthy women during treatment with continuous combined conjugated oestrogens and MPA (medroxyprogesterone acetate). For women who do not use HRT, it is estimated that the number of cases of stroke that will occur over a 5 year period is about 3 per 1000 women aged 50-59 years and 11 per 1000 women aged 60-69 years. It is estimated that for women who use conjugated oestrogens and MPA for 5 years, the number of additional cases will be between 0 and 3 (best estimate = 1) per 1000 users aged 50-59 years and between 1 and 9 (best estimate 4) per 1000 users aged 60-69 years. It is unknown whether the increased risk also extends to other HRT products.
Ovarian cancer
Long-term (at least 5-10 years) use of oestrogen-only HRT products in hysterectomised women has been associated with an increased risk of ovarian cancer in some epidemiological studies. It is uncertain whether long-term use of combined HRT confers a different risk than oestrogen-only products.
Other conditions
Oestrogens may cause fluid retention, and therefore patients with cardiac or renal dysfunction should be carefully observed. Patients with terminal renal insufficiency should be closely observed since it is expected that the level of circulating active ingredient (17β-estradiol) in Bedol is increased.
Women with pre-existing hypertriglyceridemia should be followed closely during oestrogen replacement or hormone replacement therapy since rare cases of large increases in plasma triglycerides leading to pancreatitis have been reported with oestrogen therapy in this condition.
Oestrogens increase thyroid binding globulin (TBG), leading to increased circulating total thyroid hormone, as measured by protein bound iodine (PBI), T4 levels (by column or radio-immunoassay) or T3 levels (by radioimmunoassay). T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Other binding proteins may be elevated in serum, i.e. corticoid binding globulin (CBG), sex-hormone-binding globulin (SHBG) leading to increased circulating corticosteroids and sex steroids, respectively. Free or biologically active hormone concentrations are unchanged. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).
There is no conclusive evidence for improvement of cognitive function. There is some evidence from the WHI trial of increased risk of probable dementia in women who start using continuous combined CEE and MPA after the age of 65. It is unknown whether the findings apply to younger post-menopausal women or other HRT products.
Bedol is not an oral contraceptive neither will it restore fertility. Women of child bearing potential should be advised to adhere to non-hormonal contraceptive methods.
The metabolism of oestrogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes, such as anticonvulsants (eg phenobarbital, phenytoin, carbamazepine) and anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz). Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones. Herbal preparations containing St John's wort (Hypericum Perforatum) may induce the metabolism of oestrogens.
Clinically, an increased metabolism of oestrogens may lead to decreased effect and changes in the uterine bleeding profile.
Bedol is not indicated during pregnancy. If pregnancy occurs during medication with Bedol treatment should be withdrawn immediately. The results of most epidemiological studies to date, relevant to inadvertent foetal exposure to oestrogens, indicate no teratogenic or foetotoxic effects.
Bedol is not indicated during lactation.
No effects on the ability to drive and use machines are reported.
NB: Patients with intact uteri taking progestogens for endometrial safety may report symptoms associated with this class of drugs. These include vaginal bleeding and premenstrual-like symptoms. (See also Section 4.4 for further information on endometrial hyperplasia)
Genito-urinary system - increase in size of uterine fibroids, vaginal candidiasis, change in cervical erosion and in degree of cervical secretion, cystitis like syndrome.
Breasts - tenderness, enlargement, secretion, breast cancer (see below)
Gastrointestinal - nausea, vomiting, abdominal cramps, bloating, cholestatic jaundice.
Skin - chloasma or melasma, which may persist when drug is discontinued, erythema multiforme, erythema nodusum, haemorrhagic eruption.
Eyes - steepening of corneal curvature, intolerance to contact lenses.
CNS - headaches, migraine, dizziness, chorea.
Miscellaneous - increase or decrease in weight, reduced carbohydrate tolerance, aggravation of porphyria, oedema, change in libido, leg cramps.
Breast Cancer
According to evidence from a large number of epidemiological studies and one randomised placebo-controlled trial, the Women's Health Initiative (WHI), the overall risk of breast cancer increases with increasing duration of HRT use in current or recent HRT users.
For oestrogen-only HRT, estimates of relative risk (RR) from a reanalysis of original data from 51 epidemiological studies (in which>80% of HRT use was oestrogen-only HRT) and from the epidemiological Million Women Study (MWS) are similar at 1.35 (95%CI 1.21 – 1.49) and 1.30 (95%CI 1.21 – 1.40), respectively.
For oestrogen plus progestogen combined HRT, several epidemiological studies have reported an overall higher risk for breast cancer than with oestrogens alone.
The MWS reported that, compared to never users, the use of various types of oestrogen-progestogen combined HRT was associated with a higher risk of breast cancer (RR = 2.00, 95%CI: 1.88 – 2.12) than use of oestrogens alone (RR = 1.30, 95%CI: 1.21 – 1.40) or use of tibolone (RR=1.45; 95%CI 1.25-1.68).
The WHI trial reported a risk estimate of 1.24 (95%CI 1.01 – 1.54) after 5.6 years of use of oestrogen-progestogen combined HRT (CEE + MPA) in all users compared with placebo.
The absolute risks calculated from the MWS and the WHI trial are presented below:
The MWS has estimated, from the known average incidence of breast cancer in developed countries, that:
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The WHI trial estimated that after 5.6 years of follow-up of women between the ages of 50 and 79 years, an additional 8 cases of invasive breast cancer would be due to oestrogen-progestogen combined HRT (CEE + MPA) per 10,000 women years.
According to calculations from the trial data, it is estimated that: | |
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The number of additional cases of breast cancer in women who use HRT is broadly similar for women who start HRT irrespective of age at start of use (between the ages of 45-65) (see section 4.4).
Endometrial cancer
In women with an intact uterus, the risk of endometrial hyperplasia and endometrial cancer increases with increasing duration of use of unopposed oestrogens. According to data from epidemiological studies, the best estimate of the risk is that for women not using HRT, about 5 in every 1000 are expected to have endometrial cancer diagnosed between the ages of 50 and 65. Depending on the duration of treatment and oestrogen dose, the reported increase in endometrial cancer risk among unopposed oestrogen users varies from 2-to 12-fold greater compared with non-users. Adding a progestogen to oestrogen-only therapy greatly reduces this increased risk.
Other adverse reactions have been reported in association with oestrogen treatment:
– Oestrogen dependent neoplasms benign and malignant, e.g. endometrial cancer.
– Venous thromboembolism, i.e. deep leg or pelvic venous thrombosis and pulmonary embolism, is more frequent among HRT users than among non-users. For further information see sections “4.3 Contraindications” and “4.4 Warnings and precautions for use”.
– Myocardial infarction and stroke.
– Gall bladder disease.
– Probable dementia (see section 4.4).
Nausea and vomiting may occur after overdose. Treatment should be symptomatic; there is no specific antidote.
The active ingredient, synthetic 17- β estradiol, is chemically and biologically identical to endogenous human estradiol. It substitutes for the loss of oestrogen production in menopausal women, and alleviates menopausal symptoms.
17- β estradiol is absorbed rapidly after oral administration. The rate and completeness of absorption of 17- β estradiol in Bedol were found to be bioequivalent to Zumenon as assessed by the maximum concentrations of achieved (Bedol Cmax = 187 pmol/L), time to maximum concentration (Tmax) and area under the concentration time curve (AUC).
Studies in animals have indicated that administration of very high doses of oestrogens will induce neoplastic tumours in some animal species.
The results of preclinical studies of 17- β estradiol have not suggested any unwanted effects at therapeutic doses used in humans.
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No chemical or physical incompatibilities are noted.
Three years from date of manufacture.
Store below 25°C protected from light and moisture.
PVC and aluminium foil calendar blister pack enclosed in a cardboard carton.
Not applicable.
ReSource Medical UK Limited
2 Carlton Avenue, Staincliff
Batley
WF17 7AQ, UK
PL 21812/0001
18 August 1997
February 2005
Class: Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
VA Class: AM800
Chemical Name: 2′,3′-Didehydro-3′-deoxythymidine
CAS Number: 3056-17-5
Brands: Zerit
Lactic acidosis and severe hepatomegaly with steatosis (including some fatalities) reported rarely in patients receiving nucleoside reverse transcriptase inhibitors (NRTIs) alone or in conjunction with other antiretrovirals.1 (See Lactic Acidosis and Severe Hepatomegaly with Steatosis under Cautions.)
Fatal lactic acidosis reported in pregnant women receiving stavudine and didanosine with other antiretrovirals.1 Stavudine in conjunction with didanosine should be used with caution in pregnant women and only if potential benefits outweigh potential risks.1 (See Pregnancy under Cautions.)
Fatal and nonfatal pancreatitis reported in patients receiving stavudine and didanosine with or without hydroxyurea.1 (See Pancreatitis under Cautions.)
REMS:
FDA approved a REMS for stavudine to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().
Antiretroviral; nucleoside reverse transcriptase inhibitor (NRTI).1 2 3 4 5 6 7 8 9 10 11 12 16 17 20 21 23 24
Treatment of HIV-1 infection in conjunction with other antiretrovirals.1
No longer a preferred or alternative NRTI for initial therapy in adults (increasing reports of toxicity).43
Postexposure prophylaxis of HIV infection† in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with risk for transmission of the virus.63 Used in conjunction with other antiretrovirals.63
Postexposure prophylaxis of HIV infection† in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.76 Used in conjunction with other antiretrovirals.76
Administer orally without regard to meals.1 43
Reconstitute powder for oral solution at time of dispensing by adding the amount of purified water specified to provide a solution containing 1 mg/mL.1
Agitate suspension well prior to administration of each dose.1
Must be given in conjunction with other antiretrovirals.1
Birth to 13 days of age: 0.5 mg/kg every 12 hours.1 53
≥14 days of age weighing <30 kg: 1 mg/kg every 12 hours.1 53
≥30 kg to <60 kg: 30 mg twice daily.1 53
≥60 kg: 40 mg twice daily.1 53
Temporarily interrupt stavudine if peripheral neuropathy occurs.1 If peripheral neuropathy resolves completely, reinitiate using doses 50% of the usually recommended pediatric dose.1 (See Peripheral Neuropathy under Cautions.)
<60 kg: 30 mg twice daily.1 43
≥60 kg: 40 mg twice daily.1 43
Temporarily interrupt stavudine if peripheral neuropathy occurs.1 If peripheral neuropathy resolves, reinitiate with 15 mg twice daily in those weighing <60 kg and 20 mg twice daily in those weighing ≥60 kg.1 (See Peripheral Neuropathy under Cautions.)
<60 kg: 30 mg twice daily.63
≥60 kg: 40 mg twice daily; if toxicity develops, use 20–30 mg twice daily.63
Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.63
<60 kg: 30 mg twice daily.76
≥60 kg: 40 mg twice daily.76
Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.76
Consider a reduction in the dose and/or an increase in the dosing interval in pediatric patients with renal impairment;1 53 data insufficient to recommend a specific dose adjustment.1
Clcr (mL/minute) | Weighing <60 kg | Weighing≥60 kg |
|---|---|---|
≥50 | 30 mg every 12 hours | 40 mg every 12 hours |
26–50 | 15 mg every 12 hours | 20 mg every 12 hours |
10–25 | 15 mg every 24 hours | 20 mg every 24 hours |
Hemodialysis Patients | 15 mg every 24 hours given after completion of dialysis and at the same time of day on days that patient does not undergo hemodialysis | 20 mg every 24 hours given after completion of dialysis and at the same time of day on days that patient does not undergo hemodialysis |
Known hypersensitivity to stavudine or any ingredient in the formulation.1
Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving stavudine.1 Reported most frequently in women; obesity and long-term NRTI therapy also may be risk factors.1 Has been reported in patients with no known risk factors.1
Reported in pregnant women receiving stavudine in conjunction with didanosine.1 (See Pregnancy under Cautions.)
Use with caution in patients with known risk factors for liver disease.1
Interrupt therapy if there are clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (e.g., hepatomegaly and steatosis even in the absence of marked increases in serum aminotransferase concentrations).1
Concomitant use with didanosine (with or without hydroxyurea) associated with increased risk of hepatotoxicity and pancreatitis.1 (See Specific Drugs under Interactions.)
Concomitant use with ribavirin and interferon (interferon alfa, peginterferon alfa) associated with increased risk of fatal hepatic decompensation in patients coinfected with HCV and HIV.1 80 (See Specific Drugs under Interactions.)
Peripheral neuropathy, manifested by numbness, tingling, or pain in the hands or feet, reported; these effects occur more frequently in patients with advanced HIV, a history of neuropathy, or those receiving other neurotoxic drugs, including didanosine.1
Dosage modification or discontinuance may be necessary.1 Patients whose symptoms resolve after the drug is discontinued may tolerate a reduced stavudine dosage; if neuropathy recurs, permanent discontinuance should be considered.1
Rapidly ascending neuromuscular weakness, which has been fatal in some cases, reported rarely in patients receiving stavudine in conjunction with other antiretrovirals.1 75 Most reported cases of motor weakness occurred in the setting of lactic acidosis.1 75
The evolution of motor weakness may mimic the clinical presentation of Guillain-Barré syndrome (including respiratory failure); symptoms may continue or worsen following discontinuance of antiretroviral therapy.1 Discontinue stavudine if motor weakness develops.75
Fatal and nonfatal pancreatitis reported in patients receiving stavudine in conjunction with didanosine in both treatment-naive and previously treated patients, regardless of degree of immunosuppression.1 46
Interrupt treatment with stavudine, didanosine, and any other agent toxic to the pancreas in patients with signs or symptoms of pancreatitis.1 Reinitiation of stavudine therapy following a confirmed diagnosis of pancreatitis should be undertaken with particular caution and close patient monitoring.1 If stavudine is reinitiated in these patients, didanosine should not be included in the regimen.1
Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.1
During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]); this may necessitate further evaluation and treatment.1
Category C.1 Antiretroviral Pregnancy Registry at 800-258-4263.1
Some experts state stavudine is an alternative (not a preferred) NRTI for use in multiple-drug antiretroviral regimens in pregnant women.25
Do not use stavudine in conjunction with zidovudine in pregnant women because of potential antagonist antiretroviral effects.25
Fatal lactic acidosis reported in pregnant women receiving stavudine and didanosine with other antiretrovirals.1 43 Unclear whether pregnancy potentiates risk of lactic acidosis and severe hepatotoxicity with steatosis that occurs in NRTI-treated individuals.1 Stavudine in conjunction with didanosine should be used with caution in pregnant women and only if no other options are available.1 43
Clinicians caring for pregnant patients receiving stavudine should be alert for early diagnosis of lactic acidosis and hepatitis steatosis syndrome.1
Stavudine distributed into milk in rats; not known whether distributed into human milk.1
Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.1
Use in pediatric patients from birth through adolescence supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients.1
Adverse effects in pediatric patients generally are similar to those reported in adults.1
Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults, but increased sensitivity cannot be ruled out.1
Peripheral neuropathy reported in geriatric individuals; monitor these patients for signs and symptoms of peripheral neuropathy.1
Substantially eliminated by the kidneys; geriatric patients more likely to have decreased renal function; monitor renal function and adjust dosage accordingly.1 18
Safety and efficacy not established in patients with clinically important hepatic disease.1
Increased incidence of liver function abnormalities, including potentially fatal hepatic adverse effects, reported in patients with preexisting hepatic impairment.1
Monitor patients with liver function abnormalities.1 Interrupt or discontinue therapy if liver disease worsens.1
Dosage adjustments needed based on degree of renal impairment.1 (See Renal Impairment under Dosage and Administration.)
Headache, diarrhea, peripheral neurologic symptoms/neuropathy, rash, nausea and vomiting.1
Does not inhibit CYP1A2, 2C9, 2C19, 2D6, 3A4.1
Drug | Interaction | Comments |
|---|---|---|
Abacavir | In vitro evidence of additive or synergistic antiretroviral effects1 | |
Clarithromycin | Pharmacokinetic interactions unlikely38 | |
Darunavir | Pharmacokinetic interactions unlikely78 | |
Didanosine | Pharmacokinetic interactions unlikely46 Concomitant use of didanosine and stavudine (with or without hydroxyurea): Possible increased risk of toxicities (pancreatitis, peripheral neuropathy, hyperlactatemia)1 43 In vitro evidence of additive or synergistic antiretroviral effects28 29 | Concomitant use of didanosine and stavudine: Avoid concomitant use unless potential benefits outweigh risks43 Avoid concomitant use of didanosine, hydroxyurea, and stavudine1 |
Doxorubicin | Inhibits stavudine phosphorylation in vitro1 | Clinical importance unknown; use concomitantly with caution1 |
Emtricitabine | Pharmacokinetic interaction unlikely79 In vitro evidence of additive or synergistic antiretroviral effects79 | |
Fluconazole | Pharmacokinetic interactions unlikely38 | |
Ganciclovir | Pharmacokinetic interactions unlikely54 | |
Hydroxyurea | Concomitant use of didanosine and stavudine (with or without hydroxyurea): Potential for increased risk of pancreatitis, peripheral neuropathy, hepatotoxicity1 | Avoid concomitant use of hydroxyurea and stavudine1 |
Interferon (interferon alfa, peginterferon alfa) | Possible increased risk of potentially fatal hepatic decompensation in patients coinfected with HCV and HIV who are receiving interferon alfa, ribavirin, and antiretroviral agents1 80 | If stavudine used in patients receiving interferon alfa or peginterferon alfa (with or without ribavirin), closely monitor for toxicities, especially hepatic decompensation; consider discontinuing stavudine as appropriate; if worsening toxicities (e.g., hepatic decompensation Child-Pugh >6) are observed, consider discontinuing or reducing dosage of interferon and/or ribavirin1 80 |
Lamivudine | Pharmacokinetic interactions unlikely1 In vitro evidence of additive or synergistic antiretroviral effects28 29 | |
Methadone | Decreased stavudine peak plasma concentrations and AUC;31 43 no change in methadone concentrations31 | Dosage adjustments not necessary43 |
Nelfinavir | Pharmacokinetic interactions unlikely33 In vitro evidence of additive or synergistic antiretroviral effects28 32 33 35 | Dosage adjustments not needed33 |
Ribavirin | Ribavirin can reduce phosphorylation of stavudine; no evidence of pharmacokinetic or pharmacodynamic interaction1 Possible increased risk of potentially fatal hepatic decompensation in patients coinfected with HCV and HIV who are receiving interferon alfa or peginterferon alfa, ribavirin, and antiretroviral agents1 80 Possible increase in adverse effects (lactic acidosis, pancreatitis)65 66 68 | If stavudine used in patients receiving interferon alfa or peginterferon alfa (with or without ribavirin), closely monitor for toxicities, especially hepatic decompensation; consider discontinuing stavudine as appropriate; if worsening toxicities (e.g., hepatic decompensation Child-Pugh >6) are observed, consider discontinuing or reducing dosage of interferon and/or ribavirin1 80 |
Rifabutin | Decreased stavudine peak plasma concentrations and AUC38 | |
Saquinavir | In vitro evidence of additive or synergistic antiretroviral effects28 32 33 35 | |
Tipranavir | Pharmacokinetic interaction unlikely77 In vitro evidence of additive antiretroviral effects77 | |
Zidovudine | In vitro evidence of antagonism1 26 40 | Concomitant use not recommended1 43 |
Well absorbed; peak plasma concentrations attained within 1 hour.1 Bioavailability is 86%.1
Stavudine capsules and oral solution are bioequivalent.1
Food delays time to peak concentrations; no effect on AUC.69
Peak plasma concentration and time to peak concentration not altered in patients with renal impairment.1
Not well characterized.1 Distributed into semen.74
Distributed into CSF in adults and pediatric patients.1 70 71
Not known whether crosses the placenta or is distributed into human milk.1
Negligible.1
Metabolic fate not elucidated.1
Intracellularly, stavudine is phosphorylated and converted by cellular enzymes to the active 5′-triphosphate metabolite.1 2 4 8 17 22
Eliminated in the urine (40%) by glomerular filtration and active tubular secretion; remaining 60% presumably eliminated by endogenous pathways.1
Removed by hemodialysis.1 18 Not known whether removed by peritoneal dialysis.1
1.6 hours.1
Half-life is 0.96 hours in pediatric patients 5 weeks to 15 years of age; 1.59 hours in those 14–28 days of age; 5.27 hours in those 1 day of age.1
Pharmacokinetics not altered in patients with hepatic impairment (Child-Pugh class B or C).1
Apparent oral clearance of stavudine decreases and half-life increases as Clcr decreases.1
15–30°C in tightly closed containers.1
15–30°C.1 Following reconstitution with water, oral solution stable for 30 days when refrigerated at 2–8°C.1 Unused portions of reconstituted oral solution should be discarded after 30 days.1
Analog of thymidine, a naturally occurring pyrimidine.1 2 3 4 6 8 9 16
Pharmacologically related to other NRTIs (e.g., abacavir, didanosine, emtricitabine, lamivudine, zidovudine); differs structurally from these drugs; also differs pharmacologically and structurally from other currently available antiretrovirals.1
Active in vitro against HIV-11 2 3 4 9 10 11 12 16 17 20 21 23 24 27 28 and HIV-2.27
Inhibits replication of HIV by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).1 2 3 4 9 12 16 17 21 23
Strains of HIV-1 with reduced susceptibility to stavudine have been produced in vitro and have emerged during therapy with the drug.1 27
Strains of HIV resistant to stavudine may be cross-resistant to some other NRTIs.1 27
Cross-resistance between stavudine and HIV protease inhibitors (PIs) is highly unlikely since the drugs have different target enzymes.43 Cross-resistance between stavudine and nonnucleoside reverse transcriptase inhibitors (NNRTIs) is considered to be low since the drugs bind at different sites on reverse transcriptase and have different mechanisms of action.43
Critical nature of compliance with HIV therapy.1 Importance of using stavudine in conjunction with other antiretrovirals—not for monotherapy.1
Antiretroviral therapy is not a cure for HIV infection, and opportunistic infections still may occur.1 HIV transmission via sexual contact or sharing needles is not prevented by antiretrovirals.1
Possibility of lactic acidosis; patients who experience symptoms of lactic acidosis (abdominal discomfort, nausea, vomiting, fatigue, dyspnea, motor weakness) should seek immediate medical attention.1 Discontinuation of the drug may be required.1
Possibility of peripheral neuropathy; manifestations include numbness, tingling, or pain in hands or feet.1 Advise patient to report these symptoms to their clinician.1 Dosage modification or discontinuance may be needed.1
Possibility of pancreatitis, including fatal pancreatitis if used with didanosine.1
Importance of patient reading the patient package insert from manufacturer.1
Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.1
Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of advising patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 15 mg* | Stavudine Capsules | |
Zerit | Bristol-Myers Squibb | |||
20 mg* | Stavudine Capsules | |||
Zerit | Bristol-Myers Squibb | |||
30 mg* | Stavudine Capsules | |||
Zerit | Bristol-Myers Squibb | |||
40 mg* | Stavudine Capsules | |||
Zerit | Bristol-Myers Squibb | |||
For solution | 1 mg/mL* | Stavudine for Oral Solution | ||
Zerit | Bristol-Myers Squibb |
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Stavudine 40MG Capsules (CAMBER PHARMACEUTICALS): 60/$129.99 or 180/$369.97
Zerit 1MG/ML Solution (B-M SQUIBB ONCOLOGY/IMMUNOLOGY): 200/$87.99 or 600/$255.97
Zerit 15MG Capsules (B-M SQUIBB ONCOLOGY/IMMUNOLOGY): 60/$363.99 or 180/$1,050.34
Zerit 20MG Capsules (B-M SQUIBB ONCOLOGY/IMMUNOLOGY): 60/$388.98 or 180/$1,126.01
Zerit 30MG Capsules (B-M SQUIBB ONCOLOGY/IMMUNOLOGY): 60/$416.98 or 180/$1,197.99
Zerit 40MG Capsules (B-M SQUIBB ONCOLOGY/IMMUNOLOGY): 60/$426.97 or 180/$1,225.97
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
1. Bristol-Myers Squibb. Zerit (stavudine) capsules and powder for oral solution prescribing information. Princeton, NJ; 2008 Nov.
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54. Jung D, AbdelHameed MH, Teitelbaum P et al. The pharmacokinetics and safety profile of oral ganciclovir combined with zalcitabine or stavudine in asymptomatic HIV- and CMV-seropositive patients J Clin Pharmacol. 1999; 39:505-12.
55. Wintergerst U, Hoffmann F, Solder B et al. Comparison of two antiretroviral triple combinations including the protease inhibitor indinavir in children infected with human immunodeficiency virus. Pediatr Infect Dis J. 1998; 17:495-9. [IDIS 408835] [PubMed 9655541]
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