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DRUGS & SUPPLEMENTS
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Wellcovorin
What are the side effects you encounter while taking this medicine? |
Wellcovorin uses
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Overdosage
- Dosage and administration
- How supplied
INDICATIONS AND USAGE
Wellcovorin calcium rescue is indicated after high dose methotrexate therapy in osteosarcoma. Wellcovorin calcium is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists.
Wellcovorin calcium is indicated in the treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible.
Wellcovorin is also indicated for use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. Wellcovorin should not be mixed in the same infusion as 5-fluorouracil because a precipitate may form.
CONTRAINDICATIONS
Wellcovorin is improper therapy for pernicious anemia and other megaloblastic anemias secondary to the lack of vitamin B12. A hematologic remission may occur while neurologic manifestations continue to progress.
WARNINGS
In the treatment of accidental overdosages of folic acid antagonists, intravenous Wellcovorin should be administered as promptly as possible. As the time interval between antifolate administration (e.g., methotrexate) and Wellcovorin rescue increases, leucovorin's effectiveness in counteracting toxicity decreases. In the treatment of accidental overdosages of intrathecally administered folic acid antagonists, do not administer Wellcovorin intrathecally. Wellcovorin MAY BE HARMFUL OR FATAL IF GIVEN INTRATHECALLY.
Monitoring of the serum methotrexate concentration is essential in determining the optimal dose and duration of treatment with Wellcovorin.
Delayed methotrexate excretion may be caused by a third space fluid accumulation (i.e., ascites, pleural effusion), renal insufficiency, or inadequate hydration. Under such circumstances, higher doses of Wellcovorin or prolonged administration may be indicated. Doses higher than those recommended for oral use must be given intravenously.
Because of the benzyl alcohol contained in certain diluents used for reconstituting Wellcovorin Calcium for Injection, when doses greater than 10 mg/m2 are administered, Wellcovorin Calcium for Injection should be reconstituted with Sterile Water for Injection, USP, and used immediately (see DOSAGE AND ADMINISTRATION ).
Because of the calcium content of the Wellcovorin solution, no more than 160 mg of Wellcovorin should be injected intravenously per minute (16 mL of a 10 mg/mL, or 8 mL of a 20 mg/mL solution per minute).
Wellcovorin enhances the toxicity of 5-fluorouracil. When these drugs are administered concurrently in the palliative therapy of advanced colorectal cancer, the dosage of 5-fluorouracil must be lower than usually administered. Although the toxicities observed in patients treated with the combination of Wellcovorin plus 5-fluorouracil are qualitatively similar to those observed in patients treated with 5-fluorouracil alone, gastrointestinal toxicities (particularly stomatitis and diarrhea) are observed more commonly and may be more severe and of prolonged duration in patients treated with the combination.
In the first Mayo/NCCTG controlled trial, toxicity, primarily gastrointestinal, resulted in 7% of patients requiring hospitalization when treated with 5-fluorouracil alone or 5-fluorouracil in combination with 200 mg/m2 of Wellcovorin and 20% when treated with 5-fluorouracil in combination with 20 mg/m2 of Wellcovorin. In the second Mayo/NCCTG trial, hospitalizations related to treatment toxicity also appeared to occur more often in patients treated with the low dose leucovorin/5-fluorouracil combination than in patients treated with the high dose combination - 11% versus 3%. Therapy with Wellcovorin and 5-fluorouracil must not be initiated or continued in patients who have symptoms of gastrointestinal toxicity of any severity, until those symptoms have completely resolved. Patients with diarrhea must be monitored with particular care until the diarrhea has resolved, as rapid clinical deterioration leading to death can occur. In an additional study utilizing higher weekly doses of 5-fluorouracil and Wellcovorin, elderly and/or debilitated patients were found to be at greater risk for severe gastrointestinal toxicity.
Seizures and/or syncope have been reported rarely in cancer patients receiving Wellcovorin, usually in association with fluoropyrimidine administration, and most commonly in those with CNS metastases or other predisposing factors, however, a causal relationship has not been established.
The concomitant use of Wellcovorin with trimethoprim-sulfamethoxazole for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection was associated with increased rates of treatment failure and morbidity in a placebo-controlled study.
PRECAUTIONS
General
Parenteral administration is preferable to oral dosing if there is a possibility that the patient may vomit and not absorb the Wellcovorin. Wellcovorin has no effect on non-hematologic toxicities of methotrexate such as the nephrotoxicity resulting from drug and/or metabolite precipitation in the kidney.
Since Wellcovorin enhances the toxicity of fluorouracil, leucovorin/5-fluorouracil combination therapy for advanced colorectal cancer should be administered under the supervision of a physician experienced in the use of antimetabolite cancer chemotherapy. Particular care should be taken in the treatment of elderly or debilitated colorectal cancer patients, as these patients may be at increased risk of severe toxicity.
Laboratory Tests
Patients being treated with the leucovorin/5-fluorouracil combination should have a CBC with differential and platelets prior to each treatment. During the first two courses a CBC with differential and platelets has to be repeated weekly and thereafter once each cycle at the time of anticipated WBC nadir. Electrolytes and liver function tests should be performed prior to each treatment for the first three cycles then prior to every other cycle. Dosage modifications of fluorouracil should be instituted as follows, based on the most severe toxicities:
| Diarrhea and/or Stomatitis | WBC/mm3 Nadir | Platelets/mm3 Nadir | 5-FU Dose |
| Moderate | 1,000 - 1,900 | 25 - 75,000 | decrease 20% |
| Severe | < 1,000 | < 25,000 | decrease 30% |
If no toxicity occurs, the 5-fluorouracil dose may increase 10%. Treatment should be deferred until WBCs are 4,000/mm3 and platelets 130,000/mm3. If blood counts do not reach these levels within two weeks, treatment should be discontinued. Patients should be followed up with physical examination prior to each treatment course and appropriate radiological examination as needed. Treatment should be discontinued when there is clear evidence of tumor progression.
Drug Interactions
Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone, and increase the frequency of seizures in susceptible pediatric patients.
Preliminary animal and human studies have shown that small quantities of systemically administered Wellcovorin enter the CSF primarily as 5-methyltetrahydrofolate and, in humans, remain 1 to 3 orders of magnitude lower than the usual methotrexate concentrations following intrathecal administration. However, high doses of Wellcovorin may reduce the efficacy of intrathecally administered methotrexate.
Wellcovorin may enhance the toxicity of 5-fluorouracil.
Pregnancy
Teratogenic Effects
Pregnancy Category C
Adequate animal reproduction studies have not been conducted with Wellcovorin. It is also not known whether Wellcovorin can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Wellcovorin should be given to a pregnant woman only if clearly needed.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Wellcovorin is administered to a nursing mother.
Pediatric Use
See PRECAUTIONS, Drug Interactions.
Geriatric Use
Clinical studies of Wellcovorin calcium did not show differences in safety or effectiveness between subjects over 65 and younger subjects. Other clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older patients cannot be ruled out. This drug is known to be excreted by the kidney and the risk of toxic reactions to the drug may be greater in patients with impaired renal function. Because elder patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
ADVERSE REACTIONS
Allergic sensitization, including anaphylactoid reactions and urticaria, has been reported following the administration of both oral and parenteral Wellcovorin. No other adverse reactions have been attributed to the use of Wellcovorin per se.
The following table summarizes significant adverse events occurring in 316 patients treated with the leucovorin/5-fluorouracil combinations compared against 70 patients treated with 5-fluorouracil alone for advanced colorectal carcinoma. These data are taken from the Mayo/NCCTG large multicenter prospective trial evaluating the efficacy and safety of the combination regimen.
| High LV = Wellcovorin 200 mg/m2, Low LV = Wellcovorin 20 mg/m2 | ||||||
| Any = percentage of patients reporting toxicity of any severity | ||||||
| Grade 3+ = percentage of patients reporting toxicity of Grade 3 or higher | ||||||
| (High LV)/5-FU (N=155) | (Low LV)/5-FU (N=161) | 5-FU Alone (N=70) | ||||
| Any | Grade 3+ | Any | Grade 3+ | Any | Grade 3+ | |
| (%) | (%) | (%) | (%) | (%) | (%) | |
| Leukopenia | 69 | 14 | 83 | 23 | 93 | 48 |
| Thrombocytopenia | 8 | 2 | 8 | 1 | 18 | 3 |
| Infection | 8 | 1 | 3 | 1 | 7 | 2 |
| Nausea | 74 | 10 | 80 | 9 | 60 | 6 |
| Vomiting | 46 | 8 | 44 | 9 | 40 | 7 |
| Diarrhea | 66 | 18 | 67 | 14 | 43 | 11 |
| Stomatitis | 75 | 27 | 84 | 29 | 59 | 16 |
| Constipation | 3 | 0 | 4 | 0 | 1 | - |
| Lethargy/Malaise/Fatigue | 13 | 3 | 12 | 2 | 6 | 3 |
| Alopecia | 42 | 5 | 43 | 6 | 37 | 7 |
| Dermatitis | 21 | 2 | 25 | 1 | 13 | - |
| Anorexia | 14 | 1 | 22 | 4 | 14 | - |
| Hospitalization for Toxicity | 5% | 15% | 7% | |||
To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals, Inc. at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
OVERDOSAGE
Excessive amounts of Wellcovorin may nullify the chemotherapeutic effect of folic acid antagonists.
DOSAGE AND ADMINISTRATION
Advanced Colorectal Cancer
Either of the following two regimens is recommended:
- Wellcovorin is administered at 200 mg/m2 by slow intravenous injection over a minimum of 3 minutes, followed by 5-fluorouracil at 370 mg/m2 by intravenous injection.
- Wellcovorin is administered at 20 mg/m2 by intravenous injection followed by 5-fluorouracil at 425 mg/m2 by intravenous injection.
5-Fluorouracil and Wellcovorin should be administered separately to avoid the formation of a precipitate.
Treatment is repeated daily for five days. This five-day treatment course may be repeated at 4 week intervals, for 2 courses and then repeated at 4 to 5 week (28 to 35 day) intervals provided that the patient has completely recovered from the toxic effects of the prior treatment course.
In subsequent treatment courses, the dosage of 5-fluorouracil should be adjusted based on patient tolerance of the prior treatment course. The daily dosage of 5-fluorouracil should be reduced by 20% for patients who experienced moderate hematologic or gastrointestinal toxicity in the prior treatment course, and by 30% for patients who experienced severe toxicity (see PRECAUTIONS: Laboratory Tests ). For patients who experienced no toxicity in the prior treatment course, 5-fluorouracil dosages may be increased by 10%. Wellcovorin dosages are not adjusted for toxicity.
Wellcovorin Rescue After High-Dose Methotrexate Therapy
The recommendations for Wellcovorin rescue are based on a methotrexate dose of 12 to 15 grams/m2 administered by intravenous infusion over 4 hours.
Wellcovorin rescue at a dose of 15 mg (approximately 10 mg/m2) every 6 hours for 10 doses starts 24 hours after the beginning of the methotrexate infusion. In the presence of gastrointestinal toxicity, nausea or vomiting, Wellcovorin should be administered parenterally. Do not administer Wellcovorin intrathecally.
Serum creatinine and methotrexate levels should be determined at least once daily. Wellcovorin administration, hydration, and urinary alkalization (pH of 7.0 or greater) should be continued until the methotrexate level is below 5 x 10-8 M (0.05 micromolar). The Wellcovorin dose should be adjusted or Wellcovorin rescue extended based on the following guidelines:
| DO NOT ADMINISTER Wellcovorin INTRATHECALLY | ||
| Clinical Situation | Laboratory Findings | Wellcovorin Dosage and Duration |
| Normal Methotrexate Elimination | Serum methotrexate level approximately 10 micromolar at 24 hours after administration, 1 micromolar at 48 hours, and less than 0.2 micromolar at 72 hours. | 15 mg PO, IM, or IV q 6 hours for 60 hours (10 doses starting at 24 hours after start of methotrexate infusion). |
| Delayed Late Methotrexate Elimination | Serum methotrexate level remaining above 0.2 micromolar at 72 hours, and more than 0.05 micromolar at 96 hours after administration. | Continue 15 mg PO, IM, or IV q 6 hours, until methotrexate level is less than 0.05 micromolar. |
| Delayed Early Methotrexate Elimination and/or Evidence of Acute Renal Injury | Serum methotrexate level of 50 micromolar or more at 24 hours, or 5 micromolar or more at 48 hours after administration, OR; a 100% or greater increase in serum creatinine level at 24 hours after methotrexate administration (e.g., an increase from 0.5 mg/dL to a level of 1 mg/dL or more). | 150 mg IV q 3 hours, until methotrexate level is less than 1 micromolar; then 15 mg IV q 3 hours until methotrexate level is less than 0.05 micromolar. |
Patients who experience delayed early methotrexate elimination are likely to develop reversible renal failure. In addition to appropriate Wellcovorin therapy, these patients require continuing hydration and urinary alkalization, and close monitoring of fluid and electrolyte status, until the serum methotrexate level has fallen to below 0.05 micromolar and the renal failure has resolved.
Some patients will have abnormalities in methotrexate elimination or renal function following methotrexate administration, which are significant but less severe than abnormalities described in the table above. These abnormalities may or may not be associated with significant clinical toxicity. If significant clinical toxicity is observed, Wellcovorin rescue should be extended for an additional 24 hours (total of 14 doses over 84 hours) in subsequent courses of therapy. The possibility that the patient is taking other medications which interact with methotrexate (e.g., medications which may interfere with methotrexate elimination or binding to serum albumin) should always be reconsidered when laboratory abnormalities or clinical toxicities are observed.
Impaired Methotrexate Elimination or Inadvertent Overdosage
Wellcovorin rescue should begin as soon as possible after an inadvertent overdosage and within 24 hours of methotrexate administration when there is delayed excretion. Wellcovorin 10 mg/m2 should be administered IV, IM, or PO every 6 hours until the serum methotrexate level is less than 10-8 M. In the presence of gastrointestinal toxicity, nausea, or vomiting, Wellcovorin should be administered parenterally. Do not administer Wellcovorin intrathecally.
Serum creatinine and methotrexate levels should be determined at 24 hour intervals. If the 24 hour serum creatinine has increased 50% over baseline or if the 24 hour methotrexate level is greater than 5 x 10-6 M or the 48 hour level is greater than 9 x 10-7 M, the dose of Wellcovorin should be increased to 100 mg/m2 IV every 3 hours until the methotrexate level is less than 10-8 M.
Hydration (3 L/d) and urinary alkalinization with sodium bicarbonate solution should be employed concomitantly. The bicarbonate dose should be adjusted to maintain the urine pH at 7.0 or greater.
Megaloblastic Anemia Due to Folic Acid Deficiency
Up to 1 mg daily. There is no evidence that doses greater than 1 mg/day have greater efficacy than those of 1 mg; additionally, loss of folate in urine becomes roughly logarithmic as the amount administered exceeds 1 mg.
Each 50, 100, and 200 mg vial of Wellcovorin Calcium for Injection when reconstituted with 5, 10, and 20 mL, respectively, of sterile diluent yields a Wellcovorin concentration of 10 mg per mL. Each 350 mg vial of Wellcovorin Calcium for Injection when reconstituted with 17.5 mL of sterile diluent yields a Wellcovorin concentration of 20 mg per mL. Wellcovorin Calcium for Injection contains no preservative. Reconstitute the lyophilized vial products with Bacteriostatic Water for Injection, USP (benzyl alcohol preserved), or Sterile Water for Injection, USP. When reconstituted with Bacteriostatic Water for Injection, USP, the resulting solution must be used within 7 days. If the product is reconstituted with Sterile Water for Injection, USP, use immediately and discard any unused portion.
Because of the benzyl alcohol contained in Bacteriostatic Water for Injection, USP, when doses greater than 10 mg/m2 are administered, Wellcovorin Calcium for Injection should be reconstituted with Sterile Water for Injection, USP, and used immediately (see WARNINGS ). Because of the calcium content of the Wellcovorin solution, no more than 160 mg of Wellcovorin should be injected intravenously per minute (16 mL of a 10 mg/mL, or 8 mL of a 20 mg/mL solution per minute).
Parenteral products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Wellcovorin should not be mixed in the same infusion as 5-fluorouracil, since this may lead to the formation of a precipitate.
HOW SUPPLIED
Wellcovorin Calcium for Injection is supplied as follows:
| NDC | Wellcovorin Calcium for Injection | Package Factor |
| 25021-813-10 | 50 mg Single-Dose Vial | 10 vials per carton |
| 25021-814-30 | 100 mg Single-Dose Vial | 1 vial per carton |
| 25021-815-30 | 200 mg Single-Dose Vial | 1 vial per carton |
| 25021-816-30 | 350 mg Single-Dose Vial | 1 vial per carton |
Storage Conditions
Store dry product and reconstituted solution at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F).
Protect from light. Retain in carton until time of use.
Lyophilized.
Sterile, Nonpyrogenic, Preservative-free.
The container closure is not made with natural rubber latex.
SAGENT®
Mfd. for SAGENT Pharmaceuticals
Schaumburg, IL 60195 (USA)
Made in India
©2016 Sagent Pharmaceuticals, Inc.
Revised: April 2016
PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Vial Label
NDC 25021-813-10
Rx only
Wellcovorin Calcium for Injection
50 mg per vial
For Intravenous or Intramuscular Use
Must Be Diluted
LYOPHILIZED
Single-Dose Vial
PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Vial Label
NDC 25021-814-30
Rx only
Wellcovorin Calcium for Injection
100 mg per vial
For Intravenous or Intramuscular Use
Must Be Diluted
LYOPHILIZED
Single-Dose Vial
PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Vial Label
NDC 25021-815-30
Rx only
Wellcovorin Calcium for Injection
200 mg per vial
For Intravenous or Intramuscular Use
Must Be Diluted
LYOPHILIZED
Single-Dose Vial
PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Vial Label
NDC 25021-816-30
Rx only
Wellcovorin Calcium for Injection
350 mg per vial
For Intravenous or Intramuscular Use
Must Be Diluted
LYOPHILIZED
Single-Dose Vial
Wellcovorin pharmaceutical active ingredients containing related brand and generic drugs:
Wellcovorin available forms, composition, doses:
Wellcovorin destination | category:
Wellcovorin Anatomical Therapeutic Chemical codes:
Wellcovorin pharmaceutical companies:
References
- Dailymed."LEUCOVORIN CALCIUM INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION [SAGENT PHARMACEUTICALS]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
- Dailymed."LEUCOVORIN CALCIUM: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
- "leucovorin". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
Frequently asked Questions
Can i drive or operate heavy machine after consuming Wellcovorin?Depending on the reaction of the Wellcovorin after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Wellcovorin not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Wellcovorin addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Review
sdrugs.com conducted a study on Wellcovorin, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Wellcovorin consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.Visitor reports
Visitor reported useful
No survey data has been collected yetVisitor reported side effects
No survey data has been collected yetVisitor reported price estimates
No survey data has been collected yetVisitor reported frequency of use
No survey data has been collected yetOne visitor reported doses
What is the dose of Wellcovorin drug you are taking?According to the survey conducted among sdrugs.com website users, the maximum number of people are using the following dose 11-50mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
| Visitors | % | ||
|---|---|---|---|
| 11-50mg | 1 | 100.0% | |
Visitor reported time for results
No survey data has been collected yetVisitor reported administration
No survey data has been collected yetVisitor reported age
No survey data has been collected yetVisitor reviews
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The information was verified by Dr. Rachana Salvi, MD Pharmacology