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Cabergoline — (Dostinex)

International Brand Names

Cabaser (Australia, Israel)

Drug Class Antiparkinson agents; Dopaminergics; Ergot alkaloids and derivatives; Hormones/hormone modifiers
Indications Hyperprolactinemia, lactation suppression
Mechanism Stimulates D 2 dopamine receptors
Dosage With Qualifiers Hyperprolactinemia—begin 0.25 mg 2 ×/w, then increase 0.25 mg/w qmo; max 1 mg 2 ×/w; monitor prolactin level

  • Contraindications —hypersensitivity to drug or class, uncontrolled hypertension

  • Caution —hepatic dysfunction

Maternal Considerations There are no adequate reports or well-controlled studies in pregnant women. Cabergoline is better tolerated and more effective in inducing a complete biochemical response than bromocriptine. Women become pregnant after 1–37 mo (mean 12.4 mo) with cabergoline therapy. It has been used throughout pregnancy to successfully treat macroprolactinoma; most tumors disappear with therapy. Several reports support its use for the treatment of postpartum myocardiopathy. Cabergoline is also effective in women resistant or poorly responsive to bromocriptine. Prolactin typically trends lower after delivery or 3 mo after breastfeeding. Cabergoline is used in several countries to prevent postpartum lactation (1 mg PO × 1) or block established lactation (0.25 mg PO q12h × 4).
Side effects include N/V, headache, dizziness, constipation, fatigue, abdominal pain, vertigo, hot flashes, dry mouth, depression, and hypotension.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether cabergoline crosses the human placenta. First-trimester exposure is not associated with adverse perinatal outcome. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether cabergoline enters human breast milk. Cabergoline suppressed lactation in some studies, with less rebound than bromocriptine. It should be avoided if breastfeeding is desired.
Drug Interactions Cabergoline should not be administered with D 2 antagonists, such as phenothiazines, butyrophenones, thioxanthenes, or metoclopramide.
References Bozhinova S, Porozhanova V, Penkov V. Akush Ginekol 2001; 40:11-4.
Ciccarelli E, Grottoli S, Razzore P, et al. Endocrinol Invest 1997; 20:547-51.
Colao A, Sarno AD, Pivonello R, et al. Expert Opin Investig Drugs 2002; 11:787-800.
Delgrange E, Maiter D, Donckier J. Eur J Endocrinol 1996; 134:454-6.
Liu C, Tyrrell JB. Pituitary 2001; 4:179-85.
Melo MA, Carvalho JS, Feitosa FE et al. Rev Bras Ginecol Obstet. 2016; 38: 308-13.
Molitch ME. J Reprod Med 1999; 44:1121-6.
Ricci E, Parazzini F, Motta T, et al. Reprod Toxicol 2002; 16:791-3.
Webster J. Drug Saf 1996; 14:228-38.
Summary Pregnancy Category: B
Lactation Category: U

  • Preliminary data suggest no increase in adverse fetal outcomes secondary to cabergoline use during pregnancy.

  • Cabergoline should be avoided if breastfeeding is desired.

Caffeine

Drug Class Analeptics; CNS stimulants; Xanthines
Indications Migraine, tension headache, cluster headache, prematurity apnea
Mechanism Most of the effects reflect antagonism of A1 and A2 adenosine receptors.
Dosage With Qualifiers NOTE: May be combined with ergotamine (Cafergot) or other analgesics such as ASA or acetaminophen .

  • Contraindications —hypersensitivity to drug or class, peptic ulcer disease, porphyria

  • Caution —history of abuse

Maternal Considerations There is no clear evidence caffeine at moderate ingestion levels has an adverse effect on pregnancy. It may enhance hypertension. Toxicity occurs only in very high dosages (e.g., 25 tablets of Fiorinal [ ASA, butalbital, caffeine ]). Cardiac arrhythmias are associated with maternal caffeine use in excess of 500 mg/d.
Side effects include tachycardia and anxiety. In combination with other drugs, caffeine may cause anaphylaxis, toxic epidermal necrolysis, bone marrow suppression, GI bleeding, and Stevens-Johnson syndrome.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Caffeine crosses the placenta, achieving an F:M ratio near unity. There is no substantive evidence that caffeine is either a teratogen or causes IUGR in humans. In rodents, high and sustained doses are associated with a small increase in the prevalence of cleft palate. Despite the fact that many epidemiologic studies observed a positive association between maternal caffeine intake and the risk of spontaneous abortion, the evidence is still equivocal given the biases likely present and the fact that most of the potential biases would overestimate any association.
Breastfeeding Safety Though it enters human breast milk in small amounts, caffeine is generally considered safe for breastfeeding women.
Drug Interactions Caffeine is a CYP1A2 substrate and inhibitor.
Ergotamine and caffeine tablets should not be given with other vasoconstrictors.
Sympathomimetics (pressor agents) may cause extreme elevation of blood pressure.
Propranolol may potentiate the vasoconstrictive actions of ergotamine and caffeine by blocking the vasodilating property of epinephrine.
Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy.
The blood levels of ergotamine-containing drugs associated with vasospastic reactions are reported to be increased by the co-administration of macrolide antibiotics.
References Browne ML. Epidemiology 2006; 17:324-31.
Clausson B, Granath F, Ekbom A, et al. Am J Epidemiol 2002; 155:429-36.
Cnattingius S, Signorello LB, Anneren G, et al. N Engl J Med 2000; 343:1839-45.
Grosso LM, Rosenberg KD, Belanger K, et al. Epidemiology 2001; 12:447-55.
Koren G. Can Fam Physician 2000; 46:801-3.
Pollard I, Locquet O, Solvar A, Magre S. Reprod Fertil Dev 2001; 13:435-41.
Signorello LB, McLaughlin JK. Epidemiology 2004; 15:229-39.
Signorello LB, Nordmark A, Granath F, et al. Obstet Gynecol 2001; 98:1059-66.
Summary Pregnancy Category: C
Lactation Category: S

  • Caffeine is one of the most frequently used drugs during pregnancy, often in combination with products containing aspirin, acetaminophen, and codeine.

  • No teratogenic, carcinogenic, or mutagenic effects are known in humans.

Caffeine plus ergotamine — (Cafatine; Cafergot; Cafermine; Cafetrate; Ercaf; Ercatab; Ergo-Caff; Gotamine; Micomp-Pb; Migergot; Secadol; Wigraine)

International Brand Names

Avamigran (Thailand); Cafergot (Argentina, Austria, Belgium, Canada, Denmark, England, Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, Netherlands, Norway, Russia, Spain, Sweden, Switzerland, Taiwan, Thailand); Cafergot N (Germany); Craming (Korea); Degran (Thailand); Ergocaf (Mexico); Ergofein (Czech Republic); Ergoffin (Germany); Ergokoffin (Denmark); Ergotamini Tartras Coffeinum (Netherlands); Ergoton (Taiwan); Ericaf (Indonesia); Gynergene Cafeine (France); Migranil (India); Polygot (Thailand); Trinergot (Mexico)

Drug Class Adrenergic antagonists; CNS stimulants; Ergot alkaloids; Xanthines
Indications Migraine, tension headache, cluster headache
Mechanism Combination—see individual drugs
Dosage With Qualifiers Headache—1–2 tabs/suppositories PO/PR q30min prn; max mg ergotamine qd
NOTE: Available in tablet or rectal suppository (100 mg caffeine + 1 mg ergotamine per tablet, 100/2 per suppository).

  • Contraindications —hypersensitivity, pregnancy, peptic ulcer disease, porphyria

  • Caution —older adult patients, pediatric patients, history of abuse

Maternal Considerations There are only scattered case reports of caffeine plus ergotamine use during pregnancy. This combination is contraindicated due to the oxytocic effects of ergotamine. See Caffeine and Ergotamine individually.
Side effects include tachycardia and anxiety. In combination with other drugs, Cafergot may cause anaphylaxis, toxic epidermal necrolysis, bone marrow suppression, GI bleeding, and Stevens-Johnson syndrome.
Fetal Considerations See Caffeine and Ergotamine individually. Jejunal atresia was reported in the child of a woman who ingested caffeine and ergotamine in five consecutive pregnancies. The other four ended in spontaneous abortion.
Breastfeeding Safety There is no published experience in nursing women. See Caffeine and Ergotamine individually.
Drug Interactions Caffeine is a CYP1A2 substrate and inhibitor.
Ergotamine and caffeine tablets should not be given with other vasoconstrictors.
Sympathomimetics (pressor agents) may cause extreme elevation of blood pressure.
Propranolol may potentiate the vasoconstrictive actions of ergotamine and caffeine by blocking the vasodilating property of epinephrine.
Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy.
The blood levels of ergotamine-containing drugs associated with vasospastic reactions are reported to be increased by the co-administration of macrolide antibiotics.
References Browne ML. Epidemiology 2006; 17:324-31.
Graham JM, Marin-Padilla M, Hoefnagel D. Clin Pediatr 1983; 22:226-8.
Summary Pregnancy Category: X
Lactation Category: NS

  • Contraindicated during pregnancy due to the oxytocic effects of ergotamine.

  • There are alternative agents with a higher safety profile for which there is more experience during pregnancy and lactation.

Calcifediol — (Dical-D; Calcijex)

International Brand Names

None identified.

Drug Class Vitamins/minerals
Indications Vitamin D deficiency, hypoparathyroidism, osteoporosis, hypocalcemia
Mechanism Active form of vitamin D stimulates intestinal absorption of calcium and phosphorus.
Dosage With Qualifiers Vitamin deficiency—50–100 mcg PO qd
Hypoparathyroidism—0.2–1 mg PO qd
Osteoporosis—0.6 mg PO qd

  • Contraindications —hypersensitivity to drug or class, hypercalcemia, hypervitaminosis D

  • Caution —renal failure, renal stones, hyperphosphatemia

Maternal Considerations Vitamin D supplementation is recommended during pregnancy, though there is little convincing evidence supplementation improves pregnancy outcomes in First World countries. Calcifediol is converted in the kidney to an active form of vitamin D, calcitriol. There are no adequate reports or well-controlled studies in pregnant women. Veiled or dark-skinned pregnant women have an increased risk of vitamin D deficiency, which is associated with disease.
Side effects include hypercalcemia, elevated creatinine, polydipsia, nausea, and convulsion.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. There is a weak association between vitamin D levels and gestational age and fetal heel length. It is unknown whether calcifediol crosses the human placenta, though the placenta synthesizes active vitamin D. Calcifediol is reportedly teratogenic in some rodents.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether calcifediol enters human breast milk, though vitamin D supplementation during pregnancy increases milk vitamin D levels.
Drug Interactions No interactions have been reported.
References Brunvand L, Quigstad E, Urdal P, Haug E. Early Hum Dev 1996; 45:27-33.
Cancela L, Le Boulch N, Miravet L. J Endocrinol 1986; 110:43-50.
Grover SR, Morley R. Med J Aust 2001; 175:251-2.
Kuoppala T, Tuimala R, Parviainen M, et al. Hum Nutr Clin Nutr 1986; 40:287-93.
Mallet E, Gugi B, Brunelle P, et al. Obstet Gynecol 1986; 68:300-4.
Morley R, Carlin JB, Pasco JA, Wark JD. J Clin Endocrinol Metab 2006; 91:906-12.
Wall CR, Stewart AW, Camargo CA Jr et al. Am J Clin Nutr. 2016; 103: 382-8.
Summary Pregnancy Category: B
Lactation Category: S (likely)

  • Vitamin D supplementation is generally recommended during pregnancy.

  • Most multivitamin supplements contain adequate quantities of vitamin D in one form or another.

Calcitonin — (Calcimar; Miacalcin)

International Brand Names

Biocalcin (Korea); Boncalmon (Korea); Cadens (France); Calcimar (Canada); Calcinin (Taiwan); Calcitoran (Japan); Calco (Singapore, Thailand); Calsynar (Brazil, South Africa, Taiwan); Caltine (Canada); Citonina (Argentina); Menocal (Korea, Singapore, Thailand); Miacalcic (Brazil, Chile, China, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Hong Kong, Indonesia, Israel, Malaysia, Mexico, New Zealand, Nicaragua, Panama, Peru, Philippines, Singapore, Taiwan, Thailand); Oseum (Mexico); Salmocalcin (Argentina); Salmotonin (Japan); Tonocalcin (Indonesia, Malaysia, Mexico); Zycalcit (India)

Drug Class Hormones
Indications Osteoporosis, Paget’s disease, hypercalcemia
Mechanism Unknown
Dosage With Qualifiers Osteoporosis—100 IU SC or IM qod or 200 IU NAS qd
Paget’s disease—begin 100 IU SC or IM qd, then 50 IU qod
Hypercalcemia—4 IU/kg SC or IM q12h

  • Contraindications —hypersensitivity to drug or class

  • Caution —renal failure or stones, hyperphosphatemia

Maternal Considerations Calcitonin regulates calcium homeostasis. There are no adequate reports or well-controlled studies in pregnant women.
Side effects include rhinitis, back pain, epistaxis, nasal irritation, and headache.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Calcitonin does not cross the placenta. The mechanism by which high doses of calcitonin produce IUGR in rabbits is unknown.
Breastfeeding Safety There is no published experience in nursing women. Calcitonin inhibits lactation in animals. It is unknown whether calcitonin enters human breast milk, though the high molecular weight argues against it. Further, any calcitonin in the milk would be destroyed by gastric acid. Procalcitonin is a normal constituent of human breast milk.
Drug Interactions In patients with Paget’s disease, prior diphosphonate use appears to reduce the antiresorptive response to calcitonin .
References Kovarik J, Woloszczuk W, Linkesch W, Pavelka R. Lancet 1980; 1:199-200.
Lafond J, Goyer-O’Reilly I, Laramee M, Simoneau L. Endocrine 2001; 14:285-94.
Seki K, Makimura N, Mitsui C, et al. Am J Obstet Gynecol 1991; 164:1248-52.
Woloszczuk W, Kovarik J, Pavelka P. Gynecol Obstet Invest 1981; 12:272-6.
Summary Pregnancy Category: C
Lactation Category: S (likely)

  • Calcitonin should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

Calcitriol — (Rocaltrol)

International Brand Names

Bocatriol (Germany); Bonky (Korea); Cabone (Korea); Calcijex (Australia, China, England, Hong Kong, Indonesia, Malaysia, Taiwan); Caraben SC (Korea); Cicarol (Korea); Citrihexal (Australia); Decostriol (Germany); Ecatrol (Indonesia); Ecatrol F (Indonesia); Hitrol (Indonesia); Kolkatriol (Indonesia); Kosteo (Australia); Lemytriol (Mexico); Meditrol (Thailand); Neobon (Korea); Osteotriol (Germany); Poscal (Korea); Renatriol (Germany); Rexamat (Argentina); Rocaltrol (Brazil, Canada, Chile, China, Costa Rica, Dominican Republic, Ecuador, El Salvador, Ghana, Guatemala, Honduras, Hong Kong, Indonesia, Japan, Kenya, Korea, Mexico, Nicaragua, Panama, Peru, South Africa, Taiwan, Tanzania, Thailand, Uganda, Uruguay, Venezuela); Roical (Malaysia, Singapore); Rolsical (India); Silkis (England, France, Hong Kong, Ireland, Singapore); Sitriol (Australia); Tariol (Korea); Tirocal (Mexico); Triocalcit (Peru)

Drug Class Vitamins/minerals
Indications Hypoparathyroidism, osteoporosis, hypocalcemia, supplementation during pregnancy
Mechanism Active form of vitamin D; stimulates intestinal absorption of calcium and phosphorus
Dosage With Qualifiers Hypocalcemia—0.25–1 mcg PO qd
Hypoparathyroidism—0.25–2 mcg/d IV; increase the dose every 2–4 w as needed
Supplementation during pregnancy—10 mcg/d PO

  • Contraindications —hypersensitivity to drug or class, hypercalcemia, hypervitaminosis D

  • Caution —renal failure or stones, hyperphosphatemia

Maternal Considerations Calcitriol is an active form of vitamin D. There are no adequate reports or well-controlled studies in pregnant women. Vitamin D supplementation is recommended during pregnancy. Calcitriol combined with calcium supplementation helps lower systolic BP in older women.
Side effects include N/V, anorexia, convulsion, dry mouth, bone pain, polydipsia, irritability, weight loss, increased LFTs, and conjunctivitis.
Fetal Considerations There are no adequate reports or well-controlled studies of the effect of calcitriol in human fetuses. It is unknown whether calcitriol crosses the human placenta, though the placenta synthesizes active vitamin D. Calcitriol is reportedly teratogenic in rabbits but not rats.
Breastfeeding Safety Calcitriol supplementation during pregnancy increases milk vitamin D levels.
Drug Interactions Cholestyramine may reduce intestinal absorption of fat-soluble vitamins, including calcitriol.
Phenytoin/phenobarbital may reduce endogenous levels of 25(OH)D 3 by accelerating metabolism and require higher doses of calcitriol .
Thiazides are known to induce hypercalcemia by decreasing urine calcium excretion. Caution is indicated.
Ketoconazole inhibits both synthetic and catabolic enzymes of calcitriol. Reduction in serum endogenous calcitriol was seen after 300–1200 mg/d ketoconazole for 7 d. However, in vivo drug interaction studies of ketoconazole with calcitriol have not been investigated.
As calcitriol alters intestinal, renal, and bone phosphate transport, the dose of phosphate-binding agents must be adjusted to reflect the serum phosphate concentration.
As calcitriol is the most potent active metabolite of vitamin D 3 , pharmacologic doses of vitamin D and its derivatives should be withheld during treatment with calcitriol.
Magnesium-containing preparations (e.g., antacids) may cause hypermagnesemia and should not be taken during therapy with calcitriol by patients on chronic renal dialysis.
References Brunvand L, Quigstad E, Urdal P, Haug E. Early Hum Dev 1996; 45:27-33.
Cancela L, Le Boulch N, Miravet L. J Endocrinol 1986; 110:43-50.
Kuoppala T, Tuimala R, Parviainen M, et al. Hum Nutr Clin Nutr 1986; 40:287-93.
Mallet E, Gugi B, Brunelle P, et al. Obstet Gynecol 1986; 68:300-4.
Pfeifer M, Begerow B, Minne HW, et al. J Clin Endocrinol Metab 2001; 86:1633-7.
Wall CR, Stewart AW, Camargo CA Jr et al. Am J Clin Nutr. 2016; 103: 382-8.
Summary Pregnancy Category: B
Lactation Category: S (likely)

  • Calcitriol should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

  • Most multivitamin supplements contain adequate quantities of vitamin D in one form or another.

Calcium chloride

Drug Class Electrolyte replacements; Vitamins/minerals
Indications Hypocalcemia, hypermagnesemia
Mechanism Modulator of cellular events (e.g., contraction, signaling) via specific membrane channels
Dosage With Qualifiers Hypocalcemia—500–1000 mg IV slow infusion; do not exceed 1000 mg × 1
Hypermagnesemia—500 mg IV slow infusion; follow patient for clinical signs of hypermagnesemia

  • Contraindications —VF, hypercalcemia, digitalis toxicity, liver dysfunction

  • Caution —CV defects, impaired respiratory function, acidosis

Maternal Considerations Calcium chloride is lifesaving in women with hypermagnesemia. It provides approximately 3 × more calcium than calcium gluconate. Calcium chloride reduces the incidence of parturient paresis in cows and transiently increases cardiac output in gravid ewes during hemorrhagic hypotension.
Side effects include tissue destruction after extravasation and hyperkalemia-related ECG disturbances.
Fetal Considerations It is unlikely calcium administration increases the fetal concentration. Calcium chloride decreases the aspirin toxicity in pregnant rats.
Breastfeeding Safety It is unknown whether calcium chloride supplementation increases calcium concentration in breast milk.
Drug Interactions A digitalized patient should not receive IV calcium compounds unless the indications are clearly defined.
Calcium salts should not generally be mixed with carbonates, phosphates, sulfates, or tartrates in parenteral admixtures.
References Bohman VR, Cotton DB. Obstet Gynecol 1990; 76:984-6.
Oetzel GR. J Am Vet Med Assoc 1996; 209:958-61.
Ueno K, Shimoto Y, Yokoyama A, et al. Res Commun Chem Pathol Pharmacol 1983; 39:179-88.
Vincent RD Jr, Chestnut DH, Sipes SL, et al. Anesth Analg 1992; 74:670-6.
Summary Pregnancy Category: C
Lactation Category: U

  • Calcium chloride may be lifesaving in preeclamptic or preterm laboring women with hypermagnesemia secondary to magnesium sulfate infusion.

Camphor — (found in Absorbine Arthritic Pain Lotion 10%; Act-On Rub Lotion 1.5%; Anabalm Lotion 3%; Avalgesic; Aveeno Anti-Itch Conc. Lotion 0.3%; Banalg Muscle Pain Reliever 2%; Ben Gay Children’s Vaporizing Rub 5%; Campho-Phenique First Aid Gel 10.8%)

International Brand Names

None identified.

Drug Class Anesthetics, local; Antipruritics
Indications Cold relief symptoms, muscle strain
Mechanism Unknown
Dosage With Qualifiers Found in multiple topical preparations

  • Contraindications —hypersensitivity to drug or class

  • Caution —seizures

Maternal Considerations The FDA states that OTC drug products may not exceed camphor concentrations of 11%. There are no adequate reports or well-controlled studies in pregnant women.
Side effects include local irritation and burning sensation.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Camphor crosses the placenta, but there is no evidence of embryo toxicity or teratogenicity.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether camphor enters human breast milk. Considering the route and dose, it is unlikely the breastfeeding neonate would ingest a clinically significant amount.
Drug Interactions No drug interactions reported after topical use.
References American Academy of Pediatrics, Committee on Drugs. Pediatrics 1978; 62:404-6.
Uc A, Bishop WP, Sanders KD. South Med J 2000; 93:596-8.
Weiss J, Catalano P. Pediatrics 1973; 52:713-4.
Summary Pregnancy Category: C
Lactation Category: S

  • Camphor should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

Candesartan — (Atacand)

International Brand Names

Amias (England, Ireland); Atacand (Canada, Colombia, France, Germany, Israel, Mexico, Singapore, South Africa, Sweden); Bilaten (Chile); Blopress (Austria, Brazil, Colombia, Costa Rica, El Salvador, Germany, Guatemala, Honduras, Hong Kong, Indonesia, Israel, Italy, Japan, Malaysia, Mexico, Nicaragua, Panama, Peru, Philippines, Thailand, Venezuela); Blox (Chile); Candesar (India); Kenzen (France); Tiadyl (Argentina, Paraguay)

Drug Class ACEI/A2R-antagonists; Antihypertensives
Indications Hypertension
Mechanism AT-1 receptor antagonist
Dosage With Qualifiers Hypertension—begin 16 mg PO qd and increase gradually; max 32 mg qd

  • Contraindications —hypersensitivity to drug or class, history of angioedema

  • Caution —renal artery stenosis, hepatic or renal dysfunction, hyponatremia, heart failure

Maternal Considerations The published experience for candesartan during pregnancy is limited to a few case reports. It is assumed the effects of candesartan are similar to other ACEI class agents. As such, it should be avoided throughout pregnancy unless there is no other option. The lowest effective dose should be used when candesartan is required for BP control during pregnancy. Candesartan has increasingly been used for the management of migraine headaches. This too should be avoided during pregnancy.
Side effects include fetal and neonatal morbidity/death (see Fetal Considerations), hypovolemia, asthenia, fever, paresthesia, vertigo, dyspepsia, gastroenteritis, tachycardia, palpitation, leukopenia, hepatotoxicity, neutropenia, hyperkalemia, edema, diarrhea, chest pain, cough, increased LFTs, pruritus, and rash.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Candesartan presumably crosses the human placenta since fetal renal effects are reported and other ACEIs cross. AT-1 receptors are expressed on many organs of the human fetus. ACEIs are considered both teratogenic and fetotoxic. They are contraindicated throughout pregnancy, as all members of this class may cause cranial hypoplasia, reversible or irreversible renal failure, oligohydramnios, anuria, death, prematurity, IUGR, and patent ductus arteriosus.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether candesartan enters human breast milk.
Drug Interactions Reversible increases in serum lithium along with toxicity have been reported during administration of lithium and ACEIs, including candesartan, and with some A2R-antagonists. Careful monitoring of serum lithium is recommended.
References Bald M, Holder M, Zieger M, et al. Pediatr Nephrol 2005; 20:1664-8.
Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. N Engl J Med 2006; 354:2443-51.
Hinsberger A, Wingen AM, Hoyer PF. Lancet 2001; 357:1620.
Simonetti GD, Baumann T, Pachlopnik JM, et al. Pediatr Nephrol 2006; 21:1329-30.
Summary Pregnancy Category: C (first trimester), D (second and third trimesters)
Lactation Category: U

  • Candesartan and other ACEIs should be considered human teratogens.

  • Candesartan and other inhibitors of angiotensin’s effects should be avoided during pregnancy if possible.

  • There are alternative agents for which there is more experience during pregnancy and lactation.

  • When the mother’s disease requires treatment with candesartan, the lowest dose should be used, followed by close monitoring of the fetus.

Captopril — (Capoten; Tenofax)

International Brand Names

Ace-Bloc (Taiwan); Acenorm (Australia, Germany); Acepress (Indonesia, Italy); Acepril (England); Aceril (Israel); Aceten (India, South Africa); Adocor (Germany); Alopresin (Spain); Altran (Colombia); Apuzin (Taiwan); Asisten (Argentina); Capace (South Africa); Capocard (Hong Kong); Caposan (Peru); Capotena (Mexico); Capotril (Israel); Capril (Hong Kong, Korea, Taiwan); Captace (Philippines); Captensin (Indonesia); Capti (Israel); Captoflux (Germany); Captomax (South Africa); Captopren (Colombia); Captoprilan (Dominican Republic); Captoril (Japan); Captral (Mexico); Cardipril (Mexico); Catona (Mexico); Catoplin (Singapore); Cesplon (Spain); Cryopril (Mexico); Debax (Austria); Dexacap (Hong Kong, Indonesia); Ecapres (Dominican Republic); Ecaten (Mexico); Epicordin (Germany); Epsitron (Hong Kong, Thailand); Farmoten (Indonesia); Hiperil (Portugal); Hypopress (Israel); Hypotensor (Greece); Inhibace (Israel); Insucar (Colombia); Isopresol (Argentina); Katopil (Slovenia); Ketanine (Singapore); Keyerpril (Mexico); Locap (Indonesia); Lopirin (Austria, Germany, Switzerland); Lopril (Finland, France); Medepres (Argentina); Mereprine (Portugal); Midrat (Mexico); Nolectin (Peru); Oltens Ge (France); Petacilon (Singapore); Praten (Indonesia); Primace (Philippines); Rilcapton (Hong Kong, Singapore, Taiwan); Ropril (Hong Kong); Smarten (Taiwan); Tenofax (Indonesia); Tensicap (Indonesia); Tensiomen (Bulgaria, Hungary, Thailand); Tensobon (Germany); Tensoprel (Singapore); Tensoril (Philippines); Tenzib (Belgium); Topace (Australia); Toprilem (Mexico); Typril-ACE (Philippines); Vasosta (Philippines); Zapto (South Africa); Zorkaptil (Slovenia)

Drug Class ACEI/A2R-antagonists; Antihypertensives
Indications Hypertension, CHF, diabetes, MI (acute)
Mechanism Angiotensin-converting enzyme inhibitor
Dosage With Qualifiers Hypertension—25–50 mg PO tid
CHF—12.525–50 mg PO tid
Diabetic nephropathy—25 mg PO tid
NOTE: May be combined with hydrochlorothiazide.

  • Contraindications —hypersensitivity to drug or class, renal artery stenosis

  • Caution —collagen vascular diseases, CHF, renal artery stenosis, hepatic or renal dysfunction, hyponatremia

Maternal Considerations There are no adequate reports or well-controlled studies of captopril in pregnant women. ACEIs are contraindicated across gestation unless there is no option. Improved pregnancy outcome was reported in diabetic mothers treated prenatally with low doses of captopril. The lowest effective dose should be used when captopril is required during pregnancy. Close monitoring of AF and fetal well-being is recommended.
Side effects include angioedema, hypotension, renal failure, hepatic toxicity, pancreatitis, proteinuria, neutropenia, rash, pruritus, cough, abdominal pain, N/V, diarrhea, anorexia, constipation, peptic ulcer, dizziness, headache, malaise, fatigue, insomnia, dry mouth, dyspnea, alopecia, and paresthesias.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Captopril apparently crosses the human placenta, though the kinetics remain to be elucidated. ACEIs are considered both teratogenic and fetotoxic. They are contraindicated throughout pregnancy, as all members of this class may cause cranial hypoplasia, reversible or irreversible renal failure, oligohydramnios, anuria, death, prematurity, IUGR, and patent ductus arteriosus. Captopril is embryocidal and causes stillbirths in a variety of animals (sheep, rabbits, rats).
Breastfeeding Safety Captopril is excreted in breast milk at a very low concentration and is generally considered compatible with breastfeeding.
Drug Interactions Patients on diuretics (especially if recently initiated), as well as those on severe dietary salt restriction or dialysis, may experience a precipitous drop in BP typically within an hour of receiving the initial dose of captopril. Proactive steps to avoid hypotension include discontinuing the diuretic or increasing the salt intake approximately 1 w prior to initiating captopril or initiating therapy with small doses (6.25 or 12.5 mg). If hypotension occurs, the patient should be placed in a supine position and, if necessary, receive an IV infusion of normal saline. Transient hypotension is not a contraindication to further doses.
Nitroglycerin or other nitrates (as used for management of angina) or other drugs having vasodilator activity should, if possible, be discontinued before starting captopril. If resumed during captopril therapy, such agents should be given cautiously, perhaps at a lower dose.
It is enhanced by antihypertensive agents that cause renin release (e.g., thiazides).
Agents affecting sympathetic activity (e.g., ganglionic blocking agents or adrenergic neuron blocking agents) should be used with caution.
β-Adrenergic blocking agents are somewhat additive to captopril, but the overall response is less than the individual sum.
Serum potassium may rise, because captopril decreases aldosterone production. Potassium-sparing diuretics, such as spironolactone, triamterene, and amiloride, or potassium supplements, should be given only for documented hypokalemia, and then with caution. Salt substitutes containing potassium should also be used with caution.
Indomethacin may reduce the antihypertensive effect, especially in cases of low-renin hypertension. Other NSAIDs (e.g., aspirin ) may have this effect.
Increased serum lithium levels and symptoms of toxicity are reported in patients receiving lithium and ACEI therapy. These drugs should be co-administered with caution.
References August P, Mueller FB, Sealey JE, Edersheim TG. Lancet 1995; 345:896-7.
Bar J, Chen R, Schoenfeld A, et al. J Pediatr Endocrinol Metab 1999; 12:659-65.
Burrows RF, Burrows EA. Aust NZ J Obstet Gynaecol 1998; 38:306-11.
Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. N Engl J Med 2006; 354:2443-51.
Easterling TR, Carr DB, Davis C, et al. Obstet Gynecol 2000; 96:956-61.
Summary Pregnancy Category: C (first trimester), D (second and third trimesters)
Lactation Category: S

  • Captopril and other ACEIs are considered human teratogens.

  • Captopril and other inhibitors of angiotensin’s effects should be avoided throughout pregnancy if possible.

  • There are alternative agents for which there is more experience during pregnancy.

  • Should the mother’s disease require treatment with captopril, the lowest dose should be used followed by close monitoring of the fetus.

Carbachol — (Carbastat; Carboptic; Isopto; Miostat)

International Brand Names

Carbamann (Germany); Glaumarin (Japan); Isopto Karbakolin (Sweden); Karbakolin Isopto (Denmark)

Drug Class Miotics; Ophthalmics; Parasympathomimetics
Indications Glaucoma
Mechanism Cholinergic receptor agonist; partial cholinesterase inhibitor
Dosage With Qualifiers Glaucoma—2 gtt each eye tid
NOTE: No more than 0.5 mL should be administered for satisfactory miosis.

  • Contraindications —hypersensitivity to drug or class, acute iritis

  • Caution —cardiac failure, asthma, hyperthyroidism, GI spasm, parkinsonism, recent MI, hypertension

Maternal Considerations There are no adequate reports or well-controlled studies of the effect of carbachol in pregnant women. Carbachol is a potent stimulator of myometrial contractility in rodents. Considering the dose and route, it is unlikely the maternal systemic concentration will reach a clinically relevant level.
Side effects include stinging, burning, flushing, sweating, epigastric distress, abdominal cramps, tightness in urinary bladder, and headache.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether carbachol crosses the human placenta. Considering the dose and route, it is unlikely the maternal systemic concentration will reach a clinically relevant level.
Breastfeeding Safety There is no published experience in pregnancy. It is unknown whether carbachol enters human breast milk. However, considering the dose and route, it is unlikely the breastfed neonate would ingest a clinically relevant amount.
Drug Interactions NSAIDs may decrease cholinergic efficacy.
References Boxall DK, Ford AP, Choppin A, et al. Br J Pharmacol 1998; 124:1615-22.
Garfield RE, Bytautiene E, Vedernikov YP, et al. Am J Obstet Gynecol 2000; 183:118-25.
Luckas MJ, Taggart MJ, Wray S. Am J Obstet Gynecol 1999; 181:468-76.
Summary Pregnancy Category: C
Lactation Category: U

  • Carbachol should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

Carbamazepine — (Atretol; Convuline; Epitol; Macrepan; Tegretol)

International Brand Names

Apo-Carbamazepine (Canada, Malaysia); Camapine (Taiwan, Thailand); Carbatol (India); Carbazene (Thailand); Carbazep (Mexico); Carbazina (Mexico); Carmaz (India); Carpaz (South Africa); Carzepin (Malaysia); Carzepine (Thailand); Clostedal (Mexico); Degranol (South Africa); Epileptol (Korea); Epileptol CR (Korea); Eposal Retard (Colombia); Espa-lepsin (Germany); Foxalepsin (Germany); Foxalepsin Retard (Germany); Hermolepsin (Sweden); Karbamazepin (Sweden); Kodapan (Japan); Lexin (Japan); Mazetol (India, Malaysia); Neugeron (Costa Rica, Dominican Republic, Guatemala, Honduras, Mexico, Nicaragua, Panama); Neurotol (Finland); Neurotop (Austria, Hungary, Malaysia); Neurotop Retard (Malaysia); Nordotol (Denmark, Mexico); Panitol (Thailand); Sirtal (Germany); Tardotol (Denmark); Taver (Thailand); Tegol (Taiwan); Tegretal (Germany); Tegretol CR (Israel, Korea, New Zealand, South Africa); Tegretol-S (South Africa); Telesmin (Japan); Temporal Slow (Hungary); Temporol (Bulgaria, South Africa); Teril (Hong Kong, Israel, New Zealand, Taiwan); Timonil (Germany, Israel); Timonil Retard (Germany, Israel, Switzerland)

Drug Class Anticonvulsants
Indications Seizure disorder, trigeminal neuralgia
Mechanism Unknown
Dosage With Qualifiers Seizure disorder—400–600 mg PO bid (or 12–25 mg/kg/d); max 600 mg PO bid
Trigeminal neuralgia—200–400 mg PO bid

  • Contraindications —hypersensitivity, MAOIs in the past 2 w

  • Caution —hepatic or renal failure, bone marrow depression, history of blood dyscrasia, cardiac disease

Maternal Considerations Anticonvulsant drugs should not be discontinued abruptly during pregnancy if used to prevent seizures, as there is a significant possibility of precipitating status epilepticus. There are no adequate reports or well-controlled studies of carbamazepine in pregnant women. It would seem advisable for women to continue medication during pregnancy using monotherapy at the lowest dose required to achieve seizure control. Polytherapy is best avoided when possible. The risks of serious dermatologic reactions are 10 × higher in some Asian countries and strongly linked to HLA-B*1502, and the risks of aplastic anemia/agranulocytosis have been highlighted in “Black Box” warnings.
Side effects include seizures, Stevens-Johnson syndrome, arrhythmias, agranulocytosis, thrombocytopenia, and hepatitis.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Carbamazepine rapidly crosses the human placenta and accumulates in fetal organs, including the brain. There is wide variability of the ratio of the umbilical cord/maternal level among women of both carbamazepine and carbamazepine-10,11-epoxide. Use with valproic acid was associated with a significant increase of the ratio of umbilical cord/maternal level of carbamazepine-10,11-epoxide and carbamazepine-10,11-epoxide/carbamazepine ratio in both maternal serum and umbilical cord. Further, the co-administration of enzyme-inducing antiepileptics and valproic acid increases the apparent oral clearance of carbamazepine . Some epidemiologic studies suggest carbamazepine is a teratogen causing facial dysmorphism, spina bifida, distal phalange hypoplasia, and developmental delay. In prospective studies involving 1255 exposures, carbamazepine was associated with increased rates of neural tube, CV, urinary tract, and cleft palate anomalies. However, subanalyses suggest the evidence carbamazepine is a teratogen is weak when given as monotherapy; it is certainly less than phenytoin, but possibly more than other anticonvulsant agents. The combination of carbamazepine with other antiepileptic drugs has a synergistic effect on the prevalence of birth defects. The majority of research to date does not support an association between prenatal exposure to monotherapy carbamazepine , lamotrigine, or phenytoin and neurodevelopmental outcome in comparison to control children; it does support higher abilities in comparison to children exposed to valproate There is also concern that carbamazepine exposure increases the risk of neonatal intracranial hemorrhage. Rodent studies reveal an increased prevalence of talipes, cleft palate, and anophthalmos.
Breastfeeding Safety Carbamazepine is excreted in human breast milk. Although it is generally considered safe for breastfeeding women, neonatal sequelae reported include cholestatic hepatitis. The infant should be monitored for possible adverse effects, the drug given at the lowest effective dose, and breastfeeding avoided at times of peak drug levels.
Drug Interactions Carbamazepine suspension should not be used with other liquid medicinal agents or diluents. Mixing it with either chlorpromazine solution or liquid thioridazine causes a precipitate.
CYP3A4 inhibitors inhibit carbamazepine metabolism and may increase plasma levels. Drugs that have been shown, or would be expected, to increase carbamazepine levels include acetazolamide, cimetidine, clarithromycin, dalfopristin, danazol, delavirdine, diltiazem, erythromycin, fluoxetine, grapefruit juice, isoniazid, ketoconazole, loratadine, itraconazole, macrolides, niacinamide, nicotinamide, propoxyphene, terfenadine, troleandomycin, valproate, and verapamil. If a patient has been on a stable dosage of carbamazepine and begins treatment with one of these inhibitors, it is reasonable to expect a dose reduction in carbamazepine may be necessary.
CYP3A4 inducers can increase carbamazepine metabolism. Drugs that have been shown, or would be expected, to decrease carbamazepine levels include cisplatin, doxorubicin, felbamate, phenobarbital, phenytoin, primidone, rifampin, theophylline, and troleandomycin.
Increases the plasma levels of clomipramine, phenytoin, and primidone.
Induces hepatic CYP activity (especially CYP3A4 or epoxide hydrolase) and either causes or would be expected to cause decreased levels of acetaminophen, alprazolam, amitriptyline, bupropion, buspirone, citalopram, clobazam, clonazepam, clozapine, cyclosporine, delavirdine, desipramine, diazepam, dicumarol, doxycycline, ethosuximide, haloperidol, lamotrigine, levothyroxine, lorazepam, methadone, methsuximide, midazolam, mirtazapine, nortriptyline, olanzapine, oral contraceptives, phensuximide, phenytoin, quinine, theophylline, tiagabine, topiramate, valproate, and warfarin.
Administration with lithium may increase the risk of neurotoxic side effects.
Altered thyroid function has been reported when combined with other anticonvulsant medications.
Breakthrough bleeding has been reported in women receiving oral and subdermal implant contraceptives, and their reliability may be adversely affected.
Phenytoin has been reported to increase. Careful monitoring of phenytoin after use with carbamazepine is advised.
Warfarin’s anticoagulant effect may be reduced by carbamazepine.
Because of its primary CNS effect, caution should be used when carbamazepine is taken with other centrally acting drugs and alcohol.
References Adab N, Tudur SC, Vinten J, et al. Cochrane Database Syst Rev 2004; (3):CD004848.
Bar-Oz B, Nulman I, Koren G, Ito S. Paediatr Drugs 2000; 2:113-26.
Burja S, Rakovec-Felser Z, Treiber M, et al. Wien Klin Wochenschr 2006; 118(Suppl 2):12-6.
Diav-Citrin O, Shechtman S, Arnon J, Ornoy A. Neurology 2001; 57:321-4.
Frey B, Braegger CP, Ghelfi D. Ann Pharmacother 2002; 36:644-7.
Holmes LB, Harvey EA, Coull BA, et al. N Engl J Med 2001; 344:1132-8.
Iqbal MM, Sohhan T, Mahmud SZ. J Toxicol Clin Toxicol 2001; 39:381-92.
Kaaja E, Kaaja R, Hiilesmaa V. Neurology 2003; 60:575-9.
Kacirova I, Grundmann M, Brozmanova H. Epilepsy Res. 2016; 122: 84-90.
Matalon S, Schechtman S, Goldzweig G, Ornoy A. Reprod Toxicol 2002; 16:9-17.
Meador KJ, Baker GA, Finnell RH, et al; NEAD Study Group. Neurology 2006; 67:407-12.
Samren EB, van Duijn CM, Christiaens GC, et al. Ann Neurol 1999; 46:739-46.
Summary Pregnancy Category: C
Lactation Category: S (likely)

  • Carbamazepine should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk; other anticonvulsants are preferable.

  • Monotherapy with the lowest effective quantity given in divided doses to minimize the peaks can minimize the risks.

Carbenicillin — (Geocillin)

International Brand Names

Carbachol (Poland); Carbamann (Germany); Glaumarin (Japan); Isopto Karbakolin (Sweden); Karbakolin Isopto (Denmark)

Drug Class Antibiotics; Penicillins
Indications Infections with E. coli, P. mirabilis, Staphylococcus, Streptococcus, S. faecalis (enterococci)
Mechanism Inhibits synthesis of cell wall mucopeptide
Dosage With Qualifiers Adult infection—2–4 tab qd (1 tab = 382 mg carbenicillin)

  • Contraindications —hypersensitivity to drug or class

  • Caution —cephalosporin allergy, seizure disorder, renal dysfunction

Maternal Considerations Carbenicillin is indicated for the treatment of acute and chronic infections of the upper and lower urinary tract. There are no adequate reports or well-controlled studies in pregnant women.
Side effects include seizures, anaphylaxis, Stevens-Johnson syndrome, hemolytic anemia, neutropenia, nausea, urticaria, diarrhea, rash, and fever.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether carbenicillin crosses the human placenta. Other penicillins do cross to varying degrees. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety There is no published experience in nursing women. Carbenicillin is excreted into breast milk at very low concentrations (< 0.001% adult dose) and is generally considered safe during breastfeeding.
Drug Interactions Carbenicillin blood levels may be increased and prolonged by administration with probenecid.
References Davies BI, Mummery RV, Brumfitt W. Br J Urol 1975; 47:335-41.
Elek E, Ivan E, Arr M. Int J Clin Pharmacol 1972; 6:223-8.
Summary Pregnancy Category: B
Lactation Category: S

  • Penicillin-class drugs are generally considered safe during pregnancy.

Carbidopa — (Lodosyn)

International Brand Names

None identified.

Drug Class Antiparkinson agents; Dopaminergics
Indications Parkinson’s disease
Mechanism Inhibits peripheral dopamine decarboxylation, crosses blood-brain barrier and can serve as a dopamine precursor
Dosage With Qualifiers Parkinson’s disease—optimal dose is determined by careful titration whether given alone or in combination with levodopa. Most patients respond to a 1:10 proportion of carbidopa and levodopa, provided the daily dosage of carbidopa is 70 mg or more/d; max 200 mg PO qd
NOTE: May be combined with levodopa (Sinemet).

  • Contraindications —hypersensitivity, glaucoma, melanoma

  • Caution —psychosis, asthma, gastric ulcer, renal failure

Maternal Considerations There are no adequate reports or well-controlled studies of carbidopa in pregnant women. Clinical experience is mostly limited to case reports, with medication often initiated after the first trimester. Pregnancy may exacerbate Parkinson’s disease and have a long-term negative impact on the course of the illness. Carbidopa inhibits the metabolism of levodopa and may lead to toxicity if not closely monitored.
Side effects include suicidal ideation, hemolytic anemia, leukopenia, hepatic failure, agitation, headache, and anxiety.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Carbidopa crosses the rat and human placenta as well as the fetal blood-brain barrier. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically. Its use with levodopa is associated with visceral and skeletal malformations in rabbits.
Breastfeeding Safety There are no adequate reports or well-controlled studies in nursing women. C arbidopa can reduce human breast milk production and is not recommended during lactation.
Drug Interactions Symptomatic postural hypotension may occur when carbidopa - levodopa is added to the antihypertensive treatment, and a dose adjustment of the antihypertensive agent may be required.
There are rare reports of adverse reactions, including hypertension and dyskinesia, from the concomitant use of TCAs and a carbidopa-levodopa combination.
Phenothiazines and butyrophenones may reduce the therapeutic effects of levodopa.
The beneficial effects of levodopa in Parkinson’s disease may be reversed by phenytoin or papaverine. Patients taking these drugs should be carefully observed for any loss of the therapeutic response to carbidopa - levodopa.
References Merchant CA, Cohen G, Mytilineou C, et al. J Neural Transm Park Dis Dement Sect 1995; 9:239-42.
Shulman LM, Minagar A, Weiner WJ. Mov Disord 2000; 15:132-5.
Vickers S, Stuart EK, Bianchine JR, et al. Drug Metab Dispos 1974; 2:9-22.
Summary Pregnancy Category: C
Lactation Category: U

  • Carbidopa should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

Carbinoxamine — (Rondec: carbinoxamine/dextromethorphan/pseudoephedrine)

International Brand Names

Became (Malaysia, Taiwan); Congestrin (Costa Rica, Dominican Republic, El Salvador, Honduras); Kezintea (Taiwan); Rondec-T (Taiwan); Rondex (Puerto Rico)

Drug Class Antihistamines
Indications Cold symptoms
Mechanism Nonselectively antagonizes central and peripheral H 1 receptors
Dosage With Qualifiers Cold symptoms—5 mL PO qid

  • Contraindications —hypersensitivity to drug or class, MAOI usage

  • Caution —glaucoma, hypertension, diabetes, asthma, COPD

Maternal Considerations There is no published experience with carbinoxamine during pregnancy.
Side effects include arrhythmia, hypertension, coronary vasospasm, drowsiness, thickened secretions, and dry mouth.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether carbinoxamine crosses the human placenta.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether carbinoxamine enters human breast milk.
Drug Interactions Antihistamines may enhance the effects of TCAs, barbiturates, alcohol, and other CNS depressants.
MAOIs prolong and intensify the anticholinergic effects of antihistamines.
References There is no published experience in pregnancy or during lactation.
Summary Pregnancy Category: C
Lactation Category: U

  • Carbinoxamine should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

  • There are alternative agents for which there is more experience during pregnancy and lactation.

Carboprost tromethamine — (Hemabate)

International Brand Names

Prostin 15m (Netherlands, New Zealand); Prostinfenem (Denmark, Sweden); Prostodin (India)

Drug Class Abortifacients; Oxytocics; Prostaglandins; Stimulants, uterine
Indications Pregnancy termination, uterine atony
Mechanism Stimulates prostaglandin F receptors
Dosage With Qualifiers Pregnancy termination—begin 100 mcg IM test dose, then 250 mcg IM q90–120 min; max 12 mg total or use no longer than 2 d
Uterine atony—250 mcg IM × 1, may repeat q15–90 min; max 2 mg

  • Contraindications —hypersensitivity to drug or class; acute PID; acute renal, hepatic, or pulmonary insufficiency; symptomatic CAD

  • Caution —hypertension, diabetes mellitus, asthma, hepatic or renal dysfunction, anemia, seizure disorder, uterine scar, chorioamnionitis

Maternal Considerations Carboprost is an analog of 15-methylprostaglandin PGF 2α . It is a second-line agent for the treatment of uterine atony refractive to oxytocin. It appears less effective than Methergine/Ergotrate and has a higher incidence of GI complaints (21% vs. < 1%). Some suggest it is more effective if given directly into the myometrium, but there are no trial data to support the practice. Carboprost has also been given both IM and intraamniotically for pregnancy termination, though both misoprostol and PGE 2 are superior for this indication. It can speed cervical ripening (200 mcg IM), but once administered it may be difficult to control. Misoprostol is superior for preparation for a first-trimester vacuum aspiration.
Side effects include pulmonary edema, respiratory distress, bronchospasm, hematemesis, uterine rupture, diarrhea, N/V, fever, flushing, hypertension, cough, headache, and pain.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether carboprost crosses the human placenta. The principal risk reflects that of hypoxia associated with uterine tachysystole.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether carboprost enters human breast milk.
Drug Interactions Augments the activity of other oxytocic agents, especially in the setting of myometrium previously treated with oxytocin. Antepartum use with other oxytocic agents is not recommended.
References Butwick AJ, Carvalho B, Blumenfeld YJ et al. Am J Obstet Gynecol. 2015; 212:642.e1-7.
Dildy GA 3rd. Clin Obstet Gynecol 2002; 45:330-44.
Lamont RF, Morgan DJ, Logue M, Gordon H. Prostaglandins Other Lipid Mediat 2001; 66:203-10.
Perry KG Jr, Rinehart BK, Terrone DA, et al. Am J Obstet Gynecol 1999; 181:1057-61.
Su LL, Biswas A, Choolani M, et al. Am J Obstet Gynecol 2005; 193:1410-4.
Vimala N, Mittal S, Dadhwal V. Int J Gynaecol Obstet 2005; 88:134-7.
Summary Pregnancy Category: C
Lactation Category: U

  • Carboprost should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

Carisoprodol — (Caridolin; Chinchen; Flexartal; Mus-Lax; Neotica; Rela; Rotalin; Scutamil-C; Soma)

International Brand Names

Artifar (Greece); Carisoma (England, India); Myolax (Thailand); Somadril (Denmark, Norway, Sweden)

Drug Class Muscle relaxants
Indications Muscle spasm
Mechanism Blocks interneuronal activity in the descending reticular formation and spinal cord
Dosage With Qualifiers Muscle spasm—350 mg PO tid and hs, or qid

  • Contraindications —hypersensitivity to drug or class, porphyria

  • Caution —hepatic or renal dysfunction

Maternal Considerations The major metabolite of carisoprodol is meprobamate. There are no adequate reports or well-controlled studies in pregnant women.
Side effects include anaphylaxis, erythema multiforme, drowsiness, orthostatic hypotension, vertigo, ataxia, vomiting, tremor, rash, angioedema, and headache.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Carisoprodol crosses the human placenta and in limited study does not appear to cause developmental toxicity. Rodent teratogenicity studies have not been performed.
Breastfeeding Safety Carisoprodol is concentrated in breast milk. The absolute dose ingested by an exclusively breastfed infant is estimated at 1.9 mg/kg/d, and the relative dose is 0.5%–6.3% of the weight-adjusted maternal dose. No adverse effects are reported.
Drug Interactions Concurrent azelastine nasal or dexmedetomidine may increase the risk of CNS depression.
Increased toxicity if taken with alcohol.
References Briggs GA, Ambrose PJ, Nageotte MP, Padilla G. Ann Pharmacother 2008; 42:898-901.
Grizzle TB, George JD, Fail PA, Heindel JJ. Fundam Appl Toxicol 1995; 24:132-9.
Nordeng H, Zahlsen K, Spigset O. Ther Drug Monit 2001; 23:298-300.
Summary Pregnancy Category: C
Lactation Category: S (possibly)

  • Carisoprodol should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

Carteolol — (Arteoptik; Cartrol; Ocupress; Optipress)

International Brand Names

Arteolol (Spain); Arteoptic (Czech Republic, Denmark, Germany, Hong Kong, Poland, Portugal, Switzerland, Taiwan, Thailand); Caltamol (Korea); Calte (Korea); Carteabak (France); Carteol (Belgium, France, Italy); Carteol LP (France); Catelon Eye drop (Korea); Elebloc (Argentina, Taiwan); Endak (Austria, Germany); Glauteolol (Argentina); Karol (Korea); Karteol (Taiwan); Mikelan (France, Hong Kong, India, Korea, Malaysia, Pakistan, South Africa, Thailand); Stobol (Bulgaria); Teoptic (England, Ireland, Netherlands, South Africa)

Drug Class Adrenergic antagonists; β-Blockers; Ophthalmics
Indications Hypertension, glaucoma
Mechanism Antagonizes β 1 - and β 2 -adrenergic receptors
Dosage With Qualifiers Hypertension—2.5–10 mg PO qd
Chronic open-angle glaucoma and intraocular hypertension—1 gtt of 1% solution bid
NOTE: Renal dosing.

  • Contraindications —hypersensitivity to drug or class, asthma, COPD, bradycardia, AV block, CHF

  • Caution —diabetes mellitus, hyperthyroidism

Maternal Considerations There is no published experience with carteolol during pregnancy.
Side effects include bronchospasm, asthenia, paresthesia, edema, and back pain.
Fetal Considerations There are no adequate reports or well-controlled studies of carteolol in human fetuses. Rodent studies are reassuring, revealing no evidence of teratogenicity despite the use of doses dramatically higher than those used clinically. There was, however, evidence of fetotoxicity and IUGR at these high doses.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether carteolol enters human breast milk. It does enter rat milk.
Drug Interactions Catecholamine-dependent drugs (e.g., reserpine ) may have an additive effect. Patients treated with carteolol plus a catecholamine-depleting agent must be observed for evidence of hypotension and/or excessive bradycardia, which may cause syncope or postural hypotension.
General anesthetics may exaggerate the hypotension.
NSAIDs may blunt the antihypertensive effect of β-blockers.
Calcium antagonists may be used with β-adrenergic blocking agents when heart function is normal, but they should be avoided in women with impaired cardiac function. Hypotension is more likely when the calcium antagonist is a dihydropyridine derivative (e.g., nifedipine ), whereas LV failure and AV conduction disturbances are more likely with either verapamil or diltiazem.
Use with digitalis and either IV diltiazem or verapamil may have additive effects in prolonging AV conduction time.
Use with oral antidiabetic agents or insulin may be associated with hypoglycemia or possibly hyperglycemia. The dose of the hypoglycemic agent should be adjusted accordingly.
Carteolol solution should be used with caution in women receiving an oral β-adrenergic blocking agent because of the potential for additive effects.
References Tamagawa M, Numoto T, Tanaka N, Nishino H. J Toxicol Sci 1979; 4:59-77.
Tanaka N, Shingai F, Tamagawa M, Nakatsu I. J Toxicol Sci 1979; 4:47-58.
Summary Pregnancy Category: C
Lactation Category: U

  • Carteolol should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

  • There are many alternative agents for the treatment of hypertension for which there is more experience during pregnancy and lactation.

Carvedilol — (Coreg)

International Brand Names

Cardivas (India); Carvedlol (Korea); Carvrol (Korea); Dilatrend (Austria, Colombia, Ecuador, Germany, Hong Kong, Italy, Korea, Malaysia, Mexico, Norway, Peru, Philippines, Taiwan, Thailand); Dilbloc (Indonesia); Eucardic (England, Ireland); Kredex (France); Querto (Germany); V-Bloc (Indonesia)

Drug Class Adrenergic antagonists; Antihypertensives; β-Blockers
Indications Hypertension, CHF
Mechanism Selective α 1 - and nonselective β-adrenergic receptor antagonists
Dosage With Qualifiers Hypertension—6.25–12.5 mg PO bid, reevaluate in 2 w; max 25 mg bid
CHF—3.125–50 mg PO bid; max 25–50 mg PO bid

  • Contraindications —hypersensitivity to drug or class, asthma, AV block, bradycardia, CHF (class IV)

  • Caution —hepatic or renal dysfunction

Maternal Considerations There are no adequate reports or well-controlled studies of carvedilol in pregnant women. There are reports of its use for the treatment of peripartal cardiomyopathy.
Side effects include AV block, bradycardia, thrombocytopenia, sudden death, bronchospasm, fatigue, N/V, orthostatic hypotension, headache, gout, and abdominal pain.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether carvedilol crosses the human placenta. Carvedilol crosses the rodent placenta and produces fetotoxicity and IUGR when given in doses that are multiples of the MRHD, presumably by decreasing maternal cardiac output.
Breastfeeding Safety There are no adequate reports or well-controlled studies in nursing women. It is unknown whether carvedilol enters human breast milk. It does enter the milk of some rodent species.
Drug Interactions Strong inhibitors of CYP2D6 (e.g., quinidine, fluoxetine, paroxetine, propafenone ) would be expected to increase blood levels of the ( R − ) enantiomer. Analysis of side effects in clinical trials showed that poor 2D6 metabolizers had a higher rate of dizziness during up-titration.
Patients taking a drug with β-blocking properties with one that can deplete catecholamines (e.g., reserpine, MAOIs) should be observed closely for signs of hypotension and/or severe bradycardia.
Clonidine may potentiate the antihypertensive effects of β-blocking agents. If the clonidine is to be terminated, the β-blocking agent should first be discontinued over several days.
Mean trough cyclosporine levels are increased after carvedilol treatment in renal transplant patients suffering from chronic vascular rejection. In about 30%, the cyclosporine dose has to be reduced. Due to wide interindividual variability, it is recommended that cyclosporine concentrations be monitored closely after initiation of carvedilol therapy.
Digoxin concentrations are increased by about 15%. Both digoxin and carvedilol slow AV conduction. Therefore increased monitoring of digoxin is recommended when initiating, adjusting, or discontinuing carvedilol.
Rifampin reduced plasma concentrations by about 70%.
Cimetidine increased AUC by about 30% but caused no change in C max .
Isolated cases of conduction disturbance (rarely with hemodynamic compromise) have been observed when carvedilol is co-administered with diltiazem.
β-Blocking drugs may enhance the blood glucose–reducing effect of insulin and oral hypoglycemics.
References Sliwa K, Skudicky D, Candy G, et al. Eur J Heart Fail 2002; 4:305-9.
Summary Pregnancy Category: C
Lactation Category: U

  • Carvedilol should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

  • There are alternative agents for which there is more experience during pregnancy and lactation.

Casanthranol — (Peri-Colace: casanthranol/docusate sodium)

International Brand Names

None identified.

Drug Class Anthraquinones; Purgatives
Indications Constipation
Mechanism Stimulates peristalsis
Dosage With Qualifiers Constipation—1–2 tab PO qd

  • Contraindications —hypersensitivity to drug or class, constipation, appendicitis, acute abdomen, mineral oil

  • Caution —N/V

Maternal Considerations There are no adequate reports or well-controlled studies of casanthranol in pregnant women.
Side effects include bowel obstruction, abdominal cramps, rash, and electrolyte disorders.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether casanthranol crosses the human placenta. It is not associated with an increased incidence of fetal malformations. Rodent teratogenicity studies have apparently not been performed.
Breastfeeding Safety There is no published experience during pregnancy. It is unknown whether casanthranol enters human breast milk. A metabolite, anthraquinone, is excreted into breast milk and may increase the incidence of diarrhea in infants of nursing mothers. However, casanthranol is generally considered safe during breastfeeding.
Drug Interactions Casanthranol may have an additive effect when given with mineral oil.
References Greenleaf JO, Leonard HSD. Practitioner 1973; 210:259-63.
Heinonen OP, Slone D, Shapiro B. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977.
Summary Pregnancy Category: C
Lactation Category: S (probably)

  • Casanthranol should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

Cefaclor — (Ceclor; Ceclor CD; Cefaclor)

International Brand Names

Aclor (Australia); Alfatil (France); Alfatil LP (France); Alphexine (France); Brelox (Philippines); Capabiotic (Indonesia); Castal (Hong Kong); CEC (South Africa); CEC 500 (Germany); Ceclex (Korea); Ceclobid (Philippines); Ceclor (Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Costa Rica, Czech Republic, Dominican Republic, Ecuador, El Salvador, Greece, Guatemala, Honduras, Hong Kong, Hungary, Indonesia, Israel, Korea, Mexico, Netherlands, Nicaragua, Panama, Peru, Philippines, Poland, Portugal, Spain, Switzerland, Venezuela); Ceclor AF (Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Panama, Peru); Ceclor CD (Australia, Philippines); Ceclor MR (Hong Kong, South Africa); Ceclor Retard (Colombia, Spain); Cecrocin (Korea); Cecrun (Korea); Cefabac (Israel); Cefabiocin (Germany); Cefacle (Korea); Cefaclin (Korea); Cefaclostad (Germany); Cefalan (Mexico); Cefkor (Australia); Cefkor CD (Australia); Cefler (Korea); Cefral (Argentina); Celco (Thailand); Cephalodoc (Germany); Ceracl (Korea); Cero (Taiwan); Cesid (Korea); Cleancef (China, Korea, Singapore); Clex (Korea); Cloracef (Indonesia); Cloracef MR (Israel); Clorotir (New Zealand, Philippines, Thailand); Cyclor (Korea); Distaclor (England, Ireland, Malaysia, Thailand); DistaclorMR (Malaysia); Especlor (Indonesia); Faclor (Brazil); Haxifal (France); Hefaclor (Germany); Karlor CD (Australia); Kefaclor (Tanzania); Keflor (Australia, Chile, China, India, Taiwan); Keflor AF (Taiwan); Kefolor (Denmark, Finland, Sweden); Kefral (Japan); Kemocin (Korea); Kerfenmycin (Taiwan); Kindoplex (Philippines); Kloclor BD (South Africa); Kwicap (Argentina); Mediconcef (Indonesia); Medoclor (Hong Kong); Miclor (Korea); Newgenclor (Korea); Newporine (Korea); Panacef (Italy, Peru); Panacef RM (Peru); Panoral (Germany); Panoral Forte (Germany); Pharmaclor (Israel); Qualiceclor (Hong Kong); Qualiphor (Hong Kong); Serviclor (Mexico); Sifaclor (Thailand); Soficlor (Hong Kong, Malaysia, Singapore); Swiflor (Taiwan); Syntocor (Hong Kong); Teraclox (Mexico); Vefarol (Philippines); Vercef (Malaysia); Versef (Philippines); Xelent (Philippines); Xeztron (Philippines)

Drug Class Antibiotics; Cephalosporins, second generation
Indications Bacterial infections (gram-positive aerobes: S. aureus , S. pneumoniae , S. pyogenes; gram-negative anaerobes: H. influenzae )
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Bacterial infection—375–500 mg XR PO bid within 1 h of eating, or 250–500 mg tid
NOTE: Renal dosing.

  • Contraindications —hypersensitivity to drug or class

  • Caution —penicillin allergy, renal dysfunction, antibiotic-associated colitis, seizure disorder, concomitant use of nephrotoxic drugs

Maternal Considerations Because of its antimicrobial spectrum, cefaclor is used to treat acute bronchitis, pharyngitis, and skin infections. It has poor activity against the anaerobes associated with bacterial vaginosis. There are no adequate reports or well-controlled studies in pregnant women. However, cephalosporins are usually considered safe during pregnancy.
Side effects include anaphylaxis, seizures, pseudomembranous colitis, nephrotoxicity, leukopenia, thrombocytopenia, erythema multiforme, exfoliative dermatitis, and cholestatic jaundice.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether cefaclor crosses the human placenta. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Most cephalosporins are excreted into breast milk. The relative infant dose of cefaclor for a wholly breastfed newborn is 0.4%–0.8%, and it is generally considered compatible with breastfeeding.
Drug Interactions Nephrotoxicity has been reported following co-administration of other cephalosporins and aminoglycosides.
Probenecid may decrease renal tubular secretion of cephalosporins, resulting in increased and more prolonged cephalosporin blood levels.
References Committee on Drugs, American Academy of Pediatrics. Pediatrics 1994; 93:137-50.
Puapermpoonsiri S, Watanabe K, Kato N, Ueno K. Antimicrob Agents Chemother 1997; 41:2297-9.
Summary Pregnancy Category: B
Lactation Category: S

  • Cefaclor is used to treat acute bronchitis, pharyngitis, and skin infections.

Cefadroxil — (Cedroxim; Droxicef; Duricef; Kefroxil; Nor-Dacef; Ultracef; Wincef)

International Brand Names

Adroxef (Chile); Alxil (Indonesia); Amben (Hong Kong); Ancefa (Indonesia); Baxan (England); Bidicef (Indonesia); Biodroxil (Bulgaria, Colombia, Hong Kong, Israel, Peru); Biodroxyl (Venezuela); Biofaxil (Portugal); Camex (Korea); Cedrox (Germany); Cedroxim (Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama); Cefacar (Argentina); Cefacell (Korea); Cefadril (Italy, Thailand); Cefadrol (India); Cefadrox (South Africa); Cefalom (Greece); Cefamox (Brazil, Mexico, Philippines, Sweden, Uruguay); Cefaroxil (Korea); Cefat (Indonesia); Cefaxil (Taiwan); Ceforal (Portugal); Cefoxil (Korea); Cefra-Om (Portugal); Cefroxil (Spain); Cephos (Italy); Cepotec (Mexico); Cipadur (South Africa); Crenodyn (Italy); Curisafe (Israel); Cyclomycin-K (Greece); Dacef (South Africa); Doxef (Indonesia); Drocef (Brazil, Korea); Droxicef (Israel); Droxyl (India); Drozid (Philippines); Duracef (Austria, Belgium, Colombia, Costa Rica, Czech Republic, Dominican Republic, Ecuador, El Salvador, Finland, Guatemala, Honduras, Hong Kong, Hungary, Israel, Mexico, Nicaragua, Panama, Peru, Philippines, Poland, South Africa, Spain, Switzerland, Taiwan); Duricef (Canada, Korea, Singapore); Egobiotic (Argentina); Ethicef (Indonesia); Evacef (Korea); Fadrox (Colombia); Justum (Paraguay); Kefloxcin (Malaysia); Kelfex (Indonesia); Kleotrat (Greece); Konicef (Korea); Lapicef (Indonesia); Lesporina (Colombia); Likodin (Taiwan); Lydroxil (India); Medicefa (Korea); Moxacef (Belgium, Greece, Netherlands); Nefalox (Greece); Nor-Dacef (Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua); Odoxil (India); Omnidrox (Slovenia); Oracefal (France); Oradroxil (Italy); QCef (Indonesia); Qualidrox (Hong Kong); Rafemox (Chile); Sedral (Japan, Taiwan); Sofidrox (Malaysia, Singapore); Teroxina (Mexico); Ucefa (Taiwan); Ultracef (Ireland); Urocef (Korea); Vepan (India); Versatic (Argentina); Vidcef (Korea)

Drug Class Antibiotics; Cephalosporins, first generation
Indications Bacterial infections (gram-positive aerobes: S. aureus , β 1 -hemolytic streptococci; gram-negative aerobes: E. coli , P. mirabilis , Klebsiella species, Moraxella catarrhalis )
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Bacterial infection—500–1000 mg PO qd
NOTE: renal dosing.

  • Contraindications —hypersensitivity to drug or class

  • Caution —penicillin allergy, renal dysfunction, antibiotic-associated colitis, seizure disorder, concomitant use of nephrotoxic drugs

Maternal Considerations Because of its antimicrobial spectrum, cefadroxil is used to treat UTIs and pharyngitis. There are no adequate reports or well-controlled studies in pregnant women. However, cephalosporins are usually considered safe during pregnancy.
Side effects include anaphylaxis, seizures, pseudomembranous colitis, nephrotoxicity, leukopenia, thrombocytopenia, erythema multiforme, exfoliative dermatitis, cholestatic jaundice, diarrhea, nausea, dyspepsia, urticaria, pruritus, and vaginal candidiasis.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether cefadroxil crosses the human placenta; not all cephalosporins do to the same degree. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Cefadroxil is excreted into breast milk in low concentrations, and the relative infant dose is < 1.5%. It is considered compatible with breastfeeding.
Drug Interactions Nephrotoxicity has been reported following co-administration of other cephalosporins and aminoglycosides.
Probenecid may decrease renal tubular secretion of cephalosporins, resulting in increased and more prolonged cephalosporin blood levels.
References Committee on Drugs, American Academy of Pediatrics. Pediatrics 1994; 93:137-50.
Shetty N, Shulman RI, Scott GM. J Hosp Infect 1999; 41:229-32.
Summary Pregnancy Category: B
Lactation Category: S

  • Cefadroxil is used to treat acute bronchitis, pharyngitis, and skin infections.

Cefamandole — (Mandol)

International Brand Names

Cedol (Taiwan); Cefadol (Taiwan, Thailand); Cefam (Italy); Dardokef (Indonesia); Dofacef (Indonesia); Kefadol (England, Ireland); Kefandol (France); Kefdole (Japan, South Africa); Kepadol (England); Kertet (Thailand); Mancef (Korea); Mandokef (Austria, Bulgaria, Denmark, Finland, Germany, Hungary, Portugal, South Africa, Spain, Switzerland); Mandol (Belgium, Czech Republic, Egypt, Korea, Netherlands, Taiwan)

Drug Class Antibiotics; Cephalosporins, second generation
Indications Bacterial infections (gram-positive aerobes: S. aureus, S. epidermidis, S. pneumoniae, S. pyogenes; gram-negative aerobes: E. coli, Klebsiella, Enterobacter, P. mirabilis, Morganella morganii; anaerobic organisms: Peptococcus, Peptostreptococcus, Clostridium, Bacteroides, Fusobacterium )
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Bacterial infection—500 mg-1 g IV q4–8 h
Cesarean section prophylaxis—1 g IV at umbilical cord clamping

  • Contraindications —hypersensitivity to drug or class

  • Caution —penicillin allergy, renal dysfunction, antibiotic-associated colitis, seizure disorder, concomitant use of nephrotoxic drugs

Maternal Considerations Because of its antimicrobial spectrum, cefamandole is used to treat lower respiratory tract infections, UTIs, peritonitis, and septicemia and for post–cesarean section prophylaxis. For the latter, it has no advantage over any other cephalosporin. Though used by some to treat group B streptococcus colonization, there is growing resistance. Cephalosporins are usually considered safe during pregnancy.
Side effects include anaphylaxis, seizures, pseudomembranous colitis, nephrotoxicity, leukopenia, thrombocytopenia, erythema multiforme, exfoliative dermatitis, and cholestatic jaundice.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether cefamandole crosses the human placenta; not all cephalosporins do to the same degree. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Cefamandole is excreted into breast milk in low concentrations; it is generally considered safe during breastfeeding.
Drug Interactions Nephrotoxicity has been reported following co-administration of other cephalosporins and aminoglycosides.
Probenecid may decrease renal tubular secretion of cephalosporins, resulting in increased and more prolonged cephalosporin blood levels.
References Committee on Drugs, American Academy of Pediatrics. Pediatrics 1994; 93:137-50.
Duff P, Gibbs RS, Jorgensen JH, Alexander G. Obstet Gynecol 1982; 60:409-12.
Ling FW, McNeeley SG Jr, Anderson GD, et al. Clin Ther 1984; 6:669-76.
Peterson CM, Medchill M, Gordon DS, Chard HL. Obstet Gynecol 1990; 75:179-82.
Simoes JA, Aroutcheva AA, Heimler I, Faro S. Infect Dis Obstet Gynecol 2004; 12:1-8.
Summary Pregnancy Category: B
Lactation Category: S

  • Cefamandole is used to treat acute bronchitis, pharyngitis, and skin infections.

Cefazolin — (Ancef; Cefazolin; Kefzol; Zolicef)

International Brand Names

Anzolin (India); Basocef (Germany); Biozolin (Indonesia); Cefa (Taiwan); Cefacidal (Belgium, Ecuador, France, Peru, South Africa); Cefamezin (Argentina, Hong Kong, Indonesia, Israel, Japan, Korea, Portugal, South Africa, Spain, Thailand); Cefarad (Israel, South Africa); Cefazin (Taiwan); Cefazol (Bulgaria, Indonesia, Thailand); Cefazolina (Spain); Cefazoline Panpharma (France); Cezolin (Brazil); Faxilen (Philippines); Fazol (Philippines); Fazolin (Thailand); Fonvicol (Philippines); Gramaxin (Austria); Izacef (South Africa); Kefarin (Greece); Kefazin (Israel); Kefzol (Austria, Belgium, Canada, Chile, Czech Republic, Hungary, Ireland, Israel, Netherlands, Poland, Switzerland, Taiwan, Venezuela); Kofatol (Taiwan); Lupex (Philippines); Megacef (Philippines); Oricef (Taiwan); Orizolin (South Africa); Reflin (India); Sanzol (Philippines); Stancef (Philippines); Stazolin (Taiwan); Surzolin (India); Totacef (Israel); Uzolin (Taiwan); Zaconil (Philippines); Zolecef (Israel); Zolicef (Austria, Thailand); Zolidina (Paraguay, Uruguay); Zolin (Italy)

Drug Class Antibiotics; Cephalosporins, first generation
Indications Bacterial infections (gram-positive aerobes: S. aureus, S. epidermidis, S. pneumoniae; gram-negative aerobes: E. coli, Klebsiella, Enterobacter, P. mirabilis )
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Acute infection—25–100 mg/kg/d IV/IM q8h
Cesarean section prophylaxis—1 g IV at umbilical cord clamping
Bacterial endocarditis—1 g IV/IM 30 min before procedure
NOTE: Renal dosing.

  • Contraindications —hypersensitivity to drug or class

  • Caution —penicillin allergy, renal dysfunction, antibiotic-associated colitis, seizure disorder, concomitant use of nephrotoxic drugs

Maternal Considerations Because of its antimicrobial spectrum, cefazolin is used to treat lower respiratory tract infections, GU tract infections, skin infections, peritonitis, septicemia, and endocarditis; for post–cesarean section prophylaxis; and intrapartum for group B streptococcus. Cefazolin is superior to clindamycin and erythromycin for group B streptococcus prophylaxis in patients with a nonanaphylactic penicillin allergy. The prophylactic administration of cefazolin preoperatively, intraoperatively, or postoperatively reduces the incidence of post–cesarean section infection. The timing of administration does not significantly alter efficacy. For this indication, it has no clinical advantage over any other cephalosporin, and cost is often the deciding factor. Prophylaxis is usually discontinued within 24 h of the surgical procedure. Cephalosporins are usually considered safe during pregnancy.
Side effects include seizures, pseudomembranous colitis, nephrotoxicity, leukopenia, thrombocytopenia, erythema multiforme, and Stevens-Johnson syndrome.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Cefazolin rapidly crosses the human placenta, achieving concentrations greater than or equal to the 90% MIC for group B streptococcus maternal, fetal, and AF samples. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Although there are no adequate reports or well-controlled studies in nursing women, cefazolin is excreted into human breast milk at very low levels. The relative infant dose of an unsupplemented breastfed newborn is < 1%. It is considered compatible with breastfeeding.
Drug Interactions Nephrotoxicity has been reported following co-administration of other cephalosporins and aminoglycosides.
Probenecid may decrease renal tubular secretion of cephalosporins, resulting in increased and more prolonged cephalosporin blood levels.
References Fiore Mitchell T, Pearlman MD, Chapman RL, et al. Obstet Gynecol 2001; 98:1075-9.
Millar LK, Wing DA, Paul RH, Grimes DA. Obstet Gynecol 1995; 86:560-4.
Philipson A, Stiernstedt G, Ehrnebo M. Clin Pharmacokinet 1987; 12:136-44.
Thigpen BD, Hood WA, Chauhan S, et al. Am J Obstet Gynecol 2005; 192:1864-8.
Wing DA, Hendershott CM, Debuque L, Millar LK. Obstet Gynecol 1998; 92:249-53.
Summary Pregnancy Category: B
Lactation Category: S

  • Cefazolin is superior to both clindamycin and erythromycin for group B streptococcus prophylaxis in patients with a nonanaphylactic penicillin allergy.

Cefdinir — (Omnicef)

International Brand Names

Cefzon (Japan); Omnicef (Austria, Korea, Thailand); Sefdin (India)

Drug Class Antibiotics; Cephalosporins, first generation
Indications Bacterial infections (gram-positive aerobes: S. aureus, S. epidermidis, S. pneumoniae; gram-negative aerobes: E. coli, Klebsiella, Enterobacter, P. mirabilis )
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Acute infection—600 mg PO qd × 10 d, or 300 mg PO bid × 10 d

  • Contraindications —hypersensitivity to drug or class

  • Caution —penicillin allergy, renal dysfunction, antibiotic-associated colitis, seizure disorder, concomitant use of nephrotoxic drugs

Maternal Considerations There are no adequate reports or well-controlled studies of cefdinir in pregnant women. It appears effective and safe during pregnancy for the treatment of acute infections, but it has no unique advantage over other cephalosporins for most indications. Cost is often a key decision factor.
Side effects include diarrhea, vaginal moniliasis, vaginitis, rash, N/V, headache, abdominal pain, dyspepsia, flatulence, anorexia, constipation, abnormal stools, asthenia, dizziness, insomnia, leukorrhea, pruritus, and somnolence.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether cefdinir crosses the human placenta; not all cephalosporins do to the same degree. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Most cephalosporins are excreted into breast milk. Although there is no published experience in nursing women, the manufacturer states there was no cefdinir detected in human breast milk after a 600-mg dose. It is generally considered compatible with breastfeeding.
Drug Interactions A 30-mL Maalox TC suspension reduces the rate (C max ) and extent (AUC) of absorption of cefdinir by approximately 40%. The time to C max is also prolonged by 1 h. There are no significant effects on pharmacokinetics if the antacid is administered 2 h before or 2 h after.
Probenecid inhibits the renal excretion of cefdinir, causing an approximate doubling in AUC, a 54% increase in peak cefdinir plasma levels, and a 50% prolongation in the apparent elimination t/2.
An iron supplement containing 60 mg of elemental iron (as FeSO4) or vitamins supplemented with 10 mg of elemental iron reduce absorption by 80% and 31%, respectively. Cefdinir should be taken at least 2 h before or after the supplement.
References Guay DR. Rel Clin Ther 2002; 24:473-89.
Summary Pregnancy Category: B
Lactation Category: S

  • Cefdinir is used to treat community-acquired pneumonia, acute bronchitis, maxillary sinusitis, and otitis media.

  • There are other cephalosporins for which there is more experience regarding use during pregnancy and lactation.

Cefditoren — (Spectracef)

International Brand Names

Meiact (Indonesia)

Drug Class Antibiotics; Cephalosporins, first generation
Indications Bacterial infections, hospital-acquired pneumonia
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Acute infection—200–400 mg PO with food bid × 10 d
Hospital-acquired pneumonia—400 mg PO with food bid × 14 d
NOTE: Renal dosing.

  • Contraindications —hypersensitivity to drug or class, hypersensitivity to milk proteins, carnitine deficiency

  • Caution —penicillin allergy, renal dysfunction, antibiotic-associated colitis, concomitant use of nephrotoxic drugs, seizures

Maternal Considerations There is no published experience with cefditoren during pregnancy. Cephalosporins are generally considered safe during pregnancy.
Side effects include seizures, N/V, diarrhea, pseudomembranous colitis, abdominal pain, dyspepsia, flatulence, anorexia, constipation, abnormal stools, Stevens-Johnson syndrome, vaginal moniliasis, vaginitis, headache, asthenia, dizziness, insomnia, rash, leukorrhea, pruritus, and somnolence.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether cefditoren crosses the human placenta; not all cephalosporins do to the same degree. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Most cephalosporins are excreted into breast milk. Although there is no published experience in nursing women, cefditoren is generally considered compatible with breastfeeding.
Drug Interactions Antacids that contain magnesium (800 mg) and aluminum (900 mg) reduce oral absorption of cefditoren administered after a meal, as reflected by a 14% decrease in mean C max and an 11% decrease in mean AUC.
Famotidine (20 mg) reduces the oral absorption of cefditoren after a meal, as reflected in a 27% decrease in mean C max and a 22% decrease in mean AUC.
Probenecid produced a 49% increase in mean C max , a 122% increase in mean AUC, and a 53% increase in t/2 of cefditoren.
References Guay DR. Rel Clin Ther 2002; 24:473-89.
Summary Pregnancy Category: B
Lactation Category: S (probably)

  • Cefditoren is used to treat hospital-acquired pneumonia, acute bronchitis, maxillary sinusitis, and otitis media.

  • There are other cephalosporins for which there is more experience regarding use during pregnancy and lactation.

Cefepime — (Maxipime)

International Brand Names

Axepim (France); Cefepim (Austria); Cefepitax (Brazil); Ceficad (India); Cepimax (Philippines); Forzyn Beta (Paraguay); Maxcef (Argentina, Israel, Uruguay); Maxfrom (Argentina); Maxipime (Austria, Belgium, Bulgaria, Canada, Chile, Colombia, Costa Rica, Czech Republic, Denmark, Ecuador, El Salvador, Germany, Guatemala, Honduras, Hong Kong, Hungary, Indonesia, Italy, Japan, Korea, Malaysia, Mexico, Netherlands, Nicaragua, Panama, Peru, Poland, Singapore, South Africa, Sweden, Taiwan, Thailand, Venezuela)

Drug Class Antibiotics; Cephalosporins, fourth generation
Indications Bacterial infections (gram-positive aerobes: MRSA, S. epidermidis, S. pneumoniae; gram-negative aerobes: E. coli, Klebsiella, Enterobacter, P. mirabilis, Pseudomonas aeruginosa )
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Bacterial infection—1–2 g IV/IM q12h
Uncomplicated UTI—0.5–1 g IV/IM q12h
NOTE: Renal dosing.

  • Contraindications —hypersensitivity to drug or class

  • Caution —penicillin allergy, renal dysfunction, antibiotic-associated colitis, seizure disorder, concomitant use of nephrotoxic drugs

Maternal Considerations Cefepime is used to treat lower respiratory tract infections, GU tract infections, skin infections, and neutropenic patients because of its antimicrobial spectrum. Limited study suggests it is as effective as cefotaxime for the treatment of acute obstetric and gynecologic infections. Third- and fourth-generation cephalosporins (e.g., cefotaxime, cefoperazone, ceftriaxone, ceftazidime, ceftizoxime ) are generally not recommended for surgical prophylaxis. Despite these recommendations, they have been accepted by the medical community for prophylaxis and are commonly misused. Cephalosporins are usually considered safe during pregnancy.
Side effects include anaphylaxis, seizures, pseudomembranous colitis, nephrotoxicity, leukopenia, thrombocytopenia, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and cholestatic jaundice.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether cefepime crosses the human placenta; not all cephalosporins do to the same degree. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Although there is no published experience in nursing women, small amounts of cefepime are excreted into human breast milk. The relative infant dose is <0.5%, and it is considered compatible with breastfeeding.
Drug Interactions Renal function should be monitored if given with high doses of aminoglycosides because of the increased potential of nephrotoxicity and ototoxicity of aminoglycoside antibiotics.
Nephrotoxicity has been reported following the administration of other cephalosporins with potent diuretics such as furosemide.
References Kai S, Kohmura H, Ishikawa K, et al. Jpn J Antibiot 1992; 45:642-60.
Newton ER, Yeomans ER, Pastorek JG, et al. J Antimicrob Chemother 1993; 32(Suppl B):195-204.
Summary Pregnancy Category: B
Lactation Category: S

  • Third- and fourth-generation cephalosporins are generally not recommended for surgical prophylaxis.

  • There are alternative agents for which there is more experience during pregnancy and lactation.

Cefmetazole — (Zefazone)

International Brand Names

None identified.

Drug Class Antibiotics; Cephalosporins, second generation
Indications Bacterial infection (gram-positive aerobes: S. aureus, S. epidermidis, S. pneumoniae, S. pyogenes; gram-negative aerobes: E. coli, Klebsiella, Enterobacter, P. mirabilis, Morganella morganii; anaerobic organisms: Peptococcus, Peptostreptococcus, Clostridium, Bacteroides, Fusobacterium )
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Bacterial infection—2 g IV q6–12 h for 5–14 d
Perioperative prophylaxis—1–2 g IV 30–90 min prior to procedure; may be repeated in 8–16 h

  • Contraindications —hypersensitivity to drug or class

  • Caution —penicillin allergy, renal dysfunction, antibiotic-associated colitis, seizure disorder, concomitant use of nephrotoxic drugs

Maternal Considerations There are no adequate reports or well-controlled studies in pregnant women. Cefmetazole is highly effective against most causes of bacterial vaginosis during pregnancy. Cefmetazole appears equivalent to cefoxitin in reducing post–cesarean section endometritis. Cephalosporins are usually considered safe during pregnancy.
Side effects include anaphylaxis, Stevens-Johnson syndrome, renal failure, diarrhea, headache, hypotension, nausea, rash, pruritus, fever, epigastric pain, vaginitis, pleural effusion, dyspnea, and erythema.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Cefmetazole rapidly crosses the human placenta, yielding fetal levels in excess of the typical MIC. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Only a scant amount of cefmetazole is excreted into human breast milk, and it is generally considered compatible with breastfeeding.
Drug Interactions Nephrotoxicity has been reported following co-administration of other cephalosporins and aminoglycosides.
Probenecid may decrease renal tubular secretion of cephalosporins, resulting in increased and more prolonged cephalosporin blood levels.
References Cho N, Fukunaga K, Kunii K. Jpn J Antibiot 1981; 34:915-24.
Crombleholme WR, Green JR, Ohm-Smith M, et al. J Antimicrob Chemother 1989; 23 (Suppl D):97-104.
Ninomiya K, Yoshimoto T, Hasegawa Y. Jpn J Antibiot 1984; 37:14-7.
Puapermpoonsiri S, Watanabe K, Kato N, Ueno K. Antimicrob Agents Chemother 1997; 41:2297-9.
Summary Pregnancy Category: B
Lactation Category: S (probably)

  • Cefmetazole is an effective agent for the treatment of bacterial vaginosis and postpartum endometritis.

  • Selection is often based on cost.

Cefonicid — (Monocid)

International Brand Names

Lisa (Israel); Lisa IM (Taiwan); Monocef (Israel); Monocid (Belgium, China, Italy, Korea, Portugal, Spain)

Drug Class Antibiotics; Cephalosporins, second generation
Indications Bacterial infections (gram-positive aerobes: S. aureus, S. epidermidis, S. pneumoniae; gram-negative aerobes: E. coli, Klebsiella, Enterobacter, P. mirabilis, Pseudomonas aeruginosa, N. gonorrhoeae; gram-positive anaerobes: C. perfringens, Peptostreptococcus, Peptococcus, Propionibacterium acnes; gram-negative anaerobes: Fusobacterium nucleatum )
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Bacterial infection—10–25 mg/kg (or 1 g) IV q24h
Cesarean section prophylaxis—1 g IV 30 min prior to procedure

  • Contraindications —hypersensitivity to drug or class

  • Caution —penicillin allergy, renal dysfunction, antibiotic-associated colitis, seizure disorder, concomitant use of nephrotoxic drugs

Maternal Considerations Because of its antimicrobial spectrum, cefonicid is used to treat lower respiratory tract infections, GU tract infections, skin infections, and septicemia, and for surgical prophylaxis. It appears effective and safe during pregnancy for the treatment of acute infections and post–cesarean section prophylaxis, but it has no unique advantage over other cephalosporins for most indications. Cost is often a key decision factor. Cephalosporins are usually considered safe during pregnancy.
Side effects include anaphylaxis, seizures, neutropenia, pseudomembranous colitis, thrombocytopenia, erythema multiforme, exfoliative dermatitis, cholestatic jaundice, and positive Coombs’ test.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether cefonicid crosses the human placenta; not all cephalosporins do to the same degree. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Cefonicid is excreted at low concentrations into human breast milk and is generally considered compatible with breastfeeding.
Drug Interactions Nephrotoxicity has been reported following co-administration of other cephalosporins and aminoglycosides.
Probenecid may decrease renal tubular secretion of cephalosporins, resulting in increased and more prolonged cephalosporin blood levels.
References Duff P, Robertson AW, Read JA. Obstet Gynecol 1987; 70:718-21.
Faro S, Martens MG, Hammill HA, et al. Am J Obstet Gynecol 1990; 162:900-10.
Fejgin MD, Markov S, Goshen S, et al. Int J Gynaecol Obstet 1993; 43:257-61.
Lou MA, Wu YH, Jacob LS, Pitkin DH. Infect Dis 1984; 6(Suppl 4):S816-20.
Summary Pregnancy Category: B
Lactation Category: S (probably)

  • Cefonicid is effective and safe during pregnancy for the treatment of acute obstetric infection and surgical prophylaxis.

  • A favorable cost profile is a key factor in its selection.

Cefoperazone — (Cefobid)

International Brand Names

Bifotik (Indonesia); Cefactam (Paraguay); Cefobactam (Korea); Cefobid (Argentina, Austria, Bulgaria, Chile, Colombia, Czech Republic, Egypt, Hong Kong, Hungary, Indonesia, Jordan, Korea, Malaysia, Oman, Poland, Portugal, Spain, Taiwan, Thailand, United Arab Emirates, Uruguay, Venezuela); Cefobis (Germany, Philippines, Switzerland); Cefogram (Italy); Cefolatam (Korea); Cefomycin (India); Cefopemax (Brazil); Cefoperazine (Japan); Ceforin (Korea); Cefozone (Singapore, Thailand); Ceperatam (Korea); Ceropid (Indonesia); CPZ (Taiwan); Dardum (Malaysia, Singapore); Ferzobat (Indonesia); Logafox (Indonesia); Magnamycin (India); Mediper (Italy); Medocef (Malaysia, Thailand); Peratam (Korea); Shinfomycin (Malaysia, Taiwan); Stabixin (India, Indonesia); Tomabef (Italy); Zoncef (Italy)

Drug Class Antibiotics; Cephalosporins, third generation
Indications Bacterial infections (gram-positive aerobes: S. aureus, S. epidermidis, S. pneumoniae, S. pyogenes, Enterococcus; gram-negative aerobes: E. coli, Klebsiella, Enterobacter, Citrobacter, P. mirabilis, Pseudomonas aeruginosa, N. gonorrhoeae; gram-positive anaerobes: C. perfringens, Peptostreptococcus, Peptococcus, Propionibacterium acnes )
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Bacterial infection—1–2 g IV/IM q12h
Cesarean section prophylaxis—1–2 g IV
NOTE: May be combined with sulbactam.

  • Contraindications —hypersensitivity to drug or class

  • Caution —penicillin allergy, renal dysfunction, antibiotic-associated colitis, seizure disorder, concomitant use of nephrotoxic drugs, altered hepatic function

Maternal Considerations Because of its antimicrobial spectrum, cefoperazone is used to treat lower respiratory tract infections, GU tract infections, skin infections, and septicemia, and for surgical prophylaxis. Cefoperazone appears effective and safe during pregnancy for the treatment of acute infections. Clearance is only modestly affected by pregnancy. Third- and fourth-generation cephalosporins (e.g., cefotaxime, cefoperazone, ceftriaxone, ceftazidime, ceftizoxime ) are generally not recommended for surgical prophylaxis. Despite these recommendations, they have been accepted by the medical community for prophylaxis and are commonly misused.
Side effects include anaphylaxis, serum sickness, pseudomembranous colitis, neutropenia, rash, urticaria, thrombocytopenia, and nausea.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Cefoperazone crosses the human placenta, but to a lower degree than ceftizoxime. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Cefoperazone is excreted in small amounts into human breast milk and has a relative infant dose of < 1%. It is considered compatible with breastfeeding.
Drug Interactions Nephrotoxicity has been reported following co-administration of other cephalosporins and aminoglycosides.
Probenecid may decrease renal tubular secretion of cephalosporins, resulting in increased and more prolonged cephalosporin blood levels.
References Fortunato SJ, Bawdon RE, Maberry MC, Swan KF. Obstet Gynecol 1990; 75:830-3.
Geroulanos S, Marathias K, Kriaras J, Kadas B. J Chemother 2001; 13(1):23-6.
Gilstrap LC 3rd, St Clair PJ, Gibbs RS, Maier RC. Antimicrob Agents Chemother 1986; 30:808-9.
Gonik B, Feldman S, Pickering LK, Doughtie CG. Antimicrob Agents Chemother 1986; 30:874-6.
Matsuda S, Kashiwagura T, Hirayama H. Jpn J Antibiot 1985; 38:223-9.
Ng NK, Sivalingam N. Med J Malaysia 1992; 47:273-9.
Ogita S, Imanaka M, Matsumoto M, et al. Am J Obstet Gynecol 1988; 158:23-7.
Summary Pregnancy Category: B
Lactation Category: S

  • Cefoperazone appears effective and safe during pregnancy for the treatment of acute obstetric infection.

  • Third- and fourth-generation cephalosporins are generally not recommended for surgical prophylaxis.

Ceforanide

Drug Class Antibiotics; Cephalosporins, second generation
Indications Bacterial infection, surgical prophylaxis
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Bacterial infection—500 mg–1 g IV bid
Surgical prophylaxis—500 mg–1 g IV × 1

  • Contraindications —hypersensitivity to drug or class

  • Caution —penicillin allergy, renal dysfunction, antibiotic-associated colitis, seizure disorder, concomitant use of nephrotoxic drugs

Maternal Considerations There are no adequate reports or well-controlled studies of ceforanide in pregnant women. It appears to have no unique advantage over other cephalosporins for most indications. Cephalosporins are usually considered safe during pregnancy.
Side effects include anaphylaxis, serum sickness, pseudomembranous colitis, diarrhea, N/V, constipation, headache, and fever.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether ceforanide crosses the human placenta; not all cephalosporins do to the same degree. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Most cephalosporins are excreted into breast milk. Although there is no published experience in nursing women, ceforanide is generally considered compatible with breastfeeding.
Drug Interactions Nephrotoxicity has been reported following co-administration of other cephalosporins and aminoglycosides.
Probenecid may decrease renal tubular secretion of cephalosporins, resulting in increased and more prolonged cephalosporin blood levels.
References Saravolatz LD, Lee C, Drukker B. Obstet Gynecol 1985; 66:513-6.
Summary Pregnancy Category: B
Lactation Category: S (probably)

  • Ceforanide appears safe during pregnancy for the treatment of acute obstetric infections such as chorioamnionitis.

Cefotaxime — (Claforan; Zetaxim)

International Brand Names

Baxima (Indonesia); Benaxima (Mexico); Biocef (Indonesia); Biosint (Mexico); Biotax (India); Biotaxime (Thailand); Cefacolin (Argentina); Cefajet (China); Cefaxim (Mexico); Cefirad (Korea); Cefocam (Paraguay); Cefoclin (Mexico); Cefomic (China); Cefotax (Israel, Japan, Thailand); Cefpiran (Korea); Cetax (Taiwan); Cetaxima (Malaysia); Clacef (Indonesia, Singapore); Cladex (Philippines); Claforan (Brazil, Canada, China, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Hong Kong, India, Indonesia, Japan, Malaysia, Nicaragua, Panama, Paraguay, Peru, Philippines, Taiwan, Thailand, Venezuela); Clafoxim (Philippines); Claraxim (Thailand); Clatax (Indonesia); Clavocef (Philippines); Clavox (Taiwan); Efotax (Indonesia); Fotax (Thailand); Fotexina (Colombia, Mexico); Goforon (Indonesia); Grifotaxima (Peru); Kalfoxim (Indonesia); Lancef (Indonesia); Lapixime (Indonesia); Lyforan (India); Molelant (Greece); Motaxim (Thailand); Naspor (Peru); Newtaxime (Korea); Omnatax (India); Oritaxime (Thailand); Pantaxin (Philippines); Primafen (Spain); Primocef (Indonesia); Ralopar (Portugal); Sepsilem (Mexico); Soclaf (Indonesia); Spirosine (Greece); Stoparen (Greece); Taporin (Mexico); Taximax (Indonesia); Taxime (Israel); Tirdicef (Indonesia); Tirotax (Mexico); Ultracef (Uruguay); Vantef (Philippines); Viken (Mexico); Zariviz (Italy); Zetaxim (India)

Drug Class Antibiotics; Cephalosporins, third generation
Indications Bacterial infections (gram-positive aerobes: S. aureus, S. epidermidis, S. pneumoniae, S. pyogenes, Enterococcus; gram-negative aerobes: E. coli, Klebsiella, Enterobacter, Citrobacter, P. mirabilis, Pseudomonas aeruginosa, N. gonorrhoeae; gram-positive anaerobes: C. perfringens, Peptostreptococcus, Peptococcus, Propionibacterium acnes )
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Bacterial infection—1–2 g IM/IV q8h
Gonorrhea—1 g IM × 1
Surgical prophylaxis—1 g IV/IM 30–90 min preoperatively
NOTE: Renal dosing.

  • Contraindications —hypersensitivity to drug or class

  • Caution —penicillin allergy, renal dysfunction, antibiotic-associated colitis, seizure disorder, concomitant use of nephrotoxic drugs

Maternal Considerations Cefotaxime is used to treat lower respiratory tract infections, GU tract infections, skin infections, and septicemia, and for surgical prophylaxis because of its antimicrobial spectrum. Cefotaxime appears effective and safe during pregnancy for the treatment of acute infections. High AF concentrations suggest it may be advantageous for the treatment of chorioamnionitis. Third- and fourth-generation cephalosporins (e.g., cefotaxime, cefoperazone, ceftriaxone, ceftazidime, ceftizoxime ) are generally not recommended for surgical prophylaxis. Despite these recommendations, they have been accepted by the medical community for prophylaxis and are commonly misused.
Side effects include anaphylaxis, serum sickness, pseudomembranous colitis, diarrhea, N/V, constipation, headache, fever, neutropenia, thrombocytopenia, rash, and urticaria.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Cefotaxime crosses the human placenta. Though the kinetics remain to be elucidated, it achieves amniotic fluid concentrations that exceed the 90% MIC for most strains of E. coli. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Scant quantities of cefotaxime are excreted into human breast milk, and the relative infant dose is < 0.5%. It is considered compatible with breastfeeding.
Drug Interactions Nephrotoxicity has been reported following co-administration of other cephalosporins and aminoglycosides.
Probenecid may decrease renal tubular secretion of cephalosporins, resulting in increased and more prolonged cephalosporin blood levels.
References Geroulanos S, Marathias K, Kriaras J, Kadas B. J Chemother 2001; 13(1):23-6.
Kafetzis DA, Lazarides CV, Siafas CA, et al. J Antimicrob Chemother 1980; 6(Suppl A):135-41.
Kafetzis DA, Siafas CA, Georgakopoulos PA, Papadatos CJ. Acta Paediatr Scand 1981; 70:285-8.
Ninomiya K, Hasegawa Y, Kanamoto T, et al. Jpn J Antibiot 1982; 35:1882-92.
Yasuda J, Yamamoto T, Ito M, et al. Jpn J Antibiot 1982; 35:1877-81.
Summary Pregnancy Category: B
Lactation Category: S

  • Cefotaxime appears effective and safe during pregnancy for the treatment of acute obstetric infection and surgical prophylaxis.

  • Third- and fourth-generation cephalosporins are generally not recommended for surgical prophylaxis.

Cefotetan — (Apatef; Cefotan)

International Brand Names

Apacef (Belgium, France); Apatef (Italy, Portugal, Switzerland); Cefotan (Canada); Ceftenon (Austria); Cepan (Italy); Yamatetam (Japan, Korea)

Drug Class Antibiotics; Cephalosporins, second generation
Indications Bacterial infections (gram-positive aerobes: S. aureus, S. epidermidis, S. pneumoniae, S. pyogenes, Enterococcus; gram-negative aerobes: E. coli, Klebsiella, Enterobacter, Citrobacter, P. mirabilis, Pseudomonas aeruginosa, N. gonorrhoeae; gram-positive anaerobes: C. perfringens, Peptostreptococcus, Peptococcus, Propionibacterium acnes )
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Bacterial infection—1–3 g IM/IV q12h
Preoperative prophylaxis—1–2 g IV 30–60 min prior to surgery
Cesarean section surgical prophylaxis—1–2 g IV after umbilical cord clamping
NOTE: Renal dosing.

  • Contraindications —hypersensitivity to drug or class

  • Caution —penicillin allergy, renal dysfunction, antibiotic-associated colitis, seizure disorder, concomitant use of nephrotoxic drugs

Maternal Considerations Because of its antimicrobial spectrum, cefotetan is used to treat lower respiratory tract infections, GU tract infections, skin infections, septicemia, and surgical prophylaxis. Cefotetan appears effective and safe during pregnancy for the treatment of acute infections. However, it has no activity against Chlamydia trachomatis. When used to treat PID, appropriate antichlamydial coverage should be added. Single-dose cefotetan can replace the multidose cefoxitin regimen for post–cesarean section prophylaxis with considerable cost savings. Case reports describe maternal hemolysis associated with cefotetan for post–cesarean section prophylaxis.
Side effects include anaphylaxis, agranulocytosis, prolonged INR, pseudomembranous colitis, neutropenia, thrombocytopenia, rash, urticaria, hemolysis, and hemolytic anemia.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Cefotetan crosses both rodent and human placentas, though the kinetics remain to be elucidated. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Although there are no adequate reports or well-controlled studies in nursing women, cefotetan is excreted in scant quantities into human breast milk. It has a relative infant dose of < 0.5% and is considered compatible with breastfeeding.
Drug Interactions Increases in serum creatinine have been reported after solo administration. Renal function should be carefully monitored if cefotetan and an aminoglycoside are used together.
Probenecid may decrease renal tubular secretion of cephalosporins, resulting in increased and more prolonged cephalosporin blood levels.
References Martin C, Thomachot L, Albanese J. Clin Pharmacokinet 1994; 26:248-58.
Naylor CS, Steele L, Hsi R, et al. Am J Obstet Gynecol 2000; 182:1427-8.
Noyes N, Berkeley AS, Freedman K, Ledger W. Infect Dis Obstet Gynecol 1998; 6:220-3.
Shariatmadar S, Storry JR, Sausais L, Reid ME. Immunohematol 2004; 20:63-6.
Spinnato JA, Youkilis B, Cook VD, et al. J Matern Fetal Med 2000; 9:348-50.
Suzuki H, Imamura K, Yoshida T, et al. J Antimicrob Chemother 1983; 11:179-83.
Todd MW, Benrubi G. Hosp Formul 1990; 25:446-50.
Summary Pregnancy Category: B
Lactation Category: S

  • Cefotetan appears effective and safe during pregnancy for the treatment of acute obstetric infection and for surgical prophylaxis.

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