Calmore - General Information
A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Calmore displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor-alpha from monocytes, and modulates other cytokine action.
Pharmacology of Calmore
Calmore is an immunomodulatory agent with a spectrum of activity that is not fully characterized. Calmore is racemic — it contains both left and right handed isomers in equal amounts: one enantiomer is effective against morning sickness, and the other is teratogenic. The enantiomers are converted to each other in vivo. That is, if a human is given D-thalidomide or L-thalidomide, both isomers can be found in the serum. Hence, administering only one enantiomer will not prevent the teratogenic effect in humans.
Calmore for patients
Important Information and Warnings for All Patients Taking THALOMID™ (thalidomide)
SEVERE, LIFE-THREATENING HUMAN BIRTH DEFECTS.
IF THALIDOMIDE IS TAKEN DURING PREGNANCY, IT CAN CAUSE SEVERE BIRTH DEFECTS OR DEATH TO AN UNBORN BABY. THALIDOMIDE SHOULD NEVER BE USED BY WOMEN WHO ARE PREGNANT OR WHO COULD BECOME PREGNANT WHILE TAKING THE DRUG. EVEN A SINGLE DOSE [1 CAPSULE (50 mg, 100 mg or 200 TAKEN BY A PREGNANT WOMAN CAN CAUSE SEVERE BIRTH DEFECTS.
· The patient understands that severe birth defects can occur with the use of THALOMID™ (thalidomide).
· The patient has been warned by his/her doctor that an unborn baby will almost certainly have severe birth defects and can even die, if a woman is pregnant or becomes pregnant while taking THALOMID™ (thalidomide).
· THALOMID™ (thalidomide) will be prescribed ONLY for the patient and must NOT be shared with ANYONE, even someone who has similar symptoms.
· THALOMID™ (thalidomide) must be kept out of the reach of children and should NEVER be given to women who are able to have children.
· The patient cannot donate blood while taking THALOMID™ (thalidomide).
· The patient has read the THALOMID™ (thalidomide) patient brochure and/or viewed the videotape, "Important Information for Men and Women Taking THALOMID™ (thalidomide)" and understands the contents, including other possible health problems from THALOMID™ (thalidomide), "side effects."
· The patient's doctor has answered any questions the patient has asked.
· The patient must participate in a telephone survey and patient registry, while taking THALOMID™ (thalidomide).
Female Patients of Childbearing Potential
· The patient must not take THALOMID™ (thalidomide) if she is pregnant, breast-feeding a baby, or able to get pregnant and not using the required two methods of birth control.
· The patient confirms that she is not now pregnant, nor will she try to become pregnant during THALOMID™ (thalidomide) therapy and for at least 4 weeks after she has completely finished taking THALOMID™ (thalidomide).
· If the patient is able to become pregnant, she must use at least one highly effective method and one additional effective method of birth control (contraception) AT THE SAME TIME:
One additional effective method
· These birth control methods must be used for at least 4 weeks before beginning THALOMID™ (thalidomide) therapy, during THALOMID™ (thalidomide) therapy, and for 4 weeks following discontinuation of THALOMID™ (thalidomide) therapy.
· The patient must use these birth control methods unless she completely abstains from heterosexual sexual contact.
· If a hormonal method (birth control pills, injections, or implants) or IUD is not medically possible for the patient, she may use another highly effective method or two barrier methods AT THE SAME TIME.
· The patient must have a pregnancy test done by her doctor within the 24 hours prior to starting THALOMID™ (thalidomide) therapy, then every week during the first 4 weeks of THALOMID™ (thalidomide) therapy.
· Thereafter, the patient must have a pregnancy test every 4 weeks if she has regular menstrual cycles, or every 2 weeks if her cycles are irregular while she is taking THALOMID™ (thalidomide).
· The patient must immediately stop taking THALOMID™ (thalidomide) and inform her doctor:
The patient understands that if her doctor is not available, she can call 1-888-668-2528 for information on emergency contraception.
Female Patients Not of Childbearing Potential
· The patient certifies that she is not now pregnant, nor of childbearing potential as she has been postmenopausal for at least 24 months (been through the change of life); or she has had a hysterectomy.
· The patient or guardian certifies that a prepubertal female child is not now pregnant, nor is of childbearing potential as menstruation has not yet begun, and/or the child will not be engaging in heterosexual sexual contact for at least 4 weeks before THALOMID™ (thalidomide) therapy, during THALOMID™ (thalidomide) therapy, and for at least 4 weeks after stopping therapy.
· The patient has been told by his doctor that he must NEVER have unprotected sexual contact with a woman who can become pregnant.
· Because THALOMID™ (thalidomide) is present in semen, his doctor has explained that he must either completely abstain from sexual contact with women who are pregnant or able to become pregnant, or he must use a latex condom EVERY TIME he engages in any sexual contact with women who are pregnant or may become pregnant while he is taking THALOMID™ (thalidomide) and for 4 weeks after he stops taking the drug, even if he has had a successful vasectomy.
· The patient must inform his doctor:
The patient understands that if his doctor is not available, he can call 1-888-668-2528 for information on emergency contraception.
This information has been read aloud to me in the language of my choice. I understand that if I do not follow all of my doctor's instructions, I will not be able to receive THALOMID™ (thalidomide).
I now authorize my doctor to begin my treatment with THALOMID™ (thalidomide).
Patient Signature___________________________ Date_________________________
I have fully explained to the patient the nature, purpose, and risks of the treatment described above, especially the risks to women of childbearing potential. I have asked the patient if he/she has any questions regarding his/her treatment with THALOMID™ (thalidomide) and have answered those questions to the best of my ability. I will comply with all of my obligations and responsibilities as a prescriber registered under the S.T.E.P.S™ restricted distribution program.
Prescriber Name (please type): _____________________________________________
DEA Number: ___________ Social Security Number if PA or NP: ________________
Street Address: __________________________________________________________
City: _____________ State: ____________ Zip: _______________________________
Prescriber Signature _____________________________________________________
S.T.E.P.S.™ is a registered trademark of Celgene Corporation.
U.S. Pat. Nos. 6,045,501 & 6,315,720. THALPI.008 02/04 CG
Thalidomide has been reported to enhance the sedative activity of barbiturates, alcohol, chlorpromazine, and reserpine.
Oral Contraceptives: In 10 healthy women, the pharmacokinetic profiles of norethindrone and ethinyl estradiol following administration of a single dose containing 1.0 mg of norethindrone acetate and 75 µg of ethinyl estradiol were studied. The results were similar with and without coadministration of thalidomide 200 mg/day to steady-state levels.
Important Non-Thalidomide Drug Interactions
Drugs That Interfere with Hormonal Contraceptives: Concomitant use of HIV-protease inhibitors, griseofulvin, modafinil, penicillins, rifampin, rifabutin, phenytoin, carbamazepine, or certain herbal supplements such as St. John's Wort with hormonal contraceptive agents may reduce the effectiveness of the contraception and up to one month after discontinuation of these concomitant therapies. Therefore, women requiring treatment with one or more of these drugs must use two OTHER effective or highly effective methods of contraception or abstain from heterosexual sexual contact while taking thalidomide.
Pregnancy: Category X
Due to its known human teratogenicity, even following a single dose, thalidomide is contraindicated in pregnant women and women capable of becoming pregnant. When there is no alternative treatment, women of childbearing potential may be treated with thalidomide provided adequate precautions are taken to avoid pregnancy. Women must commit either to abstain continuously from heterosexual sexual contact or to use two methods of reliable birth control, including at least one highly effective method (e.g., IUD, hormonal contraception, tubal ligation, or partner's vasectomy) and one additional effective method (e.g., latex condom, diaphragm, or cervical cap), beginning 4 weeks prior to initiating treatment with thalidomide, during therapy with thalidomide, and continuing for 4 weeks following discontinuation of thalidomide therapy. If hormonal or IUD contraception is medically contraindicated, two other effective or highly effective methods may be used.
Women of childbearing potential being treated with thalidomide should have a pregnancy test (sensitivity of at least 50 mIU/mL). The test should be performed within the 24 hours prior to beginning thalidomide therapy and then weekly during the first 4 weeks of thalidomide therapy, then at 4 week intervals in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles. Pregnancy testing and counseling should be performed if a patient misses her period or if there is any abnormality in menstrual bleeding. If pregnancy occurs during thalidomide treatment, thalidomide must be discontinued immediately. Under these conditions, the patient should be referred to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling.
Because thalidomide is present in the semen of patients receiving the drug, males receiving thalidomide must always use a latex condom during any sexual contact with women of childbearing potential. The risk to the fetus from the semen of male patients taking thalidomide is unknown.
THALOMIDÒ (thalidomide) is contraindicated in patients who have demonstrated hypersensitivity to the drug and its components.
Additional information about Calmore
Calmore Indication: For the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). Also for use as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence.
Mechanism Of Action: In patients with erythema nodosum leprosum (ENL) the mechanism of action is not fully understood. Available data from in vitro studies and preliminary clinical trials suggest that the immunologic effects of this compound can vary substantially under different conditions, but may be related to suppression of excessive tumor necrosis factor-alpha (TNF-a) production and down-modulation of selected cell surface adhesion molecules involved in leukocyte migration. For example, administration of thalidomide has been reported to decrease circulating levels of TNF-a in patients with ENL, however, it has also been shown to increase plasma TNF-a levels in HIV-seropositive patients.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Thalidomide
Synonyms: alpha-phthalimidoglutarimide; N-Phthalimidoglutamic acid imide; N-Phthaloylglutamimide; N-Phthalylglutamic acid imide; Thalidomine USP26
Drug Category: Angiogenesis Inhibitors; Immunosuppressive Agents; Leprostatic Agents; Teratogens
Drug Type: Small Molecule; Approved; Withdrawn; Investigational
Absorption: The absolute bioavailability has not yet been characterized in human subjects due to its poor aqueous solubility. In studies of both healthy volunteers and subjects with Hansen’s disease, the mean time to peak plasma concentrations (Tmax) ranged from 2.9 to 5.7 hours indicating that thalidomide is slowly absorbed from the gastrointestinal tract.
Toxicity (Overdose): The R-configuration and the S-configuration are more toxic individually than the racemic mixture. The LD50 could not be established in mice for racemic thalidomide, whereas LD50 values for the R and S configurations are reported to be 0.4 to 0.7 g/kg and 0.5 to 1.5 g/kg, respectively.
Protein Binding: 55% and 66% for the (+)R and (−)S enantiomers, respectively.
Biotransformation: Thalidomide itself does not appear to be hepatically metabolized to any large extent, but appears to undergo non-enzymatic hydrolysis in plasma to multiple metabolites. Thalidomide may be metabolized hepatically by enzymes of the cytochrome P450 enzyme system. The end product of metabolism, phthalic acid, is excreted as a glycine conjugate.
Half Life: The mean half-life of elimination ranges from approximately 5 to 7 hours following a single dose and is not altered upon multiple dosing.
Dosage Forms of Calmore: Capsule Oral
Chemical IUPAC Name: 2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
Chemical Formula: C13H10N2O4
Thalidomide on Wikipedia: https://en.wikipedia.org/wiki/Thalidomide
Organisms Affected: Humans and other mammals