Table 14-4: Commonly Used Antimicrobials for the Treatment and Prevention of Opportunistic Infections in HIV-Infected Patients
| Drug Name |
Dosing |
Adverse Effects |
FDA
Class |
Animal Data |
Human Experience in Pregnancy |
| Trimethoprim-sulfamethoxazole, TMP-SMX (Bactrim®, Septra®, Cotrim®, Sulfatrim®) |
PCP prophylaxis: 1 DS po qd, 1 SS po qd,
1 DS po tiw
PCP treatment: 5 mg/kg (based on the trimethoprim component) po or
IV q 8 h |
Fever; leukopenia; rash and/or GI intolerance (in 25–50% of HIV-infected persons, most patients tolerate readministration of lower dose after 2 wk of discontinuation); megaloblastic anemia; neutropenia; thrombocytopenia. Hematologic toxicity increased with folate depletion and high doses-treat with leucovorin 3–15 mg qd x 3 days. Reversible hyperkalemia (with high doses); photosensitivity; renal failure; hemolytic anemia with G6PD deficiency; hepatitis including cholestatic jaundice; thrush; erythema multiforme; Stevens Johnson syndrome. |
C |
Cleft palate has been observed in some animals. |
In a surveillance study of Michigan Medicaid recipients, 2296 exposures to trimethoprim/ sulfamethoxazole in the first trimester resulted in a 5.5% incidence of birth defects. This incidence suggests an association between the drug and congenital defects (cardiovascular); however, other factors such as mother’s disease, concurrent drug use, and chance may be involved (Briggs, 1998). |
Most authorities consider sulfonamides safe in pregnancy. Theoretical risk of kernicterus in the neonate if administered near term. |
| Azithromycin (Zithromax®) |
MAC prophylaxis: 1200 mg po q week;
MAC treatment: 500 mg or 600 mg po qd (in combination with ethambutol +/- rifabutin) |
GI intolerance (4%); diarrhea; nausea; abdominal pain; vaginitis; reversible hearing loss (more common with 500 mg x 30–90 days); increased transaminases |
B |
Animal studies show no harm to the fetus. |
Azithromycin and erythromycin were compared for the treatment of chlamydia in pregnancy. The authors recommended using azithromycin due to efficacy and better tolerability. Effect on the fetus was not evaluated (Adair, 1998). |
The benefit of azithromycin administration for MAC prophylaxis or treatment outweighs potential risk of congenital malformations. |
| Clarithromycin (Biaxin®) |
MAC prophylaxis: 500 mg po bid
MAC treatment: 500 mg po bid (in combination with ethambutol and/or rifabutin.) |
GI intolerance (4%); diarrhea; headache; reversible dose-related hearing loss; taste disturbances |
C |
Studies in monkeys show growth retardation, cleft palate, and embryonic loss |
The Teratogen Information Service in Philadelphia reported that the outcome of 34 first or second trimester exposures were similar to those expected in the nonexposed population. The 122 pregnancies exposed to clarithromycin in the 1st trimester did not have increased major or minor malformations when compared with matched controls. Incidence of spontaneous abortion was higher in clarithromycin-exposed group compared with controls (14% vs 7%) (p=.04) (Schick, 1996). |
Should be used with caution during pregnancy because of teratogenicity in animals. |
| Pyrazinamide |
15 mg/kg/day for latent TB (2.0 g max); 20º–25 mg/kg/day for active TB (2.0 g max); 30–50 mg/kg 2–3 times/wk (3.0–4.0 g max) for intermittent therapy |
Nongouty polyarthralgia; asymptomatic hyperuricemia; hepatitis (dose related, frequency not increased when given with INH or rifampin, rarely serious); GI intolerance; gout |
C |
No animal data available. |
No human data available. |
Due to insufficient data pyrazinamide should generally be avoided in pregnancy. INH, rifampin, and ethambutol are recommended as first-line agents for treatment of drug-sensitive TB during pregnancy. |
| Isoniazid (INH, Tubizid®, Nydrazid®) |
300 mg po qd |
Age-related hepatitis: <20 yr old-nil/35 yr old-6%/45 yr old-11%/ 55 yr old-18%; drug should be discontinued if transaminase levels are >3–5 x normal limits; allergic reactions; fever; peripheral neuropathy (especially with preexisting alcoholism, diabetes, pregnancy, malnutrition); glossitis |
C |
Animal studies show embryocidal effect, but not teratogenic. |
Retrospective analysis of more than 4900 exposures to INH did not show increased fetal malformations. (Snider, 1980). |
The American Academy of Pediatrics and the American Thoracic Society recommend that pregnant women with a positive PPD should receive INH if HIV-positive, have had recent TB contact, or have an X-ray showing old TB; start after 1st trimester if possible. |
| Rifampin (Rifadin) |
10 mg/kg/day (600 mg/day max) for TB prophylaxis or active TB; 600 mg 2–3x/wk with DOT |
Orange discoloration of urine, tears, sweat; hepatitis—usually cholestatic changes during first month (frequency not increased when given with INH); jaundice (usually reversible with dose reduction and/or continued use); GI intolerance; hypersensitivity reactions; flu-like syndrome with intermittent use characterized by dyspnea, wheezing |
C |
Animal data show congenital malformations—cleft palate, spina bifida, and embryotoxicity. |
Several reviews have evaluated treatment of TB in pregnancy. All concluded that rifampin was not teratogenic and recommended use of the drug with INH and ethambutol if necessary (American Thoracic Society, 1986). |
The American Thoracic Society recommends rifampin in combination with INH and ethambutol if treatment for drug-sensitive TB is needed during pregnancy. Many drug interactions. Because of potential increased risk of hemorrhagic disease in neonates, prophylactic vitamin K 10 mg should be administered to the neonate. |
| Rifabutin (Mycobutin®) |
300 mg po qd (dose is decreased to 150 mg qd or 300 mg 3x/wk when used with indinavir, nelfinavir, amprenavir; 150 qod with RTV or LPV/r; 450 mg qd or 600 mg 3x/wk with EFV; 300 mg 3x/wk with NVP; 150 mg 3x/wk with SQV/RTV. Not recommended with DLV or SQV alone (Fortovase).) |
Orange discoloration of urine, tears, sweat; uveitis with eye pain, photophobia, redness and blurred vision—usually seen with high doses (600 mg/day or concurrent use of fluconazole or clarithromycin); hepatitis; GI intolerance; allergic reactions |
B |
Animal data showed skeletal abnormalities. |
No human data available. |
Experience with rifabutin in pregnancy is limited. Many drug interactions with dose modifications recommended. (See Drug Interactions Table 14-6) |
| Ethambutol (Myambutol®) |
15-25 mg/kg po qd (1.6 g max); 35-50 mg/kg 2x/wk (4.0 g max); 25-30 mg/kg 3x/wk (2.4 g max) |
Optic neuritis (decreased acuity, reduced color discrimination, constricted fields, scotomata—dose related and infrequent with 15 mg/kg); GI intolerance; confusion; precipitation of acute gout. |
C |
Teratogenic in animal studies. |
No congenital defects have been reported. In 38 patients exposed to ethambutol during pregnancy, no increased risk of birth defects observed (including embryonic optic nerve toxicity). (Brobowitz, 1974). |
The CDC considers ethambutol safe in pregnancy. |
| Atovaquone (Mepron®) |
750 mg po bid for PCP treatment or prophylaxis; 1500 mg po qd for PCP prophylaxis; 1500 mg po bid for toxoplasmosis treatment (with pyrimethamine or sulfadiazine) |
GI intolerance (nausea, vomiting, diarrhea); headache; rash. 7–9% required discontinuation due to side effects |
C |
Not teratogenic in rat studies. Maternal and fetal toxicities (decreased fetal weight, early fetal resorption and post-implantation fetal loss) reported in rabbits. |
No human data available. |
Alternative regimen for PCP prophylaxis and treatment due to high cost, poor GI tolerance, and lack of safety data in pregnancy. Preferred regimens for PCP prophylaxis and treatment include trimethoprim/ sulfamethoxazole and dapsone. Third-line treatment and prophylaxis for toxoplasmosis |
| Hydroxyurea (Hydrea®, Droxia®) |
500 mg po bid |
Dose-dependent leukopenia, anemia and thrombocytopenia; GI intolerance (N/V/D, constipation), stomatitis; rash; alopecia |
D |
Hydroxyurea is teratogenic in several animal studies; anomalies include nervous system, palate, skeleton, neural tube and cardiac defects. |
Eight case reports of hydroxyurea exposure during pregnancy did not demonstrate teratogenicity, however, the data are too limited to draw any conclusions (Briggs, 1998). |
Contraindicated due to high incidence of teratogenicity in animal studies and limited human experience. No longer recommended as part of HAART. |
| Amphotericin B (Fungizone®) |
0.5–1.2 mg/kg IV qd depending on specific condition. 0.7 mg/kg for cryptococcal meningitis |
40–50% incidence of fever and chills; 30–40% incidence of renal tubular acidosis—dose dependent and reversible in absence of prior renal damage and dose <3 g (reduced with hydration and sodium loading); 20% incidence of hypokalemia; hypomagnesemia; anemia; phlebitis and pain at infusion site; hypotension; nausea; vomiting; metallic taste; headache |
B |
Animal studies demonstrated amphotericin to be harmless in pregnancy. |
The Collaborative Perinatal Project identified 9 1st trimester exposures to amphotericin and found no adverse fetal effect (Briggs, 1998). |
Can be used in pregnancy for the treatment of serious fungal infections. |
| Flucytosine (Ancobon®) |
25 mg/kg q 6 h (monitor levels – goal 50–100 mcg/mL at steady state) |
GI intolerance (N/V/D); marrow suppression with leukopenia or thrombocytopenia (dose related with renal failure, serum concentration >100 mg/mL or concurrent amphotericin); confusion; rash; hepatitis (dose related); enterocolitis; headache; photosensitivity reaction; peripheral neuropathy |
C |
Teratogenicity reported in animal studies. |
Three case reports of second and third trimester exposure resulted in no defects in the newborns, however, no conclusion can be drawn (Briggs, 1998). |
4% of administered dose converts to 5FU in the fungal organism. 5FU has been associated with congenital malformations. Use with amphotericin for the treatment of cryptococcal meningitis may reduce relapse rates but does not reduce mortality or speed recovery (van der Horst, 1997). Use in pregnancy only if benefits outweigh potential risks. |
| Nystatin |
500,000 units 5x/day (oral thrush) |
GI intolerance (N/V/D) |
B |
No animal data |
489 first trimester exposures to nystatin were observed in a Michigan Medicaid recipients surveillance study. No association between nystatin and congenital defects was observed (Briggs, 1998). |
Due to low systemic absorption nystatin may be used in the management of thrush during pregnancy. |
| Clotrimazole |
10 mg troches 5x/day (oral thrush) 100 mg intravaginal tablets bid x 3 day or qd x 7 day. 1 applicator (5g) vaginal cream q hs x 7–14 day (Candida vaginitis) |
GI intolerance (N/V); transaminase elevation. Topical treatment (rare): burning, erythema, pruritus |
C |
Embryotoxic in rats and mice. Not teratogenic in mice, rabbits, and rats. |
2624 exposures to clotrimazole (vaginal use) were observed in the first trimester in a Michigan Medicaid recipients surveillance study. No association between clotrimazole and congenital defects were observed (Briggs,1998) |
Due to minimal systemic absorption nystatin is preferred over clotrimazole in the management of thrush during pregnancy. Vaginal use in 1st trimester should be on risk/benefit basis |
| Fluconazole (Diflucan®) |
C. esophagitis: 200–800 mg/day. 150 mg po x 1 for Candida vaginitis; 150 mg po q wk for multiple recurrences
Cryptococcal infection: 200–400 mg/day. |
Dose-related GI intolerance including bloating, nausea, vomiting, pain, anorexia, weight loss (8–11% with dose <400 mg/day, 30% with dose >400 mg/day); reversible alopecia in 10–20% of patients receiving 400 mg/day for 3 months; transaminase elevation to >8 x normal; rare cases of fatal hepatitis and Stevens Johnson syndrome |
C |
Teratogenic in animal studies. |
Craniofacial, limb and cardiac defects have been reported in 4 infants with 1st trimester exposure to high-dose fluconazole (Pursley, 1996; Aleck, 1997). Anomalies do not appear to be increased among infants born after exposure to single dose fluconazole in the 1st trimester (Mastroiacovo, 1996; Sorenson, 1999). |
Contraindicated in the 1st trimester due to potential for teratogenicity. Use topical agents in treatment of C. vaginitis in pregnancy. |
| Itraconazole (Sporanox®) |
100–400 mg po qd, depending on specific condition |
Headache; GI intolerance—nausea (10%) and vomiting; rash (8%); hypokalemia reported with high doses (600 mg per day); adrenal insufficiency; impotence; gynecomastia; leg edema; transaminase elevation, rare cases of fatal hepatitis |
C |
Teratogenic in rats and mice (encephaloceles, macroglossia, and skeletal malformation). |
FDA has received 14 case reports of malformations following use of itraconazole, 4 were limb defects. However in another report of 80 exposures to single-dose itraconazole or fluconazole no malformations were reported (Rosa, 1996). |
Contraindicated in the 1st trimester due to potential for teratogenicity. |
| Voriconazole (Vfend®) |
IV: 6 mg/kg IV q12h x 2 doses (load), then 3-4 mg/kg IV q12h infused over 1-2 hours.
PO: (>40 kg) 200 mg po tid x 1 da (load), then 200-300 mg po bid; (<40 kg) 100 mg po q12h, may be increased to 150 mg po q12h (administer on an empty stomach, avoid high fat food!) |
Common: Visual disturbances (“abnormal vision” described as blurriness, color changes, and enhanced vision) seen in 20.6% of pts but less than <1% required discontinuation. Occ: Inc.LFTs (13%) and alk phos required d/c in 4–8%. hallucination (4.3%), rash (6%), nausea/vomiting. |
D |
Teratogenic in animal studies |
No data |
Avoid in pregnancy.
Do not use with EFV or RTV (400 mg bid) |
| Pyrimethamine (Daraprim®) |
Acute treatment of toxoplasmosis: Pyrimethamine 100–200 mg loading dose, then 50–75 mg po qd, in combination with sulfadiazine 4–6 g po per day in four divided doses for at least 6 wk, plus leucovorin 10–20 mg po qd; Toxoplasmosis maintenance dose: After acute treatment, pyrimethamine 25–50 mg po qd, plus sulfadiazine 2–4 g po per day in four divided doses, plus leucovorin 10–25 mg po qd Toxoplasmosis prophylaxis: Pyrimethamine 50–75 mg po q wk, in combination with dapsone, plus leucovorin 25 mg po q wk |
Folic acid deficiency with megaloblastic anemia and pancytopenia (dose-related and reversed with leucovorin); allergic reactions; GI intolerance (nausea, anorexia, vomiting) |
C |
Teratogenic in animal studies. |
No adverse fetal effects were reported in two reviews of treatment of toxoplasmosis in pregnancy (Matsui, 1994; Wong, 1994). |
If pyrimethamine is used during pregnancy, concomitant leucovorin (folinic acid) supplementation (25 mg/day) is recommended, especially during the 1st trimester, to prevent hematologic toxicity. |
| Sulfadiazine |
Acute treatment of toxoplasmosis: Sulfadiazine 4–6 g po per day in four divided doses, in combination with pyrimethamine 50–75 mg po qd for at least 6 wk, plus leucovorin 10–20 mg po qd Toxoplasmosis maintenance dose: After acute treatment, sulfadiazine 2–4 g po qd in four divided doses, plus-pyrimethamine 25–50 mg po qd, plus leucovorin 10–25 mg po qd |
Allergic reactions—rash, pruritus; crystalluria with renal damage, urolithiasis and oliguria; GI intolerance; photosensitivity; hepatitis; fever; periarteritis nodosum, Stevens Johnson syndrome; serum sickness |
C |
At high doses, animals developed cleft palate and bone abnormalities. |
Extensive use in humans without complication except one case of agranulocytosis that was possibly associated (Briggs, 1998). |
Theoretical risk of kernicterus in the neonate if administered near term. |
| Aerosolized pentamidine |
PCP prophylaxis—300 mg nebulized q mo |
Asthma reaction reported in 2–5% of patients; cough seen in 30% of patients |
C |
Systemic pentamidine is embryotoxic but not teratogenic in rats and rabbits |
Aerosolized pentamidine given to 15 women during the 2nd and 3rd trimesters did not alter pregnancy outcome or cause fetal harm (Nanda, 1992). |
CDC and manufacturer advise against the use of pentamidine during pregnancy due to the lack of data; however, aerosolized pentamidine may be considered safe due to minimal systemic absorption (Kaplan, 1995). Concerns have been raised about adequate drug distribution during pregnancy due to restrictive changes with an enlarged uterus. |
| Intravenous pentamidine |
PCP treatment—
3–4 mg/kg IV qd |
Nephrotoxicity—seen in 25% (usually reversible with discontinuation); hypotension (administer IV over 60 min to decrease risk); hypoglycemia—seen in 5–10% (usually occurs after 5 days of treatment including past treatment, may last days or weeks) may lead to insulin—dependent diabetes; marrow suppression (leukopenia; thrombocytopenia); GI intolerance with nausea, vomiting, abdominal pain, anorexia, and bad taste; transaminase elevation; pancreatitis; toxic epidermal necrolysis; fever |
C |
Not teratogenic in rat and rabbit studies, however, has been shown to be embryocidal. |
Spontaneous abortion reported, but causal relationship has not been established. |
Use in pregnancy only if benefits outweigh potential risks. Due to the toxicity profile Bactrim or clindamycin/primaquine is preferred |
| Primaquine |
15–30 mg (base) po qd (in combination with clindamycin for the treatment of PCP) |
Hemolytic anemia (G6PD deficiency); methemoglobinemia; GI intolerance; neutropenia |
C |
No animal studies available. |
No human data available. |
Theoretical concern is hemolytic anemia in G6PD-deficient fetus. Should screen for G6PD deficiency in mother before use. |
| Albendazole (Albenza®) |
400 mg po bid x 3 weeks for microsporidiosis |
Diarrhea; abdominal pain; transaminase elevation; hepatotoxicity; reversible pancytopenia and neutropenia |
C |
Teratogenic and embryotoxic in rodent and rabbit studies. |
No human data available. |
Contraindicated in pregnancy. |
| Dapsone |
100 mg po qd (PCP prophylaxis). 100 mg po qd plus trimethoprim x 3 wk (PCP treatment). 50 mg po qd or 200 mg q wk plus leucovorin and pyrimethamine (PCP + toxoplasmosis prophylaxis). |
Rash; blood dyscrasias including methemoglobinemia and sulfhemoglobinemia and hemolytic anemia (with or without G6PD deficiency); nephrotic syndrome; fever, nausea, anorexia; blurred vision; photosensitivity; tinnitis; insomnia; irritability; headache (transient); rare “sulfone syndrome”—fever, exfoliative dermatitis, jaundice, adenopathy; methemoglobinemia and anemia |
C |
No animal teratogenicity studies conducted. Carcinogenic risk in rats. |
No adverse effects reported. (Luzzi, 1993). |
Dapsone has been used extensively in the treatment of malaria and for chemoprophylaxis of leprosy without producing major fetotoxicity or causing birth defects. Recommend screening for G6PD deficiency in mother before use. |
| Acyclovir (Zovirax®) |
5–10 mg/kg IV q 8 h; 200–800 mg po x 3–5 times per day |
GI intolerance (nausea and vomiting; diarrhea); renal toxicity (especially with rapid IV infusion); dizziness; transaminase elevation; itching, headache. Toxicities are infrequent. |
C |
Not teratogenic but potential to cause chromosomal damage at high doses. |
Birth defects reported in 23 of 1002 exposures; however, this was not statistically different from the expected rate. (Glaxo Wellcome, 1996) |
Acyclovir is 1st choice for therapy of HSV infections in pregnancy and should be used for VZV if parenteral therapy indicated. |
| Valacyclovir (Valtrex®) |
1000 mg po tid (for zoster); 500 mg po bid (for recurrent HSV); 500–1000 mg po qd (for HSV suppression) |
GI intolerance—nausea, vomiting, diarrhea; headache; constipation |
B |
Not teratogenic in animal studies. |
No human data available but likely to be similar to acyclovir. |
Recommendation similar to acyclovir since valacyclovir is converted to acyclovir. Valacyclovir is preferred treatment for chicken pox in pregnancy. |
Famciclovir
Famvir®) |
500 mg po q 8 h (for zoster); 125–250 mg q 12 h (recurrent HSV and HSV suppression) |
Headache; nausea; fatigue |
B |
Carcinogenic, but not embryotoxic or teratogenic in animal studies. |
No human data. |
Until more data are available, acyclovir is 1st choice in pregnancy. |
| Ganciclovir (Cytovene®) |
CMV retinitis Induction: 5 mg/kg IV q12h x 2 wk then Maintenance: 5 mg/kg IV qd |
Neutropenia (ANC <500 in 15–20%; usually early in treatment and responds within 3–7 days to drug holiday or to G-CSF); thrombocytopenia (platelet count <20,000 in 10%, reversible). Monitor CBC 2–3 times/wk and discontinue if ANC <500-750 or platelet count <25,000; anemia; fever; rash; CNS—headache, seizures, confusion, changes in mental status; abnormal liver function tests (2–3%) |
C |
Teratogenic (in concentrations comparable to those achieved in humans) and embryotoxic: cleft palate, anophthalmia, hydrocephalus, aplastic kidney and pancreas (rabbits); growth retardation. |
No human data. |
Based on limited data and weighing toxicity of the various drugs, ganciclovir is 1st choice for treatment during pregnancy; for retinal disease intraocular implants or intravitreous injections should be considered to limit fetal exposure to systemically administered drugs. Monitor fetus with fetal movement counts in 3rd trimester and periodic ultrasound after 20 wk gestation for evidence of significant anemia, manifest as hydrops fetalis. Evaluate newborn for bone marrow suppression. |
| Valganciclovir (Valcyte®) |
Induction: 900 mg po bid w/food x 3 weeks; Maintenance: 900 mg po qd. |
Diarrhea; nausea; fever; bone marrow suppression; LFT elevation. |
C |
Teratogenic (in concentrations comparable to those achieved in humans) and embryotoxic: cleft palate, anophthalmia, hydrocephalus, aplastic kidney and pancreas (rabbits); growth retardation. |
No data. |
Concerns expected to be same as with ganciclovir. Monitor fetus with fetal movement counts in 3rd trimester and periodic ultrasounds after 20 wk gestation for evidence of significant anemia, manifest as hydrop fetalis. Evaluate newborn for bone marrow suppression. |
| Cidofovir (Vistide®) |
CMV retinitis Induction: 5 mg/kg q week x 2 weeks then q2 weeks (give concurrently with probenecid and hydration). Probenecid Regimen: 2 g given 3 hours prior to cidofovir and 1 g given at 2 and 8 hours after infusion (total 4 g); >1L normal saline 1 or 2 hrs immediately before cidofovir infusion. |
Nephropathy—dose dependent, reduced with hydration and probenecid. (Side effect of probenecid includes chills, fever, headache, rash and nausea in 30–50% of patients); uveitis; GI intolerance; neutropenia; metabolic acidosis |
C |
Embryotoxic and teratogenic (meningomyelocele, skeletal abnormalties) in rats and rabbits, |
No human data available. |
Ganciclovir is 1st choice for treatment during pregnancy. Use only if benefits appear to outweigh potential risks. |
| Foscarnet (Foscavir®) |
CMV retinitis Induction: 60 mg/kg IV q 8 hr or 90 mg/kg IV q12hr x 14 day. Maintenance: 90–120 mg/kg IV qd. Acyclovir-resistant HSV or VZV: 40 mg/kg IV q 8 h or 60 mg/kg IV q 12 h x 3 wk |
Renal failure (usually reversible; 30% get serum creatine (Cr) >2 mg/dL; (monitor Cr 1–3 times/wk and discontinue if Cr >2.9 mg/dL); mineral and electrolyte changes—reduced magnesium, phosphorus, ionized calcium, potassium (monitor serum electrolytes 1–2 times/wk and monitor for symptoms of paresthesias); seizures (10%); fever; GI intolerance; anemia; genital ulceration; neuropathy |
C |
Skeletal malformation or variation in animal studies. |
No human data available. |
Due to high incidence of nephrotoxicity, monitoring of aminiotic fluid volume by ultrasound weekly after 20 wk gestation to detect oligohydramnios is recommended. Electrolyte and renal function should be evaluated in neonate if therapy given near delivery. |
| Ribavirin (Rebetrol®) |
Treatment of hepatitis C (in combination with interferon): <75 kg—400 mg q am and 600 mg q pm. >75 kg—600 mg bid |
Hemolytic anemia (mean hgb decrease is 3 g/dL); leukopenia; hyperbilirubinemia; increased uric acid. |
X |
Ribavirin has been demonstrated teratogenic in low doses in multiple animal species (limb abnormalties, craniofacial defects, exencephaly, anophthalmia) in rodents (and in all animals tested), but not in primates when given during the first trimester. |
No data available. |
Use of ribavirin contraindicated during pregnancy and in male partners of pregnant women. |
| Interferon (Roferon®, Intron®) |
Treatment of hepatitis C (in combination with ribavirin): 3 million units 3 x/week. IM or SQ. Also used at higher doses for treatment of hepatitis B and Kaposi’s sarcoma |
Flu-like syndrome; GI intolerance (N/V/D, anorexia); CNS toxicity (delirium; obtundation and depression); neutropenia, anemia, thrombocytopenia, increased transaminase; rash; alopecia; proteinuria |
C |
Abortifacient in rhesus monkeys when given 20–500 times the human dose. |
Limited case reports of interferon exposure during pregnancy do not suggest an association with birth defects; however, data are too limited to draw a conclusion. |
Since goal of treatment of HCV is to prevent long-term sequelae, treatment in pregnancy rarely indicated and generally not recommended. |
Peg-interferon
(Peg-Intron® [alfa-2B]/ Pegasys® [alfa-2A]) |
Peg-Intron: 1mcg/kg SC q week (with ribavirin). [Dose reduction to 0.5 mcg/kg recommended for ANC<750 or plt<50k and D/C if ANC<500 or plt <25K]. Pegasys: 180mcg SC qweek (with ribavirin)[dose reduce with heme toxicity].
Peg-inteferon alfa-2A or alfa-2B and ribavirin is treatment of choice for HCV. |
Common: Flu-like symptoms, headache, dizziness, fatigue, fever, rigor, injection site inflammation, depression (29%), insomnia, alopecia, GI (abd. pain, anorexia, N/V/D.) Occasional: Thrombocytopenia, neutropenia, hypo and hyperthyroidism, LFTs elevation. |
C |
Abortifacient in rhesus monkeys. |
No data |
Since goal of treatment of HCV is to prevent long-term sequelae, treatment in pregnancy rarely indicated and generally not recommended. |
| Caspofungin |
70 mg IV load on day 1, then 50 mg IV qd (infuse over 1 hour) |
Generally well tolerated. Histamine-mediated symptoms including rash, facial swelling, pruritus and sensation of warmth have been reported. Rare: Fever, phlebitis, nausea, vomiting, headache, eosinophilia, proteinuria, increased alk phos and hypokalemia |
C |
Animal data with exposure similar to a 70 mg dose in human resulted in incomplete ossification of skull, torso, cervical ribs and talus/calcaneous. |
No data |
Avoid in pregnancy until more data becomes available. |
| Thalidomide (Thalomid®) |
50–200 mg/da po—used for treatment of aphthous ulcers, wasting |
Sedations, rash, neuropathy, constipation, neutropenia found in up to 50% |
X |
– |
High potential for birth defects, including absent or abnormal limbs; cleft lip; absent ears; heart, renal or genital abnormalties. Single dose can be associated with teratogenic effects. |
Contraindicated in pregnancy and in women at risk for pregnancy (not using effective contraception or trying to conceive). |