ALERT: U.S. Boxed Warning The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation (bel a DON a, fee noe BAR bi tal, & er GOT a meen)
U.S. Brand Names Bellamine S [DSC]; Eperbel-S [DSC]; Spastrin® [DSC]
Canadian Brand Names Bellergal® Spacetabs®
Pharmacologic Category Ergot Derivative
Use: Labeled Indications Management and treatment of menopausal disorders, GI disorders, and recurrent throbbing headache
Dosing: Adults Menopausal disorders, GI disorders, and recurrent throbbing headache: Oral: 1 tablet each morning and evening
Dosing: Elderly Refer to adult dosing and dosing in individual monographs.
Contraindications Hypersensitivity to belladonna alkaloids, phenobarbital, ergotamine, or any component of the formulation; dopamine therapy; ergot alkaloids are contraindicated with potent inhibitors of CYP3A4 (includes protease inhibitors, azole antifungals, and some macrolide antibiotics); hypertension; glaucoma; coronary heart disease and peripheral vascular disease; impaired hepatic or renal function; sepsis; history of manifest or latent porphyria; pregnancy
Allergy Considerations Aromatic Anticonvulsant Allergy/Hypersensitivity
Belladonna Alkaloid Allergy
Ergot Alkaloid Allergy
Warnings/Precautions Boxed warnings:
• CYP3A4 inhibitors: See “Concurrent drug therapy issues†below.
Concerns related to adverse effects:
• Cardiac valvular fibrosis: Ergot alkaloids have been associated with fibrotic valve thickening (eg, aortic, mitral, tricuspid); usually associated with long-term, chronic use.
• Cardiovascular effects: Vasospasm or vasoconstriction can occur, possibly resulting in decreased cerebral blood flow, ECG changes, and hypertension; sustained vasoconstriction may also lead to ischemic colitis, intermittent claudication, aggravation of angina, or precipitation of MI. Do not use is any patient at risk or predisposed to vascular effects of ergot alkaloids.
• Ergotism: Ergot alkaloid use may result in ergotism (intense vasoconstriction) resulting in peripheral vascular ischemia and possible gangrene. Ergotism is usually associated with overdosage or prolonged chronic use; do not exceed dosing guidelines and avoid prolonged administration.
• Habit-forming: May be habit-forming.
• Pleural/retroperitoneal fibrosis: Rare cases of pleural and/or retroperitoneal fibrosis have been reported with prolonged daily use.
Disease-related concerns:
• Asthma: Use with caution in patients with bronchial asthma.
• Uropathy: Use with caution in patients with obstructive uropathy.
Concurrent drug therapy issues:
• CYP3A4 inhibitors: [U.S. Boxed Warning]: Ergot alkaloids are contraindicated with potent inhibitors of CYP3A4 (includes protease inhibitors, azole antifungals, and some macrolide antibiotics); concomitant use associated with acute ergot toxicity (ergotism).
Special populations:
• Elderly: Use with extreme caution or avoid use in the elderly; due to vasoconstrictive properties and cardiovascular adverse effects associated with ergot alkaloids.
• Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions:
• Weekly dosage: Total weekly dosage of ergotamine should not exceed 10 mg.
• Withdrawal: Discontinuation after extended use may result in withdrawal symptoms (eg, rebound headache).
Pregnancy Risk Factor X
Pregnancy Considerations Potential uterotonic effects
Lactation Enters breast milk (ergotamine)/contraindicated
Adverse Reactions >10%:
Cardiovascular: Peripheral vascular effects (numbness and tingling of fingers and toes)
Central nervous system: Drowsiness, dizziness
Dermatologic: Dry skin
Gastrointestinal: Constipation, dry mouth and throat, diarrhea, nausea, vomiting
Respiratory: Dry nose
Miscellaneous: Diaphoresis decreased
1% to 10%:
Cardiovascular: Precordial distress and pain, transient tachycardia or bradycardia
Dermatologic: Photosensitivity
Endocrine & metabolic: Breast milk flow decreased
Gastrointestinal: Swallowing difficulty
Neuromuscular & skeletal: Muscle pain in extremities, weakness in legs
<1% (Limited to important or life-threatening): Orthostatic hypotension, ventricular fibrillation, tachycardia, palpitation, confusion, headache, memory loss, drowsiness, skin rash, intraocular pain increased, blurred vision
Metabolism/Transport Effects Phenobarbital: Substrate of CYP2C8/9 (minor), 2C19 (major), 2E1 (minor); Induces CYP1A2 (strong), 2A6 (strong), 2B6 (strong), 2C8/9 (strong), 3A4 (strong)
Ergotamine: Substrate of CYP3A4 (major); Inhibits 3A4 (weak)
Drug Interactions Acetaminophen: Barbiturates may increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Aminocamptothecin: PHENobarbital may decrease the serum concentration of Aminocamptothecin. Risk C: Monitor therapy
Amphetamines: May decrease the serum concentration of PHENobarbital. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Bendamustine: CYP1A2 Inducers (Strong) may decrease the serum concentration of Bendamustine. Concentrations of active metabolites may be increased. Risk C: Monitor therapy
Beta-Blockers: Barbiturates may decrease the serum concentration of Beta-Blockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol. Risk C: Monitor therapy
Calcium Channel Blockers: Barbiturates may increase the metabolism of Calcium Channel Blockers. Exceptions: Clevidipine. Risk D: Consider therapy modification
Cannabinoids: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoids. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of Anticonvulsants (Barbiturate). Specifically, osteomalacia and rickets. Exceptions: Brinzolamide; Dorzolamide. Risk C: Monitor therapy
Chloramphenicol: May decrease the metabolism of Barbiturates. Barbiturates may increase the metabolism of Chloramphenicol. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Contraceptive (Progestins): Barbiturates may diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
Corticosteroids (Systemic): Barbiturates may increase the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
CycloSPORINE: Barbiturates may increase the metabolism of CycloSPORINE. Risk D: Consider therapy modification
CYP1A2 Substrates: CYP1A2 Inducers (Strong) may increase the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP2A6 Substrates: CYP2A6 Inducers (Strong) may increase the metabolism of CYP2A6 Substrates. Risk C: Monitor therapy
CYP2B6 Substrates: CYP2B6 Inducers (Strong) may increase the metabolism of CYP2B6 Substrates. Risk C: Monitor therapy
CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Moderate): May decrease the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Strong): May decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification
CYP2C8 Substrates (High risk): CYP2C8 Inducers (Highly Effective) may increase the metabolism of CYP2C8 Substrates (High risk). Risk C: Monitor therapy
CYP2C9 Substrates (High risk): CYP2C9 Inducers (Highly Effective) may increase the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
CYP3A4 Substrates: CYP3A4 Inducers (Strong) may increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Darunavir: PHENobarbital may decrease the serum concentration of Darunavir. Risk X: Avoid combination
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Disopyramide: Barbiturates may increase the metabolism of Disopyramide. Risk D: Consider therapy modification
Doxycycline: Barbiturates may decrease the serum concentration of Doxycycline. Risk D: Consider therapy modification
Efavirenz: May enhance the adverse/toxic effect of Ergot Derivatives. Specifically, the risk for peripheral vasospasm and ischemia may be increased. Risk X: Avoid combination
Etoposide: Barbiturates may increase the metabolism of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: Barbiturates may decrease the serum concentration of Etoposide Phosphate. Barbiturates may increase the metabolism, via CYP isoenzymes, of etoposide phosphate. Risk C: Monitor therapy
Etravirine: PHENobarbital may decrease the serum concentration of Etravirine. Management: The manufacturer of etravirine states these drugs should not be used in combination Risk X: Avoid combination
Felbamate: May increase the serum concentration of Barbiturates. Risk C: Monitor therapy
Folic Acid: May decrease the serum concentration of PHENobarbital. Risk C: Monitor therapy
Griseofulvin: Barbiturates may decrease the absorption of Griseofulvin. Risk D: Consider therapy modification
Ketorolac: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
Lacosamide: PHENobarbital may decrease the serum concentration of Lacosamide. Risk C: Monitor therapy
LamoTRIgine: Barbiturates may increase the metabolism of LamoTRIgine. Risk D: Consider therapy modification
Leucovorin-Levoleucovorin: May decrease the serum concentration of PHENobarbital. Risk C: Monitor therapy
Macrolide Antibiotics: May enhance the adverse/toxic effect of Ergot Derivatives. Specifically leading the development of ergotism. Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification
Maraviroc: CYP3A4 Inducers may decrease the serum concentration of Maraviroc. Risk D: Consider therapy modification
Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated in persons with a history of convulsions. If anticonvulsant is being used for another indication monitor response to treatment closely, as concurrent mefloquine may decrease response to treatment. Risk D: Consider therapy modification
Meperidine: Barbiturates may enhance the CNS depressant effect of Meperidine. Risk C: Monitor therapy
Methadone: Barbiturates may increase the metabolism of Methadone. Risk D: Consider therapy modification
Methylfolate: May decrease the serum concentration of PHENobarbital. Risk C: Monitor therapy
Nilotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib. Risk X: Avoid combination
Oral Contraceptive (Estrogens): Barbiturates may diminish the therapeutic effect of Oral Contraceptive (Estrogens). Contraceptive failure is possible. Risk D: Consider therapy modification
OXcarbazepine: PHENobarbital may decrease the serum concentration of OXcarbazepine. Risk C: Monitor therapy
Posaconazole: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Risk D: Consider therapy modification
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Primidone: May enhance the adverse/toxic effect of Barbiturates. Primidone is converted to phenobarbital, and thus becomes additive with existing barbiturate therapy. Risk C: Monitor therapy
Propafenone: Barbiturates may increase the metabolism of Propafenone. Risk D: Consider therapy modification
Protease Inhibitors: May decrease the metabolism of Ergot Derivatives. Risk X: Avoid combination
Pyridoxine: May increase the metabolism of Barbiturates. Apparent in high pyridoxine doses (eg, 200 mg/day) Risk C: Monitor therapy
QuiNIDine: Barbiturates may increase the metabolism of QuiNIDine. Risk D: Consider therapy modification
Ranolazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of Barbiturates. Risk C: Monitor therapy
Rufinamide: May increase the serum concentration of PHENobarbital. PHENobarbital may decrease the serum concentration of Rufinamide. Risk C: Monitor therapy
Secretin: Anticholinergic Agents may diminish the stimulatory effect of Secretin. Risk D: Consider therapy modification
Serotonin 5-HT1D Receptor Agonists: Ergot Derivatives may enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Ergot Derivatives. This may cause serotonin syndrome. Risk X: Avoid combination
Sorafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sorafenib. Risk D: Consider therapy modification
Teniposide: Barbiturates may increase the metabolism of Teniposide. Risk C: Monitor therapy
Theophylline Derivatives: Barbiturates may increase the metabolism of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy
Tipranavir: PHENobarbital may decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of PHENobarbital. Risk D: Consider therapy modification
Tricyclic Antidepressants: Barbiturates may increase the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Valproic Acid: May decrease the metabolism of Barbiturates. Barbiturates may decrease the serum concentration of Valproic Acid. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Barbiturates may increase the metabolism of Vitamin K Antagonists. Risk D: Consider therapy modification
Voriconazole: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination
Voriconazole: Barbiturates may decrease the serum concentration of Voriconazole. Risk X: Avoid combination
Nursing: Physical Assessment/Monitoring Assess potential for interactions with other prescriptions, OTC medications, or herbal products patient may be taking (eg, warfarin). This combination drug interacts with many commonly prescribed drugs to potentiate adverse/toxic reactions or to reduce the effectiveness of other drugs. Use caution with prolonged use; may be habit-forming. Abrupt discontinuation after long-term use may result in withdrawal symptoms (eg, rebound headache). Assess therapeutic effect and adverse reactions at regular intervals during therapy. Teach patient proper use, possible side effects/appropriate interventions, and adverse symptoms to report. Pregnancy risk factor X: Determine that patient is not pregnant before starting therapy. Do not give to females of childbearing age unless they are capable of complying with contraceptive use. Instruct patient about appropriate contraceptives.
Patient Education Do not take any new medication during therapy unless approved by prescriber. Take exactly as directed; do not take more than recommended dose. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake and nutrition. May cause drowsiness or dizziness (use caution when driving or engaging in tasks that require alertness until response to drug is known); dry throat or mouth (frequent mouth care or sucking on lozenges may help); dry nose (use humidifier); photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight); nausea or vomiting (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); dry skin (mild skin lotion may help); or orthostatic hypotension (use caution when rising from sitting or lying position or climbing stairs). Report any signs of numbness in extremities (fingers and toes); unusual leg pain or cyanosis of extremities; difficulty swallowing; persistent muscle pain or weakness; pain in eye or vision changes; or chest pain, rapid heartbeat, or palpitations. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant and do not get pregnant during therapy. Consult prescriber for instruction on appropriate contraceptive measures. Do not breast-feed.
Dosage Forms Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet:
Bellamie S [DSC], Eperbel-S [DSC], Spastrin® [DSC]: Belladonna alkaloids 0.2 mg, phenobarbital 40 mg, and ergotamine 0.6 mg
Generic Available Yes
Pricing: U.S. (www.drugstore.com) Tablets (Bellamine S)
0.6-40-0.2 mg (60): $15.99
Pharmacodynamics/Kinetics See individual agents.
Related Information Ergotamine
PHENobarbital
Dental Health: Effects on Dental Treatment Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation), dry throat, nasal dryness, and difficulty swallowing.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions No information available to require special precautions
Mental Health: Effects on Mental Status Drowsiness and dizziness are common
Mental Health: Effects on Psychiatric Treatment Combined use with TCAs and antipsychotics may potentiate the depressant actions
Index Terms Ergotamine Tartrate, Belladonna, and Phenobarbital; Phenobarbital, Belladonna, and Ergotamine Tartrate
International Brand Names Bellergal Retard (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Bellergal Spacetabs (CA)
Copyright (c) Lexi-Comp, Inc. 1978-2008 All Rights Reserved. Sources : Drug Information Handbook, 17th Edition
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